gebhart/patrepeval huggingface dataset:
Social Network Analysis with Content and Graphs (2013)

Social network analysis has undergone a renaissance with the ubiquity and quantity of content from social media, web pages, and sensors. This content is a rich data source for constructing and analyzing social networks, but its enormity and unstructured nature also present multiple challenges. Work at Lincoln Laboratory is addressing the problems in constructing networks from unstructured data, analyzing the community structure of a network, and inferring information from networks. Graph analytics have proven to be valuable tools in solving these challenges. Through the use of these tools, Laboratory researchers have achieved promising results on real-world data. A sampling of these results are presented in this article.
Analysis of a Capsular Polysaccharide Biosynthesis Locus ofBacteroides fragilis (1999)

A major clinical manifestation of infection with Bacteroides fragilis is the formation of intra-abdominal abscesses, which are induced by the capsular polysaccharides of this organism. Transposon mutagenesis was used to locate genes involved in the synthesis of capsular polysaccharides. A 24,454-bp region was sequenced and found to contain a 15,379-bp locus (designated wcf) with 16 open reading frames (ORFs) encoding products similar to those encoded by genes of other bacterial polysaccharide biosynthesis loci. Four genes encode products that are similar to enzymes involved in nucleotide sugar biosynthesis. Seven genes encode products that are similar to sugar transferases. Two gene products are similar to O-acetyltransferases, and two products are probably involved in polysaccharide transport and polymerization. The product of one ORF, WcfH, is similar to a set of deacetylases of the NodB family. Deletion mutants demonstrated that the wcf locus is necessary for the synthesis of polysaccharide B, one of the two capsular polysaccharides of B. fragilis 9343. The virulence of the polysaccharide B-deficient mutant was comparable to that of the wild type in terms of its ability to induce abscesses in a rat model of intra-abdominal infection.
Regulation of Dioxin Receptor Function by Omeprazole (1997)

The intracellular dioxin (aryl hydrocarbon) receptor mediates signal transduction by dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) and related environmental pollutants and functions as a ligand-activated transcription factor. In this study we have examined the effects on dioxin receptor function of a potentially novel ligand, omeprazole, which is widely clinically used as a gastric anti-ulcer drug. In primary human hepatocytes omeprazole potently induced cytochrome P4501A1 mRNA expression, whereas this effect was not detected in mouse primary hepatocytes. In human hepatoma cells omeprazole was found to induce transcription of reporter genes via the xenobiotic response element that is recognized by the ligand-activated dioxin receptor. In contrast, the human dioxin receptor was not activated by omeprazole upon expression in a receptor-deficient mouse hepatoma cell line. In a reconstituted yeast (Saccharomyces cerevisiae) model system, however, both the mouse and human dioxin receptors were potently activated by omeprazole. Although omeprazole failed to displace dioxin in in vitro ligand binding assays, a residue within the ligand binding domain that is critical for dioxin binding in vitro was also critical for omeprazole responsiveness in vivo. Consistent with this observation, both omeprazole and dioxin responsiveness of the dioxin receptor was inhibited in mutant yeast cells expressing low levels of the molecular chaperone hsp90 that is critical for ligand binding activity. The sulfoxide group that is essential for formation of a planar conversion product of omeprazole was found to be critical for dioxin receptor activation. Taken together, these data suggest that omeprazole represents a precursor for a novel class of dioxin receptor agonists that are bona fide dioxin receptor ligands but generated in a strictly species-specific manner.
Induction of Immunologic Memory in Infants Primed with Haemophilus influenzae Type b Conjugate Vaccines (1993)

The ability of different Haemophilus influenzae type b conjugate vaccines to induce immunologic memory was compared in 381 infants who were vaccinated with one of three conjugate vaccines beginning at 2 months of age. All infants were vaccinated with unconjugated type b capsular polysaccharide, polyribosylribitol phosphate (PRP), at 12 months. In each group, high antibody responses were detected by 6-9 days after vaccination. One month after receiving PRP, infants primed with PRP conjugated to the outer membrane protein of Neisseria meningitidis or PRP oligomers conjugated to the cross-reactive mutant diphtheria protein, CRM197, had twofold higher total anti-PRP antibody concentrations than did infants primed with PRP conjugated to tetanus toxoid (P < .005). After the conjugate and the PRP boost, notable differences were present among vaccine groups with respect to the magnitude of the IgG anti-PRP antibody concentrations and light chain variable region usage as determined by idiotypic analysis. Thus, each of the conjugate vaccines primed infants for the ability to evoke memory antibody responses to PRP, but qualitative and quantitative differences in priming induced by different vaccines may affect their ability to confer protection against disease.
Novel combinations with oxaliplatin. (2000)

