gebhart/patrepeval huggingface dataset:
Automated Autofluorescence Background Subtraction Algorithm for Biomedical Raman Spectroscopy (2007)

A significant advantage of Raman spectroscopy as a noninvasive optical technique is its ability to detect subtle molecular or biochemical signatures within tissue. One of the major challenges for biomedical Raman spectroscopy is the removal of intrinsic autofluorescence background signals, which are usually a few orders of magnitude stronger than those arising from Raman scattering. A number of methods have been proposed for fluorescence background removal including excitation wavelength shifting, Fourier transformation, time gating, and simple or modified polynomial fitting. The single polynomial and the modified multi-polynomial fitting methods are relatively simple and effective, and thus are widely used in biological applications. However, their performance in real-time in vivo applications and low signal-to-noise ratio environments is sub-optimal. An improved automated algorithm for fluorescence removal has been developed based on modified multi-polynomial fitting, but with the addition of (1) a peak-removal procedure during the first iteration, and (2) a statistical method to account for signal noise effects. Experimental results demonstrate that this approach improves the automated rejection of the fluorescence background during real-time Raman spectroscopy and for in vivo measurements characterized by low signal-to-noise ratios.
Copper-Catalyzed Synthesis of Benzoxazoles via a Regioselective C−H Functionalization/C−O Bond Formation under an Air Atmosphere (2009)

An efficient method for the synthesis of functionalized benzoxazoles is described that involves a copper(II)-catalyzed regioselective C-H functionalization/C-O bond formation protocol. The use of dichlorobenzene as a solvent at 160 degrees C allows the use of air as the terminal oxidant in the catalytic synthesis of benzoxazoles in a process that has high functional group tolerance. The presence of a directing group at the meta position markedly improves the reaction efficacy and a variety of 7-substituted benzoxazoles are selectively produced under mild reaction conditions. The mechanism of the reaction is also discussed in this report.
Co-expression of 3-ketoacyl-ACP reductase and polyhydroxyalkanoate synthase genes induces PHA production in Escherichia coli HB101 strain (1999)

The Escherichia coli 3-ketoacyl-ACP reductase gene (fabG Ec ) was cloned using a PCR technique to investigate the metabolic link between fatty acid metabolism and polyhydroxyalkanoate (PHA) production. Three plasmids respectively harboring fabG Ec and the poly-3-hydroxyalkanoate synthesis genes phaC Ac and phaC1 Ps from Aeromonas caviae and Pseudomonas sp. 61-3 respectively were constructed and introduced into E. coli HB101 strain. On a two-stage cultivation using dodecanoate as the sole carbon source, recombinant E. coli HB101 strains harboring fabG Ec and phaC genes accumulated PHA copolymers (about 8 wt% of dry cell weight) consisting of several (R)-3-hydroxyalkanoate units of C4, C6, C8, and C10. It has been suggested that overexpression of the fabG Ec gene leads to the supply of (R)-3-hydroxyacyl-CoA for PHA synthesis via fatty acid degradation.
The physiology and pathophysiology of rapamycin resistance (2011)

Rapamycin is an inhibitor of the mammalian Target of Rapamycin, mTOR, a nutrient-sensing signaling kinase and a key regulator of cell growth and proliferation. While rapamycin and related compounds have anti-tumor activity, a prevalent characteristic of cancer cells is resistance to their anti-proliferative effects. Our studies on nutrient regulation of fetal development showed that hepatocyte proliferation in the late gestation fetal rat is resistant to rapamycin. Extension of these studies to other tissues in the fetal and neonatal rat indicated that rapamycin resistance is a characteristic of normal cell proliferation in the growing organism. In hepatic cells, ribosomal biogenesis and cap-dependent protein translation were found to be relatively insensitive to the drug even though mTOR signaling was highly sensitive. Cell cycle progression was also resistant at the level of cyclin E-dependent kinase activity. Studies on the effect of rapamycin on gene expression in vitro and in vivo demonstrated that mTOR-mediated regulation of gene expression is independent of effects on cell proliferation and cannot be accounted for by functional regulation of identifiable transcription factors. Genes involved in cell metabolism were overrepresented among rapamycin-sensitive genes. We conclude that normal cellular proliferation in the context of a developing organism can be independent of mTOR signaling, that cyclin E-containing complexes are a critical locus for rapamycin sensitivity, and that mTOR functions as a modulator of metabolic gene expression in cells that are resistant to the anti-proliferative effects of the drug.
Stearylated octaarginine and artificial virus-like particles for transfection of siRNA into primary rat neurons (2006)

