gebhart/patrepeval huggingface dataset:
Defining the Interleukin-8-binding Domain of Heparan Sulfate (1998)

Interleukin-8, a member of the CXC chemokine family, has been shown to bind to glycosaminoglycans. It has been suggested that heparan sulfate on cell surfaces could provide specific ligand sites on endothelial cells to retain the highly diffusible inflammatory chemokine for presentation to leukocytes. By using selectively modified heparin and heparan sulfate fragments in a nitrocellulose filter trapping system, we have analyzed sequence requirements for interleukin-8 binding to heparin/heparan sulfate. We demonstrate that the affinity of a monomeric interleukin-8 molecule for heparin/heparan sulfate is too weak to allow binding at physiological ionic strength, whereas the dimeric form of the protein mediates binding to two sulfated domains of heparan sulfate. These domains, each an N-sulfated block of approximately 6 monosaccharide units, are contained within an approximately 22-24-mer sequence and are separated by a region of </=14 monosaccharide residues that may be fully N-acetylated. Binding to interleukin-8 correlates with the occurrence of the di-O-sulfated disaccharide unit -IdceA(2-OSO3)-GlcNSO3(6-OSO3)-. We suggest that the heparan sulfate sequence binds in horseshoe fashion over two antiparallel-oriented helical regions on the dimeric protein.
Ovarian Abnormalities in a Mouse Model of Fragile X Primary Ovarian Insufficiency (2012)

FMR1 premutation (PM) alleles have 55-200 CGG·CCG-repeats in their 5' UTR. PM carriers are at risk of fragile X-associated tremor and ataxia syndrome (FXTAS). Females are also at risk for FX primary ovarian insufficiency (FXPOI). PM pathology is generally attributed to deleterious properties of transcripts with long CGG-tracts. For FXPOI, hormone changes suggest a reduced residual follicle pool. Whether this is due to a smaller than normal original follicle pool or an increased rate of follicle depletion is unclear. A FX-PM mouse the authors generated with 130 CGG·CCG-repeats in the endogenous Fmr1 gene recapitulates features of FXTAS. Here the authors demonstrate that the gross development of the ovary and the establishment of the primordial follicle pool is normal in these mice. However, these animals show a faster loss of follicles of all follicle classes, suggesting that the problem is intrinsic to the ovary. In addition, many oocytes show aberrant nuclear accumulation of FMRP and elevated levels of ubiquitination. Furthermore, PM follicles are smaller and have fewer granulosa cells (GCs) than normal. Thus, these animals have ovarian abnormalities involving both the oocytes and GCs that may shed light on the molecular basis of FXPOI in humans.
Fluorescence energy transfer in the rapid-diffusion limit (1978)

Energy transfer is enhanced by translational diffusion of the donor and acceptor [Steinberg, I. Z. & Katchalski, E. (1968) J. Chem. Phys. 48, 2404-2410]. The effect of diffusion on energy transfer depends on Dtau(0)/s(2), in which D is the sum of the diffusion coefficients of the donor and acceptor, tau(0) is the lifetime of the donor in the absence of transfer, and s is the mean distance between donors and acceptors. In most previous studies, Dtau(0)/s(2) << 1, corresponding to the static limit. We report here steady-state and kinetic fluorescence experiments showing that Dtau(0)/s(2) >> 1, the rapid-diffusion limit, can be attained by using Tb(3+) chelated to dipicolinate as a long-lived energy donor (tau(0) = 2.2 msec). The concentration of rhodamine B, the energy acceptor, resulting in 50% transfer was 0.67 muM, which is three orders of magnitude less than the concentration giving 50% transfer in the static limit. The dependence of the transfer efficiency on diffusion coefficients varying from 5 x 10(-11) to 1.5 x 10(-4) cm(2)/sec, spanning the range from the static limit to the rapid-diffusion limit, is in excellent agreement with theory. It is evident that energy donors with millisecond or longer excited state lifetimes can be used to probe translational motions in membranes and other assemblies. Energy transfer in the rapid diffusion limit is sensitive to the distance of closest approach (a) of the donor and acceptor. For a Tb.(DPA)(3) chelate trapped inside the aqueous space of a membrane vesicle containing eosin phosphatidylethanolamine, a = 10 A. The transverse location of chromophores in model membranes and biological membranes can be determined by this technique.
High-sensitivity surface-profile measurements by heterodyne white-light interferometer (2001)

