This research work is an extension of a previous work in which the authors created an innovative family of fuzzy implication using as t-conorm probor, as fuzzy negation the 1-x and the type of Newton's binomial. The purpose of this paper is to compare the type of fuzzy implication probor with three other constructed fuzzy implications produced by max, Einstein and Lukasiewicz t-conorms maintaining in each case the same negation. T-conorms perform the fuzzy logical operation "or" of the corresponding fuzzy sets. The main methods used for the comparisons are the basic axioms of fuzzy logic. The authors performed six combinations of t-conorm comparisons, in order to find the rank order of the five fuzzy implications. Although the general type of fuzzy implication probor came out smaller than Hamacher, Einstein and Lukasiewicz and the type of Einstein smaller than Lukasiewicz authors make extensive tests using four different membership functions and different values to the parameter m so as to examine which out of the four fuzzy implications receive the best results. The application of isosceles trapezium to the fuzzy implications probor and Einstein give the best values (most values greater than or equal to 0.9 and equal to 1).

We recently identified that cerebral mRNA expression for inducible costimulator (ICOS) and its ligans, ICOSL, both significantly increases during elimination of Toxoplasma gondii cysts from the brains of infected mice by perforin-mediated cytotoxic activity of CD8⁺ T cells. In the present study, we examined the role of ICOS in activating the effector activity of CD8⁺ T cells in response to the cysts in infected mice. Following adoptive transfer of splenic CD8⁺ T cells from chronically infected ICOS-deficient (ICOS^-/-) and wild-type (WT) mice to infected SCID mice, fewer CD8⁺ T cells were detected in the brains of the recipients of ICOS^-/- than WT CD8⁺ T cells. However, such lower numbers of ICOS^-/- CD8⁺ T cells, which migrated into the brains of the recipients, eliminated T. gondii cysts more efficiently than WT CD8⁺ T cells did. Consistently, the ICOS^-/- CD8⁺ T cells secreted greater amounts of granzyme B in response to T. gondii antigens in vitro than did WT CD8⁺T cells. We identified that ICOS^-/- CD8⁺ T cells express significantly greater levels of CD28 on their surface than WT CD8⁺ T cells, and relative expression levels of CD28 mRNA in ratios to CD8b mRNA levels in the brains of the recipients of those CD8⁺ T cells strongly correlated with their relative expression levels of mRNA for T-bet transcription factor and perforin. Furthermore, blocking of CD28 signaling by a combination of anti-CD80 and anti-CD86 antibodies abolished the increased cytotoxic activity of the ICOS^-/- CD8⁺ T cells in vitro. The present study uncovered notable compensatory interactions between ICOS and CD28 to secure the cytotoxic effector activity of CD8⁺ T cells against a microbial infection in a murine model of chronic infection with T. gondii.

Chimeric antigen receptor T cells (CAR-Ts) have shown a remarkable efficacy in hematological malignancies, but limited responses in solid tumors. Among solid tumors, CAR-T cell therapy was particularly explored in brain tumors. CAR-T cells have shown a limited clinical efficacy in various types of brain tumors due to several factors that have hampered their activity, including tumor antigen heterogeneity (not all tumor cells express the target antigen), the limited access of CAR-T cells to brain tumor cells, limited CAR-T cell trafficking and in vivo persistence and the presence of a highly immunosuppressive tumor microenvironment. Despite these considerations, some recent studies have shown promising anti-tumor activity of GD2-CAR-T cells on diffuse midline gliomas and neuroblastomas and of CARv3-TEAM-E cells in glioblastomas. However, strategies are required to improve the effect of CAR-T cells in brain tumors, including advanced CAR-T cell design with multiple antigenic targeting and incorporation of combination therapies.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

Simple Summary: Breast cancer is the most common invasive cancer among women. Triple-negative breast cancer (TNBC) accounts for 15–20% of newly diagnosed breast cancers and has the worst prognosis. However, TNBC patients are not a homogeneous group, and there are differences in the course of the disease as well as in response to treatment. For this reason, differentiation of subtypes of this tumor is important for optimal therapeutic decision and risk prediction. The presented study focuses on the expression of the androgen receptor (AR) and the infiltration of T-lymphocytes in the tumor stroma (TILs) of TNBC patients. Correlation of these tested biomarkers with standard prognostic factors. Defining new prognostic factors for 3-year overall survival (OS). Abstract: Background: Analysis of the practical benefit of testing the expression of AR and the TILs in patients with TNBC and their correlation with standard prognostic factors. Methods: The study group consisted of 86 female patients treated for TNBC. T-lymphocyte infiltration was examined in H+E staining. AR expression, CD8 and CD4 T-lymphocytes were evaluated in immunohistochemistry. Results: Significantly negative correlation was found between AR expression and the CD8 T-lymphocyte infiltration levels. A significant negative correlation was found between the AR expression and G and Ki 67, and a positive correlation between the TILs levels and G and Ki 67. Patients with AR expression and low TILs levels had the highest percentage of diagnosed distant metastases and 3-years OS. Patients with high TILs no distant metastases or deaths were diagnosed. The level of TILs turned out to be a significant independent prognostic factor. Conclusions: Based on the assessment of AR expression and TILs infiltration, the group of highest and lowest risk was determined. The prognostic factor of known parameters such as TNM and a new factor - TILs was confirmed. On the other hand, parameters such as G and Ki 67 and the tested factor - AR had no effect on the prognosis.

Immune responses to influenza (flu) antigens reflect memory to prior infections or vaccinations, which might influence immunity to new flu antigens. Memory of past antigens has been termed “original antigenic sin” or more recently “immune imprinting” and “seniority”. We have researched a comparison between the immune response to live flu infections and inactivated flu vaccina-tions. A brief history of antibody generation theories is presented culminating in new findings about the immune-network theory suggesting that a network of clones exists between an-ti-idiotypic antibodies and T cell receptors. Findings regarding the 2009 pandemic flu strain and immune responses to it are presented, including memory B cells and conserved regions within the hemagglutinin protein. The importance of CD4+ memory T cells and cytotoxic CD8+ T cells responding to both infections and vaccinations are discussed and compared. Innate immune cells like natural killer (NK) cells and macrophages are discussed regarding their roles in adaptive immune responses. Antigen presentation via macroautophagy processes are described. New vaccines in development are mentioned along with the results of some clinical trials. The manu-script concludes with how repeated vaccinations are impacting the immune system and a sketch of what might be behind the imprinting phenomenon, including future research directions.

A set of polymer composite bolted T-joints with novel configuration consisting of internal skeleton and external skin was fabricated using a prepreg-RTM co-curing molding process. Experiments were conducted to study their mechanical properties under bending load. A finite element model with a polymer resin area between the skin and skeleton was established and verified by the experimental results. Then, the damage propagation process and failure mechanism of the joint and the influence of three factors related to the layer characteristics of the skin and skeleton were investigated by the validated models. The results show that the bending stiffness and the yield limit load of the novel composite T-joint are 0.81 times and 1.65 times that of the 2A12 aluminum T-joint respectively, while at only 55.4% of its weight. The damage of the joint initiates within the resin area and leads to a degradation of the joint bending performances. The preferred stacking sequence of the skeleton is [0/+45/90/-45]ns when primarily subjected to bending loads. The decrease in bending performances is within 5% with the inclining angle of the skeleton less than 12 degrees. The more layers of 90° in the skin, the better bending performances of the joints, while the more layer of 0°, the poorer bending performances.

Calpain is delineated as a superfamily of cysteine proteases containing a CysPC motif within their genes. Among the fifteen species of mammalian homologs, calpain-1 and -2, which are categorized as conventional isozymes, execute limited proteolysis in a calcium-dependent fashion. Accordingly, the calpain system participates in physiological and pathological phenomena, encompassing cell migration, apoptosis, skeletal muscle integrity, and synaptic plasticity. The dysregulation of the calpain system has been inextricably linked to a multitude of diseases, such as ischemic and degenerative diseases, rendering it a subject of profound interest in the fields of basic research and pharmaceutical development aimed at therapeutic interventions. Recent investigations have unveiled the contributions of both conventional and unconventional calpains to the pathogenesis of cardiometabolic disorders, such as atherosclerosis, diabetes, and hepatic diseases. Consequently, the present review accentuates the pivotal role of calpains in the complications of cardiometabolic diseases and embarks upon a discourse regarding calpains as molecular targets.

Background. Waning of neutralizing and cell-mediated immune response after the primary vac-cine cycle (PVC) and the first booster dose (BD) is of concern, especially for PLWH with a CD4 count ≤200 cells/ mm3.Methods.Neutralizing antibodies (nAbs) titers by microneutralization assay against WD614G /Omicron BA.1 and IFNγ production by ELISA assay were measured in samples of PLWH at 4 time points [2 and 4 months post-PVC (T1 and T2), 2 weeks and 5 months after the BD (T3 and T4)]. Participants were stratified by CD4 count after PVC (LCD4, <200/mm3; ICD4, 201-500/mm3 and HCD4, >500/mm3). Mixed models were used to compare mean responses over T1-T4 across CD4 groups. Results. 314 PLWH on ART (LCD4=56; ICD4=120; HCD4=138) were enrolled. At T2, levels of nAbs were significantly lower in LCD4 vs ICD4/HCD4 (p=0.04). BD was crucial for increasing nAbs titres above 1:40 at T3 and up to T4 for WD614G. A positive T cell response after PVC was observed in all groups, regardless of CD4 (p=0.31). Conclusions. Waning of nAbs after PVC was more important in LCD4 group. BD managed to re-establish higher levels of nAbs against WD614G which were retained for 5 months. The level of T-cellular response was significantly higher in HCD4 and ICD4 compared to the LCD4 group although it remained above detectable levels over the entire study period regardless of CD4 count. Keywords: HIV-1 infection; SARS-CoV-2 infection;

Myelodysplastic syndromes or neoplasms (MDS) are a heterogeneous group of myeloid clonal disorders characterized by peripheral blood cytopenias, blood and marrow cell dysplasia and an increased risk for evolution to acute myeloid leukemia (AML). Non-coding RNAs, especially microRNAs and long non-coding RNAs serve as regulators of normal and malignant hematopoiesis and have been implicated in carcinogenesis. This review will present a comprehensive summary of the biology and role of non-coding RNAs, including the less studied circRNA, siRNA, piRNA, and snoRNA as potential prognostic and/or predictive biomarkers or therapeutic targets in MDS.

Ubiquitin-Specific-peptidase 22 (Usp22) cleaves ubiquitin moieties from numerous proteins, in particular transcription factors. Recently, it was reported that Usp22 acts as negative regulator of interferon-dependent responses. In the current study, we investigated the role of Usp22 deficiency upon acute viral infection with lymphocytic choriomeningitis (LCMV) virus. We found that lack of Usp22 on bone marrow derived cells (Usp22 fl/fl Vav1-Cre mice) reduced induction of type I and II interferons. Limited type I interferon response did not influence virus replication. However, restricted expression of PD-L1 led to increased frequencies of functional virus-specific CD8+ T cells and rapid death of Usp22 deficient mice. CD8+ T cell depletion experiments revealed that accelerated CD8+ T cells were responsible for enhanced lethality in Usp22 deficient mice. In conclusion, we found that the lack of Usp22 generated a pathological CD8+ T cell response, which gave rise to severe disease in mice.

B and T lymphocytes demonstrate important alterations in patients with Systemic Lupus Erythematous (SLE), with significant up-regulation of Double Negative (DN) B cells. Aim of this study was to evaluate correlation of T cell immunity changes with the distinct B cell-pattern SLE. In the present study, Flow cytometry was performed in 30 patients with SLE, on remission, and 31 healthy controls, to detect DN B cells (CD19+IgD-CD27-) and a wide range of T lymphocyte subpopulations, based on the presence of CD45RA, CCR7, CD31, CD28, CD57, defined as naive, memory and advanced differentiated/senescent T cells. Both B and T lymphocytes were significantly reduced in SLE patients. However, the percentage of DN B cells were increased, compared to HC, 12.9(2.3-74.2) vs. 8(1.7-35), p=0.04. Distribution of CD4 and CD8 lymphocytes demonstrated a shift to advanced differentiated subsets. The population of DN B cells had significant positive correlation with most of early differentiated T lymphocytes, CD4CD31+, CD4CD45RA+CD28+, CD4CD45RA+CD57-, CD4CD45RA-CD57-, CD4CD28+CD57-, CD4CD28+CD57+, CD4 CM, CD8 CD31+, CD8 NAÏVE, CD8CD45RA-CD57-, CD8CD28+CD57-, CD8CD28+CD57+. Multiple Regression analysis revealed CD4CD31+, CD8CD45RA-CD57- and CD8CD28+CD57- cells as independent parameters contributing to DN B cells, adjusted R2=0.534, p<0.0001. The predominance of DN B cells in patients with SLE is closely associated with early differentiated T lymphocyte subsets, indicating a potential causality role of DN B cells in T lymphocyte activation.

RNA interference is a highly conserved process in which non-coding small RNAs (sRNA) modulate gene expression at the post-transcriptional level influencing plant growth and development. Dicer-like (DCL), Argonaute (AGO) and RNA-dependent RNA polymerase (RDR) are the core elements involved in gene silencing and their gene families have been explored in many plants. However, these genes and their response to abiotic stresses have not yet been well in wheat. In this study, 82 AGO, 31 DCL, and 31 RDR genes were identified and phylogenetic analysis of these proteins showed that clustered into ten, four and four clades respectively. RNA-seq analysis revealed constitutive expression of AGO1, AGO9, and DCL2 family expression analysis in tissues under normal and stress conditions, whereas RDR1 which is known to engage in siRNA biogenesis showed higher expression levels in wheat leaf tissues. Our findings build the foundation for comparative genomics analyses of RNA silencing elements in cereal crops, as well as new insights into the functional complexity of RNA silencing in wheat stress responses, which is critical for understanding the processes underlying wheat stress responses.

