gebhart/patrepeval huggingface dataset:
Studies of visual function and its decay in mice with hereditary retinal degeneration (1978)

Abstract Functional implications of mouse hereditary retinal degeneration have been studied at the level of the superior colliculus and visual cortex in the C57BL/6J‐ le rd strain. On autoradiography at a light‐microscopic level, following eye injection with radioactive compounds, central visual structures appeared normal. A slight reduction in ipsilateral retinal projection was probably related to reduced retinal pigmentation associated with the light ear ( le ) mutation. In recordings from visual cortex and tectum in rd mice older than five months the cells discharged with highly rhythmic maintained activity. This ongoing activity depended on retinal input, since temporary asphyxia of the eye stopped it immediately. The frequency of the rhythm was influenced by the anesthesia. In these older mice no visual receptive fields could be mapped, but in a few tectal recordings it was possible to suppress the maintained activity by diffuse, very intense illumination. As in normal mice, no auditory or somatosensory responses were observed in the visual cortex or upper tectal layers. In recordings from tectum before the age of three weeks retinotopic topography and receptive fields were normal. By day 24 no receptive fields could be recorded from parts of the tectum representing the central 90‐100° of the visual field, whereas within a peripheral ring responses were still roughly normal under photopic conditions. Over the following four months these peripheral responses faded away slowly. Incremental thresholds, especially in the scotopic range, were elevated, rising slowly to unmeasurable values. Similarly during dark adaptation the thresholds fell to values several log units above those reached in normal mice; these values of dark adapted thresholds in rd mice rose with age. This is consistent with morphological changes known to occur in the retina as a consequence, of the rd mutation the rods degenerating before the cones.
Transformation of human fibroblasts by ionizing radiation, a chemical carcinogen, or simian virus 40 correlates with an increase in susceptibility to the autonomous parvoviruses H-1 virus and minute virus of mice (1988)

Morphologically altered and established human fibroblasts, obtained either by 60Co gamma irradiation, treatment with the carcinogen 4-nitroquinoline 1-oxide, or simian virus 40 (SV40) infection, were compared with their normal finite-life parental strains for susceptibility to the autonomous parvoviruses H-1 virus and the prototype strain of minute virus of mice (MVMp). All transformed cells suffered greater virus-induced killing than their untransformed progenitors. The cytotoxic effect of H-1 virus was more severe than that of MVMp. Moreover, the level of viral DNA replication was much (10- to 85-fold) enhanced in the transformants compared with their untransformed parent cells. Thus, in this system, cell transformation appears to correlate with an increase in both DNA amplification and cytotoxicity of the parvoviruses. However, the accumulation of parvovirus DNA in the transformants was not always accompanied by the production of infectious virus. Like in vitro-transformed fibroblasts, a fibrosarcoma-derived cell line was sensitive to the killing effect of both H-1 virus and MVMp and amplified viral DNA to high extents. The results indicate that oncogenic transformation can be included among cellular states which modulate permissiveness to parvoviruses under defined growth conditions.
An infrared-light responsive graphene-oxide incorporated poly(N-isopropylacrylamide) hydrogel nanocomposite (2011)

We demonstrate a new light-responsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel nanocomposite incorporating glycidyl methacrylate functionalized graphene oxide (GO–GMA) instead of metallic nanoparticle fillers. GO–GMA is synthesized by esterification with glycidyl methacrylate. GO–GMA incorporated hydrogels are synthesized by photopolymerization of NIPAAm including 4-dimethylaminopyridine (DMAP) and N,N′-methylenebisacrylamide (NMBA) in GO–GMA dispersed dimethyl sulfoxide (DMSO) solution. Results show that such a nanocomposite hydrogel can undergo a large volumetric change in response to infrared (IR) light illumination, due to the highly efficient photothermal conversion of GO–GMA. It also exhibits significantly larger water uptake compared to conventional PNIPAAm hydrogel by 3 times. Based on the developed IR-responsive nanocomposite hydrogel, we have also realised a microvalve that controls the fluidic flow within a microfluidic channel through remote IR light actuation.
Science, medicine and phenylketonuria (1994)

