gebhart/patrepeval huggingface dataset:
Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of (( S )-2,2-Difluorocyclopropyl)((1 R ,5 S )-3-(2-((1-methyl-1 H -pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700841) (2018)

Cytokine signaling is an important characteristic of autoimmune diseases. Many pro-inflammatory cytokines signal through the Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) pathway. JAK1 is important for the γ-common chain cytokines, interleukin (IL)-6, and type-I interferon (IFN) family, while TYK2 in addition to type-I IFN signaling also plays a role in IL-23 and IL-12 signaling. Intervention with monoclonal antibodies (mAbs) or JAK1 inhibitors has demonstrated efficacy in Phase III psoriasis, psoriatic arthritis, inflammatory bowel disease, and rheumatoid arthritis studies, leading to multiple drug approvals. We hypothesized that a dual JAK1/TYK2 inhibitor will provide additional efficacy, while managing risk by optimizing selectivity against JAK2 driven hematopoietic changes. Our program began with a conformationally constrained piperazinyl-pyrimidine Type 1 ATP site inhibitor, subsequent work led to the discovery of PF-06700841 (compound 23), which is in Phase II clinical development (NCT02969018, NCT02958865, NCT03395184, and NCT02974868).
ChemInform Abstract: Methods for in situ Spectroscopic Probing of the Synthesis of a Zeolite (2011)

Abstract Review: 69 refs.
Tau-related white-matter alterations along spatially selective pathways (2020)

Progressive accumulation of tau neurofibrillary tangles in the brain is a defining pathologic feature of Alzheimer's disease (AD). Tau pathology exhibits a predictable spatiotemporal spreading pattern, but the underlying mechanisms of this spread are poorly understood. Although AD is conventionally considered a disease of the gray matter, it is also associated with pronounced and progressive deterioration of the white matter (WM). A link between abnormal tau and WM degeneration is suggested by findings from both animal and postmortem studies, but few studies demonstrated their interplay in vivo. Recent advances in diffusion magnetic resonance imaging and the availability of tau positron emission tomography (PET) have made it possible to evaluate the association of tau and WM degeneration (tau-WM) in vivo. In this study, we explored the spatial pattern of tau-WM associations across the whole brain to evaluate the hypothesis that tau deposition is associated with WM microstructural alterations not only in isolated tracts, but in continuous structural connections in a stereotypic pattern. Sixty-two participants, including 22 cognitively normal subjects, 22 individuals with subjective cognitive decline, and 18 with mild cognitive impairment were included in the study. WM characteristics were inferred by classic diffusion tensor imaging (DTI) and a complementary diffusion compartment model - neurite orientation dispersion and density imaging (NODDI) that provides a proxy for axonal density. A data-driven iterative searching (DDIS) approach, coupled with whole-brain graph theory analyses, was developed to continuously track tau-WM association patterns. Without applying prior knowledge of the tau spread, we observed a distinct spatial pattern that resembled the typical propagation of tau pathology in AD. Such association pattern was not observed between diffusion and amyloid-β PET signal. Tau-related WM degeneration is characterized by an increase in the mean diffusivity (with a dominant change in the radial direction) and a decrease in the intra-axonal volume fraction. These findings suggest that cortical tau deposition (as measured in tau PET) is associated with a lower axonal packing density and greater diffusion freedom. In conclusion, our in vivo findings using a data-driven method on cross-sectional data underline the important role of WM alterations in the AD pathological cascade with an association pattern similar to the postmortem Braak staging of AD. Future studies will focus on longitudinal analyses to provide in vivo evidence of tau pathology spreads along neuroanatomically connected brain areas.
Bacterial inhibition of inflammatory responses via TLR-independent mechanisms (2013)

Identification of cellular processes modulated by microbial organisms that undermine and disarm mammalian host defences against bacterial invaders has been the focus of significant biomedical research. In this microreview we will illustrate the role of bacterial N-acyl homoserine lactones (AHL) as a strategy utilized by Gram-negative bacterial pathogens to enable colonization of the host through AHL-mediated inhibition of inflammation induced via innate immune receptor mechanisms. We will also highlight some of the signalling pathways in which the study of AHL-mediated effects on mammalian cells might lead to the discovery of global underlying principles linking inflammation and immunity to many chronic human diseases, including cancer and obesity.
Error-control coding for computer systems (1989)

