gebhart/patrepeval huggingface dataset:
AN INTEGRATIVE THEORY OF LOCUS COERULEUS-NOREPINEPHRINE FUNCTION: Adaptive Gain and Optimal Performance (2005)

Historically, the locus coeruleus-norepinephrine (LC-NE) system has been implicated in arousal, but recent findings suggest that this system plays a more complex and specific role in the control of behavior than investigators previously thought. We review neurophysiological and modeling studies in monkey that support a new theory of LC-NE function. LC neurons exhibit two modes of activity, phasic and tonic. Phasic LC activation is driven by the outcome of task-related decision processes and is proposed to facilitate ensuing behaviors and to help optimize task performance (exploitation). When utility in the task wanes, LC neurons exhibit a tonic activity mode, associated with disengagement from the current task and a search for alternative behaviors (exploration). Monkey LC receives prominent, direct inputs from the anterior cingulate (ACC) and orbitofrontal cortices (OFC), both of which are thought to monitor task-related utility. We propose that these frontal areas produce the above patterns of LC activity to optimize utility on both short and long timescales.
Automated NMR Structure Calculation With CYANA (2004)

This chapter gives an introduction to automated nuclear magnetic resonance (NMR) structure calculation with the program CYANA. Given a sufficiently complete list of assigned chemical shifts and one or several lists of cross-peak positions and columns from two-, three-, or four-dimensional nuclear Overhauser effect spectroscopy (NOESY) spectra, the assignment of the NOESY cross-peaks and the three-dimensional structure of the protein in solution can be calculated automatically with CYANA.
The Amino-Acid Sequences of the Double-Headed Proteinase Inhibitors from Cat, Lion and Dog Submandibular Glands (1987)

Cat and lion submandibular glands each contain a double-headed secretory proteinase inhibitor. Their amino-acid sequences were determined, and the amino-acid sequence of the inhibitor of dog submandibular glands was revised. Extensive homologies were found between these inhibitors in both domains. The trypsin-inhibiting domains of cat and lion inhibitors, however, contain a Lys residue in the reactive site in contrast to an Arg residue in the dog inhibitor. Domains I and II of cat, lion, and dog inhibitors are structurally related both to each other and to the sequenced monovalent secretory pancreatic trypsin inhibitors, Notable differences in inhibitory properties of canine and feline inhibitors are discussed with respect to sequence differences.
HIV-1 infection of human fetal thymocytes. (1992)

Some neonates with congenital human immunodeficiency virus type 1 (HIV-1) infection exhibit immune dysregulation. This suggests that fetal CD4+ cells, possibly thymocytes, may be infected during gestation. If thymocytes are infected, this may result in a disruption of T-cell differentiation. To examine this hypothesis, normal human fetal thymocytes were established in tissue culture, characterized, and then exposed to HIV-1. On initial isolation, fetal thymocytes were analyzed for phenotypic markers by flow cytometry and assessed for T-cell function by mitogen-stimulated thymidine incorporation. The thymocytes comprised greater than 70% double positive (CD4+, CD8+) cells and responded to T- but not to B-cell mitogens. Thereafter, thymocytes were incubated in either tissue culture medium containing infectious HIV-1 or in control (HIV-free) medium. Infection of fetal thymocytes was determined by light and electron microscopy in combination with immunocytochemistry, molecular hybridization, and an infectious cell center (ICC) assay. After 1 week in culture, the thymocytes exposed to HIV-1 were positive by immunocytochemistry for the HIV-1-associated protein gp41. In addition, the presence of HIV-1 DNA was detected by molecular hybridization confirming infection of these cells. The ICC assay demonstrated the production of infectious HIV-1 particles and budding of mature virions was observed by electron microscopy. These studies demonstrate that human fetal thymocytes can be infected with HIV-1 in vitro and that this infection results in production of infectious virions. These results support the hypothesis that vertical transmission of HIV-1 in vivo may result in the infection of fetal thymocytes, which may contribute to postnatal HIV-1-associated pathologic conditions.
The nuclear serine/threonine protein kinase DNA-PK. (1992)

The DNA-activated protein kinase (DNA-PK) is a nuclear serine/threonine protein kinase that phosphorylates DNA-binding proteins, including several transcription factors. DNA-PK is one of a very few enzymes known to be regulated through interaction with DNA that does not have DNA as a template or substrate. We suggest that DNA-PK may function in cell homeostasis, in part through the modulation of transcriptional activity.
Electrochemical Reduction Of Carbon Dioxide Using Gas Diffusion Electrodes Loaded With Fine Catalysts (2009)