Science addresses ignorance; medicine uses facts. The scientific approach to phenylketonuria (PKU) led to the discovery of its causes, both ultimate (allelic heterogeneity at the PAH locus) and proximate (dietary phenylalanine), the proximal phenotype (phenylalanine hydroxylase deficiency), the associated metabolic phenotype and the major distal phenotype (impaired cognitive development and neuropsychological function) for which the pathogenesis is still being investigated. By applying knowledge through newborn screening, early diagnosis and treatment, the brain disease of PKU has been greatly ameliorated. The population approach, which converted incidence into cases, revealed genetic heterogeneity in hyperphenylalaninemia involving four other loci, controlling cofactor (BH4) synthesis and recycling, and non-random geographic distribution of mutant PAH alleles of which more than 170 were known in April 1994. Various mechanisms including founder effect, genetic drift, hypermutability and selection (perhaps) explain the polymorphic aggregate frequency (approximately 0.01) and spectrum of PKU mutations in human populations.
High-throughput biochemical analysis of in vivo location data reveals novel distinct classes of POU5F1(Oct4)/DNA complexes (2008)

The transcription factor POU5F1 is a key regulator of embryonic stem (ES) cell pluripotency and a known oncoprotein. We have developed a novel high-throughput binding assay called MEGAshift (microarray evaluation of genomic aptamers by shift) that we use to pinpoint the exact location, affinity, and stoichiometry of the DNA-protein complexes identified by chromatin immunoprecipitation studies. We consider all genomic regions identified as POU5F1-ChIP-enriched in both human and mouse. Compared with regions that are ChIP-enriched in a single species, we find these regions more likely to be near actively transcribed genes in ES cells. We resynthesize these genomic regions as a pool of tiled 35-mers. This oligonucleotide pool is then assayed for binding to recombinant POU5F1 by gel shift. The degree of binding for each oligonucleotide is accurately measured on a custom oligonucleotide microarray. We explore the relationship between experimentally determined and computationally predicted binding strengths, find many novel functional combinations of POU5F1 half sites, and demonstrate efficient motif discovery by incorporating binding information into a motif finding algorithm. In addition to further refining location studies for transcription factors, this method holds promise for the high-throughput screening of promoters, SNP regions, and epigenetic modifications for factor binding.
Biocompatibility and preclinical feasibility tests of a temperature‐sensitive hydrogel for the purpose of surgical wound pain control and cartilage repair (2013)

We recently introduced a novel pluronic F127 and hyaluronic acid-based hydrogel (HG) designed to deliver a broad range of therapeutics. The reverse-thermal responsive HG exhibits physical properties that seem to be ideal for the local delivery of drug- and cell-based therapies to specific anatomic sites through percutaneous injection. However, questions related to the HG's safety and efficacy must first be addressed. To address these issues, we performed standard in vitro cytotoxicity and drug release tests and in vivo biocompatibility tests in a rat model. In addition, we determined whether the HG was an effective stem cell carrier in a rat cartilage defect model. We found that the HG showed viability and biocompatibility levels similar to those reported for F127 or hyaluronic acid alone. In vitro drug release studies with bupivacaine, a drug used clinically for local pain relief, revealed that after an initial burst bupivacaine was released continuously for 10 days. Stem cells loaded in the HG were retained in situ and stimulated cartilage regeneration in experimental defects. Taken as a whole, these findings support further efforts to develop the HG as a versatile system for the delivery of a wide range of therapeutic agents in humans.
Asymmetrically Substituted Benzene‐1,3,5‐tricarboxamides: Self‐Assembly and Odd–Even Effects in the Solid State and in Dilute Solution (2009)

