gebhart/patrepeval huggingface dataset:
Amino acid profiles correlate diagnostically with organ site in three kinds of malignant tumors (1992)

The hypothesis that tumors arising in a particular organ site impose a characteristic plasma free amino acid (PFAA) pattern was tested by analyzing PFAA in fasting venous blood of preoperative patients with breast cancer, gastrointestinal tract cancer, and head and neck cancer. Healthy volunteers served as control subjects. Levels of 28 PFAA were determined in blood samples using an amino acid analyzer, and the data were compared using discriminant analysis and chi-square testing. Compared with control subjects, the concentrations of seven amino acids (glutamine, threonine, histidine, cysteine, alanine, arginine, and ornithine) in patients with tumors correlated closely with the known diagnoses. By means of discriminant analysis, these seven amino acids had the highest correlation with the specific diagnoses, indicating that PFAA profiles correlate diagnostically with the organ-site origin of three different kinds of malignant tumors.
Synthesis of annulated and substituted pyrido[2,3‐d] pyrimidines as antimicrobial agents (2003)

Various routes to the synthesis of annulated and substituted pyrido[2,3‐d]pyrimidines are reported. In particular, the reactions of N‐{3‐cyano‐6‐[4(5‐oxo‐2‐ phenylhydrazono‐4,5‐dihydroimid‐azol‐1‐yl)phenyl]‐4‐ phenylpyridin‐2‐yl}formimidic ethyl ester (3) and 3‐[4‐(3‐amino‐4‐imino‐5‐phenyl‐3,4‐dihydropyrido [2,3‐d]pyrimidin‐7‐yl)phenyl]‐2‐phenyl‐5‐phenyl‐ hydrazono‐3,5‐dihydroimidazol‐4‐one (4) with a variety of reagents were investigated. The antimicrobial activity of some of the compounds obtained were evaluated and reported.
Helper T cells induced by an immunopurified herpes simplex virus type I (HSV-I) 115 kilodalton glycoprotein (gB) protect mice against HSV-I infection. (1985)

Three herpes simplex virus type I (HSV-I) glycoproteins of apparent molecular masses 103, 63, and 115 kD have been purified using virus-specific monoclonal antibodies (mAb) G8D1, C2D2, and T157, respectively. Both G8D1 and C2D2 neutralize HSV-I in vitro and passively protect CBA mice against HSV-I infection in vivo, whereas T157 is neither neutralizing nor passively protective. However, mice given a single subcutaneous injection of 30 micrograms 115 kD glycoprotein in saline were completely protected against lethal challenges of HSV-I administered intraperitoneally or in the footpad 7 d after immunization. In contrast, mice similarly immunized with 103 or 63 kD glycoproteins were only partially protected. The prophylactic immunity was correlated with an early induction of specific antibody, which became even more evident 3 d after virus challenge. There was a remarkable similarity in antibody isotype distribution between the responses to 115 kD glycoprotein and to heat-inactivated intact HSV-I. However, the prechallenge sera from 115 kD glycoprotein hyperimmunized mice were again neither virus-neutralizing nor passively protective. All three glycoproteins induced only low levels of delayed-type hypersensitivity (DTH). Pretreatment of mice with cyclophosphamide significantly enhanced DTH to 115 kD and 103 kD glycoproteins in the absence of antibody, but failed to confer significant immunity, indicating that DTH alone is insufficient for protection. Splenic and lymph node Ig- (B cell-depleted) cells from mice protectively immunized with 115 kD glycoprotein could adoptively transfer effective protection and enhance a virus neutralizing antibody response in normal recipients challenged with a lethal dose of HSV-I. Both the protection and the ability to enhance neutralizing antibody were diminished when the cells were treated with mAb GK 1.5 and complement. These results therefore demonstrate that the 115 kD glycoprotein, though not apparently containing accessible epitopes for the induction of virus-neutralizing antibody, possesses determinants capable of activating helper T cells. These L3T4+ cells confer strong protective immunity by enhancing protective antibody upon challenge infection, probably through associative help.
Predicting drug metabolism: Concepts and challenges (2004)

