gebhart/patrepeval huggingface dataset:
sn-1,2-diacylglycerol kinase of Escherichia coli. Diacylglycerol analogues define specificity and mechanism. (1990)

A detailed structure/function analysis of the substrate specificity of Escherichia coli sn-1,2-diacylglycerol kinase was performed with three goals in mind: (a) to define the substrate specificity; (b) to discover inhibitors; and (c) to elucidate the specificity of diacylglycerol-dependent inactivation. Forty-seven structural analogues of sn-1,2-diacylglycerol were prepared and examined as substrates, inhibitors, and irreversible inactivators of the enzyme using mixed micellar assay methods. Modification of the acyl chains or the sn-2 ester affected the apparent Km but had only small effects on Vm; modifications of the sn-1 ester, sn-3 methylene, or sn-3 hydroxyl had large effects on the apparent Vm and smaller effects on Km. Consistent with these observations, diacylglycerol analogues modified only in the acyl chains or sn-2 ester were not diacylglycerol kinase inhibitors, whereas analogues with substitutions of the sn-1 ester or sn-3 hydroxyl frequently caused inhibition. A hydrogen bond-donating group was required for an analogue to be a diacylglycerol kinase inhibitor. Studies of diacylglycerol kinase inactivation by the various analogues were consistent with the previous conclusion that this process involves an interaction of diacylglycerols with an enzyme conformation different from that active in catalysis (Walsh, J. P., and Bell, R. M. (1986) J. Biol. Chem. 261, 15062-15069). Studies with a water-soluble diacylglycerol, sn-1,2-dibutyrylglycerol, allowed direct comparison of diacylglycerol kinase activity in mixed micelles with that in native membranes. The results are discussed in relation to the structural requirements of other diacylglycerol-dependent enzymes.
Association of a transmembrane polymorphism of Fcγ receptor IIb (FCGR2B) with systemic lupus erythematosus in Taiwanese patients (2006)

The FcgammaRIIb transmembrane polymorphism is a strong disease susceptibility candidate in epistasis with other genetic effects in Taiwanese and other Asian populations. It may also play a more prominent role in male patients with SLE.
A double‐blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease (2003)

Thirty-four patients with advanced Parkinson's disease participated in a prospective 24-month double-blind, placebo-controlled trial of fetal nigral transplantation. Patients were randomized to receive bilateral transplantation with one or four donors per side or a placebo procedure. The primary end point was change between baseline and final visits in motor component of the Unified Parkinson's Disease Rating Scale in the practically defined off state. There was no significant overall treatment effect (p = 0.244). Patients in the placebo and one-donor groups deteriorated by 9.4 +/- 4.25 and 3.5 +/- 4.23 points, respectively, whereas those in the four-donor group improved by 0.72 +/- 4.05 points. Pairwise comparisons were not significant, although the four-donor versus placebo groups yielded a p value of 0.096. Stratification based on disease severity showed a treatment effect in milder patients (p = 0.006). Striatal fluorodopa uptake was significantly increased after transplantation in both groups and robust survival of dopamine neurons was observed at postmortem examination. Fifty-six percent of transplanted patients developed dyskinesia that persisted after overnight withdrawal of dopaminergic medication ("off"-medication dyskinesia). Fetal nigral transplantation currently cannot be recommended as a therapy for PD based on these results.
4-μm pixel CMOS image sensor with low-image lag and high-temperature operability (2003)

We present a development of a high image quality color VGA CMOS image sensor with 4-micron pixel pitch, especially focusing on reduction of image lag. In order to eliminate image lag, improvement of charge transfer efficiency from photodiode (PD) to floating diffusion (FD) is a key point. We implemented two novel techniques for this purpose. The first technical point is an optimum design of pixel layout, which provides both high fill factor and a large channel width of transfer gate transistor (TG). We achieved both high fill factor of 42% without microlens and large TG channel width of 1.79um, which is 2.4 times larger than the minimum channel width allowed by design rule. The second technical point is a new device structure of TG by a novel Boron implantation process. This brings a wide path of charge transfer from PD to FD. High-quality images with low image lag, less than 0.75%, were obtained. Moreover, we also achieved a CMOS image sensor with high-temperature operability. In order to stabilize an adequate black level, we developed a new scheme of a black level control that adjusts offset voltages of amplifiers with feedback signal from analog-digital converter (ADC). An adequate black level was realized up to 100 degrees centigrade for a 5.6-micron pitch monochrome CIF sensor.
Rho Kinase Inhibition Enhances Axonal Regeneration in the Injured CNS (2003)

