gebhart/patrepeval huggingface dataset:
Immunosuppressive Effects of CCL17 on Pulmonary Antifungal Responses during Pulmonary Invasive Aspergillosis (2005)

Aspergillus fumigatus-sensitized CCR4-deficient (CCR4-/-) mice exhibit an accelerated clearance of conidia during fungal asthma. In the present study, we examined the roles of CCL17 and CCL22, two CCR4 ligands, during pulmonary invasive aspergillosis in neutropenic mice. Kaplan-Meier survival curve analysis revealed that wild-type C57BL/6 (CCR4+/+) mice were significantly protected from the lethal effects of Aspergillus compared with their wild-type controls following systemic neutralization with anti-CCL17 but not anti-CCL22 antibodies. Systemic neutralization of CCL17 significantly increased whole-lung CCL2 levels. Mouse survival and histological analysis revealed that the receptor mediating the deleterious effects of CCL17 was CCR4 since mice genetically deficit in CCR4 (CCR4-/-) did not develop invasive aspergillosis. Enzyme-linked immunosorbent assay analysis of whole-lung samples at day 2 after conidial challenge in neutrophil-depleted CCR4-/- and CCR4+/+ mice revealed that whole-lung IL-12 levels were significantly increased in the CCR4-/- group compared with the wild-type group. Also at day 2 after conidial challenge, significantly greater numbers of CD11c+ F4/80+ and CD11c+/CD86+ but fewer CD3/NK1.1+ cells were present in the lungs of CCR4-/- mice compared with their wild-type counterparts. Thus, CCL17-CCR4 interactions dramatically impair the pulmonary antifungal response against A. fumigatus in neutropenic mice.
DAPK1 variants are associated with Alzheimer's disease and allele-specific expression (2006)

Genetic factors play an important role in the etiology of late-onset Alzheimer's disease (LOAD). We tested gene-centric single nucleotide polymorphisms (SNPs) on chromosome 9 and identified two SNPs in the death-associated protein kinase, DAPK1, that show significant association with LOAD. SNP rs4878104 was significantly associated with LOAD in our discovery case-control sample set (WU) and replicated in each of two initial validation case-control sample sets (P<0.05, UK1, SD). The risk-allele frequency of this SNP showed a similar direction in three other case-control sample sets. A meta-analysis of the six sample sets combined, totaling 2012 cases and 2336 controls, showed an allelic P-value of 0.0016 and an odds ratio (OR) of 0.87 (95%CI: 0.79-0.95). Minor allele homozygotes had a consistently lower risk than major allele homozygotes in the discovery and initial two replication sample sets, which remained significant in the meta-analysis of all six sample sets (OR=0.7, 95%CI: 0.58-0.85), whereas the risk for heterozygous subjects was not significantly different from that of major allele homozygotes. A second SNP, rs4877365, which is in high linkage disequilibrium with rs4878104 (r2=0.64), was also significantly associated with LOAD (meta P=0.0017 in the initial three sample sets). Furthermore, DAPK1 transcripts show differential allelic gene expression, and both rs4878104 and rs4877365 were significantly associated with DAPK1 allele-specific expression (P=0.015 to <0.0001). These data suggest that genetic variation in DAPK1 modulates susceptibility to LOAD.
Synthesis and Evaluation of Novel Inhibitors of Pim-1 and Pim-2 Protein Kinases (2008)

The Pim protein kinases are frequently overexpressed in prostate cancer and certain forms of leukemia and lymphoma. 5-(3-Trifluoromethylbenzylidene)thiazolidine-2,4-dione (4a) was identified by screening to be a Pim-1 inhibitor and was found to attenuate the autophosphorylation of tagged Pim-1 in intact cells. Although 4a is a competitive inhibitor with respect to ATP, a screen of approximately 50 diverse protein kinases demonstrated that it has high selectivity for Pim kinases. Computational docking of 4a to Pim-1 provided a model for lead optimization, and a series of substituted thiazolidine-2,4-dione congeners was synthesized. The most potent new compounds exhibited IC(50)s of 13 nM for Pim-1 and 2.3 microM for Pim-2. Additional compounds in the series demonstrated selectivities of more than 2500-fold and 400-fold for Pim-1 or Pim-2, respectively, while other congeners were essentially equally potent toward the two isozymes. Overall, these compounds are new Pim kinase inhibitors that may provide leads to novel anticancer agents.
New approaches for on-chip power switching noise reduction (2002)