The most widely spread and neglected zoonotic disease – Leptospirosis, with an estimated 1.03 million cases and 58,900 deaths occurring annually, is a concern and can be prevented only by effective immunization. Due to the urgent need for a novel vaccine, various research organizations have been evaluating the protective immune response elicited by recombinant vaccines. In this study amino-acid sequences of Outermembrane protein (OMPL) 1, LipL 32, 41 and 46 from ten pathogenic serovars of Leptospira were selected to obtain epitopes that induce CD4+ and CD8+ T cell responses by binding to the MHC molecules. These B cell and T cell epitopes were used to design multi-epitope vaccine to which an adjuvant sequence was added at the N-terminal end and appropriate linkers were used to join the different epitopes to increase the efficiency of the vaccine constructs. Using an immuno-informatics approach, constructs were analyzed for the physiochemical properties, secondary and tertiary structure and its validation, docking with different receptors and prediction of binding affinity for each docked complex, followed by molecular dynamics simulation. Taking in consideration all the results, multi-epitope constructs designed may prove to be promising vaccine candidates against Leptospirosis and warrants experimental validation.

γδT have functions of innate and adaptive immunity, with the potential to induce durable responses while being well-tolerated, with limited adverse effects, making it attractive as a tool for immunotherapy. γδT faces challenges as a frontline tool in clinical oncology, with limited response rates due to difficulties in reaching tumor sites with consistent cytotoxic activity and strength. Modulated Electro-hyperthermia (mEHT) is a loco-regional treatment, whereby energy-transmission from an electromagnetic field selectively targets the plasma membrane of tumor cells, inducing apoptosis and activating immune cells. We hypothesized that mEHT could enhance therapeutic effects by drawing γδT to tumor cells, while also rendering tumor cells to be more susceptible to cytotoxic effects. In this study, NOD/SCID mice harboring subcutaneous human HepG2 tumors were treated with intravenous injections of γδT after mEHT treatment. This method increased infiltration of γδT into the tumor site, significantly inhibiting tumor growth as compared to monotherapy with either modality. These data suggest that γδT could mediate a potent anti-tumor effect when combined with mEHT, and provide a strong rationale for combining these modalities in clinical application for cancer treatment.

Immunotherapy has been considered for years as a viable and attractive treatment option for patients with cancer. Among immunotherapy arsenal, the targeting of intratumoral immune cells by immune-checkpoint inhibitory agents has recently revolutionized the treatment of several subtypes of tumours. These approaches aimed at restoring an effective anti-tumour immunity, rapidly reached the market thanks to the simultaneous identification of inhibitory signals that dampen an effective antitumor response in a large variety of neoplastic cells, and the clinical development of monoclonal antibodies targeting checkpoint receptors. Leading therapies in solid tumours are mainly focused on the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed-death 1 (PD-1) pathways. These approaches have found a promising testing ground in both Hodgkin lymphoma and non-Hodgkin lymphoma, mainly because in these diseases the malignant cells interact with the immune system and commonly provide signals that regulate immune function. Although several trials have already demonstrated evidence of therapeutic activity with some checkpoint inhibitors in lymphoma, many of the immunologic lessons learned from solid tumours may not directly translate to lymphoid malignancies. In this sense, the mechanisms of effective antitumor responses are different between the different lymphoma subtypes, while the reasons for this substantial difference remain partially unknown. This review will discuss the current advances of immune-checkpoint blockade therapies in B-cell lymphoma and will build a projection of how the field may evolve in the near future. In particular, we will analyze the current strategies being evaluated both preclinically and clinically with the aim to foster the use of immune-checkpoint inhibitors in non-Hodgkin lymphoma, including combination approaches with chemotherapeutics, biological agents and/or different immunologic therapies.

Coronavirus disease (COVID-19) is a new discovered strain where WHO officially declares the disease as COVID-19 while the virus responsible for it called Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2. The incubation period of this disease is between 14 days. Ordinary clinical symptoms that reported around the world include fever, cough, fatigue, diarrhoea and vomiting as well as asymptomatic for certain people. Infection is spread mainly through broad droplets. In early March 2020, WHO again has announced that COVID-19 is a pandemic with currently no specific treatment. The potential use of SARS-COV-2 proteome as a vaccine candidate by analysing through B-cell and T-cell antigenicity by using a immunoinformatics approach as a vaccine development early stage. In this study, we used consensus sequence for SARS-COV-2 proteome that was retrieved from NCBI database. VaxiJen 2.0 was mainly used to identify the antigenic property of SARS-COV-2 proteins. IEDB then used to analyse the B-cell epitope, the presence of T cell immunogenic epitope in SARS-COV-2 proteins was obtained by using compromise method of MHC class I and II tools that accessible respectively using ProPred-1 server and MHC II Binding Prediction in IEDB database. The best epitopes of B and T-cell epitopes were predicted with high antigencity and the information is disseminated through web-based database resource (https://covid-19.omicstutorials.com/epitopes/). This study will be useful to find a new epitope-based candidate for SARS-COV-2. However, further study needs to be done for the next stages of vaccine development.

Neisseria gonorrhoeae is a strict human pathogen responsible for more than 100 million new sexually transmitted infections worldwide each year. Due to the global emergence of antibiotic resistance, the CDC recently listed N. gonorrhoeae as an urgent threat to public health. No vaccine is available in spite of the huge disease burden and the possibility of untreatable gonorrhea. The aim of this study is to investigate the immunogenicity of a novel whole-cell based inactivated gonococcal microparticle vaccine formulation loaded in dissolvable microneedles for transdermal administration. The nanotechnology-based vaccine formulation consists of inactivated whole-cell gonococci strain CDC-F62, spray dried and encapsulated into biodegradable cross-linked albumin matrix with sustained slow antigen release. The dry vaccine nanoparticles were then loaded in a dissolvable microneedle skin patch for transdermal delivery. The efficacy of the whole-cell microparticles vaccine formulation loaded in microneedles was assessed in vitro using dendritic ,cells and macrophages as well as in vivo mouse model. Antibody titers were measured using an ELISA and antigen-specific T lymphocytes were assessed in spleens and lymph nodes. Here we report that whole-cell based gonococcal microparticle vaccine loaded in dissolvable microneedles for transdermal administration induced significant increase in antigen-specific IgG antibody titers and antigen-specific CD4 and CD8 T lymphocytes in mice compared to gonococcal antigens in solution or empty microneedles. Significant increase in antigen-specific IgG antibody levels was observed at end of week 2 in groups that received the vaccine compared to the group receiving empty nanoparticles. The advantages of using formalin-fixed whole-cell gonococci that all immunogenic epitopes are covered and preserved from degradation. The spherical shaped micro and nanoparticles are biological mimics of gonococci, therefore present to the immune system as invaders but without the ability to suppress adaptive immunity. In conclusion, the transdermal delivery of microparticles vaccine via a microneedle patch was shown to be an effective system for vaccine delivery. The novel gonorrhea nanovaccine is cheap to produce in a stable dry powder and can be delivered in microneedle skin patch obviating the need for needle use or the cold chain.

Balanced and coordinated economic development across regions is a critical goal of regional economic development and new-type urbanization in China. However, few studies have examined economic growth convergence clubs at the county level. To extend the research on convergence clubs, this research applies a log t convergence test and a dynamic spatial ordered Probit model (DSOP) to endogenously identify economic growth convergence clubs in counties and to examine the influence of initial states and structures on club convergence probability. The study sample covers 2286 counties of China from 1992 to 2010. The results show significant convergence club patterns at the county levels, resulting in the gradual formation of six convergence clubs. The DSOP estimation results show that per capita fixed assets, population density and industrialization have promoted convergence club formation to varying degrees.

In this work, we explore Conjecture 1 proposed in the newly released pioneering paper “Volatility transformers: an optimal transport-inspired approach to arbitrage-free shaping of implied volatility surfaces” by Zetocha Valer, which posits that the “One-X” property is both a necessary and sufficient condition for convex order between non-negative continuous strictly increasing distributions with the same mean. We provide a counterexample demonstrating that the conjecture, as originally stated, does not hold. By examining stochastic orders, particularly the increasing convex order, and the “One-X” property, we propose an enhanced version of the conjecture which is shown to be valid. Furthermore, we discuss the implications of these findings in the context of equity implied volatility fitting and the construction of implied volatility surfaces, highlighting the challenges posed by real-market conditions. In the end, we propose several applications in implied volatility surface construction or simulation.

The study investigates the evolution of soil pore structure and shear strength deterioration in compacted clayey soil under controlled wetting and drying (wd) cycles, which are expected to become more frequent due to climate change. Thirty soil samples were compacted at optimal moisture content and 90% of maximum dry density. These samples were then subjected to 0, 1, 5, 10, and 15 controlled wd cycles from saturation to the wilting point, and volumetric changes were recorded during each cycle. After the wd treatment, the soil samples were scanned using X-ray Computed Tomography (CT) at 50 μm resolution and then sheared under unconsolidated-undrained and consolidated-undrained conditions in a triaxial test. Significant shrinkage and swelling of soil samples were observed during wd cycles, with average volumetric strain fluctuating between +12% at saturation and -5% at the wilting point. X-ray CT visualisation and analysis revealed higher porosity, more prominent pores and increased pore length in soil samples with increasing wd cycles. Both undrained and effective soil shear strength markedly decreased with increasing wd cycles. CT-derived macroporosity and pore length were significant predictors of the soil's undrained and effective shear strength when exposed to wd cycles. The findings emphasise the considerable impact of climate change, specifically wd cycles, on clayey soil, highlighting the need for consideration in the design of earth-based infrastructure.

For the purpose of improve the sustainability of products sold in the EU, Digital Product Passports is a mandatory solution. These passports would systematically gather information about products, such as detailing the materials involved to aid recycling and remanufacturing efforts, or recording the emissions produced throughout the manufacturing process. The overall goal is the establishment of a circular economy in the EU. Current research on Digital Product Passports is focused on collating content for sector-specific applications. However, achieving sustainability goals through Digital Product Passports will require new methods and technical solutions for digital collaboration between supply chain participants, especially in the manufacturing sector. Collaborative work on Digital Product Passports requires trust and traceability in data and access management to ensure privacy over the data contained. One way to enable this securely and confidentially is through the use of blockchain technology, in which stored data cannot be concealed, which is key to the traceability of digital product data documentation. This paper therefore presents a concept for the implementation of generically applicable cross-industry blockchain-based digital product passports. To this end, generic supply chain processes have been abstracted and condensed into the architecture of smart contracts. Great attention is paid to the establishment of traceability as well as privacy through the selection of the blockchain technology Secret Network in combination with Gaia-X functionalities. An illustrative use case for digital product passports in manufacturing is used to demonstrate the applicability of the presented concept. In this use case information about the digital nameplate and carbon footprint is exchanged securely and confidentially in a multi-tenant supply chain network based on the Industry 4.0 infomation model of the Asset Administration Shell.

The spectra and global distributions of the X-ray emissions generated by the solar wind charge-exchange (SWCX) process in the terrestrial magnetosheath are investigated based on a global hybrid model and a global geocoronal hydrogen model. The solar wind O6+ ions which are the primary charge state for oxygen ions in solar wind are considered. The line emissivity of the charge-exchange born O5+ ions are calculated by Spectral Analysis System for Astrophysical and Lab oratory (SASAL). It is found that the emission lines from the O5+ ranges from 105.607 to 118.291 eV with the strong line at 107.047 eV. We then simulated the magnetosheath X-ray emission intensity distributions with a virtual camera at two positions of north pole and dusk at six stages during the passing of a perpendicular interplanetary shock combined with a tangential discontinuity structure through the Earth’s magnetosphere. During this process, the X-ray emission intensity increases with time, and the maximum value is 27.11 keV cm-2 s-1 sr-1 on the dayside, which is 4.5 times that before the solar wind structure reaches the Earth. A clear shock structure can be seen in the magnetosheath and moves earthward. The maximum emission intensity seen at dusk is always higher than that seen at north pole.

Orthohepadnavirus causes chronic hepatitis in a broad range of mammals, including primates, cats, woodchucks, and bats. Hepatitis B virus (HBV) X protein inhibits type-I interferon (IFN) signaling, promoting HBV escape from the innate immune system to establish persistent infection. However, whether X proteins of Orthohepadnavirus viruses in the other species have similar inhibitory activity remains unknown. Here, we investigated the anti-IFN activity of 17 Orthohepadnavirus X proteins derived from various hosts. We observed conserved activity of Orthohepadnavirus X proteins in inhibiting TIR-domain-containing adaptor protein inducing IFN-β (TRIF)-mediated IFN-β signaling pathway through TRIF degradation. X proteins from domestic cat hepadnavirus (DCH), a novel member of Orthohepadnavirus, inhibited mitochondrial antiviral signaling protein (MAVS)-mediated IFNβ signaling pathway comparable with HBV X. These results indicate that inhibition of IFN signaling is conserved in Orthohepadnavirus X proteins.

This article systematically reviews the research achievements on the MnOx/TiO2 catalyst doped with transition metals or rare earth metals for the catalytic selective catalytic reduction of NH3 (SCR-NH3) reaction. The Methodi Ordinatio systematic literature analysis method was employed to rank relevant articles based on journal impact factors, publication years, and citation counts. The ranking data shows that the undoped MnOx/TiO2 catalysts exhibit a catalytic efficiency of up to approximately 90% for NOx reduction, while the doped MnOx/TiO2 catalysts with transition metals or rare earth metals can achieve a maximum reduction efficiency of 100%. Among all the doped metals, the catalyst doped with nickel demonstrates the best NOx reduction performance. The comprehensive literature research concludes that MnOx/TiO2-based SCR catalysts, especially those doped with transition metals or rare earth metals, have significant catalytic efficiency and development potential in reducing NOx emissions in SCR reactions.

