gebhart/patrepeval huggingface dataset:
PIG-A Mutations in Normal Hematopoiesis. (2004)

Abstract Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is caused by somatic mutations of the X-linked gene, PIG-A, in hematopoietic stem cells (HSCs). The product of this gene is necessary for the assembly of glycosylphosphatidylinositol (GPI) anchors. Consequently, PNH cells lack the expression of GPI-anchored proteins on their cell surface. PIG-A mutations have been found in granulocytes and T lymphocytes from most normal individuals. Although the significance of these mutations is unclear, it suggests that they are important in the pathogenesis of PNH. Methods: We isolated CD34+ progenitors from 4 PNH patients, 18 healthy donors, and 9 non-PNH patients undergoing peripheral blood stem cell tranplantation. The frequency of PIG-A mutant progenitors was determined by assaying for colony forming cells (CFC) in methylcellulose containing toxic doses of aerolysin. Aerolysin is a pore-forming toxin that uses the GPI anchor as it receptor; hence, PNH cells are unique in their resistance to aerolysin. DNA was extracted from individual day 14 aerolysin resistant CFC and the PIG-A gene was sequenced to determine clonality. We performed a Poisson distribution of the mutational frequency to determine the probability that the PIG-A mutation in controls arose from HSC. Results: In PNH patients, 67% of the CFC were aerolysin resistant. The frequency of aerolysin resistant CFC was 14.7 ± 4.0 x 10−6 in the bone marrow of healthy donors and was 57.0 ± 6.7 x 10−6 from mobilized peripheral blood. Aerolysin resistant CFC from PNH patients exhibited clonalPIG-A mutations, and thus, arose from HSC. In contrast, PIG-A mutations in the CFC from controls were polyclonal (up to 15 different mutations from one individual). Recent evidence suggests that humans and other large mammals possess only 10,000 primitive HSC, and that only 1000 of these cells are thought to contribute to hematopoiesis at any one time. Poisson statistics show that only 5% of normals would be expected to harbor a PIG-A mutation in 1000 HSC, and &amp;lt; 1 x 10−9 persons would harbor 10 or more different PIG-A mutations even if all 10,000 hematopoietic stem cells were contributing to hematopoiesis. Thus, the high frequency of PIG-A mutations in controls, coupled with their polyclonality, suggests that they do not arise at the level of HSC; rather, PIG-A mutations in normals appear to arise as a consequence of hematopoietic differentiation, between the level of an HSC and a CFC. Conclusion: Our data confirm the findings that PIG-A mutations are relatively common in normal hematopoiesis. Although we cannot rule out that a rare PIG-A mutant blood cell in normals does in fact arise from a mutant HSC, our data suggest that most of the mutations occur with differentiation. Genetic fidelity can be lost with differentiation without consequence, as mutations in differentiated cells would not be propagated. These data also call into question the relevance of PIG-A mutations in normals to the pathogenesis of PNH.
Tx-terminal phased array for satellite communication at Ka-band (2007)

The concept for an active circularly polarized phased-array terminal antenna for satellite communication at Ka-band is presented. The proposed antenna is based on a modular architecture with sub-arrays of 4times4 elements. Sequential rotation of the antenna elements is implemented to improve the polarization purity. Thermal dissipation problems are addressed.
Adaptive tuning of RED using on-line simulation (2003)

Random early detection (RED) is an active queue management mechanism designed to provide better performance than traditional DropTail. However, its parameter setting has proved to be very sensitive to network scenarios and needs constant tuning to achieve ideal performance under varying network conditions. In view of the fact that RED has not been understood well enough for an analytical approach, this paper takes advantage of network simulation techniques and formulates the optimal configuration of RED as a black-box optimization problem. An optimization objective is designed to effectively reflect the tradeoff between utilization and queueing delay. Based on the proposed RED optimization scheme, a general automatic network management system, i.e., on-line simulation system, has been used for the on-line tuning of RED under changing network conditions. The proposed approach is empirically validated with simulations and real network experiments. The simulation results show that RED controlled with on-line simulation system is able to stabilize around the expected equilibrium status under varying conditions and maintain high utilization.
A Plasminogen Activator Inhibitor-1 Promoter Polymorphism and Idiopathic Interstitial Pneumonia (2003)

