gebhart/patrepeval huggingface dataset:
RNAi-mediated knockdown of dystrophin expression in adult mice does not lead to overt muscular dystrophy pathology (2008)

Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disorder caused by mutations in the dystrophin gene. DMD has a complex and as yet incompletely defined molecular pathophysiology. The peak of the pathology attributed to dystrophin deficiency happens between 3 and 8 weeks of age in mdx mice, the animal model of DMD. Accordingly, we hypothesized that the pathology observed with dystrophin deficiency may be developmentally regulated. Initially, we demonstrated that profound small interfering RNA-mediated dystrophin knockdown could be achieved in mouse primary muscle cultures. The use of adeno-associated virus vectors to express short-hairpin RNAs targeting dystrophin in skeletal muscle in vivo yielded a potent and specific dystrophin knockdown, but only after approximately 5 months, indicating the very long half-life of dystrophin. Interestingly, and in contrast to what is observed in congenital dystrophin deficiency, long-term ( approximately 1 year) dystrophin knockdown in adult mice did not result, per se, in overt dystrophic pathology or upregulation of utrophin. This supports our hypothesis and suggests new pathophysiology of the disease. Furthermore, taking into account the rather long half-life of dystrophin, and the notion that the development of pathology is age-dependent, it indicates that a single gene therapy approach before the onset of pathology might convey a long-term cure for DMD.
Evaluation of the Effect of UGT1A1 Polymorphisms on Dolutegravir Pharmacokinetics (2013)

Increased dolutegravir exposure in carriers of UGT1A1 reduced function polymorphisms is not clinically significant based on accumulated safety data so dose adjustment in these individuals is not required.
Direct multiplex amplification of DNA from a formalin fixed, paraffin wax embedded tissue section (2000)

The extraction of DNA from formalin fixed, paraffin wax embedded tissue can be problematical, with long protocols producing low yields. This report describes a very simple and useful method for amplifying DNA from formalin fixed, paraffin wax embedded tissue without the need for prior DNA extraction. This method allows direct polymerase chain reaction (PCR) based molecular analysis of fixed tissue. It is an invaluable method if clinical biopsy specimens are to be investigated, because extraction of uncontaminated DNA from such small samples can be very difficult or even impossible. It will also facilitate the study of intratumour heterogeneity, with the analysis of multiple small areas from within a single tumour section. In addition, this method can be used for other samples where only a few tests are to be carried out and a stock of DNA is not required, thus shortening the analysis time.
Electrodeposition of Al-Mo-Mn Ternary Alloys from the Lewis Acidic AlCl[sub 3]-EtMeImCl Molten Salt (2005)

The electrodeposition of Al-Mo-Mn ternary alloys was examined in the Lewis acidic fraction (mol %) aluminum chloride-1-ethyl-3-methylimidazolium chloride molten salt containing Mo(II) and Mn(II). By adjusting the concentration ratio in the plating solution and employing different current densities, it was possible to prepare alloys with widely varying compositions and surface morphologies. All Al-Mo-Mn alloys were dense, compact, and adhered well to the copper substrate surface. The addition of small amounts of Mn to the Al-Mo alloy resulted in an improvement in the chloride pitting corrosion resistance and metallic brightness. For example, and displayed pitting potentials that were 725 and more positive than that for Al, respectively. Al-Mo-Mn alloys that contained more than about 10 atom % exhibited a metallic glass structure.
Multi-frequency and broadband hybrid - coupled circularmicrostrip antennas (1997)

Experimental investigations on hybrid coupled circular microstrip antennas (CMSA) are presented. Three circular patches with different radii with a small gap between them were fabricated. The shorting strips of different widths were used to adjust the coupling between the central fed patch and two parasitic patches, yielding dual-band, triple-band and broadband operations.
DIFFERENTIAL EXPRESSION OF THE COSTIMULATORY MOLECULES B7.1 (CD80) AND B7.2 (CD86) IN RHEUMATOID SYNOVIAL TISSUE (1996)