A tandem white-light interferometer has been developed, based on the heterodyne technique, for highly accurate and sensitive surface profiling of a three-dimensional (3-D) object. Two acousto-optic modulators (AOMs) and two spherical reflecting mirrors are used in a Michelson interferometer to provide the optical frequency shift for white light. By using this technique in the tandem interferometer, the profiles of mirrorlike and diffusing surfaces of 3-D objects are measured with heterodyne signals of 200 kHz. The optical path difference of the interferometer can be stabilized by simultaneously using coherent and incoherent light. The experimental results show a 27-fold improvement in the stability of the interferometer and the possibility of achieving high accuracy of several tens of nanometers.
Reactive Hydrogel Networks for the Fabrication of Metal–Polymer Nanocomposites (2009)

In this study, highly stable gold and silver nanoparticles evenly distributed within a crosslinked poly(acrylamide)/poly(N-(hydroxymethyl)acrylamide) (PAAm-PHMAAm) network have been fabricated without addition of a reducing agent. Remarkably, the same chemical hydrogel composition has been involved in the successful fabrication of spherical gold and silver nanoparticles within the hydrogel template. The hydrogel network acts simultaneously as an efficient reducing agent and stabilizer. The PAAm-PHMAAm hydrogel network binds metal ions and, following reduction of bound to crosslinked template metal ions, proceeds via oxidation of hydroxymethyl hydrogel fragments. A one-electron mechanism is proposed for the formation of the silver and gold nanoparticles.
Mandibular Lengthening by Distraction for Airway Obstruction in Treacher-Collins Syndrome (1994)

Mandibular lengthening by distraction was performed in a 6-year-old tracheostomy-dependent Treacher-Collins syndrome patient. Detailed preoperative imaging revealed an occluded retrotongue base pharyngeal airway, which, following mandibular distraction, became patent and permitted tracheostomy removal. Mandibular distraction as a technique must be targeted toward clinical problems--management of upper-airway obstruction may be one such scenario.
A decentralized infrastructure for the efficient management of resources in the web of data (2012)

A key requirement in linking open data refers to the rendering of such data easy to explore and consume. Such a requirement is critical for the overall quality of linked data in terms of consistency and interlinking. Although the provision of dereferenceable URIs is a step towards the right direction, current status of the semantic web indicates that such a feature alone is not enough. After all, as Berners Lee stressed, a URI is just an identifier for a resource not a recipe for its retrieval.
Vein Conduits with Interposition of Nerve Tissue for Peripheral Nerve Defects (1995)

Vein conduits with interposition of autogenous nerve tissue were used in 16 peripheral nerves to reconstruct defects of between 2.0 and 5.8 cm. This technique was applied in nine digital nerves, four ulnar nerves, two median nerves, and one radial sensory nerve. A single vein conduit was used in digital nerve defects and two or three vein segments were used in defects of nerve trunks. Nerve tissue was sectioned from the proximal nerve stump and inserted inside the vein conduits. Follow-up of 2.5 to 3.5 years has revealed motor recovery to M4 in three nerves, M3+ in three, M2 in one nerve, and sensory recovery to S4 in two nerves, S3+ in five, S3 in four, S2+ in three and S0 in two nerves. Signs of muscle reinnervation of the repaired nerves were noted on electromyography. Two digital nerves with defects of over 5.0 cm did not show any signs of sensory recovery. Sectioning and placement of autogenous nerve tissue is thought to create fresh and additional sources for the release of neurotropic factors, and may serve to convey the neurotropic effect over a longer distance. This clinical study suggests that vein conduits with the interposition of nerve tissue is a practical and reliable procedure for nerve defects between 2.0 cm and 4.5 cm.
Molecular determinants for the action of general anesthetics  at recombinant α2β3γ2γ‐aminobutyric acidA receptors (2001)

