gebhart/patrepeval huggingface dataset:
A calcitonin gene‐related peptide (CGRP) antagonist (CGRP8–37) inhibits microvascular responses induced by CGRP and capsaicin in skin (1991)

1. The effect of the calcitonin gene-related peptide (CGRP) antagonist CGRP8-37 on responses to CGRP and other mediators was investigated in rabbit dorsal skin. 2. Blood flow changes at intradermally-injected sites were measured by a multiple site 133xenon clearance technique. CGRP8-37 had little effect on blood flow at doses up to 0.3 nmol/site, when injected alone, although a significant increase in blood flow was observed at the highest dose tested (1 nmol/site). 3. CGRP8-37 dose-dependently inhibited the increased blood flow induced by human alpha CGRP and human beta CGRP, but had no effect on equivalent vasodilator responses induced by vasoactive intestinal peptide (VIP) and prostaglandin E1 (PGE1). CGRP8-37 showed a preferential ability to inhibit alpha CGRP (IC50 0.04 nmol), when compared with beta CGRP (IC50 greater than or equal to 0.3 nmol). 4. Capsaicin, which selectively activates sensory nerves, caused a dose-dependent increase in blood flow when injected intradermally into rabbit skin. The effects of capsaicin (0.01-0.1 mumol/site) were inhibited by CGRP8-37 (0.3 nmol/site), with a partial but significant attenuation of blood flow induced by the highest dose of capsaicin. 5. Oedema formation, induced by intradermal histamine injection (3 nmol/site), was measured in rabbit skin by the local accumulation of intravenously-injected 125I-labelled albumin. Vasodilator doses of CGRP, PGE1 and capsaicin potentiated, in a synergistic manner, oedema formation induced by histamine. GRP8-37 totally inhibited the potentiating effect of CGRP, partially inhibited the synergistic effect of capsaicin, but did not affect PGE1-induced responses.6. The results suggest that capsaicin acts to release a rabbit form of CGRP in skin and that CGRP8 37 is a useful antagonist for investigating the potential of CGRP as a neurogenic mediator of inflammation.
A hybrid gene to express protein epitopes from both sporozoite and merozoite surface antigens of Plasmodium falciparum (1988)

The DNA coding for parts of the repetitive amino acid sequence of Plasmodium falciparum circumsporozoite protein has been spliced to a sequence encoding part of the precursor to the major merozoite surface antigens, to produce a hybrid gene. Expression in Escherichia coli produces a protein with antigenic determinants from both malaria proteins. Antibodies raised against the expressed material react with both a peptide derived from the circumsporozoite repeat sequence, and the merozoite surface molecule. Hybrid molecules of this type may be the basis of a malaria vaccine.
Isolation and characterization of a potential biocontrol Brevibacillus laterosporus (2011)

An antagonist bacterium ZQ2 was isolated from an apple rhizosphere at Mount Tai in China.&nbsp;The bacterium strongly inhibited the growth of&nbsp;numerous apple phytopathogens&nbsp;in vitro, such as&nbsp;Rhizoctonia solani,&nbsp;Fusarium oxysporum,&nbsp;Fusarium solani,&nbsp;andPhysalospora piricola. The inhibition rates against the different fungi ranged from 55.26 to 88.17. The strain ZQ2 was identified as&nbsp;Brevibacillus laterosporus&nbsp;based on morphology, biochemical tests, and 16S rDNA sequence analysis. The antifungal metabolites produced by ZQ2 were thermally stable even after being maintained at 121&deg;C for 30 min. Meanwhile, the activity against the growth of&nbsp;R. solani&nbsp;was almost unchanged when the culture filtrate was irradiated under ultraviolet (UV) or at pH ranging from 1 to 11, and was only reduced under pH conditions from 12 to 14. When observed under a light microscope, the mycelia of&nbsp;R. solani&nbsp;inhibited by the antifungal metabolites appeared abnormal in growth. The strong antifungal activity and relatively stable active substances of&nbsp;B. laterosporus&nbsp;ZQ2 showed great potential for controlling fungal diseases in apples. &nbsp; Key words:&nbsp;Brevibacillus&nbsp;laterosporus, characterization, antifungal activity.
Lipid Nanoparticle Formulations for Enhanced Co-delivery of siRNA and mRNA (2018)