The effect of power supply switching noise is gaining importance with increasing switching speeds and density of VLSI chips. Yet, today's design methodology does not adequately address this problem at chip level. This paper proposes two approaches for on-chip power switching noise reduction. The first approach aims at reducing Delta-I noise by inserting decoupling capacitors in an optimized manner. The second approach reduces the switching noise by wire-sizing power bus segments near each power pin. Both approaches are assessed by simulation of a circuit, in which power supply rails are modeled as lossy transmission lines. The results of the simulated example demonstrate the effectiveness of our approaches.
Robotic Surgery — Squeezing into Tight Places (2006)

Interview with Dr. Lawrence Cohn on robotic surgery. (07:34)Download Back in the 1980s, the rationale for building a surgical robot was the stuff of science fiction. Intent on providing “a doctor in every foxhole,” military strategists envisioned a severely wounded soldier being loaded into a battlefield ambulance equipped with a robot so that a surgeon at a Mobile Army Surgical Hospital, or MASH unit, miles away could perform life-saving telesurgery to prevent exsanguination or some other physiological catastrophe. The National Aeronautics and Space Administration had a similar vision. A terrestrial physician would be able to remove an acutely inflamed appendix from a patient aboard a robot-equipped space station. In . . .
Transduction and expression of the human carcinoembryonic antigen gene in a murine colon carcinoma cell line. (1991)

A cell line derived from the mouse colon adenocarcinoma, MC-38, has been transduced with a retroviral construct containing complementary DNA encoding the human carcinoembryonic antigen (CEA) gene. MC-38, which forms tumors in syngeneic C57BL/6 mice, has been extensively studied as a target for active immunotherapy. Individual transduced clones that express high levels of cell surface CEA were isolated, and two clones, termed MC-38-ceal and MC-38-cea2, were extensively characterized. The levels of CEA found on the surface of these clones were considerably higher than that found in a moderately differentiated human colon carcinoma cell line (WiDr) and were comparable to those found on the human colon carcinoma cell lines GEO and CBS (among the highest CEA-expressing cells reported). Further analysis demonstrated that the CEA expressed in the MC-38-cea1 clone had a similar molecular weight to native CEA (Mr 180,000), but the MC-38-cea2 cell line expressed a single Mr 70,000 glycosylated immunoreactive product. Seven anti-CEA monoclonal antibodies were found to react with both clones. The CEA gene present in the MC-38-cea2 clone was partially sequenced and was found to contain a deletion of two of the three repeated domains present in CEA. These results provide a basis for future studies to map immunodominant epitopes of CEA and to develop a syngeneic model system that may aid in the design of reagents and protocols to study active and passive immunotherapy directed against a carcinoma expressing human CEA.
P2X7Receptors Mediate ATP Release and Amplification of Astrocytic Intercellular Ca2+Signaling (2006)

Modulation of synaptic transmission and brain microcirculation are new roles ascribed to astrocytes in CNS function. A mechanism by which astrocytes modify neuronal activity in the healthy brain depends on fluctuations of cytosolic Ca2+ levels, which regulate the release of "gliotransmitters" via an exocytic pathway. Under pathological conditions, however, the participation of other pathways, including connexin hemichannels and the pore-forming P2X7R, have been proposed but remain controversial. Through the use of genetically modified 1321N1 human astrocytoma cells and of spinal cord astrocytes derived from neonatal Cx43- and P2X7R-null mice, we provide strong evidence that P2X7Rs, but not Cx43 hemichannels, are sites of ATP release that promote the amplification of Ca2+ signal transmission within the astrocytic network after exposure to low divalent cation solution. Moreover, our results showing that gap junction channel blockers (heptanol, octanol, carbenoxolone, flufenamic acid, and mefloquine) are antagonists of the P2X7R indicate the inadequacy of using these compounds as evidence for the participation of connexin hemichannels as sites of gliotransmitter release.
Gro Harlem Brundtland, la madre de la sostenibilidad (2007)

