gebhart/patrepeval huggingface dataset:
Impaired T cell-mediated macrophage activation in CD40 ligand-deficient mice (1996)

The expression of the ligand for CD40 (CD40L) is critical for induction of T cell-dependent Ab responses. To examine how critical the expression of CD40L is for induction of cell-mediated immune responses, the ability of T cells from CD40L knockout mice to activate macrophage effector function was assessed. CD4+ T cells from CD40L-knockout mice were fourfold less effective than +/+ T cells in activating the nitric oxide response in allogeneic macrophages. CD40L-knockout T cells that were fixed with paraformaldehyde after a 6-h activation period, a time point at which CD40L dominates the macrophage-activating capability of the T cell, could activate neither macrophage production of inflammatory cytokines (TNF-alpha) nor generation of reactive nitrogen intermediates. After 24 h of activation, however, both CD40L-knockout and +/+ T cells could induce similar but weak responses from the macrophages. This study demonstrates that animals deficient in CD40L expression display a deficiency in T cell-dependent macrophage-mediated immune responses.
Über 2‐Adamantylhydrazin und einige seiner Vorstufen und Derivate (1984)

Abstract Es wird die Synthese von 2‐Adamantylhydrazin aus 2‐Adamantylamin über das Sydnon und aus Adamantanon über Adamantylidenhydrazincarbonsäureester beschrieben, sowie einige Umsetzungen, auch von Derivaten, mit Phenylisothiocyanat.
Matched molecular pairs derived by retrosynthetic fragmentation (2013)

Matched molecular pairs (MMPs) are defined as pairs of compounds that only differ by a chemical change at a single site. MMPs have become popular in medicinal chemistry to support lead optimization, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis, and other applications. Thus far, MMPs have been algorithmically defined and not on the basis of reaction information. This often limits the chemical interpretability and practical utility of MMPs. Therefore, we introduce synthetically accessible MMPs that are automatically generated by applying reaction rules following the retrosynthetic combinatorial analysis procedure (RECAP). A library of more than 92 000 RECAP-MMPs was generated from public domain compounds active against 435 different targets exclusively utilizing high-confidence activity data. This library is made freely available for use in medicinal chemistry.
The Study of a Remote-Controlled Gastrointestinal Drug Delivery and Sampling System (2008)

A micromachined capsule based on microelectromechanical systems (MEMS) technology is introduced in this paper. It is an effective tool for diagnosing and treating gastrointestinal diseases. The microcapsule can carry out real-time drug release and the gastrointestinal fluid sampling in the gastrointestinal tract. According to the structural and metabolic characters of the gastrointestinal tract, the configuration of the microcapsule was designed as a cylinder. This nondigestible oral device can smoothly pass through the gastrointestinal tract for drug delivery and liquid sampling. The working mechanism of the capsule was the mechanic movement mode of a piston, which was regulated through a MEMS calorific element. The action of drug delivery and gastrointestinal fluid sampling in the gastrointestinal tract was performed wirelessly. The remote control device can be connected with a computer through a serial port (RS-232), and it can be used in telemedicine applications. Some experimental research has been carried out to validate the design. The experimental results indicated that the microcapsule can achieve drug delivery and liquid sample reliably.
Chemoenzymatic Synthesis with Distinct Pasteurella Heparosan Synthases (2007)

Heparosan (-GlcUA-beta1,4-GlcNAc-alpha1,4-)(n) is a member of the glycosaminoglycan polysaccharide family found in the capsule of certain pathogenic bacteria as well as the precursor for the vertebrate polymers, heparin and heparan sulfate. The two heparosan synthases from the Gram-negative bacteria Pasteurella multocida, PmHS1 and PmHS2, were efficiently expressed and purified using maltose-binding protein fusion constructs. These relatively homologous synthases displayed distinct catalytic characteristics. PmHS1, but not PmHS2, was able to produce large molecular mass (100-800 kDa) monodisperse polymers in synchronized, stoichiometrically controlled reactions in vitro. PmHS2, but not PmHS1, was able to utilize many unnatural UDP-sugar analogs (including substrates with acetamido-containing uronic acids or longer acyl chain hexosamine derivatives) in vitro. Overall these findings reveal potential differences in the active sites of these two Pasteurella enzymes. In the future, these catalysts should allow the creation of a variety of heparosan and heparinoids with utility for medical applications.
Allosteric Modulation of the Dopamine D 2 Receptor by Pro-Leu-Gly-NH 2 Peptidomimetics Constrained in Either a Polyproline II Helix or a Type II β-Turn Conformation (2009)