Myelin-associated inhibitors limit axonal regeneration in the injured brain and spinal cord. A common target of many neurite outgrowth inhibitors is the Rho family of small GTPases. Activation of Rho and a downstream effector of Rho, p160ROCK, inhibits neurite outgrowth. Here, we demonstrate that Rho is directly activated by the myelin-associated inhibitor Nogo-66. Using a binding assay to measure Rho activity, we detected increased levels of GTP Rho in PC12 and dorsal root ganglion (DRG) cell lysates after Nogo-66 stimulation. Rho activity levels were not affected by Amino-Nogo stimulation. Rho inactivation with C3 transferase promotes neurite outgrowth of chick DRG neurons in vitro, but with the delivery method used here, it fails to promote neurite outgrowth after corticospinal tract (CST) lesions in the adult rat. Inhibition of p160ROCK with Y-27632 also promotes neurite outgrowth on myelin-associated inhibitors in vitro. Furthermore, Y-27632 enhances sprouting of CST fibers in vivo and accelerates locomotor recovery after CST lesions in adult rats.
The utrophin and dystrophin genes share similarities in genomic structure (1993)

Utrophin and dystrophin are highly homologous proteins which are reciprocally expressed in DMD (Duchenne muscular dystrophy) muscle. The remarkable similarity of these proteins suggests that they may play a similar cellular role in some circumstances; if this were the case then utrophin may be capable of replacing dystrophin in DMD patients. In this paper we show that the genomic structure of the utrophin gene is similar to the dystrophin gene, further exemplifying the relatedness of the two genes and their gene products. We have constructed a 1.25 Mb contig of eight yeast artificial chromosome (YAC) clones covering the utrophin gene located on chromosome 6q24. Utrophin is encoded by multiple small exons spanning approximately 900 kb. The distribution of exons within the genomic DNA has similarities to that of the dystrophin gene. In contrast to dystrophin, the utrophin gene has a long 5' untranslated region composed of two exons and a cluster of unmethylated, rare-cutting restriction enzyme sites at the 5' end of the gene. Similarities between the genomic structure suggest that utrophin and dystrophin arose through an ancient duplication event involving a large region of genomic DNA.
Is pulse transit time a good indicator of blood pressure changes during short physical exercise in a young population? (2010)

The Pulse Transit Time (PTT) is generally assumed to be a good surrogate measure to comfortably track blood pressure (BP) and blood pressure changes. This paper investigates PTT variations for healthy young subjects during a sequence of short-term physical exercises. PTT was measured by two different methodologies having different measurement accuracies as well as underlying assumptions: the total PTT from heart to fingertip and the difference of fingertip and earlobe PTTs. Small non consistent changes and very low correlation of both PTTs with systolic blood pressure (SBP) have been observed for the study population (-0.19 ± 0.45 and 0.22 ± 0.46). In conclusion, there might be a need for an improved measurement accuracy of the sensors and data processing techniques in use. The applicability of the Moens-Korteweg equation is also questionable for young people having flexible arteries. In this case, significant radius changes do occur in the large arteries during exercise, which might counteract a PTT decrease with the BP elevation. These radius effects are excluded from the Moens-Korteweg model.
Photoactivatable Porphyrin Oligonucleotide Derivatives for Sequence Specific Chemical Modification and Cleavage of DNA (1991)

Abstract Oligonucleotide derivatives bearing porphyrin groups cause site-specific modification of DNA after irradiation with visible light.
A novel, tissue-restricted zinc finger protein (HF-1b) binds to the cardiac regulatory element (HF-1b/MEF-2) in the rat myosin light-chain 2 gene. (1993)

