gebhart/patrepeval huggingface dataset:
A yeast gene required for DNA replication encodes a protein with homology to DNA helicases. (1995)

A yeast gene has been identified by screening for DNA replication mutants using a permeabilized cell replication assay. The mutant is temperature sensitive for growth and shows a cell cycle phenotype typical of DNA replication mutants. RNA synthesis is normal in the mutant but DNA synthesis ceases upon shift to the nonpermissive temperature. The DNA2 gene was cloned by complementation of the dna2ts gene phenotype. The gene is essential for viability. The gene encodes a 172-kDa protein with characteristic DNA helicase motifs. A hemagglutinin epitope-Dna2 fusion protein was prepared and purified by conventional and immunoaffinity chromatography. The purified protein is a DNA-dependent ATPase and has 3' to 5' DNA helicase activity specific for forked substrates. A nuclease activity that endonucleolytically cleaves DNA molecules having a single-stranded 5' tail adjacent to a duplex region copurifies through all steps with the fusion protein.
Overexpression and amplification of STK15 in human gliomas (2004)

The serine/threonine kinase 15 (STK15) at chromosome 20q13.2 is frequently shown to be amplified and overexpressed in several human cancers. STK15 has been reported to act as a cell cycle regulator and its overexpression induces centrosome amplification and aneuploidy. Recently we showed that STK15 even plays a role in human malignant brain tumours and we described an amplification of the gene in 31% of the investigated gliomas. In this study we scrutinized the correlation of increased STK15 on DNA and mRNA levels in gliomas of different histological grades. Southern blotting confirmed the amplification frequency of the STK15 gene, which had been previously detected by comparative PCR. In total, DNA gains were found in 26% of the investigated gliomas. Interestingly, we detected overexpression of STK15 mRNA in 60% of the analyzed brain tumours. The elevated expression does not strongly correlate with gains on DNA level, but all cases with an amplification of the STK15 gene display overexpression. Gains of the STK15 gene seem to occur irrespectively of the histological grades of the tumours, so that STK15 probably is not a progression associated factor. Amplification and overexpression of the kinase rather represent a primary alteration in human gliomas, which could play an important role as an early event in all glioma subtypes.
Update on Primary Biliary Cirrhosis (2000)

The diagnosis of primary biliary cirrhosis (PBC) is most often made in the asymptomatic phase, sometimes before the development of abnormal liver biochemistry. The antimitochondrial antibody remains the predominant hallmark, although not all patients test positive, even when the most sensitive techniques are used. The etiology of PBC remains elusive; studies suggest that the interlobular bile duct destruction is immune based, and associated autoimmune diseases are common. There are no surrogate markers that predict outcome in asymptomatic patients, whose chance of survival is less than that of age- and sex-matched populations but much better than the median survival of eight years in patients with symptomatic PBC. Symptoms common in this disease are fatigue, pruritus and xanthelasma, as well as complications of portal hypertension and osteoporosis. Treatment includes symptomatic and preventive measures, as well as specific therapeutic measures. Immunosuppressive therapy has yielded disappointing results in the long term management of PBC, and the only therapy shown to improve survival is the hydrophobic dihydroxy bile acid ursodeoxycholic acid. Treatment at a dose of 13 to 15 mg/kg/day is optimal, given in separate doses or as a single dose at least 4 h from giving the oral anion exchange resin cholestyramine, which may be used to control pruritus. However, liver transplantation remains the only cure for this disease, and the best postoperative survival is seen in patients whose serum bilirubin does not exceed 180 micromol/L at the time of liver transplantation. Recurrence takes place but is rarely symptomatic and does not deter from the benefits of transplantation.
Targeting Transcription Factors for Cancer Therapy (2005)

Advances in the molecular biology of oncogenesis have established a key role for transcription factors in malignant transformation. In some cases the activity of the transcription factor itself is altered by mutation. In many other cases, the activity of the transcription factor is affected by mutations in upstream signaling or regulatory proteins. This review highlights four transcription factors--Stat3, Stat5, NF-kappaB, and HIF-1--which are associated with cancer development. The evidence for the involvement of these factors in oncogenesis is reviewed. Further, we examine the efforts to specifically target these transcription factors for therapeutic intervention. Such strategies include using peptidomimetics, antisense oligonucleotides, small molecule inhibitors, and G-quartet oligonucleotides. Inhibition of transcription factor activity may occur at the level of activation, translocation, or DNA binding. Application of these approaches to in vitro and in vivo models of tumorigenesis is discussed.
Synthesis and Pharmacology of New Camptothecin Drugs (2005)