The article presents a technology for producing nitrogen-containing nanoporous biocarbon with high degree of elemental composition homogeneity, confirmed by electron spectroscopy. The research explores the relationship among the electronic characteristics of supramolecular nanoporous carbon, its porous structure, and the capacitance at its interface with the electrolyte. The obtained biocarbon is characterized by micro and mesopores, as evidenced by the results of studies by the method of nitrogen adsorption/desorption. The specific area of the available porous surface was found to be 1247 m2/g. Comparing this result with the data of small-angle X-ray scattering, we conclude that micropores are open while mesopores remain closed. This material was found to have a saturation magnetization σs of 1.4 A∙m2∙kg-1 and a coercive force Hc of 10 kA/m. The impedance studies of electrochemical cells of supercapacitors made of the experimental biocarbon were carried out. Equivalent electrical circuits of the studied electrochemical processes were constructed and characterized.

Industrial radiography is a pivotal non-destructive testing (NDT) method that ensures quality and safety in a wide range of industrial sectors. Conventional human-based approaches, however, are prone to challenges in defect detection accuracy and efficiency, primarily due to the high inspection demand from manufacturing industries with high production throughput. To solve this challenge, numerous computer-based alternatives have been developed, including Auto-mated Defect Recognition (ADR) using deep learning algorithms. At the core of training, these algorithms demand large volumes of data that should be representative of real-world cases. However, the availability of digital X-ray radiography data for open research is limited by non-disclosure contractual terms in the industry. This study presents a pipeline that is capable of modeling synthetic images based on statistical information acquired from X-ray intensity distribution from real digital X-ray radiography images. Through meticulous analysis of the intensity distribution in digital X-ray images, the unique statistical patterns associated with the exposure conditions used during image acquisition, type of component, thickness variations, beam divergence, anode heel effect, etc., are extracted. The realized synthetic images were utilized to train deep learning models, yielding an impressive model performance with mean intersection over union (IoU) of 0.93, and mean dice coefficient of 0.96, on real unseen digital X-ray radiography images. This methodology is scalable and adaptable, making it suitable for diverse industrial applications.

Permeability is an important transport property of porous materials, and its accurate evaluation is relevant in studying applied tasks such as CO2 injection into reservoirs and investigating groundwater quality issues. This study examines the dependence of permeability on total and connected porosity, hydraulic tortuosity, specific surface area, and mean pore radius based on the data of 408 cubic sub-volumes extracted from heterogeneous and naturally fractured cylindrical carbonate samples before and after injection of HCl solutions into them. These parameters were computed using pore-scale modeling of fluid flow. It has been shown that permeability correlates well with porosity and mean pore radius with correlation coefficients of R2≈0.65-0.79 for heterogeneous samples. It was found that the presence of natural fractures significantly influenced the relationship between permeability and other parameters. The relationship between permeability k, tortuosity τ, and specific surface area S is described by power laws k~τ-α and k~S-β, with coefficients α and β substantially exceeding those in the Kozeny-Carman equation. It was also found that there is a parabolic relationship between connected and total porosities both before and after rock dissolution with R2≈0.96-0.99. This allowed for estimation of percolation threshold porosity that are in good agreement with the literature data.

X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy resulting from dysfunction of the protein myotubularin encoded by the MTM1 gene. XLMTM has a high neonatal and infantile mortality rate due to a severe myopathic phenotype and respiratory failure. However, in a minority of XLMTM cases, patients present with milder phenotypes and achieve ambulation and adulthood. Regarding wide phenotypic variability, we investigated the genotype-phenotype correlations in newly diagnosed XLMTM patients in a patients' cohort (previously published data plus three novel variants, n=414). We found a significant association between severe phenotype and truncating variants (p < 0.001), frameshift variants (p < 0.001), nonsense variants (p = 0.006), and in/del variants (p = 0.036). On the contrary, missense variants were significantly associated with the mild and moderate phenotype (p < 0.001). We found no significant association between phenotype and the MTM1-specific functional domain, contrasting with previously published data. Based on the significant facial gestalt difference between XLMTM patients and unaffected controls (p = 0.001), we consider the Face2Gene application as an effective diagnostic tool in XLMTM when using the correct algorithm. The Face2Gene application seems to be a practical, non-invasive diagnostic approach in XLMTM.

DFT-D3 calculations based on structural X-ray diffraction data obtained for 3-oxo-camphorsulfonyl imine (1), camphorsulfonyl chloride (2) and seven camphor sulfonimines (O2SNC10H13NR, L1-L7) from which L2 (R=4-OHC6H4), L4 (R=4-ClC6H4) and L6 (R=3,5-(CH3)2C6H3) are new, provide information into the intra and inter molecular interactions with concomitant elucidation of the supramolecular arrangement of the compounds. The DFT D3 calculations performed in small clusters of 2 or 3 molecular units reproduce the interactions observed by X-ray analyses showing that as a general trend the structural arrangement of the molecules is driven by electronic rather than by packing parameters. In all compounds the self-assembly of 3D structures involves the sulfonyl imine group ( NSO2) either to establish hydrogen bonds, through the oxygen atoms or non-classic oxygen-aliphatic hydrogen or non-bonding interactions (NBI) which also involve the sulfonyl oxygens. Interestingly, the camphor sulfonimine compounds (L2, L3) having protic groups (R=C6H4X: X=OH, L2 or X=NH2, L3) at the aromatic imine substituents (=NR) present an extra π-π stacking which is absent in the other compounds aromatic derivatives. The X-ray analysis shows that all the reported camphor sulfonimine compounds display the E configuration with respect to the imine substituent (R). The study of the redox behavior of the compounds by cyclic voltammetry allows an insight into the solution properties of the compounds and the rationalization of the molecular interactions that stand in the solid and solution states. Camphor sulfonimine compounds (L) display appropriate binding atoms to coordinate transition metals. The herein results show that monodentate coordination through the nitrogen atom of the sulfonimine 5-membered ring to the {Ag(NO3)} metal center is favored. When this imine nitrogen atom is not itself involved in the Organic Framework DFT-D3 calculations shows that the complexation does not affect the non-covalent interactions that are reproduced in the MOF structure.

Cytokines are mediators of inflammation that could lead to fibrosis. The aim was to monitor cytokine levels in saliva and serum after locally fractionated radiotherapy of the head and neck in mice and investigate associations with salivary gland fibrosis and hyposalivation. C57BL/6 mice were randomized to sham or X-ray irradiation of 66 Gy in 10 fractions over 5 days. Blood and saliva were collected on day -7, 5, 35, 80 and 105 with following cytokine analysis. The harvested submandibular salivary gland was assessed for presence of fibrosis. Decision tree regression analysis was used to investigate whether cytokine levels could predict late endpoints in terms of hyposalivation or fibrosis. Significant formation of fibrosis in gland tissue and reduced saliva production was found after irradiation. The pro-inflammatory cytokines IL-1α, TNF, TIMP1, G-CSF, KC and MIP-1α showed increased levels in saliva in irradiated mice and strong correlation with late endpoints. The decision tree analysis largely separated controls from irradiated animals with IL-1α being the strongest predictor. Pro-inflammatory cytokines in saliva, but not in serum, were associated with late endpoints. This indicates that cytokine expression in saliva is a good biomarker for local salivary gland damage with IL-1α as the strongest single predictor.

A novel approach based on response surface methodology (RSM) was developed to predict and apply the best extraction conditions for the isolation of various-type polyphenolic antioxidants from the dried flower buds of Magnolia x soulangeana Soul.-Bod. var. ‘Lennei’ (Magnoliaceae). As a method of choice, ultrasound-assisted extraction was used and the optimized extraction parameters (temperature, time of extraction, the composition of aqueous-ethanolic extractants and solvent to solid ratio) have been determined using a central composite design factorial analysis, followed by appropriate spectrophotometric methods (with Folin–Ciocalteu and 2,2-diphenyl-1-picrylhydrazyl reagents) to determine the antioxidant and antiradical potential of extracts, respectively. The use of 66.8% (V/V) ethanol, as the extraction solvent during the 55.2 min extraction protocol, and the ratio of extractant volume to herbal substance of 46.8 mL/g gave the highest total yield of bioactive antioxidant phenolics in the extract obtained. For this herbal preparation, qualitative and quantitative analysis was performed using combined chromatographic (LC), spectroscopic (PDA) and tandem mass spectrometric (ESI-QTOF–MS/MS) techniques. A detailed phytochemical profiling, conducted for the first time, documented substantial amounts of polyphenolic antioxidants, especially phenylethanoids and flavonoids in the flower buds of M. soulangeana ‘Lennei’. Their average total content exceeded 30.3 and 36.5 mg/g dry weight, respectively.

The objective of this study is to clarify the effect of restoring the lowered masticatory muscle functional pressure and correcting the imbalance of bilateral masticatory muscle functional pressure on jawbone growth during growth and development with quantitative evaluation of the changes in micro/nanostructural characteristics of entheses. Male Wistar rats aged 4 weeks were divided into an experimental group injected with a botulinum toxin serotype A (BoNT/A) formulation to reduce muscle function (BTX group) and a control group (CTRL group). They were euthanized after 6, 8, 10, 12, and 16 weeks after measuring the difference between the midline of the upper and lower incisors. The mandibles were harvested for histological examination, second harmonic generation imaging, and quantitative evaluation of biological apatite (BAp) crystal alignment. The midline difference decreased with age in weeks. In rats from 6 weeks after BoNT/A administration to 12 weeks after administration, collagen fibre bundle diameter was significantly smaller in the BTX group; the difference between the two groups decreased with increasing age. BAp crystal alignment was significantly different on the X-axis and the Y-axis on the BTX group from 6 weeks after BoNT/A administration to 10 weeks after administration. Asymmetry of mandibular bone formation caused by load imbalance during growth could be corrected by adjustment of the function of the masseter muscle on either side.

The osseointegration process in and around additively manufactured (AM) lattice structures of a new titanium alloy, Ti–19Nb–14Zr, was evaluated. Three different implants, including lattices with increasing high sidewalls gradually closing them, were designed, manufactured and implanted in the tibia and metatarsal bone of two sheep for twelve weeks. After removal, they were characterized with X-ray computed tomography (XCT). The 3D XCT images were segmented using machine learning. The bone-interface implant (BII) and bone-implant contact (BIC) were studied. The results show that, since AM naturally leads to high roughness surface finish, the wettability of the implant is increased. The new alloy possesses an increased affinity to the bone enhancing the quality of osseointegration. The lattice provides crevices, in which the biological tissue can jump in and cling. The combination of these factors is pushing ossification beyond its natural limits. Therefore, the quality and speed of the ossification and osseointegration in and around these Ti–19Nb–14Zr AM laterally closed lattice implants open the possibility of bone spline key of prostheses. This enables the stabilization of the implant into the bone while keeping the possibility of punctual hooks allowing the implant to be removed more easily if required.

In response to the growing inspection demand exerted by process automation in component manufacturing, Non-destructive testing (NDT) continues to explore automated approaches that utilize deep learning algorithms for defect identification, including within digital X-ray radiography images. This necessitates a thorough understanding of the implication of image quality parameters on the performance of these deep learning models. This study investigates the influence of two image quality parameters, namely Signal-to-Noise Ratio (SNR) and Contrast-to-Noise Ratio (CNR), on the performance of U-net deep learning segmentation model. Input images were acquired with varying combinations of exposure factors such as kilovoltage, milli-ampere, and exposure time, which altered the resultant quality. The data was sorted into 5 different datasets according to their measured SNR and CNR values. The deep learning model was trained 5 distinct times, utilizing a unique dataset for each training session. Training the model with high CNR values yielded an intersection over Union (IoU) metric of 0.9594 on test data of the same category but drops to 0.5875 when tested on lower CNR test data. The result in this study emphasizes the importance of achieving a balance in training dataset according to the investigated quality parameters, to enhance the performance of deep learning segmentation models in NDT radiography applications.

Abstract: As a low-input crop, Miscanthus offers numerous advantages that, in addition to agricultural applications, permits its exploitation for energy, fuel, and material production. Depending on the Miscanthus genotype, season, and harvest time as well as plant component (leaf versus stem), correlations between structure and properties of the corresponding isolated lignins differ. Here, a comparative study is presented between lignins isolated from M. x giganteus, M. sinensis, M. robustus and M. nagara using a catalyst-free organosolv pulping process. The lignins from different plant constituents are also compared regarding their similarities and differences regarding monolignol ratio and important linkages. Results showed that the plant genotype has the weakest influence on monolignol content and interunit linkages. In contrast, structural differences are more significant among lignins of different harvest time and/or season. Analyses were performed using fast and simple methods such as nuclear magnetic resonance (NMR) spectroscopy. Data was assigned to four different linkages (A: b-O-4 linkage, B: phenylcoumaran, C: resinol, D: b-unsaturated ester). In conclusion, A content is particularly high in leaf-derived lignins at just under 70 % and significantly lower in stem and mixture lignins at around 60 % and almost 65 %. The second most common linkage pattern is D in all isolated lignins, the proportion of which is also strongly dependent on the crop portion. Both stem and mixture lignins, have a relatively high share of approximately 20 % or more (maximum is M. sinensis Sin2 with over 30 %). In the leaf-derived lignins, the proportions are significantly lower on average. Stem samples should be chosen if the highest possible lignin content is desired, specifically from the M. x giganteus genotype, which revealed lignin contents up to 27 %. Due to the better frost resistance and higher stem stability, M. nagara offers some advantages compared to M. x giganteus. Miscanthus crops are shown to be very attractive lignocellulose feedstock (LCF) for second generation biorefineries and lignin generation in Europe.

