258 research outputs found
Low temperature reduction of hexavalent chromium by a microbial enrichment consortium and a novel strain of Arthrobacter aurescens
BACKGROUND: Chromium is a transition metal most commonly found in the environment in its trivalent [Cr(III)] and hexavalent [Cr(VI)] forms. The EPA maximum total chromium contaminant level for drinking water is 0.1 mg/l (0.1 ppm). Many water sources, especially underground sources, are at low temperatures (less than or equal to 15 Centigrade) year round. It is important to evaluate the possibility of microbial remediation of Cr(VI) contamination using microorganisms adapted to these low temperatures (psychrophiles). RESULTS: Core samples obtained from a Cr(VI) contaminated aquifer at the Hanford facility in Washington were enriched in Vogel Bonner medium at 10 Centigrade with 0, 25, 50, 100, 200, 400 and 1000 mg/l Cr(VI). The extent of Cr(VI) reduction was evaluated using the diphenyl carbazide assay. Resistance to Cr(VI) up to and including 1000 mg/l Cr(VI) was observed in the consortium experiments. Reduction was slow or not observed at and above 100 mg/l Cr(VI) using the enrichment consortium. Average time to complete reduction of Cr(VI) in the 30 and 60 mg/l Cr(VI) cultures of the consortium was 8 and 17 days, respectively at 10 Centigrade. Lyophilized consortium cells did not demonstrate adsorption of Cr(VI) over a 24 hour period. Successful isolation of a Cr(VI) reducing organism (designated P4) from the consortium was confirmed by 16S rDNA amplification and sequencing. Average time to complete reduction of Cr(VI) at 10 Centigrade in the 25 and 50 mg/l Cr(VI) cultures of the isolate P4 was 3 and 5 days, respectively. The 16S rDNA sequence from isolate P4 identified this organism as a strain of Arthrobacter aurescens, a species that has not previously been shown to be capable of low temperature Cr(VI) reduction. CONCLUSION: A. aurescens, indigenous to the subsurface, has the potential to be a predominant metal reducer in enhanced, in situ subsurface bioremediation efforts involving Cr(VI) and possibly other heavy metals and radionuclides
BCX4430 – A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease
SummaryThe adenosine nucleoside analog BCX4430 is a direct-acting antiviral drug under investigation for the treatment of serious and life-threatening infections from highly pathogenic viruses, such as the Ebola virus. Cellular kinases phosphorylate BCX4430 to a triphosphate that mimics ATP; viral RNA polymerases incorporate the drug's monophosphate nucleotide into the growing RNA chain, causing premature chain termination. BCX4430 is active in vitro against many RNA viral pathogens, including the filoviruses and emerging infectious agents such as MERS-CoV and SARS-CoV. In vivo, BCX4430 is active after intramuscular, intraperitoneal, and oral administration in a variety of experimental infections. In nonclinical studies involving lethal infections with Ebola virus, Marburg virus, Rift Valley fever virus, and Yellow Fever virus, BCX4430 has demonstrated pronounced efficacy. In experiments conducted in several models, both a reduction in the viral load and an improvement in survival were found to be related to the dose of BCX4430. A Phase 1 clinical trial of intramuscular administration of BCX4430 in healthy subjects is currently ongoing
Ursinus College Alumni Journal, November 1955
Program for new dormitories underway • Business, the alumnus, and the cost of higher education • Campbell Soup Company establishes fund • James Hirst named to honor society • 18th annual performance announced of the Messiah • Attendance increases in the Ursinus College Evening School • Some notes from the Dean\u27s office • Registrar\u27s report on fall enrollment • Ursinus forum 1955-1956 • Max C. Putney \u2718 author of The Man of Galilee • South Jersey alumni honor Dr. McClure • Binder named Dean at Thiel College • Berks County alumni hold clam bake • Dr. Sherman A. Eger \u2725 describes new operation for high blood pressure • James J. Herron \u2732 elected vice-president of Dun & Bradstreet, Inc. • Alumni eligible for Fulbright scholarships • Ursinus Women\u27s Club • Committee to review alumni constitution • A Fulbrighter in Japan • 1955 Loyalty Fund report • Sick transit - or - She perks no more • Curtain Club presents The Madwoman of Chaillot • Class of \u2756 elects permanent alumni officers • Mrs. Snyder new preceptress at Duryea Hall • G. E. reports on its corporate alumnus program • Regional alumni groups plan student trip • Warren K. Hess \u2731 addresses state school directors • 51\u27ers quartet meet after four years • History art collection • Sports review: Soccer report; Facts about the coaching staff; Alumni varsity basketball game • News about ourselves • Weddings • Births • Necrologyhttps://digitalcommons.ursinus.edu/alumnijournal/1054/thumbnail.jp
Ursinus College Alumni Journal, March 1956