El concepto de sostenibilidad, tan maleado últimamente, estará siempre asociado a esta médica noruega. Tanto desde la COmisión de Medio Ambiente y Desarrollo de Naciones Unidas como desde la Organización Mundial de la Salud, ha situado en la agenda política mundial temas lacerantes y ha intentado favorecer a las capas más pobres y a los países menos desarrollados.
Advanced SOI substrate manufacturing (2004)

300 mm SOI wafers with sub-100nm thick active Si layers are currently produced in large quantities and used in advanced microprocessor circuits. To further enhance the performance of the next generation of devices, strained Si layers on insulator are being developed. The lattice mismatch between silicon and SiGe alloys, combined with layer transfer through the Smart Cut/spl trade/ technology allow forming two types of strained Si - strained Si on SiGe on insulator, known as SGOI, and strained Si directly on insulator, known as sSOI. Fabrication methods and wafer characteristics for SOI, SGOI, and sSOI are discussed here.
Mechanisms of skeletal muscle injury and repair revealed by gene expression studies in mouse models (2007)

Common acute injuries to skeletal muscle can lead to significant pain and disability. The current therapeutic approaches for treating muscle injuries are dependent on the clinical severity but not on the type of injury. In the present studies, the pathophysiology and molecular pathways associated with two different types of skeletal muscle injury, one induced by direct destruction of muscle tissue (i.e. FI) and the other induced by a contractile overload (more specifically high-force eccentric contractions, i.e. CI) were compared side by side. Histopathological evaluation and measurements of muscle strength were accompanied by analyses of expression for 12 488 known genes at four time points ranging from 6 h to 7 days after injury. Real-time RT-PCR was used to confirm some of the injury type differences in the temporal profiles of gene expression. Our data revealed several pools of genes, including early induction of transcription, myogenic and stress-responsive factors, common for both types of injury as well as pools of genes expressed specifically with one of the injury types. Only CI activated a set of genes associated with the repair of impaired proteins and structures including genes related to apoptosis, whereas FI uniquely activated gene sets involved in extensive inflammatory responses, tissue remodelling, angiogenesis and myofibre/extracellular matrix synthesis. In conclusion, knowledge of the sets of genes associated specifically with the nature of the injury may have application for development of new strategies for acceleration of the recovery process in injured skeletal muscle.
Development of Domestic Feta Cheese (1964)

A manufacturing method for Feta cheese was developed using pasteurized milk, Streptococcus lactis and Lactobacillus casei cultures, a pregastrie esterase (Capalase-KL), and liquid rennet. Cheese had a pleasant acetic acid, salty and mild characteristic rancid flavor, and a smooth, creamy, soluble, and sliceable body.
Localization of Nonpancreatic Secretory Phospholipase A 2 in Normal and Atherosclerotic Arteries (1997)

Secretory nonpancreatic type II phospholipase A2 (snpPLA2) hydrolyzes fatty acids at the sn-2 position in phospholipids releasing free fatty acids (FFAs) and lysophospholipids. These products may act as intracellular second messengers or can be further metabolized into proinflammatory lipid mediators. The presence of snpPLA2 in extracellular fluids and serum during inflammation has suggested a role of the enzyme in this process. However, the presence of snpPLA2 in a variety of normal tissues suggests that snpPLA2 may also have physiological functions. Atherosclerosis appears to have an inflammatory component. Here we report on the snpPLA2 localization in normal and atherosclerotic lesions and on the properties of the isolated enzyme. A strong snpPLA2 immunoreactivity was observed in the arterial media that was colocalized with alpha-actin-positive vascular smooth muscle cells (SMCs) in both normal and atherosclerotic vessels. In aortic atherosclerotic lesions, snpPLA2 was observed colocalized with CD68-positive macrophages and HHF-35-positive SMCs and extracellularly in the lipid core. snpPLA2 was isolated from human normal arteries and from aorta with lesions. The enzyme was isolated by acid extraction of normal arterial tissues followed by immunoaffinity chromatography. The purified snpPLA2 had an expected molecular weight of 14 kD by polyacrylamide gel electrophoresis and appeared as a single band in immunoblotting. The enzymatic activity was followed by measuring release of fatty acids from phospholipid liposomes or LDL as substrates. The enzymatic activity was inhibited with two specific inhibitors for human snpPLA2: (1) monoclonal antibody 187 and (2) LY311727, a synthetic selective inhibitor. The mRNA for snpPLA2 was detected with reverse transcriptase polymerase chain reaction. These results indicate that snpPLA2 is present in human arteries and that it is able to hydrolyze phospholipids in LDL. The results support the hypothesis that snpPLA2 can release proinflammatory lipids at places of LDL deposition in the arterial wall.
Functional identification of regulatory elements within the promoter region of platelet-derived growth factor 2. (1989)