General anesthetics modulate the activity of ligand-gated ion channels including the GABA(A) receptor. Mutational studies mainly on the benzodiazepine-insensitive alpha(2)beta(1(M286W)) and alpha(6)beta(3(N289M))gamma(2) GABA(A) receptors revealed that a serine in transmembrane domain 2 and a methionine in transmembrane domain 3 are essential for the action of most general anesthetics. We investigated whether these residues would similarly be relevant for their action at the benzodiazepine-sensitive GABA receptor subtype, alpha(2)beta(3)gamma(2). We found that not only the N265M but also the M286W mutation nearly abolished the modulatory effect of etomidate. However, the anti-convulsant loreclezole, a structural homologue of etomidate, was inactive on the N265M mutant, but displayed normal modulatory activity on the M286W mutant. Both mutations did not affect the modulatory action of the neurosteroid alphaxalone. The direct action of alphaxalone, however, was dramatically increased in the M286W mutant to about twice the maximal GABA current but not significantly affected in the N265M mutant. These data demonstrate that the structural requirements for modulatory and direct actions of various general anesthetics are distinct. The molecular switches induced by these mutations can be exploited to identify the molecular determinants for the action of general anesthetics.
Multiple control elments for theuvrCgene unit ofEscherichia coli (1986)

We have sequenced the control region of the uvrC protein including two open reading frames (ORF) encoding polypeptides of 28 kd and 23 kd molecular weight. The uvrC gene is preceded by five promoters. The P1, P2a and P2b promoter sequences are 5' to the 28 kd and the 23 kd proteins respectively. The P3 and P4 promoters are located within the structural gene for the 23 kd protein. The P3 promoter is required for adequate in vivo expression. There are three putative lexA protein binding sites, detected at the 3' end of the 28 kd protein (lexA1), within the coding sequences for the 23 kd protein (lexA2) and within the P3 promoter (lexA3). Promoter P2 is responsible for transcription of the uvrC gene, producing transcripts of 2.8 and 1.6 kb. The upstream region including the 28 kd protein is required for enhanced expression under non-induced conditions. These results show that the uvrC gene is controlled by multiple promoters and is transcribed as part of a multigene unit.
Effects of humidity on stress in thin silicon dioxide films (1982)

The stresses of thermally grown as well as chemically vapor deposited (CVD) silicon dioxide were measured by the cantilever beam technique using x-ray diffraction. Thermally grown oxide shows reversible stress changes upon heating or cooling of the films. The linear thermal expansion of such films is similar to that of bulk vitreous silica, 5×10−7 °C−1, the biaxial elastic modulus was found to be 6.3×1011 dyn/cm2. CVD oxides show extensive hysteresis in the stress-temperature curves when tested in ambient air. From stress measurements of such films, deposited on Si and GaAs, it was concluded that their average linear thermal expansion coefficient in the temperature range of −170–115 °C is 4×10−6 °C−1, much higher than that of thermally grown oxide, while their biaxial elastic modulus is only 4.6–5.1×1011 dyn/cm2. The stress in such films was found to increase when the films were exposed to a dry ambient or vacuum. The time constant for this change was found to be several minutes at room temperature.
Activity of 3β-Hydroxy-Δ5-Steroid Dehydrogenase/Δ 5-Δ4-Isomerase in the Ovine Corpus Luteum1 (1979)

The 3β-hydroxy-Δ5-steroid dehydrogenase/Δ5-Δ4-isomerase complex (HSD) is responsible for the conversion of pregnenolone to progesterone. In the ovine corpus luteum, HSD activity was found to be localized in the microsomal fraction and the activity displayed a broad pH optimum between pH 6.5 and 8.0. The HSD activity was extremely sensitive to feedback inhibition by its own product, progesterone, and the inhibition appears to be competitive in nature. The inhibition could be relieved and pseudo-zero order kinetics established with the addition of normal serum to the reaction mixture. The steroid binding proteins in serum presumably bound the progesterone as it was produced. The affinity of HSD for progesterone (product) appears to be several fold higher than for pregnenolone (substrate). Testosterone and estradiol were also potent inhibitors of HSD activity. The inhibition of HSD activity by progesterone could be demonstrated in suspensions of isolated luteal cells. Since this phenomenon was observed in preparations of intact cells, the possibility of a local autoregulation of progesterone secretion involving circulating steroids and feedback inhibition was considered. To create locally high concentrations of inhibitory steroids, testosterone was infused into the ovarian arterial circulation. When this was done there was no effect on progesterone secretion, suggesting the absence of feedback regulation of progesterone production by circulating steroids at the ovarian level.
Lupus nephritis: update on pathogenesis and disease mechanisms. (1999)