Oxaliplatin (Eloxatin) is a novel antineoplastic platinum derivative that may exert its cytotoxic effects by blocking DNA replication/transcription, thus resulting in cell death in proliferating cells, as well as apoptosis. Oxaliplatin is often more potent than other platinums such as cisplatin (Platinol) in vitro, and shows greater efficacy in preclinical studies against many tumor cell lines, including some that are resistant to cisplatin and carboplatin (Paraplatin). Oxaliplatin is approved for use with the fluoropyrimidines in the treatment of metastatic colorectal cancer in Asia, Latin America, and Europe. In light of the broad efficacy of oxaliplatin in several solid tumors and the encouraging preclinical data on combination therapy with novel agents (e.g., thymidylate synthase inhibitors, epidermal growth factor-receptor antagonists, microtubule interactive agents), this article will review the published literature on novel combinations that have been tested in the laboratory and/or the clinic.
Anti-CD33 monoclonal antibody and etoposide/cytosine arabinoside combinations for the ex vivo purification of bone marrow in acute nonlymphocytic leukemia (1991)

Pharmacologic and immunologic methods of ex-vivo bone marrow (BM) purging for acute nonlymphocytic leukemia (ANLL) were combined to augment the effect of either method alone. Etoposide (VP16; 20 to 30 micrograms/mL) with or without cytosine arabinoside (Ara C; 10 mg/mL) was used in tandem with the anti-CD33 monoclonal antibody (MoAb), MY9, chosen because CD33 is found on the stem cell pool in the majority of patients with ANLL. The agents were tested singly or sequentially, with a 1-hour incubation of the drugs preceding complement-mediated lysis using MY9. VP16 combined with Ara C killed up to 3.9 +/- 0.3 and 5.11 +/- 0.4 logs of the human ANLL cell lines HL60 and K562 at drug concentrations that killed only 1.2 +/- 0.1 logs of normal committed granulocyte/macrophage stem cells (CFU-GM). Adding a single exposure of the MY9 and complement (C′) to the drug-treated cells, greater than 5.4 logs of HL60 were killed. Similar to other pharmacologic agents, no differential kill for clonagenic leukemic cells (colony-forming unit- leukemia; CFU-L) from patients with ANLL was seen for drug only treated blasts versus normal CFU-granulocyte-macrophage (CFU-GM), with less than 1 log CFU-L kill at drug concentrations that spared 1 log of CFU- GM. Similarly, only 1.1 +/- 0.3 logs of ANLL CFU-L were eliminated using MY9 and C′. However, with the sequential VP16/Ara C----MY9 + C′ treatment, synergy was demonstrated and 2.6 +/- 0.3 logs of CFU-L were eliminated. Because CD33 is also found on the normal CFU-GM pool, two- stage long-term BM cultures were performed to determine pluripotent stem cell elimination by the drug/MoAb purging combination. No difference of CFU-GM or BFU-E production at 4 to 6 weeks of culture for VP16/Ara C, MY9 + C′, or VP16/AraC----My9 + C′ treated cells was seen compared with untreated controls indicating sparing of early progenitor cells. Sequential ex vivo treatment of human ANLL CFU-L with VP16/Ara C followed by complement-mediated lysis using MY9 synergistically kills CFU-L while sparing early normal hematopoietic progenitor cells, and thus may be a more effective way to purge BM than either alone.
Meme tags and community mirrors (1998)

