gebhart/patrepeval huggingface dataset:
Affinity isolation of active murine erythroleukemia cell chromatin: Uniform distribution of ubiquitinated histone H2A between active and inactive fractions (1991)

This laboratory recently reported the development of a biotin-cellulose/streptavidin affinity chromatography method based on the DNase I sensitivity of active chromatin to isolate a DNA fraction from murine erythroleukemia (MEL) cells that is more than 15-fold enriched in active genes (Dawson et al.: Journal of Biological Chemistry 264:12830-12837, 1989). We now report the extension of this technique to isolate and characterize chromatin that is enriched in active genes. In this approach, DNA in nuclei isolated from MEL cells was nicked with DNase I at a concentration that does not digest the active beta-globin gene, followed by repair of the nicks with a cleavable biotinylated nucleotide analog, 5-[(N-biotin-amido)hexanoamido-ethyl-1,3'-dithiopropionyl-3- aminoallyl]-2'- deoxyuridine 5'-triphosphate (Bio-19-SS-dUTP), during a nick-translation reaction. After shearing and sonication of the nuclei to solubilize chromatin, chromatin fragments containing biotin were separated from non-biotinylated fragments by sequential binding to streptavidin and biotin cellulose. The bound complex contained approximately 10% of the bulk DNA. Reduction of the disulfide bond in the biotinylated nucleotide eluted approximately one-half of the affinity isolated chromatin. Hybridization analysis of DNA revealed that whereas inactive albumin sequences were equally distributed among the chromatin fractions, virtually all of the active beta-globin sequences were associated with chromatin fragments which had bound to the affinity complex. Western blot assessment for ubiquitinate histones revealed that ubiquitinated histone H2A (uH2A) was uniformly distributed among active (bound) and inactive (unbound) chromatin fractions.
Electrically programmable fuse (eFUSE) using electromigration in silicides (2002)

For the first time we describe a positive application of electromigration, as an electrically programmable fuse device (eFUSE). Upon programming, eFUSE's show a large increase in resistance that enable easy sensing. The transient device characteristics show that the eFUSE stays in a low resistance state during programming due to the local heating of the fuse link. The programming is enhanced by a device design that uses a large cathode which increases the temperature gradient and minimizes the effect of microstructural variations.
Confidentiality of Information and Personal Privacy (1993)

Accompanying the growth of data bases in private and public institutions is a concentration of personal and other sensitive data that should be considered privileged and confidential. Because organizations are increasingly automating the processing of personal information without the consent or knowledge of the individuals affected, the opportunities to breach more people's privacy at less cost, to greater advantage, occur much more frequently today than a generation ago. Nevertheless, disseminating personal information presents the same ethical considerations today as it did before computers emerged. The secondary effects that encourage increased sharing of such personal information as reduced cost, collection opportunities, and ease of distribution or access do not change the ethicality of breaching an individual's privacy. Those who address the ethical issues surrounding sensitive data must be aware of the dilemmas posed by the various laws, regulations, and policies dealing with such data. On the one hand, sensitive data must be protected from disclosure to unauthorized individuals and organizations.
Forcing Thermodynamically Unfolded Proteins to Fold (1998)

A growing number of biologically important proteins have been identified as fully unfolded or partially disordered. Thus, an intriguing question is whether such proteins can be forced to fold by adding solutes found in the cells of some organisms. Nature has not ignored the powerful effect that the solution can have on protein stability and has developed the strategy of using specific solutes (called organic osmolytes) to maintain the structure and function cellular proteins in organisms exposed to denaturing environmental stresses (Yancey, P. H., Clark, M. E., Hand, S. C., Bowlus, R. D., and Somero, G. N. (1982) Science 217, 1214-1222). Here, we illustrate the extraordinary capability of one such osmolyte, trimethylamine N-oxide (TMAO), to force two thermodynamically unfolded proteins to fold to native-like species having significant functional activity. In one of these examples, TMAO is shown to increase the population of native state relative to the denatured ensemble by nearly five orders of magnitude. The ability of TMAO to force thermodynamically unstable proteins to fold presents an opportunity for structure determination and functional studies of an important emerging class of proteins that have little or no structure without the presence of TMAO.
Generation of skeletal muscle stem/progenitor cells from murine induced pluripotent stem cells (2010)

