gebhart/patrepeval huggingface dataset:
Emerging Biomarkers in Glioblastoma (2013)

Glioblastoma, the most common primary brain tumor, has few available therapies providing significant improvement in survival. Molecular signatures associated with tumor aggressiveness as well as with disease progression and their relation to differences in signaling pathways implicated in gliomagenesis have recently been described. A number of biomarkers which have potential in diagnosis, prognosis and prediction of response to therapy have been identified and along with imaging modalities could contribute to the clinical management of GBM. Molecular biomarkers including O(6)-methlyguanine-DNA-methyltransferase (MGMT) promoter and deoxyribonucleic acid (DNA) methylation, loss of heterozygosity (LOH) of chromosomes 1p and 19q, loss of heterozygosity 10q, isocitrate dehydrogenase (IDH) mutations, epidermal growth factor receptor (EGFR), epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1 (ELTD1), vascular endothelial growth factor (VEGF), tumor suppressor protein p53, phosphatase and tensin homolog (PTEN), p16INK4a gene, cytochrome c oxidase (CcO), phospholipid metabolites, telomerase messenger expression (hTERT messenger ribonucleic acid [mRNA]), microRNAs (miRNAs), cancer stem cell markers and imaging modalities as potential biomarkers are discussed. Inclusion of emerging biomarkers in prospective clinical trials is warranted in an effort for more effective personalized therapy in the future.
T-cell cytokine responses in human infection with Mycobacterium tuberculosis (1995)

Compared with healthy tuberculin reactors, Mycobacterium tuberculosis-stimulated peripheral blood mononuclear cells from tuberculosis patients had diminished production and mRNA expression of the Th1 cytokines gamma interferon and interleukin 2 (IL-2), with no change in production and mRNA expression for the Th2 cytokines IL-4, IL-10, and IL-13. These results were confirmed by evaluation of T cells and CD4+ cells. At the level of systemic T cells, development of tuberculosis is associated with diminished Th1 but not enhanced Th2 responses.
Oxidative Group Transfer to a Triiron Complex to Form a Nucleophilic μ3-Nitride, [Fe3(μ3-N)]− (2011)

Utilizing a hexadentate ligand platform, a high-spin trinuclear iron complex of the type ((tbs)L)Fe(3)(thf) was synthesized and characterized ([(tbs)L](6-) = [1,3,5-C(6)H(9)(NPh-o-NSi(t)BuMe(2))(3)](6-)). The silyl-amide groups only permit ligation of one solvent molecule to the tri-iron core, resulting in an asymmetric core wherein each iron ion exhibits a distinct local coordination environment. The triiron complex ((tbs)L)Fe(3)(thf) rapidly consumes inorganic azide ([N(3)]NBu(4)) to afford an anionic, trinuclear nitride complex [((tbs)L)Fe(3)(μ(3)-N)]NBu(4). The nearly C(3)-symmetric complex exhibits a highly pyramidalized nitride ligand that resides 1.205(3) Å above the mean triiron plane with short Fe-N (1.871(3) Å) distances and Fe-Fe separation (2.480(1) Å). The nucleophilic nitride can be readily alkylated via reaction with methyl iodide to afford the neutral, trinuclear methylimide complex ((tbs)L)Fe(3)(μ(3)-NCH(3)). Alkylation of the nitride maintains the approximate C(3)-symmetry in the imide complex, where the imide ligand resides 1.265(9) Å above the mean triiron plane featuring lengthened Fe-N(imide) bond distances (1.892(3) Å) with nearly equal Fe-Fe separation (2.483(1) Å).
Gene Profile of Electroconvulsive Seizures: Induction of Neurotrophic and Angiogenic Factors (2003)

