gebhart/patrepeval huggingface dataset:
Confinement in Nanodiscs Anisotropically Modifies Lipid Bilayer Elastic Properties (2020)

Lipid nanodiscs are small synthetic lipid bilayer structures that are stabilized in solution by special circumscribing (or scaffolding) proteins or polymers. Because they create native-like environments for transmembrane proteins, lipid nanodiscs have become a powerful tool for structural determination of this class of systems when combined with cryo-electron microscopy or nuclear magnetic resonance. The elastic properties of lipid bilayers determine how the lipid environment responds to membrane protein perturbations, and how the lipid in turn modifies the conformational state of the embedded protein. However, despite the abundant use of nanodiscs in determining membrane protein structure, the elastic material properties of even pure lipid nanodiscs (i.e., without embedded proteins) have not yet been quantitatively investigated. A major hurdle is due to the inherently nonlocal treatment of the elastic properties of lipid systems implemented by most existing methods, both experimental and computational. In addition, these methods are best suited for very large "infinite" size lipidic assemblies, or ones that contain periodicity, in the case of simulations. We have previously described a computational analysis of molecular dynamics simulations designed to overcome these limitations, so it allows quantification of the bending rigidity (<i>K</i><sub>C</sub>) and tilt modulus (κ<sub>t</sub>) on a local scale even for finite, nonperiodic systems, such as lipid nanodiscs. Here we use this computational approach to extract values of <i>K</i><sub>C</sub> and κ<sub>t</sub> for a set of lipid nanodisc systems that vary in size and lipid composition. We find that the material properties of lipid nanodiscs are different from those of infinite bilayers of corresponding lipid composition, highlighting the effect of nanodisc confinement. Nanodiscs tend to show higher stiffness than their corresponding macroscopic bilayers, and moreover, their material properties vary spatially within them. For small-size MSP1 nanodiscs, the stiffness decreases radially, from a value that is larger in their center than the moduli of the corresponding bilayers by a factor of ∼2-3. The larger nanodiscs (MSP1E3D1 and MSP2N2) show milder spatial changes of moduli that are composition dependent and can be maximal in the center or at some distance from it. These trends in moduli correlate with spatially varying structural properties, including the area per lipid and the nanodisc thickness. Finally, as has previously been reported, nanodiscs tend to show deformations from perfectly flat circular geometries to varying degrees, depending on size and lipid composition. The modulations of lipid elastic properties that we find should be carefully considered when making structural and functional inferences concerning embedded proteins.
Effect of pressure and ionic strength on the self-association of Apo-A-I from the human high density lipoprotein complex. (1978)

The self-association of apo-A-I isolated from the human high density lipoprotein complex has been investigated by gel permeation chromatography and sedimentation equilibrium. The apparent weight average molecular weight (MWapp) versus Apo-A-I concentration profile was found to be sensitive to ionic strength and pressure; MWapp increased with increasing ionic strength and decreasing rotor speed. The data were consistent with a monomer-dimer-tetrameroctamer association shceme over all conditions investigated if a change in the partial specific volume of apo-A-I upon association of 5.5 x 10(-2) ml/g is postulated.
Distribution of AAV2-hAADC-transduced cells after 3 years in Parkinsonian monkeys (2006)

The present report describes for the first time, the stability of recombinant adeno-associated virus serotype 2 (AAV2) human aromatic L-amino acid decarboxylase (hAADC) gene transfer after 3-year survival time in a non-human primate model of Parkinson's disease. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys were treated with six injections of 30 microl/site of AAV2-hAADC at a concentration of 2 x 10(12) vg/ml into the caudate and putamen. Stereological analysis revealed a 46.6% increase in the total number of AAV2-hAADC-transduced cells in the striatum between 8 weeks and 3 years after gene transfer survival time. In the 8-week animals, the distribution of the AADC+ cells was dispersed and heterogeneous, whereas in the 3-year animals it was widespread and homogenous. Confocal analysis demonstrated that approximately 85% of the AADC+ cells were neuronal nuclei immunoreactive.
Improved separation of phospholipids in thin layer chromatography (1980)

