gebhart/patrepeval huggingface dataset:
In situclick chemistry: a powerful means for lead discovery (2006)

Combinatorial chemistry and parallel synthesis are important and regularly applied tools for lead identification and optimisation, although they are often accompanied by challenges related to the efficiency of library synthesis and the purity of the compound library. In the last decade, novel means of lead discovery approaches have been investigated where the biological target is actively involved in the synthesis of its own inhibitory compound. These fragment-based approaches, also termed target-guided synthesis (TGS), show great promise in lead discovery applications by combining the synthesis and screening of libraries of low molecular weight compounds in a single step. Of all the TGS methods, the kinetically controlled variant is the least well known, but it has the potential to emerge as a reliable lead discovery method. The kinetically controlled TGS approach, termed in situ click chemistry, is discussed in this article.
A macrocyclic tetraether bolaamphiphile and an oligoamino .alpha.,.omega.-dicarboxylate combine to form monolayered, porous vesicle membranes, which are reversibly sealed by EDTA and other bulky anions (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA macrocyclic tetraether bolaamphiphile and an oligoamino .alpha.,.omega.-dicarboxylate combine to form monolayered, porous vesicle membranes, which are reversibly sealed by EDTA and other bulky anionsJuergen Hinrich. Fuhrhop, Ulrich. Liman, and Volker. KoeslingCite this: J. Am. Chem. Soc. 1988, 110, 20, 6840–6845Publication Date (Print):September 1, 1988Publication History Published online1 May 2002Published inissue 1 September 1988https://pubs.acs.org/doi/10.1021/ja00228a037https://doi.org/10.1021/ja00228a037research-articleACS PublicationsRequest reuse permissionsArticle Views399Altmetric-Citations83LEARN 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
Silencing BMI1 eliminates tumor formation of pediatric glioma CD133+ cells not by affecting known targets but by down-regulating a novel set of core genes (2014)

Clinical outcome of children with malignant glioma remains dismal. Here, we examined the role of over-expressed BMI1, a regulator of stem cell self-renewal, in sustaining tumor formation in pediatric glioma stem cells. Our investigation revealed BMI1 over-expression in 29 of 54 (53.7%) pediatric gliomas, 8 of 8 (100%) patient derived orthotopic xenograft (PDOX) mouse models, and in both CD133+ and CD133- glioma cells. We demonstrated that lentiviral-shRNA mediated silencing of suppressed cell proliferation in vitro in cells derived from 3 independent PDOX models and eliminated tumor-forming capacity of CD133+ and CD133- cells derived from 2 PDOX models in mouse brains. Gene expression profiling showed that most of the molecular targets of BMI1 ablation in CD133+ cells were different from that in CD133- cells. Importantly, we found that silencing BMI1 in CD133+ cells derived from 3 PDOX models did not affect most of the known genes previously associated with the activated BMI1, but modulated a novel set of core genes, including RPS6KA2, ALDH3A2, FMFB, DTL, API5, EIF4G2, KIF5c, LOC650152, C20ORF121, LOC203547, LOC653308, and LOC642489, to mediate the elimination of tumor formation. In summary, we identified the over-expressed BMI1 as a promising therapeutic target for glioma stem cells, and suggest that the signaling pathways associated with activated BMI1 in promoting tumor growth may be different from those induced by silencing BMI1 in blocking tumor formation. These findings highlighted the importance of careful re-analysis of the affected genes following the inhibition of abnormally activated oncogenic pathways to identify determinants that can potentially predict therapeutic efficacy.
Trp-Lys-Tyr-Met-Val-D-Met stimulates superoxide generation and killing of Staphylococcus aureus via phospholipase D activation in human monocytes (1999)