Error-control coding for computer systems , Error-control coding for computer systems , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
Domain Walls in Thin Ni-Fe Films (1960)

Observations of domain walls in Ni-Fe films as a function of thickness demonstrate the strong influence of magnetic stray fields on the wall structure, hence on the coercivity for wall motion. In order to reduce the stray-field energy, the Bloch walls in films thicker than 1000 A are subdivided into sections with alternating polarity which are separated by Bloch lines. In thinner films, the domain walls are of the Néel type. The position of Bloch lines in such walls is indicated by crosswalls. The motion of Bloch lines in an applied field can be observed particularly easily on scratches in negative magnetostrictive material; such scratches display properties corresponding to Néel walls. Crosswalls are also present at the ends of domains and around holes in the film material. A crosswall is distinguished from ordinary domain walls by the continuous change of the angle of magnetization along both sides of it.
Reperfusion repercussions: A review of the metabolic derangements following resuscitative endovascular balloon occlusion of the aorta (2020)

Level V.
Characterization of the ovalbumin‐specific TCR transgenic line OT‐I: MHC elements for positive and negative selection (2000)

The present report provides the first extensive characterization of the OT-I TCR transgenic line, which produces MHC class I-restricted, ovalbumin-specific, CD8+ T cells (OT-I cells). These cells are shown to be positively selected in vivo in H-2b C57BL/6 mice and in bm5 mice, which express the Kbm5 mutant molecule. In contrast, OT-I cells were not selected by mutant Kb molecules in bm1, bm3, bm8, bm10, bm11 or bm23 mice. Interestingly, however, when positive selection was examined in vitro in foetal thymic organ culture (FTOC), bm1 and bm8 were still poorly selective, but the bm3 haplotype now selected as efficiently as B6. The ability to select in vitro correlated with the capacity to present the ovalbumin (OVA) peptide to OT-I cells, as measured by induction of an OVA-specific proliferative response. These results suggest that a lower affinity TCR:MHC interaction may be necessary for positive selection in FTOC compared with selection in situ.
Optimal Control of Cross-Machine Direction Web Profile with Constraints on the Control Effort (1986)

Spatial coupling between the control points in a cross-machine profile of a sheet property is a primary concern in cross-machine control problems. The goal of the cross-machine direction (CD) control is to minimize the deviation from a desired profile with certain constraints on the control action. Two approaches, quadratic programming (QP) and quadratic penalty function (QPF), were evaluated for inclusion in a commercial CD control product. The optimal control is obtained from the QP approach, but the QPF which produces near-optimal control, is more robust and easier to implement in real-time applications. A comparison between QP and QPF results is shown by simulated examples. Field test results of the QPF method are also included. The QPF approach is well suited for practical applications and has been successfully incorporated in over 40 commercial installations.
A High throughput bioluminescent assay to monitor the activity of COVID‐19 Methyltransferases Capping Enzymes (2022)

The recent pandemic outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐Cov‐2) was first reported in Wuhan, China in late 2019 resulting in infection of over 259 million and death of over 5.17 world‐wide as of November 2021. In the USA, the number of diagnosed individuals reached 48 million with 92,000 Death cases. Despite the lower pathogenicity compared to SARS‐CoV and MERS‐CoV, the high infection rate of SARS‐CoV‐2 results in large numbers of hospitalizations and deaths worldwide. The SARS‐Cov‐2 is an enveloped virus and belongs to the beta coronavirus family containing a large and complex positive–sense single stranded RNA genome (~30kb). It binds to human ACE2 receptor with high affinity via its spike protein (S) and membrane fusion leading to the release of its genomic RNA that replicates and produce higher number of sub‐genomic RNAs. The viral RNA is then capped by nsp 14 and nsp10/16, two nonstructural proteins that catalyze the methylation of RNA to limit its degradation by cellular 5’‐3’ exonuclease and evade host immune system. These enzymes play critical role in translation of the viral RNA and its replication and thus leading to viral survival. We have used a bioluminescent high throughput enzyme assay for monitoring the activity of these enzymes in order to develop novel inhibitors which can be advanced for therapeutic treatment. We show that we can determine the activity of nanogram amounts of these enzymes and test the activity of these enzymes using different inhibitors, some of which are competitive with S‐adenosyl methionine the canonical substrate for these enzymes. We also show the effect of inhibitors that compete with the oligonucleotide substrate. Finally, we tested the effect of a peptide modulator of COVID‐2 on the activity of both nsp 10/16 and nsp 14. The assay is simple, homogenous, fast, and bioluminescent which provides a very robust platform for testing novel compounds on the viral methyltransferases leading to the generation of new drugs towards inhibiting the replication of COVID‐19.
Achievement of high cell density and high antibody productivity by a controlled-fed perfusion bioreactor process (2000)