Gas diffusion electrodes (GDEs) promising to use electrochemical reaction of gases at higher rates such as in fuel cells were used for CO2 electro‐reduction. Cu powder, Cu and ZnO mixed powder, and CuO/ZnO mixed oxides were examined as the catalysts. The reduction products with Cu‐GDEs in K2SO4 aq. soln. were CH4, C2H4, C2H5OH, CO, HCOO−, etc. The purer and the smaller particle size of the Cu powder, it shows the higher activity and efficiency for CO and hydrocarbons formation. CO2 reduction can be carried out ca. 100 times greater rate using a GDE than that with a Cu‐foil electrode. With GDEs of CuO/ZnO = 3/7, the main product was C2H5OH with an efficiency of 17% with selectivity of 88% at −1.32 V. With GDEs of Cu/ZnO = 3/7 reduced by H2, the selectivity became poorer due to additional production of n‐C3H7OH and C2H4, although the total efficiencies for CO2 reduction became 41% at −1.30 V.
A note on a relevance estimate and its improvement (1968)

In this paper the effect of iterating the improvement procedure is examined. It is shown that applications of the improvement factor beyond the first time are ineffectual, and that the factor is but a scale factor.
CD19xCD3 DART protein mediates human B-cell depletion in vivo in humanized BLT mice (2016)

Novel therapeutic strategies are needed for the treatment of hematologic malignancies; and bispecific antibody-derived molecules, such as dual-affinity re-targeting (DART) proteins, are being developed to redirect T cells to kill target cells expressing tumor or viral antigens. Here we present our findings of specific and systemic human B-cell depletion by a CD19xCD3 DART protein in humanized BLT mice. Administration of the CD19xCD3 DART protein resulted in a dramatic sustained depletion of human CD19(+) B cells from the peripheral blood, as well as a dramatic systemic reduction of human CD19(+) B-cell levels in all tissues (bone marrow, spleen, liver, lung) analyzed. When human CD8(+) T cells were depleted from the mice, no significant B-cell depletion was observed in response to CD19xCD3 DART protein treatment, confirming that human CD8(+) T cells are the primary effector cells in this in vivo model. These studies validate the use of BLT humanized mice for the in vivo evaluation and preclinical development of bispecific molecules that redirect human T cells to selectively deplete target cells.
Coexpression of different antigenic markers on moieties that bear CA 125 determinants. (1991)

CA 125 has been extensively evaluated as a serum marker for monitoring patients with epithelial ovarian carcinoma. Recently, consideration has been given to the use of CA 125 as one component in a strategy for early detection of this disease. A number of benign conditions can, however, increase CA 125 in serum, limiting the utility of a single antigen determination for identifying ovarian cancer patients. Coexpression of different epitopes on the high molecular weight complexes that express CA 125 determinants might provide a more specific test for malignant disease, provided that adequate sensitivity were maintained. To determine how frequently determinants are coexpressed, macromolecular moieties containing CA 125 determinants have been isolated from ascites fluid of ovarian cancer patients by immunoaffinity chromatography. CA 125+ moieties have been probed on Western transfers with several murine monoclonal antibodies that recognize distinct tumor-associated epitopes. Marked heterogeneity was observed between patients with regard to antigenic determinants that could be coexpressed with CA 125. A fraction of ascites fluids from different ovarian cancer patients contained moieties which bound to OC 125 on a solid phase immmunoadsorbent and which also bound 125I-labeled monoclonal antibodies NS 19-9, B72.3, DF3, or the novel murine monoclonal antibody OC 3632 in a double determinant immunoradiometric assay. Serum samples were evaluated from patients with ovarian cancer and from apparently healthy individuals. Coexpression of TAG 72 and CA 125 was observed most frequently. When the double determinant assay for coexpression of TAG 72 and CA 125 was compared to assays for the individual antigens, the assay for coexpression was substantially less sensitive than those for the individual markers.
Protective effect of mesenchymal stem cell-conditioned medium on hepatic cell apoptosis after acute liver injury. (2013)

