gebhart/patrepeval huggingface dataset:
High quality SNP calling using Illumina data at shallow coverage (2010)

Detection of single nucleotide polymorphisms (SNPs) has been a major application in processing second generation sequencing (SGS) data. In principle, SNPs are called on single base differences between a reference genome and a sequence generated from SGS short reads of a sample genome. However, this exercise is far from trivial; several parameters related to sequencing quality, and/or reference genome properties, play essential effect on the accuracy of called SNPs especially at shallow coverage data. In this work, we present Slider II, an alignment and SNP calling approach that demonstrates improved algorithmic approaches enabling larger number of called SNPs with lower false positive rate. In addition to the regular alignment and SNP calling, as an optional feature, Slider II is capable of utilizing information about known SNPs of a target genome, as priors, in the alignment and SNPs calling to enhance it's capability of detecting these known SNPs and novel SNPs and mutations in their vicinity.
Synthesis of Branched Methyl Hydroxy Stearates Including an Ester from Bio-Based Levulinic Acid (2007)

We report the synthesis of five useful branched methyl α-hydroxy stearate esters from commercially available methyl oleate and common organic acids. Of special interest is the synthesis utilizing the natural byproduct, levulinic acid. The other common organic acids, used herein, were propionic acid, hexanoic acid, octanoic acid, and 2-ethylhexanoic acid. The kinetics of the ring opening reaction were studied under pseudo-first-order conditions in the propionic acid system. An Arrhenius activation energy of 66.7 kJ mol-1 (16.0 kcal mol-1) was found. One product, the octanoic ester of methyl hydroxy stearate, was shown to have pour point, cloud point, and viscosity indices of −31 °C, −33 °C, and 101, respectively, all favorable properties in the synthesis of a bio-based lubrication fluid. These products may also prove useful in the synthesis of agriculturally based surfactants and fuel additives.
Comparison of Insulators and Promoters for Expression of the Wiskott–Aldrich Syndrome Protein Using Lentiviral Vectors (2013)

Gene therapy for the treatment of Wiskott-Aldrich syndrome (WAS) presents an alternative to the current use of allogeneic bone marrow transplantation. We describe the development of a self-inactivating lentiviral vector containing chromatin insulators for treatment of WAS and compare a gammaretroviral (MND), human cellular (EF1α), and the human WASp gene promoter for expression patterns in vivo during murine hematopoiesis using the green fluorescent protein (GFP) marker. Compared with the EF1α and the WASp promoters, expression from the MND promoter in mouse transplant recipients was much higher in all lineages examined. Importantly, there was sustained expression in the platelets of secondary recipient animals, necessary to correct the thrombocytopenia defect in WAS patients. Analysis of WAS protein expression in transduced human EBV-immortalized B-cells and transduced patient peripheral blood mononuclear cells also demonstrated stronger expression per copy from the MND promoter compared with the other promoters. In addition, when analyzed in an LM02 activation assay, the addition of an insulator to MND-promoter-containing constructs reduced transactivation of the LM02 gene. We propose a clinical trial design in which cytokine-mobilized, autologous, transduced CD34(+) cells are administered after myelosuppression.
Characterization of the Metal-Binding Sites of the β-Lactamase from Bacteroides fragilis (1996)

In an effort to better understand the structure and function of the metallo-beta-lactamase from Bacteroides fragilis, spectroscopic and metal-binding studies were performed on the native, metal-substituted, and mutant forms of the enzyme. Atomic absorption studies demonstrate that the native B. fragilis enzyme tightly binds 2 mol of Zn(II) and, along with mutagenesis studies, that the presence of both metal ions is required for full catalytic activity. EPR spectroscopy was used to confirm that the Co(II)-substituted beta-lactamase binds 2 mol of Co(II) per mole of enzyme, that the two Co(II)'s are highspin and probably uncoupled, with apparent g values of 6.5, 4.2, and 2.0, and that the coordination number of the Co(II) is 5 or 6. This number of ligands for the Co(II)-substituted enzyme is confirmed by UV-Vis spectra, which demonstrate the presence of very weak d-d transitions between 550 and 650 nm (epsilon approximately 30 M-1.cm-1) and an intense feature at 320 nm (epsilon approximately 1570 M-1.cm-1). The latter is assigned to a cysteine sulfur to Co(II) ligand-to-metal charge transfer band, and this assignment is confirmed by the disappearance of this band in the UV-Vis spectrum of a Co(II)-substituted C168S mutant. H NMR studies on the Co(II)-substituted enzyme suggest the presence of three histidine ligands bound to Co(II). Taken together, these studies support the sequence comparison study of Rasmussen et al., in which there is a catalytic metal-binding site with three histidines and one cysteine (C168). The remaining ligands are postulated to be water molecules involved in catalysis. Mutagenesis studies, in combination with activity assays and metal-binding studies, have been used to identify Asp61, Asp90, Asp152, and Asp183 as possible ligands to the second metal-binding site, with Asp90 and Asp152 having a pronounced effect on kcat. These results are discussed in light of the recent crystal structure of the metallo-beta-lactamase from B. cereus.
Salicylate-induced changes in spontaneous activity of single units in the inferior colliculus of the guinea pig (1986)

