gebhart/patrepeval huggingface dataset:
Programmed Death 1 Regulates Development of Central Memory CD8 T Cells after Acute Viral Infection (2011)

The T cell response possesses a number of inhibitory receptors to regulate the extent of the antiviral response and prevent immune pathology. These receptors are generally transiently upregulated during an effector response and then downregulated during memory. Some inhibitory receptors, such as programmed death 1 (PD-1) and LAG-3, were shown to be aberrantly upregulated during memory to chronic lymphocytic choriomeningitis virus infection, limiting functional capabilities. However, little is known about the impact of inhibitory receptors on memory development during a normal CD8 T cell response to acute virus infection. Our previous data showed that PD-1 is aberrantly upregulated during a secondary response by memory CD8 T cells that were generated without CD4 T cell help. Therefore, we examined the role of PD-1 in memory differentiation during acute vaccinia virus infection in intact mice. In the absence of PD-1, the primary and memory CD8 T cell responses were enhanced. Moreover, there were distinct phenotypic and functional changes in the memory PD-1(-/-) CD8 T cells. Higher levels of CD62L, CD27, and CCR7 were detected; cells produced more IL-2 and made an enhanced secondary response. These changes indicate a skewing of the memory population toward the central memory phenotype in the absence of PD-1 signaling.
Malignant glioma drug discovery – targeting protein kinases (2007)

Malignant gliomas are uncommon, but extremely lethal, cancers. Current standard-of-care includes surgery, radiation and chemotherapy, but recent research has generated a shift towards targeting the aberrant signal transduction components that underlie the pathogenesis of malignant gliomas. Protein kinases are a family of enzymes that are key elements in signal transduction-regulated cellular homeostasis subdivided based on their catalytic activity into tyrosine kinases and serine/threonine kinases. Protein kinases can be deregulated by several mechanisms, including genomic rearrangement, mutations of oncogenes or loss of tumour suppressor genes and overexpression or mutation of growth factor receptors to contribute to cancer initiation and maintenance. In malignant gliomas, several protein kinases are commonly over activated and may represent new therapeutic targets. Two main classes of agents targeting protein kinases are monoclonal antibodies and small-molecule inhibitors. In clinical trials, these molecularly targeted therapies have demonstrated limited efficacy as single agents in unselected malignant glioma patient populations. Several mechanisms of the failure of targeted agent monotherapies have been elucidated as new therapeutic strategies have emerged to overcome the resistance. Multi-targeted kinase inhibitors and combinations of single-targeted kinase inhibitors with one another or with traditional cytotoxics may increase treatment efficacy. Identification of biomarkers of response or resistance will be of paramount importance to enrich patients for specific targeted agents based on their genetic/molecular signature. In this review, the authors discuss the role of protein kinases in malignant glioma and how to target aberrant protein kinases with novel therapeutics.
DEL PATRIMONIO HUMANO (2007)

CARTON ACERCA DE LA DESIGNACION DE CIUDAD UNIVERSITARIA COMO PATRIMONIO CULTURAL DE LA HUMANIDAD. SU AUTOR ES TAMES Y BATTA.
A Histochemical Study of the Fibrinolytic Activity (1967)

Studied by the histochemical fibrin slide technique sections of normal cornea of man and several mammals are fibrinolytically inactive. After corneal injury plasminogen activator can be demonstrated in relation to the epithelial or endothelial linings and in detached epithelial or endothelial cells. In general, severely degenerated cells show the highest fibrinolytic activity. In fragments of corneal epithelium a weak protease effect could be demonstrated. The possible origin of the plasminogen activator and its possible physiological functions are discussed.
THE PERIPHERAL BLOOD LEUKOCYTE PHENOTYPE IN PATIENTS WITH BREAST CANCER: EFFECT OF DOXORUBICIN/PACLITAXEL COMBINATION CHEMOTHERAPY (2001)

