gebhart/patrepeval huggingface dataset:
In vivo transposition of mariner -based elements in enteric bacteria and mycobacteria (1999)

mariner family transposons are widespread among eukaryotic organisms. These transposons are apparently horizontally transmitted among diverse eukaryotes and can also transpose in vitro in the absence of added cofactors. Here we show that transposons derived from the mariner element Himar1 can efficiently transpose in bacteria in vivo. We have developed simple transposition systems by using minitransposons, made up of short inverted repeats flanking antibiotic resistance markers. These elements can efficiently transpose after expression of transposase from an appropriate bacterial promoter. We found that transposition of mariner-based elements in Escherichia coli produces diverse insertion mutations in either a targeted plasmid or a chromosomal gene. With Himar1-derived transposons we were able to isolate phage-resistant mutants of both E. coli and Mycobacterium smegmatis. mariner-based transposons will provide valuable tools for mutagenesis and genetic manipulation of bacteria that currently lack well developed genetic systems.
Concise Asymmetric Synthesis of Antimalarial Alkaloid (+)-Febrifugine (2009)

An asymmetric total synthesis of antimalarial alkaloid (+)-febrifugine is accomplished in 23% overall yield over 14 steps from readily available starting materials. The synthesis features a SmI2-mediated reductive cross-coupling of chiral N-tert-butanesulfinyl imine with aldehyde.
The use of recombinant factor VIIa in the treatment of bleeding disorders (2004)

Recombinant factor VIIa was initially developed for the treatment of hemorrhagic episodes in hemophilic patients with inhibitors to factors VIII and IX. After its introduction, it has also been used "off-label" to enhance hemostasis in nonhemophilic patients who experience bleeding episodes not responsive to conventional therapy. Evidence so far indicates that the use of factor VIIa in hemophilic patients with inhibitors is both safe and effective. Anecdotal reports also suggest that the product is safe and effective in controlling bleeding in nonhemophilic patients. However, its use in these conditions has not been approved by the FDA, and conclusive evidence of its effectiveness from controlled clinical trials is not yet available. Several questions pertaining to the use of factor VIIa require further investigation, including the mechanism of action; the optimal dose; definitive indications; ultimate safety; and laboratory tests for monitoring therapy.
Detection and location of people in video images using adaptive fusion of color and edge information (2002)

A new method of finding people in video images is presented. The detection is based on a novel background modeling and subtraction approach which uses both color and edge information. We introduce confidence maps gray-scale images whose intensity is a function of confidence that a pixel has changed - to fuse intermediate results and represent the results of background subtraction. The latter is used to delineate a person's body by guiding contour collection to segment the person from the background. The method is tolerant to scene clutter, slow illumination changes, and camera noise, and runs in near real time on a standard platform.
High Fidelity Base Pairing at the 3′-Terminus (2009)

Binding target strands with single base selectivity at a terminal position is difficult with natural DNA or RNA hybridization probes. Nature uses a degenerate genetic code that is based on RNA:RNA codon:anticodon duplexes tolerating wobble base pairs at the terminus. The importance of short RNA strands in regulatory processes in the cell make it desirable to develop receptor-like approaches for high fidelity binding, even at the very 3'-terminus of a probe. Here, we report the three-dimensional structure of a DNA duplex with a 3'-terminal 2'-anthraquinoylamido-2'-deoxyuridine (Uaq) residue that was solved by NMR and restrained molecular dynamics. The Uaq residue binds the 5'-terminus of the target strand through a combination of pi-stacking, hydrogen bonding, and interactions in the minor groove. The acylated aminonucleoside is the best molecular cap for 3'-termini reported to date. The Uaq motif assists binding of DNA strands, but is particularly effective in enhancing the affinity for RNA target strands, with a DeltaT(m) in the UV melting point of up to +18.2 degrees C per residue. Increased base pairing selectivity is induced for all sequence motifs tested, even in cases where unmodified duplexes show no preference for the canonical base pair at all. A single mismatched nucleobase facing the 3'-terminus gives DeltaDeltaT(m) values as large as -23.9 degrees C (RNA) or -29.5 degrees C (DNA). The 5'-phosphoramidite of the Uaq cap reported here allows for routine incorporation during automated syntheses.
The Role of Adiponectin in Cancer: A Review of Current Evidence (2012)