Electroconvulsive seizure therapy (ECS) is a clinically proven treatment for depression and is often effective even in patients resistant to chemical antidepressants. However, the molecular mechanisms underlying the therapeutic efficacy of ECS are not fully understood. One theory that has gained attention is that ECS and other antidepressants increase the expression of select neurotrophic factors that could reverse or block the atrophy and cell loss resulting from stress and depression. To further address this topic, we examined the expression of other neurotrophic-growth factors and related signaling pathways in the hippocampus in response to ECS using a custom growth factor microarray chip. We report the regulation of several genes that are involved in growth factor and angiogenic-endothelial signaling, including neuritin, stem cell factor, vascular endothelial growth factor (VEGF), VGF (nonacronymic), cyclooxygenase-2, and tissue inhibitor of matrix metalloproteinase-1. Some of these, as well as other growth factors identified, including VEGF, basic fibroblast growth factor, and brain-derived neurotrophic factor, have roles in mediating neurogenesis and cell proliferation in the adult brain. We also examined gene expression in the choroid plexus and found several growth factors that are enriched in this vascular tissue as well as regulated by ECS. These data suggest that an amplification of growth factor signaling combined with angiogenic mechanisms could have an important role in the molecular action of ECS. This study demonstrates the applicability of custom-focused microarray technology in addressing hypothesis-driven questions regarding the action of antidepressants.
Overexpression of the 78-kDa Glucose-regulated Protein/Immunoglobulin-binding Protein (GRP78/BiP) Inhibits Tissue Factor Procoagulant Activity (2003)

Previous studies have demonstrated that overexpression of GRP78/BiP, an endoplasmic reticulum (ER)-resident molecular chaperone, in mammalian cells inhibits the secretion of specific coagulation factors. However, the effects of GRP78/BiP on activation of the coagulation cascade leading to thrombin generation are not known. In this study, we examined whether GRP78/BiP overexpression mediates cell surface thrombin generation in a human bladder cancer cell line T24/83 having prothrombotic characteristics. We report here that cells overexpressing GRP78/BiP exhibited significant decreases in cell surface-mediated thrombin generation, prothrombin consumption and the formation of thrombin-inhibitor complexes, compared with wild-type or vector-transfected cells. This effect was attributed to the ability of GRP78/BiP to inhibit cell surface tissue factor (TF) procoagulant activity (PCA) because conversion of factor X to Xa and factor VII to VIIa were significantly lower on the surface of GRP78/BiP-overexpressing cells. The additional findings that (i) cell surface factor Xa generation was inhibited in the absence of factor VIIa and (ii) TF PCA was inhibited by a neutralizing antibody to human TF suggests that thrombin generation is mediated exclusively by TF. GRP78/BiP overexpression did not decrease cell surface levels of TF, suggesting that the inhibition in TF PCA does not result from retention of TF in the ER by GRP78/BiP. The additional observations that both adenovirus-mediated and stable GRP78/BiP overexpression attenuated TF PCA stimulated by ionomycin or hydrogen peroxide suggest that GRP78/BiP indirectly alters TF PCA through a mechanism involving cellular Ca(2+) and/or oxidative stress. Similar results were also observed in human aortic smooth muscle cells transfected with the GRP78/BiP adenovirus. Taken together, these findings demonstrate that overexpression of GRP78/BiP decreases thrombin generation by inhibiting cell surface TF PCA, thereby suppressing the prothrombotic potential of cells.
Digital beam forming and compressive sensing based DOA estimation in MIMO arrays (2011)

The paper presents different processing schemes that have been investigated in order to evaluate the direction of arrival (DOA) with a multiple-input multiple-output (MIMO) radar. Conventional digital beam forming (DBF) and super resolution algorithm (MUSIC) have been applied. The results provided by them have been compared with a compressive sensing (CS) processing of the virtual elements of the MIMO array. The possible reduction of the number of physical elements in the array, due to the application of CS techniques, has been also analyzed. Experimental validation has been carried out on a test board radar developed at TNO in the Netherlands.
Evidence of 2-Adrenoceptors in the Nasal Blood Vessels of the Dog (1984)

alpha-Adrenoceptor subtypes were demonstrated in an in vitro preparation of the vascular smooth muscle of the canine nasal mucosa. alpha 1-Receptors were located on the surface of vascular smooth muscle (postsynaptic). alpha 2 Subtypes were situated both at postsynaptic and presynaptic sites on adrenergic nerve terminals. Presynaptic alpha 2-adrenoceptor stimulation yielded an inhibition of excessive norepinephrine release from nerve terminals. Stimulation of postsynaptic receptors, either alpha 1 or alpha 2, produced vasoconstriction. Although there was good evidence of the presence of postsynaptic alpha 2-receptors, they did not appear to be dominant among the postsynaptic receptors.
A Whole-Genome Assembly of Drosophila (2000)