Controlled feeding of nutrient supplements to a cell culture to enhance monoclonal antibody productivity has been practiced widely in high-yield, fed-batch processes. In this study, a similar feeding concept has been applied to a perfused culture and evaluated for the effects on bioreactor productivity and product quality. Our experimental results show that, by using such a "controlled-fed perfusion" approach, the volumetric antibody productivity (antibody per liter per day) was significantly increased by nearly twofold over the perfusion process, and surpassed fed-batch and batch processes by almost tenfold. The substantial boost in the overall productivity is attributable primarily to the combined effects of increased cell density as well as reduced product dilution. Both were achieved through careful nutrient supplementation in conjunction with metabolite minimization. As the manufacturing process evolved from roller bottles to the controlled-fed perfusion bioreactor system, the immunoreactivity and the cDNA sequences of the antibody were well preserved. However, the product glycosylation distribution patterns did alter. The controlled-feed perfusion process demonstrated a unique encompassment of the advantages of fed-batch and perfusion methods; that is, high product concentration with high volume throughput. Therefore, it may be very suitable for large-scale production of monoclonal antibodies.
Performance Analysis of Two-Way Relay System with Antenna Correlation (2011)

This paper investigates the performance of amplify-and-forward (AF) two-way relay system with antenna correlation. Overall outage probability (OOP), average symbol error rate (SER) and ergodic capacity are analyzed. By considering general correlation structure with arbitrary eigenvalue distribution, we derive a tight lower bound for OOP and use it to evaluate average SER and ergodic capacity. Moreover, the system is studied in high signal-to-noise ratio (SNR) to obtain the insightful behavior of the performance and diversity gain. Finally Monte Carlo simulations are conducted to verify the accuracy of the results.
Expression of Inhibitory Receptors Ly49E and CD94/NKG2 on Fetal Thymic and Adult Epidermal TCR Vγ3 Lymphocytes (2002)

Ly49 and CD94/NKG2 inhibitory receptors are predominantly expressed on murine NK cells, but they are also expressed on a subpopulation of peripheral CD8 memory TCR alphabeta lymphocytes. In this study we demonstrate that Ly49E and CD94/NKG2 receptors are expressed on mature TCR Vgamma3(+) cells in the fetal thymus. Expression correlated with a memory phenotype, such as expression of CD44, 2B4, and IL-2Rbeta (CD122), and absence of IL-2Ralpha (CD25) expression. No expression of Ly49A, C, D, G2, or I receptors was observed. This phenotype is similar to that of fetal thymic NK cells. Skin-located Vgamma3 T cells, the progeny of fetal thymic Vgamma3 cells, also expressed CD94/NKG2 and Ly49E but not the other members of the Ly49 family. The development and survival of Ly49E(+) or CD94/NKG2(+) Vgamma3 T lymphocytes was not dependent upon expression of MHC class I molecules. The cytotoxicity of TCR Vgamma3 cells was inhibited when Qdm, the ligand for CD94/NKG2, was presented by Qa1(b)-transfected target cells. Also, upon cross-linking of CD94/NKG2 with mAb 3S9, TCR Vgamma3 thymocytes were prevented from killing FcgammaR(+) P815 target cells. These effects were most pronounced in the CD94/NKG2(high) subpopulation as compared with the CD94/NKG2(low) subpopulation of Vgamma3 cells. Our data demonstrate that Vgamma3 T cells expressing inhibitory Ly49E and CD94/NKG2 receptors are mature and display a memory phenotype, and that CD94/NKG2 functions as an inhibitory receptor on these T lymphocytes.
Kv1.3 inhibition as a potential microglia-targeted therapy for Alzheimer’s disease: preclinical proof of concept (2017)