Among the phagocytic leukocytes, monocytes have the important role of clearing out parasitic microorganisms. They accomplish this through production of toxic metabolites of oxygen. Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), a peptide that stimulates phosphoinositide (PI) hydrolysis in human leukocytes, including monocytes, binds to a unique cell surface receptor and stimulates superoxide generation, killing of Staphylococcus aureus, and activation of phospholipase D (PLD) in human monocytes. Preincubation of the cells with a PI-specific phospholipase C (PLC) inhibitor (U-73122), protein kinase C inhibitor (GF109203X), or intracellular Ca2+ chelator (BAPTA/AM) before the peptide stimulus totally inhibits the peptide-induced PLD activation and superoxide generation. On the other hand, tyrosine kinase inhibitor genistein only partially inhibits the peptide-induced processes. The peptide-induced bacteria killing activity shares regulatory mechanisms for PLD activation with the superoxide generation, which is inhibited in the presence of 1-butanol. We suggest that the peptide stimulates PLD downstream of PLC activation and PLD activation in turn is essential for the peptide-induced immunological functions such as the superoxide generation and killing of bacteria by human monocytes.
Correlation between Branhamella catarrhalis adherence to oropharyngeal cells and seasonal incidence of lower respiratory tract infections. (1987)

Bacterial colonization of the oropharynx is the initial event in most lower respiratory tract infections. To study the role of bacterial adherence in lower respiratory tract infections caused by Branhamella catarrhalis (B. catarrhalis) in winter, in vitro adherence assays of the organism to human oropharyngeal cells were carried out in winter, spring, summer and autumn. A total of 57 adults of both sexes were studied from January to December 1985. Forty eight persons of 57 had chronic pulmonary diseases and the remaining 9 persons had other clinical entities and served as the control group. Predominance of lower respiratory tract infections caused by B. catarrhalis with high adherence rate was observed in winter. Adherence activity was moderate in spring and autumn and low in summer and accompanied by a similar incidence of lower respiratory tract infections with this bacteria. In addition, similar results were found in patients in whom investigations were done successively in the above four seasons. Bacterial adherence activity to cells however, was weak in winter in the control group. These results indicate that seasonal variation plays a significant role in the ability of B. catarrhalis to adhere to oropharyngeal cells. This is an important pathogenic factor correlated with the incidence of lower-respiratory tract infections in these patients.
Stabilization of Flow Boiling in Microchannels Using Pressure Drop Elements and Fabricated Nucleation Sites (2005)

The flow boiling process suffers from severe instabilities induced due to nucleation of vapor bubbles in a superheated liquid environment in a minichannel or a microchannel. In an effort to improve the flow boiling stability, several modifications are introduced and experiments are performed on 1054×197μm parallel rectangular microchannels (hydraulic diameter of 332μm) with water as the working fluid. The cavity sizes and local liquid and wall conditions required at the onset of nucleation are analyzed. The effects of an inlet pressure restrictor and fabricated nucleation sites are evaluated as a means of stabilizing the flow boiling process and avoiding the backflow phenomenon. The results are compared with the unrestricted flow configurations in smooth channels.
Multilayer Reconstruction of Abdominal Wall Defects With Acellular Dermal Allograft (AlloDerm) and Component Separation (2005)

Multiple techniques have been employed for the repair of abdominal incisional hernias with varying rates of success. Primary fascial apposition and prosthetic implantation have been associated with high rates of secondary recurrence, infection, and other complications, often due to insufficient alleviation of tension and implant intolerance. This study evaluates the repair of incisional and recurrent abdominal hernias with multilayered acellular dermal allograft (AlloDerm; LifeCell Corporation, Branchburg, NJ) and musculofascial separation. Patients with incisional or recurrent abdominal hernias were treated between January 2003 and March 2004. The surgical technique involved musculofascial release of the external oblique, followed by a double-layer implantation of dermal allograft. The primary allograft layer was placed as an "underlay" interposition, sutured under moderate tension beneath the fascial edges of the defect. When minimal tension remained, the native fascial margins of the defect were directly repaired. A second allograft layer was then placed and sutured to the superficial aspect of the ventral fascia to complete the repair. Data were reviewed retrospectively. Sixteen patients were treated. There were 10 males and 6 females, mean age 56 years (range 44--72 years). Fifteen patients (94%) had previous hernia repair procedures, and 6 patients (38%) had undergone 2 or more previous procedures. Nine patients (56%) were treated with hernia site infections or prosthetic exposure. Mean follow-up is 16 months (range 9 to 23 months). There were 2 seromas (13%). One patient (6%) developed a wound dehiscence with allograft exposure that healed by secondary intention. There were no recurrences. By minimizing tension and providing a durable biocompatible matrix for support, component separation with bilaminar acellular dermal allograft should be considered for the repair of complex and recurrent ventral hernias.
Primary Structure of the γ Subunit of the DHP-Sensitive Calcium Channel from Skeletal Muscle (1990)

