gebhart/patrepeval huggingface dataset:
Selective loss of B‐cell phenotype in lymphocyte predominant Hodgkin lymphoma (2007)

The neoplastic Reed-Sternberg cells characteristic of classical Hodgkin's lymphoma (cHL) are of B-cell origin but they almost always show striking loss of a range of B-cell-associated molecules. In contrast, the neoplastic cells found in lymphocyte predominant Hodgkin's lymphoma (LPHL) (L&H cells) are traditionally thought of as possessing the full repertoire of features associated with germinal centre B cells (eg BCL-6 expression, 'ongoing' Ig gene mutation). In the present paper, we report an extensive phenotypic analysis of L&H cells which revealed down-regulation of a number of markers associated with the B-cell lineage (eg CD19, CD37) and with the germinal centre maturation stage (eg PAG, LCK). The promoter methylation status of three of these down-regulated genes (CD10, CD19, and LCK) was further studied in microdissected L&H cells, and this revealed that their promoters were unmethylated. In contrast, these genes showed promoter methylation in cell lines derived from CHL. Further investigation of the mechanisms responsible for the deregulation of these molecules in L&H cells may provide new insights into the genetic abnormalities underlying LPHL.
Through-wafer interconnect technology for silicon (2004)

This paper presents a novel method for creating through-wafer interconnects via an anisotropically etched groove in a (100)-silicon wafer. The idea is based on the realization of interconnection lines on the inclined sidewalls of the anisotropically etched grooves, which transfer the metalization to the back side of the wafer without open through-holes. The process itself is compatible with standard semiconductor technology and can be applied at the wafer level resulting in low packaging costs. All post interconnect processes are developed independently and can be added to any IC fabrication process. They are performed at the back side of the wafer at the packaging step, so during this processing the front side of the wafer can be protected from scratches and pollution. The key feature of the method presented is the coating of the anisotropically etched grooves with a polyimide and an electrodeposited photoresist. Further, methods to improve the photoresist uniformity over three-dimensional structures are discussed. Copper interconnects have been realized to show the feasibility of this through-wafer technique for front-to-back electrical interconnections. The thickness of the copper interconnects has been increased by copper electroplating to reduce their electrical resistance further and to increase their mechanical strength.
The Litigation of Financial Innovations (2008)

This paper examines the litigation of patents relating to financial products and services. I show that these grants are being litigated at a rate 27 to 39 times greater than that of patents as a whole. The patents being litigated are disproportionately those issued to individuals and to smaller, private entities, as well as those whose features may proxy for higher quality. Larger entities are disproportionately targeted in litigation. I discuss how the findings are in large part consistent with the theoretical literature on the economics of litigation.
Cloning and antisense oligodeoxynucleotide inhibition of a human homolog of cdc2 required in hematopoiesis. (1992)

Mechanisms triggering the commitment of pluripotent bone marrow stem cells to differentiated lineages such as mononuclear macrophages or multinucleated megakaryocytes are still unknown, although several lines of evidence suggested correlation between cholinergic signaling and hematopoietic differentiation. We now present cloning of a cDNA coding for CHED (cholinesterase-related cell division controller), a human homolog of the Schizosaccharomyces pombe cell division cycle 2 (cdc2)-like kinases, universal controllers of the mitotic cell cycle. Library screening, RNA blot hybridization, and direct PCR amplification of cDNA reverse-transcribed from cellular mRNA revealed that CHED mRNA is expressed in multiple tissues, including bone marrow. The CHED protein includes the consensus ATP binding and phosphorylation domains characteristic of kinases, displays 34-42% identically aligned amino acid residues with other cdc2-related kinases, and is considerably longer at its amino and carboxyl termini. An antisense oligodeoxynucleotide designed to interrupt CHED's expression (AS-CHED) significantly reduced the ratio between CHED mRNA and actin mRNA within 1 hr of its addition to cultures, a reduction that persisted for 4 days. AS-CHED treatment selectively inhibited megakaryocyte development in murine bone marrow cultures but did not prevent other hematopoietic pathways, as evidenced by increasing numbers of mononuclear cells. An oligodeoxynucleotide blocking production of the acetylcholine-hydrolyzing enzyme, butyrylcholinesterase, displayed a similar inhibition of megakaryocytopoiesis. In contrast, an oligodeoxynucleotide blocking production of the human 2Hs cdc2 homolog interfered with production of the human 2Hs cdc2 homolog interfered with cellular proliferation without altering the cell-type composition of these cultures. Therefore, these findings strengthen the link between cholinergic signaling and cell division control in hematopoiesis and implicate both CHED and cholinesterases in this differentiation process.
Characteristics and Production Costs (2004)