Excess body weight is associated not only with an increased risk of type 2 diabetes and cardiovascular disease (CVD) but also with various types of malignancies. Adiponectin, the most abundant protein secreted by adipose tissue, exhibits insulin-sensitizing, antiinflammatory, antiatherogenic, proapoptotic, and antiproliferative properties. Circulating adiponectin levels, which are determined predominantly by genetic factors, diet, physical activity, and abdominal adiposity, are decreased in patients with diabetes, CVD, and several obesity-associated cancers. Also, adiponectin levels are inversely associated with the risk of developing diabetes, CVD, and several malignancies later in life. Many cancer cell lines express adiponectin receptors, and adiponectin in vitro limits cell proliferation and induces apoptosis. Recent in vitro studies demonstrate the antiangiogenic and tumor growth-limiting properties of adiponectin. Studies in both animals and humans have investigated adiponectin and adiponectin receptor regulation and expression in several cancers. Current evidence supports a role of adiponectin as a novel risk factor and potential diagnostic and prognostic biomarker in cancer. In addition, either adiponectin per se or medications that increase adiponectin levels or up-regulate signaling pathways downstream of adiponectin may prove to be useful anticancer agents. This review presents the role of adiponectin in carcinogenesis and cancer progression and examines the pathophysiological mechanisms that underlie the association between adiponectin and malignancy in the context of a dysfunctional adipose tissue in obesity. Understanding of these mechanisms may be important for the development of preventive and therapeutic strategies against obesity-associated malignancies.
A 3-D Navier-Stokes CFD study of turbojet/ramjet nozzle plume interactions at Mach 3.0 and comparison with data (1995)

Advanced airbreathing propulsion systems used in Mach 4-6 mission scenarios, usually consist of a single integrated turboramjet or as in this study, a turbojet housed in an upper bay with a separate ramjet housed in a lower bay. As the engines transition from turbojet to ramjet, there is an operational envelope where both engines operate simultaneously. One nozzle concept under consideration has a common nozzle, where the plumes from the turbojet and ramjet interact with one another as they expand to ambient conditions. In this paper, the two plumes interact at the end of a common 2-D cowl, when they both reach an approximate Mach 3.0 condition and then jointly expand to Mach 3.6 at the common nozzle exit plane. At this condition, the turbojet engine operated at a higher NPR than the ramjet, where the turbojet overpowers the ramjet plume, deflecting it approximately 12 degrees downward and in turn the turbojet plume is deflected 6 degrees upward. In the process, shocks were formed at the deflections and a shear layer formed at the confluence of the two jets. This particular case was experimentally tested and the data used to compare with the PARC3D code with k-kl two equation turbulence model. The 2-D and 3-D centerline CFD solutions are in good agreement, but as the CFD solutions approach the outer sidewall, a slight variance occurs. The outer wall boundary layers are thin and do not present much of an interaction, however, where the confluence interaction shocks interact with the thin boundary layer on the outer wall, strong vortices run down each shock causing substantial disturbances in the boundary layer. These disturbances amplify somewhat as they propagate downstream axially from the confluence point. The nozzle coefficient (CFG) is reduced 1/2 percent as a result of this sidewall interaction, from 0.9850 to 0.9807. This three-dimensional reduction is in better agreement with the experimental value of 0.9790.
Gene therapy of cancer in the clinic: good news in sight from Asia? (2007)