Abstract The mobile phases described permit separation of the six major phospholipids of amniotic fluid in one dimension with either conventional or high performance thin layer chromatography. An example of this separation with an extract of amniotic fluid is given.
Transforming growth factor β stimulates rheumatoid synovial fibroblasts via the type II receptor (2005)

Transforming growth factor (TGF)-beta regulates the function of fibroblasts, and has been shown to have a role in the pathogenesis of rheumatoid arthritis (RA) because several studies have demonstrated the presence of TGF-beta in the synovial tissue and synovial fluids of RA patients. In this study, we examined the expression of TGF-beta receptors in synovial fibroblasts of patients with RA and demonstrated the significance in functional responses of synovial fibroblasts to TGF-beta in this disorder. Transforming growth factor beta1 stimulated the expression of connective tissue growth factor (CTGF) in fibroblasts of patients with RA more than in those of patients with osteoarthritis (OA). Transforming growth factor beta1 induced the chemotactic migration of RA synovial fibroblasts and inhibited their proliferation significantly more than OA synovial fibroblasts. Both RA and OA synovial fibroblasts expressed detectable amounts of TGF-beta receptor type II mRNA, but the expression was higher in RA patients than in OA patients, as assessed by reverse transcriptase-polymerase chain reaction. There was no significant difference in the expression of TGF-beta receptor type I or type III in synovial fibroblasts between RA and OA patients. These results indicate that synovial fibroblasts of RA patients express the increased TGF-beta receptor type II, which is associated with altered responses to TGF-beta observed in CTGF expression, chemotaxis, and proliferation of RA synovial fibroblasts, and may have an important role in the pathogenesis of RA.
Tumor Necrosis Factor–α Overexpression in Lung Disease (2005)

We conclude that TNF-alpha overexpression causes pathologic changes consistent with both emphysema and pulmonary fibrosis combined with a general lung inflammation, and consequently does not model any single human disease. Our study thus confirms the pleiotropic effects of TNF-alpha, which has been implicated in multiple inflammatory disorders, and underscores the necessity of using a wide range of investigative techniques to link gene expression and phenotype in animal models of disease.
Role of nitric oxide in maintaining vascular integrity in endotoxin‐induced acute intestinal damage in the rat (1990)

The role of endogenous nitric oxide (NO) in maintaining intestinal vascular integrity following acute endotoxin ( E. coli . lipopolysaccharide) challenge was investigated in the anaesthetized rat by use of N G ‐monomethyl‐ l ‐arginine ( l ‐NMMA), a selective inhibitor of NO synthesis. l ‐NMMA (10–50 mg kg −1 , i.v.) pretreatment enhanced both the macroscopic and histological intestinal damage and the increases in vascular permeability, measured as the leakage of [ 125 I]‐labelled human serum albumen, induced after 15 min by endotoxin (50 mg kg −1 , i.v.). The effects of l ‐NMMA (50 mg kg −1 , i.v.) were enantiomer specific, as d ‐NMMA had no effect. Furthermore, these effects were reversed by l ‐arginine (300 mg kg −1 , i.v.), the precursor of NO synthesis but not by d ‐arginine (300 mg kg −1 , i.v.). l ‐NMMA (10–50 mg kg −1 , i.v.) increased mean systemic arterial blood pressure but this does not appear to be the mechanism by which endotoxin‐induced intestinal damage was enhanced, since similar systemic pressor responses induced by phenylephrine (10 μg kg −1 min −1 , i.v.), had no such effect. The results suggest that synthesis of NO from l ‐arginine has a role in maintaining the microvascular integrity of the intestinal mucosa following acute endotoxin challenge.
CD66 family members are associated with tyrosine kinase activity in human neutrophils (1995)