Type II beta-turn mimics and polyproline II helix mimics based upon diastereoisomeric 5.6.5 spiro bicyclic scaffolds have provided two pairs of Pro-Leu-Gly-NH(2) (PLG) peptidomimetics with contrasting dopamine receptor modulating activities. Compounds 1a and 3a were found to be positive allosteric modulators of the dopamine receptor, while the corresponding diastereoisomeric compounds 1b and 3b provided the first PLG peptidomimetics with the ability to decrease the binding of agonists to the dopamine receptor. The positive allosteric modulating activity of 3a supported the hypothesis that a polyproline II helix conformation is the bioactive conformation for the PLG analogue Pro-Pro-Pro-NH(2). The results also show that a change in the bridgehead chirality of the 5.6.5 scaffold brings about opposite effects in terms of the modulation of the dopamine receptor.
Molecular Mechanisms Of Drug Action (1994)

In this book the targets of drug action are the central focus - whether they be enzymes in a pathway or membrane-bound receptors and ion channels. This approach distinguishes the book from others in the f ield which consider the subject mainly in terms of disease.; The introductory chapter is concerned with the basic principles that cover enzyme in
MEMS enabled reconfigurable frequency selective surfaces: design, simulation, fabrication, and measurement (2003)

Frequency selective surfaces have typically been static and used in applications with fixed frequencies. However, certain applications could benefit from a reconfigurable frequency response. The frequency response of an FSS can be tuned by rotating the elements off of the surface of the supporting dielectric. MEMS technology is utilized in this project to achieve this goal. Samples have been designed, simulated, fabricated and measured at UCLA demonstrating this technology.
NK Cells, Tumor Cell Transition, and Tumor Progression in Solid Malignancies: New Hints for NK-Based Immunotherapy? (2016)

Several evidences suggest that NK cells can patrol the body and eliminate tumors in their initial phases but may hardly control established solid tumors. Multiple factors, including the transition of tumor cells towards a proinvasive/prometastatic phenotype, the immunosuppressive effect of the tumor microenvironment, and the tumor structure complexity, may account for limited NK cell efficacy. Several putative mechanisms of NK cell suppression have been defined in these last years; conversely, the cross talk between NK cells and tumor cells undergoing different transitional phases remains poorly explored. Nevertheless, recent in vitro studies and immunohistochemical analyses on tumor biopsies suggest that NK cells could not only kill tumor cells but also influence their evolution. Indeed, NK cells may induce tumor cells to change the expression of HLA-I, PD-L1, or NKG2D-L and modulate their susceptibility to the immune response. Moreover, NK cells may be preferentially located in the borders of tumor masses, where, indeed, tumor cells can undergo Epithelial-to-Mesenchymal Transition (EMT) acquiring prometastatic phenotype. Finally, the recently highlighted role of HMGB1 both in EMT and in amplifying the recruitment of NK cells provides further hints on a possible effect of NK cells on tumor progression and fosters new studies on this issue.
Fermentative Butanol Production (2008)

Clostridium acetobutylicum is an anaerobic, spore-forming bacterium with the ability to ferment starch and sugars into solvents. In the past, it has been used for industrial production of acetone and butanol, until cheap crude oil rendered petrochemical synthesis more economically feasible. Both economic (price of crude oil) and environmental aspects (carbon dioxide emissions) have caused the pendulum to swing back again. Molecular biology has allowed a detailed understanding of genes and enzymes, required for solventogenesis. Thus, construction of strains with improved fermentation ability is now possible. Advances in continuous culture technology and improved downstream processing also add to economic advantages of a new biotechnological process. Two major companies have already committed themselves to biobutanol production as a biofuel additive. Thus, butanol fermentation is on the rise again.
Computational Complexity: A Modern Approach (2009)

