gebhart/patrepeval huggingface dataset:
UV-induced replication arrest in the xeroderma pigmentosum variant leads to DNA double-strand breaks, γ-H2AX formation, and Mre11 relocalization (2001)

UV-induced replication arrest in the xeroderma pigmentosum variant (XPV) but not in normal cells leads to an accumulation of the Mre11/Rad50/Nbs1 complex and phosphorylated histone H2AX (gamma-H2AX) in large nuclear foci at sites of stalled replication forks. These complexes have been shown to signal the presence of DNA damage, in particular, double-strand breaks (DSBs). This finding suggests that UV damage leads to the formation of DSBs during the course of replication arrest. After UV irradiation, XPV cells showed a fluence-dependent increase in the yield of gamma-H2AX foci that paralleled the production of Mre11 foci. The percentage of foci-positive cells increased rapidly (10-15%) up to fluences of 10 J.(-2) before saturating at higher fluences. Frequencies of gamma-H2AX and Mre11 foci both reached maxima at 4 h after UV irradiation. This pattern contrasts sharply to the situation observed after x-irradiation, where peak levels of gamma-H2AX foci were found to precede the formation of Mre11 foci by several hours. The nuclear distributions of gamma-H2AX and Mre11 were found to colocalize spatially after UV- but not x-irradiation. UV-irradiated XPV cells showed a one-to-one correspondence between Mre11 and gamma-H2AX foci-positive cells. These results show that XPV cells develop DNA DSBs during the course of UV-induced replication arrest. These UV-induced foci occur in cells that are unable to carry out efficient bypass replication of UV damage and may contribute to further genetic variation.
Gain of chromosome 3q defines the transition from severe dysplasia to invasive carcinoma of the uterine cervix. (1996)

We have chosen tumors of the uterine cervix as a model system to identify chromosomal aberrations that occur during carcinogenesis. A phenotype/genotype correlation was established in defined regions of archived, formalin-fixed, and hematoxylin/eosin-stained tissue sections that were dissected from normal cervical epithelium (n = 3), from mild (n = 4), moderate (n = 6), and severe dysplasias/carcinomas in situ (CIS) (n = 13), and from invasive carcinomas (n = 10) and investigated by comparative genomic hybridization. The same tissues were analyzed for DNA ploidy, proliferative activity, and the presence of human papillomavirus (HPV) sequences. The results show that an increase in proliferative activity and tetraploidization had occurred already in mildly dysplastic lesions. No recurrent chromosomal aberrations were observed in DNA extracted from normal epithelium or from mild and moderate dysplasias, indicating that the tetraploidization precedes the loss or gain of specific chromosomes. A gain of chromosome 3q became visible in one of the severe dysplasias/CIS. Notably, chromosome 3q was overrepresented in 90% of the carcinomas and was also found to have undergone a high-level copy-number increase (amplification). We therefore conclude that the gain of chromosome 3q that occurs in HPV16-infected, aneuploid cells represents a pivotal genetic aberration at the transition from severe dysplasia/CIS to invasive cervical carcinoma.
A metric for the breadth of tuning of gustatory neurons (1979)

Journal Article A metric for the breadth of tuning of gustatory neurons Get access David V. Smith, David V. Smith Department of Psychology, University of WyomingLaramie, Wyoming 82071, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph B. Travers Joseph B. Travers Department of Psychology, University of WyomingLaramie, Wyoming 82071, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Chemical Senses, Volume 4, Issue 3, September 1979, Pages 215–229, https://doi.org/10.1093/chemse/4.3.215 Published: 01 September 1979 Article history Received: 01 March 1979 Revision received: 01 May 1979 Accepted: 01 July 1979 Published: 01 September 1979
Neuroparalytic Accidents of Antirabies Vaccination With Suckling Mouse Brain Vaccine (1977)