CD4+ T-lymphocytes require two signals to become activated--antigen receptor (TcR) occupancy and an antigen-presenting cell (APC)-derived costimulus. The latter may be provided by B7.1 (CD80) or B7.2 (CD86) on APC interacting with CD28 on T-cells. We have studied the expression of these costimulatory molecules in rheumatoid and osteoarthritic synovial membrane. Very few B7.1-positive cells were seen in synovial tissue from either established or early rheumatoid disease, or in rheumatoid arthritis (RA) or osteoarthritis (OA) synovia at arthroplasty. In contrast, B7.2 was readily detected in rheumatoid synovia, predominantly in the lining layer, in a pattern of expression that corresponded to the presence of CD68-positive macrophages. Only occasional B7.2-positive cells were seen in OA synovia. The presence of B7.2 but the relative lack of expression of B7.1 may be partly responsible for the observations of 'frustrated' T-cell activation or T-cell hyporesponsiveness in the rheumatoid synovium.
Synthesis, SAR, Crystal Structure, and Biological Evaluation of Benzoquinoliziniums as Activators of Wild-Type and Mutant Cystic Fibrosis Transmembrane Conductance Regulator Channels (2004)

Chloride channels play important roles in homeostasis and regulate cell volume, transepithelial transport, and electrical excitability. Despite recent progress made in the genetic and molecular aspect of chloride channels, their pharmacology is still poorly understood. The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated epithelial chloride channel for which mutations cause cystic fibrosis. Here we have synthesized benzo[c]quinolizinium and benzo[f]indolo[2,3-a]quinolizinium salts (MPB) and performed a SAR to identify the structural basis for activation of the CFTR chloride channel. Synthesized compounds were evaluated on wild-type CFTR and on CFTR having the glycine-to-aspartic acid missense mutation at codon 551 (G551D-CFTR), using a robot and cell-based assay. The presence of an hydroxyl group at position 6 of the benzo[c]quinolizinium skeleton associated with a chlorine atom at position 10 or 7 and an alkyl chain at position 5 determined the highest activity. The most potent product is 5-butyl-7-chloro-6-hydroxybenzo[c]quinolizinium chloride (8u, MPB-104). 8u is 100 times more potent than the parent compound 8a (MPB-07).
A crystallographic snapshot of tyrosine trans -phosphorylation in action (2008)

Tyrosine trans-phosphorylation is a key event in receptor tyrosine kinase signaling, yet, the structural basis for this process has eluded definition. Here, we present the crystal structure of the FGF receptor 2 kinases caught in the act of trans-phosphorylation of Y769, the major C-terminal phosphorylation site. The structure reveals that enzyme- and substrate-acting kinases engage each other through elaborate and specific interactions not only in the immediate vicinity of Y769 and the enzyme active site, but also in regions that are as much of 18 A away from D626, the catalytic base in the enzyme active site. These interactions lead to an unprecedented level of specificity and precision during the trans-phosphorylation on Y769. Time-resolved mass spectrometry analysis supports the observed mechanism of trans-phosphorylation. Our data provide a molecular framework for understanding the mechanism of action of Kallmann syndrome mutations and the order of trans-phosphorylation reactions in FGFRs. We propose that the salient mechanistic features of Y769 trans-phosphorylation are applicable to trans-phosphorylation of the equivalent major phosphorylation sites in many other RTKs.
Three Dimensional, Sheathless, and High‐Throughput Microparticle Inertial Focusing Through Geometry‐Induced Secondary Flows (2012)

A novel inertial focusing platform creates a single-stream microparticle train in a single-focal plane without sheath fluids and external forces, all in a high-throughput manner. The proposed design consists of a low-aspect-ratio straight channel interspersed with a series of constrictions in height arranged orthogonally, making use of inertial focusing and geometry-induced secondary flows. Focusing efficiency as high as 99.77% is demonstrated with throughput as high as 36 000 particles s(-1) for a variety of different sized particles and cells.
Pharmacological studies of human erectile tissue: characteristics of spontaneous contractions and alterations in α‐adrenoceptor responsiveness with age and disease in isolated tissues (1990)