The AT-rich element MEF-2 plays an important role in the maintenance of the muscle-specific expression of a number of cardiac and skeletal muscle genes. In the MLC-2 gene, an AT-rich element (HF-1b) which contains a consensus MEF-2 site is required for cardiac tissue-specific expression. The present study reports the isolation and characterization of a cDNA which encodes a novel C2H2 zinc finger (HF-1b) that binds in a sequence-specific manner to the HF-1b/MEF-2 site in the MLC-2 promoter. A number of independent criteria suggest that this HF-1b zinc finger protein is a component of the endogenous HF-1b/MEF-2 binding activity in cardiac muscle cells and that it can serve as a transcriptional activator of the MLC-2 promoter in transient assays. These studies suggest that, in addition to the previously reported RSRF proteins, structurally divergent transcriptional factors can bind to MEF-2-like sites in muscle promoters. These results underscore the complexity of the regulation of the muscle gene program via these AT-rich elements in cardiac and skeletal muscle.
Pore structure analysis of purified, sodium hydroxide-treated and liquid ammonia-treated cotton celluloses (1984)

To characterize the pore structures of purified cotton, NaOH-treated cotton, and liquid-NH3-treated cotton, we have (1) investigated the feasibility of preparing useful chromatographic columns from whole cotton fibers and (2) studied the elution behavior (penetration) of three selected classes of water-soluble solutes from columns of the three types of cotton fibers. The solutes were series of common oligomeric sugars, oxyethylene glycols, and oxyethylene glycol dimethyl ethers having molecular weights or dimensions in the range of conventional dyes and finishing agents. Substantial differences in dyeing performance and in resilience have been reported for the cottons under study. Differences in performance qualities of these fibers in fabric form are explained in terms of the substantial differences in sizes and abundance of pores in the fibers.
L-selectin binds to P-selectin glycoprotein ligand-1 on leukocytes: interactions between the lectin, epidermal growth factor, and consensus repeat domains of the selectins determine ligand binding specificity (1996)

The selectins mediate cellular interactions by binding carbohydrate determinants present on a limited number of glycoprotein ligands. L-selectin binds multiple ligands expressed on endothelial cells, while P-selectin interacts exclusively with P-selectin glycoprotein ligand-1 (PSGL-1) on leukocytes. In this study, L-selectin was shown to bind leukocytes through the P-selectin ligand, PSGL-1, although at lower levels than P-selectin. L-selectin binding to PSGL-1 is specific since it was blocked by Abs to L-selectin or PSGL-1, required appropriate glycosylation of PSGL-1, and was Ca2+ dependent. The contributions of the extracellular domains of the selectins to ligand binding was assessed using a panel of chimeric selectins created by exchange of domains between L-selectin and P- or E-selectin. The lectin and epidermal growth factor domains of L- and P-selectin contributed significantly to binding through similar, if not identical, regions of PSGL-1. The different chimeric selectins revealed that the lectin domain was the dominant determinant for ligand binding, while cooperative interactions between the lectin, epidermal growth factor, and short consensus repeat domains of the selectins also modified ligand binding specificity. L-selectin binding to PSGL-1 expressed by leukocytes may mediate neutrophil rolling on stationary leukocytes bound to cytokine-induced endothelial cells, which was previously reported to be a L-selectin-dependent process.
Human umbilical cord blood cells ameliorate Huntington's disease in transgenic mice. (2001)

Human umbilical cord blood mononuclear cells given in megadose quantity (71-74 x 10(6) and 100-105 x 10(6)) were able to increase the life span of B6CBA-TgN(Hdexon1)62Gpb mice (Huntington disease) from an average of 88 days to 97.8 and 103.4 days respectively. The rate of weight loss, which begins in these mice before the onset of symptoms of chorea, was far less in the animals receiving human cord blood mononuclear cells (p<0.01) than the weight loss in untreated control mice. With the full understanding that additional histological and behavioral studies are indicated, but because of the potential clinical significance, a brief report is being submitted.
Noncytopathic Sindbis virus RNA vectors for heterologous gene expression (1998)

