gebhart/patrepeval huggingface dataset:
Novel CD4-Based Bispecific Chimeric Antigen Receptor Designed for Enhanced Anti-HIV Potency and Absence of HIV Entry Receptor Activity (2015)

HIV research has been energized by prospects for a cure for HIV infection or, at least, for a "functional cure" whereby antiretroviral therapy can be discontinued without virus rebound. This report describes a novel CD4-based "chimeric antigen receptor" (CAR) which, when genetically engineered into T cells, gives them the capability to selectively respond to and kill HIV-infected cells. This CAR displays enhanced features compared to previously described CD4-based CARs, namely, increased potency and avoidance of the undesired rendering of the genetically modified CD8 T cells susceptible to HIV infection. When adoptively transferred back to the individual, the genetically modified T cells will hopefully provide durable killing of infected cells and sustained virus suppression without continued antiretroviral therapy, i.e., a functional cure.
A Facile Preparation and Cyclopropanation of 1-Alkenylsilanols (1998)

Abstract Alkenylsilanols are prepared by the reaction of hexamethyltrisiloxane (D3) with alkenyllithiums or alternatively by the reaction of cyclic siloxanes substituted by an alkenyl group with organolithiums and transformed to the corresponding cyclopropylsilanols using diiodomethane and diethylzinc. Lithium alkenylsilanolates, primary products of the preparation, also undergo cyclopropanation. As in the case of allylic alcohols, the silanol functionality is found to enhance the rate of cyclopropanation compared with that of alkenyltrialkylsilane or alkoxydialkylsilane. The obtained cyclopropylsilanols are further converted into the corresponding cyclopropanols by the Tamao oxidation.
Rule-based query optimization, revisited (1999)

We present the architecture and a performance assessment of an extensible query optimizer written in Venus. Venus is a general-purpose active-database rule language embedded in C++. Following the developments in extensible database query optimizers, first in rule-based form, followed by optimizers written as object-oriented programs, the Venus-based optimizer avails to the advantages of both. Venus' modular structure allows us to go a step further and provide extensibility in search by defining parameterized search components in a declarative form that has the additional effect of integrating heuristic and cost-based optimization. We compare optimizers developed with Volcano, OPT++ and Venus. Venus' optimizing compiler yields code whose performance is comparable with Volcano and OPT++ on smaller queries. The ability to introduce additional pruning heuristics yields better scalability on larger queries. Evaluation of the system using quantitative software metrics supports a claim that the Venus-based optimizer is more easily maintained and extended than are its predecessors.
Utility and Accuracy of Template-Directed Dye-Terminator Incorporation with Fluorescence-Polarization Detection for Genotyping Single Nucleotide Polymorphisms (2002)

There are little independent data available about how well single nucleotide polymorphism (SNP) genotyping technologies perform in the typical molecular genetics laboratory. We evaluated the utility and accuracy of a widely used technology, template-directed dye-terminator incorporation with fluorescence-polarization detection (FP-TDI), in a sample of 177 SNPs selected solely on the basis of map location. Genotypes were generated without optimization using standard protocols. Overall, 81% of the SNPs we studied generated readable genotypes by FP-TDI. Thirty-two SNPs were genotyped in duplicate by PCR-RFLP orfluorescent dye-terminator sequencing. Out of a total of 631 duplicate genotypes, no true discrepancies were detected. The true error rate has a 95% chance of lying between 0 and 6 out of 1000 genotypes. We also tested for deviations from Hardy-Weinberg Equilibrium in 33 SNPs genotyped in 50 unrelated individuals, and no significant deviations were detected. Our FP-TDI data were readily adaptable to automated genotype calling using our own method of cluster analysis, which assigns a probability score to each genotype call. We conclude that FP-TDI is both efficient and accurate. The method can easily fill the needs of SNP genotyping projects at the scale typically used for regional or candidate-gene association studies.
Natural human antibodies to pneumococcus have distinctive molecular characteristics and protect against pneumococcal disease (2007)