Abstract The paper begins with a discussion of the needs and goals of metabolic predictions in early drug research. Major difficulties toward this objective are examined, mainly the various substrate and product selectivities characteristic of drug metabolism. In a second part, we classify and summarize the major in silico methods used to predict drug metabolism. A discrimination is thus made between “local ”and “global ”systems. In the last part of the paper, the program METEOR is presented and evaluated using the published metabolic data of 10 substrates.
Chlorination and bromination of fullerenes. Nucleophilic methoxylation of polychlorofullerenes and their aluminum trichloride catalyzed Friedel-Crafts reaction with aromatics to polyarylfullerenes (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChlorination and bromination of fullerenes. Nucleophilic methoxylation of polychlorofullerenes and their aluminum trichloride catalyzed Friedel-Crafts reaction with aromatics to polyarylfullerenesGeorge A. Olah, Imre Bucsi, Christian Lambert, Robert Aniszfeld, Nirupam J. Trivedi, Dilip K. Sensharma, and G. K. Surya PrakashCite this: J. Am. Chem. Soc. 1991, 113, 24, 9385–9387Publication Date (Print):November 1, 1991Publication History Published online1 May 2002Published inissue 1 November 1991https://pubs.acs.org/doi/10.1021/ja00024a063https://doi.org/10.1021/ja00024a063research-articleACS PublicationsRequest reuse permissionsArticle Views997Altmetric-Citations182LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Antibiotics and probiotics in treatment of inflammatory bowel disease (2006)

Many experimental and clinical observations suggest that intestinal microflora plays a potential role in the pathogenesis of inflammatory bowel disease (IBD). Manipulation of the luminal content using antibiotics or probiotics represents a potentially effective therapeutic option. The available studies do not support the use of antibiotics in ulcerative colitis (UC). Antibiotics are effective in treating septic complications of Crohn's disease (CD) but their use as a primary therapy is more controversial, although this approach is frequently and successfully adopted in clinical practice. There is evidence that probiotic therapy may be effective in the prevention and treatment of mild to moderate UC. In contrast, a lack of successful study data at present precludes the widespread use of probiotics in the treatment of CD. Both antibiotics and probiotics appear to play a beneficial role in the treatment and prevention of pouchitis and further trials are warranted to fully quantify their clinical efficacy.
Intradermally focused infrared laser pulses: Thermal effects at defined tissue depths (2005)

Spatially confined foci of thermal effects can be achieved by focusing a low-power infrared laser into skin. Size, depth, and density of microscopic, thermal damage foci may be arbitrarily controlled while sparing surrounding tissue. This may offer a new approach for nonablative laser therapy of dermal disorders.
Giant axonal neuropathy–associated gigaxonin mutations impair intermediate filament protein degradation (2013)

Giant axonal neuropathy (GAN) is an early-onset neurological disorder caused by mutations in the GAN gene (encoding for gigaxonin), which is predicted to be an E3 ligase adaptor. In GAN, aggregates of intermediate filaments (IFs) represent the main pathological feature detected in neurons and other cell types, including patients' dermal fibroblasts. The molecular mechanism by which these mutations cause IFs to aggregate is unknown. Using fibroblasts from patients and normal individuals, as well as Gan-/- mice, we demonstrated that gigaxonin was responsible for the degradation of vimentin IFs. Gigaxonin was similarly involved in the degradation of peripherin and neurofilament IF proteins in neurons. Furthermore, proteasome inhibition by MG-132 reversed the clearance of IF proteins in cells overexpressing gigaxonin, demonstrating the involvement of the proteasomal degradation pathway. Together, these findings identify gigaxonin as a major factor in the degradation of cytoskeletal IFs and provide an explanation for IF aggregate accumulation, the subcellular hallmark of this devastating human disease.
Sensitivity Improvements in an 850-nm VCSEL-Based Link Using a Two-Tap Pre-Emphasis Electronic Filter (2016)

We present an investigation of an ISI penalty reduction for on-off keying in an 850-nm VCSEL-based short optical link using a two-tap electronic pre-emphasis filter and quantify the improvement relative to an equivalent link without pre-emphasis. Error-free operation is demonstrated at bit rates above the -3 dB modulation bandwidth of the link. Sensitivity improvement up to 9 dB compared to nonemphasized signaling is shown. A maximum error-free bit rate achievable in the link is increased to 57 Gb/s, compared to 52 Gb/s without the pre-emphasis.
Cell receptors for the mammalian reovirus. I. Syngeneic monoclonal anti-idiotypic antibody identifies a cell surface receptor for reovirus. (1983)