The field of gene therapy offers promising treatment innovations that may prove to be fundamental in helping cancer patients. In this review, recent advances in this field are discussed, with particular emphasis on new trends that have emerged in clinical trials between 2005 and 2006. Notably, among these trials only 5% were phase III trials, reflecting a lack of sound clinical advancement and, possibly, underscoring reduced enthusiasm and financial support by pharmaceutical companies in western countries. Viral vectors continue to be the preferred delivery system, with an increase in exploitation of oncolytic viruses. Nevertheless, the persistent crucial hurdle--the transfer of the therapeutic gene into sufficient numbers of tumor cells--remains. Future clinical trials will aim to identify promising combinations of genetic and conventional medicine. Multicenter trials with a broad patient enrolment will be mandatory to establish definitive proof of efficacy. In this regard, China has recently emerged as a country with growth potential in this sector and it may be the country where evidence of clinical efficacy of cancer gene therapy will first be achieved.
Platelet activation by C1q results in the induction of alpha IIb/beta 3 integrins (GPIIb-IIIa) and the expression of P-selectin and procoagulant activity. (1993)

C1q receptors (C1qR) have been identified on a variety of somatic and cultured cells including peripheral blood platelets. Since platelets are likely to encounter both circulating C1q multimers and C1q associated with the extracellular matrix after complement activation by the classical pathway, the present study was designed to assess the effect of fluid phase and immobilized C1q on platelet function. Platelet adhesion to C1q-coated surfaces was accompanied by the induction of fibrinogen receptors. Scatchard analysis of fibrinogen binding to adherent platelets revealed the binding of approximately 10,000 molecules of fibrinogen per platelet with a Kd of 0.1 +/- 0.03 microM (mean +/- SD, n = 4). Furthermore, fluid phase C1q multimers were noted to aggregate platelets at doses > 5 micrograms/ml. This aggregation was preceded by a rise in inositol-1,4,5-trisphosphate (IP3) (6.9 +/- 2.4 pmoles/10(9) platelets at 15 s, n = 4), and activation of GPIIb-IIIa complexes supporting fibrinogen binding. Platelet aggregation in response to C1q multimers was accompanied by the aspirin-inhibitable release of granule contents and P-selectin (CD62) expression. Platelet aggregation was inhibited by the collagenous domain of C1q (c-Clq) and a monoclonal antibody directed against C1q receptors, suggesting the direct involvement of the 67-kD platelet C1qR. Antibodies against the very late antigen 2 or CD36 collagen receptors were without effect. Platelet exposure to C1q multimers was also accompanied by the expression of procoagulant activity, as demonstrated by the dose-dependent shortening of the kaolin recalcification time of normal plasma from 108 +/- 12 s in the presence of unstimulated platelets to 62 +/- 14 s in the presence of platelets that had been preincubated (5 min, 37 degrees C) with 100 micrograms/ml multimeric C1q (n = 3). These data suggest that platelet interactions with C1q multimers or immobilized C1q, resulting in the activation of GPIIb-IIIa fibrinogen binding sites and the expression of P-selectin as well as platelet procoagulant activity, are likely to contribute to thrombotic events associated with complement activation and inflammation.
Physical and physiological effects of stratum corneum tape stripping (2001)

The tapes utilized removed a similar amount of SC. The tapes have a different propensity to cause barrier disruption. Some individuals do not demonstrate increased TEWL despite an equivalent mass of SC being removed compared to those who do show a response.
Pediatric Invasive Pneumococcal Disease in the United States in the Era of Pneumococcal Conjugate Vaccines (2012)

Invasive infections caused by Streptococcus pneumoniae continue to be a major cause of morbidity and mortality worldwide, especially in children under 5 years of age. In the United States, 90% of invasive pneumococcal infections in children are caused by 13 serotypes of S. pneumoniae. The licensure (in 2000) and subsequent widespread use of a heptavalent pneumococcal conjugate vaccine (PCV7) have had a significant impact on decreasing the incidence of serious invasive pneumococcal disease (IPD) in all age groups, especially in children under 2 years of age. However, the emergence of replacement non-PCV7 serotypes, especially serotype 19A, has resulted in an increase in the incidence of serious and invasive infections. In 2010, a 13-valent PCV was licensed in the United States. However, the impact that this vaccine will have on IPD remains to be seen. The objectives of this review are to discuss the epidemiology of serious and invasive pneumococcal infections in the United States in the PCV era and to review some of the pneumococcal vaccines that are in development.
Arsenic-contaminated water and extent of acute childhood malnutrition (wasting) in rural Bangladesh. (2005)