Presence of functional immune system is critical for any attempt aimed at improving survival of breast cancer patients by strategies based on immune system manipulation. We evaluated by flow cytometry the phenotype of peripheral blood leukocyte of 43 breast cancer patients. In 11 patients, the phenotype was evaluated before and during the chemotherapy by combination of doxorubicin and paclitaxel (AT). Compared with controls breast cancer patients had significantly higher relative and absolute numbers of CD3 HLA-DR+, CD3+CD69+ and CD14+CD16+, and significantly lower percentages of CD3 and CD8+CD28+ cells. After one cycle of AT, the absolute numbers of CD3 , CD3+CD4+, CD3+CD8+ and CD8+CD28+ cells increased significantly. Present data show a presence of T-cell activation in breast cancer patients. Administration of AT may lead to an increase in functional T-cells in peripheral blood, indicating a potential for combining chemotherapy with immunotherapy in the treatment of breast cancer patients.
Pathogenesis of steatohepatitis: insights from the study of animal models. (2007)

Non-alcoholic steatohepatitis (NASH) is a disease of expanded clinical importance. Its pathogenesis remains poorly understood. Tools to identify patients at risk and targeted treatments are lacking. The aim of this work was to analyse potential pathogenic mechanisms for inflammatory recruitment and fibrogenesis in NASH, using animal models. We demonstrated that oxidative stress, invariably associated with NASH, is a primary and necessary event for disease progression. Inhibition of stress-activated transcription factor NF-chiB prevents NASH. NF-chiB therefore appears as a pathogenic link between oxidative stress and NASH. Increased lipid beta-oxidation in NASH could generate oxidative stress. We used a potent inducer of PPAR-alpha to stimulate beta-oxidation in a model of steatohepatitis. Such treatment induced a complete clearance of steatosis together with a significant reduction of oxidative stress and oxidative injuries and prevention of inflammation and fibrosis. Thus in a situation of steatosis, stimulation of lipid combustion depletes the substrates for lipid peroxidation and thereby decreases oxidative stress. This effect is sufficiently powerful to prevent the development of steatohepatitis. We demonstrated that leptin is a pro-fibrogenic adipocytokine and is implicated in the regulation of liver regeneration. Leptin plays this crucial physiological role in hepatic wound healing by controlling the production and the activation of cytokines. The insulin sensitising drugs thiazolidinediones have antiinflammatory and anti-fibrotic properties in rats. We demonstrated that such drugs are poorly effective in the treatment of preestablished hepatic fibrosis in rats and unable to prevent fibrogenesis in vitro as well as in vivo in mice. Direct anti-fibrotic effect of such substances remains to be demonstrated in humans. In conclusion, our work demonstrates the importance of oxidative stress in the pathogenesis of NASH, the role of intrahepatic lipid overload and underlies the links between adipose tissue and the liver.
Measuring Anxiety in Patients with Schizophrenia (2007)

This study describes the prevalence and distribution of anxiety symptomatology and anxiety disorders in a sample of hospitalized patients with schizophrenia, the estimated level of agreement between a clinician diagnostic measure and anxiety symptom status measures, and their internal consistency based on the average interitem correlations. Seventy inpatients receiving treatment for schizophrenia were assessed before discharge using a face-to-face diagnostic interview and structured questionnaires, namely the Mini International Neuropsychiatric Interview, the Hospital Anxiety and Depression Scale, the Hamilton Anxiety Scale, the Spielberger Anxiety Inventory, and the Stein Generalized Anxiety Disorder (GAD) Scale. About a quarter of patients met criteria for an anxiety disorder, with GAD and social phobia occurring most commonly. There was poor agreement between the Mini International Neuropsychiatric Interview and a diagnosis of anxiety based on symptom status measures. The Stein GAD scale demonstrated the highest internal consistency (0.85) followed by the Hamilton Anxiety Scale (0.76). Anxiety disorders and anxiety symptomatology are highly prevalent in schizophrenia. Accurate assessment is challenging yet important. More reliable measures of anxiety disorders in patients with schizophrenia and other psychotic disorders are clearly needed to allow for timely identification and treatment.
Guidance of CNS growth cones by substratum grooves and ridges: effects of inhibitors of the cytoskeleton, calcium channels and signal transduction pathways (1997)