We report herein high-resolution x-ray diffraction measurements of basal plane bending of homoepitaxial single-crystal diamond (SCD). The results reveal that growth parameters such as temperature, growth time and basal plane bending of the substrate affect the basal plane bending of SCD. First, the basal plane bending of SCD depends mainly on the substrate itself. The basal plane bending of SCD becomes more severe with increasing basal plane bending of the substrate and this type of basal plane bending cannot be recovered. The SCD growth experiments show that the basal plane bending increases at high temperature and with increasing growth time. Finally, to understand the mechanism behind basal plane bending, we investigate the substrate-surface temperature distribution as a function of basal plane bending of SCD fabricated by chemical vapour deposition (CVD). This allows us to propose a bending model and understand the origin of basal plane bending. The results indicate that an uneven temperature distribution on the substrate surface is the main cause of the CVD diamond base-plane bending.

In this study, the properties of unsaturated polyester resin were studied in the presence of recycled ceramic waste particles. Herein, composites were created that contained 28.5-50 wt% porcelain particles (particle size <180 µm). High filler contents increased the gel time and decreased the exotherm temperature of unsaturated polyester resin during curing. The obtained results showed that physical parameters, such as the resin density and porosity, increased as the filler content increased. In addition, the X-ray diffraction results indicated that the produced samples were a combination of ceramic waste particles and unsaturated polyester resin, resulting in semi crystalline structure. The results showed that the maximum water absorption at 40°C increased from 0.97 to 1.5% as the filler content increased from 28.5 to 50 wt%; in this process, the materials experienced a color change but did not lose mechanical performance. Finally, the samples were characterized by thermogravimetric analysis (TGA) to study the effect of porcelain powder on the thermal degradation of the resin. The TGA scans were analyzed with the Friedman method. The results indicated that the samples with porcelain powder exhibited substantially better thermal stability than unsaturated polyester resin.

In this research we are reporting gas sensing properties of TiO_2-x/TiO₂-based hetero-structure, which was ‘self-heated’ by current that at constant potential passed through the structure. Amperometric measurements were applied for the evaluation of sensor response towards ethanol, methanol, n-propanol and acetone gases/vapors. The sensitivity towards these gases was based on electrical resistance changes, which were determined by amperometric measurements of current at fixed voltage applied between Pt-based contacts/electrodes deposited on TiO_2-x/TiO₂-based layer. XRD analysis revealed the formation of TiO_2-x/TiO₂-based hetero-structure, which is mainly based on Ti₃O₅/TiO₂ formed during hydro-thermal oxidation based sensing layer preparation process. Additionally, photoluminescence and time-resolved photoluminescence decay kinetics based signals of this sensing structure revealed the presence of TiO₂ mainly in the anatase phase in the TiO_2-x/TiO₂-based hetero-structure, which was formed at 400°C annealing temperature. The evaluation of TiO_2-x/TiO₂-based gas sensing layer was performed at several different temperatures (25°C, 72°C, 150°C, 180°C) and at these temperatures different sensitivity to aforementioned gaseous materials was determined.

As time progresses and technology improves, biological data sets are continuously increasing in size. New methods and new implementations of existing methods are needed to keep pace with this increase. In this paper, we present a high performance computing(HPC)-capable implementation of Iterative Random Forest (iRF). This new implementation enables the explainable-AI eQTL analysis of SNP sets with over a million SNPs. Using this implementation we also present a new method, iRF Leave One Out Prediction (iRF-LOOP), for the creation of Predictive Expression Networks on the order of 40,000 genes or more. We compare the new implementation of iRF with the previous R version and analyze its time to completion on two of the world's fastest supercomputers Summit and Titan. We also show iRF-LOOP's ability to capture biologically significant results when creating Predictive Expression Networks. This new implementation of iRF will enable the analysis of biological data sets at scales that were previously not possible.

The promising antimicrobial activity of essential oils (EOs) led researchers to use them in combination with antimicrobial drugs in order to reduce drug toxicity, side effects, and resistance with single agents. In Pancalieri (Turin, Italy), there is a local production of Mentha x piperita worldwide known as “Mentha of Pancalieri”. The EO from this Mentha is considered as one of the best peppermint EO in the world. In our research, we assessed the antifungal activity of “Mentha of Pancalieri” EO either alone or in combination with azole drugs (fluconazole, itraconazole, ketoconazole) against a wide panel of yeast and dermatophyte clinical isolates. The EO was analyzed by GC-MS and its antifungal properties were evaluated by MIC/MFC parameters, according to the CLSI guidelines, with some modifications. The interaction of peppermint EO with azoles was evaluated through the chequerboard and isobologram methods. Results suggest this EO exerts a fungicidal activity against yeasts, and a fungistatic activity against dermatophytes. Interaction studies with azoles indicate mainly synergistic profiles between itraconazole and peppermint EO vs. Candida spp., Cryptococcus neoformans and Trichophyton mentagrophytes. Peppermint of Pancalieri EO may act as a potential antifungal agent and may serve as a natural adjuvant for fungal infection treatment.

Prolonged high-intensity grinding can modify the crystal structure of solid substances and/or induce chemical reaction, which is referred to as mechanochemical reaction. Such reactions can exert positive influences on hydrometallurgical processes, therefore, many researchers have applied mechanochemical reactions for metals dissolution from minerals. The mechanism of mechanochemical reaction has been investigated using solid analyses and simulations. Structural changes caused by mechanochemical reaction are not yet sufficiently clarified because the ground samples are amorphous. The objective of this study was to analyze structural changes of cerianite in weathered residual rare earth ore by mechanochemical reduction. Structural change was analyzed by x-ray absorption near-edge structure and extended x-ray absorption fine structure analysis at the cerium L_III- and K-edges. These analyses revealed that the structural change of cerianite in this ore induced by mechanochemical reduction involved oxygen vacancy production. The process of the oxygen vacancy formation was closely coupled with the quantum effect of localization–delocalization of the 4f electron of cerium.

The effect of transition metal substitution for Fe and the structural and magnetic properties of Gd2Fe16Ga0.5TM0.5 (TM=Cr, Mn, Co, Ni, Cu, and Zn) compounds were investigated. Rietveld analysis of X-ray diffraction indicates that all the samples crystallize in the hexagonal Th2Ni17 structure. The lattice parameters: a, c and unit cell volume show TM ionic radii dependence. Both Ga and TM atoms show preferred site occupancy for 12j and 12k sites. The saturation magnetization at maximum room temperature was observed for Co, Ni, and Cu of 69, 73, and 77 emu/g, respectively while minimum value was observed for Zn (62emu/g) doping Gd2Fe16Ga0.5TM0.5. Highest Curie temperature of 590 K was observed for Cu doping which is 15% and 5% and thesehigher than Gd2Fe17 and Gd2Fe16Ga compounds, respectively. The hyperfine parameters viz. hyperfine field and isomer shift, show systematic dependence on the TM atomic number. The observed magnetic and Curie temperature behavior in Gd2Fe16Ga0.5TM0.5 is explained on the basis of Fe(3d)-TM(3d) hybridization. The superior Curie temperature and magnetization value of Co, Ni, and Cu doped Gd2Fe16Ga0.5TM0.5 compounds as compared to pure Gd2Fe17 or Gd2Fe16Ga makes Gd2Fe16Ga0.5TM0.5 a potential candidate for high-temperature industrial magnet applications.

In this paper, we propose an adaptive duty-cycled hybrid X-MAC (ADX-MAC) protocol for energy-efficient forest fire prediction. The X-MAC protocol acquires the additional environmental status collected by each forest fire monitoring sensor for a certain period. And, based on these values, the length of sleep interval of duty-cycle is changed to efficiently calculate the risk of occurrence of forest fire according to the mountain environment. The performance of the proposed ADX-MAC protocol was verified through experiments the proposed ADX-MAC protocol improves throughput by 19% and was more energy-efficient by 24% compared to X-MAC protocol. As the probability of forest fires increases, the length of the duty cycle is shortened, confirming that the forest fires are detected at a faster cycle.

This paper reports on the production and mechanical properties of Ti6Al4V micro-lattice structures, with strut thickness nearing the single-track width of the laser-based powder bed fusion (LPBF) system used. Besides providing new information on the mechanical properties and manufacturability of such thin-strut lattices, this paper also reports on the in-situ deformation imaging of micro-lattice structures with 6 unit cells in every direction. LPBF lattices are of interest for medical implants, due to the possibility of creating structures with an elastic modulus close to that of the bones and small pore sizes which allow effective osseointegration. In this work four different cubes were produced by laser powder bed fusion and subsequently analyzed using microCT, compression testing and one selected lattice was subjected to in-situ microCT imaging during compression. The in-situ imaging was performed at 4 steps during yielding. The results indicate that mechanical performance (elastic modulus and strength) correlate well with actual density and that this performance is remarkably good, despite the high roughness and irregularity of the struts at this scale. In-situ yielding is visually illustrated.

This work explores the use of Kuhn verdazyl radicals as building blocks in multifunctional molecular materials in an exemplary study, focusing on the magnetic and the electron transfer (ET) characteristics, but also addressing the question whether chemical modification by cross-coupling is possible. The ET in solution is studied spectroscopically whereas solid state measurements afford information about the magnetic susceptibility or the conductivity of the given samples. The observed results are rationalized based on the chemical structures of the molecules, which have been obtained by X-ray crystallography. The crystallographically observed molecular structures as well as the interpretation based on the spectroscopic and physical measurements are backed up by DFT calculations. The measurements indicate that only weak, antiferromagnetic coupling is observed in Kuhn verdazyls owed to the low tendency to form face-to-face stacks, but also that steric reasons alone are not sufficient to explain this behavior. Furthermore, it is also demonstrated that ET reactions proceed rapidly in verdazyls/verdazylium redox couples and that Kuhn verdazyls are suited as donor molecules in ET reactions.

The current report contributes to the understanding of the stereoselectivity of the chiral dirhodium(II) carboxylate catalysts derived from N-protected amino acid ligands. Investigating the possible effect of ligand stereo-purity on catalyst structure and enantioselectivity was carried out. This was justified through a new X-ray crystal structure for Rh2(S,S,S,R-PTTL)4 diastereomer.

A gold(I) complex with a triphenylphosphine and a monodentate N,N-dimethyldithiocarbamate ligand was synthesized and characterized by Raman spectroscopy and single crystal X-ray diffraction. DFT calculations (Gaussian 09, PBE1PBE/Lanl2dz) were undertaken for a single complex in the gas-phase. The DFT-optimized structure is in good agreement with the crystal structure and the DFT-calculated Raman spectrum also is in excellent agreement with the experimental spectrum. Assignments of the Raman peaks are based on these DFT calculations. Frontier molecular orbitals were calculated and their nature is discussed.

Histone deacetylase inhibitors (HDACis) are being recognized as a potentially effective treatment approach for peripheral T-cell lymphoma (PTCL), which is a diverse group of aggressive lymphomas with a bleak prognosis. Recent evidence has shown that HDACi are effective in treating PTCL, especially in cases where the disease has relapsed or is resistant to other treatments, and there are few available options. Several clinical trials have demonstrated that HDACi, such as romidepsin and belinostat, can elicit long-lasting positive outcomes in individuals with PTCL, either when used alone or in conjunction with conventional chemotherapy. They exert their anti-tumor actions by regulating gene expression through inhibiting histone deacetylases, which results in the halting of cell division, programmed cell death, and the transformation of cancerous T-cell, as indicated by gene expression profile studies. Importantly, besides clinical trials, real-world evidence indicated that the utilization of HDACi presents a significant and beneficial treatment choice for PTCL. However, although HDACi showed potential effectiveness, they couldn’t cure most patients. Therefore, new combination with conventional drugs as well as new targeted agents are under investigation.

Background/Objectives Immune effector cell-associated hematotoxicity (ICAHT) is a frequent adverse event after chimeric antigen receptor (CAR)-T cell therapy. Grade ≥3 thrombocytopenia occurs in around one third of patients, many of whom become platelet transfusion-dependent. Without pharmacological support, platelet recovery may last for months. Eltrombopag is a thrombopoietin receptor agonist (TPO-RA) able to accelerate megakaryopoiesis, which has been used successfully in patients with bone marrow failure and immune thrombocytopenia (ITP.) Its role to manage thrombocytopenia, and other cytopenias, in CAR-T cell-treated patients has been scarcely addressed in the real-world setting. Our aim was to report the Feasibility of this approach and the outcome of patients included in the GETH-TC registry. Methods This is a retrospective, multicenter, observational study. Patients who developed platelet transfusion-dependence subsequently to CAR-T cell treatment were recruited in 10 Spanish hospitals and followed-up for at least 30 days after the first dose of eltrombopag was administered. Results Thirty-eight patients were enroled and followed-up for a median (interquartile range [IQR]) of 175 (99, 489) days since CAR-T cell infusion. At eltrombopag start, 18 patients had thrombocytopenia and another severe cytopenia, while 8 patients had severe pancytopenia. After 32 (14, 38) days on eltrombopag, 29 (76.3%) patients recovered platelet transfusion independence. The number of platelet units used correlated with the time needed to restore platelet counts to levels ³20x10⁹/L (Rho = 0.639, p <0.001). Non-responders to eltrombopag required more platelet units (58 [29, 69] vs. 12 [6, 26] in responders, p = 0.002). Nineteen out of 23 (82.6%) patients recovered from severe neutropenia after 22 (11, 31) days on eltrombopag. Twenty-nine out of 35 (82.9%) patients recovered red blood cell (RBC) transfusion independence after 29 (17, 44) days. Seven patients recovered all cell lineages while on treatment. No thromboembolic events were reported. Only 2 transient toxicities (cholestasis, hyperbilirubinemia) were reported during eltrombopag treatment, none of which compelled permanent drug withdrawal. Conclusions Eltrombopag can be safely used to manage thrombocytopenia and accelerate transfusion independence in CAR-T cell-treated patients.

