gebhart/patrepeval huggingface dataset:
Lymphocytic progenitor cell origin and clonal evolution of human B- lineage acute lymphoblastic leukemia (1996)

At presentation, bone marrow specimens from over 25% of B-lineage acute lymphoblastic leukemias (ALL) display more than two clonal rearrangements of immunoglobulin heavy chain (IgH) genes in Southern blot analyses. Nucleotide sequence analysis has shown predominantly different V(H)DJ(H) junctions among these genes, leading to the frequent description of such cases as oligoclonal leukemias. In the present study, we have analyzed the lgH genes from four patients whose leukemic cells contained different patterns of lgH gene rearrangements between presentation and relapse. Nucleotide sequence analysis of the lgH genes showed that three mechanisms could account for these differences: de novo V(H)DJ(H) rearrangement, V(H) to DJ(H) recombination, and V(H) replacement. In all cases, more than two totally different V(H)DJ(H) rearrangements appeared during evolution of the disease, formally consistent with the conclusion that these tumors were composed of apparently unrelated clones. However, the retention of some of the antigen receptor gene rearrangements, as well as the persistence of a chromosomal marker in two cases, indicated that these leukemias had a monoclonal origin. These findings support the hypothesis that some ALLs arise from a lymphoid progenitor cell at a stage of lymphocyte development before the onset of IgH gene rearrangement. These leukemic lymphocyte progenitors generate malignant daughter cells capable of an in vivo maturation that involves the completion of multiple different lgH rearrangements as well as the modification of preexisting rearrangements by V(H) to DJ(H) recombination or by a V(H) replacement.
Intron—exon structures of eukaryotic model organisms (1999)

To investigate the distribution of intron-exon structures of eukaryotic genes, we have constructed a general exon database comprising all available intron-containing genes and exon databases from 10 eukaryotic model organisms: Homo sapiens, Mus musculus, Gallus gallus, Rattus norvegicus, Arabidopsis thaliana, Zea mays, Schizosaccharomyces pombe, Aspergillus, Caenorhabditis elegans and Drosophila. We purged redundant genes to avoid the possible bias brought about by redundancy in the databases. After discarding those questionable introns that do not contain correct splice sites, the final database contained 17 102 introns, 21 019 exons and 2903 independent or quasi-independent genes. On average, a eukaryotic gene contains 3.7 introns per kb protein coding region. The exon distribution peaks around 30-40 residues and most introns are 40-125 nt long. The variable intron-exon structures of the 10 model organisms reveal two interesting statistical phenomena, which cast light on some previous speculations. (i) Genome size seems to be correlated with total intron length per gene. For example, invertebrate introns are smaller than those of human genes, while yeast introns are shorter than invertebrate introns. However, this correlation is weak, suggesting that other factors besides genome size may also affect intron size. (ii) Introns smaller than 50 nt are significantly less frequent than longer introns, possibly resulting from a minimum intron size requirement for intron splicing.
Role of PTEN in butyrate-induced colon cancer cell growth arrest, apoptosis, and differentiation. (2006)