Not to be reproduced or distributed without the authors ’ permissioniiTo our wives — Silvia and RavitivAbout this book Computational complexity theory has developed rapidly in the past three decades. The list of surprising and fundamental results proved since 1990 alone could fill a book: these include new probabilistic definitions of classical complexity classes (IP = PSPACE and the PCP Theorems) and their implications for the field of approximation algorithms; Shor’s algorithm to factor integers using a quantum computer; an understanding of why current approaches to the famous P versus NP will not be successful; a theory of derandomization and pseudorandomness based upon computational hardness; and beautiful constructions of pseudorandom objects such as extractors and expanders. This book aims to describe such recent achievements of complexity theory in the context of more classical results. It is intended to both serve as a textbook and as a reference for self-study. This means it must simultaneously cater to many audiences, and it is carefully designed with that goal. We assume essentially no computational background and very minimal mathematical background, which we review in Appendix A. We have also provided a web site for this book at
The epitope for monoclonal antibody A20 (amino acids 870-890) is located on the luminal surface of the Ca2(+)-ATPase of sarcoplasmic reticulum. (1990)

The epitope for monoclonal antibody A20 was mapped to amino acids 870-890 of the Ca2(+)-ATPase of rabbit fast-twitch skeletal muscle sarcoplasmic reticulum. The antibody did not react with the epitope in intact sarcoplasmic reticulum vesicles but reacted with the epitope when the vesicles were solubilized with the detergent C12E8 or made permeable by incubation in a hypotonic medium. By contrast, antibody A52, which binds to a cytoplasmic epitope consisting of amino acids 657-672, reacted with the Ca2(+)-ATPase in vesicular, permeabilized vesicular, and C12E8-solubilized states. These results clearly demonstrate that antibody A20 binds to a luminal epitope and provide the first demonstration that a specific segment of the Ca2(+)-ATPase is located on the luminal surface of the sarcoplasmic reticulum. These results are consistent with, and support, our model for folding of the Ca2(+)-ATPase (Brandl, C. J., Korczak, B., Green, N. M., and MacLennan, D. H. (1986) Cell 44, 597-607) in which residues 657-672 were proposed to form part of the cytoplasmic nucleotide binding domain, while residues 870-890 were proposed to form a luminal loop between proposed transmembrane sequences M7 and M8.
Receiver structures for time-varying frequency-selective fading channels (1999)

Several receiver structures for linearly modulated signals are proposed for time-varying frequency-selective channels. Their channel estimators explicitly model the time variation of the channel taps via polynomials. These structures are constructed from the following building blocks: (i) sliding or fixed block channel estimators; (ii) maximum likelihood sequence detectors (MLSDs) or decision feedback equalizers (DFEs); and (iii) single or multiple passes. A sliding window channel estimator uses a window of received samples to estimate the channel taps within or at the end of the window. Every symbol period, the window of samples is slid along another symbol period, and a new estimate is calculated. A fixed block channel estimator uses all received samples to estimate the channel taps throughout the packet, all at once. A single pass receiver estimates the channel and detects data once only. A multipass receiver performs channel estimation and data detection repetitively. The effect of the training symbol positions on the performance of the block multipass approach is studied. The bit error rate (BER) performance of the MLSD structures is characterized through simulation and analysis. The proposed receivers offer a range of performance/complexity tradeoffs, but all are well suited to time-varying channels. In fast fading channels, as the signal-to-noise ratio (SNR) increases, they begin to significantly outperform the per-survivor processing-based MLSD receivers which employ the least mean-squares (LMS) algorithm for channel estimation.
Ribosome Stalling during Translation Elongation Induces Cleavage of mRNA Being Translated in Escherichia coli (2004)

Recently, it has been found that ribosome pausing at stop codons caused by certain nascent peptides induces cleavage of mRNA in Escherichia coli cells (1, 2). The question we addressed in the present study is whether mRNA cleavage occurs when translation elongation is prevented. We focused on a specific peptide sequence (AS17), derived from SecM, that is known to cause elongation arrest. When the crp-crr fusion gene encoding CRP-AS17-IIA(Glc) was expressed, cAMP receptor protein (CRP) proteins truncated around the arrest sequence were efficiently produced, and they were tagged by the transfer-messenger RNA (tmRNA) system. Northern blot analysis revealed that both truncated upstream crp and downstream crr mRNAs were generated along with reduced amounts of the full-length crp-crr mRNA. The truncated crp mRNA dramatically decreased in the presence of tmRNA due to rapid degradation. The 3' ends of truncated crp mRNA correspond well to the C termini of the truncated CRP proteins. We conclude that ribosome stalling by the arrest sequence induces mRNA cleavage near the arrest point, resulting in nonstop mRNAs that are recognized by tmRNA. We propose that the mRNA cleavage induced by ribosome stalling acts in concert with the tmRNA system as a way to ensure quality control of protein synthesis and possibly to regulate the expression of certain genes.
Amelioration of Long-Term Renal Changes in Obese Type 2 Diabetic Mice by a Neutralizing Vascular Endothelial Growth Factor Antibody (2002)