Molecular organization: Chiral benzene tricarboxamides with methyl substituents at defined positions self-assemble into supramolecular polymers of preferred helicity by three-fold alpha-helical-type hydrogen bonding. The odd-even effect is operative and all derivatives are liquid crystalline showing a Col(ho) phase (see figure).Asymmetric benzene-1,3,5-tricarboxamides (aBTAs) comprising two n-octyl and one chiral methyl-alkyl side chain were synthesised and characterised. The influence of the position and the configuration of the chiral methyl group (methyl at the alpha, beta or gamma position) in the aliphatic side chains on the liquid-crystalline properties and the aggregation behaviour of the aBTAs was systematically studied and compared to symmetrical benzene-1,3,5-tricarboxamides (sBTAs). Solid-state characterisation (polarised optical microscopy, IR spectroscopy, X-ray diffraction and differential scanning calorimetry) revealed that all aBTAs show threefold, alpha-helical-type intermolecular hydrogen bonding between neighbouring molecules and exhibit a columnar hexagonal organisation from room temperature to well above 200 degrees C. Moving the chiral methyl group closer to the amide group stabilises the liquid-crystalline state, as evidenced by a higher clearing temperature and corresponding enthalpy. The self-assembly of dilute solutions of the aBTAs in methylcyclohexane ( approximately 10(-5) mol L(-1)) was investigated with circular dichroism (CD) spectroscopy. The sign of the Cotton effect demonstrated a pronounced odd-even effect, whereas the value of the molar ellipticity, Deltaepsilon, in the aBTAs was independent of the position of the methyl group. Subsequent temperature-dependent CD measurements showed that the aggregation of all aBTAs can quantitatively be described by the nucleation-growth model and that the stability of the aggregates increases when the chiral methyl group is closer to the amide moiety. The results presented herein illustrate that even small changes in the molecular structure of substituted benzene-1,3,5-tri-carboxamides affect their solid-state properties and their self-assembly behaviour in dilute solutions.
Leukocyte Recruitment and Vascular Injury in Diabetic Nephropathy (2006)

Different types of activated leukocytes play a crucial role in the pathogenesis of most kidney diseases from acute to chronic stages; however, diabetic nephropathy was not considered an inflammatory disease in the past. This view is changing now because there is a growing body of evidence implicating inflammatory cells at every stage of diabetic nephropathy. Renal tissue macrophages, T cells, and neutrophils produce various reactive oxygen species, proinflammatory cytokines, metalloproteinases, and growth factors, which modulate the local response and increase inflammation within the diabetic kidney. Although the precise mechanisms that direct leukocyte homing into renal tissues are not fully identified, it has been reported that intercellular adhesion molecule-1 and the chemokines CCL2 and CX3CL1 probably are involved in leukocyte migration in diabetic nephropathy. This review focuses on the molecular mechanisms of leukocyte recruitment into the diabetic kidney and the involvement of immigrated immune cells in the damage to renal tissues.
Dual Blockade of Cyclic AMP Response Element- (CRE) and AP-1-directed Transcription by CRE-transcription Factor Decoy Oligonucleotide (1999)

Alteration of gene transcription by inhibition of specific transcriptional regulatory proteins has important therapeutic potential. Synthetic double-stranded phosphorothioate oligonucleotides with high affinity for a target transcription factor can be introduced into cells as decoy cis-elements to bind the factors and alter gene expression. The CRE (cyclic AMP response element)-transcription factor complex is a pleiotropic activator that participates in the induction of a wide variety of cellular and viral genes. Because the CRE cis-element, TGACGTCA, is palindromic, a synthetic single-stranded oligonucleotide composed of the CRE sequence self-hybridizes to form a duplex/hairpin. Herein we report that the CRE-palindromic oligonucleotide can penetrate into cells, compete with CRE enhancers for binding transcription factors, and specifically interfere with CRE- and AP-1-directed transcription in vivo. These oligonucleotides restrained tumor cell proliferation, without affecting the growth of noncancerous cells. This decoy oligonucleotide approach offers great promise as a tool for defining cellular regulatory processes and treating cancer and other diseases.
Interaction of phosducin and phosducin isoforms with a 26S proteasomal subunit, SUG1. (1998)

Based on these experimental results, Phd, PhLP1 and PhLOP1 have protein-protein interaction with SUG1. PhLOP1, a truncated amino-terminal splice variant of Phd, is the best candidate for the interaction with SUG1 among the four Phd isoforms studied, which suggests a potential function for PhLOP1.
[Methods and results of treating late thrombosis of vascular grafts caused by fibromuscular lesions of vascular anastomosis]. (1994)

In the years 1989-1991 at the I Chair and Department of Surgery, II Faculty, Medical Academy in Warsaw, 56 patients were treated with vascular graft thrombosis. The studies involved patients in whom thrombosis developed between 3 and 24 months after the operation. Hyperplasia of the vascular anastomosis was the cause of the occlusion. The purpose of the work was determination of therapeutic methods and results. It was found that hyperplasia led to vascular graft occlusion in some patients even with very good early results. The treatment of thrombosis should be surgical. The methods giving the best results were thrombectomy and angioplasty of distal anastomosis or graft exchange.
A low-power asynchronous data-path for a FIR filter bank (2002)

