gebhart/patrepeval huggingface dataset:
Hepatic Endothelial CCL25 Mediates the Recruitment of CCR9+ Gut-homing Lymphocytes to the Liver in Primary Sclerosing Cholangitis (2004)

Primary sclerosing cholangitis (PSC), a chronic inflammatory liver disease characterized by progressive bile duct destruction, develops as an extra-intestinal complication of inflammatory bowel disease (IBD) (Chapman, R.W. 1991. Gut. 32:1433-1435). However, the liver and bowel inflammation are rarely concomitant, and PSC can develop in patients whose colons have been removed previously. We hypothesized that PSC is mediated by long-lived memory T cells originally activated in the gut, but able to mediate extra-intestinal inflammation in the absence of active IBD (Grant, A.J., P.F. Lalor, M. Salmi, S. Jalkanen, and D.H. Adams. 2002. Lancet. 359:150-157). In support of this, we show that liver-infiltrating lymphocytes in PSC include mucosal T cells recruited to the liver by aberrant expression of the gut-specific chemokine CCL25 that activates alpha4beta7 binding to mucosal addressin cell adhesion molecule 1 on the hepatic endothelium. This is the first demonstration in humans that T cells activated in the gut can be recruited to an extra-intestinal site of disease and provides a paradigm to explain the pathogenesis of extra-intestinal complications of IBD.
NuMA is a major acceptor of poly(ADP-ribosyl)ation by tankyrase 1 in mitosis (2005)

Tankyrase 1 is a PARP [poly(ADP-ribose) polymerase] that localizes to multiple subcellular sites, including telomeres and mitotic centrosomes. Previous studies demonstrated that cells deficient in tankyrase 1 suffered a block in resolution of sister telomeres and arrested in early anaphase [Dynek and Smith (2004) Science 304, 97-100]. This phenotype was dependent on the catalytic PARP activity of tankyrase 1. To identify critical acceptors of PARsylation [poly(ADP-ribosyl)ation] by tankyrase 1 in mitosis, tankyrase 1 immunoprecipitates were analysed for associated PARsylated proteins. We identified NuMA (nuclear mitotic apparatus protein) as a major acceptor of poly(ADP-ribose) from tankyrase 1 in mitosis. We showed by immunofluorescence and immunoprecipitation that association between tankyrase 1 and NuMA increases dramatically at the onset of mitosis, concomitant with PARsylation of NuMA. Knockdown of tankyrase 1 by siRNA (small interfering RNA) eliminates PARsylation of NuMA in mitosis, confirming tankyrase 1 as the PARP responsible for this modification. However, even in the absence of tankyrase 1 and PARsylation, NuMA localizes to spindle poles. By contrast, siRNA knockdown of NuMA results in complete loss of tankyrase 1 from spindle poles. We discuss our result in terms of a model where PARsylation of NuMA by tankyrase 1 in mitosis could play a role in sister telomere separation and/or mitotic progression.
The role of interleukin 6 and interleukin 1 in megakaryocyte development. (1989)

The effect of human interleukin 6 (IL-6) and interleukin 1 (IL-1) on cells of the megakaryocyte lineage from murine bone marrow was examined. In bone marrow liquid culture, IL-6 but not IL-1 increases the amount of acetylcholinesterase, a megakaryocyte marker. In semisolid colony assays, a low level of interleukin 3 (IL-3) was used as a growth factor, and IL-6 and IL-1 were tested for their ability to potentiate the activity of IL-3 to stimulate megakaryocyte colony formation. IL-6 and/or IL-1 had no effect on megakaryocyte colony formation in the absence of IL-3. However, IL-6 was able to stimulate increased megakaryocyte colonies in the presence of IL-3. IL-1 was able to potentiate colony formation only in the presence of both IL-3 and IL-6.
Integrated IP/WDM routing in GMPLS-based optical networks (2003)

Future transport networks will have to cope with the continuous growth of IP traffic. Furthermore, transport networks need to evolve so as to drastically reduce both deployment costs and operating expenses. A reasonable strategy to achieve this goal consists of simplifying the network architecture by reducing the number of layers. Assuming a peer model IP over optical network, we propose an integrated routing strategy that takes into account constraints and dynamic occupancy of both the IP and optical layers. The collaboration of both layers in the routing process leads to optimization of network performance. The main emphasis is on the implementation requirements of this grooming functionality using GMPLS-TE mechanisms. Simulation results show the benefits obtained by applying this strategy.
Notch signaling inhibits muscle cell differentiation through a CBF1-independent pathway (1996)