The molecular and functional characteristics of natural antibody from the preimmune repertoire have not been explored in detail in man. We describe seven human IgM monoclonal antibodies selected on the basis of pneumococcal polysaccharide binding that share both molecular and functional characteristics with natural antibody, suggesting a common B cell lineage origin. Unlike class-switched antibodies, which are serotype-specific, the antibodies were polyreactive and bound all pneumococcal polysaccharide capsular serotypes tested. Some bound endogenous antigens, including blood group antigens and intermediate filament proteins. All the antibodies used unmutated heavy chain V (IGHV) that are expressed at an increased frequency in the elderly and in the preimmune repertoire. The CDR3 was characterized by long length (mean aa 18.4 (+/-4.2) and selective use of IGHD6 (P < 0.001) and IGHJ6 (P < 0.01) family genes. The clones expressing IGHV1-69 and IGHV 3-21 provided significant passive protection against invasive pneumococcal disease in vivo.
Murine mammary FM3A carcinoma cells transformed with the herpes simplex virus type 1 thymidine kinase gene are highly sensitive to the growth‐inhibitory properties of (E)‐5‐(2‐bromovinyl)‐2'‐deoxyuridine and related compounds (1985)

Murine mammary carcinoma (FM3A TK-/HSV-1 TK+) cells, which are thymidine kinase (TK)-deficient but have been transformed with the herpes simplex virus type 1 (HSV-1) TK gene are inhibited in their growth by (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU) and (E)-5-(2-bromovinyl)-2'-deoxycytidine (BVDC) at 0.5, 0.5 and 0.8 ng/ml, respectively; i.e., a concentration 5000 to 20 000-fold lower than that required to inhibit the growth of the corresponding wild-type FM3A/0 cells. Hence, transformation of tumor cells with the HSV-1 TK gene makes them particularly sensitive to the cytostatic action of BVDU and related compounds.
Eine Reihe definierter Metathesekatalysatoren – Synthese von und Reaktionen mit [RuCl2 ( CHR′)(PR3)2] (1995)

Wesentlich bessere Initiatoren und demzufolge erheblich reaktiver als die Komplexe des Typs A sind die Metathesekatalysatoren B , die durch Umsetzung von [RuCl 2 (PPh 3 ) 3 ] mit den entsprechenden Diazoalkanen und nachfolgenden Phosphanaustausch erhältlich sind. Während die PPh 3 ‐Derivate ausgezeichnete Katalysatoren für die lebende ROMP von Norbornen sind, erweist sich der Komplex mit R  Cy, R′  Ph zusätzlich als sehr wirksamer Katalysator für die Metathese acyclischer Alkene. magnified image
Endothelial injury: cause and effect of alloimmune inflammation (2002)

This review discusses the concept that endothelial cells may facilitate inflammation, but are also targets of the inflammatory response. Endothelial cells express several molecules that promote leukocyte recruitment, and other molecules, such as MHC class I that enable endothelial injury. Circulating alloantibodies produced following transplantation may also target the endothelium for injury. It has been shown that the expression of select protective genes within endothelial cells, including anti-apoptotic genes, may provide resistance to immune-mediated injury. Thus, an understanding of the mechanisms by which endothelial cells are injured and by which endothelial cells are protected is important for our understanding of allograft rejection.
Plasma membrane targeting of SNAP-25 increases its local concentration and is necessary for SNARE complex formation and regulated exocytosis (2002)

SNAP-25 is an integral protein of the plasma membrane involved in neurotransmission and hormone secretion. The cysteine-rich domain of SNAP-25 is essential for membrane binding and plasma-membrane targeting. However, this domain is not required for SNARE complex formation and fusion of membranes in vitro. In this paper, we describe an 'intact-cell'-based system designed to compare the effect of similar amounts of membrane-bound and soluble SNAP-25 proteins on regulated exocytosis. In transfected neuroblastoma cells, Botulinum neurotoxin E (BoNT/E), a protease that cleaves SNAP-25, blocks regulated release of hormone. However, hormone release is rescued by expressing a wild-type SNAP-25 protein resistant to the toxin. BoNT/E-resistant SNAP-25 proteins lacking the cysteine-rich domain or with all the cysteines substituted by alanines do not form SNARE complexes or rescue regulated exocytosis when expressed at the same level as membrane-bound SNAP-25, which is approximately four-fold higher than the endogenous protein. We conclude that the cysteine-rich domain of SNAP-25 is essential for Ca(2+)-dependent hormone release because, by targeting SNAP-25 to the plasma membrane, it increases its local concentration, leading to the formation of enough SNARE complexes to support exocytosis.
Creatine supplementation and age influence muscle metabolism during exercise (1998)