The aim of this study was to investigate the role of Mesenchymal Stem Cell (MSC) conditioned medium (CM(MSC)) on apoptosis of cultured mouse primary hepatocytes after in vivo carbon tetrachloride (CCl4)-induced acute liver injury. The acute liver injury was induced by injecting CCl4 intraperitoneally in C57/BL6 mice. Hepatocytes were isolated by liver perfusion, cultured in a defined medium to maintain their differentiation and characterized by reverse transcriptase polymerase chain reaction (RT-PCR) using the hepatic cell specific genes albumin, hepatocyte nuclear factor 4 (HNF4) and cytokeratin 18 (CK18). CM(MSC) was generated from cultured bone marrow-derived MSCs (BM-MSCs). BM-MSCs were positive for CD73, CD90, CD44 by flow cytometry and able to differentiate into chondrocytes, adipocytes and osteocytes. Apoptosis was evaluated by both annexin V. CM(MSC) were examined by flow cytometry to detect MSC-derived annexin V- and CD54/CD44-positive microparticles (MPs). In the CCl4-CM(MSC) treated hepatocytes, interleukin-6 (IL-6) was increased on the first day of culture compared to control and CCl4 and was followed by upregulation of fibroblast-like-protein (FGL1) expression after 48 hrs. This was associated with a significant decrease of annexin V positive CCl4-CM(MSC) treated hepatocytes at day 3 post plating. Recombinant IL-6 was induced FGL1 expression in hepatocytes derived from CCl4-treated mice suggesting that CM(MSC), which is enriched also in microparticles, attenuates CCl4-induced early apoptosis in hepatocytes through activation of FGL1.
Reactogenicity and Immunogenicity of a Protein-Conjugated Pneumococcal Oligosaccharide Vaccine in Older Adults (1996)

Healthy adults > or = 50 years old were immunized with either pentavalent Corynebacterium diphtheriae C7 (beta197) cross-reactive material (CRM197) protein-conjugated pneumococcal vaccine (CV) containing 10 microgram each of capsular oligosaccharides from serotypes 6B, 14, 18C, 19F, and 23F or with licensed (23-valent, 25 microgram/serotype) pneumococcal polysaccharide vaccine (PV). Adverse reactions, predominantly local in nature, occurred in 20 of 23 CV recipients versus 13 of 23 PV recipients (P<.05). Compared with mean postvaccination antibody concentrations in PV recipients, those induced by CV were not significantly different for serotypes 6B, 14, 18C, and 23F and were lower for 19F (P<.05). Six months later, reimmunization with PV of subjects who had initially received CV elicited a slight boost in antibody concentrations to levels that were not significantly higher than those achieved after the primary vaccination or than those in persons given a single dose of PV. Pneumococcal vaccines containing protein-conjugated oligosaccharides may offer no advantage over currently licensed preparations containing unconjugated polysaccharides for immunization of healthy older adults.
Bacteria and the aetiology of cancer of the large bowel. (1969)

Cancer of the large bowel shows marked variations in geographical distribution (Doll, 1967; Doll, Payne, and Waterhouse, 1966; Davis, Knowelden, and Wilson, 1965) and, with the exception of Japan, the disease is more prevalent in developed than in underdeveloped countries. The reason for this variation is not known but epidemiological evidence suggests that environmental factors may be involved. It is claimed that immigrants from areas with a low incidence of cancer of the large bowel tend to show the same high incidence of this cancer as the local population (Haenszel and Dawson, 1965; Buell and Dunn, 1965). Changes in dietary habit may be especially important (Wynder and Shigematsu, 1967;
Botulinum toxin type A and short-term electrical stimulation in the treatment of upper limb flexor spasticity after stroke: a randomized, double-blind, placebo-controlled trial (1998)

The placebo-controlled trial favours the concept that electrical stimulation enhances the effectiveness of BtxA in the treatment of chronic upper limb flexor spasticity after stroke.
PCPP-260, a Purkinje cell-specific cyclic AMP-regulated membrane phosphoprotein of Mr 260,000 (1986)

The present study reports the existence of Purkinje cell-specific phosphoprotein, Mr 260,000 (PCPP-260), a neuronal membrane phosphoprotein, in cerebellar Purkinje cells. PCPP-260, which on sodium dodecyl sulfate-polyacrylamide gel electrophoresis has an apparent molecular mass of 260,000 Da, has been found to be phosphorylated in particulate preparations by endogenous or added exogenous cyclic AMP-dependent protein kinase, but not by cyclic GMP-dependent, calcium/calmodulin-dependent or calcium/phospholipid-dependent protein kinases. The protein has been found in high concentrations in all mammalian cerebella so far analyzed, including human cerebellum. One-and two-dimensional electrophoretic and peptide mapping analyses of proteins in other brain regions show that a closely related 265,000 Da phosphoprotein also exists, albeit in low concentrations, outside the cerebellum. Analysis of cerebella from mutant mice, deficient in either Purkinje cells or in granule cells, indicates that PCPP-260 within the cerebellum is restricted to Purkinje cells. Furthermore, subcellular fractionation of rat cerebella indicates that the protein is an integral membrane protein. The cAMP-regulated phosphorylation of PCPP-260 is presumably involved in membrane functions important to Purkinje cells.
OX40 engagement and chemotherapy combination provides potent antitumor immunity with concomitant regulatory T cell apoptosis (2009)