Notch controls cell fate by inhibiting cellular differentiation, presumably through activation of the transcriptional regulator human C promoter Binding Factor (CBF1), which transactivates the hairy and Enhancer of split (HES-1) gene. However, we describe constitutively active forms of Notch1, which inhibit muscle cell differentiation but do not interact with CBF1 or upregulate endogenous HES-1 expression. In addition, Jagged-Notch interactions that prevent the expression of muscle cell specific genes do not involve the upregulation of endogenous HES-1. In fact, exogenous expression of HES-1 in C2C12 myoblasts does not block myogenesis. Our data demonstrate the existence of a CBF1-independent pathway by which Notch inhibits differentiation. We therefore propose that Notch signaling activates at least two different pathways: one which involves CBF1 as an intermediate and one which does not.
Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease (2005)

Macroautophagy, which is a lysosomal pathway for the turnover of organelles and long-lived proteins, is a key determinant of cell survival and longevity. In this study, we show that neuronal macroautophagy is induced early in Alzheimer's disease (AD) and before beta-amyloid (Abeta) deposits extracellularly in the presenilin (PS) 1/Abeta precursor protein (APP) mouse model of beta-amyloidosis. Subsequently, autophagosomes and late autophagic vacuoles (AVs) accumulate markedly in dystrophic dendrites, implying an impaired maturation of AVs to lysosomes. Immunolabeling identifies AVs in the brain as a major reservoir of intracellular Abeta. Purified AVs contain APP and beta-cleaved APP and are highly enriched in PS1, nicastrin, and PS-dependent gamma-secretase activity. Inducing or inhibiting macroautophagy in neuronal and nonneuronal cells by modulating mammalian target of rapamycin kinase elicits parallel changes in AV proliferation and Abeta production. Our results, therefore, link beta-amyloidogenic and cell survival pathways through macroautophagy, which is activated and is abnormal in AD.
Purinergic Mechanosensory Transduction and Visceral Pain (2009)

In this review, evidence is presented to support the hypothesis that mechanosensory transduction occurs in tubes and sacs and can initiate visceral pain. Experimental evidence for this mechanism in urinary bladder, ureter, gut, lung, uterus, tooth-pulp and tongue is reviewed. Potential therapeutic strategies are considered for the treatment of visceral pain in such conditions as renal colic, interstitial cystitis and inflammatory bowel disease by agents that interfere with mechanosensory transduction in the organs considered, including P2X3 and P2X2/3 receptor antagonists that are orally bioavailable and stable in vivo and agents that inhibit or enhance ATP release and breakdown.
Evaluation of Grouping Strategies for an Hierarchical SDMA/TDMA Scheduling Process (2007)

Adding SDMA capabilities to modern wireless communication systems like IEEE 802.16 WiMAX promises high system capacity gains but raises the problem of combining orthogonal medium access schemes like TDMA with the non- orthogonal SDMA. In order to reduce the complexity and to improve the flexibility of a joint SDMA/TDMA scheduler, the scheduling process can be subdivided into two parts. First, a spatial grouping algorithm forms groups of users that can be co-scheduled because of their spatial separability. Then, a group scheduling algorithm allocates resources of the time domain to the spatial groups. This paper focuses on the first part of the hierarchical SDMA/TDMA scheduling process, i.e., the spatial grouping. It outlines different grouping strategies and it analyzes their computational complexity. Their respective grouping performance is evaluated according to a metric introduced in the paper. Finally, a tree-based grouping strategy is recommended based on its low complexity and good performance.
Designs, formats and applications of lateral flow assay: A literature review (2014)

This manuscript provides a brief overview of latest research involving the use of lateral flow assay for qualitative and quantitative analysis in different areas. The excellent features and versatility of detection formats make these strips an ideal choice for point of care applications. We outline and critically discuss detection formats, molecular recognition probes, labels, and detection systems used in lateral flow assay. Applications in different fields along with selected examples from the literature have been included to show analytical performance of these devices. At the end, we summarize accomplishments, weaknesses and future challenges in the area of lateral flow strips.
Enhancement of methionine production by methionine analogue ethionine resistant mutants of Brevibacterium heali (1994)