1. The pathophysiology of impotence related to vascular smooth muscle dysfunction in the male corpus cavernosum was studied on human isolated erectile tissue (HET). Studies were conducted on 140 sections of HET obtained from 38 male patients undergoing surgery for implantation of penile prostheses to correct underlying erectile dysfunction. 2. Spontaneous myotonic oscillations were characteristic of greater than 90% of all HET preparations at 37 degrees C. These spontaneous oscillations were markedly attenuated by indomethacin, BW755C, nifedipine, removal of extracellular Ca2+, or lower temperatures (less than or equal to 32 degrees C), but were not sensitive to inhibition by atropine, phentolamine or tetrodotoxin. Our data suggest that the oscillations may, at least in part, result from the generation and/or release of a stable cyclo-oxygenase product and a consequent increase in transmembrane Ca2+ influx. 3. The phenylephrine-induced contractions in HET may be reliably assayed up to 24 h after surgical removal, without significant alterations in the EC50, maximum response (Emax) or slope index of the steady-state concentration-response curve to phenylephrine. 4. The competitive and surmountable nature of the antagonism of phenylephrine-induced contractions by prazosin and yohimbine allowed calculation of antagonist dissociation constants. The calculated pKb values for prazosin and yohimbine, respectively, were 9.47 +/- 0.49 and 5.54 +/- 0.22. The rank order of agonist potency in HET was: noradrenaline = phenylephrine much greater than clonidine. These data indicate the presence of a population of membrane receptors that are predominantly of the alpha 1-adrenoceptor subtype. 5. The entire patient population was stratified on a decennial basis into five age groups, and each age group was subsequently subdivided into diabetic and nondiabetic diagnostic categories. With respect to the steady-state phenylephrine concentration-response curves, a Winer two-factor analysis of variance revealed a significant effect of age on the calculated pEC50 value, as well as a significant age-diagnosis interaction. A post hoc statistical analysis for unpaired samples yielded significant differences between pEC50 values for diabetic and nondiabetic patients in age groups 41-50 and 61-70 years. In addition, a Winer two-factor analysis of variance also detected a significant effect of age on the calculated E.., value. 6. In conclusion, our studies demonstrate that spontaneous contractions in HET are likely to be mediated by the generation and release of a stable cyclo-oxygenase product. Furthermore, the results of both agonist and antagonist studies are consistent with the presence of a homogeneous alpha x-adrenoceptor population. Lastly, the responsiveness of isolated HET to phenylephrine was shown to be altered by both age and disease.
Properties of L-methionine γ-lyase from Pseudomonas ovalis (1977)

The distribution of bacterial L-methionine gamma-lyase (L-methionine methanethiollyase (deaminating) (EC 4.4.1.11) was investigated, and Pseudomonas ovalis (IFO 3738) was found to have the highest activity of enzyme, which was inducibly formed by addition of L-methionine to the medium. L-Methionine gamma-lyase, purified to homogeneity from Ps. ovalis, has a molecular weight of about 173 000 and consists of nonidentical subunits (mol wt: 40 000 and 48 000). The enzyme exhibits absorption maxima at 278 and 420 nm, and a shoulder around 330 nm, which are independent of the pH (6.0 to 10.0), and contains 4 mol of pyridoxal 5'-phosphate per mol of the enzyme. The formyl group of pyridoxal 5'-phosphate is bound in an aldimine linkage to the epsilon-amino group of lysine residues of the protein. The holoenzyme is resolved to the apoenzyme by incubation with hydroxylamine, and reconstituted by addition of pyridoxal 5'-phosphate. The enzyme activity is significantly affected by both carbonyl and sulfhydryl reagents. L-Methionine gamma-lyase catalyzes alpha,gamma- and alpha,beta-elimination reactions of, in addition to L-methionine, several derivatives of L-methionine and L-cysteine, e.g., L-ethionine, DL-methionine sulfone, L-homocysteine, and S-methyl-L-cysteine. The enzyme catalyzes also gamma-replacement reactions of the thiomethyl group of methionine with various alkanethiols (C2-C7), arylthio alcohols (benzenethiol and beta-naphthalenethiol) and the derivatives of ethanethiol (2-mercaptoethanol and cysteamine) to yield the corresponding S-substituted homocysteine. The thiomethyl group of S-methyl-L-cysteine also is replaced by ethanethiol to form S-ethyl-L-cysteine.
Turbo decoding of error control coded and unitary precoded OFDM (2003)

This paper addresses the design of a novel scheme that combines error control coding (EC) and unitary precoding (UP) in order to obtain high diversity gains in OFDM systems with low complexity. The overall diversity of the proposed system is shown to be the product of the individual diversities achievable by the error control coding and by the unitary precoding, while the complexity is just a linear multiple of the sum of their individual complexities. In a practical HiperLan/2 setup, the proposed system achieves a gain of 4 dB, (3.3 dB), at a bit error rate (BER) of 10/sup -3/, relative to conventional OFDM systems that only deploy convolutional (turbo) coding.
Genetic transformation of mouse cultured cells with the help of high‐velocity mechanical DNA injection (1989)

