gebhart/patrepeval huggingface dataset:
The Use of Oral Mexiletine for the Treatment of Pain after Peripheral Nerve Injury (1992)

Neuropathic pain is often a difficult condition to treat. Clinical and laboratory studies using intravenously administered local anesthetics or antiarrhythmic agents support the use of these drugs for the treatment of neuropathic pain. The availability of the oral antiarrhythmic medication, mexiletine, has made it possible to study the effects of an orally administered medication on chronic neuropathic pain. The study used a double-blind placebo-controlled design to examine 11 subjects in whom treatment with conventional pain medications had been unsuccessful. Subjects had a history of peripheral nerve injury or dysfunction, and all complained of symptoms consistent with neuropathic pain. After baseline pain measurements, mexiletine or placebo was given in gradually increasing doses to a maximum daily dose of 750 mg mexiletine. After 1 month at steady state, the subject received the alternative medication. Mexiletine was found to produce a statistically significant reduction in reported pain when compared to baseline or placebo. Pain scores were rated on a scale from 0 (no pain) to 10 (unbearable pain). Median pain scores prior to mexiletine were 7, after placebo treatment 7, and while receiving mexiletine (750 mg/day) 4. Side effects were mild and well-tolerated. Mexiletine may be effective in reducing neuropathic pain for patients in whom alternative pain medications have been unsatisfactory.
Purification and Characterization of TrzF: Biuret Hydrolysis by Allophanate Hydrolase Supports Growth (2006)

TrzF, the allophanate hydrolase from Enterobacter cloacae strain 99, was cloned, overexpressed in the presence of a chaperone protein, and purified to homogeneity. Native TrzF had a subunit molecular weight of 65,401 and a subunit stoichiometry of alpha(2) and did not contain significant levels of metals. TrzF showed time-dependent inhibition by phenyl phosphorodiamidate and is a member of the amidase signature protein family. TrzF was highly active in the hydrolysis of allophanate but was not active with urea, despite having been previously considered a urea amidolyase. TrzF showed lower activity with malonamate, malonamide, and biuret. The allophanate hydrolase from Pseudomonas sp. strain ADP, AtzF, was also shown to hydrolyze biuret slowly. Since biuret and allophanate are consecutive metabolites in cyanuric acid metabolism, the low level of biuret hydrolase activity can have physiological significance. A recombinant Escherichia coli strain containing atzD, encoding cyanuric acid hydrolase that produces biuret, and atzF grew slowly on cyanuric acid as a source of nitrogen. The amount of growth produced was consistent with the liberation of 3 mol of ammonia from cyanuric acid. In vitro, TrzF was shown to hydrolyze biuret to liberate 3 mol of ammonia. The biuret hydrolyzing activity of TrzF might also be physiologically relevant in native strains. E. cloacae strain 99 grows on cyanuric acid with a significant accumulation of biuret.
Breast-feeding: second thoughts. (1974)

Studies have shown that breast-feeding supplies nourishment to the infant while providing immunologic protection against infection. Breast-fed infants have been less likely to develop respiratory and gastrointestinal infections and allergic reactions when compared with infants brought up on cows milk alone or in addition to breast milk. In addition breast-feeding insures a smooth infantile transition from entire dependence upon his mother nutritionally and immunologically to complete independence. If the infant receives breast milk alone for the first 6 months of life best protection is assured. In areas where contamination of cows milk unsanitary conditions and inadequate medical facilities are likely breast-feeding during the first 6 months is particularly important. Limitations of formula feeding as seen and reinforced by animal models prompt increased appreciation of breast-feeding.
A Case for Clumsy Packet Processors (2005)

Hardware faults can occur in any computer system. Although faults cannot be tolerated for most systems (e.g., servers or desktop processors), many applications (e.g., networking applications) provide robustness in software. However, processors do not utilize this resiliency, i.e., regardless of the application at hand, a processor is expected to operate completely fault-free. In this paper, we will question this traditional approach of complete correctness and investigate possible performance and energy optimizations when this correctness constraint is released. We first develop a realistic model that estimates the change in the fault rates according to the clock frequency of the cache. Then, we present a scheme that dynamically adjusts the clock frequency of the data caches to achieve the desired optimization goal, e.g., reduced energy or reduced access latency. Finally, we present simulation results investigating the optimal operation frequency of the data caches, where reliability is compromised in exchange of reduced energy and increased performance. Our simulation results indicate that the clock frequency of the data caches can be increased as much as 4 times without incurring a major penalty on the reliability. This also results in 41% reduction in the energy consumed in the data caches and a 24% reduction in the energy-delay-fallibility product.
Influence of divalent cations on the structural thermostability and thermal inactivation kinetics of class II xylose isomerases (2005)