Camptothecin (CPT) drugs exhibit antineoplastic activity against colorectal, breast, lung and ovarian cancers. This review briefly summarizes the pharmacology of CPT drugs, examines four strategies and methods for the synthesis of camptothecins, and finally discusses homocamptothecins and silatecans, two new classes of CPT analog.
Improved backing-off for M-gram language modeling (2002)

In stochastic language modeling, backing-off is a widely used method to cope with the sparse data problem. In case of unseen events this method backs off to a less specific distribution. In this paper we propose to use distributions which are especially optimized for the task of backing-off. Two different theoretical derivations lead to distributions which are quite different from the probability distributions that are usually used for backing-off. Experiments show an improvement of about 10% in terms of perplexity and 5% in terms of word error rate.
A degron created by SMN2 exon 7 skipping is a principal contributor to spinal muscular atrophy severity (2010)

Spinal muscular atrophy (SMA) is caused by homozygous survival of motor neurons 1 (SMN1) gene deletions, leaving a duplicate gene, SMN2, as the sole source of SMN protein. However, most of the mRNA produced from SMN2 pre-mRNA is exon 7-skipped ( approximately 80%), resulting in a highly unstable and almost undetectable protein (SMNDelta7). We show that this splicing defect creates a potent degradation signal (degron; SMNDelta7-DEG) at SMNDelta7's C-terminal 15 amino acids. The S270A mutation inactivates SMNDelta7-DEG, generating a stable SMNDelta7 that rescues viability of SMN-deleted cells. These findings explain a key aspect of the SMA disease mechanism, and suggest new treatment approaches based on interference with SMNDelta7-DEG activity.
Synthesis of hyaluronate in differentiated teratocarcinoma cells. Characterization of the synthase (1983)

Differentiation of teratocarcinoma cells led to induction of hyaluronate synthesis. The synthase was recovered in the membrane fraction of cell lysates. Hyaluronate was synthesized at the membranes and was then released as a soluble product. The synthase could be stimulated by a variety of phosphate esters which prevented the degradation of the substrates UDP-GlcNAc and UDP-GlcA and the release of the growing hyaluronic acid chain from the membrane. Hyaluronidases or oligosaccharides derived from hyaluronate did not affect the synthesis. The chains grew at a rate of 60 repeating units/min. Continuous new chain initiation occurred during prolonged synthesis. Digestion of pulse-chase-labelled hyaluronate with beta-N-acetylglucosaminidase and beta-glucuronidase showed that the chains grew at the reducing end.
Sibling correlations and segregation analysis of age‐related maculopathy: The beaver dam eye study (1994)

Sibling correlations were evaluated and segregation analysis was performed on age-dependent maculopathy scores of the right and left eyes of individuals from 564 families in the Beaver Dam Eye study. There is evidence of significant sibling correlations. The data fit a mixture of two normal distributions, especially after undergoing the Box and Cox power transformation. In each eye, the hypothesis of mendelian transmission of a major effect cannot be rejected under the tau AB free model, but is rejected under the tau's free model. The hypothesis of a random environmental major effect is rejected. Similar major gene parameter estimates are found for both eyes. The results are consistent with a major effect accounting for 62% and 59%, in the right and left eyes, respectively, of the determination of age-related maculopathy scores. A single major gene can account for about 89% and 97% of this variability due to a major effect, or for about 55% and 57% of the total variability, in the right and left eyes, respectively.
Impact of Protein Denaturants and Stabilizers on Water Structure (2004)