Abstract We have prepared and characterized a syngeneic monoclonal anti-idiotype directed against the idiotype (Id3) of the anti-reovirus type 3 hemagglutinin B cell hybridoma 9BG5. We have shown this monoclonal antibody to be anti-idiotypic in a series of inhibition studies with purified sigma 1 (hemagglutinin) protein and with absorption studies on the idiotypic R1.1 cell line. That the idiotype Id 3 defined by the monoclonal anti-idiotype is distinct from H-2 was demonstrated by its presence on an idiotype-expressing H-2 negative cell line (R1.E). Binding of the anti-idiotype is relatively tunicamycin resistant and pronase/trypsin sensitive, which suggests that the recognition site of the anti-idiotypic receptor is poorly glycosylated. The presence of idiotype-like receptors on reovirus type 3 susceptible neurons may have important implications for the presence of related gene families between neural and lymphoid tissue. The implications of recognition by neuronal cells of an anti-idiotypic monoclonal antibody directed against the reovirus 3 attachment receptor for the pathogenesis of viral-induced auto-immunity are discussed.
Block copolymer conjugates prepared by sequentially grafting from proteins via RAFT (2011)

Well-defined thermoresponsive block copolymer conjugates were prepared by two consecutive grafting-from polymerizationsvia reversible addition–fragmentation chain transfer (RAFT) polymerization. A RAFT agent containing an activated ester was conjugated to amines on lysozyme, and N-isopropylacrylamide was polymerized by grafting directly from the modified protein in aqueous buffer. Retention of the active thiocarbonylthio moieties on the ω end of the conjugated chains allowed chain extension viapolymerization of N,N-dimethylacrylamide to yield lysozyme–poly(N-isopropylacrylamide)-b-poly(N,N-dimethylacrylamide) (LYS–PNIPAM-b-PDMA) block copolymer conjugates. Analysis of the conjugates, as well as the cleaved homopolymers and block copolymers, indicated the grafting-from polymerizations were well controlled and that chain extension during block copolymerization was efficient. The temperature-responsive aqueous solution behavior of the resulting conjugates was investigated.
Characterization of a bovine synovial fluid lubricating factor. I. Chemical, Surface activity and lubricating properties (1992)

A lubricating glycoprotein (PSLF) with an apparent molecular weight of 280 kDa was purified from bovine synovial fluid by anion exchange, molecular sieve chromatography, and density gradient centrifugation. Lubrication was measured under boundary conditions as lowering of the coefficient of friction (mu) between oscillating natural latex and polished glass. Lubricating ability was first observed at a concentration of 200 micrograms/ml and became maximal at 260 micrograms/ml. Hydrophobic interfacial tension measurements indicated that at the former concentration, monolayers of PSLF formed. Sugar digestions showed that lubricating ability depends upon the terminal galactose of the molecule. PSLF is similar if not identical to lubricin. It is proposed that a repulsive hydration force is the molecular mechanism for lubricating activity.
Protein kinase A‐mediated enhancement of miniature IPSC frequency by noradrenaline in rat cerebellar stellate cells. (1997)