The normal fibrinolytic activity within the alveolar space is suppressed in fibrotic lung diseases in part because of increased levels of plasminogen activator inhibitor-1 (PAI-1). Studies with animals have shown that inhibition of the plasminogen system by PAI-1 increases the generation of pulmonary fibrosis. To determine if a similar relationship occurs in human fibrotic lung diseases, we took advantage of a polymorphism (4G/5G) that occurs in the promoter region of the human PAI-1 gene and influences the expression of PAI-1. We hypothesized that the 4G/4G genotype, because of its association with higher levels of PAI-1, would occur in patients with idiopathic interstitial pneumonia more frequently than in a control population. PAI-1 promoter genotype was determined in 88 well-characterized patients with idiopathic interstitial pneumonia consisting of 62 patients with usual interstitial pneumonia and 26 with nonspecific interstitial pneumonia. DNA was extracted from paraffin-embedded biopsy tissue and the genotype identified by polymerase chain reaction and restriction endonuclease digestion. We found that the distribution of PAI-1 genotypes in the idiopathic interstitial pneumonia population was similar to that of a large control population. However, subgroup analysis showed that patients with nonspecific interstitial pneumonia were more likely than the control population to have the promoter genotype (4G/4G) that is associated with higher levels of PAI-1. A similar pattern in PAI-1 polymorphism was not seen in the usual interstitial pneumonia subgroup. The results of this study support the conclusion that PAl-1 expression influences the development of nonspecific interstitial pneumonia in a similar manner to what occurs in animal models of pulmonary fibrosis. Patients with usual interstitial pneumonia did not show the same relationship with PAl-1 genotype.
On crowd density estimation for surveillance (2006)

The goal of this work is to use computer vision to measure crowd density in outdoor scenes. Crowd density estimation is an important task in crowd monitoring. The assessment is carried out using images of a graduation scene which illustrated variation of illumination due to textured brick surface, clothing and changes of weather. Image features were extracted using grey level dependency matrix, Minkowski fractal dimension and a new method called translation invariant orthonormal Chebyshev moments. The features were then classified into a range of density by using a self organizing map. Three different techniques were used and a comparison on the classification results investigates the best performance for measuring crowd density by vision.
p21-activated kinase 4 regulates ovarian cancer cell proliferation, migration, and invasion and contributes to poor prognosis in patients (2010)

Ovarian cancer is a lethal gynecological malignancy, and to improve survival, it is important to identify novel prognostic and therapeutic targets. In this study, we present a role for p21-activated kinase 4 (Pak4) in ovarian cancer progression. We show a significant association between increased expression of Pak4 and its activated form, phosphorylated (p)-Pak4 Ser(474), with metastasis of ovarian cancers, shorter overall and disease-free survival, advanced stage and high-grade cancers, serous/clear cell histological subtypes, and reduced chemosensitivity. Pak4 overexpression was also observed in ovarian cancer cell lines. Pak4 and p-Pak4 expression were detected both in the nucleus and cytoplasm of ovarian cancer cells, in vitro as well as in vivo. Stable knockdown of Pak4 in ovarian cancer cell lines led to reduced cell migration, invasion, and proliferation, along with reduced c-Src, ERK1/2, and epidermal growth factor receptor (EGFR) activation and decreased matrix metalloproteinase 2 (MMP2) expression. Conversely, Pak4 overexpression promoted ovarian cancer cell migration and invasion in a c-Src, MEK-1, MMP2, and kinase-dependent manner, and induced cell proliferation through the Pak4/c-Src/EGFR pathway that controls cyclin D1 and CDC25A expression. Stable knockdown of Pak4 also impeded tumor growth and dissemination in nude mice. This report reveals the association between Pak4 and important clinicopathologic parameters, suggesting Pak4 to be a significant prognostic marker and potential therapeutic molecular target in ovarian cancer. The implied possible cross-talk between Pak4 and EGFR suggests the potential of dual targeting of EGFR and Pak4 as a unique therapeutic approach for cancer therapy.
Secure and Flexible Monitoring of Virtual Machines (2007)