RNA interference (RNAi) provides a powerful experimental tool for sequence-specific gene silencing, allowing efficient analysis of gene function in a multitude of cell types. However, application of RNAi in primary mammalian neurons has been limited by low-transfection efficiency and considerable toxicity of conventional transfection methods. In this study, we evaluated a peptide-mediated and a polymer/lipid-based cellular delivery method for siRNA into rat primary neurons and compared the results with a commonly used liposomal transfection reagent. Stearylated octaarginine (Stearyl-R8) was used as polypeptide and artificial virus-like particles (AVPs) were used as a combined liposomal-polymeric vector, since both reagents have been previously shown to successfully transfect DNA into cell lines. Stearyl-R8 and AVPs both promoted siRNA transfection into primary hippocampal neurons via the endosomal pathway. SiRNA-mediated gene silencing could be effectively induced in primary neuron cultures. In comparison with the commonly used cationic liposome transfection agent, both novel reagents were less detrimental to cell metabolic activity. We conclude that these novel transfection methods yield performances comparable to cationic liposome-mediated transfection for siRNA, while being less cytotoxic in primary neurons. Stearyl-R8 and AVPs may therefore represent novel and more cost-efficient alternatives to conventional siRNA-transfection reagents.
Transfer of Therapeutic Genes into Fetal Rhesus Monkeys Using Recombinant Adeno-Associated Type I Viral Vectors (2016)

Neuromuscular disorders such as Pompe disease (glycogen storage disease, type II), result in early and potentially irreversible cellular damage with a very limited opportunity for intervention in the newborn period. Pompe disease is due to deficiency in acid α-glucosidase (GAA) leading to lysosomal accumulation of glycogen in all cell types, abnormal myofibrillogenesis, respiratory insufficiency, neurological deficits, and reduced contractile function in striated muscle. Previous studies have shown that fetal delivery of recombinant adeno-associated virus (rAAV) encoding GAA to the peritoneal cavity of Gaa<sup>-/-</sup> mice resulted in high-level transduction of the diaphragm. While progression of other genetic disorders may occur later in life, the potential of fetal gene delivery to avoid the onset of irreversible damage suggests it is an attractive option for many inherited diseases. In this study, rhesus monkey fetuses were administered 4.5 × 10<sup>12</sup> particles of rAAV type 1 expressing human GAA (rAAV1-CMV-hGAA), human α-1-antitrypsin (rAAV1-CBA-hAAT), or human mini-dystrophin (rAAV1-CMV-miniDMD) in the late first trimester using an established intraperitoneal ultrasound-guided approach. Fetuses were monitored sonographically and newborns delivered at term for postnatal studies. All animals remained healthy during the study period (growth, hematology, and clinical chemistry), with no evidence of adverse effects. Tissues were collected at a postnatal age of 3 months (∼7 months post-fetal gene transfer) for immunohistochemistry (IHC) and quantitative PCR. Both the diaphragm and peritoneum from vector-treated animals were strongly positive for expression of human GAA, AAT, or dystrophin by IHC, similar to findings when reporter genes were used. Protein expression in the diaphragm and peritoneum correlated with high vector copy numbers detected by real-time PCR. Other anatomical areas were negative, although the liver showed minimal evidence of human GAA, AAT, and DMD, vector genomes. In summary, delivery of rAAV vectors provided stable transduction of the muscular component of the diaphragm without any evidence of adverse effects.
Mixed Matrix PVDF Membranes With in Situ Synthesized PAMAM Dendrimer-Like Particles: A New Class of Sorbents for Cu(II) Recovery from Aqueous Solutions by Ultrafiltration (2015)

