gebhart/patrepeval huggingface dataset:
Identification of Endogenous SsrA-tagged Proteins Reveals Tagging at Positions Corresponding to Stop Codons (2001)

The SsrA.SmpB quality control system adds a C-terminal degradation peptide (AANDENYALAA) to nascent chains on stalled ribosomes, thereby freeing the ribosome and ensuring proteolysis of the tagged protein. An SsrA mutant with the tag sequence AANDEHHHHHH was used to slow degradation and facilitate Ni2+-nitrilotriacetic acid affinity purification. Display of affinity-purified Escherichia coli proteins on two-dimensional gels revealed small quantities of a diverse set of SsrA-H6-tagged proteins, and mass spectroscopy identified LacI repressor, lambda cI repressor, YbeL, GalE, RbsK, and a SlyD-kan(R) fusion protein as members of this set. For lambda repressor and YbeL, the SsrA-H6 tag was added after the natural C terminus of the protein, suggesting that tagging occurred while the ribosome idled at the termination codon of these genes. Potential causes of tagging for the other proteins include interference from translation of downstream reading frames, rare codons, and gene disruption. These and previous results support a broad role for the SsrA.SmpB system in freeing stalled ribosomes and in directing degradation of the products of these frustrated protein synthesis reactions.
Insertion, Evasion, and Denial of Service: Eluding Network Intrusion Detection (1998)

All currently available network intrusion detection (ID) systems rely upon a mechanism of data collection passive protocol analysis-which is fundamentally flawed. In passive protocol analysis, the intrusion detection system (IDS) unobtrusively watches all traffic on the network, and scrutinizes it for patterns of suspicious activity. We outline in this paper two basic problems with the reliability of passive protocol analysis: (1) there isn't enough information on the wire on which to base conclusions about what is actually happening on networked machines, and (2) the fact that the system is passive makes it inherently "fail-open," meaning that a compromise in the availability of the IDS doesn't compromise the availability of the network. We define three classes of attacks which exploit these fundamentally problems---insertion, evasion and denial of service attacks--and describe how to apply these three types of attacks to IP and TCP protocol analysis. We present the results of tests of the efficacy of our attacks against four of the most popular network intrusion detection systems on the market. All of the ID systems tested were found to be vulnerable to each of our attacks. This indicates that network ID systems cannot be fully trusted until they are fundamentally redesigned.
Cutting Edge: A Potent Adjuvant Effect of Ligand to Receptor Activator of NF-κB Gene for Inducing Antigen-Specific CD8+ T Cell Response by DNA and Viral Vector Vaccination (2003)

The ligand to receptor activator of NF-kappaB (RANK-L)/RANK interaction has been implicated in CD40 ligand/CD40-independent T cell priming by dendritic cells. In this report, we show that the coadministration of the RANK-L gene with a Trypanosoma cruzi gene markedly enhances the induction of Trypanosoma Ag-specific CD8(+) T cells and improves the DNA vaccine efficacy. A similarly potent adjuvant effect of the RANK-L gene on the induction of Ag-specific CD8(+) T cells was also observed when recombinant influenza virus expressing murine malaria Ag was used as an immunogen. In contrast, the coadministration of the CD40L gene was not effective in these systems. Our results demonstrated, for the first time, the potent immunostimulatory effect of the RANK-L gene to improve the CD8(+) T cell-mediated immunity against infectious agents.
Serial circulating concentrations of c‐reactive protein, interleukin (il)‐4, and il‐6 in patients with acute left heart decompensation (1999)

In patients with acute left heart decompensation in the absence of infection or coronary events, CRP, IL-4, and IL-6 increased and returned toward normal levels as the symptoms of heart failure resolved. Since the changes in concentrations of CRP, IL-4, and IL-6 in patients with heart failure are dynamic, the distinction between compensated and decompensated state is important when discussing the significance of acute reactive proteins or cytokines in the pathogenesis of heart failure.
Unchanged frequency of loss of heterozygosity and size of the deleted region at 8p21-23 during metastasis of lung cancer (2001)