Changes in spontaneous neuronal activity of the inferior colliculus in albino guinea pigs before and after administration of sodium salicylate were analyzed. Animals were anesthetized with pentobarbital, and two microelectrodes separated by a few hundred microns were driven through the inferior colliculus. After collecting a sufficiently large sample of cells, sodium salicylate (450 mg/kg) was injected i.p. and recordings again made 2 h after the injection. Comparison of spontaneous activity recorded before and after salicylate administration revealed highly statistically significant differences (p less than 0.001). After salicylate, the mean rate of the cell population increased from 29 to 83 Hz and the median from 26 to 74 Hz. Control experiments in which sodium salicylate was replaced by saline injection revealed no statistically significant differences in cell discharges. Recordings made during the same experiments from lobulus V of the cerebellar vermis revealed no changes in response to salicylate. The observed changes in single-unit activity due to salicylate administration may represent the first systematic evidence of a tinnituslike phenomenon in animals.
IL-22 Participates in an Innate Anti-HIV-1 Host-Resistance Network through Acute-Phase Protein Induction (2007)

Certain individuals are resistant to HIV-1 infection, despite repeated exposure to the virus. Although protection against HIV-1 infection in a small proportion of Caucasian individuals is associated with mutant alleles of the CCR5 HIV-1 coreceptor, the molecular mechanism underlying resistance in repeatedly HIV-1-exposed, uninfected individuals (EU) is unclear. In this study, we performed complementary transcriptome and proteome analyses on peripheral blood T cells, and plasma or serum from EU, their HIV-1-infected sexual partners, and healthy controls, all expressing wild-type CCR5. We report that activated T cells from EU overproduce several proteins involved in the innate immunity response, principally those including high levels of peroxiredoxin II, a NK-enhancing factor possessing strong anti-HIV activity, and IL-22, a cytokine involved in the production of acute-phase proteins such as the acute-phase serum amyloid A (A-SAA). Cell supernatants and serum levels of these proteins were up-regulated in EU. Moreover, a specific biomarker for EU detected in plasma was identified as an 8.6-kDa A-SAA cleavage product. Incubation of in vitro-generated myeloid immature dendritic cells with A-SAA resulted in CCR5 phosphorylation, down-regulation of CCR5 expression, and strongly decreased susceptibility of these cells to in vitro infection with a primary HIV-1 isolate. Taken together, these results suggest new correlates of EU protection and identify a cascade involving IL-22 and the acute phase protein pathway that is associated with innate host resistance to HIV infection.
A Survey of Complex Object Technologies for Digital Libraries (2001)

Many early web-based digital libraries (DLs) had implicit assumptions reflected in their architecture that the unit of focus in the DL (frequently &amp;quot;reports&amp;quot; or &amp;quot;e-prints&amp;quot;) would only be manifested in a single, or at most a few, common file formats such as PDF or PostScript. DLs have now matured to the point where their contents are commonly no longer simple files. Complex objects in DLs have emerged in response to various requirements, including: simple aggregation of formats and supporting files, bundling additional information to aid digital preservation, creating opaque digital objects for e-commerce applications, and the incorporation of dynamic services with the traditional data files. We examine a representative (but not necessarily exhaustive) number of current and recent historical web-based complex object technologies and projects that are applicable to DLs: Aurora, Buckets, ComMentor, Cryptolopes, Digibox, Document Management Alliance, FEDORA, Kahn-Wilensky Framework Digital Objects, Metadata Encoding &amp;amp; Transmission Standard, Multivalent Documents, Open eBooks, VERS Encapsulated Objects, and the Warwick Framework.
Analysis of the role of the Pseudomonas syringae pv. syringae HrpZ harpin in elicitation of the hypersensitive response in tobacco using functionally non‐polar hrpZ deletion mutations, truncated HrpZ fragments, and hrmA mutations (1996)