We exploited our observation that embryonic Xenopus spinal neurites align parallel to grooves in a quartz surface and that embryonic rat hippocampal neurites align perpendicular to shallow, narrow grooves (see companion paper: A. M. Rajnicek, S. Britland and C. D. McCaig, 1997) (J. Cell Sci. 110, 2905-2913) to investigate the mechanism of growth cone contact guidance. Substratum topography affected the pattern of growth cone filopodia and microtubules but parallel orientation of Xenopus neurites and perpendicular orientation of hippocampal neurites were unperturbed by cytochalasin B, which virtually eliminated filopodia. Hippocampal growth cone orientation and turning in response to grooves was unaffected by disruption of microtubules using taxol or nocodazole. Gross cytoskeletal reorganization on grooved substrata was therefore not required for growth cone steering. Inhibitors were used to identify the signal transduction pathway for perpendicular alignment of hippocampal neurites. Alignment persisted in the presence of gadolinium chloride, a blocker of stretch-activated calcium channels, the G protein inhibitor pertussis toxin, the protein tyrosine kinase inhibitor genistein, the protein kinase A and G inhibitor HA1004, the protein kinase A inhibitor KT5720and the protein kinase G inhibitor KT5823. Low concentrations of the protein kinase C inhibitors stauro-sporine, bisindolylmaleimide or H-7 did not affect perpendicular orientation but higher concentrations inhibited it. The calcium channel blockers flunarizine, nifedipine and diltiazem also inhibited perpendicular orientation. Influx of calcium and protein kinase C activity therefore appear to be involved in perpendicular contact guidance.
Regulation of Melanogenesis in Melanocytes (1988)

Melanogenesis refers to the biosynthesis of melanin pigment in pigment cells called melanocytes. Melanins are mixed biopolymers formed during a series of oxidation/reduction reactions that are initiated by the enzymatic hydroxylation of L‐tyrosine to L‐dopa. In living cells, melanogenesis is limited to melanosomes, the membrane bounded microscopic secretory granules of melanocytes. Melanosomes may be secreted into the environment as, for example, from the squid's ink gland; or be transferred to neighboring cells, such as the keratinocytes in human skin and hair; or they may remain within the pigment cell and change only their subcellular localization, as in the rapidly color‐changing dermis of lower vertebrates. Regulation of the melanocytic phenotype involves synthesis of the biosynthetically active subcellular apparatus of melanogenesis, premelanosomes and tyrosinase, and the utilization of the final product, melanized melanosomes, in the translocation and secretory processes mentioned above. Genetic information for this regulation is stored in the nuclear genome whose expression is controlled by the intra‐ and extracellular environment. As premelanosomes become biosynthetically active, they mature into melanosomes by fusing with vesicles derived from the trans‐Golgi network and the plasmalemma, thereby internalizing and incorporating contents and membrane components from inside the cell and the cell surface. In the process, melanosomes become acidified. The thesis pursued in this review explores the importance of the melanosome as the final common pathway of regulation of melanin biosynthesis.
Effectiveness of two radiofrequency ablation systems in atrial tissue (2001)

The Boston Scientific system (70 degrees C set point) requires a minimum in vitro application of 40 s to transmurally increase 4-6 mm atrial tissue temperature above 55 degrees C, and 120-s duration per application would appear to be a reasonable clinical recommendation. The Osypka system transfers thermal energy more effectively, requiring less than 10 s in vitro to achieve a similar transmural temperature, and a 30-s application can be recommended. However, a tendency to overshoot both probe and set point temperature, suggests that a lower set point of 65 degrees C might be safer and as effective.
A cross-layer based intrusion detection approach for wireless ad hoc networks (2005)

Wireless ad-hoc networks are vulnerable to various kinds of security threats and attacks due to relative ease of access to wireless medium and lack of a centralized infrastructure. In this paper, we seek to detect and mitigate the denial of service (DoS) attacks that prevent authorized users from gaining access to the networks. These attacks affect the service availability and connectivity of the wireless networks and hence reduce the network performance. To this end, we propose a novel cross-layer based intrusion detection system (CIDS) to identify the malicious node(s). Exploiting the information available across different layers of the protocol stack by triggering multiple levels of detection, enhances the accuracy of detection. We validate our design through simulations and also demonstrate lower occurrence of false positives
Derivation of the first Swiss human embryonic stem cell line from a single blastomere of an arrested four-cell stage embryo (2008)

As the destruction of viable developing embryos, even spare ones, raises serious ethical concerns, deriving hESC lines from arrested embryos may be an alternative approach to avoid embryo destruction. However, given the reduced derivation efficiency they should not be considered a unique and/or selective source of hESC lines.
Computation of Shortest Path in a Fuzzy Network: Case Study with Rajasthan Roadways Network (2010)