We report on the quality of a whole-genome assembly of Drosophila melanogaster and the nature of the computer algorithms that accomplished it. Three independent external data sources essentially agree with and support the assembly's sequence and ordering of contigs across the euchromatic portion of the genome. In addition, there are isolated contigs that we believe represent nonrepetitive pockets within the heterochromatin of the centromeres. Comparison with a previously sequenced 2.9- megabase region indicates that sequencing accuracy within nonrepetitive segments is greater than 99. 99% without manual curation. As such, this initial reconstruction of the Drosophila sequence should be of substantial value to the scientific community.
Attosecond electron pulses for 4D diffraction and microscopy (2007)

In this contribution, we consider the advancement of ultrafast electron diffraction and microscopy to cover the attosecond time domain. The concept is centered on the compression of femtosecond electron packets to trains of 15-attosecond pulses by the use of the ponderomotive force in synthesized gratings of optical fields. Such attosecond electron pulses are significantly shorter than those achievable with extreme UV light sources near 25 nm ( approximately 50 eV) and have the potential for applications in the visualization of ultrafast electron dynamics, especially of atomic structures, clusters of atoms, and some materials.
Plants that express a potyvirus proteinase gene are resistant to virus infection. (1993)

Transgenic tobacco plants that express the genome-linked protein/proteinase-coding region of the potyvirus tobacco vein mottling virus (TVMV) were produced and tested for their reaction to inoculation with TVMV and two other potyviruses. These plants did not develop disease symptoms after being inoculated with large doses of TVMV but were as susceptible to infection by the other potyviruses as were control plants. Lines of tobacco that express the coat protein- or the nonstructural cylindrical inclusion protein-coding regions were also produced. The coat protein transgenic plants were protected against all three potyviruses, and the cylindrical inclusion transgenic plants were susceptible to all three potyviruses. These results indicate that some, but not all, TVMV genes can be used to confer protection against potyviruses in plants. The results also suggest that combinations of viral genes in transgenic plants might improve protection against potyviruses.
Clostridium perfringens Enterotoxin Fragment Removes Specific Claudins from Tight Junction Strands (1999)

Claudins, comprising a multigene family, constitute tight junction (TJ) strands. Clostridium perfringens enterotoxin (CPE), a single approximately 35-kD polypeptide, was reported to specifically bind to claudin-3/RVP1 and claudin-4/CPE-R at its COOH-terminal half. We examined the effects of the COOH-terminal half fragment of CPE (C-CPE) on TJs in L transfectants expressing claudin-1 to -4 (C1L to C4L, respectively), and in MDCK I cells expressing claudin-1 and -4. C-CPE bound to claudin-3 and -4 with high affinity, but not to claudin-1 or -2. In the presence of C-CPE, reconstituted TJ strands in C3L cells gradually disintegrated and disappeared from their cell surface. In MDCK I cells incubated with C-CPE, claudin-4 was selectively removed from TJs with its concomitant degradation. At 4 h after incubation with C-CPE, TJ strands were disintegrated, and the number of TJ strands and the complexity of their network were markedly decreased. In good agreement with the time course of these morphological changes, the TJ barrier (TER and paracellular flux) of MDCK I cells was downregulated by C-CPE in a dose-dependent manner. These findings provided evidence for the direct involvement of claudins in the barrier functions of TJs.
Lenalidomide plus dexamethasone is more effective than dexamethasone alone in patients with relapsed or refractory multiple myeloma regardless of prior thalidomide exposure (2008)

This analysis assessed the efficacy and safety of lenalidomide + dexamethasone in patients with relapsed or refractory multiple myeloma (MM) previously treated with thalidomide. Of 704 patients, 39% were thalidomide exposed. Thalidomide-exposed patients had more prior lines of therapy and longer duration of myeloma than thalidomide-naive patients. Lenalidomide + dexamethasone led to higher overall response rate (ORR), longer time to progression (TTP), and progression-free survival (PFS) versus placebo + dexamethasone despite prior thalidomide exposure. Among lenalidomide + dexamethasone-treated patients, ORR was higher in thalidomide-naive versus thalidomide-exposed patients (P = .04), with longer median TTP (P = .04) and PFS (P = .02). Likewise for dexamethasone alone-treated patients (P = .03 for ORR, P = .03 for TTP, P = .06 for PFS). Prior thalidomide did not affect survival in lenalidomide + dexamethasone-treated patients (36.1 vs 33.3 months, P > .05). Thalidomide-naive and thalidomide-exposed patients had similar toxicities. Lenalidomide + dexamethasone resulted in higher rates of venous thromboembolism, myelosuppression, and infections versus placebo + dexamethasone, independent of prior thalidomide exposure. Lenalido-mide + dexamethasone was superior to placebo + dexamethasone, independent of prior thalidomide exposure. Although prior thalidomide may have contributed to inferior TTP and PFS compared with thalidomide-naive patients, these parameters remained superior compared with placebo + dexamethasone; similar benefits compared with placebo + dexamethasone were not evident for thalidomide-exposed patients in terms of overall survival. Studies were registered at http://www.clinicaltrials.gov under NCT00056160 and NCT00424047.
Polymer translocation through a hole (1999)