Abstract In order to improve the methionine yield of the isolate B. heali , attempts were made to isolate mutants resistant to the methionine analogue DL ‐ethionine after mutagenesis with N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (NTG). The minimum inhibitory concentration (MIC) of ethionine for B. heali was found to be 2 mM. After mutagenesis and screening, five mutants resistant to 50 mM of ethionine were isolated. The yield of the best ethionine resistant mutant, B. heali Br EthR , was 13 mg/l of methionine medium under optimum cultivation conditions.
High-affinity Anticalins with aggregation-blocking activity directed against the Alzheimer β-amyloid peptide (2016)

Amyloid beta (Aβ) peptides, in particular Aβ42 and Aβ40, exert neurotoxic effects and their overproduction leads to amyloid deposits in the brain, thus constituting an important biomolecular target for treatments of Alzheimer's disease (AD). We describe the engineering of cognate Anticalins as a novel type of neutralizing protein reagent based on the human lipocalin scaffold. Phage display selection from a genetic random library comprising variants of the human lipocalin 2 (Lcn2) with mutations targeted at 20 exposed amino acid positions in the four loops that form the natural binding site was performed using both recombinant and synthetic target peptides and resulted in three different Anticalins. Biochemical characterization of the purified proteins produced by periplasmic secretion in Escherichia coli revealed high folding stability in a monomeric state, with Tm values ranging from 53.4°C to 74.5°C, as well as high affinities for Aβ40, between 95 pM and 563 pM, as measured by real-time surface plasmon resonance analysis. The central linear VFFAED epitope within the Aβ sequence was mapped using a synthetic peptide array on membranes and was shared by all three Anticalins, despite up to 13 mutual amino acid differences in their binding sites. All Anticalins had the ability-with varying extent-to inhibit Aβ aggregation in vitro according to the thioflavin-T fluorescence assay and, furthermore, they abolished Aβ42-mediated toxicity in neuronal cell culture. Thus, these Anticalins provide not only useful protein reagents to study the molecular pathology of AD but they also show potential as alternative drug candidates compared with antibodies.
A Thermotropic Mesophase Comprised of Closed Micellar Aggregates of the Normal Type (2002)

A new mesophase, composed of closed spheroidal aggregates that contain lipophilic alkyl chains within a continuum of hydrogen-bonding networks, was realized with the low molecular weight amphiphile 1 in the absence of water or any other solvent.
Trogocytosis generates acquired regulatory T cells adding further complexity to the dysfunctional immune response in multiple myeloma (2012)

Trogocytosis, which results in the acquisition of myeloma cell-derived membrane proteins by T cells, and hence generates novel regulatory T cells, adds to the growing list of immune defects of multiple myeloma patients. The increasing complexity of the cancer-associated immune defects must be attentively considered for attempting to improve the so-far unsatisfactory rates of clinical responses to immunotherapy in patients affected by multiple myeloma and other malignancies.
α‐Amido boronic acids: A synthetic challenge and their properties as serine protease inhibitors (2007)

This review includes a personal account of the history of the development of the alpha-amido boronic acid synthesis and related chemistry in the author's laboratory, as well as a review of some of the more significant developments that have occurred elsewhere more recently. The simple initial target, suggested by biochemist G. E. Lienhard, proved much more elusive to reach than anticipated. The circuitous effort that ultimately revealed the deceptively simple successful route, for which there is still no alternative, will be described. The properties of these compounds as enzyme inhibitors will be described very briefly. More extensive reviews of the enzyme inhibiting properties of alpha-amido boronic acids have appeared recently.
TIED, LibsafePlus: tools for runtime buffer overflow protection (2004)