Advances in industrial ecology, desalination, and resource recovery have established that industrial wastewater, seawater, and brines are important and largely untapped sources of critical metals and elements. A Grand Challenge in metal recovery from industrial wastewater is to design and synthesize high capacity, recyclable and robust chelating ligands with tunable metal ion selectivity that can be efficiently processed into low-energy separation materials and modules. In our efforts to develop high capacity chelating membranes for metal recovery from impaired water, we report a one-pot method for the preparation of a new family of mixed matrix polyvinylidene fluoride (PVDF) membranes with in situ synthesized poly(amidoamine) [PAMAM] particles. The key feature of our new membrane preparation method is the in situ synthesis of PAMAM dendrimer-like particles in the dope solutions prior to membrane casting using low-generation dendrimers (G0 and G1-NH2) with terminal primary amine groups as precursors and epichlorohydrin (ECH) as cross-linker. By using a combined thermally induced phase separation (TIPS) and nonsolvent induced phase separation (NIPS) casting process, we successfully prepared a new family of asymmetric PVDF ultrafiltration membranes with (i) neutral and hydrophilic surface layers of average pore diameters of 22-45 nm, (ii) high loadings (∼48 wt %) of dendrimer-like PAMAM particles with average diameters of ∼1.3-2.4 μm, and (iii) matrices with sponge-like microstructures characteristics of membranes with strong mechanical integrity. Preliminary experiments show that these new mixed matrix PVDF membranes can serve as high capacity sorbents for Cu(II) recovery from aqueous solutions by ultrafiltration.
Structure and Mutational Analysis of the PhoN Protein of Salmonella typhimurium Provide Insight into Mechanistic Details (2007)

The Salmonella typhimurium PhoN protein is a nonspecific acid phosphatase and belongs to the phosphatidic acid phosphatase type 2 (PAP2) superfamily. We report here the crystal structures of phosphate-bound PhoN, the PhoN−tungstate complex, and the T159D mutant of PhoN along with functional characterization of three mutants: L39T, T159D, and D201N. Invariant active site residues, Lys-123, Arg-130, Ser-156, Gly-157, His-158, and Arg-191, interact with phosphate and tungstate oxyanions. Ser-156 also accepts a hydrogen bond from Thr-159. The T159D mutation, surprisingly, severely diminishes phosphatase activity, apparently by disturbing the active site scaffold: Arg-191 is swung out of the active site resulting in conformational changes in His-158 and His-197 residues. Our results reveal a hitherto unknown functional role of Arg-191, namely, restricting the active conformation of catalytic His-158 and His-197 residues. Consistent with the conserved nature of Asp-201 in the PAP2 superfamily, the D201N mutation completely abolished phosphatase activity. On the basis of this observation and in silico analysis we suggest that the crucial mechanistic role of Asp-201 is to stabilize the positive charge on the phosphohistidine intermediate generated by the transfer of phosphoryl to the nucleophile, His-197, located within hydrogen bond distance to the invariant Asp-201. This is in contrast to earlier suggestions that Asp-201 stabilizes His-197 and the His197−Asp201 dyad facilitates formation of the phosphoenzyme intermediate through a charge-relay system. Finally, the L39T mutation in the conserved polyproline motif (39LPPPP43) of dimeric PhoN leads to a marginal reduction in activity, in contrast to the nearly 50-fold reduction observed for monomeric Prevotella intermedia acid phosphatase, suggesting that the varying quaternary structure of PhoN orthologues may have functional significance.
Communication preserving protocols for secure function evaluation (2001)

A secure function evaluation protocol allows two parties to jointly compute a function f(x,y) of their inputs in a manner not leaking more information than necessary. A major result in this field is: “any function f that can be computed using polynomial resources can be computed securely using polynomial resources” (where “resources” refers to communication and computation). This result follows by a general transformation from any circuit for f to a secure protocol that evaluates f. Although the resources used by protocols resulting from this transformation are polynomial in the circuit size, they are much higher (in general) than those required for an insecure computation of f.We propose a new methodology for designing secure protocols, utilizing the communication complexity tree (or branching program) representation of f. We start with an efficient (insecure) protocol for f and transform it into a secure protocol. In other words, ``any function f that can be computed using communication complexity c can be can be computed securely using communication complexity that is polynomial in c and a security parameter''. We show several simple applications of this new methodology resulting in protocols efficient either in communication or in computation. In particular, we exemplify a protocol for the Millionaires problem, where two participants want to compare their values but reveal no other information. Our protocol is more efficient than previously known ones in either communication or computation.
Adamantyl-substituted phenolic polymers (1996)

