gebhart/patrepeval huggingface dataset:
Alcohol and violence : epidemiology neurobiology psychology family issues (1997)

Epidemiology. Epidemiological Issues in Alcohol-Related Violence J. Roizen. The Relationship of Alcohol to Injury in Assault Cases S.E. Martin, R. Bachman. Alcohol and Spouse Abuse: Ethnic Differences G.K. Kantor. Longitudinal Perspectives on Alcohol Use and Aggression During Adolescence H.R. White. Alcohol and Violence-Related Injuries in the Emergency Room C.J. Cherpitel. Neurobiology. Emerging Themes in Preclinical Research on Alcohol and Aggression E. Yudko, et al. Alcohol, GABAA-benzodiazepine Receptor Complex and Aggression K.A. Miczek, et al. Serotonin in Early-Onset Alcoholism M. Virkkunen, M. Linnoila. Psychology. Effects of Alcohol on Human Aggression: Validity of Proposed Explanations B.J. Bushman. Is There a Causal Relationship between Alcohol and Violence: A Synthesis of Evidence M.W. Lipsey, et al. Family Issues. When Women Are Under the Influence: Does Drinking Or Drug Use by Women Provoke Beatings by Men? G.K. Kantor, N. Asdigian. How Far Have We Come? A Critical Review of the Research on Men Who Batter W.V. Lee, S.P. Weinstein. 4 Additional Articles. Index.
Fibroblast Growth Factor Signaling Regulates Pillar Cell Development in the Organ of Corti (2002)

One of the most striking aspects of the cellular pattern within the sensory epithelium of the mammalian cochlea is the presence of two rows of pillar cells in the region between the single row of inner hair cells and the first row of outer hair cells. The factors that regulate pillar cell development have not been determined; however, previous results suggested a key role for fibroblast growth factor receptor 3 (FGFR3). To examine the specific effects of FGFR3 on pillar cell development, we inhibited receptor activation in embryonic cochlear explant cultures. Results indicated that differentiation of pillar cells is dependent on continuous activation of FGFR3. Moreover, transient inhibition of FGFR3 did not inhibit the pillar cell fate permanently, because reactivation of FGFR3 resulted in the resumption of pillar cell differentiation. The effects of increased FGFR3 activation were determined by exposing cochlear explants to FGF2, a strong ligand for several FGF receptors. Treatment with FGF2 led to a significant increase in the number of pillar cells and to a small increase in the number of inner hair cells. These effects were not dependent on cellular proliferation, suggesting that additional pillar cells and inner hair cells were a result of increased recruitment into the prosensory domain. These results indicate that FGF signaling plays a critical role in the commitment and differentiation of pillar cells. Moreover, the position of the pillar cells appears to be determined by the activation of FGFR3 in a subset of the progenitor cells that initially express this receptor.
Symptomatic Treatment and Management of Huntington's Disease: An Overview (2010)

5 Abstract: Huntington's disease (HD) is an inherited disease of the central nervous system that usually has its onset between 30 and 50 years of age. The patient has progressive dementia with bizarre involvantary movements of chorea. The disease slowly progresses and death is usually due to an intercurrent infection. Huntington's disease affects someone's ability to think, talk and move by destroying cells in the basal ganglia, the part of the brain that controls these capacities. A patient with Huntington's disease may present with neurological or psychiatric symptoms, or both. The movement disorder may begin with simple twitching or jerking or with clumsiness or coordination problems. Huntington's disease caused by the expansion of the ployglutamine tract in the N-terminus of the HD protein (Huntingtin). Although there is currently no cure for this disease, there are ways to manage symptoms effectively. Symptomatic treatment of Huntington's disease involves use of Dopamine antagonists, presynaptic dopamine depleters, Antidepressants, Tranquillizers, Anxiolytic Benzodiazepines, Anticonvulsants and Antibiotics. Several medications including baclofen, idebenone and vitamin E have studied in clinical trials with limited samples. In the present article, we have concentrated on clinical features, diagnosis, symptomatic approaches and other possible therapies involved in the management of Huntington's disease. The aim of present article is to provide in depth knowledge about symptomatic treatment and other therapies involved in the management of Huntington's disease. This article reviews current therapeutic agents for treatment of the symptoms of Huntington's disease.
Structural basis for endotoxic and antagonistic activities: investigation with novel synthetic lipid A analogs (2003)