2004, ERS participated in the Southern Regional Social Science Association (SRSA) meetings in New Orleans, Louisiana.SRSA provides intellectual leadership in the study of social, economic, political, and behavioral phenomena that have a spatial dimension.ERS researchers presented findings on the economic impacts of public infrastructure projects on rural and urban communities; the impact of school quality on migration in rural areas; the effects of welfare caseload change on local labor markets; the effects of landscape, climate, and settlement on nonmetropolitan migration; and the economic and fiscal conditions in rural recreation counties.
The genome of Methanosarcina mazei: evidence for lateral gene transfer between bacteria and archaea. (2002)

The Archaeon Methanosarcina mazei and related species are of great ecological importance as they are the only organisms fermenting acetate, methylamines and methanol to methane, carbon dioxide and ammonia (in case of methylamines). Since acetate is the precursor of 60% of the methane produced on earth these organisms contribute significantly to the production of this greenhouse gas, e.g. in rice paddies. The 4,096,345 base pairs circular chromosome of M. mazei is more than twice as large as the genomes of the methanogenic Archaea currently completely sequenced (Bult et al., 1996; Smith et al., 1997). 3,371 open reading frames (ORFs) were identified. Based on currently available sequence data 376 of these ORFs are Methanosarcina-specific and 1,043 ORFs find their closest homologue in the bacterial domain. 544 of these ORFs reach significant similarity values only in the bacterial domain. They include 56 of the 102 transposases, and proteins involved in gluconeogenesis, proline biosynthesis, transport processes, DNA-repair, environmental sensing, gene regulation, and stress response. Striking examples are the occurrence of the bacterial GroEL/GroES chaperone system and the presence of tetrahydrofolate-dependent enzymes. These findings might indicate that lateral gene transfer has played an important evolutionary role in forging the physiology of this metabolically versatile methanogen.
Mesenchymal stem cell inhibition of T‐helper 17 cell‐ differentiation is triggered by cell–cell contact and mediated by prostaglandin E2 via the EP4 receptor (2011)

Mesenchymal stem cells (MSCs) inhibit T-cell activation and proliferation but their effects on individual T-cell-effector pathways and on memory versus naïve T cells remain unclear. MSC influence on the differentiation of naïve and memory CD4(+) T cells toward the Th17 phenotype was examined. CD4(+) T cells exposed to Th17-skewing conditions exhibited reduced CD25 and IL-17A expression following MSC co-culture. Inhibition of IL-17A production persisted upon re-stimulation in the absence of MSCs. These effects were attenuated when cell-cell contact was prevented. Th17 cultures from highly purified naïve- and memory-phenotype responders were similarly inhibited. Th17 inhibition by MSCs was reversed by indomethacin and a selective COX-2 inhibitor. Media from MSC/Th17 co-cultures contained increased prostaglandin E2 (PGE2) levels and potently suppressed Th17 differentiation in fresh cultures. MSC-mediated Th17 inhibition was reversed by a selective EP4 antagonist and was mimicked by synthetic PGE2 and a selective EP4 agonist. Activation-induced IL-17A secretion by naturally occurring, effector-memory Th17 cells from a urinary obstruction model was also inhibited by MSC co-culture in a COX-dependent manner. Overall, MSCs potently inhibit Th17 differentiation from naïve and memory T-cell precursors and inhibit naturally-occurring Th17 cells derived from a site of inflammation. Suppression entails cell-contact-dependent COX-2 induction resulting in direct Th17 inhibition by PGE2 via EP4.
Digital Microfluidics for Automated Proteomic Processing (2009)