4-(1-Adamantyl)phenol was synthesized via Friedel-Crafts reaction of 1-bromoadamantane and phenol. Substitution in the phenol para position forces polymerization to occur only in the ortho positions to give a linear polymer. Variations in formaldehyde amount, reaction time, and catalyst were evaluated. Increasing the amount of paraformaldehyde increased formation of cyclic octamer, an easily identified by-product due to its insolubility in common organic solvents. The cyclic octamer was acetylated to give a soluble model compound for comparison to acetylated polymers by IR and NMR. All of the synthetic variations employed produced low molecular weight polymers as indicated by NMR end-group analysis and SEC. The polymers showed number-average molecular weights of ca. 3000 (versus polystyrene standards by SEC), and exhibited glass transition temperatures ranging from 175–230°C, an increase of ca. 100°C over unsubstituted and para-alkyl substituted analogs. All of the samples exhibited a 10% weight loss at 400°C in nitrogen, indicating thermal stability much greater than the parent and alkyl-substituted polymers. © 1996 John Wiley & Sons, Inc.
Antigen-driven clonal proliferation of B cells within the target tissue of an autoimmune disease. The salivary glands of patients with Sjögren's syndrome. (1998)

Structures resembling germinal centers are seen in the salivary glands of patients with Sjögren's syndrome, but it is not known whether the microenvironment of these cell clusters is sufficient for the induction of a germinal center response. Therefore, we cloned and sequenced rearranged Ig V genes expressed by B cells isolated from sections of labial salivary gland biopsies from two Sjögren's syndrome patients. Rearranged V genes from B cells within one cell cluster were polyclonal and most had few somatic mutations. Two adjacent clusters from another patient each contained one dominant B cell clone expressing hypermutated V genes. None of the rearranged V genes was found in both clusters, suggesting that cells are unable to migrate out into the surrounding tissue and seed new clusters. The ratios of replacement to silent mutations in the framework and complementarity determining regions suggest antigen selection of high-affinity mutants. These results show that an antigen-driven, germinal center-type B cell response is taking place within the salivary glands of Sjögren's syndrome patients. In view of the recent demonstration of a germinal center response within the rheumatoid synovial membrane and the existence of similar structures in the target tissues of other autoimmune diseases, we propose that germinal center- type responses can be induced in the nonlymphoid target tissues of a variety of autoimmune diseases.
Cancer cell kill, in vivo biodistribution and antitumor properties of AS1411, a G-rich oligonucleotide aptamer (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4713 

AS1411 (formerly AGRO100) is a 26 mer unmodified guanosine rich oligonucleotide (GRO) that has been shown to bind as an aptamer to cell surface nucleolin and induce S-phase cell cycle arrest. AS1411 is the first nucleic acid aptamer to be used systemically for the treatment of cancer. In an initial Phase I trial involving 17 patients at the Brown Cancer Center, Louisville, promising signs of anticancer efficacy have been reported, especially in renal cancer patients, at doses causing no significant adverse effects (up to 10mg/kg/day given over 7 days). The aim of these studies was to further define the preclinical pharmacological properties of AS1411 in order to guide clinical dosing and scheduling and identify possible sensitive tumor types. AS1411 induced kill of a broad range of human cancer cell lines, derived from both hematological and solid cancers, typically requiring a 4-day exposure to concentrations of around 5μM. Biodistribution studies used intravenously administered tritiated AS1411 (1, 10 and 25 mg/kg) and mice bearing subcutaneous lung (A549) or renal (A498) cancer human xenografts. Results showed that AS1411 was taken up preferentially in xenografted tumors of renal and, to a lesser extent, lung; tumor to blood ratios were typically 3-5 and were maintained up to 4 days post dosing. Across the 1 to 25mg/kg dose-range studied approximately linear pharmacokinetics were obtained between dose administered and both plasma and tumor drug levels. Significant levels of AS1411 were also detected in the colon and small intestine although to date, in rodents, dogs and patients, no gastrointestinal related toxicities have been observed. Efficacy determinations (using AS1411 given iv daily for 5 days at doses of 5, 10, 40 mg/kg) are ongoing in mice bearing A549 and A498 xenografts. The Phase I study has now re-opened to allow further dose escalation in patients with renal cancer and NSCLC.
Genetically Engineered Saccharomyces Yeast Capable of Effective Cofermentation of Glucose and Xylose (1998)