Microglia significantly contribute to the pathophysiology of Alzheimer's disease but an effective microglia-targeted therapeutic approach is not yet available clinically. The potassium channels Kv1.3 and Kir2.1 play important roles in regulating immune cell functions and have been implicated by in vitro studies in the 'M1-like pro-inflammatory' or 'M2-like anti-inflammatory' state of microglia, respectively. We here found that amyloid-β oligomer-induced expression of Kv1.3 and Kir2.1 in cultured primary microglia. Likewise, ex vivo microglia acutely isolated from the Alzheimer's model 5xFAD mice co-expressed Kv1.3 and Kir2.1 as well as markers traditionally associated with M1 and M2 activation suggesting that amyloid-β oligomer induces a microglial activation state that is more complex than previously thought. Using the orally available, brain penetrant small molecule Kv1.3 blocker PAP-1 as a tool, we showed that pro-inflammatory and neurotoxic microglial responses induced by amyloid-β oligomer required Kv1.3 activity in vitro and in hippocampal slices. Since we further observed that Kv1.3 was highly expressed in microglia of transgenic Alzheimer's mouse models and human Alzheimer's disease brains, we hypothesized that pharmacological Kv1.3 inhibition could mitigate the pathology induced by amyloid-β aggregates. Indeed, treating APP/PS1 transgenic mice with a 5-month oral regimen of PAP-1, starting at 9 months of age, when the animals already manifest cognitive deficits and amyloid pathology, reduced neuroinflammation, decreased cerebral amyloid load, enhanced hippocampal neuronal plasticity, and improved behavioural deficits. The observed decrease in cerebral amyloid deposition was consistent with the in vitro finding that PAP-1 enhanced amyloid-β uptake by microglia. Collectively, these results provide proof-of-concept data to advance Kv1.3 blockers to Alzheimer's disease clinical trials.
Three-Dimensional Finite-Element Model for Stratified Coastal Seas (1998)

An efficient semi-implicit finite-element model for stratified coastal seas is proposed. Nine-node Lagrangian quadratic isoparametric elements are employed for spatial discretization in the horizontal domain and a three-mode Lagrangian interpolation formula is used to approximate the vertical gradients of the two horizontal velocity components. The distinguishing feature of the proposed numerical scheme is that only nodal values on the same vertical line are coupled, resulting in a drastic reduction of computer time. The model is applicable even in situations where there are great variabilities in the water depth in the computational domain, which leads to orders of magnitude difference in the thicknesses of the different water layers in the water body. The model is first verified by a test case for which analytic solutions are available and then applied to simulate the flow in a stratified sea for which solution by a combined finite-difference–Galerkin method is available in the literature for comparison.
The structure-forming role of magnesium pyrophosphate in the formation of DNA-containing microparticles during PCR (2015)

This work is devoted to studying the mechanisms of formation of DNA-containing microparticles (MPs) during PCR. It was found that pyrophosphate, a byproduct of DNA synthesis, and magnesium cations are required for their formation, as evidenced by the results of biochemical and electron microscopy studies.
Resveratrol enhances the sensitivity of doxorubicin‐mediated cell proliferation, invasion, and migration in human breast cancer cell lines (2010)

The aims of this study were to investigate the synergistic anticancer effects of resveratrol with doxorubicin against human breast cancer cell lines. In this study, the doxorubicin‐resistance MCF‐7 (MCF‐7/ADR) and MDA‐MB‐231 cells were treated with resveratrol and doxorubicin, alone or in combination, and we examined cell viability, cell cycle, apoptosis, migration and invasion. Treatment with doxorubicin 1 μM for 24 hr had no effect on the cell viability of MCF‐7/ADR and MDA‐MB‐231 cells. However, combination of doxorubicin and resveratrol significantly reduced viability of MCF‐7/ADR and MDA‐MB‐231 cells, respectively. Although MCF‐7/ADR and MDA‐MB‐231 cells are relatively resistant to the doxorubicin, resveratrol improved the doxorubicin‐induced cytotoxicity in both cell lines. Taken together, combination treatment with resveratrol and doxorubicin decreased MCF‐7/ADR and MDA‐MB‐231 cells migration up to 60% and 80%, respectively, as compared to doxorubicin treatment alone. Similar to migration assay, there was significant reduced the number of invaded cells in assay using Matrigel‐coated chambers. To determine the pathway of anti‐invasive effects, the expression levels of genes involved in migration and invasion were examined in both cell lines. The MMP‐2, MMP‐9 and plasminogen activator (u‐PA) expression levels were significantly decreased following combination treatment. In addition, the expression levels of TIMPs and RECK were markedly increased in case of combination treatment in both cell lines. In conclusion, these findings suggest that resveratrol might be used as a synergistic agent in the treatment of doxorubicin‐resistance breast cancer.
FREQUENCIES OF NUCLEAR ANOMALIES IN THE RYTHROCYTES OF PERIPHERAL BLOOD OF CLINICALLY HEALTHY TURKEYS AT THE AGE OF 6 AND 17 WEEKS OLD (2019)