Buffer overflow exploits make use of the treatment of strings in C as character arrays rather than as first-class objects. Manipulation of arrays as pointers and primitive pointer arithmetic make it possible for a program to access memory locations which it is not supposed to access. There have been many efforts in the past to overcome this vulnerability by performing array bounds checking in C. Most of these solutions are either inadequate, inefficient or incompatible with legacy code. In this paper, we present an efficient and transparent runtime approach for protection against all known forms of buffer overflow attacks. Our solution consists of two tools: TIED (Type Information Extractor and Depositor) and LibsafePlus. TIED extracts size information of all global and automatic buffers defined in the program from the debugging information produced by the compiler and inserts it back in the program binary as a data structure available at runtime. LibsafePlus is a dynamic library which provides wrapper functions for unsafe C library functions such as strcpy. These wrapper functions check the source and target buffer sizes using the information made available by TIED and perform the requested operation only when it is safe to do so. For dynamically allocated buffers, the sizes and starting addresses are recorded at runtime. With our simple design we are able to protect most applications with a performance overhead of less than 10%.
Inositol-1,4,5-Trisphosphate Receptor-Mediated Ca Mobilization Is Not Required for Cerebellar Long-Term Depression in Reduced Preparations (1998)

Narasimhan, Kalyani, Isaac N. Pessah, and David J. Linden. Inositol-1,4,5-trisphosphate receptor-mediated Ca mobilization is not required for cerebellar long-term depression in reduced preparations. J. Neurophysiol. 80: 2963–2974, 1998. Cerebellar long-term depression (LTD) is a cellular model system of information storage in which coincident parallel fiber and climbing fiber activation of a Purkinje neuron (PN) gives rise to a sustained attenuation of parallel fiber–PN synaptic strength. Climbing fiber and parallel fiber inputs may be replaced by direct depolarization of the PN and exogenous glutamate pulses, respectively. The parallel fiber–PN synapse has a high-density of mGluR1 receptors that are coupled to phosphoinositide turnover. Several lines of evidence indicated that activation of mGluR1 by parallel fiber stimulation is necessary for the induction of cerebellar LTD. Because phosphoinositide hydrolysis has two initial products, 1,2-diacylglycerol and inositol-1,4,5-trisphosphate (IP3), we wished to determine whether IP3 signaling via IP3 receptors and consequent Ca mobilization were necessary for the induction of cerebellar LTD. First, ratiometric imaging of free cytosolic Ca was performed on both acutely dissociated and cultured PNs. It was determined that the threshold for glutamate pulses to contribute to LTD induction was below the threshold for producing a Ca transient. Furthermore, the Ca transients produced by depolarization alone and glutamate plus depolarization were not significantly different. Second, the potent and selective IP3 receptor channel blocker xestospongin C was not found to affect the induction of LTD in either acutely dissociated or cultured PNs at a concentration that was sufficient to block mGluR1-evoked Ca mobilization. Third, replacement of mGluR activation by exogenous synthetic diacylglycerol in an LTD induction protocol was successful. Taken together, these results suggest that activation of an IP3 signaling cascade is not required for induction of cerebellar LTD in reduced preparations.
DNA amplification in drug resistant cells and in tumours. (1986)

DNA amplification is a pervasive phenomenon in continuous cell lines and in tumours. It can occur in many different parts of the genome with high frequency, and a very large amount of DNA, probably including many genes, is often involved in a single amplification event. In tumours, it is likely that a common mechanism underlies the amplification of genes which confer drug resistance and genes which give a growth advantage to the tumour. DNA amplification may be caused by defects in the regulation of DNA replication, and similar defects may lead to other chromosomal abnormalities such as translocations, inversions and heteroploidy. Two recent observations should facilitate identification and study of the underlying defects: agents or treatments which damage DNA can increase the rate of amplification, and mutant cell lines can be selected which amplify their DNA at a greatly increased frequency.
An immunocytochemical and morphometric study of the rat pancreatic islets. (1995)