It is of great interest to determine how solutes such as urea, sugars, guanidinium salts, and trimethylamine N-oxide affect the stability, solubility, and solvation of globular proteins. A key hypothesis in this field states that solutes affect protein stability indirectly by making or breaking water structure. We used a new technique, pressure perturbation calorimetry, to measure the temperature dependence of a solute's partial compressibility. Using fundamental thermodynamic relations, we converted these data to the pressure dependence of the partial heat capacity to examine the impact of protein stabilizing and denaturing solutes on water structure by applying the classic two-state mixture model for water. Contrary to widely held expectations, we found no correlation between a solute's impact on water structure and its effect on protein stability. Our results indicate that efforts to explain solute effects should focus on other hypotheses, including those based on preferential interaction and excluded volume.
Implementing Curve25519 for Side-Channel--Protected Elliptic Curve Cryptography (2015)

For security-critical embedded applications Elliptic Curve Cryptography (ECC) has become the predominant cryptographic system for efficient key agreement and digital signatures. However, ECC still involves complex modular arithmetic that is a particular burden for small processors. In this context, Bernstein proposed the highly efficient ECC instance Curve25519 that particularly enables efficient software implementations at a security level comparable to AES-128 with inherent resistance to simple power analysis (SPA) and timing attacks. In this work, we show that Curve25519 is likewise competitive on FPGAs even when countermeasures to thwart side-channel power analysis are included. Our basic multicore DSP-based architectures achieves a maximal performance of more than 32,000 point multiplications per second on a Xilinx Zynq 7020 FPGA. Including a mix of side-channel countermeasures to impede simple and differential power analysis, we still achieve more than 27,500 point multiplications per second with a moderate increase in logic resources.
Phasic three-dimensional impedance imaging of cardiac activity (2002)

Electrical impedance images were made using the ACT 3 instrument, which applies currents simultaneously to 32 electrodes and measures the resulting voltages on those same electrodes. A reconstruction algorithm was written for a three-dimensional cylinder having electrodes in two or four layers, using current patterns that pass current among different planes of electrodes, as well as within each plane. We have previously reported useful vertical resolution by the use of added layers of electrodes. The aim of the present study was to demonstrate that physiologically useful information can be obtained by examining cephalo-caudal differences in three-dimensional images. Phasic changes throughout the cardiac cycle are seen to be markedly different at the heart compared to lung region, both above and beside it. We formed hydrogel electrodes each 3 cm tall and 7 cm wide and applied them to the thorax of an upright human subject in four horizontal rows; each row contained eight electrodes. During breath-holding, cardiac activity was seen in all layers. With systole, conductivity in the anterior of the lowest layers decreased, but not in the upper layer. In the upper layers, conductivity increased with systole in many regions. These observations are consistent with the opposite changes in blood volume of the heart and lungs and the locations of these organs. This paper demonstrates the feasibility of producing and displaying physiologically interpretable three-dimensional images of the chest in real time.
A Novel Computational Approach for Modeling Stent Reconstructing of an Aortic Bifurcation (2006)

Stent reconstruction of the aorta-iliac bifurcation was studied using computational fluid dynamics. Stents were modeled using a novel method, whereby the stents were represented as porous media. Three-dimensional numerical simulations using FLUENT were performed to determine how stent orientation affects the fluid dynamics. Three cases were studied and compared for both iliacs unstented, one iliac stented, and both iliacs stented. The stents lowered wall shear stress along the stented artery walls as compared to the unstented aorta-iliac model. However, the stent presence elevated vorticity, both in magnitude and size of the region. Additional studies were conducted to determine the effects for stent mis-alignment, where one stent protruded more into the aorta. It was found that when the stents were misaligned, wall shear stress increased near the stent inlet for the stent further inserted into the iliac. The resulting flow phenomena were consistent with other numerical models and medical investigations of stent reconstruction.
Analysis of 4-1BB Ligand (4-1BBL)-Deficient Mice and of Mice Lacking Both 4-1BBL and CD28 Reveals a Role for 4-1BBL in Skin Allograft Rejection and in the Cytotoxic T Cell Response to Influenza Virus (1999)

