gebhart/patrepeval huggingface dataset:
Absence of α-Syntrophin Leads to Structurally Aberrant Neuromuscular Synapses Deficient in Utrophin (2000)

The syntrophins are a family of structurally related proteins that contain multiple protein interaction motifs. Syntrophins associate directly with dystrophin, the product of the Duchenne muscular dystrophy locus, and its homologues. We have generated alpha-syntrophin null mice by targeted gene disruption to test the function of this association. The alpha-Syn(-/)- mice show no evidence of myopathy, despite reduced levels of alpha-dystrobrevin-2. Neuronal nitric oxide synthase, a component of the dystrophin protein complex, is absent from the sarcolemma of the alpha-Syn(-/)- mice, even where other syntrophin isoforms are present. alpha-Syn(-/)- neuromuscular junctions have undetectable levels of postsynaptic utrophin and reduced levels of acetylcholine receptor and acetylcholinesterase. The mutant junctions have shallow nerve gutters, abnormal distributions of acetylcholine receptors, and postjunctional folds that are generally less organized and have fewer openings to the synaptic cleft than controls. Thus, alpha-syntrophin has an important role in synapse formation and in the organization of utrophin, acetylcholine receptor, and acetylcholinesterase at the neuromuscular synapse.
Mice transgenic for human CD4 and CCR5 are susceptible to HIV infection (1997)

HIV entry into human cells is mediated by CD4 acting in concert with one of several members of the chemokine receptor superfamily. The resistance to HIV infection observed in individuals with defective CCR5 alleles indicated that this particular chemokine receptor plays a crucial role in the initiation of in vivo HIV infection. Expression of human CD4 transgene does not render mice susceptible to HIV infection because of structural differences between human and mouse CCR5. To ascertain whether expression of human CD4 and CCR5 is sufficient to make murine T lymphocytes susceptible to HIV infection, the lck promoter was used to direct the T cell-specific expression of human CD4 and CCR5 in transgenic mice. Peripheral blood mononuclear cells and splenocytes isolated from these mice expressed human CD4 and CCR5 and were infectible with selected M-tropic HIV isolates. After in vivo inoculation, HIV-infected cells were detected by DNA PCR in the spleen and lymph nodes of these transgenic mice, but HIV could not be cultured from these cells. This indicated that although transgenic expression of human CD4 and CCR5 permitted entry of HIV into the mouse cells, significant HIV infection was prevented by other blocks to HIV replication present in mouse cells. In addition to providing in vivo verification for the important role of CCR5 in T lymphocyte HIV infection, these transgenic mice represent a new in vivo model for understanding HIV pathogenesis by delineating species-specific cellular factors required for productive in vivo HIV infection. These mice should also prove useful for the assessment of potential therapeutic and preventative modalities, particularly vaccines.
The developmental origins of adult disease (Barker) hypothesis (2006)

Many studies have provided evidence for the hypothesis that size at birth is related to the risk of developing disease in later life. In particular, links are well established between reduced birthweight and increased risk of coronary heart disease, diabetes, hypertension and stroke in adulthood. These relationships are modified by patterns of postnatal growth. The most widely accepted mechanisms thought to underlie these relationships are those of fetal programming by nutritional stimuli or excess fetal glucocorticoid exposure. It is suggested that the fetus makes physiological adaptations in response to changes in its environment to prepare itself for postnatal life. These changes may include epigenetic modification of gene expression. Less clear at this time are the relevance of fetal programming phenomena to twins and preterm babies, and whether any of these effects can be reversed after birth. Much current active research in this field will be of direct relevance to future obstetric practice.
Protein Kinase A Phosphorylation of Human Phosphodiesterase 3B Promotes 14-3-3 Protein Binding and Inhibits Phosphatase-catalyzed Inactivation (2007)