Induced pluripotent stem (iPS) cells, which are a type of pluripotent stem cell generated from reprogrammed somatic cells, are expected to have potential for patient-oriented disease investigation, drug screening, toxicity tests, and transplantation therapies. Here, we demonstrated that murine iPS cells have the potential to develop in vitro into skeletal muscle stem/progenitor cells, which are almost equivalent to murine embryonic stem cells. Cells with strong in vitro myogenic potential effectively were enriched by fluorescence-activated cell sorting using the anti-satellite cell antibody SM/C-2.6. Furthermore, on transplantation into mdx mice, SM/C-2.6(+) cells exerted sustained myogenic lineage differentiation in injured muscles, while providing long-lived muscle stem cell support. Our data suggest that iPS cells have the potential to be used in clinical treatment of muscular dystrophies.
Lidocaine attenuates the hypotensive and inflammatory responses to endotoxemia in rabbits (1996)

Lidocaine attenuated the hemodynamic and inflammatory responses to endotoxemia in rabbits. Findings suggest that lidocaine administration may prevent the development of hypotension and metabolic acidosis during endotoxemia.
Characterization of a novel N-terminal peptide in human aspartyl-tRNA synthetase. Roles in the transfer of aminoacyl-tRNA from aminoacyl-tRNA synthetase to the elongation factor 1 alpha (1994)

The kinetics of the N-terminal 32 residue-deleted human aspartyl-tRNA synthetase (hDRS delta 32) was analyzed. The kinetics of aspartyl-adenylate formation and Asp-tRNA synthesis by hDRS delta 32 were indistinguishable from those of hDRS. However, the dissociation of Asp-tRNA from hDRS delta 32 was much faster than that of hDRS. Unlike hDRS delta 32-catalyzed aspartylation of tRNA was not affected by the elongation factor 1 alpha. Two N-terminal peptides of hDRS, hDRS(T5-E26) and hDRS(D12-R27), were synthesized. Both peptides bind to tRNA-Sepharose. Both peptides, hDRS(T5-E26) and hDRS(D12-R27), are monomeric and oligomerize at high peptide concentration or in 50% propylene glycol. The peptide hDRS(T5-E26) showed little alpha-helical content as analyzed by CD spectroscopy, while hDRS(D12-R27) showed appreciable alpha-helical contents in nonpolar solvents. These results suggest that the N terminus in hDRS may mediate the slow release of Asp-tRNA and facilitate the interaction of the hDRS.Asp-tRNA complex with the elongation factor 1 alpha. The demonstration of alpha-helix formation of the hDRS N-terminal peptide is consistent with the hypothetical amphiphilic helix of the N-terminal extension in hDRS. A model for the transfer of Asp-tRNA from hDRS to elongation factor 1 alpha is presented.
Quisqualic acid analogs: synthesis of .beta.-heterocyclic 2-aminopropanoic acid derivatives and their activity at a novel quisqualate-sensitized site (1992)

Hippocampal CA1 pyramidal cell neurons are sensitized over 30-fold to depolarization by L-2-amino-4-phosphonobutanoic acid (L-AP4) following exposure to L-quisqualic acid. This phenomenon has been termed the QUIS effect. In the present study several novel L-quisqualic acid analogues have been synthesized and tested for their interaction with the different components of the QUIS-effect system. Replacement of the oxadiazolidinedione ring of L-quisqualic acid with several other types of heterocyclic rings yielded the following quisqualic acid analogues: maleimide 2, N-methylmaleimide 3, N-(carboxymethyl)maleimide 4, succinimides 5A and 5B, and imidazolidinedione 6. None of these analogues were able to mimic the effects of L-quisqualic acid and sensitize hippocampal CA1 neurons to depolarization by L-AP4. Also, unlike L-serine O-sulfate, L-homocysteinesulfinic acid, or L-alpha-aminoadipic acid, none of the analogues were able to preblock or reverse the QUIS effect. However, when the IC50 values for inhibition of the CA1 synaptic field potential of analogues 2-6 were determined both before and after hippocampal slices were exposed to L-quisqualic acid, the IC50 values of analogues 3 and 4 were found to decrease more than 7-fold. Thus, these two compounds behave like L-AP4 rather than L-quisqualic acid in this system in that they exhibit increased potencies in slices that have been pretreated with L-quisqualic acid even though they cannot themselves induce this sensitization. Compounds 3 and 4, therefore, represent the first non-phosphorus-containing compounds to which hippocampal neurons become sensitized following exposure to L-quisqualic acid. No change in the IC50 values was observed for 5A or 5B. Analogues 2 and 6, on the other hand, displayed a high potency for inhibition of the evoked field potential even prior to treatment of the slices with L-quisqualic acid.
Absorption of Diltiazem in Beagle Dog from Pulsatile Release Tablet. (1992)