Pseudomonas syringae pv. syringae, like many plant pathogenic bacteria, secretes a 'harpin' protein that can elicit the hypersensitive response (HR), a defensive cellular suicide, in non-host plants. The harpin-encoding hrpZ gene is located in an operon that also encodes Hrp secretion pathway components and is part of the functional cluster of hrp genes carried on cosmid pHIR11 that enables saprophytic bacteria like Escherichia coli and Pseudomonas fluorescens to elicit the HR in tobacco leaves. We have constructed functionally non-polar hrpZ deletion mutations, revealing that HrpZ is necessary for saprophytic bacteria carrying pHIR11 to elicit a typical HR, whereas it only enhances the elicitation activity of P. s. syringae. Partial deletion mutations revealed that the N-terminal 153 amino acids of HrpZ can enable E. coli MC4100-(pHIR11) to elicit a strong HR. hrpZ subclone products comprising the N-terminal 109 amino acids and C-terminal 216 amino acids, respectively, of the 341 amino acid protein were isolated and found to elicit the HR. P. fluorescens (pHIR11 hrmA::TnphoA) mutants do not elicit the HR, but cell fractionation and immunoblot analysis revealed that they produce and secrete wild-type levels of HrpZ. Therefore, elicitor activity resides in multiple regions of HrpZ, P. syringae produces elicitor(s) in addition to HrpZ, and HrpZ is essential but not sufficient for HR elicitation by saprophytic bacteria carrying pHIR11.
A triazole-templated ring-closing metathesis for constructing novel fused and bridged triazoles (2007)

The feasibility of trapping the vinyl copper intermediate generated in situ from azide-[3 + 2] cycloadditions and viability of employing these triazoles as unique templates for ring-closing metathesis are described here; this work effectively combines the two powerful reactions for the first time to construct various de novo fused and bridged triazoles that are otherwise not trivial to synthesize.
Sol–gel synthesis of the P2O5–CaO–Na2O–SiO2 system as a novel bioresorbable glass (2005)

A series of phosphate-based sol–gel glasses in the system P2O5–CaO–Na2O–SiO2 were synthesised using PO(OH)3−x(OC2H5)x (x = 1, 2) as a phosphorus precursor and alkoxides of sodium, calcium and silicon in an ethylene glycol solution. It has been found that the upper limit for gel formation is about 22 mol% phosphorus and that the gelation time increases with increasing phosphorus content of the sol. X-ray diffraction (XRD) along with X-ray fluorescence chemical analysis (XRF) have been performed on samples containing 45 mol% of P2O5 and 0, 10, 15 and 25 mol% of SiO2 with varying amount of modifier oxides (CaO, Na2O). All the samples are predominantly amorphous up to 400 °C and some of them, depending on the composition, retain their amorphous structure up to 600 and 800 °C. To the knowledge of the authors, this is the first time that phosphate-based glasses having these compositions have successfully been synthesised via the sol–gel method.
Pathophysiology and Histopathology of Group B Streptococcal Sepsis in Macaca nemestrina Primates Induced after Intraamniotic Inoculation: Evidence for Bacterial Cellular Invasion (1991)

Four pregnant Macaca nemestrina dams at 140-145 days of gestation received an intraamniotic inoculation of group B streptococci (GBS). All four premature infants were born by cesarean delivery, were bacteremic at birth, and showed symptoms of GBS sepsis similar to infected human infants with early-onset disease. Three infants did not receive antibiotics and died of GBS sepsis by 10 h of age despite mechanical ventilation and fluids for blood pressure support. Penicillin treatment of the fourth infant prolonged survival and decreased the requirement for supportive therapy. Quantitative cultures and histopathology were done on all four infants. Transmission electron microscopy of lung tissue demonstrated GBS within membrane-bound vacuoles of type I and II alveolar epithelium and interstitial fibroblasts. This model should be useful for studying the early steps in the pathogenesis of early-onset GBS infections. GBS may enter alveolar epithelial cells to transit this barrier and ultimately disseminate via the blood-stream.
Consistent response to treatment with cetuximab monotherapy in patients with metastatic colorectal cancer (2005)