Clinical proteomics has emerged as an important new discipline, promising the discovery of biomarkers that will be useful for early diagnosis and prognosis of disease. While clinical proteomic methods vary widely, a common characteristic is the need for (i) extraction of proteins from extremely heterogeneous fluids (i.e. serum, whole blood, etc.) and (ii) extensive biochemical processing prior to analysis. Here, we report a new digital microfluidics (DMF) based method integrating several processing steps used in clinical proteomics. This includes protein extraction, resolubilization, reduction, alkylation and enzymatic digestion. Digital microfluidics is a microscale fluid-handling technique in which nanoliter-microliter sized droplets are manipulated on an open surface. Droplets are positioned on top of an array of electrodes that are coated by a dielectric layer - when an electrical potential is applied to the droplet, charges accumulate on either side of the dielectric. The charges serve as electrostatic handles that can be used to control droplet position, and by biasing a sequence of electrodes in series, droplets can be made to dispense, move, merge, mix, and split on the surface. Therefore, DMF is a natural fit for carrying rapid, sequential, multistep, miniaturized automated biochemical assays. This represents a significant advance over conventional methods (relying on manual pipetting or robots), and has the potential to be a useful new tool in clinical proteomics.
Mouse Model for Efficacy Testing of Antituberculosis Agents via Intrapulmonary Delivery (2012)

Here we describe an experimental murine model that allows for aerosolized antituberculosis drug efficacy testing. Intrapulmonary aerosol delivery of isoniazid, capreomycin, and amikacin to mice with pulmonary infection of Mycobacterium tuberculosis demonstrated efficacy in reducing pulmonary bacterial loads similar to that seen by standard drug delivery methods, even when lower concentrations of drugs and fewer doses were used in the aerosolized drug regimens. Interestingly, intrapulmonary delivery of isoniazid also reduced the bacterial load in the spleen.
N-Terminal Fragment of c-FLIP(L) Processed by Caspase 8 Specifically Interacts with TRAF2 and Induces Activation of the NF-κB Signaling Pathway (2004)

Caspase 8 is required not only for death receptor-mediated apoptosis but also for lymphocyte activation in the immune system. FLIP(L), the long-splice form of c-FLIP, is one of the specific substrates for caspase 8, and increased expression of FLIP(L) promotes activation of the NF-kappaB signaling pathway. The synthetic caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk) markedly blocked NF-kappaB activation induced by overexpression of FLIP(L). FLIP(L) is specifically processed by caspase 8 into N-terminal FLIP(p43) and C-terminal FLIP(p12). Only FLIP(p43) was able to induce NF-kappaB activation as efficiently as FLIP(L), and FLIP(p43)-induced NF-kappaB activation became insensitive to zVAD-fmk. In caspase 8-deficient cells, FLIP(p43) provoked NF-kappaB activation only when procaspase 8 or caspase 8(p43) was complemented. FLIP(p43)-induced NF-kappaB activation was profoundly blocked by the dominant-negative TRAF2. Moreover, endogenous TRAF2 interacted specifically with FLIP(p43), and the formation of the FLIP(p43)-caspase 8-TRAF2 tertiary complex was a prerequisite to induction of NF-kappaB activation. zVAD-fmk prevented the recruitment of TRAF2 into the death-inducing signaling complex. Thus, our present results demonstrate that FLIP(p43) processed by caspase 8 specifically interacts with TRAF2 and subsequently induces activation of the NF-kappaB signaling pathway.
Metabolic Impairment Elicits Brain Cell Type‐Selective Changes in Oxidative Stress and Cell Death in Culture (2000)