The average residence time τ of a polymer of length N passing through a narrow hole under a chemical potential gradient is calculated. In the proposed model, details of the hole parametrize the rate constant k0 for transporting a monomer across the hole, independent of the chain length. We show that any asymmetry in the average conformations of the polymer across the hole is sufficient to generate the driving force for the polymer translocation. If chemical potential gradient is absent, τ∼N2, with the proportionality constant depending on the size exponent of the polymer before and after the translocation. For translocation along the chemical potential gradient Δμ, τ is proportional to N(T/k0Δμ) and N2/k0, respectively, for large and small NΔμ/T. For translocation against the chemical potential gradient, τ∼exp(N) for long polymers.
Role of Reactive Oxygen Species and Protein Kinase C in Ischemic Tolerance in the Brain (2005)

It is now understood that the mechanisms leading to neuronal cell death after cerebral ischemia are highly complex. A well established fact in this field is that neurons continue to die over days and months after ischemia, and that reperfusion following cerebral ischemia contributes substantially to ischemic injury. It is now well accepted that central to ischemic/reperfusion-induced injury is what occurs to mitochondria hours to days following the ischemic insult. For many years, it has been established that reactive oxygen species (ROS) and reactive nitrogen species (RNS) promote lipid, protein, and DNA oxidation that affects normal cell physiology and eventually leads to neuronal demise. In addition to oxidation of neuronal molecules by ROS and RNS, a novel pathway for molecular modifications has risen from the concept that ROS can activate specific signal transduction pathways that, depending on the insult degree, can lead to either normal plasticity or pathology. Two examples of these pathways could explain why lethal ischemic insults lead to the translocation of protein kinase Cdelta (deltaPKC), which plays a role in apoptosis after cerebral ischemia, or why sublethal ischemic insults, such as in ischemic preconditioning, lead to the translocation of epsilonPKC, which plays a pivotal role in neuroprotection. A better understanding of the mechanisms by which ROS and/or RNS modulate key protein kinases that are involved in signaling pathways that lead to cell death and survival after cerebral ischemia will help devise novel therapeutic strategies.
Spontaneously produced anti‐DNA/DNase I autoantibodies modulate nuclear apoptosis in living cells (1996)

Apoptosis has received increased attention over the past decade, and it is established as an essential process in physiological and disease states. Much effort has been devoted to understanding the intracellular mechanisms culminating in apoptosis; intense investigation has also focused on its role during inflammation. Despite these efforts, these events remain incompletely understood. It has been suggested that the Ca(2+)- and Mg2+-dependent endonuclease that mediates DNA fragmentation is DNase I; however, the precise role of DNase I during apoptosis has been debated. Recent observations using anti-DNA antibodies derived from autoimmune mice (MRL-lpr/lpr) provided both the means and the reagents to approach these issues in a more direct manner. We previously discovered that many anti-DNA antibodies cross-react with DNase I, and a subset of these Ig inhibited DNase I enzymatic activity in vitro. Serendipitously, in separate studies, a subset of these antibodies were observed to enter and localize within the nuclei of living cells. The aim of the present investigation was to determine whether these nuclear-localizing anti-DNA antibodies could interact with DNase I in living cells. We found that, once internalized, these autoantibodies bound DNase I and inhibited activity of the enzyme. Furthermore, living cells containing the intracellular antibodies appeared resistant to apoptotic stimuli; both morphological features of nuclear apoptosis and DNA fragmentation were inhibited. These results support a pivotal role for DNase I in apoptosis, and they provide a novel paradigm for autoantibody-mediated inflammatory disease.
Chronic pancreatitis: evolution of the disease. (1991)