Although mRNA and siRNA have significant therapeutic potential, their simultaneous delivery has not been previously explored. To facilitate the treatment of diseases associated with aberrant gene upregulation and downregulation, we sought to co-formulate siRNA and mRNA in a single lipidoid nanoparticle (LNP) formulation. We accommodated the distinct molecular characteristics of mRNA and siRNA in a formulation consisting of an ionizable and biodegradable amine-containing lipidoid, cholesterol, DSPC, DOPE, and PEG-lipid. Surprisingly, the co-formulation of siRNA and mRNA in the same LNP enhanced the efficacy of both drugs in vitro and in vivo. Compared to LNPs encapsulating siRNA only, co-formulated LNPs improved Factor VII gene silencing in mice from 44 to 87% at an siRNA dose of 0.03 mg/kg. Co-formulation also improved mRNA delivery, as a 0.5 mg/kg dose of mRNA co-formulated with siRNA induced three times the luciferase protein expression compared to when siRNA was not included. As not all gene therapy applications require both RNA drugs, we sought to extend the benefit of co-formulated LNPs to formulations encapsulating only a single type of RNA. We accomplished this by substituting the "helper" RNA with a negatively charged polymer, polystyrenesulfonate (PSS). LNPs containing PSS mediated the same level of protein silencing or expression as standard LNPs using 2-3-fold less RNA. For example, LNPs formulated with and without PSS induced 50% Factor VII silencing at siRNA doses of 0.01 and 0.03 mg/kg, respectively. Together, these studies demonstrate potent co-delivery of siRNA and mRNA and show that inclusion of a negatively charged "helper polymer" enhances the efficacy of LNP delivery systems.
Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy (2014)

Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy.
Prolonged Therapeutic Hypothermia After Traumatic Brain Injury in Adults (2003)

Therapeutic hypothermia may reduce the risks of mortality and poor neurologic outcome in adults with TBI. Outcomes were influenced, however, by depth and duration of hypothermia as well as rate of rewarming (<or=24 hours) after discontinuation of hypothermia. Nonetheless, the evidence is not yet sufficient to recommend routine use of therapeutic hypothermia for TBI outside of research settings.
Achieving logarithmic growth of temporal and spatial complexity in reverse automatic differentiation (1992)

In its basic form the reverse mode of automatic differentiation yields gradient vectors at a small multiple of the computational work needed to evaluate the underlying scalar function. The practical applicability of this temporal complexity result, due originally to Linnainmaa, seemed to be severely limited by the fact that the memory requirement of the basic implementation is proportional to the run timeT, of the original evaluation program. It is shown here that, by a recursive scheme related to the multilevel differentiation approach of Volin and Ostrovskii, the growth in both temporal and spatial complexity can be limited to a fixed multiple of log(T). Other compromises between the run time and memory requirement are possible, so that the reverse mode becomes applicable to computational problems of virtually any size.
Structure and mechanism of galactose oxidase. The free radical site. (1994)

Crystallographic and spectroscopic studies on galactose oxidase have shown that the active site involves a free radical on tyrosine 272, one of the ligands coordinated to the Cu2+ cofactor. A novel thioether bond between tyrosine 272 and cysteine 228, and a stacking tryptophan 290, over this bond, are features of the crystal structure. The present study describes the development of a high level heterologous expression system for galactose oxidase and the construction of mutational variants at these key active site residues. The expressed wild-type enzyme and mutational variants (W290H and C228G) have been characterized by x-ray crystallography, visible spectroscopy, and catalytic activity measurements. A further variant protein, Y272F, could not be purified. The data establish that the thioether bond and stacking tryptophan are essential for activity and further support a role for tryptophan 290 as a component of the free radical site.
2. Cytogenetic and Genetic Abnormalities in Leukemia (2013)

白血病は，染色体異常の情報がもっとも早くから臨床現場で用いられてきた疾患である．染色体検査による予後分類は，急性骨髄性白血病における治療戦略上の基本情報である．また，染色体転座関連遺伝子の解析が進み，融合遺伝子を同定ないし定量する技術は，診断や微小残存病変の検出に広く臨床応用されている．さらに近年，染色体異常とは独立に多数の遺伝子異常が同定され，これらの遺伝子異常の組み合わせでより詳細な予後予測が可能になりつつある．早晩，これらの情報が日常診療で利用できるようになると期待される．
Optical trapping (2004)