Recent studies confirm that intracellular cAMP concentrations are nonuniform and that localized subcellular cAMP hydrolysis by cyclic nucleotide phosphodiesterases (PDEs) is important in maintaining these cAMP compartments. Human phosphodiesterase 3B (HSPDE3B), a member of the PDE3 family of PDEs, represents the dominant particulate cAMP-PDE activity in many cell types, including adipocytes and cells of hematopoietic lineage. Although several previous reports have shown that phosphorylation of HSPDE3B by either protein kinase A (PKA) or protein kinase B (PKB) activates this enzyme, the mechanisms that allow cells to distinguish these two activated forms of HSPDE3B are unknown. Here we report that PKA phosphorylates HSPDE3B at several distinct sites (Ser-73, Ser-296, and Ser-318), and we show that phosphorylation of HSPDE3B at Ser-318 activates this PDE and stimulates its interaction with 14-3-3 proteins. In contrast, although PKB-catalyzed phosphorylation of HSPDE3B activates this enzyme, it does not promote 14-3-3 protein binding. Interestingly, we report that the PKA-phosphorylated, 14-3-3 protein-bound, form of HSPDE3B is protected from phosphatase-dependent dephosphorylation and inactivation. In contrast, PKA-phosphorylated HSPDE3B that is not bound to 14-3-3 proteins is readily dephosphorylated and inactivated. Our data are presented in the context that a selective interaction between PKA-activated HSPDE3B and 14-3-3 proteins represents a mechanism by which cells can protect this enzyme from deactivation. Moreover, we propose that this mechanism may allow cells to distinguish between PKA- and PKB-activated HSPDE3B.
The biochemical mechanisms of action of the interferons. (1988)

The interferon family of proteins consists of a variety of antigenically distinct types that are encoded by different genes. Several of these genes have been cloned and the availability of large amounts of the recombinant interferons has greatly facilitated characterization of their biochemical and biological activities. The specificity of interaction of interferons with cell surface receptors has been investigated in binding and covalent cross-linking experiments employing 125I-labeled interferons. In addition to their antiviral activity, the interferons have effects on cell growth and differentiation. The interferons also are potent modulators of the immune response. The interferons exert their biological activities by altering the expression of several cellular proteins. Current knowledge about the mechanisms of signal transduction and the regulation of expression of interferon-induced mRNAs and proteins are discussed.
Inheritance of susceptibility to bleomycin-induced pulmonary fibrosis in the mouse. (1996)

Based on the range of patient responses to treatment, and on animal studies, it is hypothesized that individual variation in sensitivity to bleomycin-induced pulmonary fibrosis is controlled genetically. A genetic model has been developed by (a) establishing a distinct difference in bleomycin-induced lung damage in two inbred strains of mice [parental generation: C57BL/6J (fibrosis-prone phenotype) and C3Hf/Kam (fibrosis-resistant phenotype)] and (b) characterizing inheritance of the fibrosing phenotype in the F1 (first filial) and F2 (F1 intercross; second filial) generations derived from the parental strains. Male mice received 100 mg/kg and female mice 125 mg/kg of bleomycin via s.c. osmotic minipump. The animals were sacrificed 8 weeks after treatment or when their breathing rate indicated respiratory distress. The percentage of lung with fibrosis for each mouse was quantified with image analysis of a histological section of the left lung. The mean percentage of fibrosis for the C57BL/6J males was 8.4 +/- 0.8% (SE) and 4.4 +/- 0.8% for females, and the C3Hf/Kam mice of either sex did not present the fibrosing lesion (mean score, 0%). Significant difference (P = 6 x 10(-6)) was measured in percentage of fibrosis between the two strains of F1 males, but not F1 females (P = 0.38), suggesting the presence of an X-linked factor associated with the fibrosing phenotype. From an ANOVA the X-linked factor is estimated to contribute 19% of the fibrosis phenotype. A genetic model of two or three loci controlling the fibrosing phenotype is proposed from the data of the parental, F1, and F2 generations. The mouse model demonstrates that susceptibility to bleomycin-induced pulmonary fibrosis is a heritable trait controlled by a few genetic loci.
Serum Enzymes in Diabetes Mellitus (1973)