An orally applicable pulsatile drug delivery system in dry-coated tablet form was prepared using diltiazem hydrochloride as the model drug, and a polyvinyl chloride-hydrogenated castor oil-polyethyleneglycol mixture as the outer shell of the tablet. In vitro drug release from the prepared tablet exhibited a typical pulsatile pattern with a 7 h lag phase (non-drug release period). This dosage form was orally administered to three beagle dogs under non-fasting and fasting conditions, and the plasma concentration level of diltiazem was determined according to time after administration. The result of the in vivo study in non-fasting dogs suggested that the drug could be released in the gastrointestinal tract as in the in vitro test. However, under the fasting condition, a large difference in the plasma concentration profile was found, suggesting that the disintegration time of the tablet tended to be influenced by the feeding condition of subject.
A new class of compounds for stroke and trauma: effects of 21-aminosteroids on lipid peroxidation. (1987)

The Lazaroids are the result of a blend of reasonable objectives which sprang from experience and hypothesis with a strong dose of serendipity. We believe that these compounds inhibit lipid peroxidation at a membrane level and, thus, blunt the damage from the secondary wave of injury which follows stroke, trauma and other insults to cell membranes. Certainly, these compounds are superior in animal models in potency and efficacy to older glucocorticoids. One compound, U74006F, has been selected for clinical development. Clinical trials in head injury will begin soon in selected centers in the United States.
Antibodies to VLA4 Integrin Mobilize Long-Term Repopulating Cells and Augment Cytokine-Induced Mobilization in Primates and Mice (1997)

Although the use of cytokine-mobilized peripheral blood stem cells has gained a significant momentum in clinical transplantation, the mobilization schemes practiced are guided by a great deal of empiricism. The mechanism(s) by which cytokines or chemokines, alone or in combination, bring about redistribution of stem/progenitor cells from bone marrow to peripheral blood are poorly understood. Likewise the fate of mobilized stem/progenitor cells and their biological properties are incompletely defined. One of the leading hypotheses to explain the mechanism of cytokine-induced mobilization encompasses the view that cytokines disrupt, directly or indirectly, cytoadhesive interactions of stem/progenitor cells with their bone marrow stroma. Compatible with this view are changes in the expression and/or function of several cytoadhesion molecules, especially integrins, postmobilization, and extensive in vitro experimentation supporting the concept of cytokine/integrin interactions. To provide a further insight on the cytokine/integrin interplay in vivo, we have combined cytokine treatments with anti-integrin treatments for mobilization in primates and mice. We found that anti-VLA4 treatment combined with either granulocyte colony-stimulating factor (G-CSF ) treatment or kit ligand treatment leads to significant enhancement of mobilization efficiency (fivefold to eightfold) well above the levels produced by either cytokine alone or anti-VLA4 treatment alone. Similar enhancement was seen when combinations of cytokines, ie, G-CSF plus kit ligand or G-CSF plus Flt3-ligand were used with anti-VLA4 in primates and mice. Furthermore, when anti-VLA4 was given in 5-Fluorouracil-treated primates, significant numbers of progenitor cells were circulating for several days during the recovery period only in the anti-VLA4 treated animals. These data suggest that (1) the effect of anti-VLA4 on mobilization, when used alone, is unlikely to be mediated by secondary cytokine elaboration in vivo; (2) three different cytokines and their combinations do not appear to influence the in vivo responsiveness to anti-VLA4 in coadministration schemes; (3) even if cytokine treatments on their own exert downmodulation of VLA4 function, the target progenitor cells influenced by anti-VLA4 or by cytokines may not necessarily overlap; and (4) augmentation of mobilization in cytokine/anti-VLA4 treatments is most likely caused by an amplification of the pool of target cells on which anti-VLA4 exerts its effects. Because cytokines or anti-VLA4 are each capable of mobilizing long-term repopulating cells and because we show with the present studies that anti-VLA4 in an autologous bone marrow cell transplantation setting does not cause any delay in engraftment, the combination of cytokine/anti-integrin treatment enhancing mobilization may have a clinical use.
Bacteria and Virus Removal from Secondary Effluent in Sand and Red Mud Columns (1991)

