gebhart/patrepeval huggingface dataset:
Systemic Microdystrophin Gene Delivery Improves Skeletal Muscle Structure and Function in Old Dystrophic mdx Mice (2008)

Restoring dystrophin expression in the muscles of patients with Duchenne muscular dystrophy (DMD) may halt or reverse the degenerative wasting and weakness that causes premature death. However, the therapeutic efficacy of an intervention may be limited by the extent of disease progression prior to treatment. In this study, we considered the potential for ameliorating the pathology in a mouse model of advanced-stage muscular dystrophy by systemic administration of recombinant adeno-associated viral (rAAV6) vectors encoding a microdystrophin expression construct. The treatment of 20-month-old mdx mice restored body-wide expression of a dystrophin-based protein in striated musculature. In aged mice that received treatment, the resultant dystrophin expression was associated with improved hindlimb and respiratory muscle morphology and function, concomitant with reduced muscle fiber degeneration. The findings demonstrate that an established dystrophic state remains amenable to improvement with appropriate intervention and, by some measures, may even achieve benefits similar to those observed with intervention early in disease progression. The capacity to ameliorate the pathology in an animal model of advanced-stage muscular dystrophy suggests that interventions ultimately proven to exert a therapeutic effect in young patients may offer benefits to older patients or those with advanced conditions of progressive muscular dystrophy.
Human mesenchymal stromal/stem cells acquire immunostimulatory capacity upon cross-talk with natural killer cells and might improve the NK cell function of immunocompromised patients (2016)

A positive feedback loop driven by NK cell-derived IFN-γ and MSC-derived CCL2 increases the inflammatory response of cytokine-stimulated NK cells not only from healthy donors but also from immunocompromised patients. Therapeutic application of MSCs or their soluble factors might thus improve the NK function after severe injury.
Endothelial function and coronary artery disease (2001)

The endothelium produces a number of vasodilator and vasoconstrictor substances that not only regulate vasomotor tone, but also the recruitment and activity of inflammatory cells and the propensity towards thrombosis. Endothelial vasomotor function is a convenient way to assess these other functions, and is related to the long-term risk of cardiovascular disease. Lipids (particularly low density lipoprotein cholesterol) and oxidant stress play a major role in impairing these functions, by reducing the bioavailability of nitric oxide and activating pro-inflammatory signalling pathways such as nuclear factor kappa B. Biomechanical forces on the endothelium, including low shear stress from disturbed blood flow, also activate the endothelium increasing vasomotor dysfunction and promoting inflammation by upregulating pro-atherogenic genes. In contrast, normal laminar shear stress promotes the expression of genes that may protect against atherosclerosis. The sub-cellular structure of endothelial cells includes caveolae that play an integral part in regulating the activity of endothelial nitric oxide synthase. Low density lipoprotein cholesterol and oxidant stress impair caveolae structure and function and adversely affect endothelial function. Lipid-independent pathways of endothelial cell activation are increasingly recognized, and may provide new therapeutic targets. Endothelial vasoconstrictors, such as endothelin, antagonize endothelium-derived vasodilators and contribute to endothelial dysfunction. Some but not all studies have linked certain genetic polymorphisms of the nitric oxide synthase enzyme to vascular disease and impaired endothelial function. Such genetic heterogeneity may nonetheless offer new insights into the variability of endothelial function.
ChemInform Abstract: Reaction of Ferrocene Carboxylic Acid with Dicyclohexylcarbodiimide. (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Dysregulated methylation at imprinted genes in prostate tumor tissue detected by methylation microarray (2013)

Together, these findings suggest a more widespread dysregulation of genetic imprinting in prostate cancer than previously reported and warrant further investigation.
Induction of Pyk-2

Fhosphorylation

During Lfa-l/Icam-1-Dependent Homotypic Adhesion of Fresh Human B-Cells (2000)

Stimulation with the combination of PDB plus ionomycin induced LFA-1/ICAM-1-dependent homotypic adhesion of tonsil B cells. Adhesion of tonsil B cells in our system induced tyrosine phosphorylation of Pyk-2. Disruption of homotypic adhesion and concomitant inhibition of induction of protein tyrosine phosphorylation was achieved by physical separation of the cells and by treatment with methyl-2.5-dihydroxycinnamate (MDHC), an inhibitor of protein tyrosine phosphorylation. These results suggest that protein tyrosine phosphorylation that is associated with homotypic adhesion is mediated by LFA-1/ICAM-1 interactions.
Condensed Huffman coding, a new efficient decoding technique (2003)