Our early work using homogeneous synthetic preparations demonstrated the presence of a lipid A analog which antagonizes endotoxic activities of LPS and lipid A. The first example was a tetraacylated biosynthetic precursor, now known as precursor Ia or lipid IVa, that contains four 3-hydroxytetradecanoyl moieties linked to the bisphosphorylated disaccharide backbone common to the endotoxic hexa-acyl Escherichia coli lipid A. Various compounds with both endotoxic and antagonistic activities have subsequently been reported from either natural or synthetic sources, but little is known about the factors determining the type of the activities of the respective compounds. To approach this issue, we have synthesized a series of lipid A analogs with various numbers and chain lengths of acyl groups on the backbone. Some were prepared by the aid of a novel affinity separation procedure. The phosphate moieties were also synthetically replaced. Biological tests showed that at least three acyl groups are required for antagonistic activity but one or even both of the phosphates can be replaced with other acidic moieties without losing the activity. The effect of Kdo residues linked to lipid A is also briefly discussed. Molecular dynamics calculations reasonably explain possible conformations required for the biological activity.
Examination of HER3 targeting in cancer using monoclonal antibodies (2015)

The human EGF receptor (HER/EGFR) family of receptor tyrosine kinases serves as a key target for cancer therapy. Specifically, EGFR and HER2 have been repeatedly targeted because of their genetic aberrations in tumors. The therapeutic potential of targeting HER3 has long been underestimated, due to relatively low expression in tumors and impaired kinase activity. Nevertheless, in addition to serving as a dimerization partner of EGFR and HER2, HER3 acts as a key player in tumor cells' ability to acquire resistance to cancer drugs. In this study, we generated several monoclonal antibodies to HER3. Comparisons of their ability to degrade HER3, decrease downstream signaling, and inhibit growth of cultured cells, as well as recruit immune effector cells, selected an antibody that later emerged as the most potent inhibitor of pancreatic cancer cells grown as tumors in animals. Our data predict that anti-HER3 antibodies able to intercept autocrine and stroma-tumor interactions might strongly inhibit tumor growth, in analogy to the mechanism of action of anti-EGFR antibodies routinely used now to treat colorectal cancer patients.
Primary Structures of Fungal Fructosyl Amino Acid Oxidases and their Application to the Measurement of Glycated Proteins (1996)

Fructosyl amino acid oxidase (FAOD), which is active toward model compounds of the glycated proteins in blood, N epsilon-fructosyl N sigma-Z-lysine and N-fructosyl valine, was purified to homogeneity from Aspergillus terreus GP1. Though the enzyme did not use glycated proteins directly as its substrate, it used glycated human serum albumin (HSA) when HSA was treated with a protease. Linear relationships between both the concentration and the increase in absorbance and the glycation rate of glycated HSA and the increase in absorbance were observed. cDNAs coding for FAODs were cloned from cDNA libraries of A. terreus GP1 and Penicillium janthinellum AKU 3413. The coding region for both fungal FAODs consisted of 1314 bp encoding 437 amino acids. The sequence of a dinucleotide-binding motif, GXGXXG, was in the deduced N-terminal region and a similar sequence to that the active site of bacterial sarcosine oxidases was found near the C-terminal region of FAOD. The of C-terminal tripeptides SKL and AKL of FAODs from A. terreus and P. janthinellum, respectively, represent typical peroxisomal-targeting signals. Finally, FAOD protein was produced in Escherichia coli transformants in an active form, and at the same level as in the original fungi.
Highly Selective Sub-Nanomolar Cathepsin S Inhibitors by Merging Fragment Binders with Nitrile Inhibitors (2020)

Pharmacological inhibition of cathepsin S (CatS) allows for a specific modulation of the adaptive immune system and many major diseases. Here, we used NMR fragment screening and crystal structure-aided merging to synthesize novel, highly selective CatS inhibitors with picomolar enzymatic Ki values and nanomolar functional activity in human Raji cells. Noncovalent fragment hits revealed binding hotspots, while the covalent inhibitor structure-activity relationship enabled efficient potency optimization.
Determinants of the intracellular fate of truncated forms of the platelet glycoproteins IIb and IIIa. (1993)