Article Free Access Share on Meme tags and community mirrors: moving from conferences to collaboration Authors: Richard Borovoy MIT Media Laboratory, 20 Ames Street, Cambridge, MA MIT Media Laboratory, 20 Ames Street, Cambridge, MAView Profile , Fred Martin MIT Media Laboratory, 20 Ames Street, Cambridge, MA MIT Media Laboratory, 20 Ames Street, Cambridge, MAView Profile , Sunil Vemuri MIT Media Laboratory, 20 Ames Street, Cambridge, MA MIT Media Laboratory, 20 Ames Street, Cambridge, MAView Profile , Mitchel Resnick MIT Media Laboratory, 20 Ames Street, Cambridge, MA MIT Media Laboratory, 20 Ames Street, Cambridge, MAView Profile , Brian Silverman MIT Media Laboratory, 20 Ames Street, Cambridge, MA MIT Media Laboratory, 20 Ames Street, Cambridge, MAView Profile , Chris Hancock MIT Media Laboratory, 20 Ames Street, Cambridge, MA MIT Media Laboratory, 20 Ames Street, Cambridge, MAView Profile Authors Info & Claims CSCW '98: Proceedings of the 1998 ACM conference on Computer supported cooperative workNovember 1998 Pages 159–168https://doi.org/10.1145/289444.289490Online:01 November 1998Publication History 112citation991DownloadsMetricsTotal Citations112Total Downloads991Last 12 Months46Last 6 weeks10 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Disruption of Microtubules Post-Virus Entry Enhances Adeno-Associated Virus Vector Transduction (2016)

Perinuclear retention of viral particles is a poorly understood phenomenon observed during many virus infections. In this study, we investigated whether perinuclear accumulation acts as a barrier to limit recombinant adeno-associated virus (rAAV) transduction. After nocodazole treatment to disrupt microtubules at microtubule-organization center (MT-MTOC) after virus entry, we observed higher rAAV transduction. To elucidate the role of MT-MTOC in rAAV infection and study its underlying mechanisms, we demonstrated that rAAV's perinuclear localization was retained by MT-MTOC with fluorescent analysis, and enhanced rAAV transduction from MT-MTOC disruption was dependent on the rAAV capsid's nuclear import signals. Interestingly, after knocking down RhoA or inhibiting its downstream effectors (ROCK and Actin), MT-MTOC disruption failed to increase rAAV transduction or nuclear entry. These data suggest that enhancement of rAAV transduction is the result of increased trafficking to the nucleus via the RhoA-ROCK-Actin pathway. Ten-fold higher rAAV transduction was also observed by disrupting MT-MTOC in brain, liver, and tumor in vivo. In summary, this study indicates that virus perinuclear accumulation at MT-MTOC is a barrier-limiting parameter for effective rAAV transduction and defines a novel defense mechanism by which host cells restrain viral invasion.
Characterization of the Importance ofStaphylococcus epidermidisAutolysin and Polysaccharide Intercellular Adhesin in the Pathogenesis of Intravascular Catheter–Associated Infection in a Rat Model (2001)

A rat central venous catheter (CVC) infection model was used to assess the importance of the proteinacious autolysin (AtlE) and the polysaccharide intercellular adhesin (PIA) in the pathogenesis of Staphylococcus epidermidis CVC-associated infection. Wild-type (wt) S. epidermidis O-47 was significantly more likely to cause a CVC infection than was either of the isogenic mutant strains (AtlE-negative [O-47mut1] or PIA-negative [O-47mut2]). Bacteria were retrieved from the explanted catheters of 87.5% of rats inoculated with S. epidermidis O-47, compared with 25% of rats challenged with either S. epidermidis O-47mut1 or O-47mut2 (P=.007). Peripheral bacteremia was documented in 75% of rats challenged with S. epidermidis O-47, compared with 12.5% and 25% challenged with O-47mut1 and O-47mut2, respectively (P=.009). Metastatic disease was more common in rats inoculated with wt S. epidermidis, compared with AtlE- or PIA-deficient mutants. These results confirm the importance of initial adherence, associated with AtlE, and biofilm production, mediated by PIA, in the pathogenesis of S. epidermidis experimental CVC infection.
Differential Display: A General Protocol (2003)

One of the greatest unsolved mysteries of life is how the hundreds of thousands of genes embedded in the genome of an organism are selectively expressed into the mRNA and proteins in a temporally and spatially regulated manner that gives rise to different tissues and organs. The abnormality in this intricate regulatory circuitry is believed to be one of the underlining causes of a variety of pathological alterations or disease states. The isolation and characterization of differentially expressed genes becomes one of the first steps toward the understanding of these important biological questions. Differential display (1) and a related RAP-PCR method (2) were developed to more efficiently identify and isolate these genes.
Cerebral small-vessel disease protein HTRA1 controls the amount of TGF-β1 via cleavage of proTGF-β1 (2011)