Expansion and recruitment of CD4(+) Foxp3(+) regulatory T (T reg) cells are mechanisms used by growing tumors to evade immune elimination. In addition to expansion of effector T cells, successful therapeutic interventions may require reduction of T reg cells within the tumor microenvironment. We report that the combined use of the alkylating agent cyclophosphamide (CTX) and an agonist antibody targeting the co-stimulatory receptor OX40 (OX86) provides potent antitumor immunity capable of regressing established, poorly immunogenic B16 melanoma tumors. CTX administration resulted in tumor antigen release, which after OX86 treatment significantly enhanced the antitumor T cell response. We demonstrated that T reg cells are an important cellular target of the combination therapy. Paradoxically, the combination therapy led to an expansion of T reg cells in the periphery. In the tumor, however, the combination therapy induced a profound T reg cell depletion that was accompanied by an influx of effector CD8(+) T cells leading to a favorable T effector/T reg cell ratio. Closer examination revealed that diminished intratumoral T reg cell levels resulted from hyperactivation and T reg cell-specific apoptosis. Thus, we propose that CTX and OX40 engagement represents a novel and rational chemoimmunotherapy.
CXCR4+/FLK-1+ Biomarkers Select a Cardiopoietic Lineage from Embryonic Stem Cells (2008)

Pluripotent stem cells demonstrate an inherent propensity for unrestricted multi-lineage differentiation. Translation into regenerative applications requires identification and isolation of tissue-specified progenitor cells. From a comprehensive pool of 11,272 quality-filtered genes, profiling embryonic stem cells at discrete stages of cardiopoiesis revealed 736 transcripts encoding membrane-associated proteins, where 306 were specifically upregulated with cardiogenic differentiation. Bioinformatic dissection of exposed surface biomarkers prioritized the chemokine receptor cluster as the most significantly over-represented gene receptor family during pre cardiac induction, with CXCR4 uniquely associated with mesendoderm formation. CXCR4(+) progenitors were sorted from the embryonic stem cell pool into mesoderm-restricted progeny according to co-expression with the early mesoderm marker Flk-1. In contrast to CXCR4(-)/Flk-1(-) cells, the CXCR4(+)/Flk-1(+) subpopulation demonstrated overexpressed cardiac lineage transcription factors (Mef2C, Myocardin, Nkx2.5), whereas pluripotent genes (Oct4, Fgf4, Sox2) as well as neuroectoderm (Sox1) and endoderm alpha-fetoprotein markers were all depleted. In fact, the CXCR4(+)/Flk-1(+) biomarker combination identified embryonic stem cell progeny significantly enriched with Mesp-1, GATA-4, and Tbx5, indicative of pre cardiac mesoderm and the primary heart field. Although the CXCR4(+)/Flk-1(+) transcriptome shared 97% identity with the CXCR4(-)/Flk-1(-) counterpart, the 818 divergent gene set represented predominantly cardiovascular developmental functions and formed a primitive cardiac network. Differentiation of CXCR4(+)/Flk-1(+) progenitors yielded nuclear translocation of myocardial transcription factors and robust sarcomerogenesis with nascent cardiac tissue demonstrating beating activity and calcium transients. Thus, the CXCR4/Flk-1 biomarker pair predicts the emergence of cardiogenic specification within a pluripotent stem cell pool, enabling targeted selection of cardiopoietic lineage. Disclosure of potential conflicts of interest is found at the end of this article.
Structure, Endothelial Function, Cell Growth, and Inflammation in Blood Vessels of Angiotensin II–Infused Rats (2002)

Thiazolidinedione PPAR-gamma activators attenuated the development of hypertension, corrected structural abnormalities, normalized cell growth, and improved endothelial dysfunction induced by Ang II and prevented upregulation of angiotensin II type 1 receptors, cell cycle proteins, and proinflammatory mediators. Thiazolidinediones may be useful in the prevention and/or treatment of hypertension, particularly when it is associated with insulin resistance or diabetes mellitus.
Residual adenylosuccinase activities in fibroblasts of adenylosuccinase‐deficient children: Parallel deficiency with adenylosuccinate and succinyl‐AICAR in profoundly retarded patients and non‐parallel deficiency in a mildly retarded girl (1993)