Abstract 4-1BB ligand (4-1BBL) is a member of the TNF family expressed on activated APC. 4-1BBL binds to 4-1BB (CD137) on activated CD4 and CD8 T cells and in conjunction with strong signals through the TCR provides a CD28-independent costimulatory signal leading to high level IL-2 production by primary resting T cells. Here we report the immunological characterization of mice lacking 4-1BBL and of mice lacking both 4-1BBL and CD28. 4-1BBL−/− mice mount neutralizing IgM and IgG responses to vesicular stomatitis virus that are indistinguishable from those of wild-type mice. 4-1BBL−/− mice show unimpaired CTL responses to lymphocytic choriomeningitis virus (LCMV) and exhibit normal skin allograft rejection but have a weaker CTL response to influenza virus than wild-type mice. 4-1BBL−/−CD28−/− mice retain the CTL response to LCMV, respond poorly to influenza virus, and exhibit a delay in skin allograft rejection. In agreement with these in vivo results, allogeneic CTL responses of CD28−/− but not CD28+/+ T cells to 4-1BBL-expressing APC are substantially inhibited by soluble 4-1BB receptor as is the in vitro secondary response of CD28+ T cells to influenza virus peptides. TCR-transgenic CD28−/− LCMV glycoprotein-specific T cells are insensitive to the presence of 4-1BBL when a wild-type peptide is used, but the response to a weak agonist peptide is greatly augmented by the presence of 4-1BBL. These results further substantiate the idea that different immune responses vary in their dependence on costimulation and suggest a role for 4-1BBL in augmenting suboptimal CTL responses in vivo.
Serum IL-15 in patients with early systemic sclerosis: a potential novel marker of lung disease (2007)

The pathogenesis of systemic sclerosis (SSc) is characterized by autoimmunity, vasculopathy and fibrosis. IL-15 is a pleiotropic cytokine that has impact on immune, vascular and connective tissue cells. We therefore investigated IL-15 in the circulation of patients with early SSc and explored possible associations of serum IL-15 with vasculopathy and fibrosis. Serum levels of IL-15 were analysed in 63 consecutive patients with SSc of disease duration less than 4 years and without disease-modifying treatment. Thirty-three age-matched healthy control individuals were enrolled. Serum IL-15 levels were increased in the sera of SSc patients compared with that of healthy control individuals (P < 0.01). Serum IL-15 levels correlated with impaired lung function, assessed both by the vital capacity (P < 0.05) and by the carbon monoxide diffusion capacity (P < 0.05). The association between IL-15 and the vital capacity remained after multiple linear regression analysis. Patients with intermediate serum IL-15 levels had a higher prevalence of increased systolic pulmonary pressure compared with patients with either low or high serum IL-15 levels (P < 0.05). Moreover, increased serum IL-15 levels were associated with a reduced nailfold capillary density in multivariable logistic regression analysis (P < 0.01). Serum IL-15 levels also correlated inversely with the systolic blood pressure (P < 0.01). We conclude that IL-15 is associated with fibrotic as well as vascular lung disease and vasculopathy in early SSc. IL-15 may contribute to the pathogenesis of SSc. IL-15 could also be a candidate biomarker for pulmonary involvement and a target for therapy in SSc.
Germline copy number polymorphisms involving larger than 100 kb are uncommon in normal subjects (2006)

We have demonstrated the utility of this approach, which has an important advantage over other methods because it is able to simultaneously assess both CNPs and SNPs, and therefore has great potential in genetic association studies of common diseases.
Amazing SAR Imaging Effects - Explained by SAR Simulation (2014)

Direct returns in SAR images can be rather easily interpreted, while specular returns often lead to very interesting effects, since they are not only caused by the scene geometry but are also processed during image formation. In this paper, several striking signatures encountered in real SAR images are introduced. For each of these a detailed explanation of the underlying causes is given using the SAR simulator CohRaS® (Coherent Raytracing SAR simulator) developed at Fraunhofer IOSB. The successful simulation of these effects using the extended narrow-beam simulator CohRaS® also shows that the narrow-beam concept is valid for the simulation of SAR images.
Diurnal and Seasonal Mood Vary with Work, Sleep, and Daylength Across Diverse Cultures (2011)

We identified individual-level diurnal and seasonal mood rhythms in cultures across the globe, using data from millions of public Twitter messages. We found that individuals awaken in a good mood that deteriorates as the day progresses--which is consistent with the effects of sleep and circadian rhythm--and that seasonal change in baseline positive affect varies with change in daylength. People are happier on weekends, but the morning peak in positive affect is delayed by 2 hours, which suggests that people awaken later on weekends.
Low Molecular Weight Heparin Novo (LHN-1) Does Not Cross the Placenta During the Second Trimester of Pregnancy (1989)