The granulocyte activation Ags, CD66a, CD66b, CD66c, and CD66d, are expressed at low levels on resting blood granulocytes, but their surface expression is up-regulated following stimulation. CD66a, in contrast to CD66b and CD66c which are anchored to the membrane via a glycosyl-phosphatidylinositol linkage, is a transmembrane protein with a cytoplasmic domain. We have previously reported that CD66a is phosphorylated in human neutrophils, largely on tyrosine, with a lower level of phosphoserine. We have now found that CD66a undergoes a rapid increase in phosphorylation following stimulation with FMLP, platelet-activating factor, and 12-O-tetradecanoyl-phorbol-13-acetate. This increase in phosphorylation was transient, with maximal phosphorylation observed by 1 min and a return to base line by 5 min following stimulation. Protein kinase activity was detected in neutrophils associated with CD66a, CD66b, and CD66c. Most of the protein kinase activity associated with these Ags was tyrosine kinase activity, with a lesser amount of threonine and serine kinase activities. Lyn and Hck accounted for much of the associated tyrosine kinase activity. The data suggest that phosphorylation of CD66a on tyrosine by an associated tyrosine kinase may play a role in the function of CD66a. In addition, associated tyrosine kinase activity may play a role in signal transduction from CD66a, CD66b, and CD66c to regulate other cell functions.
Fatal myocardial infarction in the Scottish adjuvant tamoxifen trial. The Scottish Breast Cancer Committee. (1991)

Tamoxifen given for at least five years as adjuvant therapy for breast cancer seems to have a cardioprotective oestrogen-like effect in postmenopausal women.
I ka Piko, To the Summit: Resistance from the Mountain to the Sea (2019)

This paper focuses on Mauna Kea, the highest mountain in Hawaiʻi, and uses it as a case example for examining articulations of place and space, or how areas can be understood, read, and interpreted to push particular agendas. Furthermore, it comments on the often-conflicting expressions of belonging and possession, how they are enacted and embodied both on and off the mountain, and how they have been used in contemporary discourse regarding the sacred. Finally, it offers insight into how resistance efforts may be grounded and motivated by connections to place.
NotI flanking sequences: a tool for gene discovery and verification of the human genome (2002)

A set of 22 551 unique human NotI flanking sequences (16.2 Mb) was generated. More than 40% of the set had regions with significant similarity to known proteins and expressed sequences. The data demonstrate that regions flanking NotI sites are less likely to form nucleosomes efficiently and resemble promoter regions. The draft human genome sequence contained 55.7% of the NotI flanking sequences, Celera's database contained matches to 57.2% of the clones and all public databases (including non-human and previously sequenced NotI flanks) matched 89.2% of the NotI flanking sequences (identity > or =90% over at least 50 bp, data from December 2001). The data suggest that the shotgun sequencing approach used to generate the draft human genome sequence resulted in a bias against cloning and sequencing of NotI flanks. A rough estimation (based primarily on chromosomes 21 and 22) is that the human genome contains 15 000-20 000 NotI sites, of which 6000-9000 are unmethylated in any particular cell. The results of the study suggest that the existing tools for computational determination of CpG islands fail to identify a significant fraction of functional CpG islands, and unmethylated DNA stretches with a high frequency of CpG dinucleotides can be found even in regions with low CG content.
Neonatal Coinfection Model of Coagulase-Negative Staphylococcus ( Staphylococcus epidermidis ) and Candida albicans : Fluconazole Prophylaxis Enhances Survival and Growth (2007)