The genetic mechanisms involved in lung cancer development and progression are beginning to be understood. Many studies have documented frequent loss of heterozygosity (LOH) at specific chromosomal regions in cancer cells; this implies that tumor suppressor genes (TSG) are usually present in those regions. Recently, it has been reported that LOH or chromosomal deletions at chromosome 8p21-23 represent early events frequently occurring in lung cancer. In addition, the size of these chromosome 8 deletions, as well as their frequency, was also reported to increase during lung cancer progression. To determine the spectrum and frequency of alterations of chromosome 8p21-23 in human lung cancer and whether these increase with progression of the tumors, we performed LOH analysis of chromosome 8p and 3p in the genomic DNA from cells from primary and metastatic sites of lung cancer, as well as from normal lung. We studied 35 subjects with primary lung cancer including 30 tumors with distant metastasis. Detection of allelic deletion utilized a PCR-based approach of microsatellite polymorphism analysis, which was performed using the microsatellite markers D8S1130, D8S1106, D8S511, D8S1827, D8S549, D8S261, LPL, D8S258, D8S136, NEFL, D3S1295, D3S1313, D3S1234, D3S1300, D3S1351, D3S1339, and D3S1340. The overall allelic deletion rates were 10 of 28 (35.7%) at 8p and 13 of 33 (39.4%) at 3p. The allelic deletions in the primary cancer and its metastatic sites were in each case identical in both frequency and size of the deleted regions. In our analysis, 8p21-23 deletions were not always associated with 3p deletions in primary lung cancer. These results therefore suggest that allelic deletion at chromosome 8p21-23 is an early and frequent event in the carcinogenesis and development of lung cancer, independent of chromosome 3p deletion. However, a continuing increase in the frequency of LOH at 8p21-23 and in the size of the deleted region rarely occurs during the process of metastasis.
Avermectin and avermectin derivatives are antagonists at the 4-aminobutyric acid (GABA) receptor on the somatic muscle cells ofAscaris; is this the site of anthelmintic action? (1990)

The mechanism underlying the ability of the anthelmintic avermectin to paralyse the nematode Ascaris is not yet fully understood. Using conventional two-electrode electrophysiological recording techniques we have demonstrated that micromolar concentrations of ivermectin block the inhibitory GABA response on the muscle cells of the parasitic nematode Ascaris. The ability of a number of avermectin derivatives to act as receptor antagonists for the Ascaris muscle GABA receptor has been determined. This provides useful information to compare with the in vivo anthelmintic potency of these compounds. Abamectin, the most potent anthelmintic, was the most potent compound at inhibiting the GABA response whilst octahydroavermectin, a compound which lacks anthelmintic activity, did not block the GABA receptor. This is consistent with the notion that the GABA receptor antagonist properties of the avermectins could contribute to their anthelmintic action.
Generation of Angiostatin by Reduction and Proteolysis of Plasmin (1997)

Extracellular manipulation of protein disulfide bonds has been implied in diverse biological processes, including penetration of viruses and endotoxin into cells and activation of certain cytokine receptors. We now demonstrate reduction of one or more disulfide bonds in the serine proteinase, plasmin, by a reductase secreted by Chinese hamster ovary or HT1080 cells. Reduction of plasmin disulfide bond(s) triggered proteolysis of the enzyme, generating fragments with the domain structure of the angiogenesis inhibitor, angiostatin. Two of the known reductases secreted by cultured cells are protein disulfide isomerase and thioredoxin, and incubation of plasmin with these purified reductases resulted in angiostatin fragments comparable with those generated from plasmin in cell culture. Thioredoxin-derived angiostatin inhibited proliferation of human dermal microvascular endothelial cells with half-maximal effect at approximately 0.2 microg/ml. Angiostatin made by cells and by purified reductases contained free sulfhydryl group(s), and S-carbamidomethylation of these thiol group(s) ablated biological activity. Neither protein disulfide isomerase nor thioredoxin were the reductases used by cultured cells, because immunodepletion of conditioned medium of these proteins did not affect angiostatin generating activity. The plasmin reductase secreted by HT1080 cells required a small cofactor for activity, and physiologically relevant concentrations of reduced glutathione fulfilled this role. These results have consequences for plasmin activity and angiogenesis, particularly in the context of tumor growth and metastasis. Moreover, this is the first demonstration of extracellular reduction of a protein disulfide bond, which has general implications for cell biology.
Photolysis of a protecting group for the carboxyl function of neurotransmitters within 3 microseconds and with product quantum yield of 0.2. (1993)