Column experiments were conducted to determine the improvement in the removal of Escherichia coli, Salmonella adelaide and poliovirus-1 through sands by amendment with bauxite refining residue. The residue (red mud) was neutralized using 5 % gypsum and incorporated to form 30% of the amended sands. In 65 cm long soil columns the removal of the three organisms in the amended sand columns was excellent with over seven orders of magnitude reduction in concentration. Removal in unamended sands was poor. From breakthrough curves in unamended sand columns filtration, die-off and adsorption all appear to play a role in organism removal. The results also show that E. coli can be used as an indicator for contamination, though S.adelaide was less efficiently removed than E. coli. Poliovirus was on the other hand better removed than E. coli.
Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17–secreting T cells (2010)

Mucosal-associated invariant T (MAIT) cells are very abundant in humans and have antimicrobial specificity, but their functions remain unclear. MAIT cells are CD161(hi)IL-18Rα(+) and either CD4(-)CD8(-) (DN) or CD8αβ(int) T cells. We now show that they display an effector-memory phenotype (CD45RA(-)CD45RO(+)CD95(hi)CD62L(lo)), and their chemokine receptor expression pattern (CCR9(int)CCR7(-)CCR5(hi)CXCR6(hi)CCR6(hi)) indicates preferential homing to tissues and particularly the intestine and the liver. MAIT cells can represent up to 45% of the liver lymphocytes. They produce interferon-γ and Granzyme-B as well as high levels of interleukin-17 after phorbol myristate acetate + ionomycin stimulation. Most MAIT cells are noncycling cells (< 1% are Ki-67(+)) and express the multidrug resistance transporter (ABCB1). As expected from this phenotype, MAIT cells are more resistant to chemotherapy than other T-cell populations. These features might also allow MAIT cells to resist the xenobiotics potentially secreted by the gut bacteria. We also show that this population does not appear to have antiviral specificity and that CD8 MAIT cells include almost all the ABCB1(+)CD161(hi) CD8 T cells. Together with their already known abundance and antimicrobial specificity, the gut-liver homing characteristics, high expression of ABCB1, and ability to secrete interleukin-17 probably participate in the antibacterial properties of MAIT cells.
7-Aroyl-aminoindoline-1-sulfonamides as a Novel Class of Potent Antitubulin Agents (2006)

A novel series of 7-aroyl-aminoindoline-1-benzenesulfonamides showed excellent activity as inhibitors of tubulin polymerization through binding with the colchicine binding site of microtubules. Compound 15 and 16 display IC50 values of 1.1 and 1.2 microM, respectively. Compound 15 inhibited the human cancer cell growth of KB, MKN45, H460, HT29, and TSGH, as well as one human-resistant cancer line of KB-vin 10, with an IC50 of 9.6, 8.8, 9.4, 8.6, 10.8, and 8.9 nM, respectively.
Growth performance and health status in weanling piglets fed spray‐dried porcine plasma under typical Northern European conditions (2002)

The effect of inclusion of spray-dried porcine plasma (SDPP) in diets for weanling piglets was studied. The objectives were to determine whether SDPP would have positive effects on post-weaning piglet performance and health under typical Northern European conditions. In experiment 1, 160 weanling piglets were assigned randomly to a control diet or a diet containing 3% SDPP, which was added at the expense of both fishmeal and dried skim milk. In experiment 2, 264 weanling piglets were assigned to a control diet containing whey protein, a diet without whey protein but with SDPP or a diet containing both whey protein and SDPP. In essence, SDPP was added to the test diets at the expense of either whey protein or fishmeal. Piglets were fed the diets for 3 weeks. In experiment 1, the piglets fed the SDPP diet had a 7% higher average daily gain (ADG) and a 4% lower feed conversion ratio (FCR) (p < 0.05) during the first 3 weeks after weaning than did those fed the control diet. There were no differences in leucocyte counts or gamma-globulin. In experiment 2 there were no significant differences in ADG and FCR among the dietary treatments. It is concluded that low amounts of SDPP in weanling diets can have positive effects on growth performance under Northern European conditions.
Coupling compiler-enabled and conventional memory accessing for energy efficiency (2004)