1. Cellular mechanisms underlying the enhancement by noradrenaline (NA) of inhibitory postsynaptic currents (IPSCs) were studied at inhibitory synapses in the molecular layer of the cerebellum. IPSCs were obtained from stellate cells in rat cerebellar slices using tight-seal whole-cell recording. 2. Miniature IPSCs (mIPSCs) were recorded in the presence of tetrodotoxin (TTX; 100 nM). NA (10 microM) markedly increased the frequency of mIPSCs, but did not alter their mean amplitude. Bath application of the inhibitor of adenylyl cyclase 9-(tetrahydro-2'-furyl) adenine (SQ 22,536; 300 microM), of the wide spectrum protein kinase inhibitor staurosporine (1 microM), and of the Rp-diastereomer of adenosine-3',5'-cyclic monophosphothioate (Rp-cAMPS; 500 microM), a specific inhibitor of cAMP-dependent protein kinase (PKA), inhibited the mIPSC frequency increase induced by NA. 3. The increase in mIPSC frequency was not attenuated by Cd2+ (100 microM), a blocker of voltage dependent calcium channels. However, after a 12-15 min pre-incubation in Ca(2+)-free saline, the effect of NA on mIPSCs was markedly inhibited. If Ca2+ ions were readmitted in the presence of NA, enhancement of the mIPSC frequency was largely restored. 4. Application of the membrane permeant analogue of cAMP, 8-Br-cAMP (1 mM), together with the inhibitor of cAMP phosphodiesterase, 3-isobutyl-1-methylxanthine (IBMX; 100 microM), caused a frequency increase of mIPSCs. Forskolin also mimicked the stimulatory effect of NA on mIPSC frequency. The effects of both 8-Br-cAMP and forskolin persisted in Ca(2+)-free saline, suggesting that the modulation of transmitter release does not require Ca2+ influx. 5. On the whole, the results indicate that the potentiation of mIPSC frequency by NA is mediated through the sequential activation of adenylyl cyclase and protein kinase A (PKA), and that PKA modulates the vesicle release mechanism rather than Ca2+ influx. The lack of effect of NA after prolonged incubation in Ca(2+)-free solution may be due to an inhibition of adenylyl cyclase by a gradual lowering of the cytosolic presynaptic Ca2+ concentration.
Northern Fowl Mite, Ornithonyssus Sylviarum (Acari: Macronyssidae), Ingests Large Quantities of Blood from White Leghorn Hens1 (1981)

Journal Article Northern Fowl Mite, Ornithonyssus Sylviarum (Acari: Macronyssidae), Ingests Large Quantities of Blood from White Leghorn Hens Get access John R. DeLoach, John R. DeLoach 2Veterinary Toxicology and Entomology Research Laboratory, AR, SEA, USDA, P.O. Drawer GE, College Station, Texas 77841, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Joyce A. DeVaney Joyce A. DeVaney 2Veterinary Toxicology and Entomology Research Laboratory, AR, SEA, USDA, P.O. Drawer GE, College Station, Texas 77841, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Medical Entomology, Volume 18, Issue 5, 30 September 1981, Pages 374–377, https://doi.org/10.1093/jmedent/18.5.374 Published: 30 September 1981
SNX9 regulates tubular invagination of the plasma membrane through interaction with actin cytoskeleton and dynamin 2 (2008)

Dynamic membrane remodeling during intracellular trafficking is controlled by the intricate interplay between lipids and proteins. BAR domains are modules that participate in endocytic processes by binding and deforming the lipid bilayer. Sorting nexin 9 (SNX9), which functions in clathrin-mediated endocytosis, contains a BAR domain, however, the properties of this domain are not well understood. Here we show that SNX9 shares many properties with other BAR domain-containing proteins, such as amphiphysin and endophilin. SNX9 is able to deform the plasma membrane, as well as liposomes, into narrow tubules and recruit N-WASP and dynamin 2 to these tubules via its SH3 domain. SNX9-induced tubulation is antagonized by N-WASP and dynamin 2 while it is enhanced by perturbation of actin dynamics. However, SNX9 also has several unique properties. The tubulating activity requires the BAR and PX domains, as well as the low-complexity (LC) domain, which binds the Arp2/3 complex. SNX9 also binds to PtdIns(4)P-5-kinases via its PX domain and its tubulating activity is regulated by phosphoinositides. In addition, the kinase activity of PtdIns(4)P-5-kinases is stimulated by interaction with SNX9, suggesting a positive feedback interaction between SNX9 and PtdIns(4)P-5-kinases. These results suggest that SNX9 functions in the coordination of membrane remodeling and fission via interactions with actin-regulating proteins, endocytic proteins and PtdIns(4,5)P2-metabolizing enzymes.
Insights into Cytokine–Receptor Interactions from Cytokine Engineering (2014)

Cytokines exert a vast array of immunoregulatory actions critical to human biology and disease. However, the desired immunotherapeutic effects of native cytokines are often mitigated by toxicity or lack of efficacy, either of which results from cytokine receptor pleiotropy and/or undesired activation of off-target cells. As our understanding of the structural principles of cytokine-receptor interactions has advanced, mechanism-based manipulation of cytokine signaling through protein engineering has become an increasingly feasible and powerful approach. Modified cytokines, both agonists and antagonists, have been engineered with narrowed target cell specificities, and they have also yielded important mechanistic insights into cytokine biology and signaling. Here we review the theory and practice of cytokine engineering and rationalize the mechanisms of several engineered cytokines in the context of structure. We discuss specific examples of how structure-based cytokine engineering has opened new opportunities for cytokines as drugs, with a focus on the immunotherapeutic cytokines interferon, interleukin-2, and interleukin-4.
Neuroinflammation in traumatic brain injury: A chronic response to an acute injury (2017)