Abstract Serum enzymes that show changed activities in diabetes mellitus can be divided into four groups: Group I includes some lysosomal enzymes—β-glucuronidase N-acetyl-β-glucosaminidase, acid phosphatase, and amylase—that show increased activity correlated with blood sugar concentration. Because lysosomal enzymes as well as liver amylase show latency and may be "activated" by several agents, their increased activity in the serum of diabetics might be a manifestation of an activation occurring in tissues. Group II includes alkaline phosphatase and trehalase, which are increased but not correlated with blood sugar concentration. Their enhanced activity may reflect tissue metabolic disorders. Group III includes enzymes that increase in the postketotic period almost regularly—phosphohexose isomerase —or in only the most severe cases—aminotransferases and several dehydrogenases—because of tissue damage caused by metabolic and circulatory alterations. Cholinesterase, on the other hand, is decreased. Group IV includes any of the above-mentioned enzymes, and still others, that may be more active in diabetics with complications such as hepatic and renal involvement and obesity.
Low-voltage and high-field-effect mobility organic transistors with a polymer insulator (2006)

A key issue in research into organic thin-film transistors (OTFTs) is low-voltage operation. In this study, we fabricated a pentacene thin-film transistor with an ultrathin layer of polyvinyl alcohol (9nm) as a gate insulator, and obtained a device with excellent electrical characteristics at low operating voltages (below 2V). This device was found to have a field-effect mobility of 1.1cm2∕Vs, a threshold voltage of −0.98V, an exceptionally low subthreshold slope of 180mV/decade, and an on/off current ratio of 106. This favorable combination of properties means that such OTFTs can be operated successfully at voltages below 2V.
Host-Defense Activities of Cyclotides (2012)

Cyclotides are plant mini-proteins whose natural function is thought to be to protect plants from pest or pathogens, particularly insect pests. They are approximately 30 amino acids in size and are characterized by a cyclic peptide backbone and a cystine knot arrangement of three conserved disulfide bonds. This article provides an overview of the reported pesticidal or toxic activities of cyclotides, discusses a possible common mechanism of action involving disruption of biological membranes in pest species, and describes methods that can be used to produce cyclotides for potential applications as novel pesticidal agents.
Language Family Relationship Preserved in Non-native English (2014)

Mother tongue interference is the phenomenon where linguistic systems of a mother tongue are transferred to another language. Recently, Nagata and Whittaker (2013) have shown that language family relationship among mother tongues is preserved in English written by IndoEuropean language speakers because of mother tongue interference. At the same time, their findings further introduce the following two research questions: (1) Does the preservation universally hold in non-native English other than in English of Indo-European language speakers? (2) Is the preservation independent of proficiency in English? In this paper, we address these research questions. We first explore the two research questions empirically by reconstructing language family trees from English texts written by speakers of Asian languages. We then discuss theoretical reasons for the empirical results. We finally introduce another hypothesis called the existence of a probabilistic module to explain why the preservation does or does not hold in particular situations.
Conformational analysis of the immunodominant epitopes of the circumsporozoite protein of Plasmodium falciparum and knowlesi (1990)

All of the coat proteins of the sporozoite and merozoite stages of Plasmodium, determined to date, contain tandem repeats and most of these contain at least one proline residue. These tandemly repeated segments of the circumsporozite (CS) proteins of P. falciparum and P. knowlesi have been shown to constitute an immunodominant epitope. Antibodies to these peptide segments have been shown to be protective and cause the shedding of the CS protein, known as the CSP reaction. In this study, four synthetic peptides were prepared by solid-phase peptide synthesis. The first peptide corresponds to the tetrapeptide tandem repeat in the CS protein of P. falciparum, repeated eight times, (NANP)8. The second peptide is an analogue of the first in which glycine is substituted for proline, (NANG)8. The third peptide corresponds to the tandem repeat of P. knowlesi, PK(1-24), which is repeated twice (QAQGDGANAGQP)2. The fourth peptide is a tetrapeptide repeat, corresponding to the C-terminal tetrapeptide of PK(1-24) and is repeated eight times, (AGQP)8. It is shown by CD measurements that the presence of proline in these repeats induces an increase in beta-sheet (beta-turn) content in the (NANP)8 peptide relative to the repeat of (NANG)8 and PK(1-24) peptide in aqueous media. The (AGQP)8 peptide has the highest beta-sheet (beta-turn) content of all peptides studied. The Chou-Fasman predictive algorithm indicates a high beta-turn content in the synthetic peptides. It is concluded that this increase in defined structure correlates well with and hence may contribute to the increased antigenicity in these repeats.
Dose‐Related Antagonism of the Emetic Effect of Morphine by Methylnaltrexone in Dogs (1993)