Unfractionated heparin (UF-H) has been the drug of choice for the treatment of thromboembolic disorders during pregnancy. Low molecular weight heparin (LMW-H) preparations may present some advantages over UF-H. They have longer half-lives and a better bioavailability after subcutaneous (s. c.) injection and may cause less bleeding. It has not yet been established whether LMW-H Novo (LHN-1) crosses the placenta. 17 women admitted for abortion during the second trimester of pregnancy (induced by application of prostaglandine PGE2 gel at a concentration of 0.25 mg/ml into the cervix) were given s. c. 35 anti-Xa units per kg of body weight of LHN-1 (Novo). 10 patients not receiving LHN-1 and their fetuses served as a control group. 7 women in whom the time interval between injection of LHN-1 and expulsion of the fetus was less than 3 h or more than 7 h were excluded from further study. In one fetus blood collection failed. Anti-Xa and anti-IIa levels increased approximately ten-fold in women receiving LHN-1 [anti-Xa units/ml from 0.02 +/- 0.01 (mean +/- SD) to 0.17 +/- 0.01, p less than 0.001; anti-Ha units/ml from less than 0.01 +/- 0.01 to 0.07 +/- 0.03], but remained below the detection limit in their fetuses as well as in the women and fetuses of the control group. We conclude that LHN-1 at these doses does not cross the placenta during the second trimester of pregnancy to suggest that LHN-1 may be a safe alternative to heparin in the management of the thromboembolic complications during pregnancy.
Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways (1990)

Endotoxemia was evoked by bolus injection of Escherichia coli endotoxin (2 ng/kg body weight) in six healthy subjects to investigate the early kinetics of cytokine release in relation to the development of clinical and hematologic abnormalities frequently seen in gram-negative septicemia. The plasma concentration of tumor necrosis factor (TNF) increased markedly after 30 to 45 minutes, and reached a maximal level after 60 to 90 minutes. In each volunteer, the initial increase of plasma interleukin 6 (IL-6) concentrations occurred 15 minutes after the initial TNF increase, and maximal IL-6 concentrations were reached at 120 to 150 minutes. A transient increase in body temperature and pulse rate occurred simultaneously with the initial TNF and IL-6 increases, whereas a significant decrease in blood pressure occurred after 120 minutes. These changes were proportional to the changes in TNF and IL-6 concentrations. Coagulation activation, as assessed by a rise of prothrombin fragments and thrombin-antithrombin III complexes, was noted after 120 minutes, in the absence of activation of the contact system. A two- to sixfold increase in the concentrations of tissue plasminogen activator (t-PA) and von Willebrand factor antigen indicated endothelial cell activation. This increase started at 120 and 90 minutes, respectively. The release of t-PA coincided with activation of the fibrinolytic pathway, as measured by plasmin-alpha 2-antiplasmin complexes. The fibrinolytic activity of t-PA was subsequently offset by release of plasminogen activator inhibitor, observed 150 minutes after the endotoxin injection, and reaching a peak at 240 minutes. No complement activation was detected. These results show that in humans endotoxin induces an early, rapidly counteracted fibrinolytic response, and a more long-lasting activation of thrombin by a mechanism other than contact system activation. In addition, our data suggest that endotoxin-induced leukopenia and endothelial cell activation are mediated by TNF.
Ferroelectric-liquid-crystal/silicon-integrated-circuit spatial light modulator (1990)

We present the design and characterization of a spatial light modulator (SLM) comprising a ferroelectric-liquid-crystal light-modulating layer on top of a silicon integrated circuit. Our SLM consists of two electrically addressed arrays on the same integrated-circuit die. The first, a 1 x 128 linear array with a 20-microm center-to-center element spacing, used shift register addressing, while the second, a 64 x 64 square array with 60-microm pitch, used static random access memory addressing. The resulting SLM could be addressed at frame rates of up to 4.5 kHz and gave singleelement intensity contrast ratios of 12:1.