A new technique is proposed for decoding Huffman codes. In this technique a Condensed Huffman Table (CHT) for decoding purposes replaces a typical Huffman table. It is shown that a CHT is much smaller in size and the decoding becomes significantly faster. In an example with a typical Huffman table containing 108 codewords, it is shown that a CHT with only 14 codewords is sufficient to perform the decoding.
Anti-Colony-Stimulating Factor-1 Antibody Staining in Primary Breast Adenocarcinomas Correlates With Marked Inflammatory Cell Infiltrates and Prognosis (1994)

Nuclear retention of CSF-1 could reflect CSF-1 turnover and function in tumor cells, but new approaches are needed to establish the significance of these observations. Secreted CSF-1 appears to cause monocyte recruitment and activation, thereby modulating immune functions and potentially the expression of the CD45RO phenotype in T cells.
Ethnic variation in the clinical manifestations of rheumatoid arthritis: Role of HLA–DRB1 alleles (2003)

There is ethnic variation in the clinical expression of RA and in both the frequency and types of SE-carrying HLA-DRB1 alleles. Some ethnic variation in clinical findings is associated with differences in SE frequency. However, we found that the effect of the SE on the clinical features of RA varies little between ethnic groups.
Cellular Actions of Insulin-Like Growth Factor Binding Proteins (1999)

The insulin-like growth factors (IGFs), insulin-like growth factor binding proteins (IGFBPs), and the IGFBP proteases are involved in the regulation of somatic growth and cellular proliferation both in vivo and in vitro. IGFs are potent mitogenic agents whose actions are determined by the availability of free IGFs to interact with the IGF receptors. IGFBPs comprise a family of proteins that bind IGFs with high affinity and specificity and thereby regulate IGF-dependent actions. IGFBPs have recently emerged as IGF-independent regulators of cell growth. Various IGFBP association proteins as well as cleavage of IGFBPs by specific proteases modulate levels of free IGFs and IGFBPs. The ubiquity and complexity of the IGF axis promise exciting discoveries and applications for the future.
Direct DNA and PNA probe binding to telomeric regions without classical in situ hybridization (2013)

Certain PNA probes are able to hybridize with their targets with minimal to no denaturing of the DNA itself. This limited denaturing preserves the chromosome structure and may lead to more effective and specific staining.
Cilostazol Has Beneficial Effects in Treatment of Intermittent Claudication (1998)

Cilostazol improved walking distances, significantly increasing ICD and ACD. The data suggest cilostazol is safe and well tolerated for the treatment of intermittent claudication.
A preliminary evaluation of the Parent–Child Mother Goose Program in relation to children’s language and parenting stress (2012)

The purpose of this study was to assess changes in children’s language skills and parenting stress following participation in the Parent–Child Mother Goose Program (PCMGP). The intervention group consisted of 29 parents (age range 24 to 43 years, M = 33.5, SD = 4.1) and 30 children (18 females and 12 males) with ages ranging from 1 to 46 months ( M = 14.2, SD = 13.0), who were participating in the PCMGP. The comparison group consisted of 22 parents (age range 28 to 43 years, M = 34.5, SD = 3.7) and 25 children (14 females and 11 males) with ages ranging from 5 to 37 months ( M = 18.2, SD = 10.7), who were participating in community playgroups. Children’s scores on receptive and expressive language using the Preschool Language Scale-3, and parenting stress scores using three subscales of the Parenting Stress Index were obtained at the beginning of the research (pre-test) and again 15 weeks later (post-test). Results revealed that the PCMGP children showed greater improvement in language skills, especially their expressive communication skills. The parents participating in the PCMGP also reported a more positive impact on their perceptions of their child’s demandingness compared to the comparison playgroup parents. This study highlights the potential effectiveness of the PCMGP as an early intervention program in relation to aspects of both receptive and expressive language and parental stress, and adds to the limited existing literature evaluating this program.
Cargo‐dependent mode of uptake and bioavailability of TAT‐containing proteins and peptides in living cells (2006)