To investigate whether children's nutritional status, especially the extent of wasting [acute malnutrition as measured by weight-for-height Z (WHZ) score] is associated with arsenic contamination of drinking water, a survey was carried out in two discrete rural areas located less than 30 km southeast and northeast of Dhaka, the capital of Bangladesh. 761 children between 7 and 14 years of age were randomly selected, one child per household. The arsenic concentration in the tube well water used by each child and the prevalence and intensity of infection of three geo-helminths [Ascaris lumbricoides, Trichuris trichiura and hookworm (Ancylostoma duodenale or Necator americanus)] were determined. Each child had their height and weight measured and WHZ score determined using the World Health Organization (WHO) reference values. Basic socio-demographic data and knowledge of arsenic poisoning were collected using a questionnaire. 62.2% of the households studied were using well water with arsenic concentrations above the 0.01 mg/L WHO guideline (i.e. arsenic-contaminated households). The mean WHZ score of all the 761 children was -0.843 (sd 1.227) but children living in contaminated households were significantly more wasted than children living in noncontaminated households (mean difference = -0.361, p 0.001). When the effects of the differences in socio-economic status and prevalence of geo-helminths were also taken into account, the difference in means remained highly significant (-0.330, p = 0.006). This study suggests that arsenic contamination has a negative impact on children's acute nutritional status.
IFN‐α antagonistic activity of HCV core protein involves induction of suppressor of cytokine signaling‐3 (2003)

Eighty percent of patients newly infected with the hepatitis C virus (HCV) develop chronic infection, suggesting that HCV can develop effective strategies to escape the unspecific and specific immune response of the host. Because SOCS molecules have been recognized to be powerful inhibitors of cytokine signaling via the Jak/STAT pathway, virus-induced expression of these molecules should be an efficient instrument to counteract the cellular response toward interferons (IFNs), an essential part of first line antiviral immune response. This study shows that overexpression of HCV core protein inhibits IFN-alpha-induced tyrosine phosphorylation and activation of STAT1 in hepatic cells. With the use of a STAT1-YFP fusion protein, further evidence is given that HCV core is capable to inhibit nuclear translocation of STAT1. Inhibition of STAT1-tyrosine phosphorylation was accompanied by the induction of SOCS3-mRNA expression, suggesting that the HCV core protein impairs IFN-alpha-induced signal transduction via induction of SOCS3 expression. HCV core protein was competent to partially rescue growth of a genetically engineered influenza A virus lacking its own IFN antagonist. These IFN-antagonistic properties of the HCV core protein may be part of the molecular basis of IFN-alpha unresponsiveness in about one-half of chronically infected HCV-patients.
Innovative techniques cut costs in wetlands drilling (1991)

This paper reports on an approach to drilling oil and gas wells in sensitive wetlands areas contributed to a savings of over $1.2 million on a three-well, $3 million drilling project in south Louisiana. ARCO Oil and Gas Co. drilled a three-well project in the Bayou Sale field with a truck-mounted workover rig and a modified solids-control system. This smaller equipment eliminated the need to build a large location in the marsh. Traditional drilling techniques require a large drillsite to accommodate all the equipment of a modern drilling complex. However, recently imposed environmental regulations substantially limit, and in some cases prohibit, the use of these conventional techniques for drilling wells in wetlands areas. Based on the potentially huge economic and operational impact on the drilling industry because of these stricter regulations, alternatives to these traditional practices are essential.
A Multifunctional Chimeric Chaperone Serves as a Novel Immune Modulator Inducing Therapeutic Antitumor Immunity (2013)