The platelet glycoproteins GPIIb and GPIIIa are integral membrane proteins and form calcium-dependent heterodimers in the endoplasmic reticulum (ER). In the absence of heterodimer formation, GPIIb and GPIIIa are retained in the ER and degraded. To produce soluble forms of these proteins, we truncated each at a site just proximal to its transmembrane anchor and expressed the mutants in COS-1 cells. We found that both truncated GPIIIa (GPIIIatr) and GPIIIatr were secreted by the transfected cells. However, GPIIbtr was retained by the cells and was immunoprecipitated as a doublet with a 115,000 molecular weight protein. Incubation of transfected cells with the calcium ionophore A23187 or the calcium chelator 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl) ester (BAPTA-AM) failed to induce appreciable GPIIbtr secretion, suggesting that formation of intracellular calcium complexes was not a factor in GPIIbtr retention. Further, immunoblotting of immunoprecipitated GPIIbtr and GPIIIatr revealed that the chaperone binding protein (BiP) was associated with each, arguing that BiP alone was not responsible for GPIIbtr retention. These studies indicate that the intracellular retention of GPIIIa involves sequences located in the transmembrane or cytoplasmic domains of the molecule. GPIIb contains an additional retention signal located in the extracellular portion of the molecule whose effect is abrogated by formation of a GPIIb-IIIa heterodimer. This signal may be involved in the fate of nascent GPIIb monomers and the generation of correctly configured GPIIb-IIIa heterodimers.
CCAT1 promotes laryngeal squamous cell carcinoma cell proliferation and invasion. (2016)

Long noncoding RNAs (lncRNAs) are proved tobe deregulated in a number of cancers and play important roles in tumor biology. Colon cancer-associated transcript-1 (CCAT1) was initially found in colon cancer and promoted cancer cell development. However, the role of CCAT1 in laryngeal squamous cell carcinoma (LSCC) is still unknown. In this study, we demonstrated that CCAT1 expression was upregulated in the LSCC tissues compared with the normal adjacent tissues. Moreover, CCAT1 expression was higher in LSCC tissues thanin adjacent normal tissues in 70% of patients. In addition, higher expression of CCAT1 was correlated with T3-4 grade and advanced clinical stage. Overexpression of CCAT1 promoted Hep-2 cell proliferation, migration and invasion. Ectopic expression of CCAT1 suppressed E-cadherin expression while enhanced the expressionof N-cadherin and Vimentin. Furthermore, CCAT1 overexpression increased Hep-2 cell colony formation and cell cycle. We also demonstrated that CCAT1 overexpression suppressed the expression of let-7 and enhanced the expression of HMGA2 and Myc, the direct target genes of let-7. To conclude, our data demonstrated that CCAT1 played an oncogenic role in the development of LSCC.
Low pH Is Required for Avian Sarcoma and Leukosis Virus Env-Induced Hemifusion and Fusion Pore Formation but Not for Pore Growth (2004)

Binding of avian sarcoma and leukosis virus (ASLV) to its cognate receptor on the cell surface causes conformational changes in its envelope protein (Env). It is currently debated whether low pH is required for ASLV infection. To elucidate the role of low pH, we studied the association between ASLV subgroup B (ASLV-B) and liposomes and fusion between effector cells expressing Env from ASLV-A and ASLV-B and target cells expressing cognate receptors. Neither EnvA nor EnvB promoted cell-cell fusion at neutral pH, but lowering the pH resulted in quick and extensive fusion. As expected for a low-pH-triggered reaction, fusion was a steep function of pH. Steps that required low pH were identified. Binding a soluble form of the receptor caused ASLV-B to hydrophobically associate with liposome membranes at neutral pH, indicating that low pH is not required for insertion of Env's fusion peptides into membranes. But both cell-cell hemifusion and fusion pore formation were pH dependent. It is proposed that fusion peptide insertion stabilizes the conformation of ASLV Env into a form that can be acted upon by low pH. At this point, but not before, low pH can induce fusion and is in fact required for fusion to occur. However, low pH is no longer necessary after formation of the initial fusion pore: pore enlargement does not require low pH.
Evaluation of alternative solvents in common amide coupling reactions: replacement of dichloromethane and N,N-dimethylformamide (2012)

A range of alternative solvents have been evaluated within amidation reactions employing common coupling reagents with a view to identifying suitable replacements for dichloromethane and N,N-dimethylformamide.
Immunotherapy with Mycobacterium vaccae in the treatment of psoriasis (1998)