Cerebral small-vessel disease is a common disorder in elderly populations; however, its molecular basis is not well understood. We recently demonstrated that mutations in the high-temperature requirement A (HTRA) serine peptidase 1 (HTRA1) gene cause a hereditary cerebral small-vessel disease, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). HTRA1 belongs to the HTRA protein family, whose members have dual activities as chaperones and serine proteases and also repress transforming growth factor-β (TGF-β) family signaling. We demonstrated that CARASIL-associated mutant HTRA1s decrease protease activity and fail to decrease TGF-β family signaling. However, the precise molecular mechanism for decreasing the signaling remains unknown. Here we show that increased expression of ED-A fibronectin is limited to cerebral small arteries and is not observed in coronary, renal arterial or aortic walls in patients with CARASIL. Using a cell-mixing assay, we found that HTRA1 decreases TGF-β1 signaling triggered by proTGF-β1 in the intracellular space. HTRA1 binds and cleaves the pro-domain of proTGF-β1 in the endoplasmic reticulum (ER), and cleaved proTGF-β1 is degraded by ER-associated degradation. Consequently, the amount of mature TGF-β1 is reduced. These results establish a novel mechanism for regulating the amount of TGF-β1, specifically, the intracellular cleavage of proTGF-β1 in the ER.
Tolerance and Chimerism after Renal and Hematopoietic-Cell Transplantation (2008)

We describe a recipient of combined kidney and hematopoietic-cell transplants from an HLA-matched donor. A post-transplantation conditioning regimen of total lymphoid irradiation and antithymocyte globulin allowed engraftment of the donor's hematopoietic cells. The patient had persistent mixed chimerism, and the function of the kidney allograft has been normal for more than 28 months since discontinuation of all immunosuppressive drugs. Adverse events requiring hospitalization were limited to a 2-day episode of fever with neutropenia. The patient has had neither rejection episodes nor clinical manifestations of graft-versus-host disease.
Influence of biotin lipid surface density and accessibility on avidin binding to the tip of an optical fiber sensor (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInfluence of biotin lipid surface density and accessibility on avidin binding to the tip of an optical fiber sensorShulei Zhao and W. M. ReichertCite this: Langmuir 1992, 8, 11, 2785–2791Publication Date (Print):November 1, 1992Publication History Published online1 May 2002Published inissue 1 November 1992https://pubs.acs.org/doi/10.1021/la00047a034https://doi.org/10.1021/la00047a034research-articleACS PublicationsRequest reuse permissionsArticle Views410Altmetric-Citations68LEARN 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 optionsGet e-Alertsclose Get e-Alerts
CD45 Modulates Galectin-1-Induced T Cell Death: Regulation by Expression of Core 2 O -Glycans (2001)

Galectin-1 induces death of immature thymocytes and activated T cells. Galectin-1 binds to T cell-surface glycoproteins CD45, CD43, and CD7, although the precise roles of each receptor in cell death are unknown. We have determined that CD45 can positively and negatively regulate galectin-1-induced T cell death, depending on the glycosylation status of the cells. CD45(+) BW5147 T cells lacking the core 2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT) were resistant to galectin-1 death. The inhibitory effect of CD45 in C2GnT(-) cells appeared to require the CD45 cytoplasmic domain, because Rev1.1 cells expressing only CD45 transmembrane and extracellular domains were susceptible to galectin-1 death. Moreover, treatment with the phosphotyrosine-phosphatase inhibitor potassium bisperoxo(1,10-phenanthroline)oxovanadate(V) enhanced galectin-1 susceptibility of CD45(+) T cell lines, but had no effect on the death of CD45(-) T cells, indicating that the CD45 inhibitory effect involved the phosphatase domain. Expression of the C2GnT in CD45(+) T cell lines rendered the cells susceptible to galectin-1, while expression of the C2GnT in CD45(-) cells had no effect on galectin-1 susceptibility. When CD45(+) T cells bound to galectin-1 on murine thymic stromal cells, only C2GnT(+) T cells underwent death. On C2GnT(+) cells, CD45 and galectin-1 co-localized in patches on membrane blebs while no segregation of CD45 was seen on C2GnT(-) T cells, suggesting that oligosaccharide-mediated clustering of CD45 facilitated galectin-1-induced cell death.
Empleo juvenil : entre el desempleo y la precariedad (2016)