This paper propose a shortest path problem with fuzzy parameters in the domain of Operations Research which is based on Bellman Dynamic Programming algorithm. Attention has been paid to the study of fuzzy network with topological ordering.. Here we discuss the shortest path problem from a specified vertex to all other vertices in a network. For illustration a real life example has been considered from Rajasthan State Roadways Transport Network.
Mechanism of Transcriptional Regulation by Methyl-CpG Binding Protein MBD1 (2000)

MBD1 is a mammalian protein that binds symmetrically methylated CpG sequences and regulates gene expression in association with DNA methylation. This protein possesses a conserved sequence, named methyl-CpG binding domain (MBD), among a family of methyl-CpG binding proteins that mediate the biological consequences of the methylation. In addition, MBD1 has at least five isoforms due to alternative splicing events, resulting in the presence of CXXC1, CXXC2, and CXXC3 in MBD1 isoforms v1 (MBD1v1) and MBD1v2, and CXXC1 and CXXC2 in MBD1v3 and -v4. In the present study, we have investigated the significance of MBD, CXXC, and the C-terminal transcriptional repression domain (TRD) in MBD1. A bacterially expressed MBD binds efficiently to densely methylated rather than to sparsely methylated DNAs. In both methylation-deficient Drosophila melanogaster SL2 cells and mammalian CHO-K1 cells, MBD1v1 represses transcription preferentially from both unmethylated and sparsely methylated promoters, while MBD1v3 inhibits densely methylated but not unmethylated promoter activities. The CXXC3 sequence in MBD1v1 is responsible for the ability to bind unmethylated promoter. Furthermore, we have constructed mutant-type MBD1s in which the functionally important residues Arg22, Arg30, Asp32, Tyr34, Arg44, Ser45, and Tyr52 are changed to alanine to investigate the correlation between the structure and function of the MBD in MBD1. Excepting those for Ser45 and Tyr52, none of the recombinant MBD mutants bound to the densely methylated or unmethylated DNAs, and green fluorescent protein-fused MBD1 mutants did not localize properly in the nucleus. All the MBD1v1 and -v3 mutants lost the activity of methylation-dependent gene repression. Based on these findings we have concluded that MBD1 acts as a transcriptional regulator depending on the density of methyl-CpG pairs through the cooperation of MBD, CXXC, and TRD sequences.
Chemokine inhibition in rat stab wound brain injury using antisense oligodeoxynucleotides (1998)

Traumatic injury to the central nervous system (CNS) results in the breakdown of the blood-brain barrier and recruitment of hematogenous cells at the site of injury. The role of chemokines in this process has been well recognized and they have been regarded as promising targets for development of anti-inflammatory therapies. The expression of monocyte chemoattractant protein (MCP-1), in particular, has been closely linked to macrophage infiltration following trauma in rat brain. In this study we determined whether inhibition of MCP-1 following stab wound injury would reduce macrophage infiltration. Stab wound injured Sprague-Dawley rats were infused with MCP-1 sense or antisense oligonucleotides using an Alzet miniosmotic pump (1 microl/h for 3 days). Three days following injury, widespread gliosis was observed in both groups of rats as judged by glial fibrillary acidic protein (GFAP) immunoreactivity. Immunohistochemistry showed significantly less staining for MCP-1 in antisense treated animals. In addition, the number of macrophages were reduced by 30% in the antisense compared to the sense treated animals (P < 0.05). These results demonstrate that modulation of MCP-1 expression in stab wound injury directly affects monocytic infiltration and provide a basis for MCP-1 inhibition as a therapeutic strategy for controlling inflammatory events of traumatic brain injury.
The Mycobacterium xenopi GyrA protein splicing element: characterization of a minimal intein (1997)

The 198-amino-acid in-frame insertion in the gyrA gene of Mycobacterium xenopi is the smallest known naturally occurring active protein splicing element (intein). Comparison with other mycobacterial gyrA inteins suggests that the M. xenopi intein underwent a complex series of events including (i) removal of 222 amino acids that encompass most of the central intein domain, and (ii) addition of a linker of unrelated residues. This naturally occurring genetic rearrangement is a representative characteristic of the taxon. The deletion process removes the conserved motifs involved in homing endonuclease activity. The linker insertion represents a structural requirement, as its mutation resulted in failure to splice. The M. xenopi GyrA intein thus provides a paradigm for a minimal protein splicing element.
Generation of a truncated hepatocyte growth factor receptor in the endoplasmic reticulum. (1994)