Abnormalities in oxidative metabolism and inflammation accompany many neurodegenerative diseases. Thiamine deficiency (TD) is an animal model in which chronic oxidative stress and inflammation lead to selective neuronal death, whereas other cell types show an inflammatory response. Therefore, the current studies determined the response of different brain cell types to TD and/or inflammation in vitro and tested whether their responses reflect inherent properties of the cells. The cells that have been implicated in TD-induced neurotoxicity, including neurons, microglia, astrocytes, and brain endothelial cells, as well as neuroblastoma and BV-2 microglial cell lines, were cultured in either thiamine-depleted media or in normal culture media with amprolium, a thiamine transport inhibitor. The activity levels of a key mitochondrial enzyme, alpha-ketoglutarate dehydrogenase complex (KGDHC), were uniquely distributed among different cell types: The highest activity was in the endothelial cells, and the lowest was in primary microglia and neurons. The unique distribution of the activity did not account for the selective response to TD. TD slightly inhibited general cellular dehydrogenases in all cell types, whereas it significantly reduced the activity of KGDHC exclusively in primary neurons and neuroblastoma cells. Among the cell types tested, only in neurons did TD induce apoptosis and cause the accumulation of 4-hydroxy-2-nonenal, a lipid peroxidation product. On the other hand, chronic lipopolysaccharide-induced inflammation significantly inhibited cellular dehydrogenase and KGDHC activities in microglia and astrocytes but not in neurons or endothelial cells. The results demonstrate that the selective cell changes during TD in vivo reflect inherent properties of the different brain cell types.
Metabolite Profiling Identifies a Key Role for Glycine in Rapid Cancer Cell Proliferation (2012)

Metabolic reprogramming has been proposed to be a hallmark of cancer, yet a systematic characterization of the metabolic pathways active in transformed cells is currently lacking. Using mass spectrometry, we measured the consumption and release (CORE) profiles of 219 metabolites from media across the NCI-60 cancer cell lines, and integrated these data with a preexisting atlas of gene expression. This analysis identified glycine consumption and expression of the mitochondrial glycine biosynthetic pathway as strongly correlated with rates of proliferation across cancer cells. Antagonizing glycine uptake and its mitochondrial biosynthesis preferentially impaired rapidly proliferating cells. Moreover, higher expression of this pathway was associated with greater mortality in breast cancer patients. Increased reliance on glycine may represent a metabolic vulnerability for selectively targeting rapid cancer cell proliferation.
Molecular cloning and chromosomal assignment of the human homolog of int-1, a mouse gene implicated in mammary tumorigenesis. (1984)

Viral mammary tumorigenesis in mice is frequently initiated by proviral activation of a highly conserved cellular gene called int-1. We have cloned the human homolog of this putative mammary oncogene and compared its structure to that of the mouse gene by heteroduplex analysis. The human int-1 gene was localized on chromosome 12 by use of somatic cell hybrids.
Excimer laser crystallized poly-Si TFTs on plastic substrates (2002)

Excimer laser crystallized poly-Si TFTs, integrated both for drive circuits and pixels, on a glass substrate for use in various applications, such as, flat panel display are now available in the market. These poly-Si TFTs on glass are generally prepared by excimer laser crystallization of plasma enhanced chemical vapor deposited amorphous silicon films, which, are generally deposited in the substrate temperature range of 300 degree(s)C-400 degree(s)C. Changing the TFT backplate from glass to plastic will reduce the wight, but transparent plastic substrates are generally only temperature-resistant up to 125 degree(s)C. We have focused therefore, on reducing the maximum processing temperature to 110 degree(s)C. Our approach utilizes sputtered a- Si films for crystallization, because they contain no hydrogen and can be crystallized by an excimer laser even if deposited at room temperature. We report high-quality poly-Si obtained by pulse laser crystallization on a plastic substrate coated with a buffer layer. Transmission electron microscope was used to confirm the crystallinity of the films. A doping technique for source and drain compatible with a low temperature wide area substrate, based on excimer laser annealing, has been developed. Self-aligned top-gate TFTs fabricated on a plastic substrate at a substrate temperature of 100 degree(s)C are reported. Transistor field effect mobility of 250 cm<SUP>2</SUP>/V.s and s sub-threshold swing of 0.16 V/decade were measured in these devices.
Synthetic Studies on Cephalotaxus Alkaloids. A synthesis of (.+-.)-Cephalotaxine. (1993)

A stereoselective total synthesis of (±)-cephalotaxine (1) has been achieved. Palladium-catalyzed [3+2] cycloaddition of 2-(trimethylsilylmethyl)-2-propenyl acetate to the nitrostyrene 7 gave the methylenecyclopentane 6, which was converted into the α-sulfinylacetamide 19. Treatment of 19 either with trifluoroacetic anhydride in dichloromethane at room temperature or with p-toluenesulfonic acid in boiling 1, 2-dichloroethane gave the benzazepinone 20 in good yield, and this was transformed to (±)-1 via Hanaoka's key intermediate 4.
Transient Ischemic Attacks and Minor Stroke During Sleep (1995)