Young [n = 5, 30 +/- 5 (SD) yr] and middle-aged (n = 4, 58 +/- 4 yr) men and women performed single-leg knee-extension exercise inside a whole body magnetic resonance system. Two trials were performed 7 days apart and consisted of two 2-min bouts and a third bout continued to exhaustion, all separated by 3 min of recovery. 31P spectra were used to determine pH and relative concentrations of Pi, phosphocreatine (PCr), and beta-ATP every 10 s. The subjects consumed 0.3 g . kg-1 . day-1 of a placebo (trial 1) or creatine (trial 2) for 5 days before each trial. During the placebo trial, the middle-aged group had a lower resting PCr compared with the young group (35.0 +/- 5.2 vs. 39.5 +/- 5.1 mmol/kg, P < 0.05) and a lower mean initial PCr resynthesis rate (18.1 +/- 3.5 vs. 23.2 +/- 6.0 mmol . kg-1 . min-1, P < 0.05). After creatine supplementation, resting PCr increased 15% (P < 0.05) in the young group and 30% (P < 0.05) in the middle-aged group to 45.7 +/- 7.5 vs. 45.7 +/- 5.5 mmol/kg, respectively. Mean initial PCr resynthesis rate also increased in the middle-aged group (P < 0.05) to a level not different from the young group (24.3 +/- 3.8 vs. 24.2 +/- 3.2 mmol . kg-1 . min-1). Time to exhaustion was increased in both groups combined after creatine supplementation (118 +/- 34 vs. 154 +/- 70 s, P < 0.05). In conclusion, creatine supplementation has a greater effect on PCr availability and resynthesis rate in middle-aged compared with younger persons.
Amelioration of doxorubicin-induced cardiotoxicity by resveratrol (2014)

Doxorubicin (DOX), is a highly active anticancer agent, but its clinical use is limited by its severe cardiotoxic side‑effects associated with increased oxidative stress and apoptosis. Resveratrol (RSVL) is a naturally occurring polyphenolic compound (trans-3,5,4'-trihydroxystilbene) found primarily in root extracts of the oriental plant Polygonum cuspidatum and of numerous additional plant species. It has recently been shown that RSVL has a number of beneficial effects in different biological systems, which include anti-oxidant, antineoplastic, anticarcinogenic, cardioprotective and antiviral effects. In this study, we examined whether RSVL has protective effects against DOX‑induced free radical production and cardiotoxicity in male rats. The tested dose of DOX (20 mg/kg) caused a significant increase in the serum activities of the cardiac enzymes lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) and the level of malondialdehyde (MDA) in the heart tissue. However, there was a significant decrease in the glutathione level in the heart tissue. Simultaneous treatment of rats with RSVL [10 mg/kg, intraperitoneal (i.p.) injection] reduced the activity of LDH and CPK and significantly reduced MDA production in the heart. The total antioxidant capacity was increased following RSVL administration. Electron microscopy examination of the heart tissue showed that DOX treatment results in massive fragmentation and lysis of the myofibrils, and that mitochondria show either vacuolization or complete loss of the cristae. Simultaneous treatment with RSVL ameliorated the effect of DOX administration on cardiac tissue, with cardiomyocytes appearing normal compared to the control samples, and mitochondria retaining their normal structure.
Cancer genome sequencing: a review (2009)

A genomic era of cancer studies is developing rapidly, fueled by the emergence of next-generation sequencing technologies that provide exquisite sensitivity and resolution. This article discusses several areas within cancer genomics that are being transformed by the application of new technology, and in the process are dramatically expanding our understanding of this disease. Although, we anticipate that there will be many exciting discoveries in the near future, the ultimate success of these endeavors rests on our ability to translate what is learned into better diagnosis, treatment and prevention of cancer.
Isolation of two new polymyxin group antibiotics. Studies on antibiotics from the genus Bacillus. XX. (1977)

Two new members of polymyxin group antibiotics, polymyxins S1 and T1, were isolated from the culture broths of strains identified as Bacillus polymyxa Rs-6 and Bacillus polymyxa E-12, respectively. These antibiotics are strongly basic substances, their hydrochloric acid salts are soluble in water and methanol. They are primarily active against Gram-negative bacteria in vitro and in vivo though polymyxin T1 exhibits higher activities against Gram-positive bacteria than other polymyxin group antibiotics.
Pyranonaphthoquinone Lactones: A New Class of AKT Selective Kinase Inhibitors Alkylate a Regulatory Loop Cysteine (2009)