The effects of divalent metal cations on structural thermostability and the inactivation kinetics of homologous class II d-xylose isomerases (XI; EC 5.3.1.5) from mesophilic (Escherichia coli and Bacillus licheniformis), thermophilic (Thermoanaerobacterium thermosulfurigenes), and hyperthermophilic (Thermotoga neapolitana) bacteria were examined. Unlike the three less thermophilic XIs that were substantially structurally stabilized in the presence of Co2+ or Mn2+ (and Mg2+ to a lesser extent), the melting temperature [(Tm) approximately 100 degrees C] of T. neapolitana XI (TNXI) varied little in the presence or absence of a single type of metal. In the presence of any two of these metals, TNXI exhibited a second melting transition between 110 degrees C and 114 degrees C. TNXI kinetic inactivation, which was non-first order, could be modeled as a two-step sequential process. TNXI inactivation in the presence of 5 mm metal at 99-100 degrees C was slowest in the presence of Mn2+[half-life (t(1/2)) of 84 min], compared to Co2+ (t(1/2) of 14 min) and Mg2+ (t(1/2) of 2 min). While adding Co2+ to Mg2+ increased TNXI's t(1/2) at 99-100 degrees C from 2 to 7.5 min, TNXI showed no significant activity at temperatures above the first melting transition. The results reported here suggest that, unlike the other class II XIs examined, single metals are required for TNXI activity, but are not essential for its structural thermostability. The structural form corresponding to the second melting transition of TNXI in the presence of two metals is not known, but likely results from cooperative interactions between dissimilar metals in the two metal binding sites.
Glutathione S-transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to breast cancer. (2001)

This study was undertaken to examine if glutathione S-transferase (GST) M1, M3, P1, and T1 genotypes affected breast cancer risk in Finnish women. The study population consisted of 483 incident breast cancer cases and 482 healthy population controls. Genotyping analyses were performed by PCR-based methods, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for known or suspected risk factors for breast cancer. When the genes were studied separately, the only significant finding was between GSTM1 null genotype and postmenopausal breast cancer risk (OR, 1.49; 95% CI, 1.03-2.15). Conversely, when the potential combined effects of the at-risk genotypes were examined, significant associations were observed only among premenopausal women. Although only a moderate risk of breast cancer was seen for premenopausal women concurrently carrying the GSTM3*B allele containing genotypes and the GSTP1 Ile/ Ile genotype (OR, 2.07; 95% CI, 1.02-4.18), the risk rose steeply if they simultaneously lacked the GSTT1 gene (OR, 9.93, 95% CI, 1.10-90.0). A borderline significant increase in the risk of breast cancer was also seen for premenopausal women with the combination of GSTM1 null, GSTP1 Ile/Ile, and GSTT1 null genotypes (OR, 3.96; 95% CI, 0.99-15.8). Our findings support the view that GST genotypes contribute to the individual breast cancer risk, especially in certain combinations.
Targeting of drugs and nanoparticles to tumors (2010)

The various types of cells that comprise the tumor mass all carry molecular markers that are not expressed or are expressed at much lower levels in normal cells. These differentially expressed molecules can be used as docking sites to concentrate drug conjugates and nanoparticles at tumors. Specific markers in tumor vessels are particularly well suited for targeting because molecules at the surface of blood vessels are readily accessible to circulating compounds. The increased concentration of a drug in the site of disease made possible by targeted delivery can be used to increase efficacy, reduce side effects, or achieve some of both. We review the recent advances in this delivery approach with a focus on the use of molecular markers of tumor vasculature as the primary target and nanoparticles as the delivery vehicle.
A new MSBF-based HDR image processing algorithm (2008)