The synthesis of a photosensitive blocking group for the carboxyl function of neurotransmitters, in this case glycine, is reported. The compound, 2-methoxy-5-nitrophenyl glycine ester (caged glycine), is photolyzed by a laser pulse at 308 or 337 nm within 3 microseconds and with a product quantum yield of 0.2. The compound is hydrolyzed in water with a time constant tau of 6.1 min at pH 7.1 and 3 hr at pH 4.0. Mouse cerebral cortical neurons containing glycine receptors were used in biological assays. A cell-flow device, in which solutions of caged glycine at pH 4.0 were mixed with buffer to give a final pH of 7.1, was used to equilibrate the compound with receptors on the cell surface. Neither the caged compound nor the 2-methoxy-5-nitrophenol photolysis product affected the glycine receptors or modified their response to glycine. When cells equilibrated with caged glycine are irradiated by a laser pulse at 337 nm, glycine receptor channels are opened, as detected in whole-cell current recordings. The approach described may be used in the synthesis and characterization of photolabile precursors of neurotransmitters and other compounds that contain carboxyl groups and for kinetic investigations of neurotransmitter receptors in central nervous system cells in the microsecond time domain.
A Gutsy Task: Generating Intestinal Tissue from Human Pluripotent Stem Cells (2013)

Many significant advances in our understanding of intestine development, intestinal stem cell homeostasis and differentiation have been made in recent years. These advances include novel techniques to culture primary human and mouse intestinal epithelium in three-dimensional matrices, and de novo generation of human intestinal tissue from embryonic and induced pluripotent stem cells. This short review will focus on the directed differentiation of human pluripotent stem cells into intestinal tissue, highlight novel uses of this tissue, and compare and contrast this system to primary intestinal epithelial cultures.
Photochemically Enhanced Gene Delivery of EGF Receptor-targeted DNA Polyplexes (2004)

Epidermal growth factor receptor (EGFR) targeted DNA polyplexes, containing polyethylenimine (PEI) conjugated with EGF protein as cell-binding ligand for endocytosis and polyethylene glycol (PEG) for masking the polyplex surface charge, mediated a 3- to 30-fold higher luciferase gene expression in HUH7, HepG2 and A431 cell transfections than analogous untargeted PEG-PEI polyplexes. Transfection levels can be further enhanced by treatment of cells with amphiphilic photosensitizers followed by illumination. In this process photosensitizers localized in membranes of endocytic vesicles are activated by light, resulting in the destruction of endocytic membrane structures and releasing co-endocytosed polyplexes into the cell cytosol. Photochemical enhanced gene expression was observed in all cell lines, with the magnitude of enhancement depending on the particular PEI polyplex formulation and cell line, ranging between 2- and 600-fold. Importantly, improved gene transfer retained EGF receptor specificity, as demonstrated by comparison with ligand-free polyplexes and by receptor antibody or ligand competition experiments. These results suggest that this combined procedure enables a dual mode of targeting polyplexes: biological targeting via EGFR interaction, combined with physical targeting with light to direct a photochemical delivery of therapeutic genes to a desired location.
Phase Segregation Assisted Morphology Sculpting:  Growth of Graphite and Silicon Crystals via Vapor−Solid Reactions (2007)

Crystalline graphite and Si showing fertile morphologies are prepared via vapor−solid reaction growth (VSRG). By reacting CaC2 with vapors of CxCly (CxCly: CCl4, C2Cl4, C4Cl6, and C5Cl6), porous, fibrous, and planar graphite were obtained at 973−1023, 1073−1123, and 1123−1223 K, respectively. Employing SiCl4 to react with MxSiy (MxSiy: Mg2Si and CaSi2) generated many Si structures. These include clustered-particle and porous, wirelike, corallike, and planar or platelike at 1023, 1073, 1123, and 1223 K, respectively. The reaction products, the network solids (graphite and Si) and the ionic solids MCl2, phase-segregated into self-templating molds and casts and develop cooperatively into various three-dimensional structures. Final morphology of the network solids depends not only on the reaction temperature but their molar volume ratio to the MCl2 salt products.
Synthesis and Antibacterial Activity of 2-[5'-Alkyl-1',3',4'-thiadiazol-2'-yl]amino-benzothiazole, -benzoxazole,-benzimidazole and -imidazolidines (1991)