The naturally occurring pyranonaphthoquinone (PNQ) antibiotic lactoquinomycin and related aglycones were found to be selective inhibitors of the serine-threonine kinase AKT. A set of synthetic PNQs were prepared and a minimum active feature set and preliminary SAR were determined. PNQ lactones inhibit the proliferation of human tumor cell lines containing constitutively activated AKT and show expected effects on cellular biomarkers. Biochemical data are presented supporting a proposed bioreductive alkylation mechanism of action.
Phosphatidylinositol (PI) 3-kinase and PI 4-kinase binding to the CD4-p56lck complex: the p56lck SH3 domain binds to PI 3-kinase but not PI 4-kinase. (1993)

CD4 serves as a receptor for major histocompatibility complex class II antigens and as a receptor for the human immunodeficiency virus type 1 (HIV-1) viral coat protein gp120. It is coupled to the protein-tyrosine kinase p56lck, an interaction necessary for an optimal response of certain T cells to antigen. In addition to the protein-tyrosine kinase domain, p56lck possesses Src homology 2 and 3 (SH2 and SH3) domains as well as a unique N-terminal region. The mechanism by which p56lck generates intracellular signals is unclear, although it has the potential to interact with various downstream molecules. One such downstream target is the lipid kinase phosphatidylinositol 3-kinase (PI 3-kinase), which has been found to bind to activated pp60src and receptor-tyrosine kinases. In this study, we verified that PI 3-kinase associates with the CD4:p56lck complex as judged by the presence of PI 3-phosphate generated from anti-CD4 immunoprecipitates and detected by high-pressure liquid chromatographic analysis. However, surprisingly, CD4-p56lck was also found to associate with another lipid kinase, phosphatidylinositol 4-kinase (PI 4-kinase). The level of associated PI 4-kinase was generally higher than PI 3-kinase activity. HIV-1 gp120 and antibody-mediated cross-linking induced a 5- to 10-fold increase in the level of CD4-associated PI 4- and PI 3-kinases. The use of glutathione S-transferase fusion proteins carrying Lck-SH2, Lck-SH3, and Lck-SH2/SH3 domains showed PI 3-kinase binding to the SH3 domain of p56lck, an interaction facilitated by the presence of an adjacent SH2 domain. PI 4-kinase bound to neither the SH2 nor the SH3 domain of p56lck. CD4-p56lck contributes PI 3- and PI 4-kinase to the activation process of T cells and may play a role in HIV-1-induced immune defects.
Activated Renal Macrophages Are Markers of Disease Onset and Disease Remission in Lupus Nephritis (2008)

Costimulatory blockade with CTLA4Ig and anti-CD40L along with a single dose of cyclophosphamide induces remission of systemic lupus erythematosus nephritis in NZB/W F(1) mice. To understand the mechanisms for remission and for impending relapse, we examined the expression profiles of 61 inflammatory molecules in the perfused kidneys of treated mice and untreated mice at different stages of disease. Further studies using flow cytometry and immunohistochemistry allowed us to determine the cellular origins of several key markers. We show that only a limited set of inflammatory mediators is expressed in the kidney following glomerular immune complex deposition but before the onset of proteinuria. Formation of a lymphoid aggregate in the renal pelvis precedes the invasion of the kidney by inflammatory cells. Regulatory molecules are expressed early in the disease process and during remission but do not prevent the inevitable progression of active inflammation. Onset of proliferative glomerulonephritis and proteinuria is associated with activation of the renal endothelium, expression of chemokines that mediate glomerular cell infiltration, and infiltration by activated dendritic cells and macrophages that migrate to different topographical areas of the kidney but express a similar profile of inflammatory cytokines. Increasing interstitial infiltration by macrophages and progressive tubular damage, manifested by production of lipocalin-2, occur later in the disease process. Studies of treated mice identify a type II (M2b)-activated macrophage as a marker of remission induction and impending relapse and suggest that therapy for systemic lupus erythematosus nephritis should include strategies that prevent both activation of monocytes and their migration to the kidney.
Synthetic studies via the cross-coupling reaction of organoboron derivatives with organic halides (1991)

Abstract
MALE PHENOTYPES AND MATING EFFICIENCY IN CAENORHABDITIS ELEGANS (1983)

Mating behavior in adult male nematodes can be assayed by mating efficiency, i.e., the number of cross progeny sired by males under standard conditions. Mutant males from 220 strains, representing most of the known complementation groups of C. elegans, have been examined for mating efficiency and for anatomical abnormalities of the specialized male copulatory organs. These data extend the phenotypic description of these mutants and indicate what anatomical and behavioral components are necessary for the ability to mate successfully. Also, mutants with specific defects in the male were sought by establishing superficially wild-type hermaphrodite stocks after mutagenesis and testing the males segregated by these stocks for mating efficiency. Forty-nine of 1119 stocks yielded abnormal males. Seventeen were characterized in detail and found to be abnormal in sensory behavior (carrying mutations in the genes che-2 or che-3) or male genital anatomy (carrying mutations in one of the genes mab-1 to mab-10). Four of the mab (male abnormal) genes affect specific postembryonic cell lineages.
The Second Nuclear Era: A New Start for Nuclear Power (1985)