Human platelet-derived growth factor (PDGF) is composed of two polypeptide chains, PDGF-1 and PDGF-2, the human homolog of the v-sis oncogene. Deregulation of PDGF-2 expression can confer a growth advantage to cells possessing the cognate receptor and, thus, may contribute to the malignant phenotype. We investigated the regulation of PDGF-2 mRNA expression during megakaryocytic differentiation of K562 cells. Induction by 12-O-tetradecanoylphorbol-13-acetate (TPA) led to a greater than 200-fold increase in PDGF-2 transcript levels in these cells. Induction was dependent on protein synthesis and was not enhanced by cycloheximide exposure. In our initial investigation of the PDGF-2 promoter, a minimal promoter region, which included sequences extending only 42 base pairs upstream of the TATA signal, was found to be as efficient as 4 kilobase pairs upstream of the TATA signal in driving expression of a reporter gene in uninduced K562 cells. We also functionally identified different regulatory sequence elements of the PDGF-2 promoter in TPA-induced K562 cells. One region acted as a transcriptional silencer, while another region was necessary for maximal activity of the promoter in megakaryoblasts. This region was shown to bind nuclear factors and was the target for trans-activation in normal and tumor cells. In one tumor cell line, which expressed high PDGF-2 mRNA levels, the presence of the positive regulatory region resulted in a 30-fold increase in promoter activity. However, the ability of the minimal PDGF-2 promoter to drive reporter gene expression in uninduced K562 cells and normal fibroblasts, which contained no detectable PDGF-2 transcripts, implies the existence of other negative control mechanisms beyond the regulation of promoter activity.
Reduced Volume And Hexa-Source Marine Acquisition In The Barents Sea (2018)

In this paper we present results from a reduced volume and a hexa-source test recently conducted in the Barents Sea offshore Norway. In this relatively shallow water environment with 200-300m water depth, we show that good quality seismic imaging can be obtained with significantly smaller air-gun source volumes than what the marine seismic industry have traditionally deployed. Furthermore, we present data results from, to the best of our knowledge, an industry first wide source tow hexa-source acquisition, with very high resolution and quality down to the reservoir level of 1-2sec seismic two-way travel time.
Runaway growth in two-dimensional electrodeposition (1996)

We have investigated electrochemical deposition of copper along a very thin gold edge. Exploration of the transition between compact and branched morphologies reveals a faceted morphology, at very low current densities, which is composed of a pentagonal arrangement of twinned crystals. For higher current densities, repeated nucleation gives a tip-splitting regime. A transition between tip-splitting and side-branching morphology is obtained by inducing anisotropy on the substrate, in the form of microscopic teflon furrows. The growth speed of the different morphologies is very different.
Tubular proteinuria in acute kidney injury: a critical evaluation of current status and future promise (2010)

