gebhart/patrepeval huggingface dataset:
Cleavage of Influenza Virus Hemagglutinin by Airway Proteases TMPRSS2 and HAT Differs in Subcellular Localization and Susceptibility to Protease Inhibitors (2010)

Proteolytic cleavage of the influenza virus surface glycoprotein hemagglutinin (HA) by host cell proteases is crucial for infectivity and virus spread. The proteases HAT (human airway trypsin-like protease) and TMPRSS2 (transmembrane protease serine S1 member 2) known to be present in the human airways were previously identified as proteases that cleave HA. We studied subcellular localization of HA cleavage and cleavage inhibition of seasonal influenza virus A/Memphis/14/96 (H1N1) and pandemic virus A/Hamburg/5/2009 (H1N1) in MDCK cells that express HAT and TMPRSS2 under doxycycline-induced transcriptional activation. We made the following observations: (i) HA is cleaved by membrane-bound TMPRSS2 and HAT and not by soluble forms released into the supernatant; (ii) HAT cleaves newly synthesized HA before or during the release of progeny virions and HA of incoming viruses prior to endocytosis at the cell surface, whereas TMPRSS2 cleaves newly synthesized HA within the cell and is not able to support the proteolytic activation of HA of incoming virions; and (iii) cleavage activation of HA and virus spread in TMPRSS2- and HAT-expressing cells can be suppressed by peptide mimetic protease inhibitors. The further development of these inhibitors could lead to new drugs for influenza treatment.
VisIVO Workflow-Oriented Science Gateway for Astrophysical Visualization (2013)

Nowadays visualization-based knowledge discovery can play an important role in astrophysics. Collaborative visualization can enable multiple users to share visualization experiences, e.g. by interacting simultaneously with astrophysical datasets giving feedback on what other participants are doing/seeing. Further, workflow-driven applications allow reproduction of specific visualization results, a challenging task as selecting suitable visualization parameters may not be a straightforward process. This paper presents VisIVO Science Gateway, a web-based workflow-enabled framework integrating large-scale, multidimensional datasets and applications for visualization and data filtering on Distributed Computing Infrastructures (DCIs). Advanced users are able to create, change, invoke, and monitor workflows while standard users are provided with easy-to-use customised web interfaces hiding all technical aspects of the visualization algorithms and DCI configurations.
Biological activities of human granulocyte‐macrophage colony‐stimulating factor (1988)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has emerged as an important regulation for hematopoietic cell development and function. Within the myeloid lineages, GM-CSF serves as a growth and developmental factor for intermediate-stage progenitors between early, interleukin 3-responsive and late granulocyte colony-stimulating factor-responsive precursors. GM-CSF also serves as an activator of circulating effector cells. The ability of GM-CSF to induce monocyte expression of tumor necrosis factor, interleukin 1 and other factors, further ties this hormone into a network of cytokines that interact to regulate many hematologic and immunologic responses. The availability of large quantities of recombinant GM-CSF now provides the opportunity and challenge not only for unraveling the mechanisms regulating hematopoiesis, but also for developing new therapies for enhancement of host defense against infection that were not previously possible.
Measurement of stand-sit and sit-stand transitions using a miniature gyroscope and its application in fall risk evaluation in the elderly (2002)

A new method of evaluating the characteristics of postural transition (PT) and their correlation with falling risk in elderly people is described. The time of sit-to-stand and stand-to-sit transitions and their duration were measured using a miniature gyroscope attached to the chest and a portable recorder placed on the waist. Based on a simple model and the discrete wavelet transform, three parameters related to the PT were measured, namely, the average and standard deviation of transition duration and the occurrence of abnormal successive transitions (number of attempts to have a successful transition). The comparison between two groups of elderly subjects (with high and low fall-risk) showed that the computed parameters were significantly correlated with the falling risk as determined by the record of falls during the previous year, balance and gait disorders (Tinetti score), visual disorders, and cognitive and depressive disorders (p < 0.01). In this study, the wavelet transform has provided a powerful technique for enhancing the pattern of PT, which was mainly concentrated into the frequency range of 0.04-0.68 Hz. The system is especially adapted for long-term ambulatory monitoring of elderly people.
Covalent Scavengers for Primary and Secondary Amines (2000)