Infection of vertebrate cells with alphaviruses normally leads to prodigious expression of virus-encoded genes and a dramatic inhibition of host protein synthesis. Recombinant Sindbis viruses and replicons have been useful as vectors for high level foreign gene expression, but the cytopathic effects of viral replication have limited their use to transient studies. We recently selected Sindbis replicons capable of persistent, noncytopathic growth in BHK cells and describe here a new generation of Sindbis vectors useful for long-term foreign gene expression based on such replicons. Foreign genes of interest as well as the dominant selectable marker puromycin N-acteyltransferase, which confers resistance to the drug puromycin, were expressed as subgenomic transcripts of noncytopathic replicons or defective-interfering genomes complemented in trans by a replicon. Based on these strategies, we developed vectors that can be initiated via either RNA or DNA transfection and analyzed them for their level and stability of foreign gene expression. Noncytopathic Sindbis vectors express reasonably high levels of protein in nearly every cell. These vectors should prove to be flexible tools for the rapid expression of heterologous genes under conditions in which cellular metabolism is not perturbed, and we illustrate their utility with a number of foreign proteins.
Polyol Content of Bostrychia and Stictosiphonia (Rhodomelaceae, Rhodophyta) from Field and Culture (1992)

Field and culture samples of Bostrycha and Stictosiphonia species were analyzed for D-dulcitol and D-sorbitol that function as osmoregulatory solutes and photoassimilation products. Bostrychia bispora West et Zuccarello, B. calliptera (Montagne) Montagne, B. montagnei Harvey, B. moritziana (Sonder ex Kutzing) J. Agardh, B. pinnata J. Tanaka et Chihara, B. radicans (Montagne) Montagne, B. simpliciuscula Harvey ex J. Agardh and B. tenella (Lamouroux) J. Agardh contain both polyols, except for one isolate of B. radicans (2879/80/81) that contains only D-sorbitol (...)
Pharmacological Targeting of Anaphylatoxin Receptors during the Effector Phase of Allergic Asthma Suppresses Airway Hyperresponsiveness and Airway Inflammation (2005)

Airway hyperresponsiveness and airway inflammation are hallmarks of allergic asthma, the etiology of which is crucially linked to the presence of Th2 cytokines. A role for the complement anaphylatoxins C3a and C5a in allergic asthma was suggested, as deficiencies of the C3a receptor (C3aR) and of complement factor C5 modulate airway hyperresponsiveness, airway inflammation, and Th2 cytokine levels. However, such models do not allow differentiation of effects on the sensitization phase and the effector phase of the allergic response, respectively. In this study, we determined the role of the anaphylatoxins on the effector phase of asthma by pharmacological targeting of the anaphylatoxin receptors. C3aR and C5a receptor (C5aR) signaling was blocked using the nonpeptidic C3aR antagonist SB290157 and the neutralizing C5aR mAb 20/70 in a murine model of Aspergillus fumigatus extract induced pulmonary allergy. Airway hyperresponsiveness was substantially improved after C5aR blockade but not after C3aR blockade. Airway inflammation was significantly reduced in mice treated with the C3aR antagonist or the anti-C5aR mAb, as demonstrated by reduced numbers of neutrophils and eosinophils in bronchoalveolar lavage fluid. Of note, C5aR but not C3aR inhibition reduced lymphocyte numbers in bronchoalveolar lavage fluid. Cytokine levels of IL-5 and IL-13 in bronchoalveolar lavage fluid were not altered by C3aR or C5aR blockade. However, blockade of both anaphylatoxin receptors markedly reduced IL-4 levels. These data suggest an important and exclusive role for C5aR signaling on the development of airway hyperresponsiveness during pulmonary allergen challenge, whereas both anaphylatoxins contribute to airway inflammation and IL-4 production.
Cell Therapy with Human Renal Cell Cultures Containing Erythropoietin-Positive Cells Improves Chronic Kidney Injury (2012)