This paper describes a number of design issues relating to the implementation of low-power asynchronous signal processing circuits. Specifically, the paper addresses the design of a dedicated processor structure that implements an audio FIR filter bank which is part of an industrial application. The algorithm requires a fixed number of steps and the moderate speed requirement allows a sequential implementation. The latter, in combination with a huge predominance of numerically small data values in the input data stream, is the key to a low-power asynchronous implementation. Power is minimized in two ways: by reducing the switching activity in the circuit, and by applying adaptive scaling of the supply voltage, in order to exploit the fact that the average case latency as 2-3 times better than the worst case. The paper reports on a study of properties of real life data, and discusses the implications it has on the choice of architecture, handshake-protocol, data-encoding, and circuit design. This includes a tagging scheme that divides the data-path into slices, and an asynchronous ripple carry adder that avoids a completion tree.
Predictors of Clinical Outcomes in the Laparoscopic Management of Adnexal Masses (2003)

In Brief OBJECTIVE Laparoscopy has become an accepted approach in the management of adnexal masses. We evaluated clinical outcomes of laparoscopic management of adnexal masses thought to be benign preoperatively. METHODS We performed a retrospective study of patients undergoing laparoscopic evaluation of adnexal masses over a 7-year period. Regression models evaluated predictors of blood loss, length of stay, complications, mass rupture, conversion to laparotomy, and operating time. Preoperative predictors of malignant and borderline disease were evaluated using a separate model. RESULTS Complications occurred in 8% of 396 patients undergoing laparoscopic evaluation of adnexal masses and were associated with concurrent hysterectomy (P = .01) and smaller mass (P = .01). Conversion to laparotomy occurred in 25% and was associated with larger mass (P = .001), prior hysterectomy (P = .002), and younger age (P = .002). Mass rupture occurred in 25% and was associated with prior (P < .001) or concurrent (P = .003) hysterectomy and younger age (P = .001). Blood loss greater than 500 mL was associated with concurrent hysterectomy (P < .001). Length of stay was associated with concurrent (P < .001) and prior (P < .001) hysterectomy, larger mass (P = .01), prior abdominal surgery (P = .009), and medical comorbidities (P = .007). Malignancy occurred in 2%, and laparoscopic management was not associated with adverse outcomes. CONCLUSION Adnexal masses thought to be benign preoperatively were successfully managed laparoscopically in three fourths of cases and clinical outcomes were acceptable. To a great extent, adverse events were attributable to concurrent hysterectomy rather than removal of the adnexal mass. Laparoscopic management of adnexal masses thought to be benign preoperatively is associated with good clinical outcomes.
Variable number of tandem repeats in clinical strains of Haemophilus influenzae (1997)

An algorithm capable of identifying short repeat motifs was developed and used to screen the whole genome sequence available for Haemophilus influenzae, since some of these repeats have been shown to affect bacterial virulence. Various di- to hexanucleotide repeats were identified, confirming and extending previous findings on the existence of variable-number-of-tandem-repeat loci (VNTRs). Repeats with units of 7 or 8 nucleotides were not encountered. For all of the 3- to 6-nucleotide repeats in the H. influenzae chromosome, PCR tests capable of detecting allelic polymorphisms were designed. Fourteen of 18 of the potential VNTRs were indeed highly polymorphic when different strains were screened. Two of the potential VNTRs appeared to be short and homogeneous in length; another one may be specific for the H. influenzae Rd strain only. One of the primer sets generated fingerprint-type DNA banding patterns. The various repeat types differed with respect to intrinsic stability as well. It was noted for separate colonies derived from a single clinical specimen or strains passaged for several weeks on chocolate agar plates that the lengths of the VNTRs did not change. When several strains from different patients infected during an outbreak of lung disease were analyzed, increased but limited variation was encountered in all VNTR sites analyzed. One of the 5-nucleotide VNTRs proved to be hypervariable. This variability may reflect the molecular basis of a mechanism used by H. influenzae bacteria to successfully colonize and infect different human individuals.
AH RECEPTOR SIGNALING PATHWAYS (1996)