Covalent scavenging strategies which rely upon the chemical reactivity of primary and secondary amines have found application in the separation of amine starting materials from combinatorial synthesis products. The use of solid-supported scavengers, sequestration enabling reagents, and the technique of impurity annihilation all allow the removal of structurally diverse amines by procedures that are easily carried out in parallel and are amenable to automation. 1 Introduction 2 Covalent Scavenging 2 3 Covalent Scavengers for Amines 4 Conclusions and Outlook
Quasi-trapezoidal pulses to selectively block the activation of intrinsic laryngeal muscles during vagal nerve stimulation (2007)

The stimulation of the vagus nerve has been used as an anti-epileptic treatment for over a decade, and its use for depression and chronic heart failure is currently under investigation. Co-activation of the intrinsic laryngeal muscles may limit the clinical use of vagal stimulation, especially in the case of prolonged activation. To prevent this, the use of a selective stimulation paradigm has been tested in seven acute pig experiments. Quasi-trapezoidal pulses successfully blocked the population of the largest and fastest vagal myelinated fibers being responsible for the co-activation. The first response in the vagus compound action potential was reduced by 75 +/- 22% (mean +/- SD) and the co-activated muscle action potential by 67 +/- 25%. The vagal bradycardic effects remained unchanged during the selective block, confirming the leading role of thin nerve fibers for the vagal control of the heart. Quasi-trapezoidal pulses may be an alternative to rectangular pulses in clinical vagal stimulation when the co-activation of laryngeal muscles must be avoided.
Receptor-mediated endocytosis of low density lipoprotein: somatic cell mutants define multiple genes required for expression of surface-receptor activity. (1984)

We have used cell fusion and mutant reversion analysis to study a collection of Chinese hamster ovary (CHO) cell mutants that are unable to bind and internalize low density lipoprotein (LDL). Pairwise cell fusions show that these LDL receptor-deficient mutants fall into three recessive complementation groups, ldlA, ldlB, and ldlC. Complementation was detected by observing the uptake of fluorescent LDL and was quantitated by measuring the degradation of 125I-labeled LDL by isolated hybrid cells. Previous studies had defined a fourth recessive complementation group, ldlD. Complementation tests between CHO cells and human fibroblasts suggested that the defects in mutants of the ldlA complementation group are analogous to those in a patient with homozygous familial hypercholesterolemia. A revertant of an ldlA mutant was isolated and appeared to be heterozygous at the ldlA locus. The phenotype of this revertant was similar to that of cells from patients with the heterozygous form of familial hypercholesterolemia. Together with recent DNA transfection studies, these results suggest that the ldlA locus is the structural gene for the LDL receptor in CHO cells. Mutants in the ldlB, ldlC, and ldlD complementation groups must have defects in genes that are required for either the regulation, synthesis, transport, recycling, or turnover of LDL receptors.
CpG-depleted adeno-associated virus vectors evade immune detection (2013)

Due to their efficient transduction potential, adeno-associated virus (AAV) vectors are leading candidates for gene therapy in skeletal muscle diseases. However, immune responses toward the vector or transgene product have been observed in preclinical and clinical studies. TLR9 has been implicated in promoting AAV-directed immune responses, but vectors have not been developed to circumvent this barrier. To assess the requirement of TLR9 in promoting immunity toward AAV-associated antigens following skeletal muscle gene transfer in mice, we compared immunological responses in WT and Tlr9-deficient mice that received an AAV vector with an immunogenic capsid, AAVrh32.33. In Tlr9-deficient mice, IFN-γ T cell responses toward capsid and transgene antigen were suppressed, resulting in minimal cellular infiltrate and stable transgene expression in target muscles. These findings suggest that AAV-directed immune responses may be circumvented by depleting the ligand for TLR9 (CpG sequences) from the vector genome. Indeed, we found that CpG-depleted AAVrh32.33 vectors could establish persistent transgene expression, evade immunity, and minimize infiltration of effector cells. Thus, CpG-depleted AAV vectors could improve outcome of clinical trials of gene therapy for skeletal muscle disease.
Trace gas Raman spectroscopy using functionalized waveguides (2016)