The monitoring of virtual machines has many applications in areas such as security and systems management. A monitoring technique known as introspection has received significant discussion in the research literature, but these prior works have focused on the applications of introspection rather than how to properly build a monitoring architecture. In this paper we propose a set of requirements that should guide the development of virtual machine monitoring solutions. To illustrate the viability of these requirements, we describe the design of XenAccess, a monitoring library for operating systems running on Xen. XenAccess incorporates virtual memory introspection and virtual disk monitoring capabilities, allowing monitor applications to safely and efficiently access the memory state and disk activity of a target operating system. XenAccess' efficiency and functionality are illustrated through a series of performance tests and practical examples.
DRD4 and DAT1 Polymorphisms Modulate Human Gamma Band Responses (2006)

Gamma oscillations (30-80 Hz) have been demonstrated to be important for perceptual and cognitive processes. Animal and in vitro studies have revealed possible underlying generation mechanisms of the gamma rhythm. However, little is known about the neurochemical modulation of these oscillations during human cognition. Schizophrenia and Attention Deficit Hyperactivity Disorder, which lead to failure of attentional modulation and working memory, introduce significant changes in gamma responses and have significant associations with genetic polymorphisms of dopamine receptor D4 (DRD4), dopamine transporter (DAT), and catechol-O-methyltransferase (COMT). Therefore, the presence of direct relations between these polymorphisms and gamma oscillations was investigated in human subjects using an auditory target detection paradigm. The 7-repeat isoform of the DRD4 polymorphism that produces a subsensitive variant of the D4 receptor enhanced the auditory evoked and induced gamma responses to both standard and target stimuli. The 10/10 genotype of the DAT1 polymorphism, which reduces DAT expression and hence yields an increase in extracellular dopamine, specifically enhanced evoked gamma responses to target stimuli. The COMT polymorphism did not significantly change gamma responses. It seems plausible to assume that the modulation pattern of the evoked gamma response by DRD4 polymorphism relates to reduced inhibition via the D4 receptor, whereas the DAT1 effect is related to the target detection mechanism probably mediated by the D1 receptor.
Inhibition of tumor growth by a dominant negative mutant of the insulin-like growth factor I receptor with a bystander effect. (1998)

The insulin-like growth factor I receptor is known to play a major role in transformation and apoptosis. The dominant negative mutant of the insulin-like growth factor I receptor, designated 486/STOP, causes massive apoptosis of tumor cells and inhibition of tumor growth and metastases. We now show that: (a) the stable expression of 486/STOP inhibits transformation (colony formation in soft agar) and/or tumor growth in nude mice of five different types of human tumor cell lines; and (b) more importantly, it has a bystander effect, inhibiting the growth of wild-type tumor cells when cells expressing 486/STOP are coinjected with wild-type tumor cells. These findings suggest that it is not necessary to infect all tumor cells with 486/STOP to inhibit tumor growth, and they also open the possibility of using the product of 486/STOP directly against tumor cells.
Optimal Step-Size Constant Modulus Algorithm (2008)

The step size leading to the absolute minimum of the constant modulus (CM) criterion along the search direction can be obtained algebraically at each iteration among the roots of a third-degree polynomial. The resulting optimal step-size CMA (OS-CMA) is compared with, other CM-based iterative techniques in terms of performance-versus-complexity trade-off.
Cloning of Human Junctional Adhesion Molecule 3 (JAM3) and Its Identification as the JAM2 Counter-receptor (2001)