3536 Background: Erbitux (Cetuximab), an IgG1 monoclonal antibody, is active in patients with metastatic colorectal cancer (CRC). A phase II study explored the activity of cetuximab in patients with heavily pretreated CRC. Methods: Patients with metastatic CRC were eligible if they had failed at least two prior chemotherapy regimens, containing irinotecan, oxaliplatin, and a fluoropyrimidine. There was no limit in the number of lines of prior treatment. Patients received cetuximab at an initial dose of 400 mg/m2, followed by weekly doses of 250 mg/m2, until disease progression or unacceptable toxicity. Response was assessed by an independent review committee, using a modified version of WHO criteria. Results: 346 patients treated had a median age of 59 years; 54% were male, and an ECOG performance status of 0 (42%) or 1 (58%). Patients received a median of 4 regimens of prior CRC therapy (range 2–9). Median cetuximab therapy was 9 doses (range 1–56+). Patients achieved a 12% PR rate (95% CI 8%–15%) and a median survival time of 6.6 months (95% CI 5.6–7.6 months). 259 patients received oxaliplatin after irinotecan. The other 87 patients received irinotecan after or with oxaliplatin. The response rate was 12% in both groups. 282 patients (81%) progressed on, or within 30 days of the last dose of the latest prior regimen with a response rate of 11%. 64 patients (19%) either progressed after 30 days of the last dose or were intolerant of the latest prior regimen, with a response rate of 14%. Conclusion: Cetuximab is active in patients with heavily pre-treated metastatic colorectal cancer with a consistent response rate regardless of the number of the lines of prior therapy, or sequence of prior agents. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ImClone Systems Bristol-Myers Squibb, Chiron, Response Genetics, Genentech Bristol-Myers Squibb, Roche, Pfizer, Lilly Oncology, Sanofi Bristol-Myers Squibb, National Cancer Institute, National Institutes of Health
Rat monoclonal antibodies produced against rat colorectal adenocarcinomas define tumor‐ and colon‐associated, auto‐immunogenic antigens (1990)

Monoclonal antibodies (MAbs) were derived from rats immunized against allo- and syngeneic rat colon carcinomas. Screening was performed by immunohistochemistry modified for MAbs of the same species as the tissue used for frozen sections. From 2 fusions, several MAbs were found that bound to syngeneic tumor tissue but showed little or no staining of normal adult tissues. Another group of MAbs demonstrated an intracellular staining of tumor cells and staining of mucus and goblet cells in the distal 2/3 of the normal colon. A third group of MAbs showed staining of both tumor and normal colon tissue. Staining patterns were reproduced with 6 MAbs selected from the first 2 groups after purification and biotinylation. One MAb, 10B12, recognized an antigen expressed in 10/11 colon carcinomas, the lowest parts of colonic crypts, intracellularly in a subpopulation of pancreatic acinar cells and mucus in antrum. It was used for affinity purification of a high-molecular-weight antigen, to which 3 of the other rat MAbs also bound. This antigen was also bound by antibodies to blood group A and isogloboseries carbohydrate determinants. Competition with the labelled 10B12 MAb for binding to the purified antigen was demonstrated in sera of tumor-bearing and immune rats. Thus, this high-molecular-weight glycoprotein expressed both auto-antigenic, tumor-associated and tissue-type-restricted epitopes. The 10B12 MAb homogeneously stained the majority of colorectal carcinomas and the antigenic determinant was expressed on the cell surface of 12/13 tissue-cultured colon-carcinoma clones. Modulation of the cell-surface antigen phenotype by recombinant rat interferon-gamma markedly increased expression of this determinant.
Control of Follicle‐Stimulating Hormone and Luteinizing Hormone Release by Hypothalamic Peptidesa (1993)