NIH 3T3 mouse cells were transfected by the plasmid pSV3neo (G418-resistant) with the help of high-velocity mechanical DNA injection based on the principle of bombarding cells with tungsten particles covered with the DNA. Stable transformants were obtained. Dot-hybridization and Southern analysis revealed the integration into the genome of 5-20 copies per cell of original plasmid DNA. The plasmid DNA was shown to have tandem organization.
Pre-treatment of daily teriparatide enhances the increase of bone mineral density in cortical bones by denosumab therapy (2018)

These findings suggest that the pretreatment of TPTD might have enhanced the increase of BMD in cortical bones treated by DMAb. Thus, it is favorable that TPTD can be used for osteoporotic patients who have high fracture risks with cortical bones.
On the design of a high-performance ATM bridge (2002)

This paper presents the design and implementation of a high-performance ATM bridge. The proposed ATM bridge can be used to interconnect IEEE 802.3/Ethernet, IEEE 802.3u/fast Ethernet, and IEEE 802.11N/wireless LANs. Data traffic is filtered out or forwarded to other homogeneous LANs by a proprietary LAN emulation technology, which is compatible with the ATM LAN emulation (LANE) specification. Enhanced capability including the support for emulated fast Ethernets and wireless LANs are provided by the proposed ATM bridge. A QoS guaranteed traffic scheduling algorithm is also proposed for the wireless LANs.
A Genetic Screen for Aminophospholipid Transport Mutants Identifies the Phosphatidylinositol 4-Kinase, Stt4p, as an Essential Component in Phosphatidylserine Metabolism (1998)

In an effort to understand molecular mechanisms of intracellular lipid transport, we have focused upon specific events required for de novo aminophospholipid synthesis in the yeast Saccharomyces cerevisiae. A genetic system for examining the steps between phosphatidylserine (PtdSer) synthesis in the endoplasmic reticulum and its transport to and decarboxylation by PtdSer decarboxylase 2 in the Golgi/vacuole has been developed. We have isolated a mutant, denoted pstB1, that accumulates PtdSer and has diminished phosphatidylethanolamine formation despite normal PtdSer decarboxylase 2 activity. The lesion in PtdSer metabolism is consistent with a defect in interorganelle lipid transport. A genomic DNA clone that complements the mutation was isolated, and sequencing revealed that the clone contains the STT4 gene, encoding a phosphatidylinositol 4-kinase. The pstB1 mutant exhibits a defect in Stt4p-type phosphatidylinositol 4-kinase activity, and direct gene replacement indicates that STT4 is the defective gene in the mutant. Creation of an STT4 null allele (stt4Delta::HIS3) demonstrates the gene is essential. These results provide evidence that implicates phosphoinositides in the regulation of intracellular aminophospholipid transport.
Fiber-optic acoustic Fourier transducer for audio sound processing (1992)

We demonstrate a fiber-optic acoustic transducer operating in the audio-frequency regime. The device is made of an array of 120 multimode optical fibers and a photorefractive novelty filter. Each fiber in the array acts as a cantilevered mechanical resonator. The resonant frequencies of the fibers logarithmically sample the acoustic spectrum from approximately 100 Hz to 5 kHz. Laser light is injected into all fibers simultaneously and is reflected from the end of each fiber. An optical novelty filter extracts the acoustic information from the reflected light. The output of the novelty filter is essentially a Fourier transform of the acoustic signal. The background intensity in the transducer output corresponds to a driving amplitude of approximately 50 A. We describe holographic storage of complex sound patterns that use a LiNbO(3) crystal and an acoustic transducer.
Participation of glomerular endothelial cells in the capillary repair of glomerulonephritis. (1995)