Opioids administered to produce analgesia cause unwanted emesis in patients (incidence 20%-30%, depending on situation). Tests in animals show that quaternary narcotic antagonists like methylnaltrexone (MNTX) do not affect the analgesic potency of morphine, but such compounds have not been examined for their potential to antagonize morphine-induced emesis. To determine the effects of MNTX on emetic response, we assigned 85 dogs to one of 11 groups challenged with morphine alone or morphine and various doses of MNTX IM or i.v. Antagonism of the emetic response was dose related: MNTX, 0.25 mg/kg IM or 0.2 mg/kg i.v., completely blocked the emetic effect of morphine in dogs for approximately 60 minutes. If morphine-induced emesis is mediated by receptors available to a quaternary antagonist (perhaps on the peripheral side of the blood-brain barrier), MNTX may prevent opioid-induced emesis. These data indicate that opioid-induced emesis might be prevented without affecting analgesia.
Augmentation of apoptosis and tumor regression by flavopiridol in the presence of CPT-11 in Hct116 colon cancer monolayers and xenografts. (2001)

CPT-11, a DNA topoisomerase I inhibitor, has demonstrated clinical activity in colorectal cancer. Flavopiridol, a cyclin-dependent kinase inhibitor, is rapidly emerging as a chemotherapy modulator. To enhance the therapeutic index of CPT-11 in colon cancer, we studied the combination of these two drugs in relatively resistant human colon cancer cells, Hct116. Exposure of parental Hct116 cells to clinically achievable concentrations of SN-38 (the active metabolite of CPT-11) induces p21 and a G(2) arrest. However, these conditions fail to induce apoptosis. In contrast, Hct116 cells that are p21 deficient (p21-/- Hct116) readily undergo apoptosis after treatment with SN-38. In this study we show that the parental Hct116 cells can be sensitized to undergo apoptosis by the addition of flavopiridol after SN-38 treatment. The induction of apoptosis was greatest with sequential therapy consisting of SN-38 followed by flavopiridol. Clonogenic assays also showed greatest inhibition with this sequence. Sequential treatment with SN-38 followed by flavopiridol was associated with higher activation of caspase-3 and greater cleavage of both p21 and XIAP, an inhibitor of apoptosis, compared with other treatment schedules. CPT-11 induced some tumor regressions but no complete responses in the p21-intact Hct116 xenografts. CPT-11 with flavopiridol more than doubled tumor regression, compared with CPT-11 alone, and produced a 30% complete response rate. Our studies indicate that CPT-11 induces cell cycle arrest rather than cell death and that flavopiridol, by activating the caspase cascade, cleaves the inhibitors of apoptosis and sensitizes the cells to undergo cell death. Thus, flavopiridol combined with CPT-11 may provide a completely new therapeutic approach in the treatment of colon cancer.
Isolation and oncogenic potential of a novel human src-like gene. (1986)

We have isolated cDNA molecules representing the complete coding sequence of a new human gene which is a member of the src family of oncogenes. Nucleotide sequence analysis revealed that this gene, termed slk, encoded a 537-residue protein which was 86% identical to the chicken proto-oncogene product, p60c-src, over a stretch of 191 amino acids at its carboxy terminus. In contrast, only 6% amino acid homology was observed within the amino-terminal 82 amino acid residues of these two proteins. It was possible to activate slk as a transforming gene by substituting approximately two-thirds of the slk coding sequence for an analogous region of the v-fgr onc gene present in Gardner-Rasheed feline sarcoma virus. The resulting hybrid protein molecule expressed in transformed cells demonstrated protein kinase activity with specificity for tyrosine residues.
922. Cephalosporanic acids. Part II. Displacement of the acetoxy-group by nucleophiles (1965)

J. D. Cocker, B. R. Cowley, J. S. G. Cox, S. Eardley, G. I. Gregory, J. K. Lazenby, A. G. Long, J. C. P. Sly and G. A. Somerfield, J. Chem. Soc., 1965, 5015 DOI: 10.1039/JR9650005015
High-gain In 0.53 Ga 0.47 As:Fe photoconductive detectors (1984)