Cell-penetrating peptides (CPPs) are capable of introducing a wide range of cargoes into living cells. Descriptions of the internalization process vary from energy-independent cell penetration of membranes to endocytic uptake. To elucidate whether the mechanism of entry of CPP constructs might be influenced by the properties of the cargo, we used time lapse confocal microscopy analysis of living mammalian cells to directly compare the uptake of the well-studied CPP TAT fused to a protein (>50 amino acids) or peptide (<50 amino acids) cargo. We also analyzed various constructs for their subcellular distribution and mobility after the internalization event. TAT fusion proteins were taken up largely into cytoplasmic vesicles whereas peptides fused to TAT entered the cell in a rapid manner that was dependent on membrane potential. Despite their accumulation in the nucleolus, photobleaching of TAT fusion peptides revealed their mobility. The bioavailability of internalized TAT peptides was tested and confirmed by the strong inhibitory effect on cell cycle progression of two TAT fusion peptides derived from the tumor suppressor p21(WAF/Cip) and DNA Ligase I measured in living cells.
IL-1 Signaling Cascade in Liver Cells and the Involvement of a Soluble Form of the IL-1 Receptor Accessory Protein (2000)

The proinflammatory cytokine IL-1 induces the biosynthesis of a number of immunologically important proteins during infection, tissue damage, and/or stress, in part through the activation of the transcription factor NF-kappaB. Signal transduction is initiated at the cell membrane by complex formation between extracellular IL-1 and the transmembrane IL-1R type I (IL-1RI) and IL-1R accessory protein (IL-1RAcP). The intracellular signaling cascade involves recruitment of two IL-1R-associated kinases, IRAK1 and IRAK2, and the adapter protein MyD88, events which are dependent on the intracellular domain of membrane-bound IL-1RAcP (mIL-1RAcP). In mouse liver, IL-1RAcP is expressed as a soluble protein (sIL-1RAcP), the function of which is unknown. We have cloned the human sIL-1RAcP and established by sequence analysis that the human sIL-1RAcP mRNA arises from alternative splicing of the IL-1RAcP gene (shown here to encompass 12 exons spanning more than 56 kb). Furthermore, we demonstrate that human HepG2 hepatoma cells express both mIL-1RAcP and sIL-1RAcP and that signal transduction in these cells is mediated through IRAK1, IRAK2, and MyD88. We show that phorbol esters induce a change in the pre-mRNA splice pattern such that sIL-1RAcP mRNA becomes the dominant form. Overexpression of a membrane-anchored fusion protein of sIL-1RAcP and MHC in HepG2 cells inhibits IL-1-mediated NF-kappaB activation, whereas coexpression of IL-1RI with membrane-anchored sIL-1RAcP restores the capacity of the cells to respond to IL-1. This suggests that sIL-1RAcP may act as an inhibitor of IL-1 by directly interacting with IL-1RI to abolish its capacity to transduce signal.
Evidence-Based Medicine: Options for Dupuytren’s Contracture: Incise, Excise, and Dissolve (2016)

The literature on Dupuytren's disease encompasses many specialties. Its treatment is generally by perforating, excising, or dissolving the affected tissues. This article reviews the changing understanding of this disease and treatment options.
Lamb Wave Basis for Impact-Echo Method Analysis (2005)

The impact-echo method has been developed over the past 20years and is now widely used in the nondestructive evaluation of concrete. However, some practical issues remain unresolved, such as the physical basis for the empirical correction factor (β) used to obtain thickness mode frequency. A new approach based on guided wave theory is proposed in this paper: that the impact-echo resonance in plates corresponds to the zero-group-velocity frequency of the S1 Lamb mode. A numerical model is developed, verified by experiment, and then shown to adequately simulate the dynamic response of a concrete plate. Using this model the thickness resonance mode is identified and found to accurately match that particular Lamb mode in terms of shape and frequency. New values for β based on the Lamb mode model are computed and dependence on material Poisson’s ratio is demonstrated.
Argon2: New Generation of Memory-Hard Functions for Password Hashing and Other Applications (2016)