Coagulase-negative staphylococci (CoNS) and Candida are among the most common causes of single infections and coinfections in neonates after 72 h of age. In neonates, coinfection increases the rate of mortality threefold and results in significantly greater morbidity compared to those that result from single infections. In an effort to better understand this phenomenon, we developed the first neonatal animal model of coinfection (with CoNS and Candida) and evaluated its effects on mortality and morbidity and the impact of antifungal prophylaxis with fluconazole. Neonatal Wistar rats were infected with Candida albicans and/or Staphylococcus epidermidis with doses of 2x10(8) and 2x10(6) CFU subcutaneously in different combinations and were monitored for mortality, weight gain, and bacteremia. The in vitro sensitivity of C. albicans to fluconazole was evaluated and the MIC was determined. A subset of rats in these experiments received fluconazole at 10 mg/kg of body weight/dose intraperitoneally starting 24 h before infection for 4 days, and the serum trough levels of fluconazole were measured. Coinfection in the suckling rat significantly increased the rate of mortality compared to that after infection with a single species (P<0.001) and resulted in deaths even at sublethal doses. Coinfection also impaired weight gain significantly in severely infected pups compared to that achieved after infection with a single species (P<0.001). Fluconazole prophylaxis significantly reduced mortality by 30% in the Candida group and 36% in the coinfection group and improved weight gain in this neonatal model of coinfection (P<0.001). We developed a neonatal model of coinfection with Candida and CoNS, observed significantly greater mortality and morbidity with coinfection, and found that fluconazole prophylaxis significantly reduced the rates of both mortality and morbidity. Further research on neonatal coinfection is urgently needed to improve clinical outcomes.
Enhanced Engraftment of a Very Low-Dose Cord Blood Unit in an Adult Haemopoietic Transplant by Addition of Six Mismatched Viable Cord Units (2009)

The report describes the feasibility of the addition of multiple viable HLA-mismatched unrelated cord blood units, to a low cell number matched unrelated cord, to assist clinical engraftment. An ablative stem cell transplant was performed in an adult with relapsed acute lymphoblastic leukaemia (ALL), using a single HLA-matched cord blood unit (mononuclear cell dose 0.8 × 10(7)), supported by six mismatched cord blood units (one unit per 10 kg recipient weight). No adverse reaction occurred following the infusion of mismatched units and engraftment of the suboptimal-dose matched unit occurred rapidly, with no molecular evidence of engraftment of mismatched cords. Early molecular remission of ALL was demonstrated using a novel PCR for a mitochondrial DNA mutation in the leukaemic clone. The cell dose of the matched cord was well below that recommended to engraft a 70 kg recipient. We suggest that a factor or factors in the mismatched cords enhanced/supported engraftment of the matched cord.
Multiplication-free vector quantization using L/sub 1/ distortion measure and its variants (2003)

The authors first consider vector quantization that uses the L/sub 1/ distortion measure for its implementation. The L/sub 1/ distortion measure is very attractive from an implementational point of view, since no multiplication is required for computing the distortion measure. Unfortunately, the traditional Linde-Buzo-Gray method (1980) for designing the codebook for the L/sub 1/ distortion measure can become extremely time-consuming, since it involves several computations of medians of very large arrays. The authors propose a gradient-based approach for codebook design that does not require any multiplications or median computations. The codebook design algorithm is then extended to a distortion measure that has piecewise-linear characteristics. By appropriate selection of the parameters of the distortion measure, the encoding as well as the codebook design can be implemented with zero multiplications. The authors apply the proposed techniques in predictive vector quantization of images and demonstrate the viability of multiplication-free predictive vector quantization of image data.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Enhanced Biofilm Formation and Loss of Capsule Synthesis: Deletion of a Putative Glycosyltransferase inPorphyromonas gingivalis (2006)

Periodontitis is a biofilm-mediated disease. Porphyromonas gingivalis is an obligate anaerobe consistently associated with severe manifestations of this disease. As an opportunistic pathogen, the ability to proliferate within and disseminate from subgingival biofilm (plaque) is central to its virulence. Here, we report the isolation of a P. gingivalis transposon insertion mutant altered in biofilm development and the reconstruction and characterization of this mutation in three different wild-type strains. The mutation responsible for the altered biofilm phenotype was in a gene with high sequence similarity ( approximately 61%) to a glycosyltransferase gene. The gene is located in a region of the chromosome that includes up to 16 genes predicted to be involved in the synthesis and transport of capsular polysaccharide. The phenotype of the reconstructed mutation in all three wild-type backgrounds is that of enhanced biofilm formation. In addition, in strain W83, a strain that is encapsulated, the glycosyltransferase mutation resulted in a loss of capsule. Further experiments showed that the W83 mutant strain was more hydrophobic and exhibited increased auto-aggregation. Our results indicate that we have identified a gene involved in capsular-polysaccharide synthesis in P. gingivalis and that the production of capsule prevented attachment and the initiation of in vitro biofilm formation on polystyrene microtiter plates.
The Role of Innate Immunity in the Pathogenesis of Acne (2003)