Every year, approximately 1.4 million US citizens visit emergency rooms for traumatic brain injuries. Formerly known as an acute injury, chronic neurodegenerative symptoms such as compromised motor skills, decreased cognitive abilities, and emotional and behavioral changes have caused the scientific community to consider chronic aspects of the disorder. The injury causing impact prompts multiple cell death processes, starting with neuronal necrosis, and progressing to various secondary cell death mechanisms. Secondary cell death mechanisms, including excitotoxicity, oxidative stress, mitochondrial dysfunction, blood-brain barrier disruption, and inflammation accompany chronic traumatic brain injury (TBI) and often contribute to long-term disabilities. One hallmark of both acute and chronic TBI is neuroinflammation. In acute stages, neuroinflammation is beneficial and stimulates an anti-inflammatory response to the damage. Conversely, in chronic TBI, excessive inflammation stimulates the aforementioned secondary cell death. Converting inflammatory cells from pro-inflammatory to anti-inflammatory may expand the therapeutic window for treating TBI, as inflammation plays a role in all stages of the injury. By expanding current research on the role of inflammation in TBI, treatment options and clinical outcomes for afflicted individuals may improve. This paper is a review article. Referred literature in this paper has been listed in the references section. The data sets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.
Functional Activity of Anti-Neisserial Surface Protein A Monoclonal Antibodies against Strains ofNeisseria meningitidisSerogroup B (2001)

Neisserial surface protein A (NspA) is currently being investigated with humans as a candidate vaccine for the prevention of meningococcal disease. Although NspA is highly conserved, the ability of anti-NspA antibodies to bind to or elicit complement-mediated bactericidal activity against diverse Neisseria meningitidis serogroup B strains is controversial. To evaluate strain differences in NspA surface accessibility and susceptibility to bactericidal activity, we prepared murine immunoglobulin G2a anti-NspA monoclonal antibodies (MAbs) and evaluated their functional activity against 10 genetically diverse N. meningitidis serogroup B strains. By colony Western blot, all 10 strains expressed NspA as detected by one or more MAbs. By flow cytometry, two MAbs were found to bind to the bacterial surface of 6 of the 10 strains. In addition, two strains showed variable NspA surface accessibility for the MAbs despite being uniformly positive for NspA expression by colony Western blotting. Only 4 of the 10 strains were susceptible to anti-NspA complement-mediated bacteriolysis. Passively administered MAb protected infant rats from developing bacteremia after challenge with N. meningitidis serogroup B strain 8047 (surface binding positive, susceptible to anti-NspA bacteriolysis), was poorly protective against strain BZ232 (surface binding variable, resistant to bacteriolysis), and did not protect against strain M986 (surface binding negative, resistant to bacteriolysis). Finally, NspA does not appear to be critical for causing bacteremia, as an NspA knockout from strain 8047 was highly virulent in infant rats. Taken together, these findings suggest that an NspA-based vaccine will need to incorporate additional antigens to elicit broad protection against N. meningitidis serogroup B.
Resonant-cavity InGaAs/InAlGaAs/InP photodetector arrays for wavelength demultiplexing applications (1997)

Resonant-cavity photodetector arrays are demonstrated in the InGaAs/InAlAs/InP material system grown by solid-source molecular beam epitaxy. To reduce crosstalk between channels, these devices are designed with a high-Q cavity to obtain narrow-band photoresponse. In addition, a novel double-absorber design has been proposed and implemented to avoid position sensitivity related to the cavity standing wave and eliminate the need for in situ cavity-mode adjustment. Both Schottky and P-i-N diode structures are studied and compared. Eight element arrays with linearly distributed resonant wavelengths spanning over 30 nm are fabricated by using a three-level anodic oxidation process. An experimental channel rejection ratio of 14.5 dB at 4 nm away from the resonant peak has been achieved.