We present a new hash function Argon2, which is oriented at protection of low-entropy secrets without secret keys. It requires a certain (but tunable) amount of memory, imposes prohibitive time-memory and computation-memory tradeoffs on memory-saving users, and is exceptionally fast on regular PC. Overall, it can provide ASIC-and botnet-resistance by filling the memory in 0.6 cycles per byte in the non-compressible way.
Bandwidth efficient coding for fading channels: code construction and performance analysis (1989)

The authors apply a general method of bounding the event error probability of TCM (trellis-coded modulation) schemes to fading channels and use the effective length and the minimum-squared-product distance to replace the minimum-free-squared-Euclidean distance as code design parameters for Rayleigh and Rician fading channels with a substantial multipath component. They present 8-PSK (phase-shift-keying) trellis codes specifically constructed for fading channels that outperform equivalent codes designed for the AWGN (additive white Gaussian noise) channel when v>or=5. For quasiregular trellis codes there exists an efficient algorithm for evaluating event error probability, and numerical results which demonstrate the importance of the effective length as a code design parameter for fading channels with or without side information have been obtained. This is consistent with the case for binary signaling, where the Hamming distance remains the best code design parameter for fading channels. The authors show that the use of Reed-Solomon block codes with expanded signal sets becomes interesting only for large value of E/sub s//N/sub 0/, where they begin to outperform trellis codes.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Visualization of Vacuolar Acidification-induced Transcription of Genes of Pathogens inside Macrophages (2005)

The objective of these studies was to analyze the role of the ionic environment of phagosomal vacuoles in the control of pathogens by macrophages. Digital imaging and flow cytometry were used to follow the induction of the phoP promoter of Salmonella enterica Typhimurium within live macrophages. Manipulating the Mg2+ concentration within the Salmonella-containing vacuole (SCV) was without effect on the early induction of PhoPQ. Moreover, direct measurement of [Mg2+] within the SCV using nanosensor particles showed that, during this initial period of phoP activation, the concentration of the divalent cation is rapidly regulated and stabilizes around 1 mm. Extrusion of other divalent cations via the Nramp1 efflux pump was similarly ruled out as an important contributor to the activation of the regulon. By contrast, induction of PhoP was greatly attenuated when the pH gradient across the SCV membrane was dissipated. A second, more modest pH-independent component of PhoP induction was unmasked by inhibition of the vacuolar proton pump. This second component was eliminated by pretreatment of cells with IFNgamma, even though the cytokine augmented the overall PhoP response. These findings demonstrate the existence of at least three separate activators of phoP transcription: resting and IFNgamma-stimulated pH-sensitive components, plus a pH-independent component.
Flavodoxin Mutants of Escherichia coli K-12 (2000)

The flavodoxins are flavin mononucleotide-containing electron transferases. Flavodoxin I has been presumed to be the only flavodoxin of Escherichia coli, and its gene, fldA, is known to belong to the soxRS (superoxide response) oxidative stress regulon. An insertion mutation of fldA was constructed and was lethal under both aerobic and anaerobic conditions; only cells that also had an intact (fldA(+)) allele could carry it. A second flavodoxin, flavodoxin II, was postulated, based on the sequence of its gene, fldB. Unlike the fldA mutant, an fldB insertion mutant is a viable prototroph in the presence or absence of oxygen. A high-copy-number fldB(+) plasmid did not complement the fldA mutation. Therefore, there must be a vital function for which FldB cannot substitute for flavodoxin I. An fldB-lacZ fusion was not induced by H(2)O(2) and is therefore not a member of the oxyR regulon. However, it displayed a soxS-dependent induction by paraquat (methyl viologen), and the fldB gene is preceded by two overlapping regions that resemble known soxS binding sites. The fldB insertion mutant did not have an increased sensitivity to the effects of paraquat on either cellular viability or the expression of a soxS-lacZ fusion. Therefore, fldB is a new member of the soxRS (superoxide response) regulon, a group of genes that is induced primarily by univalent oxidants and redox cycling compounds. However, the reactions in which flavodoxin II participates and its role during oxidative stress are unknown.
A New Reagent for the Induction of T-Cell Depletion, Anti-CD3-CRM9 (1996)