Weak scattering and short optical interaction lengths have, until this work, prevented the observation of trace gas Raman spectra using photonic integrated circuitry. Raman spectroscopy is a powerful analytical tool, and its implementation using chip-scale waveguide devices represents a critical step toward trace gas detection and identification in small handheld systems. Here, we report the first Raman scattering measurements of trace gases using integrated nanophotonic waveguides. These measurements were made possible using highly evanescent rib waveguides functionalized with a thin cladding layer designed to reversibly sorb organophosphonates and other hazardous chemical species. Raman spectra were collected using 9.6 mm-long waveguides exposed to ambient trace concentrations of ethyl acetate, methyl salicylate, and dimethyl sulfoxide with one-sigma limits of detection in 100 s integration times equal to 600 ppm, 360 ppb, and 7.6 ppb, respectively. Our analysis shows that the functionalized waveguide Raman efficiency can be enhanced by over nine orders of magnitude compared to traditional micro-Raman spectroscopy, paving the way toward a sensitive, low-cost, miniature, spectroscopy-based trace gas sensor inherently suitable for foundry-level photonic integrated circuit manufacturing.
Parthenogenetic development and protein patterns of newly matured bovine oocytes after chemical activation (1998)

Development of an effective activation protocol is of great importance for studying oocyte competence and embryo cloning. Experiments were designed to examine effects of intracellular calcium elevating agents such as calcium ionophore A23187 (CaA) and ethanol, or protein synthesis and phosphorylation inhibitors such as cycloheximide (CH) and 6-dimethylaminopurine (6-DMAP), or a sequential combination of these agents on both parthenogenetic development and protein patterns of newly matured bovine oocytes. Oocytes were matured for 24 hr in M-199 supplemented with follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol at 39 degrees C in humidified air. They were then activated by various treatments and cultured in KSOM. Protein patterns at 15 hr after treatment were determined on 8-15% gradient SDS-PAGE and silver stained. Results demonstrated that none of the chemical agents--CaA, ethanol, 6-DMAP, or cycloheximide--could effectively induce parthenogenetic development of young bovine oocytes. When compared with the single treatments, sequentially combined treatments of CaA with 6-DMAP or with cycloheximide plus cytochalasin D (CD) significantly increased the rates of cleavage (78-82% versus 3-13%) and blastocyst development (31-40% versus 0%), which were comparable with those of IVF group (80% and 35%, respectively; P > 0.05). Supplementation with CD to the combined CaA and CH treatment improved rates of cleavage and blastocyst development versus without CD supplementation (31% versus 7%; P < 0.05). Fluorescent microscopy revealed that 95% (n = 40) of oocytes treated with CaA plus 6-DMAP had one pronucleus (PN) and one polar body (PB), while 88% (n = 40) in the CaA plus cycloheximide-treated group had one PN and two PBs and 85% (n = 40) in CaA plus cycloheximide and CD group had two PNs and one PB. Treatment by CaA alone resulted in 73% of oocytes (n = 40) arrested at a metaphase stage with two PBs (named as metaphase III or MIII). Protein patterns were similar for chemically activated and in vitro-fertilized (IVF) oocytes in that the 138- and 133-kDa proteins, whose functions are not yet known, were present in the metaphase-stage (MII 24 hr, MII 40 hr, and MIII) oocytes but were absent in PN-stage oocytes regardless of treatment. Therefore, these proteins seem to be metaphase-associated proteins. Taken together, we conclude that optimal parthenogenetic development of newly matured bovine oocytes can be obtained by calcium ionophore treatment followed by incubation in either 6-DMAP or cycloheximide plus cytochalasin D and that the reduction of the 138- and 133-kDa proteins might be necessary for the full activation of bovine oocytes.
The potential of drug-carrying immunoliposomes as anticancer agents. Commentary re: J. W. Park et al., Anti-HER2 immunoliposomes: enhanced efficacy due to targeted delivery. Clin. Cancer Res., 8: 1172-1181, 2002. (2002)