The diagnosis and prognosis of acute kidney injury (AKI) by current clinical means is inadequate. Biomarkers of kidney injury that are easily measured and unaffected by physiological variables could revolutionize the management of AKI. Our objective was to systematically review the diagnostic and prognostic utility of urine and serum biomarkers of AKI in humans. We searched MEDLINE, PubMed and EMBASE databases (January 2000-August 2009) for biomarker studies that could be classified into the following categories: (a) confirmation of the diagnosis of established AKI, (b) early prediction of AKI, and (c) prognostication of AKI. We identified 54 manuscripts published since 2000 that met our inclusion and exclusion criteria. Urinary interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl-beta-D-glucosaminidase (NAG) are potentially useful biomarkers for the diagnosis of established AKI. Urinary NGAL, IL-18, and liver-type fatty acid binding protein, and serum NGAL and cystatin C represent the most promising biomarkers for early prediction of AKI. Urinary cystatin C, alpha1-microglobulin, NAG and retinol-binding protein may be useful to predict severity and outcomes of AKI. In conclusion, we identified several studies of promising biomarkers for the diagnosis, prediction and prognostication of AKI. However, we note several limitations, including small sample sizes, inadequate gold standard, exclusion of patients with chronic kidney disease, incomplete statistical analyses, utilization of research-based assays and a paucity of studies examining prediction for clinical outcomes. Future studies will need to address these limitations in order for further progress to be made.
[Serum immunoglobulins in chronic diseases of the gastrointestinal organs in children]. (1977)

Download at: http://se.wtb.tue.nl/~vanbeek/. Several techniques exist for index reduction and consistent initialization of higher index DAEs. Many such techniques change the original set of equations by differentiation, substitution, and/or introduction of new variables. This paper introduces substitute equations as a new language element. By means of a substitute equation, the value of a continuous variable or its time derivative is specified by an expression. This expression is evaluated each time that the variable or its time derivative, respectively, is referenced in the model. The advantage of substitute equations is that they enable index reduction and consistent initialization of higher index DAEs without changing the original equations; no existing variables are removed and no new variables are introduced. Substitute equations can also be used to enable the use of general purpose numerical solvers for equations where one or more of the unknowns are discontinuous, and they can be used to prevent functions to be called outside of their domain.
Substitutions in Conserved Dodecapeptide Motifs That Uncouple the DNA Binding and DNA Cleavage Activities of PI-SceI Endonuclease (1995)

The PI-SceI endonuclease from yeast belongs to a protein family whose members contain two conserved dodecapeptide motifs within their primary sequences. The function of two acidic residues within these motifs, Asp218 and Asp326, was examined by substituting alanine, asparagine, and glutamic acid residues at these positions. All of the purified mutant proteins bind to the PI-SceI recognition site with the same affinity and specificity as the wild-type enzyme. By contrast, substituting alanine or asparagine amino acids at the two positions completely eliminates strand cleavage of substrate DNA, whereas substitution with glutamic acid markedly reduces the cleavage activity. Experiments using nicked substrates demonstrate that the wild-type enzyme shows no strand preference during cleavage. These results are consistent with a model in which both acidic residues are part of a single catalytic center that cleaves both DNA strands. Furthermore, substrate binding by wild-type PI-SceI stimulates hydroxyl radical or hydroxide ion attack at the cleavage site while binding by the alanine-substituted proteins either stimulates this attack significantly less or protects the DNA at this position. These finding are discussed in terms of possible reaction mechanisms for PI-SceI-mediated endonucleolytic cleavage.
Kinetic measurements of molecular interactions by spectrofluorometry (1993)

The kinetics of antibody-antigen interactions are reviewed in terms of general trends observed in both polyclonal and monoclonal antibody populations. Anti-fluorescein antibodies are featured in the review as model proteins to explore fluorescence-based kinetic measurements. Since the fluorescence of the fluorescein ligand is significantly quenched upon interaction with both polyclonal and monoclonal anti-fluorescein antibodies, the quenching parameter can be advantageously employed in measuring the rates of association (k1) and dissociation (k2). The near diffusion-limited k1 rates and the prolonged k2 rates are discussed in terms of antibody affinity and mechanisms involved in ligand binding. Specific prolongation effects of reagents, such as anti-metatype antibodies, on the dissociation rate are discussed in terms of antibody dynamics and conformational substates.