For monitoring of chimeric antigen receptor (CAR) T-cell therapies antigen-based CAR detection methods are usually applied. However, for each target-antigen a separate detection system is required. Furthermore, when monitoring CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods producing false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment, promise an universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19 targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection by using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel the sensitivity was significant lower compared to antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel or Ide-cel, respectively. Cilta-cel (containing an monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but not universal applicable.

Before the emergence of SARS-CoV-1, MERS-CoV, and most recently SARS-CoV-2, al-ready four other coronaviruses have been circulating in the human population. The alpha coronaviruses NL63 and 229E and the beta coronaviruses OC34 and HKU1. These circulating coronaviruses all cause mild respiratory illness during the winter seasons and most people are already infected in early life. Could antibodies and/or T cells, es-pecially against the beta coronaviruses have offered some form of protection against SARS-CoV-2? Related is the question whether survivors of SARS-CoV-1 or MERS-CoV would be relatively protected against SARS-CoV-2. More importantly, would humoral and cellular immunological memory, generated during the SARS-CoV-2 pandemic, ei-ther by infection or vaccination offer protection against future coronaviruses? Or rather than protection, could antibody dependent enhancement have taken place, a mecha-nism by which circulating corona antibodies enhance the severity of COVID-19? An-other related phenomenon, the original antigen sin, would also predict that the effec-tivity of the immune response to future coronaviruses would be impaired because of reactivation of memory against irrelevant epitopes. Current available evidence indicates that latter scenarios are highly unlikely and that especially cytotoxic memory T cells directed against conserved epitopes of human coronaviruses could at least offer partial protection against future coronaviruses.

Targeted cancer therapy has grown exponentially in the last decade, representing the largest frontier in the modern concept of precision medicine. This renaissance is largely due to our rapidly evolving ability to biochemically harness our immune systems to target cancer-specific antigens. Combined with an increasing armamentarium of surgical and non-invasive techniques for cancer mitigation we have upgraded cancer therapy from a non-specific assault on cell-division to a multi-modal, targeted approach. This renaissance has resulted in an increase in the perioperative footprint of patients with advanced cancer. The scope of the perioperative clinician has evolved from one of passive/reactive management of complications to a proactive approach that starts in the preoperative optimization phase and continues into the postoperative period. The perioperative world should not exist in a silo, and thus involvement of the oncology team is paramount. To provide safe oncologic care, it is essential to be up to date in newer cancer therapies, lest we act on erroneous and/or outdated information. Oncologists should weigh in on immune status, recent chemotherapeutic exposures, and potentially evolving toxicities. These might involve critical changes to perioperative infectious prophylaxis, steroid administration, and coagulopathy management. First, patients living beyond the typical life-expectancy for their cancer will carry a high burden of cancer-related downstream effects. General metabolic issues will include malnutrition, cachexia, and gastric outlet obstruction. Severe protein-calorie malnutrition, as well as hepatic and renal dysfunction can impact the metabolism and clearance of drugs. The cardiovascular, endocrinologic, pulmonary, and central nervous system implications of new cancer therapies will be discussed extensively below. Second, we have to enhance our ability to manage a cancer population who may be experiencing increasing novel chemotherapeutic toxicities. Newer agents differ from historical agents, which were blunt-force tools aimed at nonspecific destruction of cell-division. These drugs are efficacious but physiologically costly. Newer immunogenic therapies have a slightly improved acute safety profile, and a more complex chronic toxicity profile that may be overt or insidious. Chronic toxicities can present overtly or as a smoldering undertone to other active medical conditions such as sepsis, pneumonia, failure to thrive, or renal failure. The new therapies discussed in this review occur in the context of an overall increasingly multi-faceted cancer care machine. An example is screening for esophageal cancer in patients with Barrett's esophagus, or periodic chest CTs for patients with a strong history of tobacco use. These interventions are more likely to detect disease while it is still resectable, and resections will commonly accompany neo-adjuvant therapy. These approaches commonly involve new immunotherapies whose efficacy is higher-yield with a lower disease burden. In a recent example, the immune-checkpoint inhibitors (ICIs) ipilimumab plus nivolumab have significantly increased survival rate for squamous cell esophageal cancer when combined with standard chemotherapy. Surgical resection has evolved to one that often accompanies neoadjuvant chemo and radiation. The increasing efficacy of this approach may de-necessitate many major resections, and increase the number of sub-anatomic resections and minimally invasive procedures. Improved techniques - notably for hepatectomy, whipple procedure, prostatectomy, nephrectomy - have increased the safety profile and decreased the perioperative physiologic burden. This has enabled a broader subset of patients (due to cancer burden or due to medical comorbidities) to qualify for the operation, and increased the involvement of anesthesia and their perioperative services. With an increase in surgical candidacy comes an increase in post-surgical complications, and post-surgical maintenance such as drains, embolizations, imaging studies, etc. In the non-OR anesthesia realm, there have been considerable advancements in cancer “micro-treatments” such as hepatic metastasis embolization, tumor ablation, and peri-tumor vascular embolization. There are an ever-increasing number of IR-guided embolizations for bleeding tumors, aspiration of malignant effusions, and drainage of abscesses. This review serves to provide insight into new categories of chemotherapy and their perioperative implications.

Hepatocellular carcinoma (HCC) is one of the most common cancers and the main cause of cancer-related death globally. Immune dysregulation of CD4+ T cells has been identified as a role in the development of HCC. Nevertheless, the underlying molecular pathways of CD4+ T cells in HCC are not completely known. Thus, a better understanding of the dysregulation of lncRNA-miRNA/mRNA network might yield novel insights into the etiology or progression of HCC. In this study, circulating CD4+ T cells were isolated from the whole blood of 10 healthy controls and 10 HCC patients for next-generation sequencing of the expression of lncRNAs, miRNAs, and mRNAs. Our data showed that there was different expression of 34 transcripts (two lncRNAs, XIST and MIR222HG, 29 mRNA, and 3 other types of RNA) and 13 miRNAs in the circulating CD4+ T cells of HCC patients. The expression of the lncRNA XIST-related miRNAs and their target mRNAs was confirmed using real-time quantitative polymerase chain reaction (qPCR) on samples from 100 healthy controls and 60 HCC patients. The lncRNA–miRNA/mRNA regulation network was created using interaction data generated from ENCORI and revealed there are positive correlations in the infiltration of total CD4+ T cells and negative correlations in the infiltration of Th1 CD4+ T cells.

Keywords: Hypertensive emergency; diagnosis; lactate dehydrogenase; high sensitivity cardiac troponin T; brain natriuretic peptide; area under the curve.

Six-Transmembrane Epithelial Antigen of the Prostate 1-4 (STEAP1-4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. Thus far, five homologs are known: STEAP1, STEAP1B, STEAP2, STEAP3, and STEAP4. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed while STEAP3 expression is downregulated. Although the metalloreductase activities of STEAP1-4 are well-documented, their other biological functions are not. Furthermore, the properties and expression levels of STEAP heterotrimers, homotrimers, heterodimers, and homodimers are not well-understood. Nevertheless, studies over the last few decades have provided sufficient impetus to investigate STEAP1-4 as potential biomarkers and therapeutic targets for prostate cancer. In particular, STEAP1 is the target of many emerging immunotherapies. Herein, we give an overview of the structure, physiology, and pathophysiology of STEAP1-4 to provide context for past and current efforts to translate STEAP1-4 into the clinic.

New setting is introduced to study co-neighborhood, neutrosophic t-neighborhood, neutrosophic quasi-vertex set, neutrosophic quasi-order, neutrosophic neighborhood, neutrosophic co-t-neighborhood, neutrosophic quasi-edge set, neutrosophic quasi-size, Neutrosophic number, neutrosophic co-neighborhood, co-neutrosophic number, quasi-number and quasi-co-number. Some classes of neutrosophic graphs are investigated.

Among the biggest challenges facing the contemporary human condition, and therefore also education, is responding to the climate crisis. The source of the crisis is assumed to be absent-mindedness, presented by Leslie Dewart as a distortion of the development of human consciousness. Dewart's poorly-known philosophical consciousness study is presented in this paper in broad outline. The problems in the study of consciousness, the most important of which are the qualitative representations – qualia – and the question of free will, are also briefly discussed. These problems are then examined transcendental analytically, with the question of what one must assume in order to allow the emergence of these phenomena. From the resulting conception of causal relationship, we proceed to the circular causality as a prerequisite for life, namely the homeostatic systems and negative feedback. An organization of action that is essential to animals and humans is presented, using William Powers’ perceptual control theory (PCT), and the role of consciousness in this organization is drafted according to the studies of Martin Taylor. Action is seen as continuous problem solving, in which negative feedback is used to bring perceptions into line with the goals. The fundamental function of consciousness is revealed as the direction and enhancement of learning. Based on PCT, it can be shown that the main practical problems in animal and, especially, human action, are related to adverse side effects of action and the resulting various conflicts. The climate crisis is a typical example of the problematic side effects of collective action. Dewart's concept of absent-mindedness can therefore be defined as an inability to responsibly account for the side effects of action. Thus, the main task of education is to forestall, through negative feedback and in cooperation with learner consciousness, absent-mindedness and the problems it causes.

Black hole collision produce gravitational radiation which is generally thought in a quantum limit to be gravitons. The stretched horizon of a black hole contains quantum information, or a form of quantum hair, which in a coalescence of black holes participates in the generation of gravitons. This may be facilitated with a Bohr-like approach to black hole (BH) quantum physics with quasi-normal mode (QNM) approach to BH quantum mechanics. Quantum gravity and quantum hair on event horizons is excited to higher energy in BH coalescence. The near horizon condition for two BHs right before collision is a deformed AdS spacetime. These excited states of BH quantum hair then relax with the production of gravitons. This is then argued to define RT entropy given by quantum hair on the horizons. These qubits of information from a BH coalescence should then appear in gravitational wave (GW) data. This is a form of the standard AdS/CF T correspondence and the Ryu-Takayanagi (RT) formula [1]. The foundations of physics is proposed to be quantum information and a duality between spacetime observables and quantum fields.

This study investigated whether biogas reactor performance, including microbial community development, in response to a change in substrate composition is influenced by initial inoculum source. Test reactors were first started with two different inocula and operated with the same grass-manure mixture for more than 120 days. These reactors initially showed great differences depending on inoculum source, but eventually showed similar performance and overall microbial community structure. At the start of the present experiment, the substrate was complemented with milled feed wheat, added all at once or divided into two portions. The starting hypothesis was that process performance depends on initial inoculum source and microbial diversity, and thus that reactor performance is influenced by the feeding regime. In response to the substrate change, all reactors showed increases and decreases in volumetric and specific methane production, respectively. However, specific methane yield and development of the microbial community showed differences related to initial inoculum source, confirming the hypothesis. The different feeding strategies had however only minor effects on process performance and overall community structure, but still induced differences in the cellulose-degrading community and in cellulose degradation.

The effectiveness of a hybrid technique for identifying seismic damage in planar, multistory, steel X or V-braced frames is demonstrated here through an example of a six-story frame. This proposed technique, referred to as “M and P”, combines the instrumental Monitoring (M) with Pushover analysis (P). According to the methodology, the diagram of stepping eigenfrequencies of the frame in the inelastic region is initially plotted against seismic roof displacement. The fundamental natural frequency detected via the monitoring process is then utilized in this key diagram to reveal the inelastic roof displacement that corresponds to the damage state of the steel braced frame. This displacement is subsequently used as the target in the pushover analysis, facilitating the identification of seismic damage in the existing steel braced frame. Finally, the damage image is correlated with the damage stiffness matrix of the frame at the same inelastic roof displacement. The investigation results indicate that combining instrumental monitoring with pushover analysis enables accurate identification of seismic damage potential in existing steel braced frames.

The ACEtabular rim eXtension (ACE-X) implant is a custom-made 3-dimensional-printed titanium device designed for the treatment of canine hip dysplasia. Thirty-four dogs (61 hips) underwent ACE-X implantation, and assessments were conducted using computed tomography, force plate analysis, Ortolani’s test, and Helsinki Chronic Pain Index (HCPI) questionnaires at five intervals: pre-operative day, surgery day, 1.5-month, 3-month, and 12-month follow-up. Statistically significant increases in femoral head coverage with negative Ortolani subluxation test were observed immediately after surgery and persisted throughout the study. Osteoarthritis (OA) scores remained stable, but osteophyte size significantly increased between the surgery day and the 12-month follow-up, especially in hips with a baseline OA score of 2 compared to those with a score of 1. Force plate data showed no significant changes during the study. The HCPI demonstrated a significant decrease in pain score from pre-operative value to 6-week follow-up and gradually decreased over time. Major complications were identified in 6 hips (9.8%) of 4 dogs. In conclusion, the ACE-X implant effectively increased femoral head coverage, eliminated subluxation, and provided long-term pain relief with minimal complications, benefiting over 90% of the study population. The study supports the ACE-X implant as a secure and valuable treatment for canine hip dysplasia.