New therapeutic strategies for chronic kidney disease (CKD) are necessary to offset the rising incidence of CKD and donor shortage. Erythropoietin (EPO), a cytokine produced by fibroblast-like cells in the kidney, has recently emerged as a renoprotective factor with anti-inflammatory, antioxidant properties. This study (a) determined whether human renal cultures (human primary kidney cells [hPKC]) can be enriched in EPO-positive cells (hPKC(F+)) by using magnetic-bead sorting; (b) characterized hPKC(F+) following cell separation; and (c) established that intrarenal delivery of enriched hPKC(F+) cells would be more beneficial in treatment of renal injury, inflammation, and oxidative stress than unsorted hPKC cultures in a chronic kidney injury model. Fluorescence-activated cell sorting analysis revealed higher expression of EPO (36%) and CD73 (27%) in hPKC(F+) as compared with hPKC. After induction of renal injury, intrarenal delivery of hPKC(F+) or hPKC significantly reduced serum creatinine, interstitial fibrosis in the medulla, and abundance of CD68-positive cells in the cortex and medulla (p < .05). However, only hPKC(F+) attenuated interstitial fibrosis in the renal cortex and decreased urinary albumin (3.5-fold) and urinary tubular injury marker kidney injury molecule 1 (16-fold). hPKC(F+) also significantly reduced levels of renal cortical monocyte chemotactic protein 1 (1.8-fold) and oxidative DNA marker 8-hydroxy-deoxyguanosine (8-OHdG) (2.4-fold). After 12 weeks, we detected few injected cells, which were localized mostly to the cortical interstitium. Although cell therapy with either hPKC(F+) or hPKC improved renal function, the hPKC(F+) subpopulation provides greater renoprotection, perhaps through attenuation of inflammation and oxidative stress. We conclude that hPKC(F+) may be used as components of cell-based therapies for degenerative kidney diseases.
A multimodal registration algorithm of eye fundus images using vessels detection and Hough transform (1999)

Image registration is a real challenge because physicians handle many images. Temporal registration is necessary in order to follow the various steps of a disease, whereas multimodal registration allows us to improve the identification of some lesions or to compare pieces of information gathered from different sources. This paper presents an algorithm for temporal and/or multimodal registration of retinal images based on point correspondence. As an example, the algorithm has been applied to the registration of fluorescein images (obtained after a fluorescein dye injection) with green images (green filter of a color image). The vascular tree is first detected in each type of images and bifurcation points are labeled with surrounding vessel orientations. An angle-based invariant is then computed in order to give a probability for two points to match. Then a Bayesian Hough transform is used to sort the transformations with their respective likelihoods. A precise affine estimate is finally computed for most likely transformations. The best transformation is chosen for registration.
Experimental Studies of Potential Analgesics for the Treatment of Chemotherapy-Evoked Painful Peripheral Neuropathies (2007)

The present data and data from the literature review suggest that there are several potential treatments for chemotherapy-evoked neuropathic pain. Nonsteroidal anti-inflammatory drugs have little or no efficacy. Opioids have an effect, but probably only with high doses. At least some antidepressants are analgesic in these conditions. Some, but clearly not all, anticonvulsants and sodium channel blockers have efficacy. Tramadol is a particularly promising candidate. Topiramate, acetyl-L-carnitine, carbamazepine, and venlafaxine may have protective or restorative effects. Clinical trials of these candidates are needed to advance the treatment of chemotherapy-evoked pain.
The Role of Adhesion Molecules in Multiple Myeloma (1997)

The neoplastic plasma cells of multiple myeloma differ from normal plasma cells and other B-cell malignancies by an almost exclusive homing to the bone marrow microenvironment which clearly provides the appropriate support, both physical and cytokine, to mediate clonal proliferation and terminal differentiation. Cellular adhesion molecules are involved in the homing of malignant plasma cells to the bone marrow, the production of growth factors and the recirculation of these tumour cells in the advanced stages of disease. Neoplastic plasma cells express H-CAM (CD44), VLA-4 (CD49d/CD29), ICAM-1 (CD54), N-CAM (CD56) and LFA-3 (CD58). In addition VLA-5 (CD49e/CD29) expression seems to be related to cells with less proliferative potential and more potential for paraprotein production. In addition there are fundamental changes in the bone marrow stroma of patients with multiple myeloma including altered composition of the extracellular matrix, increased growth capability of the cellular elements and increased synthesis of interleukin-6 and interleukin-3, which are features postulated to localise and promote growth of the circulating neoplastic progenitors in the bone marrow. However, the evidence to date does not fully explain the inter-relationship of the clonal B cells and the bone marrow stroma in patients with myeloma, including factors which trigger and facilitate the extravasation and recirculation of neoplastic plasma cells as seen in advanced disease.