Immune-mediated nephritis is a common complication of systemic lupus erythematosus (SLE). It is now clear that multiple and independent mechanisms contribute to disease onset and pathogenesis, which may explain the remarkable phenotypic and histopathological heterogeneity observed in human SLE. Identification and characterization of disease-relevant autoantibodies, cellular effectors, and soluble immune elements have provided crucial insight into the immunologic interactions that promote renal immune injury. It is now clear that nephritogenic autoantibodies of diverse specificity localize to the kidney by a variety of mechanisms. They are accompanied by activated macrophages and T cells recruited in part through enhanced and abnormal production of macrophage growth factors and cytokines. These pathways provide novel targets for therapeutic intervention to prevent or ameliorate the aggressive autoimmune nephritis that characterizes SLE.
Rituximab for steroid-refractory chronic graft-versus-host disease (2006)

B cells may be implicated in the pathophysiology of chronic graft-versus-host disease (GVHD), as evidenced by antibody production against sex-mismatched, Y chromosome–encoded minor HLA antigens in association with chronic GVHD. We therefore designed a phase 1/2 study of anti–B-cell therapy with rituximab in steroid-refractory chronic GVHD. Twenty-one patients were treated with 38 cycles of rituximab. Rituximab was tolerated well, and toxicity was limited to infectious events. The clinical response rate was 70%, including 2 patients with complete responses. Responses were limited to patients with cutaneous and musculoskeletal manifestations of chronic GVHD and were durable through 1 year after therapy. The median dose of prednisone among treated subjects fell from 40 mg/day to 10 mg/day, 1 year after rituximab therapy (P &lt; .001). A chronic GVHD symptom score improved in the majority of treated patients. Antibody titers against Y chromosome–encoded minor HLA antigens fell and remained low, whereas titers against infectious antigens (EBV, tetanus) remained stable or rose during the treatment period. We conclude that specific anti–B-cell therapy with rituximab may be beneficial for patients with steroidrefractory chronic GVHD. This trial was registered at www.clinicaltrials.gov as #NCT00136396.
High delta‐like 1 expression in a subset of neuroblastoma cell lines corresponds to a differentiated chromaffin cell type (2003)

The childhood tumour neuroblastoma originates from neural crest-derived progenitors of the sympathetic nervous system. By Serial Analysis of Gene Expression (SAGE), we previously identified the Drosophila Delta homologue Dlk1 as one of the genes most highly expressed in the neuroblastoma cell line SK-N-FI. The Delta-Notch pathway controls many differentiation steps in Drosophila and man. We analysed expression of 21 genes of this pathway in 21 neuroblastoma cell lines. Dlk1 expression was very high in 5 cell lines, while another subset expressed Notch3. The imprinting of Dlk1 was faithfully preserved in neuroblastomas. The single paternal allele can therefore produce over 0.5% of all cellular mRNAs. Dlk1 maps to 14q32, a region that exhibited LOH in 31/170 (18%) tumours. The random parental origin of the deleted alleles excluded Dlk1 as target of the LOH. In addition, Dlk1 was not amplified, rearranged or mutated in neuroblastoma cell lines and tumours. We therefore analysed whether high Dlk1 expression marks a specific differentiation stage of the sympatho-adrenal lineage. Many neuroblastomas arise in the adrenal medulla, which predominantly consists of chromaffin cells. Normal adrenal medulla exhibited equally high Dlk1 levels as the SK-N-FI cell line. Chromaffin cells in young children are marked by noradrenalin production, which is mediated by dopamine-beta-hydroxylase (DBH). DBH expression in the neuroblastoma cell lines almost perfectly corresponded to Dlk1 expression. Neuroblastoma cell lines with high Dlk1 expression are therefore arrested in a relatively late stage of chromaffin lineage differentiation, while Notch3 expression might correspond to earlier precursor stages or to an alternative developmental fate.
HLA-DQA1 and HLA-DQB1 in Celiac disease predisposition: practical implications of the HLA molecular typing (2012)