High dynamic range (HDR) image is increasingly comprehensive in digital image applications recently. But conventional output equipments and algorithm only provide to support 8 bit image. Here, a new algorithm based on multi-scale bilateral filtering (MSBF) is presented to deal with HDR image, which not only keeps imagepsilas details and colors, but also compresses imagepsilas brightness distributions. Consequently dynamic range compression based on MSR algorithm may be realized in four scales. Wherein, the Gaussian kernel whose scale is small is used to suppress halo, the Gaussian kernel of middle scale and bigger scale is used to keep natural whole colour tune. But the dynamic range compression based on this algorithm just partly weakens local contrast reversal, and can not effectively control the extent of edge diffusion. By edge-cutoff function, bilateral filter may effectively suppress halo, which is formed by local contrast reversal derived from Gaussian filter. In space domain the scale of Gaussian kernel was not sensitive to filtering result when edge-cutoff function based on Gaussian kernel was used, therefore, constant may be chosen as scale of filter. At last, a series of experiments were conducted to test this algorithm. A conclusion can be draw that the MSBF-based algorithm is rather effective in processing HDR image.
Untangling tau-related dementia (2000)

Abundant cytoplasmic inclusions consisting of aggregated hyperphosphorylated protein tau are a characteristic pathological observation in several neurodegenerative disorders such as Alzheimer's disease, Pick's disease, frontotemporal dementia, cortico-basal degeneration and progressive supranuclear palsy. The recent finding that mutations in the tau gene are responsible for frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) has provided convincing evidence that tau protein plays a key role in neurodegeneration. In the short period since the identification of pathogenic mutations in tau, remarkable progress has been made in understanding some of the mechanisms by which these mutations lead to neurodegeneration. Understanding the disease processes will hopefully provide us with new leads in developing effective therapies for dementia.
Refining Vancomycin Protein Binding Estimates: Identification of Clinical Factors That Influence Protein Binding (2011)

While current data indicate only free (unbound) drug is pharmacologically active and is most predictive of response, pharmacodynamic studies of vancomycin have been limited to measurement of total concentrations. The protein binding of vancomycin is thought to be approximately 50%, but considerable variability surrounds this estimate. The present study sought to determine the extent of vancomycin protein binding, to identify factors that modulate its binding, and to create and validate a prediction tool to estimate the extent of protein binding based on individual clinical factors. This single-site prospective cohort study included hospitalized adult patients treated with vancomycin and with a vancomycin serum concentration determination available. Linear regression was used to predict the free vancomycin concentration (f[vanco]) and to determine the clinical factors modulating vancomycin protein binding. Among the 50 patients in the study, the mean protein binding was 41.5%. The strongest predictor of f[vanco] was the total vancomycin concentration (total [vanco]), and this was modified by dialysis and total protein of ≥6.7 g/dl as covariates. The algebraic expression from the final prediction model was f[vanco] = 0.643 + 0.560 × total [vanco] - {0.067 × total [vanco] × D} - {0.071 × total [vanco] × TP} where D = 1 if dialysis dependent or 0 if not dialysis dependent, and TP = 1 if total protein is ≥6.7 g/dl or 0 if total protein is <6.7 g/dl. The R(2) of the final prediction model was 0.959 (P < 0.001). Validation of our model was performed in 13 patients, and the predictive performance was highly favorable (R(2) was 0.9, and bias and precision were 0.18 and 0.18, respectively). Prediction models such as ours can be utilized in future pharmacokinetics and pharmacodynamics studies evaluating the exposure-response profile and to determine the pharmacodynamic target of interest as it relates to the free concentration.
Inhibition of interleukin‐1β–induced cyclooxygenase 2 expression in human synovial fibroblasts by 15‐deoxy‐Δ12,14‐prostaglandin J2 through a histone deacetylase–independent mechanism (2005)

These data suggest that 15d-PGJ(2) can inhibit IL-1beta-induced COX-2 expression by an HDAC-independent mechanism, probably by interfering with HAT p300.
Effect of Minicolumnar Disturbance on Dyslexic Brains: An MRI Study (2006)