Department of Pharmaceutical Sciences, Dr. H. S. Gour Vishwavidyalaya, Sagar-470 003<br> <em>Manuscript received 1 August 1990, revised 7 December 1990, accepted 7 March 1991</em> Some new 1 3,4-thiadiazolyiamino-benzothiazole, -benzoxazole, -benzimidazole and -imidazolidines have been synthesised and screened for their antibacterial activity.
Estimation of cardiac output and systemic vascular resistance using a multivariate regression model with features selected from the finger photoplethysmogram and routine cardiovascular measurements (2013)

These promising results indicate the feasibility of using the method described as a non-invasive preliminary diagnostic tool in supervised or unsupervised clinical settings.
Heart Failure with Preserved Ejection Fraction: Pathophysiology and Emerging Therapies (2010)

Approximately half of patients with heart failure (HF) have a preserved ejection fraction (HFpEF). Morbidity and mortality are similar to HF with reduced EF (HFrEF), yet therapies with unequivocal benefit in HFrEF have not been shown to be effective in HFpEF. Recent studies have shown that the pathophysiology of HFpEF, initially believed to be due principally to diastolic dysfunction, is more complex. Appreciation of this complexity has shed new light into how HFpEF patients might respond to traditional HF treatments, while also suggesting new applications for novel therapies and strategies. In this review, we shall briefly review the pathophysiologic mechanisms in HFpEF, currently available clinical trial data, and finally explore new investigational therapies that are being developed and tested in ongoing and forthcoming trials.
Cytotoxic T lymphocytes as immune‐therapy in haematological practice (2008)

Viral infections are a significant cause of morbidity and mortality, particularly in pediatric allogeneic haematopoietic stem cell transplant recipients. Effective therapies are limited and often associated with significant side effects. Adoptive transfer of virus-reactive T cells offers a means of reconstituting antiviral immunity and this approach has been successfully used to prevent and treat cytomegalovirus, Epstein-Barr virus, and adenovirus infections in vivo. This review outlines the clinical trials that have been performed to date, and will describe future initiatives to (a) develop strategies that can increase the breadth of the viruses that can be targeted, and (b) simplify the process to extend this technology to more centers so that cellular therapy to reconstitute immunity can be more widely applied.
Simulation of human autosomal dominant retinitis pigmentosa in transgenic mice expressing a mutated murine opsin gene. (1993)

Autosomal dominant retinitis pigmentosa (ADRP), slowly progressing over decades, leads to severe visual impairment and in some cases to complete blindness. More than 40 mutations in the human opsin gene have been linked to some forms of this genetically heterogeneous disease. In photoreceptor cells of ADRP patients with mutations in the opsin gene, normal rhodopsin is thought to be synthesized concomitantly with mutated rhodopsin, which, by an unknown mechanism, causes the slow degeneration of the photoreceptor cells. To establish a transgenic mouse line that carries a mutated mouse opsin gene in addition to the endogenous opsin gene, we introduced a mouse opsin gene containing mutations in exon 1 into the germ line of a normal mouse. The alterations consisted of three amino acid substitutions near the N terminus of rhodopsin, Val-20-->Gly (V20G), Pro-23-->His (P23H), and Pro-27-->Leu (P27L). The P23H mutation is the most prevalent mutation in human ADRP patients. During early postnatal development, mice heterozygous for the mutated opsin gene appear to develop normal photoreceptors, but their light-sensitive outer segments never reach normal length. With advancing age, both rod and cone photoreceptors are reduced progressively in number. The slow degeneration of the transgenic retina is associated with a gradual decrease of light-evoked electroretinogram responses. Our results show that simultaneous expression of mutated and normal opsin genes induces a slow degeneration of both rod and cone photoreceptors and that the course of the retinal degeneration of the mutant mouse retina mimics the course of human ADRP.
Context-Aware Active Services in Ubiquitous Computing Environments (2007)