• Twenty-one cases of neuroparalytic accidents of rabies vaccination (with suckling mouse brain vaccine), 11 of them fatal, were observed, occurring predominantly in men; the mean age of the patients was 29 years. On the average, 13 doses of the vaccine were used. Only three patients received less than seven doses. The mean latent period was 14 days (range, 4 to 24 days). In 16 patients (76%), a Guillain-Barré syndrome occurred that was moderate in three, severe in seven, and fatal in six. Pathologically, this was shown to be a typical polyradiculoneuritis. Five patients had fatal involvement of the central nervous system. Three had an acute disseminated perivenous leukoencephalopathy, with concurrent rabies encephalitis in one case. One patient had a perivenous myeloradiculopathy and one a chronic encephalomyelopathy of six years' duration with demyelinating plaques in the periventricular white matter, cerebellum, and spinal cord. Since the reduction of postexposure rabies vaccination to seven doses, no new cases have been observed in Colombia.
Gamma-aminobutyric acidA receptor structure and function. (1992)

The major type of receptor for the most important inhibitory neurotransmitter y-aminobutyric acid (GABA)' in the mammalian central nervous system is the GABAA receptor.The far reaching functional significance of GABA suggests a role for GABAA receptors in human neurological and psychiatric disorders (1) and in the mechanism of action of numerous clinically important drugs (2).The GABAA receptor is a member of a gene superfamily of ligand-gated ion channel receptors which are typified by a hetero-oligomeric complex that spans the membrane to form an ion channel.Binding of a specific neurotransmitter ligand to the receptor protein controls the opening and closing of the ion channel (3, 4).The GABAA receptor channel is constituted from a family of 15 or so genes encoding for related but different polypeptides.Homologous sequence domains among members of the family and superfamily are believed to have conserved structural and functional features.This article will briefly summarize the latest information available on the GABAA receptor-ion channel complex.The literature cited is illustrative, not exhaustive. GABA Receptor Physiology and PharmacologyThe GABAA receptor is a macromolecular complex, the GABA-benzodiazepine receptor/chloride channel protein (2, 4).The complex consists of five major binding domains: sites for GABA, benzodiazepines, barbiturates, picrotoxin, and the anesthetic steroids.These binding domains serve to modulate the receptor's response to GABA activation.An integral part of this complex is the chloride channel.GABA analogs such as muscimol, an ingredient of the hallucinogenic mushroom Amanita muscaria, act as agonists, binding to the GABA site and opening the C1-channel.The plant-derived convulsant bicuculline is considered the definitive competitive antagonist of GABAA receptors (2).Electrophysiological investigations of GABAA receptor function including single channel recording indicate that it mediates an increase in membrane chloride permeability, resulting in inhibition of electrical activity of the postsynaptic cell (5, 6).Ion channel activation involves complex kinetics of opening and closing on a millisecond time scale and desensitizes in the continuing presence of GABA.36Cl-flux studies NS22071, NS28772, AA07680, and HD06576.
Teaching Protein Purification and Characterization Techniques. A Student-Initiated, Project-Oriented Biochemistry Laboratory Course (2008)

This report describes a biochemistry laboratory that is completely project-oriented. Upper-level biology and chemistry majors work in teams to purify a protein of their choice. After the student groups have completed literature searches, ordered reagents, and made buffers they continue to learn basic protein purification and biochemical techniques as needed during the semester. As the protein purifications progress the students encounter many common problems associated with attempting to reproduce published protein purifications. The students gain valuable problem-solving skills and work in a research group environment. The culmination of the course requires some characterization of the protein, a formal laboratory report, and a final presentation. Students characterize their proteins using activity assays or techniques such as infrared or circular dichroism to study protein structure or unfolding. Day-to-day laboratory experiences resemble an active undergraduate research laboratory. This laboratory is unstructured and works to integrate research and education and retain students in the sciences by exposing them to a completely open-ended, inquiry-based laboratory.
476. 2-Cyano-4-nitrophenylhydrazine and 3-amino-5-nitroindazole (1959)

E. W. Parnell, J. Chem. Soc., 1959, 2363 DOI: 10.1039/JR9590002363
Characterization of CD33/CD3 Tetravalent Bispecific Tandem Diabodies (TandAbs) for the Treatment of Acute Myeloid Leukemia (2016)