La presente monografia aborda el fenomeno del desempleo juvenil, mediante la identificacion y cuantificacion del colectivo de los jovenes desempleados, la diferenciacion de los diferentes grupos de jovenes que conforman este colectivo, con sus caracteristicas y necesidades especificas, asi como tambie, mediante el analisis de las diferentes medidas que desde diferentes ambitos, pero especialmente, desde la vertiente juridico laboral y de seguridad social, se han propuesto para mitigar las elevadas tasas de desempleo de este colectivo.
Activation of interferon signaling pathways in spinal cord astrocytes from an ALS mouse model (2011)

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting predominantly motor neurons. Recent studies suggest that the disease progression of ALS is non-cell-autonomous, although the interaction between neurons and glial cells in different disease stages is not entirely clear. Here, we demonstrate that the interferon (IFN) signaling pathway is activated in human SOD1(G93A) transgenic mice, a rodent model of ALS. IFN-stimulated genes (ISGs) increased in the spinal cord of SOD1(G93A) mice at a presymptomatic age. In addition, the up-regulated ISGs, and most likely their transcriptional activators, were found specifically in astrocytes surrounding motor neurons, suggesting that IFN signaling in astrocytes was triggered by specific pathologic changes in motor neurons. Furthermore, induction of ISGs in cultured astrocytes was highly sensitive to IFN, especially Type I IFN. ISGs in astrocytes were activated specifically by endoplasmic reticulum stress-induced neurodegeneration in vitro, implicating a similar process in the presymptomatic stage of SOD1 mutant mice. Finally, reduction or deletion of IFNα receptor 1 inhibited IFN signaling and increased the life-span of SOD1(G93A) mice. Thus, the activation of IFN signaling pathways represents an early "dialogue" between motor neurons and astrocytes in response to pathological changes in ALS.
In vivofluorescence imaging of atherosclerotic plaques with activatable cell-penetrating peptides targeting thrombin activity (2012)

Thrombin and other coagulation enzymes have been shown to be important during atherosclerotic disease development. Study of these proteases is currently limited because of lack of robust molecular imaging agents for imaging protease activity in vivo. Activatable cell penetrating peptides (ACPPs) have been used to monitor MMP activity in tumors and, in principle, can be modified to detect other proteases. We have developed a probe that incorporates the peptide sequence DPRSFL from the proteinase activated receptor 1 (PAR-1) into an ACPP and shown that it is preferentially cleaved by purified thrombin. Active thrombin in serum cleaves DPRSFL-ACPP with >90% inhibition by lepirudin or argatroban. The DPRSFL-ACPP cleavage product accumulated in advanced atherosclerotic lesions in living mice, with 85% reduction in retention upon pre-injection of mice with hirudin. Uptake of the ACPP cleavage product was highest in plaques with histological features associated with more severe disease. Freshly resected human atheromas bathed in DPRSFL-ACPP retained 63% greater cleavage product compared to control ACPP. In conclusion, DPRSFL-ACPP can be used to study thrombin activity in coagulation and atherosclerosis with good spatial and temporal resolution. Thrombin-sensitive ACPPs may be developed into probes for early detection and intraoperative imaging of high risk atherosclerotic plaques.
Increasing HDL Cholesterol Levels (2004)

In the past decade, high-density lipoproteins (HDL) have emerged as a new potential therapeutic target for the treatment of cardiovascular disease. The key role of HDL as a carrier of excess cellular cholesterol in the reverse cholesterol transport pathway is believed to provide protection against atherosclerosis. In reverse cholesterol transport, peripheral tissues (e.g., vessel-wall macrophages) remove their excess cholesterol through the ATP-binding cassette transporter 1 (ABCA1) to poorly lipidated apolipoprotein A-I, forming pre-β-HDL. Lecithin–cholesterol acyltransferase then esterifies free cholesterol to cholesteryl esters, converting pre-β-HDL to mature spherical α-HDL (see Figure).HDL cholesterol is transported to the liver by two pathways: . . .