Chitosan (CS) nanoparticles are under investigation for a wide range of applications in nanomedicine. The structural, molecular and physicochemical properties of chitosan nanoparticles have a direct bearing on their efficacy in drug conjugation and delivery, gene delivery, and tissue engineering. Herein we report on the structural, morphological and molecular properties of chitosan nanoparticles synthesized using the ionic gelation method with the intended purpose of being used for drug delivery. The chitosan nanoparticles (CS-NPs) were prepared in the 0.25 to 1.0% w/v concentration range, whereas separate samples of the 1.0% w/v CS-NPs were also functionalized with polyethylene oxide (PEO) alone and with a diblock copolymer of PEO and polypropylene glycol (PPG). The average size of the CS-NPs was determined from TEM imaging to be in the range of 11.3 to 14.8 nm. The XRD and TEM analyses show that the CS-NPs have semi-crystalline structure with the degree of crystallinity depending upon the nature of synthesis. Our results show that functionalizing the 1.0% w/v CS-NPs with PEO increases the degree of crystallinity whereas functionalizing with the diblock copolymer PEO - PPG results in a significant increase in their degree crystallinity. The CS/TPP concentration (CS:TPP fixed at 1:1 ratio) had no apparent effect on the degree of crystallinity of the CS-NPs. The results from the FTIR analysis confirm incorporation of TPP with CS in the CS-NPs. Additionally, FTIR analysis shows an enhancement of hydrogen bonding that is consistent with the increase in the degree of crystallinity of the CS-NPs.

A hydrothermal technique with microwave heating (200 °C, 2 hours, 2 magnetrons, 2.45 GHz) was modified to obtain UV-C luminescent LaPO4: Pr3+ colloidal nanorods for the potential use in X-ray cancer theranostics. For further possible biofunctionalization, a compound of tartaric acid formed under basic conditions was used as a coating and stabilizing agent to provide colloidal properties to the surface of nanoparticles in basic to neutral aqueous media, which was confirmed by zeta potential measurements. In addition, the colloidal properties and clustering processes of synthesized LaPO4:Pr3+ nanorods in aqueous solutions with different pH values were studied in real time using a highly sensitive laser ultramicroscope operating according to the “light-sheet” scheme. A comparative analysis of the transmission electron microscopy, X-ray powder diffraction and high-energy spectroscopy showed the different effects of synthesis parameters on the morphological, crystalline and luminescent properties of the obtained nanorods. Through optimization of the synthesis parameters, stable aqueous solutions of m-LaPO4:Pr3+ nanorods with sizes less than 30 nm and an intensity of UV-C luminescence equal to 5-10% of the unmodified nanofibers were obtained.

The radiation stability of polymer test objects fabricated by direct laser writing is studied. The two groups of 6 cubes (50×50×50 μm3) were printed on a common silicon substrate. 6 cubes were irradiated with X-rays in the synchrotron radiation beam (12 keV, 1010 photons/mm2/s), the other 6 kept non-irradiated for the reference. In each group, the fabrication parameters (laser power and slicing step) were uniformly varied from cube to cube. Each irradiated cube was exposed with the dose of 1013 X-ray photons. The calibration of this dose in the radiological units (Gy) was carried out using the tissue-equivalent thermoluminescent detectors (TLD-800). The corresponding exposition dose was estimated as 30 kGy for each cube. The radiation effects were evaluated by Raman spectroscopy and by morphological changes observed with the raster electron microscope. The primary radiation effect appears in the essential increase of the polymerization degree with consuming carbon-carbon double bonds in favor of the polymer cross-linking. Only one cube of 6 has changed the size and shape due to this effect, while the others retained the initial shape. Morphological changes are connected with the improper fabrication parameters (laser power and slicing step). Properly fabricated objects withstand the X-rays of the synchrotron radiation beam.

Contrast agents developed for X-ray computed tomography (CT) offer extremely valuable tools and techniques in diagnostics via contrast enhancements. Heavy metal-based nanoparticles (NPs) can provide high contrast in CT images. These result from a high density of heavy metal atoms with high X-ray attenuation coefficients that exceed that of iodine (I), which is currently used in hydrophilic organic CT contrast agents. Nontoxicity and colloidal stability are vital characteristics in designing heavy metal-based NPs as CT contrast agents. In addition, the particle size must be small for in vivo renal excretion. In vitro phantom imaging studies can provide X-ray attenuation efficiency, which is a critical parameter for CT contrast agents, and the imaging performance of CT contrast agents can be demonstrated via in vivo experiments. This review focuses on in vitro and in vivo studies of various heavy metal-based NPs (metal: Au, Pt, Pd, Ag, Ce, Gd, Dy, Ho, Yb, Ta, W, and Bi) and provides an outlook on their use as high-performance CT contrast agents.

Three-layer structures based on various multi-component films of III–V semiconductors heavily doped with Fe were grown by pulsed laser sputtering of InSb, GaSb, InAs, GaAs and Fe solid targets. The structures comprising InAsSb:Fe, InGaSb:Fe and InSb:Fe layers with Fe concentrations up to 24 at. % separated by GaAs spacers were deposited on (001) i-GaAs substrates at 200ºC. Transmission electron microscopy showed that the structures have a rather high crystalline quality and do not contain secondary-phase inclusions. X-ray photoelectron spectroscopy investigations revealed significant diffusion of Ga atoms from the GaAs regions into the InAsSb:Fe layers, which has led to the formation of an InGaAsSb:Fe compound with a Ga content up to 20 at. %. It has been found that the ferromagnetic properties of the InAsSb:Fe magnetic semiconductor improve with increasing Sb:As ratio. It has been concluded that the indirect ferromagnetic exchange interaction between Fe atoms occurs predominantly via Sb atoms.

Optimum design and accurate control of the internal structure of the laser target materials remain an important goal for various laser physics experiments, especially for generating high flux photon and neutron beams. The low-density material is considered to be one of the most difficult for X-ray study due to its high transparency and imperceptible contrast. To produce clear visualization of foam containing sparse structures we used a high-quality monochromatic X-ray beam of synchrotron radiation source PETRA-III at DESY. The X-ray beam parameters allow tomographic scanning with application of phase contrast retrieval algorithms. A series of 3D images of foam-suspended glass microsphere inside the plastic cylinder were obtained with the quality high enough to observe the internal structure and to visualize uniformity, displacement and surface roughness on both sides of the microsphere. The main object under investigation was a CH-plastic capillary including 10 mg/cc CHO-foam with the centered glass microsphere. The results of this work demonstrate that tomographic visualization based on a high quality X-ray radiation and phase contrast analysis is an effective and useful technique for development of new laser targets containing structured low density materials.

Serial femtosecond crystallography (SFX) using an X-ray free-electron laser (XFEL) enables determination of room-temperature structures without causing radiation damage. Using an optical pump-probe or mix-and-injection, SFX enables the intermediate state visualization of a molecular reaction. In SFX experiments, serial and stable microcrystal delivery to the X-ray interaction point is vital for reasonable data collection and efficient beam time. The Pohang Accelerator Laboratory X-ray Free Electron Laser (PAL-XFEL) facility established SFX instruments at a nanocrystallography and coherent imaging (NCI) experimental station. Various sample delivery methods, including injection, fixed-target scanning, and hybrid methods, have been developed and applied to collect XFEL diffraction data. Herein, we review the currently available sample delivery methods for SFX at the NCI experimental station at the PAL-XFEL. This article will help PAL-XFEL users access the SFX system for their experiments.

The X-linked FMR1 gene contains a non-coding trinucleotide repeat in its 5’ region that in normal, healthy individuals contains 20-44 copies. Large expansions of this region (>200 copies) cause fragile X syndrome (FXS), but expansions of 55-199 copies (referred to as premutation alleles) predispose carriers to a neurodegenerative disease called fragile X-associated tremor/ataxia syndrome (FXTAS). The cytopathological mechanisms underlying FXTAS are poorly understood, but abnormalities in mitochondrial function are believed to play a role. We previously reported that lymphoblastoid cell lines (LCLs, or lymphoblasts) of premutation carriers have elevated mitochondrial respiratory activities. In the carriers, especially those not clinically affected with FXTAS, AMPK activity was shown to be elevated. In the FXTAS patients, however, it was negatively correlated with brain white matter lesions, suggesting a protective role in the molecular mechanisms. Here we report an enlarged and extended study of mitochondrial function and associated cellular stress-signalling pathways in lymphoblasts isolated from male and female premutation carriers, regardless of their clinical status, and healthy controls. The results confirmed the elevation of AMPK and mitochondrial respiratory activities and reduction of reactive O2 species (ROS) levels in premutation cells and revealed for the first time that TORC1 activities are reduced. Extensive correlation, multiple regression and Principal Components analysis revealed the best fitting statistical explanations of these changes in terms of the other variables measured. These suggested which variables might be the most “proximal” regulators of the others in the extensive network of known causal interactions amongst the measured parameters of mitochondrial function and cellular stress signalling. In the resulting model, the premutation alleles activate AMPK and inhibit both TORC1 and ROS production, the reduced TORC1 activity contributes to activation of AMPK activation and of nonmitochondrial metabolism, and the higher AMPK activity results in elevated catabolic metabolism, mitochondrial respiration and ATP steady state levels. In addition the results suggest a separate CGG repeat number-dependent elevation of TORC1 activity that is insufficient to overcome the inhibition of TORC1 in premutation cells, but may presage the previously reported activation of TORC1 in FXS cells.

In laser joining of copper (Cu) and aluminum (Al) sheets, the Al sheet is widely chosen as the top surface for laser irradiation because of increased absorption of laser beam and lower melting temperature of Al in contrast to Cu. This research focus on welding from Cu side to Al sheet. The main objective of irradiating the laser beam from the copper side (Cu on top) is to exploit higher solubility of Al in Cu. A significantly lower laser power can be used with 515 nm laser in comparison to 1030 nm. In addition to low laser power, a stable welding is obtained with 515 nm. Because of this advantage, 515 nm is selected for the current research. By fusion of Cu and Al the two sheet metals are welded, with presence of beneficial Cu solid solution phase and Al+Al2Cu in the joint with the brittle phases intermixed between the ductile phase. Therefore the mixed composition strengthens the joint. However excessive mixing leads to formation of more detrimental phases and less ductile phases. Therefore optimum mixing must be maintained. Energy dispersive X-ray spectroscopy (EDS) analysis indicate that large amount of beneficial Cu solid solution and Al rich phases is formed in the strong joint. From the tensile shear test for a strong joint, fracture is obtained on the heat-affected zone (HAZ) of Al. Therefore the key for welding from copper side is to have optimum melt with beneficial phases like Cu and Al+ Al2Cu and the detrimental phases intermixed between the ductile phases

Different contact materials along with optimization of the deposition techniques expand the possibilities to obtain high performance room temperature CdTe-based X/γ-ray detectors. The heterostructures with ohmic (MoOx) and Schottky (MoOx, TiOx, TiN, and In) contacts, created by DC reactive magnetron sputtering and vacuum thermal evaporation, as well as In/CdTe/Au diodes with a p-n junction, formed by laser-induced doping, were developed and investigated. Depending on the pre-treatment of the surface of semi-insulating p-CdTe crystals, deposition of a MoOx film formed an ohmic or Schottky contact. Based on the calculations and IV characteristics of the fabricated Mo-MoOx/р-CdTe/MoOx-Mo, In/CdTe/MoOx-Mo, Ti-TiOx/р-CdTe/MoOx-Mo, and Ti-TiN/р-CdTe/MoOx-Mo Schottky-diode detectors, the current transport processes were described in the models of the carrier generation-recombination within the space-charge region (SCR) at low bias voltages, and space-charge limited current at higher voltages, respectively. The energies of generation–recombination centers, density of trapping centers, and carrier lifetimes were determined. A sharp increase in the reverse current in the Mo-MoOx/р-CdTe/MoOx-Mo, Ti-TiOx/р-CdTe/MoOx-Mo, and Ti-TiN/р-CdTe/MoOx-Mo heterostructures at high bias was discussed in frames of the Poole–Frenkel emission model. Nanosecond laser irradiation of the In electrode, pre-deposited on the p-CdTe crystals, resulted in an increase in the voltage range, corresponding to the carrier generation-recombination in the SCR, in the IV characteristics of the In/CdTe/Au diodes. Such In/CdTe/Au p-n junction diodes demonstrated high energy resolutions (7%@59.5 keV, 4%@122 keV, and 1.6%@662 keV).

Classical k-ratio models, e.g. ZAF and phi(rho z), used in electron probe microanalysis (EPMA) assume a homogeneous or multi-layered material structure, which essentially limits the spatial resolution of EPMA to the size of the interaction volume where characteristic x-rays are produced. We present a new model for characteristic x-ray emission that avoids assumptions on the material structure to not restrict the resolution of EPMA a-priori. Our model bases on the spherical harmonic (PN) approximation of the Boltzmann equation for electron transport in continuous slowing down approximation. PN models have a simple structure, are hierarchical in accuracy and well-suited for efficient adjoint-based gradient computation, which makes our model a promising alternative to classical models in terms of improving the resolution of EPMA in the future. We present results of various test cases including a comparison of the PN model to a minimum entropy moment model as well as Monte-Carlo (MC) trajectory sampling, a comparison of PN-based k-ratios to k-ratios obtained with MC, a comparison with experimental data of electron backscattering yields as well as a comparison of PN and Monte-Carlo based on characteristic X-ray generation in a three-dimensional material probe with fine structures.