Our data show high efficacy of CD33/CD3 TandAbs in various preclinical models of human AML. Together, these findings support further study of CD33/CD3 TandAbs as novel immunotherapeutics for patients with AML. Clin Cancer Res; 22(23); 5829-38. ©2016 AACR.
Gene-for-Gene Defense of Wheat Against the Hessian Fly Lacks a Classical Oxidative Burst (2006)

Genetic similarities between plant interactions with microbial pathogens and wheat interactions with Hessian fly larvae prompted us to investigate defense and counterdefense mechanisms. Plant oxidative burst, a rapid increase in the levels of active oxygen species (AOS) within the initial 24 h of an interaction with pathogens, commonly is associated with defenses that are triggered by gene-for-gene recognition events similar to those involving wheat and Hessian fly larvae. RNAs encoded by Hessian fly superoxide dismutase (SOD) and catalase (CAT) genes, involved in detoxification of AOS, increased in first-instar larvae during both compatible and incompatible interactions. However, mRNA levels of a wheat NADPH oxidase (NOX) gene that generates superoxide (O2-) did not increase. In addition, inhibiting wheat NOX enzyme with diphenyleneiodonium did not result in increased survival of avirulent larvae. However, nitro blue tetrazolium staining indicated that basal levels of O2- are present in both uninfested and infested wheat tissue. mRNA encoded by wheat genes involved in detoxification of the cellular environment, SOD, CAT, and glutathione-S-transferase did not increase in abundance. Histochemical staining with 3,3-diaminobenzidine revealed no increases in wheat hydrogen peroxide (H2O2) during infestation that were correlated with the changes in larval SOD and CAT mRNA. However, treatment with 2',7'-dichlorofluorescin demonstrated the presence of basal levels of H2O2 in the elongation zone of both infested and uninfested plants. The accumulation of a wheat flavanone 3-hydroxylase mRNA did show some parallels with larval gene mRNA profiles. These results suggested that larvae encounter stresses imposed by mechanisms other than an oxidative burst in wheat seedlings.
Messenger RNA Export from the Nucleus: A Series of Molecular Wardrobe Changes (2009)

The advent of the nucleus during the evolutionary development of the eukaryotic cell necessitated the development of a transport system to convey messenger RNA (mRNA) from the site of transcription in the nucleus to ribosomes in the cytoplasm. In this review, we highlight components of each step in mRNA biogenesis, from transcription to processing, that are coupled with mRNA export from the nucleus. We also review the mechanism by which proteins from one step in the mRNA assembly line are replaced by those required for the next. These 'molecular wardrobe changes' appear to be key steps in facilitating the rapid and efficient nuclear export of mRNA transcripts.
Deprivation of arginine by recombinant human arginase in prostate cancer cells (2012)

rhArg causes significant cytotoxicity in LNCaP, DU-145 and PC-3 prostate cancer cells which all demonstrate decreased OCT expression. Inhibition of mTOR manifested by hypophosphorylation of 4E-BP1 suggests autophagy is involved as alternative cell death mechanism. rhArg demonstrates a promising novel agent for prostate cancer treatment.
Review on recent progress of nanostructured anode materials for Li-ion batteries (2014)

This review highlights the recent research advances in active nanostructured anode materials for the next generation of Li-ion batteries (LIBs). In fact, in order to address both energy and power demands of secondary LIBs for future energy storage applications, it is required the development of innovative kinds of electrodes. Nanostructured materials based on carbon, metal/semiconductor, metal oxides and metal phosphides/nitrides/sulfides show a variety of admirable properties for LIBs applications such as high surface area, low diffusion distance, high electrical and ionic conductivity. Therefore, nanosized active materials are extremely promising for bridging the gap towards the realization of the next generation of LIBs with high reversible capacities, increased power capability, long cycling stability and free from safety concerns. In this review, anode materials are classified, depending on their electrochemical reaction with lithium, into three groups: intercalation/de-intercalation, alloy/de-alloy and conversion materials. Furthermore, the effect of nanoscale size and morphology on the electrochemical performance is presented. Synthesis of the nanostructures, lithium battery performance and electrode reaction mechanisms are also discussed. To conclude, the main aim of this review is to provide an organic outline of the wide range of recent research progresses and perspectives on nanosized active anode materials for future LIBs.
Metabolic and cellular plasticity in white adipose tissue I: effects of β3-adrenergic receptor activation (2005)