The demand for increased specificity of anticancer agents to target tumors has resulted in numerous strategies, including oncogene-selective inhibitors, gene and antisense therapies, and mAbs,[2][1] as well as combinations thereof. Although many of the regimens are already in use, the need for more
Circulating tumor cells (CTCs) in lung cancer: current status and future perspectives (2010)

Primary lung cancer is the leading cause of cancer-related deaths in most industrialized countries, and it is important to detect and control metastases distant from the lungs for improvement of a patient's prognosis. Circulating tumor cells (CTCs) are tumor cells that are shed from the primary site and circulate in the peripheral blood, and recent studies have shown that CTCs can be useful clinical markers in some solid tumors such as those of breast cancer. In primary lung cancer, the clinical significance of CTCs remains unclear, but some promising results have been recently reported. Here, we reviewed the current status and future perspectives of CTCs in primary lung cancer.
Co-recognition of endogenous antigens with HLA-DR1 by alloreactive human T cell clones. (1989)

The fine specificity of anti-HLA-DR1 alloreactive, human T cells was investigated by using DR1-expressing human and murine stimulator cells. All three bulk cell lines and six out of seven T cell clones proliferated in response to DR1-expressing mouse L cells. In addition to these species non specific T cells, three clones were identified which proliferated only in response to DR1 expressed by human or by murine stimulator cells. The patterns of response of these clones may reflect specificity for species or lineage-specific peptides with DR1. The results of aldehyde fixation and cytotoxicity experiments suggested that some of the T cell clones which proliferated in response to human and murine DR1 stimulators also required to recognize species-specific antigens. The responses of four of the six clones were abolished by fixation of DR1-L cells but not of a DR-1 EBV transformed lymphoblastoid cell line before co-culture. In addition, these clones were also cytotoxic for DR1-expressing human targets. The same clones which failed to recognize fixed L cells also failed to lyse DR1-L cells in a short term chromium release assay. Taken together these results suggest that some alloreactive anti-DR1, T cells are specific for peptides of cellular proteins seen in the context of the allo-MHC molecule. It is envisaged that L cells when co-cultured with human T cells, process and present peptides derived from proteins that are shed or secreted by the human cells, for co-recognition with DR1 on the L cell surface. The presentation of multiple peptides derived from endogenous proteins by allogeneic cells may contribute to the high precursor frequency of allo-reactive T cells.
The anticancer activity of the transcription inhibitor terameprocol (meso-tetra-O-methyl nordihydroguaiaretic acid) formulated for systemic administration (2007)

Terameprocol (meso-tetra-O-methyl nordihydroguaiaretic acid, formerly known as EM-1421 and M4N) is a semi-synthetic small molecule with antitumor activity occurring via selective targeting of Sp1-regulated proteins, including survivin and cdc2 that control cell cycle and apoptosis. Terameprocol is in clinical development as a site-specific transcription inhibitor in solid refractory tumors. The present studies were designed to investigate the in-vitro and in-vivo anticancer activity of terameprocol in a novel hydroxypropyl beta-cyclodextrin and polyethylene glycol solvent formulation (designated CPE) designed for safe parenteral administration. Terameprocol powder was dissolved in CPE (20% hydroxypropyl beta-cyclodextrin and 50% polyethylene glycol 300 or 30% hydroxypropyl beta-cyclodextrin and 25% polyethylene glycol 300) or dimethyl sulfoxide and used for in-vitro cell proliferation assays, and in human carcinoma xenograft studies using female athymic nude mice injected with SW-780 human bladder cells. Terameprocol (50 and 100 mg/kg), paclitaxel (5 mg/kg), terameprocol and paclitaxel or vehicle was administered intraperitoneally daily for 21 days. Stock solutions of the CPE formulation were stable for up to 12 months. Terameprocol CPE formulation showed concentration-dependent inhibition of HeLa and C33A cell proliferation, and was less toxic than terameprocol dimethyl sulfoxide formulation. The terameprocol CPE formulation showed no overt toxicities in tumor-bearing mice. Terameprocol alone reduced the rate of tumor growth, and a combination of terameprocol/paclitaxel reduced both the rate and extent of tumor growth. These preclinical results confirm the tumoricidal activity of terameprocol formulated in a solvent suitable for parenteral administration and suggest that terameprocol has improved efficacy when coadministered with paclitaxel.
Inhibitory effects of 5-(2-pyrazinyl)-4-methyl-1,2-dithioI-3-thione (Oltipraz) on carcinogenesis induced by benzo[a]pyrene, diethylnitrosamine and uracil mustard (1986)