▪ Abstract The aryl hydrocarbon (Ah) receptor has occupied the attention of toxicologists for over two decades. Interest arose from the early observation that this soluble protein played key roles in the adaptive metabolic response to polycyclic aromatic hydrocarbons and in the toxic mechanism of halogenated dioxins and dibenzofurans. More recent investigations have provided a fairly clear picture of the primary adaptive signaling pathway, from agonist binding to the transcriptional activation of genes involved in the metabolism of xenobiotics. Structure-activity studies have provided an understanding of the pharmacology of this receptor; recombinant DNA approaches have identified the enhancer sequences through which this factor regulates gene expression; and functional analysis of cloned cDNAs has allowed the characterization of the major signaling components in this pathway. Our objective is to review the Ah receptor's role in regulation of xenobiotic metabolism and use this model as a framework for understanding the less well-characterized mechanism of dioxin toxicity. In addition, it is hoped that this information can serve as a model for future efforts to understand an emerging superfamily of related signaling pathways that control biological responses to an array of environmental stimuli.
Metalloproteinase Disintegrins ADAM8 and ADAM19 Are Highly Regulated in Human Primary Brain Tumors and their Expression Levels and Activities Are Associated with Invasiveness (2006)

Patients with primary brain tumors have bleak prognoses and there is an urgent desire to identify new markers for sensitive diagnosis and new therapeutic targets for effective treatment. A family of proteins, the disintegrin and metalloproteinases (ADAMs or adamalysins), are cell surface and extracellular multidomain proteins implicated in cell-cell signaling, cell adhesion, and cell migration. Their putative biological and pathological roles make them candidates for promoting tumor growth and malignancy. We investigated the expression levels of 12 cerebrally expressed ADAM genes in human primary brain tumors (astrocytoma WHO grade I-III, glioblastoma WHO grade IV, oligoastrocytoma WHO grade II and III, oligodendroglioma WHO grade II and III, ependymoma WHO grade II and III, and primitive neuroectodermal tumor WHO grade IV) using real-time PCR. The mRNAs of the five ADAMs 8, 12, 15, 17, and 19 were significantly upregulated. The ADAM8 and ADAM19 proteins were mainly located in tumor cells and in some tumors in endothelia of blood vessels. In brain tumor tissue, ADAM8 and ADAM19 undergo activation by prodomain removal resulting in active proteases. By using specific peptide substrates for ADAM8 and ADAM19, respectively, we demonstrated that the proteases exert enhanced proteolytic activity in those tumor specimens with the highest expression levels. In addition, expression levels and the protease activities of ADAM8 and ADAM19 correlated with invasive activity of glioma cells, indicating that ADAM8 and ADAM19 may play a significant role in tumor invasion that may be detrimental to patients survival.
The Inhibition of Urokinase by Aromatic Diamidines (1975)

1. Structure-activity relationships have been established for the inhibition of urokinase by aromatic diamidines. In an assay system employing purified urokinase and human plasminogen the most potent inhibitor was found in 4',4''-diamidino-2-hydroxy-1,4-diphenoxybutane which proved 5600 times more active on a molar bases than epsilon-aminocaproic acid (E-ACA). 2. 4',4''-diamidino-2-hydroxy-1,4-diphenoxybutane behaved as a competitive inhibitor of the urokinase catalyzed hydrolysis of N-alpha-acetyl-L-lysine methyl ester. At pH 7.85 and 37 degrees C the K-1 value was determined as 3.18 times 10-6 M which compares with a value of 6.79 times 10-5 M for p-aminobenzamidine and 3.57 times 10-2 M for E-ACA. 3. In two fibrinolytic tests including urokinase as activator the superiority of diamidines over E-ACA was less marked than in the pure plasminogen activation system. This was due to the presence of certain plasma proteins in the fibrinolysis assays which augmented the inhibitory strength of E-ACA. The order of effectiveness of diamidines in the lysis tests was also different from the one in the activation test. In a human fibrin clot lysis test the most active inhibitor was 3',3''-diamidino-2-hydroxy-1,4-diphenoxybutane which was 1700 times more effective on a molar basis than E-ACA. In a human plasma clot lysis test the strongest inhibitor, 2-hydroxy-stilbamidine, was 70 times more powerful than E-ACA.