Selective agonists of beta(3)-adrenergic receptors (Adrb3) exhibit potent anti-diabetes properties in rodent models when given chronically, yet the mechanisms involved are poorly understood. A salient feature of chronic Adrb3 activation is pronounced remodeling of white adipose tissue (WAT), which includes mitochondrial biogenesis and elevation of metabolic rate. To gain insights into potential mechanisms underlying WAT remodeling, the time course of remodeling induced by the Adrb3 agonist CL-316,243 (CL) was analyzed using histological, physiological, and global gene profiling approaches. The results indicate that continuous CL treatment induced a transient proinflammatory response that was followed by cellular proliferation among stromal cells and multilocular adipocytes. CL treatment strongly fragmented the central lipid storage droplet of mature adipocytes and induced mitochondrial biogenesis within these cells. Mitochondrial biogenesis was correlated with the upregulation of genes involved in fatty acid oxidation and mitochondrial electron transport activity. The elevated catabolic activity of WAT was temporally correlated with upregulation of peroxisome proliferator-activated receptor-alpha and its target genes, suggesting involvement of this transcription factor in coordinating the gene program that elevates WAT catabolic activity.
Temperature modulation of the optical transitions involving the Fermi surface in Ag: Experimental (1974)

Thermoreflection and thermotransmission measurements were made on thin semitransparent films of Ag at about 320, 120, and 15 K in the range 3.40-4.40 eV. The results are in fairly good agreement with the theory presented in the preceding paper but show that thin metal films evaporated on amorphous substrates become strained upon cooling to low temperature. The onset of the ${L}_{3}\ensuremath{\rightarrow}L_{2}^{\ensuremath{'}}({E}_{F})$ transition is found to be at 4.03 eV, while the onset of the $L_{2}^{\ensuremath{'}}({E}_{F})\ensuremath{\rightarrow}{L}_{1}$ transition occurs at 3.87 eV.
Microfluidic devices fabricated in Poly(dimethylsiloxane) for biological studies (2003)

This review describes microfluidic systems in poly(dimethylsiloxane) (PDMS) for biological studies. Properties of PDMS that make it a suitable platform for miniaturized biological studies, techniques for fabricating PDMS microstructures, and methods for controlling fluid flow in microchannels are discussed. Biological procedures that have been miniaturized into PDMS-based microdevices include immunoassays, separation of proteins and DNA, sorting and manipulation of cells, studies of cells in microchannels exposed to laminar flows of fluids, and large-scale, combinatorial screening. The review emphasizes the advantages of miniaturization for biological analysis, such as efficiency of the device and special insights into cell biology.
Oncogenic PI3K and its role in cancer (2005)

The PI3K signaling pathway is dysregulated by a variety of mechanisms in a large fraction of human tumors. Both mutational and functional analyses have shown that PIK3CA is an oncogene that plays an important role in tumor progression. Mutant members of the PI3K pathway, including PIK3CA, are good targets for therapeutic intervention because most of them are kinases, making them attractive for drug development. Gaining further insights into PIK3CA oncogenic mechanisms may produce new biomarkers and help the development of targeted therapeutics.
Proteolytic cleavage of pertussis toxin S1 subunit is not essential for its activity in mammalian cells (2005)

S1 processing is not essential for the cellular activity of PT. This distinguishes it from the processing of various other bacterial toxins, which has been shown to be important for their cytotoxicity. S1 processing may be mediated primarily by a metalloprotease, but the cleavage site on S1 is not sequence-dependent and processing appears to depend on the general topology of the protein in that region, indicating that multiple proteases may contribute to this cleavage.
Branched‐Chain Amino Acid–Rich Supplements Containing Microelements Have Antioxidant Effects on Nonalcoholic Steatohepatitis in Mice (2014)