Электронные книги и статьи из каталога «ЧАСТОТЫ ЯДЕРНЫХ АНОМАЛИЙ В ЭРИТРОЦИТАХ ПЕРИФЕРИЧЕСКОЙ КРОВИ КЛИНИЧЕСКИ ЗДОРОВЫХ ИНДЕЕК В ВОЗРАСТЕ 6 И 17 НЕДЕЛЬ (90,00 руб.)». Скачайте в онлайн-библиотеке Rucont.
The Addition of 7.5% Glucose Does Not Alter the Neurotoxicity of 5% Lidocaine Administered Intrathecally in the Rat (1995)

The presence of 7.5% glucose does not affect the potential of intrathecally administered 5% lidocaine to induce sensory impairment. These findings provide further support for the hypothesis that recent injuries after spinal anesthesia resulted from a direct neurotoxic effect of the local anesthetic.
My Opinion on Improving Vocational Guidance of Higher Vocational College (2004)

It's very necessary to strengthen vocational guidance in vocafional college. However, there exists soms serious problems at present. So we should pay much attention to the following points:working out teaching plan; constructing teachers troop for guidance, improving teaching process and connecting the relations between different trades.
Autonomous Model Predictive Controlled Smart Inverter With Proactive Grid Fault Ride-Through Capability (2020)

This article presents an autonomous model predictive controlled smart photovoltaic (PV) inverter with proactive grid fault-ride through capability. The proposed smart inverter control features decoupled active and reactive power. It can seamlessly switch between the anticipated modes of operation based on grid condition or grid operator command. The smart inverter autonomously adjusts its active and reactive power set-points according to the grid condition, it operates in maximum power point tracking (MPPT) and low voltage ride through (LVRT) modes in normal grid and faulty grid condition modes, respectively. The proposed novel autonomous model predictive control (AMPC) scheme is leveraged to enhance the operation of the smart inverter. The AMPC includes online weight factor auto-tuning and control objective normalization to eliminate the required trial-and-error weight factor design stage in conventional model predictive control. This feature is particularly beneficial to the dual-mode smart inverter operation. The performance of the proposed grid-tied smart inverter based on the AMPC is verified experimentally. The results demonstrate that the proposed AMPC-based smart inverter features robust grid fault detection, autonomous adjustment of active and reactive power set-points, seamless transition between modes of operation, and elimination of controller tuning effort.
The effect of heparin on the viscoelasticity of whole blood clots (1975)

It was demonstrated that pharmacological alteration of coagulating whole blood can influence the mechanical properties of the clot and can be assessed rheologically. The clot viscoelasticity was measured in a Weissenberg Rheogoniomcter as a function of the concentration of anticoagulant sodium hepa rin. The storage component of the elastic modulus was seen to be significantly and reproducibly lowered by heparin. Variation between donors was found to be minimized by adjustment of hematocrit, platelet count, and fibrinogen content to common values.
Integration of spin valves and GaAs diodes in magnetoresistive random access memory cells (1999)

A magnetoresistive random access memory, based on a dynamic random access memory-like floor plan, is demonstrated for an array of magnetic memory cells. Each memory cell consists of a giant magnetoresistive spin-valve structure in series with a GaAs diode. Any single bit in the matrix can be addressed using a coincident current scheme, both for write and read operations. The integration of a series diode in the memory cell yields, for this first demonstrator, read signals of approximately 10 mV.
STEREOSPECIFIC TOTAL SYNTHESES OF THE THREE DIASTEREOISOMERS OF CYCLOEUDESMOL (1979)

Abstract The stereospecific total syntheses of the three diastereoisomers of cycloeudesmol (Ia, Ib, and Ic) were carried out with the object of establishing the structure of cycloeudesmol.