Celiac disease (CD) is a multifactorial disorder with an estimated prevalence in Europe and USA of 1:100 and a female:male ratio of approximately 2:1. The disorder has a multifactorial etiology in which the triggering environmental factor, the gluten, and the main genetic factors, Human Leukocyte Antigen (HLA)-DQA1 and HLA-DQB1 loci, are well known. About 90-95% of CD patients carry DQ2.5 heterodimers, encoded by DQA1*05 and DQB1*02 alleles both in cis or in trans configuration, and DQ8 molecules, encoded by DQB1*03:02 generally in combination with DQA1*03 variant. Less frequently, CD occurs in individuals positive for the DQ2.x heterodimers (DQA1≠*05 and DQB1*02) and very rarely in patients negative for these DQ predisposing markers. HLA molecular typing for Celiac disease is, therefore, a genetic test with a negative predictive value. Nevertheless, it is an important tool able to discriminate individuals genetically susceptible to CD, especially in at-risk groups such as first-degree relatives (parents, siblings and offspring) of patients and in presence of autoimmune conditions (type 1 diabetes, thyroiditis, multiple sclerosis) or specific genetic disorders (Down, Turner or Williams syndromes).
Pulmonary vascular involvement in chronic obstructive pulmonary disease (2003)

Chronic obstructive lung disease affects the entire lung, not just the airways. Although pulmonary hypertension (PH) has long been recognised in a subset of patients with COLD, the important pathophysiological questions remain unanswered. Oxygen supplementation, however, has been shown to blunt the exercise-induced PH in these patients. Hypercoagulability has also been described in patients with COLD. This may, in part, be due to the inflammatory aspects of COLD exacerbation events. In addition to perivascular inflammation, the pathology of vessels in COLD includes intimal thickening, muscularisation of arterioles, in situ thrombosis, loss of capillaries and precapillary arterioles, and vascular congestion and stasis. Recent work describes apoptosis of septal endothelial cells and decreased expression of vascular endothelial growth factor (VEGF) and one of its receptors, VEGFRII, in lungs from patients with emphysema. Based on this work, a rat model was developed that shows chronic blockade of VEGF receptors leads to septal cell apoptosis and results in emphysema and PH. This animal model has led to prevention trials using 1) a broad-spectrum caspase inhibitor, 2) a superoxide dismutase mimetic, and 3) alpha1-antitrypsin. These findings highlight the importance of vascular endothelial growth factor, apoptosis, oxidative stress and protease activity in the pathogenesis of emphysema. They also underscore the importance of the vasculature in what is traditionally thought of as an airways disease. Future treatment strategies need to address the vascular components of chronic obstructive lung disease.
SYNTHESIS OF NEW CHIRAL PEPTIDE NUCLEIC ACID (PNA) MONOMERS (2001)

We have synthesised a series of new chiral type I peptide nucleic acid monomers in total yields of 36-53%, derived from Val, Ile, Ser(Bzl), Pro, and Trp, employing convenient procedure.
Pain modulation by release of the endogenous cannabinoid anandamide (1999)

Synthetic cannabinoids produce behavioral analgesia and suppress pain neurotransmission, raising the possibility that endogenous cannabinoids serve naturally to modulate pain. Here, the development of a sensitive method for measuring cannabinoids by atmospheric pressure-chemical ionization mass spectrometry permitted measurement of the release of the endogenous cannabinoid anandamide in the periaqueductal gray (PAG) by in vivo microdialysis in the rat. Electrical stimulation of the dorsal and lateral PAG produced CB1 cannabinoid receptor-mediated analgesia accompanied by a marked increase in the release of anandamide in the PAG, suggesting that endogenous anandamide mediates the behavioral analgesia. Furthermore, pain triggered by subcutaneous injections of the chemical irritant formalin substantially increased the release of anandamide in the PAG. These findings indicate that the endogenous cannabinoid anandamide plays an important role in a cannabinergic pain-suppression system existing within the dorsal and lateral PAG. The existence of a cannabinergic pain-modulatory system may have relevance for the treatment of pain, particularly in instances where opiates are ineffective.