Affinity-purified, polyclonal antibodies to the gamma subunit of the dihydropyridine (DHP)-sensitive, voltage-dependent calcium channel have been used to isolate complementary DNAs to the rabbit skeletal muscle protein from an expression library. The deduced primary structure indicates that the gamma subunit is a 25,058-dalton protein that contains four transmembrane domains and two N-linked glycosylation sites, consistent with biochemical analyses showing that the gamma subunit is a glycosylated hydrophobic protein. Nucleic acid hybridization studies indicate that there is a 1200-nucleotide transcript in skeletal muscle but not in brain or heart. The gamma subunit may play a role in assembly, modulation, or the structure of the skeletal muscle calcium channel.
Multiple Mechanisms for Wnt11-mediated Repression of the Canonical Wnt Signaling Pathway (2004)

The effect of a noncanonical Wnt, Wnt11, on canonical Wnt signaling stimulated by Wnt1 and activated forms of LRP5 (low density lipoprotein receptor-related protein-5), Dishevelled1 (Dvl1), and beta-catenin was examined in NIH3T3 cells and P19 embryonic carcinoma cells. Wnt11 repressed Wnt1-mediated activation of LEF-1 reporter activity in both cell lines. However, Wnt11 was unable to inhibit canonical signaling activated by LRP5, Dvl1, or beta-catenin in NIH3T3 cells, although it could in P19 cells. In addition, Wnt11-mediated inhibition of canonical signaling in NIH3T3 cells is ligand-specific; Wnt11 could effectively repress canonical signaling activated by Wnt1, Wnt3, or Wnt3a but not by Wnt7a or Wnt7b. Co-culture experiments with NIH3T3 cells showed that the co-expression of Wnt11 with Wnt1 was not an essential requirement for the inhibition, suggesting receptor competition as a possible mechanism. Moreover, in both cell types, elevation of intracellular Ca(2+) levels, which can result from Wnt11 treatment, led to the inhibition of canonical signaling. This result suggests that Wnt11 might not be able to signal in NIH3T3. Furthermore, P19 cells were found to express both endogenous canonical Wnts and Wnt11. Knockdown of Wnt11 expression using siRNA resulted in increased LEF-1 reporter activity, thus indicating that Wnt11-mediated suppression of canonical signaling exists in vivo.
Effect of urokinase on disseminated intravascular coagulation (1998)

Our study evaluated the possible therapeutic effect of urokinase in treating the microthrombiotic effects of disseminated intravascular coagulation by assisting the activation of endogenous plasminogen. Twenty-six pigs were anesthetized, intubated, mechanically ventilated, and surgically catheterized. Septic shock was induced in all 26 pigs by an intravenous infusion of heat-killed Escherichia coli. The pigs were divided into two sets of experiments: in experiment 2 (n = 14), one-half received an intravenous dose of urokinase 1 h after heat-killed E. coli infusion and in experiment 3 (n = 12) one-half received an intravenous bolus dose and a continuous drip of urokinase 2 h after heat-killed E. coli infusion. The untreated pigs served as controls. Hemodynamic parameters, blood chemistries, and blood gases were analyzed. Urokinase given 1 h after bacterial toxin infusion significantly restored blood flow, resulting in an increase in cardiovascular and pulmonary function and improved survival rate (43% control vs. 100% treated, 24-h experimental period). Treatment given after 2 h showed some significant effect on pulmonary function; however, within 10 h of E. coli infusion, mortality rates in control and treated groups were 100 and 83%, respectively. Early administration of urokinase after onset of disseminated intravascular coagulation restored blood flow and helped resolve organ damage.
Cyclophosphamide therapy for rheumatoid arthritis (1975)