5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione (Oltipraz) was studied for its capacity to inhibit carcinogen-induced neoplasia in female ICR/Ha mice. When administered by oral intubation 48 h prior to benzo[a]pyrene (BP), also given by oral intubation, Oltipraz inhibited the occurrence of pulmonary adenomas and tumors of the forestomach. The ratio of the number of tumors occurring in the mice receiving Oltipraz to that of the corresponding controls was: lung, 0.36 and forestomach 0.38. Inhibition also occurred when Oltipraz was given p.o. 24 h prior to BP. In other experiments, oral administration of Oltipraz 48 h prior to p.o. administration of diethylnitrosamine or uracil mustard inhibited pulmonary adenoma formation but to a lesser extent than with BP as the carcinogen. The low toxicity of Oltipraz found previously, coupled with evidence of protective effects against chemically diverse carcinogens, suggests that this compound should be studied further for its possible use as an agent for the chemoprevention of neoplasia.
Tissue dispersion, cell harvest and fluid suspension culture by the use of bacterial neutral protease. (1975)

Bacterial neutral protease of Bacillus polymyxa was found to disperse mammalian tissues and cells. Primary cell cultures were obtained from several tissues after treatments with 200 to 2,000 Kunitz unit per ml of this protease in either a phosphate buffer solution, a balanced salt solution or a tissue culture medium supplemented with serum. Monolayer cultures wither in their early passage levels or of established strains were harvested by a treatment with this protease, and proliferated again in monolayer after its removal. A growing culture of strain L-929 was kept in monodisperse suspension in the presence of this protease. In contrast to trypsin, this protease was found active in the presence of serum, stable during incubation and scarcely injured cells.
Epidemiology, Comorbidity, and Behavioral Genetics of Antisocial Personality Disorder and Psychopathy (2015)

Psychopathy is theorized as a disorder of personality and affective deficits while antisocial personality disorder (ASPD) diagnosis is primarily behaviorally based. While ASPD and psychopathy are similar and are highly comorbid with each other, they are not synonymous. ASPD has been well studied in community samples with estimates of its lifetime prevalence ranging from 1-4% of the general population.<sup>4,5</sup> In contrast, psychopathy is almost exclusively investigated within criminal populations so that its prevalence in the general population has been inferred by psychopathic traits rather than disorder (1%). Differences in etiology and comorbidity with each other and other psychiatric disorders of these two disorders are also evident. The current article will briefly review the epidemiology, etiology, and comorbidity of ASPD and psychopathy, focusing predominately on research completed in community and clinical populations. This paper aims to highlight ASPD and psychopathy as related, but distinct disorders.
Molecular complexity and dynamics of cell-matrix adhesions (2001)

Currently >50 proteins have been reported to be associated with focal contacts and related ECM adhesions. Most of these contain multiple domains through which they can interact with different molecular partners, potentially forming a dense and heterogeneous protein network at the cytoplasmic faces of the adhesion site. The molecular and structural diversity of this 'submembrane plaque' is regulated by a wide variety of mechanisms, including competition between different partner proteins for the same binding sites, interactions triggered or suppressed by tyrosine phosphorylation, and conformational changes in component proteins, which can affect their reactivity. Indeed, integrin-mediated adhesions can undergo dynamic changes in structure and molecular properties from dot-like focal complexes to stress-fiber-associated focal contacts, which can further 'mature' to form fibronectin-bound fibrillar adhesions. These changes are driven by mechanical force generated by the actin- and myosin-containing contractile machinery of the cells, or by external forces applied to the cells, and regulated by matrix rigidity.