Xylose is one of the major fermentable sugars present in cellulosic biomass, second only to glucose. However, Saccharomyces spp., the best sugar-fermenting microorganisms, are not able to metabolize xylose. We developed recombinant plasmids that can transform Saccharomyces spp. into xylose-fermenting yeasts. These plasmids, designated pLNH31, -32, -33, and -34, are 2 microns-based high-copy-number yeast-E. coli shuttle plasmids. In addition to the geneticin resistance and ampicillin resistance genes that serve as dominant selectable markers, these plasmids also contain three xylose-metabolizing genes, a xylose reductase gene, a xylitol dehydrogenase gene (both from Pichia stipitis), and a xylulokinase gene (from Saccharomyces cerevisiae). These xylose-metabolizing genes were also fused to signals controlling gene expression from S. cerevisiae glycolytic genes. Transformation of Saccharomyces sp. strain 1400 with each of these plasmids resulted in the conversion of strain 1400 from a non-xylose-metabolizing yeast to a xylose-metabolizing yeast that can effectively ferment xylose to ethanol and also effectively utilizes xylose for aerobic growth. Furthermore, the resulting recombinant yeasts also have additional extraordinary properties. For example, the synthesis of the xylose-metabolizing enzymes directed by the cloned genes in these recombinant yeasts does not require the presence of xylose for induction, nor is the synthesis repressed by the presence of glucose in the medium. These properties make the recombinant yeasts able to efficiently ferment xylose to ethanol and also able to efficiently coferment glucose and xylose present in the same medium to ethanol simultaneously.
Healing of Arterial Prostheses in Man (1972)

Berger, Knute M.D.; Sauvage, Lester R. M.D.; Rao, Alloju M. M.D.; Wood, Stephen J. M.D. Author Information
Early Onset of Action with Fremanezumab Versus Placebo for the Preventive Treatment of Chronic Migraine (P4.102) (2018)

Assess the early onset of action of fremanezumab in the prevention of chronic migraine.
Probing VH gene-family utilization in human peripheral B cells by in situ hybridization (1991)

Recent studies on the genomic organization of the human Ig VH locus have revealed the presence of an important proportion of VH pseudogenes and a high degree of interspersion among VH gene-family members. The mechanisms of selection of VH genes expressed by differentiating B cells remain to be elucidated. We have made use of RNA-RNA in situ hybridization to probe the repertoire of VH gene-families assembled in peripheral B cells of normal adults. Cells were in vitro activated with mitogens and then hybridized to [35S]-labeled anti-sense RNA probes specific for C mu and C gamma genes, and for the six known human VH gene-families. We found that the numbers of cells expressing C mu and C gamma mRNA were similar to the total numbers of cells expressing members of the six VH gene-families. Therefore, the six known VH gene-families represent essentially the human VH locus. We also found that expression of VH gene-families does not closely correlate with their relative genomic complexity. This apparently biased expression may suggest that in some VH gene-families the ratio of pseudogenes/functional genes is particularly high, and/or that regulatory mechanisms play a major role in shaping the available VH gene repertoire in differentiating B cells.
Transaortic TAVI Is a Valid Alternative to Transapical Approach (2015)

Comparison of TAo and TA approaches revealed equivalent outcomes in 30-day mortality, procedural success, major bleeding, stroke/TIA incidence, pacemaker insertion rates and paravalvular leak. Heart teams should be familiar with the use of both TA and TAo access and tailor their selection on a case-to-case basis.