Snoring and obstructive sleep apnea not only increase the statistical risk of CVA but could be the proximal trigger that precipitates these events during sleep. These two cases provide clinical support for this relationship. Successful diagnosis and treatment of obstructive sleep apnea in the patient with transient ischemic attacks and minor stroke may be an important tool for preventing recurrence.
CD20 monoclonal antibody (rituximab) for therapy of Epstein-Barr virus lymphoma after hemopoietic stem-cell transplantation (2000)

After bone marrow transplantation (BMT) using T-cell-depleted marrow from an unrelated donor or HLA-mismatched related donor, the risk of developing lymphoproliferative disease associated with the Epstein-Barr virus (EBV) ranges from 1% to 25%. We have shown that administration of donor-derived EBV-specific cytotoxic T lymphocytes (CTL) is effective prophylaxis and treatment for this complication, and we routinely generate CTL for high-risk patients. However, EBV lymphoma can occur in recipients of matched-sibling transplants for whom CTL are unavailable or in patients for whom CTL administration is contraindicated. We report on 3 such patients, who were successfully and safely treated with rituximab, a CD20 monoclonal antibody. The patients remain disease free 7, 8, and 9 months, respectively, after therapy. We conclude that CD20 antibody may be a useful alternative treatment strategy in patients with EBV lymphoma after BMT. (Blood. 2000;95:1502-1505)
Experimental investigations of organic molecular nonlinear optical polarizabilities. 1. Methods and results on benzene and stilbene derivatives (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTExperimental investigations of organic molecular nonlinear optical polarizabilities. 1. Methods and results on benzene and stilbene derivativesLap Tak Cheng, Wilson Tam, Sylvia H. Stevenson, Gerald R. Meredith, Geert Rikken, and Seth R. MarderCite this: J. Phys. Chem. 1991, 95, 26, 10631–10643Publication Date (Print):December 1, 1991Publication History Published online1 May 2002Published inissue 1 December 1991https://pubs.acs.org/doi/10.1021/j100179a026https://doi.org/10.1021/j100179a026research-articleACS PublicationsRequest reuse permissionsArticle Views2013Altmetric-Citations731LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
Identification and Characterization of a Liver Stage-Specific Promoter Region of the Malaria Parasite Plasmodium (2010)

During the blood meal of a Plasmodium-infected mosquito, 10 to 100 parasites are inoculated into the skin and a proportion of these migrate via the bloodstream to the liver where they infect hepatocytes. The Plasmodium liver stage, despite its clinical silence, represents a highly promising target for antimalarial drug and vaccine approaches. Successfully invaded parasites undergo a massive proliferation in hepatocytes, producing thousands of merozoites that are transported into a blood vessel to infect red blood cells. To successfully develop from the liver stage into infective merozoites, a tight regulation of gene expression is needed. Although this is a very interesting aspect in the biology of Plasmodium, little is known about gene regulation in Plasmodium parasites in general and in the liver stage in particular. We have functionally analyzed a novel promoter region of the rodent parasite Plasmodium berghei that is exclusively active during the liver stage of the parasite. To prove stage-specific activity of the promoter, GFP and luciferase reporter assays have been successfully established, allowing both qualitative and accurate quantitative analysis. To further characterize the promoter region, the transcription start site was mapped by rapid amplification of cDNA ends (5'-RACE). Using promoter truncation experiments and site-directed mutagenesis within potential transcription factor binding sites, we suggest that the minimal promoter contains more than one binding site for the recently identified parasite-specific ApiAP2 transcription factors. The identification of a liver stage-specific promoter in P. berghei confirms that the parasite is able to tightly regulate gene expression during its life cycle. The identified promoter region might now be used to study the biology of the Plasmodium liver stage, which has thus far proven problematic on a molecular level. Stage-specific expression of dominant-negative mutant proteins and overexpression of proteins normally active in other life cycle stages will help to understand the function of the proteins investigated.