The administration of a combination of antioxidant-rich nutrients, including BCAAs and microelements, is likely to suppress the progression of NASH by reducing oxidative stress, primarily via the downregulation of the ER stress pathway.
Methylprednisolone selectively affects dystrophin expression in human muscle cultures (1993)

Glucocorticoid therapy slows the progression of Duchenne muscular dystrophy. In muscle cultures, the addition of the glucocorticoid methylprednisolone increases myogenesis in most normal mixed and clonal cultures. Conversely, in some normal clonal and most dystrophic cultures, methylprednisolone inhibits fusion. However, in fusion-arrested normal and Becker muscular dystrophy cultures, dystrophin is expressed independently of fusion and of myosin heavy chain expression, and in some cases, expression is apparently enhanced by methylprednisolone. We suggest that dystrophin is a muscle-specific protein that does not require fusion for expression, and the methylprednisolone-induced enhancement of dystrophin expression may account for some of the clinical benefits of glucocorticoids in vivo.
Immune Checkpoint Blockade in Cancer Treatment: A Double-Edged Sword Cross-Targeting the Host as an “Innocent Bystander” (2014)

Targeted immune checkpoint blockade augments anti-tumor immunity and induces durable responses in patients with melanoma and other solid tumors. It also induces specific "immune-related adverse events" (irAEs). IrAEs mainly include gastrointestinal, dermatological, hepatic and endocrinological toxicities. Off-target effects that arise appear to account for much of the toxicity of the immune checkpoint blockade. These unique "innocent bystander" effects are likely a direct result of breaking immune tolerance upon immune check point blockade and require specific treatment guidelines that include symptomatic therapies or systemic corticosteroids. What do we need going forward to limit immune checkpoint blockade-induced toxicity? Most importantly, we need a better understanding of the roles played by these agents in normal tissues, so that we can begin to predict potentially problematic side effects on the basis of their selectivity profile. Second, we need to focus on the predictive factors of the response and toxicity of the host rather than serially focusing on individual agents. Third, rigorous biomarker-driven clinical trials are needed to further elucidate the mechanisms of both the benefit and toxicity. We will summarize the double-edged sword effect of immunotherapeutics in cancer treatment.
Building a metal-responsive promoter with synthetic regulatory elements. (1985)

A fusion gene consisting of the promoter region from the mouse metallothionein-I gene joined to the coding region of the herpes simplex virus thymidine kinase gene is efficiently regulated by zinc in a transient assay when transfected into baby hamster kidney cells. Analysis of similar plasmids in which the metallothionein-I promoter region was mutated indicated the presence of multiple metal regulatory elements (MREs) between -176 and -44 base pairs from the cap site. To further investigate the function of MREs, we inserted a synthetic DNA fragment containing the sequence of MRE-a (the element between -55 and -44 base pairs) into the nonresponsive promoter of the thymidine kinase gene in various positions and configurations. Little or no induction by zinc was observed with single insertions of the regulatory sequence, whereas many different constructions having two copies of MRE-a were inducible. The precise position of the two MREs relative to each other or to the thymidine kinase promoter elements had a relatively small effect on the efficiency of induction, but the inducibility could be further increased by the introduction of more MRE-a sequences. MRE-a can function synergistically with the thymidine kinase distal promoter elements, but in the presence of the TATA box alone it functions as a positive, zinc-dependent promoter element.
Teicoplanin, antibiotics from Actinoplanes teichomyceticus nov. sp. VI. Chemical degradation: physico-chemical and biological properties of acid hydrolysis products. (1984)

Teicoplanin is an antibiotic complex consisting of five closely related factors, T-A2-1, 2, 3, 4 and 5 and a more polar factor, T-A3-1. By controlled acid hydrolysis the complex is transformed into pseudoaglycones and finally into a single aglycone with consecutive removal of three sugar units. Quantitative determination of sugars obtained by degradative reactions and NMR/LC-MS studies on suitable derivatives confirmed that all the components carry one N-acyl-D-glucosamine and that at least two of them are characterized by N-decanoyl and N-undecanoyl chains on the D-glucosamine unit. The hydrolysis products still possess in vitro and in vivo activity.