A placebo-controlled study of immunotherapy with Mycobacterium vaccae for chronic plaque psoriasis showed improvement in the psoriasis area severity index in 19 of 21 immunotherapy recipients (P<0.005). Minor improvement, not reaching statistical significance for the group, occurred in nine of 14 placebo recipients. There were losses to follow-up and the placebo used, tetanus toxoid, was not ideal. Clinical improvement after immunotherapy persisted for 6 months and another injection of the immunotherapeutic given to a few volunteers from either group resulted in benefits lasting a year. Lymphoproliferative tests were carried out at each clinic visit, and on 50 matched controls. Starting with reduced responses to mycobacterial antigens and concanavalin A, both treatment groups showed a fall after 3 months, and diverged at 6 months with M. vaccae recipients rising to values similar to those of healthy controls, whereas placebo recipients continued to fall. Conclusions reached were that immunotherapy with M. vaccae gave long-lasting clinical benefit to most patients, with minimal side effects. This accompanied a return towards normal cellular immune responsiveness to mycobacterial antigens, which did not follow the use of the placebo.
Proton and carbon-13 NMR of 3-O and 4-O conjugates of dopamine and other catecholamines (1993)

Dopamine and its conjugates are widely distributed among biological species and are utilized for a variety of functions. Insects metabolize dopamine for cuticle melanization and sclerotization. Among the most abundant dopamines found in the larval and pupal development stages of Manduca sexta, the tobacco hornworm, are N-acetyldopamine and N-beta-alanyldopamine. In addition, glycosylated derivatives of these dopamines are found mainly in the hemolymph just prior to cuticulogenesis. The 1H and 13C NMR resonances of dopamine, its 3-O-methyl, 4-O-methyl, N-acetyl, and N-beta-alanyl derivatives, norepinephrine, 4-O-(beta-D-glucuronopyranosyl)dopamine, and the glycosylated products of N-beta-alanyldopamine and dopamine have largely been assigned. Assignments were based on one- and two-dimensional NMR analyses of the above compounds combined with that of specifically enriched [C7-13C]dopamine. 1H NMR showed that the major glycosylated natural product isolated from M. sexta pupal hemolymph was a 3-O-glycosyl derivative of N-beta-alanyldopamine. 13C NMR confirmed that the carbohydrate was D-glucose probably in a beta-linkage. 1H NMR of the aromatic ring protons provided the most definitive method to distinguish 3-O- from 4-O-derivatives of dopamine. In addition, the 3-O-glucosyl conjugate of N-beta-alanyldopamine had unique chemical shifts and coupling patterns compared to those of 4-O-(beta-D-glucuronosyl)- and 3-O-(beta-D-glucopyranosyl)dopamine.
Making Catalytic DNAs (2000)

Although cells routinely use enzymes based on RNA and protein, catalytic DNAs are valuable enzymes that seem to have been ignored by Nature. Enzyme engineers, however, have no intention of ignoring catalytic DNAs (or deoxyribozymes as they are known) and are busy synthesizing them in the laboratory and finding applications for them in biotechnology and therapeutics, as Ronald Breaker reveals in his Techview article.
The synthesis of (S)-(+)-gossypol via an asymmetric Ullmann coupling (1997)

A. I. Meyers and J. J. Willemsen, Chem. Commun., 1997, 1573 DOI: 10.1039/A703043F
Synthesis of the C20−C26 Building Block of Halichondrins via a Regiospecific and Stereoselective SN2‘ Reaction (2002)

[reaction: see text] A regiospecific and stereoselective S(N)2' reaction to convert the trisylate into the vinyl iodide is presented. The homoallylic alcohol is used to direct the delivery of LiCu(Me)(2).
Detection beyond the Debye Screening Length in a High-Frequency Nanoelectronic Biosensor (2012)

Nanosensors based on the unique electronic properties of nanotubes and nanowires offer high sensitivity and have the potential to revolutionize the field of Point-of-Care (POC) medical diagnosis. The direct current (dc) detection of a wide array of organic and inorganic molecules has been demonstrated on these devices. However, sensing mechanism based on measuring changes in dc conductance fails at high background salt concentrations, where the sensitivity of the devices suffers from the ionic screening due to mobile ions present in the solution. Here, we successfully demonstrate that the fundamental ionic screening effect can be mitigated by operating single-walled carbon nanotube field effect transistor as a high-frequency biosensor. The nonlinear mixing between the alternating current excitation field and the molecular dipole field can generate mixing current sensitive to the surface-bound biomolecules. Electrical detection of monolayer streptavidin binding to biotin in 100 mM buffer solution is achieved at a frequency beyond 1 MHz. Theoretical modeling confirms improved sensitivity at high frequency through mitigation of the ionic screening effect. The results should promise a new biosensing platform for POC detection, where biosensors functioning directly in physiologically relevant condition are desired.
Cloning and characterization of cbl-b: a SH3 binding protein with homology to the c-cbl proto-oncogene. (1995)