Converting the immunosuppressive tumor environment into one that is favorable to the induction of antitumor immunity is indispensable for effective cancer immunotherapy. Here, we strategically incorporate a pathogen (i.e., flagellin)-derived, NF-κB-stimulating "danger" signal into the large stress protein or chaperone Grp170 (HYOU1/ORP150) that was previously shown to facilitate antigen crosspresentation. This engineered chimeric molecule (i.e., Flagrp170) is capable of transporting tumor antigens and concurrently inducing functional activation of dendritic cells (DC). Intratumoral administration of adenoviruses expressing Flagrp170 induces a superior antitumor response against B16 melanoma and its distant lung metastasis compared with unmodified Grp170 and flagellin. The enhanced tumor destruction is accompanied with significantly increased tumor infiltration by CD8(+) cells as well as elevation of IFN-γ and interleukin (IL)-12 levels in the tumor sites. In situ Ad.Flagrp170 therapy provokes systemic activation of CTLs that recognize several antigens naturally expressing in melanoma (e.g., gp100/PMEL and TRP2/DCT). The mechanistic studies using CD11c-DTR transgenic mice and Batf3-deficient mice reveal that CD8α(+) DCs are required for the improved T-cell crosspriming. Antibody neutralization assays show that IL-12 and IFN-γ are essential for the Flagrp170-elicited antitumor response, which also involves CD8(+) T cells and natural killer cells. The therapeutic efficacy of Flagrp170 and its immunostimulating activity are also confirmed in mouse prostate cancer and colon carcinoma. Together, targeting the tumor microenvironment with this chimeric chaperone is highly effective in mobilizing or restoring antitumor immunity, supporting the potential therapeutic use of this novel immunomodulator in the treatment of metastatic diseases.
Demographics of Students in Christian Higher Education: A National Study of Part-Time Enrollment, Ethnicity, and Gender (2008)

The research reported in this paper examined fall 2005 enrollment status, ethnicity, and gender for Christian and public colleges and universities awarding four-year degrees. Data were extracted from the Integrated Postsecondary Education Data System (IPEDS). The study included 235 Christian and 659 public colleges and universities. The indicated demographics were analyzed for fall 2005, then evaluated for disparities between Christian and public institutions. Statistical differences in the percentage of part-time enrollments, ethnicity, and female students were identified. Suggestions for improved practice and further research are provided.
Comparison of red and infrared low-level laser therapy in the treatment of acne vulgaris (2012)

Red wavelength is safe and effective to be used to treat acne vulgaris by LLLT compared to infrared wavelength.
Studies on the Synthesis of Quinoline Compounds. XII (1961)

Application of one mole of bromine to 4-chloro-2-methyl-3-vinyl-8-quinolinol (I) in a suitable solvent results in stepwise bromination, each product precipitating out as crystals insoluble in the solvent.1) (I) forms a monobromo compound, 5-bromo-4-chloro-2-methyl-3-vinyl-8-quinolinol (II), in glacial acetic acid solution.2) (II) forms 5, 7-dibromo compound (V) in chloroform.3) (V) forms a tetrabromo compound, 3-(1, 2-dibromoethyl)-5, 7-dibromo compound (VIII) in carbon tetrachloride solution.4) (VIII) forms a hexabromo compound, 2-dibromomethyl-3-(1, 2-dibromoethyl)-5, 7-dibromo compound (IX) in chloroform solution.5) Further bromination of the methyl group in (IX) was attempted but 2-tribro-methyl compound was not produced.
Using high-resolution variant frequencies to empower clinical genome interpretation (2017)

PurposeWhole-exome and whole-genome sequencing have transformed the discovery of genetic variants that cause human Mendelian disease, but discriminating pathogenic from benign variants remains a daunting challenge. Rarity is recognized as a necessary, although not sufficient, criterion for pathogenicity, but frequency cutoffs used in Mendelian analysis are often arbitrary and overly lenient. Recent very large reference datasets, such as the Exome Aggregation Consortium (ExAC), provide an unprecedented opportunity to obtain robust frequency estimates even for very rare variants.MethodsWe present a statistical framework for the frequency-based filtering of candidate disease-causing variants, accounting for disease prevalence, genetic and allelic heterogeneity, inheritance mode, penetrance, and sampling variance in reference datasets.ResultsUsing the example of cardiomyopathy, we show that our approach reduces by two-thirds the number of candidate variants under consideration in the average exome, without removing true pathogenic variants (false-positive rate<0.001).ConclusionWe outline a statistically robust framework for assessing whether a variant is "too common" to be causative for a Mendelian disorder of interest. We present precomputed allele frequency cutoffs for all variants in the ExAC dataset.