Diabetic nephropathy in type 2 diabetic patients is a frequent complication associated with increased morbidity and mortality. Various growth factors and cytokines have been implicated in the pathogenesis of diabetic kidney disease, including vascular endothelial growth factor (VEGF). To explore a role for VEGF in renal changes in type 2 diabetes, we examined the renal effects of a neutralizing murine VEGF antibody in the diabetic db/db mouse, a model of obese type 2 diabetes. One group of db/db mice was treated for 2 months with a VEGF antibody, while another db/db group was treated for the same period with an isotype-matched irrelevant IgG. A third group consisting of nondiabetic db/+ mice was treated with the same isotype-matched IgG for 2 months. Placebo-treated db/db mice showed a pronounced increase in kidney weight, glomerular volume, basement membrane thickness (BMT), total mesangial volume, urinary albumin excretion (UAE), and creatinine clearance (CrCl) when compared with nondiabetic controls. In VEGF antibody-treated db/db mice, increases in kidney weight, glomerular volume, BMT, and UAE were attenuated, whereas the increase in CrCl was abolished. VEGF antibody administration tended to reduce expansion in total mesangial volume. These effects in diabetic animals were seen without impact on body weight, blood glucose, insulin levels, or food consumption. In conclusion, chronic inhibition of VEGF in db/db mice ameliorates the diabetic renal changes seen in type 2 diabetes.
Adaptive circuits using pFET floating-gate devices (1999)

In this paper, we describe our floating-gate pFET device, with its many circuit applications and supporting experimental measurements. We developed these devices in standard double-poly CMOS technologies by utilizing many effects inherent in these processes. We add floating-gate charge by electron tunneling, and we remove floating-gate charge by hot-electron injection. With this floating-gate technology, we cannot only build analog EEPROMs, we can also implement adaptation and learning when we consider floating-gate devices to be circuit elements with important time-domain dynamics. We start by discussing non-adaptive properties of floating-gate devices and we present two representative non-adaptive applications. First, we discuss using the floating-gate pFETs as non-volatile voltage sources or potentiometers (e-pots). Second, we discuss using floating-gate pFETs to build translinear circuits that compute the product of powers of the input currents. We then discuss the physics, behavior, and applications of adaptation using floating-gate pFETs. The physics of adaptation starts with floating-gate pFETs with continuous tunneling and injection currents. A single floating-gate MOS device operating with continuous-time tunneling and injection currents can exhibit either stabilizing or destabilizing behaviors. One particular application is an autozeroing floating-gate amplifier (AFGA) that uses tunneling and pFET hot-electron injection to adaptively set its DC operating point. Continuous-time circuits comprising multiple floating-gate MOS devices show various competitive and cooperative behaviors between devices. These floating-gate circuits can be used to build silicon systems that adapt and learn.
THE KINETICS OF CELLULAR PROLIFERATION IN REGENERATING LIVER (1968)

The study concerns the kinetics of cellular proliferation in the different cell populations of the normal and regenerating rat liver. A detailed analysis is presented, which includes techniques of in vivo labeling of DNA with tritiated thymidine and high-resolution radioautography, of the temporal and spatial patterns of DNA synthesis and cell division in the parenchymal cells, littoral cells, bile duct epithelium, and other cellular components in the liver during the first 64 hr of regeneration after partial hepatectomy. The analysis of cell population kinetics indicates that (a) the rate of entry of parenchymal cells into synthesis, after an initial burst of proliferative activity, was an orderly progression at 3-4%/hr; (b) most cells divided once and a few twice, a large proportion of the cell deficit being replaced by 72 hr after the onset of proliferation; (c) T(s) was approximately 8.0 hr; T(gg2+m/2), 3.0 hr; and M, approximately 1.0 hr. Littoral cell proliferation began about 24 hr after the onset of parenchymal cell proliferation; the rate of entry of littoral cells into synthesis was greater than 4%/hr. Interlobular bile duct cell proliferation lagged well behind the parenchymal and littoral cell populations both in time and extent of proliferation.
Sporozoite-Induced Immunity in Mammalian Malaria (1972)