In many glomerular diseases severe injury to the mesangium may occur, leading to matrix dissolution and damage to the glomerular capillaries. Although the destruction of glomerular architecture may lead to permanent injury, in some cases spontaneous recovery occurs. The mechanisms that mediate this recovery are unknown. In this study we provide evidence for glomerular capillary repair (angiogenesis) in the adult injured glomerulus. Injection of anti-Thy 1 antibody into rats results in severe mesangiolysis with capillary ballooning, microaneurysm formation, and loss of endothelial cells in addition to mesangial cells. Although mesangial proliferation is a major response to injury, proliferation of endothelial cells also can be documented from days 2 to 14 in association with repair of the capillaries. The endothelial cell proliferation peaks on days 2 and 7, when it is seven- to ninefold greater than normal. Many of the endothelial cells display morphological features of angiogenesis. The initial wave of endothelial cell proliferation can be reduced by 40% with neutralizing anti-basic fibroblast growth factor antibodies (P < 0.001). The later glomerular endothelial cell proliferation is associated with upregulated expression of vascular permeability factor/endothelial cell growth factor (VPF/VEGF) and an increase of flk, a VPF/VEGF receptor. Although PDGF is expressed in this model, anti-PDGF antibody treatment did not affect the endothelial cell proliferative response. In summary, glomerular endothelial cells have an active role in the glomerular response to injury. Glomeruli are capable of healing microaneurysms, and the mechanism involves basic fibroblast growth factor- and VPF/VEGF-mediated endothelial proliferative responses.
Effect of Physical Forces on Bladder Smooth Muscle and Urothelium (1993)

Abnormalities in bladder physiology may be due to obstruction (pressure) and/or neurological impairment. Clinically they can result in an increase in connective tissue and a decrease in bladder compliance. To study the effects of physical forces on the bladder without the influence of the nerves we developed a cellular model system by isolating the 2 major cell types in the bladder: smooth muscle and urothelial cells. Extracellular matrix protein biosynthesis by these 2 cell types in vitro has been characterized by metabolic labeling of proteins with [14C] radiolabeled proline and analysis by gel electrophoresis. These studies demonstrate that fetal bovine bladder smooth muscle and urothelial cells synthesize fibronectin and types I and III interstitial collagen. Since bladder cells exist in an active physical environment, we have attempted to simulate this at the cellular level. Using a device developed in our laboratory, we applied a precise and reproducible mechanical strain (physical force) to these 2 cell types. By enzyme linked immunosorbent assay we quantitated collagen types I and III and fibronectin synthesized by fetal bovine bladder smooth muscle and urothelial cells undergoing mechanical strain (4.9%). These cells were compared to unstrained control cells that were exposed to the same experimental conditions. For bladder smooth muscle cells we found a significant increase in collagen type III and fibronectin synthesis when compared to unstrained cells. In contrast, collagen type I synthesis decreased with mechanical strain. For bladder urothelial cells we found an increase in collagen type I and fibronectin while collagen type III remained unchanged. These studies demonstrate that extracellular matrix synthesis by urothelial and smooth muscle cells can be modulated by stretch (strain) in the absence of neurological input. It is likely that bladder function may be impaired as a result of abnormal synthesis of connective tissue.
The Endothelium-Derived Relaxing Factor (1989)

Over the past 25 years, it has become clear that the vascular endothelium plays an important role in the function of the cardiovascular system. Most recently, it has been established that endothelial cells can determine or modulate the response of vascular smooth muscle cells to vasoactive stimuli, by production of a labile factor (or factors) that has been named the "Endothelium-Derived Relaxing Factor" (EDRF). While much remains to be learned about the pathways responsible for the production and the effects of EDRF, and its role in cardiovascular physiology, it is apparent that the loss of this endothelium-derived vasodilator can have profound effects on vascular pharmacology and physiology that could be important to the pathologies associated with disease states.
Role of Type X Collagen on Experimental Mineralization of Eggshell Membranes (1997)

Type X collagen is a transient and developmentally regulated collagen that has been postulated to be involved in controlling the later stages of endochondral bone formation. However, the role of this collagen in these events is not yet known. In order to understand the function of type X collagen, if any, in the process of biomineralization, the properties of type X collagen in eggshell membranes were further investigated. Specifically, calvaria-derived osteogenic cells were tested for their ability to mineralize eggshell membranes in vitro. Immunohistochemistry with specific monoclonal antibodies was used to correlate the presence or absence of type X collagen or its propeptide domains with the ability of shell membranes to be mineralized. The extent of mineralization was assessed by Von Kossa staining, scanning electron microscopy and energy-dispersive spectroscopy. The results indicate that the non-helical domains of type X collagen must be removed to facilitate the cell-mediated mineralization of eggshell membranes. In this tissue, intact type X collagen does not appear to stimulate or support cell-mediated mineralization. We postulate that the non-helical domains of type X collagen function in vivo to inhibit mineralization and thereby establish boundaries which are protected from mineral deposition.