The aim of this study was to review the pathology of acute pancreatitis, resolving acute pancreatitis and chronic pancreatitis in order to find an answer to the unresolved question as to whether chronic pancreatitis is a primary disease or may be due to recurrent acute pancreatitis. Our series consisted of 71 pancreatic resection specimens and 15 autopsy pancreases from 8 patients with acute pancreatitis, 5 patients with pancreatitis 5-7 weeks prior to examination (resolving acute pancreatitis), and 66 patients with chronic pancreatitis. Peripancreatic and intrapancreatic fat necrosis was the key finding in acute pancreatitis. Organization of fat necrosis with early perilobular fibrosis and/or peripancreatic pseudocysts characterized the pancreas with resolving acute pancreatitis. Pseudocysts were present in 52% of pancreases with an early stage of chronic pancreatitis that was characterized by a focally accentuated fibrosis of the perilobular and, to a lesser degree, intralobular type. Marked fibrosis, ductal distortions and presence of intraductal calculi were the main features of advanced chronic pancreatitis. Pseudocysts were less frequent (36%) than in the early stage of the disease. On the basis of these findings it is suggested that acute pancreatitis, if it is severe and also affects the intrapancreatic fat deposits, may evolve into chronic pancreatitis.
Enabling technology for knowledge sharing (1991)

Building new knowledge-based systems today usually entails constructing new knowledge bases from scratch. It could instead be done by assembling reusable components. System developers would then only need to worry about creating the specialized knowledge and reasoners new to the specific task of their system. This new system would interoperate with existing systems, using them to perform some of its reasoning. In this way, declarative knowledge, problem- solving techniques, and reasoning services could all be shared among systems. This approach would facilitate building bigger and better systems cheaply. The infrastructure to support such sharing and reuse would lead to greater ubiquity of these systems, potentially transforming the knowledge industry. This article presents a vision of the future in which knowledge-based system development and operation is facilitated by infrastructure and technology for knowledge sharing. It describes an initiative currently under way to develop these ideas and suggests steps that must be taken in the future to try to realize this vision.
The Promyelotic Leukemia Zinc Finger Promotes Osteoblastic Differentiation of Human Mesenchymal Stem Cells as an Upstream Regulator of CBFA1 (2004)

Ossification of the posterior longitudinal ligament of the spine (OPLL) is the leading cause of myelopathy in Japan and is diagnosed by ectopic bone formation in the paravertebral ligament. OPLL is a systemic high bone mass disease with a strong genetic background. To detect genes relevant to the pathogenesis of OPLL, we performed a cDNA microarray analysis of systematic gene expression profiles during the osteoblastic differentiation of ligament cells from OPLL patients (OPLL cells), patients with a disorder called ossification of yellow ligament (OYL), and non-OPLL controls together with human mesenchymal stem cells (hMSCs) after stimulating them with osteogenic differentiation medium (OS). Twenty-four genes were up-regulated during osteoblastic differentiation in OPLL cells. Zinc finger protein 145 (promyelotic leukemia zinc finger or PLZF) was one of the highly expressed genes during osteoblastic differentiation in all the cells examined. We investigated the roles of PLZF in the regulation of osteoblastic differentiation of hMSCs and C2C12 cells. Small interfering RNA-mediated gene silencing of PLZF resulted in a reduction in the expression of osteoblast-specific genes such as the alkaline phosphatase, collagen 1A1 (Col1a1), Runx2/core-binding factor 1 (Cbfa1), and osteocalcin genes, even in the presence of OS in hMSCs. The expression of PLZF was unaffected by the addition of bone morphogenetic protein 2 (BMP-2), and the expression of BMP-2 was not affected by PLZF in hMSCs. In C2C12 cells, overexpression of PLZF increased the expression of Cbfa1 and Col1a1; on the other hand, the overexpression of CBFA1 did not affect the expression of Plzf. These findings indicate that PLZF plays important roles in early osteoblastic differentiation as an upstream regulator of CBFA1 and thereby might participate in promoting the ossification of spinal ligament cells in OPLL patients.
Infection of cynomolgus monkeys with a chimeric HIV-1/SIVmac virus that expresses the HIV-1 envelope glycoproteins. (1992)

Replication competent chimeric viruses that express the gag and pol proteins of SIVmac and the env proteins of HIV-1 were made. One such chimeric virus, SHIV-4, that expresses the vif, vpx, vpr, and nef regulatory genes of SIV and the tat and rev regulatory genes of HIV-1 replicated efficiently in cynomolgus monkeys. This model system can be used to evaluate the efficacy of anti-HIV-1 vaccines directed at the envelope glycoproteins, anti-HIV-1 envelope glycoprotein antiserum or monoclonal antibodies, and anti-HIV-1 drugs designed to inhibit the tat, rev, or env functions.