Acne is a multifactorial disease of the pilosebaceous follicle. The most significant pathogenetic factors of acne are: abnormal ductal keratinization, increased sebum secretion, abnormalities of the microbial flora and inflammation. The pilosebaceous unit is an immunocompetent organ. Keratinocytes and sebocytes may act as immune cells capable of pathogen recognition and abnormal lipid presentation, and they might have an important role in initiating and perpetuating the activation of both innate and adaptive immune responses. The elements of the skin immune system are involved in the development of both noninflammatory and inflammatory acne lesions.
Screening for Chlamydia and Gonorrhea by Strand Displacement Amplification in Homeless Adolescents Attending Youth Shelters in Korea (2004)

We conducted the screening of sexually transmitted infections to define the prevalence of genital Chlamydia trachomatis and Neisseria gonorrhoeae infections and status of sexual risk behavior among homeless adolescents (10-19 yr old) in Korea. Adolescents who ran away from home and are under the care of youth shelters in ten cities in Korea served as the study population. Participants filled out a self-administered questionnaire related to sexuality. First-void urine was analyzed for chlamydial and gonococcal infection by strand displacement amplification (BDProbTec ET, BD Diagnostic Systems, MD, U.S.A.). A total of 175 adolescents from 15 youth shelters took part in the study. Their median age was 16 yr, and 54.9% of them reported having sexual intercourse at least once. The prevalence of C. trachomatis and N. gonorrhoeae among homeless adolescents was 12.6% and 15.4%, respectively. Factors significantly associated with the infections were number of sexual partners during the past year and lifetime. This is the first community-based sexually transmitted infection (STI) screening among adolescent in Korea. Screening programs targeting sexually active adolescents are important for detection of STIs. They should be considered an alternative population-based surveillance system in order to control STIs nationally.
Capillary passive valve in microfluidic systems (2004)

This work reports the theoretical and experimental investigations of capillary bust valves to regulate liquid flow in microchannels. The theoretical analysis uses the Young-Laplace equation and geometrical considerations to predict the pressure at the edge of the valve opening. Numerical simulations are employed to predict the meniscus shape evolution while the interface is pinned at the valve edge. Microchannel and valves are fabricated using the soft lithography. A wafer-rotating system, which can adjust a driving pressure by rotational speed, induces a liquid flow. Experimentally measured valve-bursting pressure agrees with theoretical predictions.
MEMS resonators that are robust to process-induced feature width variations (2002)

A stability analysis and design method for MEMS resonators is presented. The frequency characteristics of a laterally vibrating resonator are analyzed. With the fabrication error on the sidewall of the structure being considered, the first and second order frequency sensitivities to the fabrication error are derived. A simple relationship between the proof mass area and perimeter, and the beam width, is developed for single material structures, which expresses that the proof mass perimeter times the beam width should equal six times the area of the proof mass. Design examples are given for the single material and multi-layer structures. The results and principles presented in the paper can be used to analyze and design other MEMS resonators.
Tavaxy: Integrating Taverna and Galaxy workflows with cloud computing support (2012)

Tavaxy reduces the workflow development cycle by introducing the use of workflow patterns to simplify workflow creation. It enables the re-use and integration of existing (sub-) workflows from Taverna and Galaxy, and allows the creation of hybrid workflows. Its additional features exploit recent advances in high performance cloud computing to cope with the increasing data size and complexity of analysis.The system can be accessed either through a cloud-enabled web-interface or downloaded and installed to run within the user's local environment. All resources related to Tavaxy are available at http://www.tavaxy.org.