Photoconductive detectors were fabricated on semi-insulating liquid phase epitaxial In0.53Ga0.47As/InP doped with Fe for the first time. Their performance characteristics have been compared with identical devices made from Zn-doped p-In0.53Ga0.47As/InP. Internal optical gains up to 10 were measured in the Fe-doped devices. The bias and intensity-dependent gain characteristics of these devices are discussed.
Innovative therapies for systemic sclerosis (2010)

Although there is still no treatment that is unequivocally effective for scleroderma, there have been some promising developments over the past number of years with identification of novel candidate targets and innovative strategies, including targeted immunomodulatory therapies, tyrosine kinase inhibitors and agents that may promote vascular repair. These recent findings will need to be confirmed by larger, multicentre, randomized controlled trials, but they provide hope that these novel therapeutic agents may broaden the currently restricted therapeutic armamentarium of the disease.
Functionalized carbon nanotube doping of P3HT:PCBM photovoltaic devices for enhancing short circuit current and efficiency (2016)

We have successfully functionalized multiwalled carbon nanotubes (MWCNTs) using nitrene approach employing the two aryl azides as a precursor for nitrene generation. The dispersion of functionalized MWCNTs has been enhanced in various organic solvents. These functionalized MWCNTs have been successfully doped in various concentrations in the bulk heterojunction (BHJ) organic photovoltaic (OPV) cells with a poly (3-hexyl thiophene) (P3HT) and [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) photoactive blended layer. The incorporation of MWCNTs with aryl functional groups, in active the layer, results in enhanced performance with respect to a reference cell. The maximum power conversion efficiency of 1.86% is achieved with adduct I while in the case of adduct II it gets double to 2.0% in comparison with a reference cell. This improvement in the device performance is attributed to enhanced exciton dissociation and improved charge transport properties due to the formation of a nanotube percolation network in the photoactive composite layer.
Artifact analysis and image enhancement in three-dimensional computational integral imaging using smooth windowing technique (2011)

We propose an artifact analysis in computational integral imaging and the image enhancement method based on the analysis using the smooth windowing technique. Blurring and lenslet artifacts, which are major problems in computational integral imaging, are defined and analyzed using a signal model. Applying a smooth and continuous window such as the triangular window to computational integral imaging reconstruction provides a dramatic improvement in terms of image quality. Experimental results are presented to show the validity of our method. To our best knowledge, this is the first trial to control a window function in computational integral imaging.
Transcription factor EGR-1 suppresses the growth and transformation of human HT-1080 fibrosarcoma cells by induction of transforming growth factor beta 1. (1996)

The early growth response 1 (EGR-1) gene product is a transcription factor with role in differentiation and growth. We have previously shown that expression of exogenous EGR-1 in various human tumor cells unexpectedly and markedly reduces growth and tumorigenicity and, conversely, that suppression of endogenous Egr-1 expression by antisense RNA eliminates protein expression, enhances growth, and promotes phenotypic transformation. However, the mechanism of these effects remained unknown. The promoter of human transforming growth factor beta 1 (TGF-beta 1) contains two GC-rich EGR-1 binding sites. We show that expression of EGR-1 in human HT-1080 fibrosarcoma cells uses increased secretion of biologically active TGF-beta 1 in direct proportion (rPearson = 0.96) to the amount of EGR-1 expressed and addition of recombinant human TGF-beta 1 is strongly growth-suppressive for these cells. Addition of monoclonal anti-TGF-beta 1 antibodies to EGR-1-expressing HT-1080 cells completely reverses the growth inhibitory effects of EGR-1. Reporter constructs bearing the EGR-1 binding segment of the TGF-beta 1 promoter was activated 4- to 6-fold relative to a control reporter in either HT-1080 cells that stably expressed or parental cells cotransfected with an EGR-1 expression vector. Expression of delta EGR-1, a mutant that cannot interact with the corepressors, nerve growth factor-activated factor binding proteins NAB1 and NAB2, due to deletion of the repressor domain, exhibited enhanced transactivation of 2- to 3.5-fold over that of wild-type EGR-1 showing that the reporter construct reflected the appropriate in vivo regulatory context. The EGR-1-stimulated transactivation was inhibited by expression of the Wilms tumor suppressor, a known specific DNA-binding competitor. These results indicate that EGR-1 suppresses growth of human HT-1080 fibrosarcoma cells by induction of TGF-beta 1.