Metandienone and methyltestosterone are orally active anabolic-androgenic steroids with a 17α-methyl structure that are prohibited in sports but are frequently detected in anti-doping analysis. After the previously reported detection of long-term metabolites with a 17ξ-hydroxymethyl-17ξ-methyl-18-nor-5ξ-androst-13-en-3ξ-ol structure in the chlorinated metandienone analog dehydrochloromethyltestosterone (“Oral Turinabol”), in this study we investigated the formation of similar metabolites of metandienone and 17α-methyltestosterone with a rearranged D-ring and a fully reduced A-ring. Using a semi-targeted approach including synthesis of reference compounds, two diastereomeric substances, viz. 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-13-en-3α-ol and its 5α-analog, were identified following an administration of methyltestosterone. In post-administration urines of metandienone, only the 5β-metabolite was detected. Additionally, 3α,5β-tetrahydro-epi-methyltestosterone was identified in the urines of both administrations besides the classical metabolites included in the screening procedures. Besides their applicability for anti-doping analysis, the results provide new insights on the metabolism of 17α-methyl steroids with respect to the order of reductions in the A-ring, the participation of different enzymes, and alterations of the D-ring.

Despite huge effort has been devoted to the design of the initiators and reaction conditions, it remains challenging to synthesize high molecular weight polypeptides with conventional solution phase synthesis. In this work, surface-initiated vapor deposition polymerization (SI-VDP) was utilized to graft synthetic polypeptides poly (γ-benzyl L-glutamate) (PBLG) from polystyrene (PS) resin beads by ring-opening polymerization of N-carboxyanhydrides (NCAs). It was demonstrated for the first time that high molecular weight bulk PBLG (> 500,000) could be readily obtained within one hour via solvent-free synthetic method which paves the way for the synthesis of copolypeptides with high molecular weight.

In case of a discrete-time Hopfield neural network of two neurons with two delays and no self- connections at 23 bifurcation values 23 voltage trajectories appear.Among the 23 voltage trajectories 14 voltage trajectory are not what we call orbits in classic sense. The geometrical aspect of these trajectories suggest that they are fractals. Our conjecture is that the 14 trajectories in discussion are fractals having real couterpart. In case of a discrete-time Hopfield neural network of five neuron with delay and ring architecture at 9 bifurcation values 9 voltage trajectories appear.Among the 9 voltage trajectories we find 5 voltage trajectory which are not what we call orbits in classic sense.The geometrical aspect of these trajectories suggest that they are fractals.Our conjecture is that the 5 trajectories in discussion are fractals having real couterpart.. In case of a discrete-time Hopfield neural network of two neurons with a single delay and self- connections the computed trajectories are what we call orbits in classic sense. In case of a discrete-time Hopfield neural network of two neurons with two delays and self- connections the computed trajectories are what we call orbits in classic sense.

Drug functionalization through formation of hydrophilic groups is the norm in phase I metabolism of drugs for modification of drug action. The reactions involved are mainly oxidative catalyzed mostly by CYP isoenzymes. The benzene ring, as phenyl or fused with other rings, is the most common hydrophobic pharmacophoric moiety in drug molecules. On the other hand the alkoxy group (mainly methoxy) bonded to the benzene ring assumes an important and sometimes essential pharmacophoric status in some drug classes. Upon metabolic oxidation, both moieties, i.e. the benzene ring and the alkoxy group, produce hydroxy groups; the products are arenolic in nature. Through a pharmacokinetic effect, the hydroxy group enhances the water solubility and elimination of the metabolite with the consequent termination of drug action. However, through hydrogen bonding, the hydroxy group may modify the pharmacodynamics of the interaction of the metabolite with the site of parent drug action (i.e. the receptor). Accordingly, the expected pharmacologic outcome will be enhancement, retaining, attenuation, or loss of activity of the metabolite relative to the parent drug. All the above issues have been presented and discussed in this review using selected members of different classes of drugs with inferences regarding mechanisms, drug design and drug development.

Background: Classical Hodgkin's lymphoma (cHL) is a lymph node disease, however, extranodal involvement is present in about 10% of affected individuals. Various forms of direct central nervous system (CNS) involvement have been reported, including intracranial, epidural, leptomeningeal, and intramedullary spinal cord cHL (Table 1). We hereby describe the clinical presentation, work up, and outcomes of two distinctive cases of cHL with intracranial extra-axial spread in patients receiving novel combination and traditional chemotherapy. Methods: This case series (n=2) was conducted following the CARE guidelines. Institutional review board (IRB) approved protocol #24-015 for HIPPA waiver of subjects in our retrospective study. Results: Patients with cHL exhibiting CNS symptoms or relapse refractory cases benefit from neuroimaging and excluding infectious etiologies. Suspicious lesions include iso- to hypointensity on T1 weighted and iso- to hyperintensity on T2 MR scans. Diagnosis is confirmed with biopsy. Treatment with A-AVD has shown more benefit than traditional ABVD chemotherapy. There has been shown progression free survival with nivolumab-AVD (N-AVD) over brentuximab-AVD (B-AVD). Conclusion: cHL with CNS involvement is rare and requires comprehensive workup to exclude infectious and other malignancies. Diagnosis relies on neuroimaging and subsequent brain biopsy. Treatment with novel N-AVD has shown greater PFS in patients with advanced cHL.