With the advent of ubiquitous computing environments, it has become increasingly important for applications to take full advantage of contextual information, such as the user's location, to offer greater services to the user without any explicit requests. In this paper, we propose context-aware active services based on context-aware middleware for URC systems (CAMUS). The CAMUS is a middleware that provides context-aware applications with a development and execution methodology. Accordingly, the applications based on CAMUS respond in a timely fashion to contextual information. This paper presents the system architecture of CAMUS and illustrates the content recommendation and control service agents with the properties, operations, and tasks for context-aware active services. To evaluate CAMUS, we apply the proposed active services to a TV application domain. We implement and experiment with a TV content recommendation service agent, a control service agent, and TV tasks based on CAMUS. The implemented content recommendation service agent divides the user's preferences into common and specific models to apply other recommendations and applications easily, including the TV content recommendations.
Room-temperature continuous-wave operation of an AlGaInP double heterostructure laser grown by atmospheric pressure metalorganic chemical vapor deposition (1985)

Continuous-wave (cw) operation at temperatures up to 23 °C of an Al0.26Ga0.26In0.48P/Ga0.52In0.48P/ Al0.26Ga0.26In0.48P double heterostructure (DH) laser has been achieved for the first time. The threshold current was 160 mA at 20 °C for a device with a 10-μm-wide and 250-μm-long ion-implanted stripe geometry. The emission wavelength was 671 nm during cw operation at 10 °C. To reduce thermal resistance to a heat sink, a dually stacked structure made of a thin (∼0.3 μm) p-AlGaInP layer and a p-Al0.76Ga0.24As layer was used as a cladding layer. The DH wafer was grown by atmospheric pressure metalorganic chemical vapor deposition.
An open source eye-gaze interface (2010)

There is no standard software interface in the eye-tracking industry, making it difficult for developers to integrate eye-gaze into their applications. The combination of high cost eye-trackers and lack of applications has resulted in a slow adoption of the technology. To expand the adoption of eye-gaze in everyday applications, we present an eye-gaze specific application programming interface that is platform and language neutral, based on open standards, easily used and extended and free of cost.
Inhaled nitric oxide in the evaluation of heart transplant candidates with elevated pulmonary vascular resistance. (1994)

The reversibility of elevated pulmonary vascular resistance in heart transplant candidates is currently evaluated with intravenous vasodilators. The aim of this study was to evaluate the effects of increased concentrations of inhaled nitric oxide (20, 40, and 80 ppm) on central hemodynamics and right ventricular function in heart transplant candidates with elevated pulmonary vascular resistance (> 2.5 Wood units). Comparison was made with intravenous vasodilators, sodium nitroprusside, and prostacyclin in doses that lowered the mean arterial pressure by about 15%. Inhalation of nitric oxide did not change systemic or pulmonary arterial pressure, cardiac output, right ventricular function, or systemic vascular resistance. Pulmonary capillary wedge pressure increased and transpulmonary pressure gradient and pulmonary vascular resistance decreased (-34% +/- 4% and -36% +/- 4%, respectively; p < 0.01) during 20 ppm nitric oxide, with no further effects at higher doses. Prostacyclin and sodium nitroprusside decreased pulmonary vascular resistance (-50% +/- 6% and -33% +/- 5%; p < 0.01). Prostacyclin reduced to some extent (p = 0.08) transpulmonary pressure gradient, which was not seen during sodium nitroprusside infusion. Systemic vascular resistance decreased during both sodium nitroprusside (-37% +/- 5%) and prostacyclin (-44% +/- 4%) infusion. The pulmonary vascular resistance/systemic vascular resistance ratio, used as an index of pulmonary selectivity, was decreased by nitric oxide (p < 0.01) but not by the intravenous vasodilators. Metabolic data indicate that inhaled nitric oxide is metabolized in the same way as that formed endogenously. In conclusion, inhaled nitric oxide is a selective pulmonary vasodilator that can be used safely in the hemodynamic evaluation of heart transplant candidates with elevated pulmonary vascular resistance.