The thrust of this book is that nuclear power should be fixed, not buried. It is based on a study sponsored by the Andrew W. Mellon Foundation at Oak Ridge National Laboratory. This book is a sober, technically based study of how to make the second nuclear era safe and successful.
Development of a Glycoprotein D-Expressing Dominant-Negative and Replication-Defective Herpes Simplex Virus 2 (HSV-2) Recombinant Viral Vaccine against HSV-2 Infection in Mice (2011)

Using the T-REx (Invitrogen, California) gene switch technology and a dominant-negative mutant polypeptide of herpes simplex virus 1 (HSV-1)-origin binding protein UL9, we previously constructed a glycoprotein D-expressing replication-defective and dominant-negative HSV-1 recombinant viral vaccine, CJ9-gD, for protection against HSV infection and disease. It was demonstrated that CJ9-gD is avirulent following intracerebral inoculation in mice, cannot establish detectable latent infection following different routes of infection, and offers highly effective protective immunity against primary HSV-1 and HSV-2 infection and disease in mouse and guinea pig models of HSV infections. Given these favorable safety and immunological profiles of CJ9-gD, aiming to maximize levels of HSV-2 glycoprotein D (gD2) expression, we have constructed an ICP0 null mutant-based dominant-negative and replication-defective HSV-2 recombinant, CJ2-gD2, that contains 2 copies of the gD2 gene driven by the tetracycline operator (tetO)-bearing HSV-1 major immediate-early ICP4 promoter. CJ2-gD2 expresses gD2 as efficiently as wild-type HSV-2 infection and can lead to a 150-fold reduction in wild-type HSV-2 viral replication in cells coinfected with CJ2-gD2 and wild-type HSV-2 at the same multiplicity of infection. CJ2-gD2 is avirulent following intracerebral injection and cannot establish a detectable latent infection following subcutaneous (s.c.) immunization. CJ2-gD2 is a more effective vaccine than HSV-1 CJ9-gD and a non-gD2-expressing dominant-negative and replication-defective HSV-2 recombinant in protection against wild-type HSV-2 genital disease. Using recall response, we showed that immunization with CJ2-gD2 elicited strong HSV-2-specific memory CD4(+) and CD8(+) T-cell responses. Collectively, given the demonstrated preclinical immunogenicity and its unique safety profiles, CJ2-gD2 represents a new class of HSV-2 replication-defective recombinant viral vaccines in protection against HSV-2 genital infection and disease.
Improving thin-film crystalline silicon solar cell efficiencies with photonic crystals (2007)

Most photovoltaic (solar) cells are made from crystalline silicon (c-Si), which has an indirect band gap. This gives rise to weak absorption of one-third of usable solar photons. Therefore, improved light trapping schemes are needed, particularly for c-Si thin film solar cells. Here, a photonic crystal-based light-trapping approach is analyzed and compared to previous approaches. For a solar cell made of a 2 mum thin film of c-Si and a 6 bilayer distributed Bragg reflector (DBR) in the back, power generation can be enhanced by a relative amount of 24.0% by adding a 1D grating, 26.3% by replacing the DBR with a six-period triangular photonic crystal made of air holes in silicon, 31.3% by a DBR plus 2D grating, and 26.5% by replacing it with an eight-period inverse opal photonic crystal.
Distributed Node Counting in Wireless Sensor Networks in the Presence of Communication Noise (2016)

Distributed node counting in wireless sensor networks can be important in various applications, such as network maintenance and information aggregation. In this paper, a distributed consensus algorithm for estimating the number of nodes in a wireless sensor network in the presence of communication noise is introduced. In networks with a fusion center, counting the number of nodes can easily be done by letting each node to transmit a fixed constant value to the fusion center. In a network without a fusion center, where nodes do not know the graph structure, estimating the number of nodes is not straightforward. The proposed algorithm is based on distributed average consensus and norm estimation. Different sources of error are explicitly discussed; the Fisher information and the distribution of the final estimate are derived. Several design parameters and how they affect the performance of the algorithm are studied, which provide guidelines toward making the estimation error smaller. Simulation results corroborating the theory are also provided.