Cyclophosphamide in high doses was given for six months to 19 patients with rheumatoid arthritis. A second group of patients with rheumatoid arthritis whose conditions were stable on low-dose prednisone received in addition either cyclophosphamide or placebo for six months. Measurements of joint function and joint inflammation were used to estimate disease activity. Joint inflammation progressively decreased and joint function improved in the high-dose group. The low-dose cyclophosphamide-plus-prednisone group had a similar response that was different from the prednisone-plus-placebo group. Cyclophosphamide toxicity was common in the high-dose group and minimal in the low-dose-plus-prednisone group. Cyclophosphamide therapy improved the arthritis of these patients. The results were almost as good in the low-dose-plus-prednisone group, and the toxicity was much less.
Immunoelectron microscopic localization of small, acid-soluble spore proteins in sporulating cells of Bacillus subtilis (1988)

Small, acid-soluble spore proteins SASP-alpha, SASP-beta, and SASP-gamma as well as a SASP-beta-lacZ gene fusion product were found only within the forespore compartment of sporulating Bacillus subtilis cells by using immunoelectron microscopy. The alpha/beta-type SASP were associated almost exclusively with the forespore nucleoid, while SASP-gamma was somewhat excluded from the nucleoid. These different locations of alpha/beta-type and gamma-type small, acid-soluble spore proteins within the forespore are consistent with the different roles for these two types of proteins in spore resistance to UV light.
Cassandra (2010)

Cassandra is a distributed storage system for managing very large amounts of structured data spread out across many commodity servers, while providing highly available service with no single point of failure. Cassandra aims to run on top of an infrastructure of hundreds of nodes (possibly spread across different data centers). At this scale, small and large components fail continuously. The way Cassandra manages the persistent state in the face of these failures drives the reliability and scalability of the software systems relying on this service. While in many ways Cassandra resembles a database and shares many design and implementation strategies therewith, Cassandra does not support a full relational data model; instead, it provides clients with a simple data model that supports dynamic control over data layout and format. Cassandra system was designed to run on cheap commodity hardware and handle high write throughput while not sacrificing read efficiency.
<title>Copper interconnection schemes: elimination of the need of diffusion barrier/adhesion promoter by the use of corrosion-resistant low-resistivity-doped copper</title> (1994)

Copper is known to diffuse in dielectrics subjected to high electrical bias at temperatures as low as 100 degree(s)C. Also, it does not adhere to the interlayer dielectrics like SiO<SUB>2</SUB> and polymers. In addition, copper corrodes readily in the corrosive environments. These properties of copper have inhibited the early acceptance of copper as the interconnection metal in the high performance integrated electronic circuit/devices. We have investigated the use of possible diffusion barrier (DB) and adhesion promoter (AP) materials in the conventional layered structures which lead to an increase in the total interconnection resistance negating the advantages of copper. Also, since the subquarter micron circuits necessitates the need of &lt; 10 nm thick DBAP material, such layered structures are generally not stable under the interconnection processing, chip packaging, and/or actual use conditions. In this paper, we present results of our study of the electrically stable and corrosion resistant doped copper as the interconnection material. Al, Mg, and Ta, all of which have considerably higher free energy of formation for their oxides compared to that for Cu or Si oxides, have been added as the dopant in concentration range of 0.5 - 10 atomic percent in copper. Resistivity, adhesion to dielectric surfaces, effect of annealing to temperatures as high as 800 degree(s)C on such properties, corrosion resistance in air, and I-V/C-V characteristics of the metal/SiO<SUB>2</SUB>/Si capacitors have been investigated. It is found that addition of such dopants provides the necessary passivation. Doped films are very smooth even after anneals to temperatures as high as 800 degree(s)C. They did not lose adherence to SiO<SUB>2</SUB> substrates after such anneals as demonstrated by the adhesive tape-peel tests. Preliminary indications are that doping has reduced the overall stress in the film. There is a small increase in the resistivity of copper, caused by the addition of these dopants. For example, for Cu with Mg (less than 2 atomic percent) the resistivity remains at or below 2 (mu) (Omega) cm. These results are compared with layered Al/Cu, Mg/Cu, Ti/Cu and TiN/Cu and show that doped films of copper satisfy all the reliability requirements at a small sacrifice of the resistivity in a manner similar to Al containing small amounts of copper.
NON-A, NON-B HEPATITIS VIRUSES (1983)