Adenylosuccinase (ASase) catalyses both the conversion of succinyl-aminoimidazole carboxamide ribotide (succinyl-AICAR) into AICAR and that of adenylosuccinate into AMP in the synthesis of purine nucleotides. Its deficiency results in the accumulation in body fluids of the nucleosides corresponding to both substrates, succinyl-AICAriboside and succinyladenosine. Two main subtypes of the defect are type I with severe mental retardation and succinyladenosine/succinyl-AICAriboside ratios around 1, and type II with slight mental delay and succinyladenosine/succinyl-AICAriboside ratios around 4. We report that in fibroblasts of type I patients, the activity of ASase with both adenylosuccinate and succinyl-AICAR is about 30% of normal. In contrast, in type II fibroblasts, the activity with adenylosuccinate is only 3% of normal, whereas that with succinyl-AICAR is also 30% of normal. If also present in other tissues, this non-parallel deficiency provides an explanation for the higher concentration of succinyladenosine in type II. In type I fibroblasts, ASase is further characterized mainly by a 3-fold to 4-fold increase in Km for succinyl-AICAR, and by retarded elution from an anion exchanger. In type II fibroblasts, ASase is characterized by a similar increase in Km for succinyl-AICAR but by a potent inhibition by KCl and nucleoside triphosphates, and by a normal elution profile. These results suggest a modification of the surface charge of ASase in type I, and the addition of one or more positively charged residues in the active site in type II.
Pathological Mechanisms and Clinical Features of Eosinophilic Chronic Rhinosinusitis in the Japanese Population (2010)

The overall pathological view of paranasal sinus inflammation in the Japanese population has profoundly changed in recent years. Eosinophilic chronic rhinosinusitis (ECRS) is a clinical entity of intractable chronic sinus inflammation accompanied by numerous infiltrations of activated eosinophils in the paranasal sinus mucosa and/or nasal polyps. Several pathologic processes are considered to act in concert to promote the accumulation of eosinophils in ECRS. They include infiltration of progenitor cells, increase in local IL-3, IL-5, IL-13, GM-CSF and eotaxin production, and upregulation of adhesion molecules. The role of nasal allergen sensitization and innate immunity responses in the sinus mucosa has also been proposed in the development of ECRS. Various pathogens including TLRs ligands may trigger an abnormal immune response at the mucosal surface. The objectives of ECRS management should focus directly on inhibition of local eosinophil infiltration. Surgical procedures include widely opening the bony wall septum of every affected sinus and mechanical removal of diseased mucosal lesion. The use of local and/or systemic steroids, leukotriene receptor antagonists, and Th2 cytokine antagonists is recommended. Local administration of steroids is a potent treatment strategy for preventing relapse of nasal polyposis and is considered to be the first-line treatment for ECRS patients.
Deactivation of the boron acceptor in silicon by hydrogen (1983)

Two new experiments are presented which suggest that the ‘‘bulk-compensating donor’’ phenomenon observed in p-Si is probably a deactivation process of the boron acceptor by hydrogen with the formation of a B−H+ pair. The two experiments are (i) avalanche hole injection in Al-gate metal-oxide-silicon capacitor from boron-diffused n-Si substrate and (ii) 5-keV electron irradiation of Al/p-Si Schottky diodes. Atomic hydrogen may be released by the avalanche injected energetic electrons or holes or keV electrons from the Al–H, AlO–H, Si–H, and SiO–H sites in the Al gate and the SiO2 film as well as at the Al/SiO2 and SiO2/Si interfaces, which may then migrate to the boron acceptor sites to form the B−H+ pair. Observed hydrogen bond breaking rate by holes is as much as two orders of magnitude larger than by electrons, which is consistent with the thermal hole capture and energetic electron impact bond-breaking models.
Early Changes in Refractive Error Following Radial Keratotomy (1988)

One hundred twenty-six eyes that had undergone radial keratotomy were analyzed to assess the early changes in refractive error after surgery. Between two weeks and three months, 38% of eyes became more myopic by less than 1 diopter (D), 34% by 1.00 to 1.87 D, and 25% by 2.00 to 3.50 D. Four eyes (3%) had a decrease of 0.25 to 1.25 D. The average increase between two weeks and three months was 1.31 D (SD, 0.9 D). To decrease this change, 15 eyes were semi-pressure patched at night and treated with topical steroids for four weeks following surgery. The average change between two weeks and three months in these eyes was 0.3 D (SD, 1.0 D). This retrospective study suggests that semi-pressure patching after surgery may be useful for eyes that are undercorrected or overcorrected by less than 1 D.