Lesion, stimulation, and pharmacological studies point to separate hypothalamic control of pulsatile FSH and LH secretion. LH release is controlled by a region extending from the preoptic area to the anterior and mid-median eminence, whereas FSH release is controlled by a region extending from the dorsal anterior hypothalamic area to the caudal median eminence. We have separated an FSH-releasing factor from LHRH by gel-filtration on Sephadex G-25, confirming results obtained over 25 years ago; and we are attempting its isolation in collaboration with Vale and River. In the meantime, reasoning that FSH-releasing factor might be related to LHRH, we tested many analogs of LHRH and found one that has selective FSH-releasing activity over a 50-fold dose range; however, it is relatively weak. This led us to the possibility that the GAP might be FSH-RF. Indeed, GAP1-13 has FSH but no LH-releasing activity over a 100-fold dose range; however, it is less potent than we would expect of the natural product. Substituting D-Trp-9 into the molecule to inhibit enzymatic degradation yielded a more potent and completely selective FSH-releasing peptide,24 which could be clinically useful. Alpha-inhibin-92 of Li et al. has been shown to have a highly selective dose-related suppressive action on FSH release in castrate male rats.25 Smaller fragments (35-65 and 66-92) of this molecule also possess the activity, albeit at higher doses. That this molecule may be physiologically significant is indicated by elevations in plasma FSH in immature rats obtained following intravenous injection of antisera raised against the peptide. Because of its much smaller size than that of 32-kDa alpha, beta inhibins and the lack of carbohydrate in the molecule, this can be relatively easily synthesized and might have clinical utility as an FSH release-inhibiting peptide.
Doping effects of dimethyl-tin-dichloride on material properties of CdS films and on formation of CdS∕CdTe heterostructures (2005)

A series of systematic investigations has been conducted to examine the doping effects of dimethyl-tin-dichloride (DMTC) on the structural, electrical, and optical properties of CdS films used for photovoltaic applications. After the DMTC doping, Sn and Cl concentrations in CdS are found to increase to 6×1017 and 4.5×1018atoms∕cm3, respectively; the CdS grain size also tends to increase. A slight increase in the electrical conductivity is discussed in conjunction with the increase in the grain size and the Cl donor concentration. In addition, the optical-absorption spectra reveal almost no change in the band gap of CdS due to the doping, while the spectra indicate a deterioration of the crystallinity of the heavily doped CdS. The influence of the DMTC doping into the CdS films on the formation of the CdS∕CdTe heterostructure is also discussed. With an increase in the grain size of the CdS underlayer due to the DMTC doping, the degree of the (111) preferential orientation of CdTe increases, which generally corresponds to an improvement in the photovoltaic performance. On the other hand, a fairly small reduction is observed in the sulfur fraction in the CdTe1−xSx mixed-crystal interlayer, which indicates no marked deterioration at the CdS∕CdTe interface. The DMTC doping is also effective in reducing the optical reflectance in almost the entire active spectral region of the CdS∕CdTe solar cell.
Toxicity to Protozoa of Thalidomide Breakdown Products; Counteraction By Nicotinic Acid and Glutamine. (1963)

The toxicity of thalidomide and some of its breakdown products were tested on protozoa, mainly the flagellate Ochromonas danica. Toxicity attributed to the phthalimide ring or phthalic acid was reversed by nicotinic acid. Glutamine contributed to this reversal, especially with compounds having a phthalimide group or a partly hydrogenated phthalic acid; glutamine was especially effective with Doriden which has a glutarimide group, but lacks a phthalimide group. These results with protozoa are in accord with the reported teratogenicity of nicotinamide antagonists.
Alloyed Semiconductor Quantum Dots:  Tuning the Optical Properties without Changing the Particle Size (2003)

Alloyed semiconductor quantum dots (cadmium selenium telluride) with both homogeneous and gradient internal structures have been prepared to achieve continuous tuning of the optical properties without changing the particle size. Our results demonstrate that composition and internal structure are two important parameters that can be used to tune the optical and electronic properties of multicomponent, alloyed quantum dots. A surprising finding is a nonlinear relationship between the composition and the absorption/emission energies, leading to new properties not obtainable from the parent binary systems. With red-shifted light emission up to 850 nm and quantum yields up to 60%, this new class of alloyed quantum dots opens new possibilities in band gap engineering and in developing near-infrared fluorescent probes for in vivo molecular imaging and biomarker detection.