We have developed a new reagent for inducing in vivo T-cell depletion and have tested this reagent in rhesus monkeys. The reagent is an anti-CD3 epsilon immunotoxin based on a diphtheria toxin binding-site mutant, CRM9. After administration to monkeys, T cells are depleted from both the blood and lymph node compartments to < 1% of their initial values. T-cell depletion is associated with transient immunosuppression, as judged by delayed rejection of RhLA-mismatched skin allografts. T cells are repopulated in both compartments; however, the rate of repopulation is age dependent. The rate is rapid in juvenile animals (12 days) and requires > 30 days in old animals. The correlation between repopulation rate and age suggests that the repopulation is thymus dependent and that the repopulated T cells are probably naive T cells. This reagent should be a valuable tool in studying the role of memory T cells in rhesus models of autoimmune diseases and protocols of tolerance induction after organ transplantation.
Crystal Structure of the Extracellular Domain of Mouse RANK Ligand at 2.2-Å Resolution (2002)

Bone remodeling involves the resorption of bone by osteoclasts and the synthesis of bone matrix by osteoblasts. Receptor activator of NF-kappa B ligand (RANKL, also known as ODF and OPGL), a member of the tumor necrosis factor (TNF) family, triggers osteoclastogenesis by forming a complex with its receptor, RANK. We have determined the crystal structure of the extracellular domain of mouse RANKL at 2.2-A resolution. The structure reveals that the RANKL extracellular domain is trimeric, which was also shown by analytical ultracentrifugation, and each subunit has a beta-strand jellyroll topology like the other members of the TNF family. A comparison of RANKL with TNF beta and TNF-related apoptosis-inducing ligand (TRAIL), whose structures were determined to be in the complex form with their respective receptor, reveals conserved and specific features of RANKL in the TNF superfamily and suggests the presence of key residues of RANKL for receptor binding.
Toward Second Generation Hepatitis C Virus NS3 Serine Protease Inhibitors: Discovery of Novel P4 Modified Analogues with Improved Potency and Pharmacokinetic Profile (2009)

Hepatitis C virus (HCV) infection is a global health crisis leading to liver cirrhosis, hepatocellular carcinoma, and liver failure in humans. Recently, we disclosed the discovery of Boceprevir, SCH 503034 (1), a novel, potent, selective, orally bioavailable NS3 protease inhibitor that is currently undergoing phase III clinical trials. Our efforts toward a second generation HCV NS3 serine protease inhibitor were directed at improving the overall profile of the inhibitor. This article will elaborate on our studies leading to the discovery of new P4 modified inhibitors with enhanced potency and improved oral bioavailability. Thus, introduction of ether and carbamate-derived P4 moieties resulted in improving the replicon potency significantly. Incorporation of the P' secondary amide residue afforded significant improvement in pharmacokinetic properties. Combining the preferred moieties, identified from comprehensive SAR studies, resulted in inhibitors that displayed superior potency and very good oral as well as target organ exposure in rats.
Expression of the Smooth Muscle Myosin Heavy Chain Gene Is Regulated by a Negative-acting GC-rich Element Located between Two Positive-acting Serum Response Factor-binding Elements (1997)

To identify cis- and trans-acting factors that regulate smooth muscle-specific gene expression, we studied the smooth muscle myosin heavy chain gene, a rigorous marker of differentiated smooth muscle. A comparison of smooth muscle myosin heavy chain promoter sequences from multiple species revealed the presence of a highly conserved 227-base pair domain (nucleotides -1321 to -1095 in rat). Results of a deletion analysis of a 4.3-kilobase pair segment of the rat promoter (nucleotides -4220 to +88) demonstrated that this domain was necessary for maximal transcriptional activity in smooth muscle cells. Gel-shift analysis and site-directed mutagenesis demonstrated that one true CArG and another CArG-like element contained within this domain were both recognized by the serum response factor and were both required for the positive activity attributable to this domain. Additional studies demonstrated that mutation of a GC-rich sequence within the 227-base pair conserved domain resulted in a nearly 100% increase in transcriptional activity. Gel-shift analysis showed that this GC-rich repressor element was recognized by both Sp1 and Sp3. These data demonstrate that transcriptional control of the smooth muscle myosin heavy chain gene is highly complex, involving both negative and positive regulatory elements, including CArG sequences found in the promoters of multiple smooth muscle differentiation marker genes.