We have cloned a new gene, cbl-b, with homology to the c-cbl proto-oncogene. A large protein is predicted (approx. MW 108,000) that has a proline rich domain, a nuclear localization signal, a C3HC4 zinc finger and a putative leucine zipper. There is striking nucleotide and amino acid homology to the c-cbl proto-oncogene most notably in the structural motifs described above. Cbl-b is expressed in normal and malignant mammary epithelial cells, in a variety of normal tissues, and in hematopoietic tissue and cell lines. Cbl-b expressions is up-regulated with macrophage/monocyte differentiation of the HL60 and U937 cell lines. There is direct association of the cbl-b protein with the Src Homology 3 domains of several proteins including signaling, cytoskeletal and adaptor proteins. Our data suggest that cbl-b encodes a protein which can interact with signal transduction proteins to regulate their function or to be regulated by them. Together, cbl-b and c-cbl are members of a novel family of proto-oncogenes involved in signal transduction.
Dominant cell death induction by extramitochondrially targeted apoptosis‐inducing factor (2001)

The complete AIF cDNA comprising the amino-terminal mitochondrial localization sequence (MLS) and the oxidoreductase domain has been fused in its carboxyl terminus to enhanced green fluorescent protein (GFP), thereby engineering an AIF-GFP fusion protein that is selectively targeted to the mitochondrial intermembrane space. Upon induction of apoptosis, the AIF-GFP protein translocates together with cytochrome c (Cyt-c) to the extramitochondrial compartment. Microinjection of recombinant AIF leads to the release of AIF-GFP and Cyt-c-GFP, indicating that ectopic AIF can favor permeabilization of the outer mitochondrial membrane. These mitochondrial effects of AIF are caspase independent, whereas the Cyt-c-microinjection induced translocation of AIF-GFP and Cyt-c-GFP is suppressed by the pan-caspase inhibitor Z-VAD.fmk. Upon prolonged culture, transfection-enforced overexpression of AIF results in spontaneous translocation of AIF-GFP from mitochondria, nuclear chromatin condensation, and cell death. These effects are caspase independent and do not rely on the oxidoreductase function of AIF. Spontaneous AIF-GFP translocation and subsequent nuclear apoptosis can be retarded by overexpression of a Bcl-2 protein selectively targeted to mitochondria, but not by a Bcl-2 protein targeted to the endoplasmic reticulum. Overexpression of a mutant AIF protein in which the MLS has been deleted (AIF Delta 1-100) results in the primary cytosolic accumulation of AIF. AIF Delta 1-100-induced cell death is suppressed by neither Z-VAD.fmk or by Bcl-2. Thus, extramitochondrially targeted AIF is a dominant cell death inducer.
Reclassification of Treponema hyodysenteriae and Treponema innocens in a New Genus, Serpula gen. nov., as Serpula hyodysenteriae comb. nov. and Serpula innocens comb. nov. (1991)

The intestinal anaerobic spirochetes Treponema hyodysenteriae B78T (T = type strain), B204, B169, and A-1, Treponema innocens B256T and 4/71, Treponema succinifaciens 6091T, and Treponema bryantii RUS-1T were compared by performing DNA-DNA reassociation experiments, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cell proteins, restriction endonuclease analysis of DNA, and 16S rRNA sequence analysis. DNA-DNA relative reassociation experiments in which the S1 nuclease method was used showed that T. hyodysenteriae B78T and B204 had 93% sequence homology with each other and approximately 40% sequence homology with T. innocens B256T and 4/71. Both T. hyodysenteriae B78T and T. innocens B256T exhibited negligible levels of DNA homology (less than or equal to 5%) with T. succinifaciens 6091T. The results of comparisons of protein electrophoretic profiles corroborated the DNA-DNA reassociation results. We found high levels of similarity (greater than or equal to 96%) in electrophoretic profiles among T. hyodysenteriae strains, moderate levels of similarity (43 to 49%) between T. hyodysenteriae and T. innocens, and no detectable similarity between the profiles of either T. hyodysenteriae or T. innocens and those of T. succinifaciens, T. bryantii, and Escherichia coli. Restriction endonuclease analysis of DNA was not useful in assessing genetic relationships since there was heterogeneity even between strains of T. hyodysenteriae. Partial 16S rRNA sequences of the intestinal spirochetes were determined by using a modified Sanger method and were compared in order to evaluate the phylogenetic relationships among these and other spirochetes.(ABSTRACT TRUNCATED AT 250 WORDS)