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and ...Read More
Irradiation-Induced Expression of Hyaluronan (HA) Synthase 2 and Hyaluronidase 2 Genes in Rat Lung Tissue Accompanies Active Turnover of HA and Induction of Types I and III Collagen Gene Expression (2000)

Hyaluronan (HA) is a linear glycosaminoglycan that accumulates in the interstitium of injured lung and inhibits gas exchange between air and blood. In the present study we investigated the molecular mechanisms behind the local turnover of HA during the early phase of irradiation-evoked lung fibrosis in rats. Irradiation with a single dose of 30 Gy to the lower part of the right lung of rats induced an accumulation of HA in bronchoalveolar lavage fluid 6 wk after irradiation, followed by return to almost normal levels at 10 wk after irradiation. This was parallelled with a transient downregulation of HA receptors on alveolar macrophages (AMs); 4 and 6 wk after irradiation the binding of [(3)H]HA to AMs was decreased to about 50% of that of AMs from nonirradiated control rats, returning to almost normal level at 10 wk after irradiation. Analysis of the expression of rat HA synthase (HAS) isoforms (rHAS1, rHAS2, and rHAS3) and rat hyaluronidases (rHYAL1 and rHYAL2) by Northern blotting revealed an upregulation of rHAS2 messenger RNA at 4, 6, and 10 wk after irradiation, but a progressive decrease in the constitutive expression of rHYAL2 at 6 and 10 wk after irradiation; rHAS1 was undetectable, whereas rHAS3 and rHYAL1 were faintly detectable. Although transforming growth factor-beta1 stimulated HA production by normal lung fibroblasts, it inhibited HYAL activity in lysosomes and HYAL activity released into the culture media. Another interesting observation was that HA fragments, which likely result from the action of HYAL, induced expression of types I and III collagen genes. Our results indicate that rHAS2 and rHYAL2 are involved in the turnover of HA during the early phase of lung injury and that rHAS2 and rHYAL2 as well as HA fragments may play important roles in the pathogenesis of lung fibrosis.
Role of trans-cellular IL-15 presentation in the activation of NK cell–mediated killing, which leads to enhanced tumor immunosurveillance (2004)

Abstract Interleukin 15 (IL-15) is a critical factor for the proliferation and activation of natural killer (NK) and CD8 T cells. Recently, we demonstrated that IL-15Rα expressed on monocytes/dendritic cells captures and presents IL-15 to neighboring cells in trans (trans-presentation of IL-15) through cell-cell contact. In the current study, we provide evidence that the IL-15 presented in trans, but not soluble IL-15 at physiologic concentrations, augments the killing activity mediated by NK cells in vitro. In addition, transfection of IL-15Rα into a colon carcinoma cell line (MC38) enabled these cells to present IL-15 in trans to NK cells and augmented their killing activity, resulting in the efficient lysis of MC38 cells by NK cells in vitro. Furthermore, these transfected MC38 cells no longer form fatal pulmonary metastases in mice. It was also shown that NK cells play an important role in the rejection of MC38 cells under these circumstances. These results collectively suggest that the IL-15 trans-presentation mechanism operates in vivo to augment the tumor immune surveillance mechanism. Furthermore, our observation provides the scientific basis for a novel strategy to prevent cancer development/metastasis.