SummaryBased on experimental evidence the following fundamental characteristics of sporozoite-induced immunity have, so far, been established. 1. The sporozoite stage of malaria parasites is strongly immunogenic. The intravenous injection of small numbers of attenuated, X-irradiated sporozoites induces a high degree of protective immunity and formation of anti-sporozoite antibodies. 2. Sporozoite-induced immunity is highly stage-specific. Its effects are mainly directed against the sporozoite stage. The erythrocytic stages of the parasite are not affected by this immune mechanism. 3. Considerable cross-protection and serologic cross-reactivity occur among sporozoites of different rodent malaria strains and species. 4. Sporozoites undergo antigenic changes during their process of maturation. These might possibly be correlated with the development of sporozoite infectivity. 5. The spleen does not play an essential role in sporozoite-induced protective immunity. The immunization of splenectomized animals renders them resistant to sporozoite challenge in the absence of antibodies detectable by the CSP reaction. 6. Sporozoite-induced immunity is, at least in part, serum-mediated. The incubation of sporozoites with immune serum considerably reduces their infectivity. The passive transfer of immune serum considerably increases the rate of sporozite clearance observed in normal animals. 7. The non-specific stimulation of the reticulo-endothelial system which occurs during sporozoite immunization is very shortlived. This reticulo-endothelial system stimulation does not play an important role in protection against sporozoite challenge.
Induction of Antigen-Specific Cytotoxic T Lymphocytes in Humans by a Malaria DNA Vaccine (1998)

CD8+ cytotoxic T lymphocytes (CTLs) are critical for protection against intracellular pathogens but often have been difficult to induce by subunit vaccines in animals. DNA vaccines elicit protective CD8+ T cell responses. Malaria-naïve volunteers who were vaccinated with plasmid DNA encoding a malaria protein developed antigen-specific, genetically restricted, CD8+ T cell-dependent CTLs. Responses were directed against all 10 peptides tested and were restricted by six human lymphocyte antigen (HLA) class I alleles. This first demonstration in healthy naïve humans of the induction of CD8+ CTLs by DNA vaccines, including CTLs that were restricted by multiple HLA alleles in the same individual, provides a foundation for further human testing of this potentially revolutionary vaccine technology.
Recent Validation Efforts for a Comprehensive Modal Emissions Model (2001)

Mobile source emissions estimation techniques play a critical role for regional planning and development of emission control strategies. The primary models for mobile source emissions estimation have been the U.S. Environmental Protection Agency’s MOBILE model and the California Air Resources Board’s EMFAC model. These models work well for large regional areas but are not as well suited for “microscale” evaluation. Over the last several years, the College of Engineering–Center for Environmental Research and Technology (CE-CERT) has been evaluating in-use, light-duty vehicles as part of NCHRP Project 25-11, resulting in the development of a Comprehensive Modal Emissions Model (CMEM). An essential part of any model development process is validating the model. Various validation techniques have been applied to CMEM. This paper describes some of the latest validation work carried out in comparing CMEM results to independent emission testing results (independent in both vehicles and driving cycles). Further, CMEM has been compared with the latest versions of EMFAC and MOBILE. In general, compared with the independent emission measurements, CMEM predicts well. It has been found that CMEM is consistent with MOBILE and EMFAC at low to medium speeds. Greater deviations were found at very low speeds and very high speeds. At high speeds, CMEM tends to predict higher hydrocarbon (HC) emissions and lower oxides of nitrogen (NO x ) emissions. At the very low speeds, CMEM tends to predict lower than EMFAC and MOBILE for all emissions. These comparisons are part of an ongoing validation process for development of CMEM.
[Effect of histone deacetylase inhibitor NL101 on rat neurons]. (2014)

NL101 has protective effect on HCA-induced neuronal injury but it is neurotoxic at high concentrations, which is similar to the typical histone deacetylase inhibitor SAHA.