This article presents Cool-Mem, a family of memory system architectures that integrate conventional memory system mechanisms, energy-aware address translation, and compiler-enabled cache disambiguation techniques, to reduce energy consumption in general-purpose architectures. The solutions provided in this article leverage on interlayer tradeoffs between architecture, compiler, and operating system layers. Cool-Mem achieves power reduction by statically matching memory operations with energy-efficient cache and virtual memory access mechanisms. It combines statically speculative cache access modes, a dynamic content addressable memory-based (CAM-based) Tag-Cache used as backup for statically mispredicted accesses, different conventional multilevel associative cache organizations, embedded protection checking along all cache access mechanisms, as well as architectural organizations to reduce the power consumed by address translation in virtual memory. Because it is based on speculative static information, a superset of the predictable program information available at compile-time, our approach removes the burden of provable correctness in compiler analysis passes that extract static information. This makes Cool-Mem highly practical, applicable for large and complex applications, without having any limitations due to complexity issues in our compiler passes or the presence of precompiled static libraries. Based on extensive evaluation, for both SPEC2000 and Mediabench applications, we obtain from 6% to 19% total energy savings in the processor, with performance ranging from 1.5% degradation to 6% improvement, for the applications studied. We have also compared Cool-Mem to several prior arts and have found Cool-Mem to perform better in almost all cases.
Cutaneous Wound Healing: An Update (2001)

Our understanding of wound-healing mechanisms has progressed over the past decade. Wound healing is traditionally divided into three phases--the inflammatory phase, the proliferation phase, and the remodeling phase--and involves a well-orchestrated interaction among blood vessels (platelets, macrophages, neutrophils, endothelial cells, and smooth muscle cells), epidermis (keratinocytes, melanocytes, and Langerhans cells), adnexal structures (outer root sheath cells and hair dermal papilla cells), dermis (fibroblasts and myofibroblasts), nervous system (neurons), and subcutaneous fatty layers (adipocytes). We review recent discoveries of basic and clinical aspects of wound healing including several revolutions that occurred in wound management: occlusive dressing therapy, use of living skin equivalents, and topical administration of growth factors. As we previously proposed, the use of tissue substitutes and autologous epidermal sheets led to a new concept of skin grafting through the keratinocyte activation phase in the graft healing mechanism. In this review, we also discuss a representative patient who presented with plantar wounds caused by calcaneal osteomyelitis and healed by the coverage of epidermal grafting.
Clinical Orthopaedics and Related Research Board of Trustees (1974)

Pickett, Justus C.; Chrisman, O. Donald; Clawson, D. Kay; Cobey, Milton C.; Linscheid, Ronald L.; Nordby, Eugene J.; Urist, Marshall R.; Waugh, Theodore R. Author Information
Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies (2020)

Although the total body of evidence in the literature was mainly rated as low or very low, these consensus guidelines will help to harmonize clinical practice and to standardize and improve care for BH<sub>4</sub> deficient patients.
Sialosyl-Tn Antigen: Its Distribution in Normal Human Tissues and Expression in Adenocarcinomas (1992)

In normal adult human tissues, sialosyl-Tn antigen, detected by monoclonal antibody TKH2, was uniformly found in the bronchus, uterus, salivary gland, palatine tonsil, testis, stomach, duodenum, and capillary endothelium of several organs. It was also sporadically found in the small intestine, appendix, colorectum, gallbladder, urinary bladder, skin, and esophagus. The antigen was absent in the other organs. Even in the organs showing positive findings, the antigen was observed only in the limited areas. In contrast, sialosyl-Tn antigen was expressed in a large number of adenocarcinomas in many kinds of organs. It was expressed in more than one half the adenocarcinomas of the pancreas, ovary, uterus, stomach, colorectum, and gallbladder, but not in hepatocellular carcinomas, renal cell carcinomas, and papillary carcinomas of the thyroid gland. Sialosyl-Tn antigen expression also was observed in intestinal metaplasia of the stomach and in transitional mucosa adjacent to the colorectal carcinoma, which are considered to be cancer-related lesions. These results indicate that sialosyl-Tn antigen is a useful tumor marker, especially in adenocarcinomas of the mucin-producing organs, and suggest that the regulation of sialosyl-Tn antigen synthesis in adenocarcinomas is different from that in normal tissues.