We have identified a third member of the junctional adhesion molecule (JAM) family. At the protein level JAM3 displays 36 and 32% identity to JAM2 and JAM1, respectively. The coding region is distributed over 9 exons and maps to chromosome 11q25. The gene shows widespread tissue expression with higher levels apparent in the kidney, brain, and placenta. At the cellular level we show expression of JAM3 transcript within endothelial cells. Our major finding is that JAM3 and JAM2 are binding partners. Thus, JAM3 ectodomain binds firmly to JAM2-Fc. This heterotypic interaction is maintained when JAM3-Fc is used to capture Chinese hamster ovary cells expressing full-length JAM2. In static adhesion assays we show that JAM3 is unable to bind to leukocyte cell lines. This is consistent with the lack of JAM2 expression. However, using JAM2-Fc pull-down experiments in combination with polyclonal anti-JAM3 serum, we demonstrate that JAM3 is the previously uncharacterized 43-kDa counter-receptor that mediates JAM2 adhesion to T cells. Most significantly we demonstrate up-regulation of JAM3 protein on peripheral blood lymphocytes following activation. Finally we show the utility of JAM3 ectodomain as an inhibitor of JAM2 adhesion.
Effect of real-time feedback during cardiopulmonary resuscitation outside hospital: prospective, cluster-randomised trial (2011)

Real-time visual and audible feedback during CPR altered performance to more closely conform with guidelines. However, these changes in CPR performance were not associated with improvements in return of spontaneous circulation or other clinical outcomes. Trial Registration Clinical Trials NCT00539539.
Compression of Subrelativistic Space-Charge-Dominated Electron Bunches for Single-Shot Femtosecond Electron Diffraction (2010)

We demonstrate the compression of 95 keV, space-charge-dominated electron bunches to sub-100 fs durations. These bunches have sufficient charge (200 fC) and are of sufficient quality to capture a diffraction pattern with a single shot, which we demonstrate by a diffraction experiment on a polycrystalline gold foil. Compression is realized by means of velocity bunching by inverting the positive space-charge-induced velocity chirp. This inversion is induced by the oscillatory longitudinal electric field of a 3 GHz radio-frequency cavity. The arrival time jitter is measured to be 80 fs.
Protein hydrolysates in sports nutrition (2009)

It has been suggested that protein hydrolysates providing mainly di- and tripeptides are superior to intact (whole) proteins and free amino acids in terms of skeletal muscle protein anabolism. This review provides a critical examination of protein hydrolysate studies conducted in healthy humans with special reference to sports nutrition. The effects of protein hydrolysate ingestion on blood amino acid levels, muscle protein anabolism, body composition, exercise performance and muscle glycogen resynthesis are discussed.
HdcB, a novel enzyme catalysing maturation of pyruvoyl‐dependent histidine decarboxylase (2011)

Pyruvoyl-dependent histidine decarboxylases are produced as proenzymes that mature by cleavage followed by formation of the pyruvoyl prosthetic group. The histidine decarboxylation pathway of Streptococcus thermophilus CHCC1524 that consists of the pyruvoyl-dependent histidine decarboxylase HdcA and the histidine/histamine exchanger HdcP was functionally expressed in Lactococcus lactis. The operon encoding the pathway contains in addition to the hdcA and hdcP genes a third gene hdcB. Expression of different combinations of the genes in L. lactis and Escherichia coli followed by analysis of the protein products demonstrated the involvement of HdcB in the cleavage of the HdcA proenzyme. The HdcA proenzyme and HdcB protein were purified to homogeneity and cleavage and activation of the histidine decarboxylase activity was demonstrated in vitro. Substoichiometric amounts of HdcB were required to cleave HdcA showing that HdcB functions as an enzyme. In agreement, expression levels of HdcB in the cells were low relative to those of HdcA. The turnover number of HdcB in vitro was extremely low (0.05 min⁻¹) which was due to a very slow association/dissociation of the enzyme/substrate complex. In fact, HdcB was shown to co-purify both with the HdcA S82A mutant that mimics the proenzyme and with the mature HdcA complex.
The Fat Mass and Obesity Associated Gene FTO Functions in the Brain to Regulate Postnatal Growth in Mice (2010)