Since their invention just over 20 years ago, optical traps have emerged as a powerful tool with broad-reaching applications in biology and physics. Capabilities have evolved from simple manipulation to the application of calibrated forces on-and the measurement of nanometer-level displacements of-optically trapped objects. We review progress in the development of optical trapping apparatus, including instrument design considerations, position detection schemes and calibration techniques, with an emphasis on recent advances. We conclude with a brief summary of innovative optical trapping configurations and applications.
Cooperative binding of ATP and RNA induces a closed conformation in a DEAD box RNA helicase (2008)

RNA helicases couple the energy from ATP hydrolysis with structural changes of their RNA substrates. DEAD box helicases form the largest class of RNA helicases and share a helicase core comprising two RecA-like domains. An opening and closing of the interdomain cleft during RNA unwinding has been postulated but not shown experimentally. Single-molecule FRET experiments with the Bacillus subtilis DEAD box helicase YxiN carrying donor and acceptor fluorophores on different sides of the interdomain cleft reveal an open helicase conformation in the absence of nucleotides, or in the presence of ATP, or ADP, or RNA. In the presence of ADP and RNA, the open conformation is retained. By contrast, cooperative binding of ATP and RNA leads to a compact helicase structure, proving that the ATP- and ADP-bound states of RNA helicases display substantially different structures only when the RNA substrate is bound. These results establish a closure of the interdomain cleft in the helicase core at the beginning of the unwinding reaction, and suggest a conserved mechanism of energy conversion among DEAD box helicases across kingdoms.
Enhancing uniformity and overall quality of red cell concentrate with anaerobic storage. (2017)

The surprisingly high variability in starting %SO<sub>2</sub> levels, coupled with negative impacts of high oxygen saturation on red blood cell quality indicates that oxygen levels may be an important and under-appreciated source of unit-to-unit variability in RBC quality.
Variants of the Adiponectin and Adiponectin Receptor-1 Genes and Posttransplantation Diabetes Mellitus in Renal Allograft Recipients (2011)

Genetic variation in ADIPOQ rs1501299 is associated with PTDM in a sex-specific manner.
Human immunodeficiency virus (HIV) Tat-reactive antibodies present in normal HIV-negative sera and depleted in HIV-positive sera. Identification of the epitope. (1992)

We have detected, in sera of normal human immunodeficiency virus (HIV)-free subjects, IgM antibodies reactive with the Tat protein of HIV in significant titers and at very high frequency, and, in HIV-positive sera, progressively lower titers as HIV pathogenesis ensues. Epitope analysis indicates that the Tat-reactive antibodies of both HIV-negative and HIV-positive sera are homologous, suggesting, therefore, that their decline in HIV-positive sera may represent attrition of a host defense factor. The identified epitope displays minimal homology with that previously defined for another set of IgM antibodies shown to be present in normal sera, deficient in HIV-positive sera, and postulated to be natural antibodies. We propose that the Tat-reactive antibodies, as well, are a set of natural antibodies and that the normal humoral immune system includes a repertoire of antibodies, nonimmunogenic in origin, that contribute to immune homeostasis and, consequently, to host resistance to HIV pathogenesis.
The Classic Wells−Dawson Polyoxometalate, K6[α-P2W18O62]·14H2O. Answering an 88 Year-Old Question: What Is Its Preferred, Optimum Synthesis? (2008)