Concern over potential antimony mediated toxicity from mining and smelting activities has instigated novel concepts toward removing aqueous antimony ions. The iron based adsorbent Fe3O4/HCO was found to be efficient for treating antimony-containing wastewater However, ineffective methodology for preparation limited its effective adsorption capacity and thus wider application. In this study, a new type of HCO-doped-(Fe3O4)x adsorbent was prepared by co-precipitation method for doping Fe3O4 into HCO sludge (HCO), thereby improving adsorption performance for Sb(III) and Sb(V) ions, with the maximum adsorbing capacity being 44.46 mg/g and 47.91 mg/g, respectively. According to the results of BET, SEM-EDS, XRD and XPS, it were confirmed that the FeOOH and X≡Fe-OH were formed during the preparation process, bring about the increased the surface area, thus resulting in further increase of surface area, hydroxyl groups and the net negative ionic charge. Moreover, the adsorption kinetics followed the pseudo-second-order kinetic model which indicated that adsorption process of Sb(III)/Sb(V) by HCO-doped-(Fe3O4)x adsorbent was controlled by chemical reaction. The main adsorption mechanism is that antimony ion and amorphous iron oxide X≡Fe-OH undergo coordination exchange reaction and complexation reaction with CeO2 or Ce2O3. Furthermore, HCO-doped-(Fe3O4)x could adapt to wide pH and had stable adsorption ability after regeneration. The good adsorption performance of HCO-doped-(Fe3O4)x makes it a potential applications of adsorbent for removal of antimony.

Recently the use of food by products as natural sources of biologically active substances has been extensively investigated especially for the development of functional foods fortified with natural antioxidants. Due to their content of bioactive compounds, such as carotenoids, flavonoids and limonoids, Citrus peels could be suitable to formulate enriched olive oils able to boost a healthy nutrition. The aim of this study was: (i) to determine the compositional and sensory profiles of the Citrus olive oil and (ii) to evaluate its nutraceutical properties in rats with high fat diet-induced-metabolic syndrome and oxidative stress. The results obtained show the potential of using the Citrus peels as a source of bioactive compounds to improve the sensory profile as well as the phytochemical composition of olive oil. We demonstrated that the production system of C. aurantium olive oil and C. limon olive oil improves their organoleptic properties without altering their beneficial effects, which, like control extra virgin olive oil, showed protective effects on glucose and serum lipid levels, metabolic activity of adipocytes, myocardial tissue functionality, oxidative stress markers and endothelial function at blood vessel level.

The alignment of nanostructures in materials such as lyotropic liquid crystals (LLCs) templated materials has the potential to signicantly improve their performances. However, accurately characterising and quantifying the alignement of such fine structures remains very challenging. In situ small angle X-ray scattering (SAXS) and molecular dynamics were employed for the first time to understand the hexagonal LLC alignment process with magnetic nanoparticles under a magnetic field. The enhanced alignment has been illustrated from the distribution of azimuthal intensity in the samples exposed to magnetic field. Molecular dynamics simulations reveal the relationship between the imposed force of the magenetic nanoparticles under magnetic field and the force transferred to the LLC cylinders which leads to the LLC alignment. The combinational study with experimental measurement and computational simulation will enable the development and control of nanostructures in novel materials for various applications.

The XChem facility at Diamond Light Source offers fragment screening by X-ray crystallography as a general access user program. The main advantage of X-ray crystallography as a primary fragment screen is that it yields directly the location and pose of the fragment hits, whether within pockets of interest or merely on surface sites: this is the key information for structure-based design and for enabling synthesis of follow-up molecules. Extensive streamlining of the screening experiment at XChem has engendered a very active user programme that is generating large amounts of data: in 2017, 36 academic and industry groups generated 35,000 datasets of uniquely soaked crystals. It has also generated a large number of learnings concerning the main remaining bottleneck, namely obtaining a suitable crystal system that will support a successful fragment screen. Here we discuss the practicalities of generating screen-ready crystals that have useful electron density maps, and how to ensure they will be successfully reproduced and usable at a facility outside the home lab.

Since coffee has been shown to influence positively the metabolism of subjects with metabolic syndrome (MetS), we aimed to evaluate the short- and long-term effects of a coffee-based supplement on different features of diet-induced MetS. 24 Sprague Dawley rats were divided into control or nutraceuticals groups to receive a high-fat/high fructose diet with or without a mixture of caffeic acid (30 mg/day), trigonelline (20 mg/day), and cafestol (1 mg/day) for 12 weeks. An additional 11 rats were assigned to an acute crossover study. In the chronic experiment, nutraceuticals did not alter body weight or glycemic control but improved fed hyperinsulinemia and HOMA-IR, and plasma adiponectin levels. The impact of nutraceuticals on post-prandial glycemia tended to be more pronounced after acute administration than at the end of the chronic study. Circulating and intrahepatocellular alanine transaminase activity, assessed by hyperpolarized-¹³C NMR spectroscopy, were reduced by coffee nutraceuticals at endpoint. There was also a tendency towards lower liver triglyceride content and histological steatosis score in the intervention group. In conclusion, a mixture of coffee nutraceuticals improved insulin sensitivity and exhibited hepatoprotective effects in a rat model of MetS. Higher dosages with or without caffeine deserve to be studied in the future.

The crack geometry and associated strain field around Berkovich and Vickers indents on silicon have been studied by X-ray diffraction imaging and micro-Raman spectroscopy scanning. The techniques are complementary, the Raman data coming from within a few micrometers of the indentation, whereas the X-ray image probes the strain field at a distance of typically tens of micrometers. For example, Raman data provides an explanation for the central contrast feature in the X-ray images of an indent. Strain relaxation from breakout and high temperature annealing are examined and it is demonstrated that millimeter length cracks, similar to those produced by mechanical damage from misaligned handling tools, can be generated in a controlled fashion by indentation within 75 micrometers of the bevel edge of 200mm diameter wafers.

Polylactic Acid (PLA) is an organic polymer commonly used in fused deposition (FDM) printing and biomedical scaffolding that is biocompatible and immunologically inert. However, variations in source material quality and chemistry make it necessary to characterize the filament and determine potential changes in chemistry occurring as a result of the FDM process. We used several spectroscopic techniques, including laser confocal microscopy, Fourier-Transform Infrared (FTIR) spectroscopy and photoacousitc FTIR spectroscopy, Raman spectroscopy, and X-ray photoelectron Spectroscopy (XPS) in order to characterize both the bulk and surface chemistry of the source material and printed samples. Scanning Electron Microscopy (SEM) and Differential Scanning Calorimetry (DSC) were used to characterize morphology, crystallinity, and the glass transition temperature following printing. Analysis revealed calcium carbonate-based additives which were reacted with organic ligands and potentially trace metal impurities, both before and following printing. These additives became concentrated in voids in the printed structure. This finding is important for biomedical applications as carbonate will impact subsequent cell growth on printed tissue scaffolds. Results of chemical analysis also provided evidence of the hygroscopic nature of the source material and oxidation of the printed surface, and SEM imaging revealed micro and sub-micron scale roughness that will also impact potential applications.

Interactions between human immunodeficiency virus type 1 (HIV-1) and the host factors or restriction factors of its target cells determine the cell’s susceptibility to, and outcome of, infection. Factors intrinsic to the cell are involved at every step of HIV-1’s replication cycle, contributing to productive infection and replication, or severely attenuating HIV-1’s chances of success. Furthermore, factors unique to certain cell types contribute to the differences in infection between these cell types. Understanding the involvement of these factors in HIV-1 infection is a key requirement for the development of anti-HIV-1 therapies. As the list of factors grows, and the dynamic interactions between these factors and the virus are elucidated, comprehensive and up-to-date summaries that recount the knowledge gathered after decades of research are beneficial to the field, displaying what is known so that researchers can build off the groundwork of others to investigate what is unknown. Herein, we aim to provide a review focusing on protein host factors, both well-known and relatively new, that impact HIV-1 replication in a positive or negative manner at each stage of the replication cycle, highlighting factors unique to HIV-1’s various target cell types where appropriate.

This study aimed (1) to map the immunogenic epitopes (B and T cells) within the major BCoV structural proteins. These epitopes are believed to induce a robust im-mune response through the interaction with major histocompatibility complex (MHC class II) molecules (2) to design some novel BCoV multi-epitope-based vac-cines. To achieve these goals, we applied several integrated In-silico prediction computational tools to map these epitopes within the major BCoV structural pro-teins. The predicted epitopes were linked to some immunostimulants such as Toll-like receptors-2 (TLR2) and TLR-4. The tertiary structure of each epitope was modeled through the Alpha fold-2 colab machine learning tools. The stability and purity of each epitope were assessed using the Ramachandran plot and the Z Score values. Each multiepitope-based vaccine candidate conjugated with the Chlorotox-in B toxin as an adjuvant. We designed the vaccine constructs using various expres-sion vectors. We also predicted the affinity binding of these vaccines with the target protein using molecular docking. Our designed multiepitope vaccine candidates per each BCoV structural protein showed high antigenicity, immunogenicity, non-allergic, non-toxic, and high water solubility. Further studies are highly en-couraged to validate the efficacy of these novel BCoV vaccines in the natural host.

Small peptides are an important component of the vertebrate immune system. They are important molecules for distinguishing proteins that originate in the host from proteins derived of a pathogenic organism, such as a virus or bacterium. Consequently, these peptides are central for the vertebrate host response to intracellular and extracellular pathogens. Computational models for prediction of these peptides have been based on a narrow sample of data with an emphasis on the position and chemical properties of the amino acids. In past literature, this approach has resulted in higher predictability than models that rely on the geometrical arrangement of atoms. However, protein structure data from experiment and theory are a source for building models at scale, and, therefore, knowledge on the role of small peptides and their immunogenicity in the vertebrate immune system. The following sections introduce procedures that contribute to theoretical prediction of peptides and role in immunogenicity. Lastly, deep learning is discussed as it applies to immunogenetics and the acceleration of knowledge by a capability for modeling the complexity of natural phenomena.

One of the most common subgroups of cutaneous T-cell lymphomas is the that of primary cutaneous CD30 positive lymphoproliferative disorders. The group includes lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (pcALCL), as well as some borderline cases. Recently, significant progress has been made in understanding the genetics and treatment of these disorders. This review article summarizes the clinical evidence supporting the current treatment options in these diseases. Recent years have seen the introduction of novel agents into clinical practice; most of these target CD30, such as anti-CD30 monoclonal antibodies and conjugated antibodies (brentuximab vedotin), bispecific antibodies and cellular therapies, particularly anti-CD30 CAR-T cells. This paper briefly reviews the biology of CD30 that makes it a good therapeutic target, and describes the anti-CD30 therapies that have emerged to date.

Biosensors based on an oxygen electrode, a mediator electrode and a mediator microbial biofuel cell (MFC) using on the bacteria Gluconobacter oxydans B-1280 have been formed and tested to determine the integral toxicity. G. oxydans bacteria exhibit high sensitivity to the toxic effects of phenol, 2,4-dinitrophenol, salicylic and trichloroacetic acid and a number of heavy metal ions. The system “G. oxydans bacteria – ferrocene – graphite-paste electrode” is superior in sensitivity to biosensors formed using an oxygen electrode and MFC, in particular regarding heavy metal ions (EC50 of chromium (II), manganese (II) and cadmium (II) was 0.8 mg/dm3, 0.3 mg/dm3 and 1.6 mg/dm3, respectively). It has been determined that the period of stable functioning of electrochemical systems during measurements is reduced by half due (from 30 to 15 days) due to changes in the enzyme system of microbial cells when exposed to toxicants. Samples of products made from polymeric materials were analyzed using developed biosensor systems and standard biotesting methods based on inhibiting the growth of duckweed L. minor, reducing the motility of bull sperm and quenching the luminescence of the commercial test system "Ecolum". The developed bioelectrocatalytic systems are comparable in sensitivity to commercial biosensors, which made it possible to correlate the results and identify by all methods a highly toxic sample containing diphenylmethane-4,4'-diisocyanate according to GC-MS data.

The intercomparison among different atmospheric monitoring systems is key for instrument calibration and validation. Common cases involve satellites, radiosonde, radio occultation (e.g. GNSS-RO) and atmospheric model outputs (e.g. ERA5 reanalysis). Since instruments and/or measures are not perfectly collocated, the miss-collocation uncertainty must be considered in the related intercomparison uncertainty budgets.

Background: Cord blood represents a link between intrauterine and early extrauterine development. Cord blood cells map an important time frame in human immune imprinting processes. It is unknown whether sex of the newborn affects the lymphocyte subpopulations in cord blood. Methods: 9 B and 21 T cell subpopulations were characterized by flow cytometry in human cord blood from 16 male and 21 female newborns, respectively. Results: Except for marginal zone B cells and transitional B cells, B cell count in all subsets was higher in cord blood of male newborns than in female newborns. Frequency of naive thymus negative Th cells was significantly higher in male cord blood whereas the remaining T cell subpopulations showed a higher count in cord blood of female newborns. Conclusion: Our study is the first revealing sex differences in B and T cell subpopulations of human cord blood. These results indicate that sex might have a higher impact for the developing immune system urging the need to expand research in this area.

Malaria comprises a spectrum of disease syndromes and the immune system is a major participant in malarial disease. This is particularly true in relation to the immune responses elicited against blood stages of Plasmodium-parasites that are responsible for the pathogenesis of infection. Mouse models of malaria are commonly used to dissect the immune mechanisms underlying disease. While no one mouse model of Plasmodium infection completely recapitulates all the features of malaria in humans, collectively the existing models are invaluable for defining the events that lead to the immunopathogenesis of malaria. Here we review the different mouse models of Plasmodium infection that are available, and highlight some of the main contributions these models have made with regards to identifying immune mechanisms of parasite control and the immunopathogenesis of malaria.