FTO (fat mass and obesity associated) was identified as an obesity-susceptibility gene by several independent large-scale genome association studies. A cluster of SNPs (single nucleotide polymorphism) located in the first intron of FTO was found to be significantly associated with obesity-related traits, such as body mass index, hip circumference, and body weight. FTO encodes a protein with a novel C-terminal α-helical domain and an N-terminal double-strand β-helix domain which is conserved in Fe(II) and 2-oxoglutarate-dependent oxygenase family. In vitro, FTO protein can demethylate single-stranded DNA or RNA with a preference for 3-methylthymine or 3-methyluracil. Its physiological substrates and function, however, remain to be defined. Here we report the generation and analysis of mice carrying a conditional deletion allele of Fto. Our results demonstrate that Fto plays an essential role in postnatal growth. The mice lacking Fto completely display immediate postnatal growth retardation with shorter body length, lower body weight, and lower bone mineral density than control mice, but their body compositions are relatively normal. Consistent with the growth retardation, the Fto mutant mice have reduced serum levels of IGF-1. Moreover, despite the ubiquitous expression of Fto, its specific deletion in the nervous system results in similar phenotypes as the whole body deletion, indicating that Fto functions in the central nerve system to regulate postnatal growth.
Behavioral stress alters coronary vascular reactivity in borderline hypertensive rats (1997)

These results indicate that behavioral stress impairs endothelium-dependent and nitric oxide-mediated coronary relaxation, but does not alter alpha1-adrenoceptor or endothelin-1-mediated contraction. By impairing coronary artery vascular relaxation, chronic exposure to behavioral stress may contribute to myocardial ischemia.
Capsazepine: a competitive antagonist of the sensory neurone excitant capsaicin (1992)

1. Capsazepine is a synthetic analogue of the sensory neurone excitotoxin, capsaicin. The present study shows the capsazepine acts as a competitive antagonist of capsaicin. 2. Capsazepine (10 microM) reversibly reduced or abolished the current response to capsaicin (500 nM) of voltage-clamped dorsal root ganglion (DRG) neurones from rats. In contrast, the responses to 50 microM gamma-aminobutyric acid (GABA) and 5 microM adenosine 5'-triphosphate (ATP) were unaffected. 3. The effects of capsazepine were examined quantitatively with radioactive ion flux experiments. Capsazepine inhibited the capsaicin (500 nM)-induced 45Ca2+ uptake in cultures of rat DRG neurones with an IC50 of 420 +/- 46 nM (mean +/- s.e.mean, n = 6). The 45Ca2+ uptake evoked by resiniferatoxin (RTX), a potent capsaicin-like agonist was also inhibited. (Log concentration)-effect curves for RTX (0.3 nM-1 microM) were shifted in a competitive manner by capsazepine. The Schild plot of the data had a slope of 1.08 +/- 0.15 (s.e.) and gave an apparent Kd estimate for capsazepine of 220 nM (95% confidence limits, 57-400 nM). 4. Capsazepine also inhibited the capsaicin- and RTX-evoked efflux of 86Rb+ from cultured DRG neurones. The inhibition appeared to be competitive and Schild plots yielded apparent Kd estimates of 148 nM (95% confidence limits, 30-332 nM) with capsaicin as the agonist and 107 nM (95% confidence limits, 49-162 nM) with RTX as agonist. 5. A similar competitive inhibition by capsazepine was seen for capsaicin-induced [14C]-guanidinium efflux from segments of adult rat vagus nerves (apparent Kd = 690 nM; 95% confidence limits, 63 nM-1.45 microM). No significant difference was noted in the apparent Kd estimates for capsazepine in assays on cultured DRG neurones and vagus nerve as shown by the overlap in the 95% confidence limits.6. Capsazepine, at concentrations up to 1O microM, had no significant effects on the efflux of 86Rb+ from cultured DRG neurones evoked either by depolarization with high (50 mM) K' solutions or by acidification of the external medium to pH 5.0-5.6. Similarly capsazepine had no significant effect on he depolarization (50 mM KCl)-induced efflux of [14C]-guanidinium from vagus nerve preparations.7. Ruthenium Red was also tested for antagonism against capsaicin evoked ['4C]-guanidinium release from vague nerves and capsaicin induced 45Ca2" uptake in cultures of DRG neurones. In contrast to capsazepine the inhibition by Ruthenium Red (10-500nM in DRG and 0.5-10microM in vagus nerve experiments) was not consistent with a competitive antagonism, but rather suggested a more complex,non-competitive inhibition.