The minicolumn is generally considered the basic unit of the neocortex in all the mammalian brains. Enlargement of the cortical surface is believed to occur through the addition of minicolumns rather than a single neuron. This study aims at testing the hypothesis that brain developmental disorders can be diagnosed and analyzed in terms of the minicolumnar disturbance. To do this, we propose to correlate the pathological findings in terms of the minicolumnar structure to the MRI findings in terms of volumetric analysis
RacGAP1 expression, increasing tumor malignant potential, as a predictive biomarker for lymph node metastasis and poor prognosis in colorectal cancer (2015)

Rac GTPase-activating protein (RacGAP) 1 plays a key role in controlling various cellular phenomena including cytokinesis, transformation, invasive migration and metastasis. This study investigated the function and clinical significance of RacGAP1 expression in colorectal cancer (CRC). The intrinsic functions of RacGAP1 in CRC cells were analyzed using small interfering RNA (siRNA). We analyzed RacGAP1 mRNA expression in surgical specimens from 193 CRC patients (Cohort 1) by real-time PCR. Finally, we validated RacGAP1 protein expression using formalin-fixed paraffin-embedded samples from 298 CRC patients (Cohort 2) by immunohistochemistry. Reduced RacGAP1 expression by siRNA in CRC cell lines showed significantly decreased cellular proliferation, migration and invasion. In Cohort 1, RacGAP1 expression in CRC was significantly higher than in adjacent normal mucosa and increased according to tumor node metastasis stage progression. High RacGAP1 expression in tumors was significantly associated with progression and prognosis. In Cohort 2, RacGAP1 protein was overexpressed mainly in the nuclei of CRC cells; however, its expression was scarcely observed in normal colorectal mucosa. RacGAP1 protein expression was significantly higher in CRC patients with higher T stage, vessel invasion and lymph node and distant metastasis. Increased expression of RacGAP1 protein was significantly associated with poor disease-free and overall survival. Multivariate analyses revealed that high RacGAP1 expression was an independent predictive marker for lymph node metastasis, recurrence and poor prognosis in CRC. Our data provide novel evidence for the biological and clinical significance of RacGAP1 as a potential biomarker for identifying patients with lymph node metastasis and poor prognosis in CRC.
The difference between human C3F and C3S results from a single amino acid change from an asparagine to an aspartate residue at position 1216 on the alpha chain of the complement component, C3. (1989)

The third component of the human C system, C3, exhibits two common genetic variants. These variants have been characterized by high voltage agarose electrophoresis and are designated C3 fast (C3F) and C3 slow (C3S). C3F occurs at appreciable frequencies only in Caucasian populations and has been shown to be associated with an increased incidence of certain diseases, such as partial lipodystrophy, IgA nephropathy, and Indian childhood cirrhosis. It has been shown that C3F differs from C3S with regard to isoelectric point as well as its ability to bind macrophages. The availability of a full-length cDNA probe for human C3 has made it possible to study the polymorphism at the genomic level. We have used RNA/RNA hybridization to demonstrate that the difference between C3F and C3S occurs in the C3d region. We subsequently used oligonucleotide-primed DNA amplification to show that C3F arises from a point mutation at codon 1216 converting a deoxyadenosine for a deoxyguanosine. The result of this point mutation at the translational level is the substitution of an asparagine residue in C3S for an aspartic acid residue in C3F. It is known that C3d contains the binding site for CR2 as well as the internal thioester site and multiple protease cleavage sites. The identification of the structural basis of the differences between C3F and C3S will assist our continuing studies of the mechanism of the functional differences between the two alleles and the disease associations of C3F. It also allows us to use DNA based techniques to allotype C3 in subjects with little or no C3 in their serum.
Interactions of HPV E6 and E7 oncoproteins with tumour suppressor gene products. (1992)