President\u27s page • Sigma Rho scholarship fund grows • Three Ursinus alumni honored at Founders\u27 Day ceremony • 191,400 to Ursinus College • Enrollment increases in Evening School • Notes from the Dean\u27s office • Ursinus presentation of Messiah recorded • From the Office of Admissions • Faculty corner • Philadelphia alumni to meet at Casa Conti • Plan now to return Alumni Day, June 2 • Spring banquet planned by Lehigh Valley • May 2nd, date for New York alumni • South Jersey alumni plan dinner-dance • Woman\u27s Club plans spring activities • Booster committee holds banquet for athletes • Ditter, Warden, Tredinnick, Assistant District Attorneys • Alumni invited to Varsity Club dinner • Dr. Gilbert Bayne \u2743 speaks to science societies • Isaac Norris of Norristown, PA • Alumni elections • Schoolmen\u27s Week teachers luncheon • Washington area alumni reorganize • Report of the loyalty fund campaign • Sports review: Football season 1955; Dave Burger named to All-American soccer team; Soccer season 1955; Wrestling; 1955 alumnae hockey; Heller and Dawkins excel in women\u27s hockey • News about ourselves • Births • Weddings • Necrologyhttps://digitalcommons.ursinus.edu/alumnijournal/1055/thumbnail.jp
A constructive approach for discovering new drug leads: Using a kernel methodology for the inverse-QSAR problem
<p>Abstract</p> <p>Background</p> <p>The inverse-QSAR problem seeks to find a new molecular descriptor from which one can recover the structure of a molecule that possess a desired activity or property. Surprisingly, there are very few papers providing solutions to this problem. It is a difficult problem because the molecular descriptors involved with the inverse-QSAR algorithm must adequately address the forward QSAR problem for a given biological activity if the subsequent recovery phase is to be meaningful. In addition, one should be able to construct a feasible molecule from such a descriptor. The difficulty of recovering the molecule from its descriptor is the major limitation of most inverse-QSAR methods.</p> <p>Results</p> <p>In this paper, we describe the reversibility of our previously reported descriptor, the vector space model molecular descriptor (VSMMD) based on a vector space model that is suitable for kernel studies in QSAR modeling. Our inverse-QSAR approach can be described using five steps: (1) generate the VSMMD for the compounds in the training set; (2) map the VSMMD in the input space to the kernel feature space using an appropriate kernel function; (3) design or generate a new point in the kernel feature space using a kernel feature space algorithm; (4) map the feature space point back to the input space of descriptors using a pre-image approximation algorithm; (5) build the molecular structure template using our VSMMD molecule recovery algorithm.</p> <p>Conclusion</p> <p>The empirical results reported in this paper show that our strategy of using kernel methodology for an inverse-Quantitative Structure-Activity Relationship is sufficiently powerful to find a meaningful solution for practical problems.</p
Novel Marine Phenazines as Potential Cancer Chemopreventive and Anti-Inflammatory Agents
Two new (1 and 2) and one known phenazine derivative (lavanducyanin, 3) were isolated and identified from the fermentation broth of a marine-derived Streptomyces sp. (strain CNS284). In mammalian cell culture studies, compounds 1, 2 and 3 inhibited TNF-α-induced NFκB activity (IC50 values of 4.1, 24.2, and 16.3 μM, respectively) and LPS-induced nitric oxide production (IC50 values of >48.6, 15.1, and 8.0 μM, respectively). PGE2 production was blocked with greater efficacy (IC50 values of 7.5, 0.89, and 0.63 μM, respectively), possibly due to inhibition of cyclooxygenases in addition to the expression of COX-2. Treatment of cultured HL-60 cells led to dose-dependent accumulation in the subG1 compartment of the cell cycle, as a result of apoptosis. These data provide greater insight on the biological potential of phenazine derivatives, and some guidance on how various substituents may alter potential anti-inflammatory and anti-cancer effects
Weight loss with bariatric surgery or behaviour modification and the impact on female obesity-related urine incontinence : a comprehensive systematic review and meta-analysis
Women with obesity are at risk of pelvic floor dysfunction with a 3-fold increased incidence of urge urinary incontinence (UUI) and double the risk of stress urinary incontinence (SUI). The National Institute for Health and Care Excellence (NICE) and European Association of Urology (EAU) recommend that women with a body mass index ≥30 kg/m2 should consider weight loss prior to consideration for incontinence surgery. This systematic review and meta-analysis will assess this recommendation to aid in the counselling of women with obesity-related urinary incontinence (UI). Medical Literature Analysis and Retrieval System online (MEDLINE), EMBASE, Cochrane, ClinicalTrials.gov, and SCOPUS were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori and presented original, empirical data relevant to weight loss intervention in the management of urinary incontinence. Thirty-three studies and their outcomes were meta-analysed. Weight loss interventions were associated in a decreased prevalence in UI (OR 0.222, 95% CI [0.147, 0.336]), SUI (OR 0.354, 95% CI [0.256, 0.489]), UUI (OR 0.437, 95% CI [0.295, 0.649]) and improved quality of life (PFDI-20, SMD -0.774 (95% CI [−1.236, −0.312]). This systematic review and meta-analysis provide evidence that weight loss interventions are effective in reducing the prevalence of obesity-related UI symptoms in women. Bariatric surgery in particular shows greater sustained weight loss and improvements in UI prevalence. Further large scale, randomized control trials assessing the effect of bariatric surgery on women with obesity-related UI are needed to confirm this study's findings
Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
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