The 88-year-old problem of developing a preferred, optimized synthesis of the prototype Wells-Dawson polyoxometalate, K6[alpha-P2W18O62].14H2O, is addressed herein. Specifically, six published syntheses of K6[alpha-P2W18O62].14H2O are listed and discussed, with emphasis given to the two most recent syntheses, Nadjo and co-workers' 2004 synthesis and a 1997 Inorganic Syntheses procedure by Droege, Randall, Finke et al. (hereafter D-R-F). For the starting experiment, the synthesis by Nadjo and co-workers was repeated. Next, the D-R-F synthesis and then the earlier (1984) synthesis in Droege's Ph.D. thesis were repeated and reinvestigated. The results demonstrate that the Nadjo synthesis produces over 200 g of high alpha-isomer purity (> or =97% by (31)P NMR) K6[alpha-P 2W18O62].14H2O in four steps over 8 days in 93% yield in our hands. A recrystallization step added as part of this work (for a total of five steps over 12 days) produces an increase in purity (>99%) with a concomitant loss of 8% yield (i.e., 85% overall yield) for the Nadjo-plus-recrystallization synthesis. Next, the D-R-F Inorganic Syntheses procedure was reinvestigated to determine the cause of "failed syntheses" occasionally encountered in our laboratories, the most recent and worst example to date being when one of us (C.R.G.) found 150 g of K10[alpha2-P 2W17O61] as an undesired side product when, as it turns out, the D-R-F Inorganic Syntheses procedure is followed rather than the earlier Droege synthesis. Specifically, it is shown that the problem in the Inorganic Syntheses procedure is that it ambiguously says to add 210 mL of HCl until a pH of 3-4 is reached when, in fact, it takes only 130-150 mL of HCL to reach a pH 3-4. Adding the full 210 mL of HCl ensures that a pH <2 is reached, as is required to produce isomerically pure K6[alpha-P 2W18O62].14H2O from the K 10[alpha 2-P 2W 17O 61] intermediate. The result is K6[alpha-P2W18O62].14H2O in five steps over 10 days in 82% yield and > or =97% purity. A table is provided comparing the details of the two best syntheses as reported herein: the Nadjo-plus-recrystallization synthesis and the D-R-F synthesis (with sufficient added HCl/proper pH control). That table makes apparent that the Nadjo-plus-recrystallization synthesis is improved on the basis of its better atom economy, its slightly higher product yields (85% vs 82%), slightly better purity (>99% vs >97%), and its comparable time (2 days shorter without recrystallization but 2 days longer with recrystallization) in comparison to the D-R-F synthesis with proper pH <2 control. Perhaps most importantly, some take-home messages concerning polyoxometalate synthesis illustrated by the iterative, 88 year-old quest to the best K6[alpha-P 2W18O62].14H2O synthesis are summarized and briefly discussed.
Automatic thresholding of three‐dimensional microvascular structures from confocal microscopy images (2007)

We have combined confocal microscopy, image processing, and optimization techniques to obtain automated, accurate volumetric measurements of microvasculature. Initially, we made tissue phantoms containing 15-microm FocalCheck microspheres suspended in type I collagen. Using these phantoms we obtained a stack of confocal images and examined the accuracy of various thresholding schemes. Thresholding algorithms from the literature that utilize a unimodal histogram, a bimodal histogram, or an intensity and edge-based algorithm all significantly overestimated the volume of foreground structures in the image stack. Instead, we developed a heuristic technique to automatically determine good-quality threshold values based on the depth, intensity, and (optionally) gradient of each voxel. This method analyzed intensity and gradient threshold methods for each individual image stack, taking into account the intensity attenuation that is seen in deeper images of the stack. Finally, we generated a microvascular construct comprised of rat fat microvessel fragments embedded in collagen I gels and obtained stacks of confocal images. Using our new thresholding scheme we were able to obtain automatic volume measurements of growing microvessel fragments.
Polymers having stable radicals. I. Synthesis of nitroxyl polymers from 4‐methacryloyl derivatives of 2,2,6,6‐tetramethylpiperidine (1972)

Abstract Polymers having stable nitroxyl free radicals, poly‐4‐methacryloylamino‐ and poly‐4‐methacryloyloxy‐2,2,6,6‐tetramethylpiperidine‐1‐oxyls, were synthesized from their precursor polymers by oxidizing them in a methanolic solution of hydrogen peroxide. The precursor polymers were prepared by radical polymerization of 4‐methacryloyl‐amino/oxy‐2,2,6,6‐tetramethylpiperidines in various solvents. These polymerizations in acetic acid were found to yield polymers of high molecular weight. The copolymers of the precursor monomers with styrene and methyl methacrylate were also prepared as precursor copolymers. These precursor polymers of a piperidine type were converted to the polymers having stable nitroxyl free radicals by the hydrogen peroxide method. In this report, it was assumed that the post‐oxidation reaction introduced a nitroxyl group smoothly and quantitatively at room temperature. Elucidations of the stable radical formation and the electron spin behavior of the stable radical polymers were made in terms of elemental analyses, infrared, ultraviolet, and ESR spectroscopy.
Synthesis of Novel Cationic Lipids:  Effect of Structural Modification on the Efficiency of Gene Transfer (2001)