In this paper, a low-power Injection-Locked Clock and Data Recovery (ILCDR) using 28nm FDSOI technology is presented. The back-gate auto-biasing of UTBB-FDSOI transistors allows us to create a QRO (Quadrature Ring Oscillator) reducing both size and power consumption. By injecting a digital signal into this circuit, we realize an Injection-Locked Oscillator (ILO) with low jitter. Thanks to the good performance of this oscillator, we propose a low power ILCDR with fast locking time and low jitter for burst-mode applications. The main novelty consists in the implementation of a complementary QRO based on back-gate control using FDSOI technology to realize a simple and efficient ILCDR circuit. With a Pseudo-Random Binary Sequence (PRBS7) at 868Mbps, the recovered clock jitter is 26.7ps (2.3%UIp-p) and the recovered data jitter is 11.9ps (1%UIp-p). With a 0.6V power supply, the power consumption is 318μW. The estimated Chip area is around 6600μm².

Louis de Broglie in the beginning 20th century voices his theory of a double solution, according to which a pilot wave accompanies a particle, simulated as a point singularity, along the most optimal path from its creation on a source up to the detection. The pilot wave is a real hidden wave, which is similar to the wave function resulting from the solution of the Schrödinger equation. This theory is in agreement with de Broglie’s postulate about the matter waves. In this article we are based on the Helmholtz decomposition theorem according to which any velocity may be represented as a sum of two velocities – irrotational and solenoidal ones. The first velocity stems from the gradient of the scalar field. The second occurs from a pseudo-vector field. We proclaim that the gradients of the scalar field define guiding paths of the pilot wave. While the pseudo-vector field defines a particle solenoidal filling. We give mathematical models of the irrotational and solenoidal flows simulating the position of a particle in a guiding wave. Modified Navier-Stokes equation in pair with the continuity equation resulting in the Schrödinger equation gives such solutions consisting of superposition of the irrotational and solenoidal flow. It is declared that the guiding wave forms from the irrotational flows. In turn, the solenoidal flows underlie forming particles that travel along optimal paths slave by the guiding wave. There are described mathematical solutions of the spherical particle washed by the superfluid representing the guiding wave along which it travels.

This work presents first time successfully fabricated silica few-mode microstructured optical fiber (MOF) with hollow GeO2-doped ring core and strongly induced twisting up to 790 revolutions per meter. Some technological issues for manufacturing of GeO2-doped supporting elements for large hollow cores as well as described above complicated spun MOFs are discussed. We introduce some results of tests, performed for pilot samples of designed and manufactured described above untwisted and twisted MOFs with outer diameter 65 µm and hollow ring core inner diameter 30.5 µm under wall thickness 1.7 µm and refractive index difference n=0.030, including their geometrical parameters, basic transmission characteristics and measurements of far-field laser beam profile patterns.

Thanks to advanced semiconductor microfabrication technology, chip-scale integration and miniaturization of lab-on-a-chip components, silicon-based optical biosensors have made significant progress for the purpose of point-of-care diagnosis. In this review, we provide an overview of the state-of-the-art in evanescent field biosensing technologies including interferometer, microcavity, photonic crystal, and Bragg grating waveguide-based sensors. Their sensing mechanisms and sensor performances, as well as real biomarkers for label-free detection, are exhibited and compared. We also review the development of chip-level integration for lab-on-a-chip photonic sensing platforms, which consist of the optical sensing device, flow delivery system, optical input and readout equipment. At last, some advanced system-level CMOS-chip packaging examples are presented, indicating the commercialization potential for the low cost, high yield, portable biosensing platform leveraging CMOS processes.

The Ayers Rock of Australia which is known for its charming colors at different time is actually the Celestial Body Ring of the planet Earth that implies the great Celestial Body Love happened on Earth long long ago. The Tasmania island of Australia which is known for the World Heart is actually in the state of face to face with the main island of Australia, which implies the image spokesperson for the inner core (the heart) of the planet Earth. In other words, with the outline of the main island of Australia, the basic key information of the inner core of the planet Earth could be easily obtained by deducing logically, just like the similarity between the fists and heart of human body. Similar to the mechanism of the blood circulation dominated by the heart of human body, it is dominated and motivated by the inner core of the Earth which forms the circulation of mantle magma between the crust and the inner core, and what leads to the formation of expanding and active area on the equatorial and middle-lower latitude area and the silent and convergent area on the North and South Pole central area. Therefore, the mantle magma whirlpools under the crust on the North and South Pole are supposed to exist logically. The walking sideways of the crabs just implies the celestial body language of the motive trend of the main island of Australia based on their similar outline.