The HPVs associated with anogenital cancers encode two oncoproteins, E6 and E7. Both E6 and E7 can form specific complexes with tumour suppressor gene products. The E7 protein binds to the retinoblastoma tumour suppressor gene product pRB, with a preference for the underphosphorylated, "active" form of pRB. The E7 proteins derived from the "high risk" HPVs bind to pRB with a higher affinity than the E7 proteins from the "low risk" HPVs. The "high risk" HPV E6 proteins can associate with the p53 tumour suppressor protein. This interaction promotes the degradation of p53 in vitro, which presumably accounts for the very low levels of p53 in cervical carcinoma cell lines. The functional inactivation of pRB and p53 by the HPV oncoproteins E7 and E6, respectively, are likely to be important steps in cervical carcinogenesis, since mutations in the RB and p53 genes were detected in HPV negative but not HPV positive cervical carcinoma cell lines. Cytogenetic studies strongly suggest, however, that additional chromosomal changes may be necessary for carcinogenic progression of HPV induced anogenital lesions.
Development of NTU wearable exoskeleton system for assistive technologies (2006)

This paper presents a wearable lower extremity exoskeleton (LEE) developed as a platform for research works on enhancement and assistive the ability of human's walking and load carrying. The whole process of the first prototype design is introduced together with the sub-systems, inner/outer exoskeleton, the attached flexible waist and footpad with sensors. Simulation model and feedback control with the ZMP method were established using Adams and Matlab. The ultimate goal of the current research work is to design and control a power assisted system, which integrates human's intellect as the control system for manipulating the wearable power-aided device. The feasibility and initial performance of the designed system are also discussed.
Synthesis and isomerization of N,N'-diaryl-2,2'-bi(1,4-naphthoquinone) 4,4'-diimines (1986)

N,N'-Diaryl-2,2'-bi(1,4-naphthoquinone) 4,4'-diimines were obtained by the oxidation of N-aryl-1,4-naphthoquione monoimines in an alkaline medium. When boiled in acetic acid, they isomerize to 5-arylamino-13-aryldibenzo(a,h)carbazole-7,12-quinones.
Substantial expression of mature elastin in arterial constructs (2011)

Mature elastin synthesis is a key challenge in arterial tissue engineering. Most engineered vessels lack elastic fibers in the medial layer and those present are poorly organized. The objective of this study is to increase mature elastin synthesis in small-diameter arterial constructs. Adult primary baboon smooth muscle cells (SMCs) were seeded in the lumen of porous tubular scaffolds fabricated from a biodegradable elastomer, poly(glycerol sebacate) (PGS) and cultured in a pulsatile flow bioreactor for 3 wk. We tested the effect of pore sizes on construct properties by histological, biochemical, and mechanical evaluations. Histological analysis revealed circumferentially organized extracellular matrix proteins including elastin and the presence of multilayered SMCs expressing calponin and α-smooth muscle actin. Biochemical analysis demonstrated that the constructs contained mature elastin equivalent to 19% of the native arteries. Mechanical tests indicated that the constructs could withstand up to 200 mmHg burst pressure and exhibited compliance comparable to native arteries. These results show that nontransfected cells in PGS scaffolds in unsupplemented medium produced a substantial amount of mature elastin within 3 wk and the elastic fibers had similar orientation as those in native arteries. The 25-32 μm pore size supported cell organization and elastin synthesis more than larger pore sizes. To our knowledge, there was no prior report of the synthesis of mature and organized elastin in arterial constructs without exogenous factors or viral transduction.
The Sleeping Beauty Transposable Element: Evolution, Regulation and Genetic Applications (2004)

Members of the Tc1/mariner superfamily of transposable elements isolated from vertebrate species are inactive due to the accumulation of mutations. A representative of a subfamily of fish elements estimated to be last active > 10 million years ago has been reconstructed, and named Sleeping Beauty(SB). This element opened up new avenues for studies on DNA transposition in vertebrates, and for the development of transposon tools for genetic manipulation in important model species and in humans. Multiple transposase binding sites within the terminal inverted repeats, a transpositional enhancer sequence, unequal affinity of the transposase to the binding sites and the activity of the cellular HMGB1 protein all contribute to a highly regulated assembly of SB synaptic complexes, which is likely a requirement for the subsequent catalytic steps. Host proteins involved in double-strand DNA break repair are limiting factors of SB transposition in mammalian cells, underscoring evolutionary, structural and functional links between DNA transposition, retroviral integration and V(D)J recombination. SB catalyzes efficient cut-and-paste transposition in a wide range of vertebrate cells in tissue culture, and in somatic tissues as well as the germline of the mouse and zebrafish in vivo, indicating its usefulness as a vector for transgenesis and insertional mutagenesis.