A series of novel cationic lipids was designed and synthesized in an effort to understand the importance of the various structural features with respect to transfection efficiency. Particular attention has been paid to the hydrophobic domain and the cationic headgroup. An efficient method of synthesizing asymmetric diether lipids is described, using alkyl chains ranging from C(12) to C(18) and the unsaturated oleyl group. The ternary formulations including the diether lipid 3beta-[N-(N',N'-dimethylaminoethyl)carbamoyl]cholesterol (DC-Chol) and dioleoyl phosphatidylethanolamine (DOPE) were up to 10-fold more efficacious in in vitro assays than the DC-Chol/DOPE control. The shorter and most asymmetric diether lipids performed the best. The chemical nature and basicity of the headgroups have been varied by the coupling of the four naturally occurring amino acids with cationic side chains-arginine, histidine, lysine, and tryptophan. Transfection efficiency was highest for arginine/lysine derivatives, with binary formulations containing the amino acid derivative alone and DOPE proving superior.
Differential expression and regulation of Cyclin D1 protein in normal and tumor human cells: association with Cdk4 is required for Cyclin D1 function in G1 progression. (1994)

In this study we have surveyed by immunoblotting the protein levels of Cyclin D1, D2, D3 and their catalytic partners, Cdk4 and Cdk6 in normal and transformed human cells. We found that all these proteins were differentially expressed in diploid cells derived from different tissues, in contrast to Cyclin E, Cyclin A and Cdk2 which are ubiquitously expressed. D-type Cyclins were never dramatically overexpressed and often very poorly expressed in tumor cell lines when compared to the levels in their normal counterparts. In contrast, Cdk4 was expressed at high levels in several tumor cell lines and Cdk6 was ectopically expressed in two sarcoma lines, suggesting a possible involvement of these two Cdks in oncogenesis. Interestingly, low levels of Cyclin D1 and D3 proteins always correlated with functional inactivation of the retinoblastoma gene product (pRb). In cells displaying active pRb, Cyclin D1 was found associated with Cdk4 regardless of whether the p53 gene was wild-type or mutant. Microinjection during G1 of Cyclin D1 anti-sense cDNA or anti-Cyclin D1 antibody in these cells arrested the cell cycle in G1. In cells lacking pRb function, Cyclin D1 was dissociated from Cdk4. Microinjection during G1 of Cyclin D1 antisense cDNA or anti-Cyclin D1 antibody in these cells did not affect G1 progression. These results show that (i) in the absence of pRb, Cyclin D1 is expressed at low levels, is dissociated from Cdk4 and becomes dispensable in G1; (ii) Cyclin D1 needs to be associated with its catalytic subunit, Cdk4, to function as a positive regulator of G1 progression.
Streptomycin and Other Inhibitors as Selection Agents in Corn Tissue Cultures1 (1983)

We were interested in developing a tissue culture selection system to use in identifying potential extranuclear genetic markers in corn ( Zea mays L.). Streptomycin, kanamycin, chloramphenicol, aurin tricarboxylic acid, rifampicin, and erythromycin were evaluated for inhibition of seedling root growth and nonregenerable callus cultures of the inbred A619(N). All compounds caused inhibition at one or more concentrations in one or both bioassays. In additional tests on established, regenerable tissue cultures of the inbred A188(T), streptomycin and kanamycin inhibited growth at 100 μmol L −1 but not 10 μmol L −1 , while chloramphenicol was inhibitory at 10 μmol L −1 . Although all six compounds probably could be used as inhibitors in a tissue culture selection system, streptomycin, kanamycin, and chloramphenicol were the most inhibitory and appeared to be the most feasible to use. A188(T) and A188(N) regenerable tissue cultures were exposed to various levels of streptomycin for eight or five culture periods (cycles of selection), respectively. Culture growth was not inhibited at 50 μmol L −1 or less streptomycin, but was at 75 and 100 μmol L −1 . Three cycles of selection (40 days each) on 75 or 100 μmol L −1 were required for the cultures to lose all green pigmentation, after which selection for streptomycin resistance could be based on reappearance of green tissues. A culture sector that exhibited green tissues and a faster growth rate was identified after five cycles of selection on 100 μmol L −1 streptomycin. Six plantlets were regenerated from this source, but none developed past the third leaf stage so mature plant tests and progeny were not obtained to verify the resistance of this potentially variant culture line.