The rat pancreas has frequently been used as an animal model to study changes in islet cells in pathological conditions, such as diabetes mellitus and islet cell tumours, but detailed quantitative data on the islets are not available. This study was therefore undertaken to investigate (1) the volume density of pancreatic islets, (2) islet diameter, islet volume and islet cell number and (3) islet cell pattern, i.e. the distribution, volume and number of each cell type per islet. The study also investigated the possibility of differences in various pancreatic regions derived from the dorsal primordium. The rat pancreas was divided into 4 regions: lower duodenal (derived from the ventral primordium) and upper duodenal, gastric and splenic regions (derived from the dorsal primordium). Sections were stained immunocytochemically with anti-insulin (B cells), antiglucagon (A cells), antisomatostatin (D cells) and antipancreatic polypeptide (PP cells) antibodies, and were used for morphometric analysis. A total of 1292 islets was examined, 328 from the lower duodenal, 245 from the upper duodenal, 314 from the gastric and 405 from the splenic regions. The mean volume density of the islets per pancreatic tissue was found to be 2.6 +/- 0.1%, 2.3 +/- 0.1%, 2.9 +/- 0.2% and 3.3 +/- 0.2%, in the lower duodenal, upper duodenal, gastric and splenic regions, respectively. The size-frequency distribution of the profile diameters of the islets showed an overall shift of all the size classes towards smaller sizes in the upper duodenal region, and towards larger sizes in the splenic region, as compared with the corresponding classes of the other regions.(ABSTRACT TRUNCATED AT 250 WORDS)
Degenerative disk disease: assessment of changes in vertebral body marrow with MR imaging. (1988)

The authors reviewed magnetic resonance (MR) images of 474 consecutive patients referred for lumbar spine MR imaging. Type 1 changes (decreased signal intensity on T1-weighted spin-echo images and increased signal intensity on T2-weighted images) were identified in 20 patients (4%) and type 2 (increased signal intensity on T1-weighted images and isointense or slightly increased signal intensity on T2-weighted images) in 77 patients (16%). In all cases there was evidence of associated degenerative disk disease at the level of involvement. Histopathologic sections in three cases of type 1 change demonstrated disruption and fissuring of the end plates and vascularized fibrous tissue, while in three cases of type 2 change they demonstrated yellow marrow replacement. In addition, 16 patients with end-plate changes documented with MR were studied longitudinally. Type 1 changes in five of six patients converted to a type 2 pattern in 14 months to 3 years. Type 2 changes in ten patients remained stable over a 2-3-year period. These signal intensity changes appear to reflect a spectrum of vertebral body marrow changes associated with degenerative disk disease.
An introduction to molecular neurobiology (1992)

Introduction/The Cells of the Nervous System Zach W. Hall. Signalling in the Nervous'System /Electrical Signals in the Nenous System PeterB. Sargentllon Channels Zach W Hall/Chemical Signals in the Nervous System RichardH. Scheller and Zach W Hall/The Nene Terminal Zach W. HAII. The Cell Biology of Neurons and Glia/ G Proteins and Their Receptors Elliott M. Rossl Second Messengers and Neuronal Function Mary B. Kennedy), The Neuronal Cytoskeleton Ron D. Vale, Gary Banker, and Zach W Hall/Myelin and Myelination Greg Lemke/IV. Neuronal Development/Gene Regulation in the Nervous System Greg Lemke/Generation of Cellular Diversity and Pattern Formation in the Nervous System baz-idy. Anderson/Process Outgrowth and the Specificity of Neuronal Connections Paul H. Patterson/Neuron-Target Interactions ,Paul H. Patterson/V. Complex Interactions of Neurons and Neuronal Disorders/Cellular and Molecular Niechanisms of Neuronal Plasticity Mary B Kennedy and Eve Marder/Genetic Diseases of the Nenous System Xalldra 0. Breakefield.
Efficient CRISPR/Cas9-Mediated Genome Editing Using a Chimeric Single-Guide RNA Molecule (2017)

The CRISPR/Cas9 system has been applied in diverse eukaryotic organisms for targeted mutagenesis. However, targeted gene editing is inefficient and requires the simultaneous delivery of a DNA template for homology-directed repair (HDR). Here, we used CRISPR/Cas9 to generate targeted double-strand breaks and to deliver an RNA repair template for HDR in rice (<i>Oryza sativa</i>). We used chimeric single-guide RNA (cgRNA) molecules carrying both sequences for target site specificity (to generate the double-strand breaks) and repair template sequences (to direct HDR), flanked by regions of homology to the target. Gene editing was more efficient in rice protoplasts using repair templates complementary to the non-target DNA strand, rather than the target strand. We applied this cgRNA repair method to generate herbicide resistance in rice, which showed that this cgRNA repair method can be used for targeted gene editing in plants. Our findings will facilitate applications in functional genomics and targeted improvement of crop traits.