The hepatocyte growth factor (HGF) receptor (p190MET) is a tyrosine kinase composed of two disulfide-linked chains, alpha of 50 kDa and beta of 145 kDa. We have previously described an isoform (p140MET) containing a beta chain of 85 kDa, lacking the cytoplasmic kinase domain. The two receptor variants originate by post-translational processing of a common single-chain precursor of 170 kDa (Pr170). In the endoplasmic reticulum a fraction of Pr170 is cleaved at the cytosolic side generating an intermediate product of 120 kDa (Pr120). This molecule 1) is already detectable after 15 min of pulse labeling, 2) contains high mannose-branched oligosaccharides, and 3) accumulates upon treatments inhibiting the export from the endoplasmic reticulum. A second cleavage, occurring after 30 min of chase in the trans-Golgi network, converts the single-chain precursors Pr170 and Pr120 into the mature heterodimers p190MET and p140MET. This process is inhibited by brefeldin A treatment. Conditions leading to Pr170 accumulation in the endoplasmic reticulum, such as receptor overexpression, induce kinase activation and overproduction of Pr120. Conversely, cells expressing a kinase-defective HGF receptor lack the truncated isoform. The proteolytic cleavage of the cytoplasmic domain may thus represent a safety mechanism aimed at preventing ligand-independent intracellular activation of the HGF receptor kinase.
Function Keys to the Rescue (1987)

We have 15 OCLC terminals, 4 of which are used exclusively for cataloging and are connected to a CLSI interface and a printer used for labels. The four cataloging terminals are M300 Workstations; one was recently replaced with an XT. After acquiring an Epson printer in the fall of 1986, we found to our dismay that the sl6 labels we'd been using since 1975 wouldn't print correctly with this configuration. Specifically, our sl6 screen has one too many lines, so the last line prints off the bottom of one label and on to the next. This was, and still is, puzzling to us, as our sl6 labels conform to specifications for that size.
Internet-based mobile ad hoc networking (1999)

Internet-based mobile ad hoc networking is an emerging technology that supports self-organizing, mobile networking infrastructures. The technology enables an autonomous system of mobile nodes, which can operate in isolation or be connected to the greater Internet. Mobile ad hoc networks (Manets) are designed to operate in widely varying environments, from forward-deployed military Manets with hundreds of nodes per mobile domain to applications of low-power sensor networks and other embedded systems. Before Manet technology can be easily deployed, however, improvements must be made in such areas as high-capacity wireless technologies, address and location management, interoperability and security. The authors give an overview of Manet technology and current IETF efforts toward producing routing and interface definition standards that support it within the IP suite.
Comparative study of delayed hypersensitivity skin reactions and antibodies to human papilloma virus (HPV). (1977)

Purified human papilloma virus (HPV) was prepared from plantar warts, inactivated by formalin, adjusted to 10(10) particles per 0·1 ml and used in intradermal tests (IDT) on 120 patients having warts at that time, or having had warts in the past, together with sixty-three controls. Antibodies were evaluated in the sera from most of the patients by the indirect immunofluorescence (IF) test before and after the skin tests. The results showed a specific delayed-hypersensitivity reaction (DHR) to HPV, especially in patients with `regressing' or `past' warts (76%). DHR was most frequent in patients with a wart of 6 months–2 years duration (77·0–68·8%) and persisted much longer than antibodies, which disappeared with the passage of time. The incidence of antibodies was much higher after IDT in patients with a positive reaction, thus suggesting a booster effect.
Nanoscale Metal–Organic Frameworks for Ratiometric Oxygen Sensing in Live Cells (2016)

We report the design of a phosphorescence/fluorescence dual-emissive nanoscale metal-organic framework (NMOF), R-UiO, as an intracellular oxygen (O2) sensor. R-UiO contains a Pt(II)-porphyrin ligand as an O2-sensitive probe and a Rhodamine-B isothiocyanate ligand as an O2-insensitive reference probe. It exhibits good crystallinity, high stability, and excellent ratiometric luminescence response to O2 partial pressure. In vitro experiments confirmed the applicability of R-UiO as an intracellular O2 biosensor. This work is the first report of a NMOF-based intracellular oxygen sensor and should inspire the design of ratiometric NMOF sensors for other important analytes in biological systems.