The domestic pig (Sus scrofa) is a species representative of the Suina, one of the four suborders within Cetartiodactyla. In this paper, we reported our analysis of the pig TRG locus in comparison with the loci of species representative of the Ruminantia, Tylopoda and Cetacea suborders. The pig TRG genomic structure reiterates the peculiarity of the organization of Cetartiodactyla loci in TRGC “cassettes”, each containing the basic V-J-J-C unit. Eighteen genes arranged in four TRGC cassettes, form the pig TRG locus. All the functional TRG genes were expressed, and the TRGV genes preferentially rearrange with the TRGJ genes within their own cassette, which correlates the diversity of the gamma-chain repertoire with the number of cassettes. Among them, the TRGC5, located at the 5’ end of the locus, is the only cassette that retains a marked homology with the corresponding TRGC cassettes of all the analyzed species. The preservation of the TRGC5 cassette for such a long evolutionary time presumes a highly specialized function of its genes, which could be essential for the survival of species. Therefore, the maintenance of this cassette in pigs confirms that it is the most evolutionarily ancient within Cetartiodactyla, and it has undergone a process of duplication to give rise to the other TRGC cassettes in the different artiodactyl species in a lineage-specific manner.

Our knowledge on the plastic functions of the serotonin (5-HT) receptor subtype 7 (5-HT7R) in the brain physiology and pathology considerably advanced in the last few years. A wealth of data show that the 5-HT7R is a key player in the establishment and remodeling of neuronal cytoarchitecture during development and in the mature brain, and its dysfunction is linked to neuropsychiatric and neurodevelopmental diseases. The involvement of this receptor in synaptic plasticity is further demonstrated by data showing that its activation allows to rescue long term potentiation (LTP) and long term depression (LTD) deficits in various animal models of neurodevelopmental diseases. In addition, it is becoming clear that the 5-HT7R is involved in inflammatory intestinal diseases, possibly playing a role in the gut-brain axis, and modulates the function of immune cells. In this review, we will mainly focus on recent findings on this receptor’s role in the structural and synaptic plasticity of the mammalian brain, although we will also illustrate novel aspects highlighted in gut and immune system.

Fructus Amomi (FA) is usually regarded as the dried ripe fruits of Amomum villosum Lour. (FAL) or Amomum villosum Lour. var. xanthioides T. L.Wu et Senjenis (FALX) However, FAL, which always has a much higher price because of its better quality, is confused with FALX in the market. As volatile oil is the main constituent of FA, a strategy of chromatography-mass spectrometry (GC-MS) and chemometric approches was applied to compare the chemical composition of FAL and FALX. The results showed that the oil yield of FAL was significantly higher than that of FALX. Total ion chromatograph (TIC) showed that cis-nerolidol existed only in FALX. Bornyl acetate and camphor, could be considered as the most important ones in FAL and FALX respectively. Moreover, hierarchical cluster analysis (HCA) and principal component analysis (PCA) successfully distinguished the chemical constitutes of the volatile oils in FAL and FALX. Additionally, bornyl acetate, α-cadinol, linalool, β-myrcene, camphor, d-limonene, terpinolene and endo-borneol were selected as the potential markers for discriminating FAL and FALX by partial least squares discrimination analysis (PLS-DA). In conclusion, this present study first developed a scientific approach to separate FAL and FALX based on volatile oils by GC-MS combined with chemometric techniques.

The past two decades have seen a revolution in multiple myeloma (MM) therapy with the introduction of several small molecules, mostly orally effective, whose mechanisms are based on proteasome inhibition, histone deacetylase (HDAC) blockade, and immunomodulation. Immunotherapeutic approaches to MM treatment using monoclonal antibodies (mAbs), while long in development, began to reap success with the identification of CD38 and SLAMF7 as suitable targets for development, culminating in the 2015 FDA approval of daratumumab and elotuzumab, respectively. This review highlights additional mAbs now in the developmental pipeline. Isatuximab, another anti-CD38 mAb, currently is under study in four phase III trials and may offer certain advantages over daratumumab. Several antibody-drug conjugates (ADCs) in the early stages of development are described, including JNJ-63723283, which has attained FDA breakthrough status for MM. Other mAbs described in this review include denosumab, recently approved for myeloma-associated bone loss, and checkpoint inhibitors, although the future status of the latter combined with immunomodulators has been clouded by unacceptably high death rates that caused the FDA to issue clinical holds on several of these trials. Also highlighted are therapies based on the B Cell Maturation Antigen (BCMA), another very promising target for anti-myeloma development.

Studies employing Arellano-Bond and Blundell-Bond GMM estimation for single linear dynamic panel data models are growing exponentially in number. However, for researchers it is hard to make a reasoned choice between many different possible implementations of these estimators and associated tests. By simulation the effects are examined of many options regarding: (i) reducing, extending or modifying the set of instruments; (ii) specifying the weighting matrix in relation to the type of heteroskedasticity; (iii) using (robustified) 1-step or (corrected) 2-step variance estimators; (iv) employing 1-step or 2-step residuals in Sargan-Hansen overall or incremental overidentification restrictions tests. This is all done for models in which some regressors may be either strictly exogenous, predetermined or endogenous. Surprisingly, particular asymptotically optimal and relatively robust weighting matrices are found to be superior in finite samples to ostensibly more appropriate versions. Most of the variants of tests for overidentification restrictions show serious deficiencies. A recently developed modification of GMM is found to have great potential when the cross-sectional heteroskedasticity is pronounced and the time-series dimension of the sample not too small. Finally all techniques are employed to actual data and lead to some profound insights.

Understanding the genotype x environment (GE) interaction for traget trait is valuable for growers, agronomists, breeders and the seed industry. The objective of this study was to see and explore the genotype x environment interaction for grain yield of wheat to better guide genotype selection and breeding. The genotype main effect and GE interaction effect (GGE) biplots resolved the following three genotypes: 85 (ETW17-377), 82 (ETW17-374) and 13 (ETW17-281) for being the best yielding and stable. The Kulumsa site planted on 4^th of July 2017 (environment 7=E7) and the DebreZeit site on 20^th of July 2017 (E3) were the most effective environments in distinguishing the test genotypes and are thus suitable environments for future evaluation and selection with specific adaptation. Melkasa site planted on 4^th July (E9) was a representative environment where genotypes can be evaluated for wide adpaptation. The genetic covariate biplot indicated that thousand kernel weight (TKW) and plant height (PH) had significant positive associations with grain yield implying the possible concurrent indirect selection of both traits for exploiting GE interaction for grain yield of wheat.

The reduction of Ce cations in CeO2 can be enhanced by its partial substitution by Fe cations. The enhanced reduction of Ce cations results in a considerable increase in the reaction rates for thermal water splitting reaction when compared to CeO2 alone. This mixed oxide has a smaller crystallite size when compared to CeO2 in addition to a smaller lattice size. In this work, two Fe-substituted Ce oxides are studied (Ce0.95Fe0.05O2 and Ce0.75Fe0.25O2) by core and valence level spectroscopy in their as-prepared and Ar-ions sputtered states. Ar-ions sputtering substantially increases Ce4f lines at about 1.5 eV below the Fermi level. In addition, it is found that the XPS Ce5p/O2s ratio is sensitive to the degree of reduction, most likely due to a higher charge transfer from the oxygen to Ce ions upon reduction. Quantitatively it is also found that XPS Ce3d of the fraction of Ce3+ (uo, u’ and vo, v’) formed upon Ar-ions sputtering and the ratio Ce5p/O2s lines are higher for reduced Ce0.95Fe0.05O2 than for reduced Ce0.75Fe0.25O2. XPS Fe2p showed however no preferential increase for Fe3+ reduction to Fe0 with increasing time for both oxides. Since water splitting was higher on Ce0.95Fe0.05O2 when compared to Ce0.75Fe0.25O2, it is inferred that the reaction centers for the thermal water splitting to hydrogen are the reduced Ce cations and not the reduced Fe cations. These reduced Ce cations can be tracked by their XPS Ce5p/O2s ratio in addition to the common XPS Ce3d lines.

The World Health Organization (WHO) added Disease X to their shortlist of blueprint priority diseases to represent a hypothetical, unknown pathogen that could cause a future epidemic. During different virus outbreaks of the past, such as COVID-19, Influenza, Lyme Disease, and Zika virus, researchers from various disciplines utilized Google Trends to mine multimodal components of web behavior to study, investigate, and analyze the global awareness, preparedness, and response associated with these respective virus outbreaks. As the world prepares for Disease X, a dataset on web behavior related to Disease X would be crucial to contribute towards the timely advancement of research in this field. Furthermore, none of the prior works in this field have focused on the development of a dataset to compile relevant web behavior data, which would help to prepare for Disease X. To address these research challenges, this work presents a dataset of web behavior related to Disease X, which emerged from different geographic regions of the world, between February 2018 to August 2023. Specifically, this dataset presents the search interests related to Disease X from 94 geographic regions. These regions were chosen for data mining as these regions recorded significant search interests related to Disease X during this timeframe. The dataset was developed by collecting data using Google Trends. The relevant search interests for all these regions for each month in this time range are available in this dataset. This paper also discusses the compliance of this dataset with the FAIR principles of scientific data management. Finally, a brief analysis of specific features of this dataset is presented to uphold the applicability, relevance, and usefulness of this dataset for the investigation of different research questions in the interrelated fields of Big Data, Data Mining, Healthcare, Epidemiology, and Data Analysis.

The majority of Candida species are known as non-pathogenic yeasts and rarely involved in human diseases. However, recently case reports of human infections caused by non-albicans Candida species have increased, mostly in immunocompromised hosts. Our study aimed to describe and caracterise as thoroughly as possible, a new species of the Candida genus, named here Candida massiliensis (PMML0037), isolated from a clinical sample of human sputum. We compared genetic data based on the sequences of four genetic regions: "Internal Transcribed Spacers" of rRNA, D1/D2 domains (28S large subunit rRNA) and part of the genes encoding Translation Elongation Factor 1-α and β-tubulin2, to morphological characters, from scanning electron microscopy (TM 4000 Plus, SU5000), physiological, including the results of oxidation and assimilation tests of different carbon sources by the Biolog system, and chemical mapping by Energy-Dispersive X-ray Spectroscopy. Lastly, the in vitro antifungal susceptibility profile was performed using the E-testTM exponential gradient method. The multilocus analysis supported the genetic position of Candida massiliensis (PMML0037) as a new species of the genus Candida, and the phenotypic analysis highlighted its unique morphological and chemical profile when compared to other Candida species included in the study.

Shot peening has become a well-established technique for the introduction of beneficial compressive Residual Stresses (RS) into the near-surface layers of metallic materials for the purpose of preventing or suppressing fatigue crack nucleation and growth. Ti-alloys are widely used to fabricate compressor blades of aeroengines. Titanium blades that may be susceptible to different modes of damage under cyclic loading (high cycle fatigue, fretting fatigue) are often subjected to shot peening to extend their safe operating time. The control and monitoring of residual stresses in titanium blades is of great importance to assure the safety of aeroengines. The techniques for residual stress evaluation include mechanical methods (material removal) as well as physical methods such as X-ray diffraction. Perhaps the most common and practically accessible form of the latter is the method. Conventional laboratory X-ray diffractometers typically probe samples to the depths up to ~20 µm that correspond to 1x...5x the average grain size for typical metals and alloys. The limitations of the method have been identified and reviewed in the literature, motivating the use of other semi-destructive approaches to evaluate the residual stresses in deeper layers and at more sharply defined locations. In the present report we present a case study of the comparison between non-destructive and semi-destructive evaluation techniques, namely the X-ray diffraction method against the mechanical and FIB-DIC ring-core drilling applied to the samples of VT6 (Russian designation of Ti-6Al-4V) titanium alloy after shot peening with 1 mm steel balls. Mechanical drilling of circular holes of ~2 mm diameter with laser speckle interferometry monitoring of strains gives a rough spatial resolution of a few millimeters, while the Korsunsky FIB-DIC method of Ga-ion beam micro-ring core milling within FIB-SEM with Digital Image Correlation (DIC) deformation analysis delivers spatial resolution down to a few micrometers. Good agreement has been found between the X-ray and FIB-DIC estimates of RS variation profiles as a function of depth in shot peened titanium alloy samples. Some advances in the FIB-DIC method are presented and discussed in terms of the acceleration of data acquisition and interpretation.

One of the critical tools for early detection and subsequent evaluation of the incidence of lung diseases is chest radiography. At a time when the speed and reliability of results, especially for COVID-19 positive patients, is important, the development of applications that would facilitate the work of untrained staff involved in the evaluation is also crucial. Our model takes the form of a simple and intuitive application, into which you only need to upload X-rays: tens or hundreds at once. In just a few seconds, the physician will determine the patient's diagnosis, including the percentage accuracy of the estimate. While the original idea was a mere binary classifier that could tell if a patient was suffering from pneumonia or not, in this paper we present a model that distinguishes between a bacterial disease, a viral infection, or a finding caused by COVID-19. The aim of this research is to demonstrate whether pneumonia can be detected or even spatially localized using a uniform, supervised classification.

Mitochondrial disorders, although heterogeneous, are traditionally described as conditions characterized by encephalomyopathy, hypotonia and progressive postnatal organ failure. Here we provide a systematic review of Linear Skin Defects with Multiple Congenital Anomalies (LSDMCA), a rare unconventional mitochondrial disorder which presents as a developmental disease; its main clinical features include microphthalmia with different degrees of severity, linear skin lesions, and central nervous system malformations. The molecular basis of this disorder has been elusive for several years. Mutations were eventually identified in three X-linked genes, i.e., HCCS, COX7B, and NDUFB11, which are all endowed with defined roles in the mitochondrial respiratory chain. A peculiar feature of this condition is its inheritance pattern: X-linked dominant male-lethal. Only female or XX male individuals can be observed, implying that nullisomy for these transcripts is incompatible with normal embryonic development in mammals. All three genes undergo X-inactivation that, according to our hypothesis, may contribute to the extreme variable expressivity observed in this condition. We propose that mitochondrial dysfunction should be considered as an underlying cause in developmental disorders. Moreover, LSDMCA should be taken into consideration by clinicians when dealing with patients with microphthalmia with or without associated skin phenotypes.