5084 HDAC inhibitors induce cell-cycle arrest in the G1 and/or G2 phase, apoptosis and/or differentiation in cancer cells and are showing promise as treatment for a variety of human cancers. Their precise mechanism of action however, has not been fully elucidated. We identified a significant upregulation of PTEN mRNA in a microarray database of Caco-2 colon carcinoma cells treated with the HDAC inhibitor, sodium butyrate. PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a dual phosphatase, acting at both serine-threonine and tyrosine sites. PTEN inhibits the activation of Akt/protein kinase B by phosphatidylinositol 3,4,5-triphosphate, thus modulating a major pathway controlling cell proliferation and survival. This study, therefore, aimed to examine the role of PTEN in HDAC inhibitor-induced colon cell maturation. Consistent with the microarray data, we found that butyrate upregulated PTEN mRNA and protein expression in a dose- and time-dependent manner in Caco-2, HT-29, and HCT116 colon cancer cells. PTEN induction was first observed 48-72 hours following butyrate treatment suggesting its upregulation is an indirect effect of butyrate treatment. Upregulated PTEN expression in response to butyrate was also observed in Hela cells, indicating this effect was not specific to colon cancer cells. The structurally related HDAC inhibitor, valproic acid, also induced PTEN expression in colon cancer cells. To determine whether upregulation of PTEN is specific to butyrate induced differentiation or a consistent feature of intestinal cell differentiation, we examined its expression in the Caco-2 in vitro model of colon cell differentiation and along the crypt-villus axis in vivo. PTEN expression was increased during spontaneous differentiation of Caco-2 cells, and along the mouse small intestinal crypt to villus axis in vivo, indicating PTEN is consistently upregulated during intestinal cell differentiation. To directly determine the role of PTEN in butyrate-induced growth inhibition, differentiation and apoptosis in colon cancer cells, PTEN was inhibited using siRNA in colon cancer cells. Western blot analysis confirmed a >80% inhibition of PTEN protein expression following 72-120h exposure to small interfering RNA. Silencing of PTEN partially attenuated butyrate-induced growth inhibition and apoptosis in HCT116 cells, and butyrate-mediated induction of the differentiation marker, alkaline phosphatase activity, in Caco-2 cells. Screening of a panel of 30 colon cancer cell lines identified 2 cell lines, LIM2405 and KM12 that had no detectable PTEN expression, and PTEN was not induced by butyrate in these cell lines. Collectively, these results demonstrate that upregulation of PTEN plays a role in mediating butyrate-induced growth inhibition, apoptosis and differentiation in vitro.
Unequal-arm adaptive rood pattern search for fast block-matching motion estimation in the JVT/H.26L (2004)

The adaptive rood pattern search (ARPS) algorithm proposed by Nie and Ma (2002) has shown two to three times of search speed-up improvement over that of diamond search (DS) based on the MPEG-4 verification model encoding platform. In this paper, first we have shown that the distribution of motion vectors bears a rood shape. An improved ARPS algorithm, called ARPS-3 or unequal-arm ARPS, is then proposed and experimented on the JVT/H.26L JM encoding platform. Due to complex modes and multiframe prediction, a new normalized computational cost metrics is also proposed for objectively measuring the computational gain or search speed-up. Experimental results show that ARPS-3 has achieved superb performance on many accounts while maintaining fairly close rate-distortion performance compared with that of the full search. It also outperforms its predecessors, ARPS and ARPS-2 (or equal-arm ARPS).
Inhibition of Hsp90 activates osteoclast c-Src signaling and promotes growth of prostate carcinoma cells in bone (2008)

Hsp90 inhibitors are being evaluated extensively in patients with advanced cancers. However, the impact of Hsp90 inhibition on signaling pathways in normal tissues and the effect that this may have on the antitumor activity of these molecularly targeted drugs have not been rigorously examined. Breast and prostate carcinomas are among those cancers that respond to Hsp90 inhibitors in animal xenograft models and in early studies in patients. Because these cancers frequently metastasize to bone, it is important to determine the impact of Hsp90 inhibitors in the bone environment. In the current study, we show that, in contrast to its activity against prostate cancer cells in vitro and its inhibition of s.c. prostate cancer xenografts, the Hsp90 inhibitor 17-AAG stimulates the intraosseous growth of PC-3M prostate carcinoma cells. This activity is mediated not by a direct effect on the tumor but by Hsp90-dependent stimulation of osteoclast maturation. Hsp90 inhibition transiently activates osteoclast Src kinase and promotes Src-dependent Akt activation. Both kinases are key drivers of osteoclast maturation, and three agents that block osteoclastogenesis, the Src inhibitor dasatinib, the bisphosphonate alendronate, and the osteoclast-specific apoptosis-inducer reveromycin A, markedly reduced 17-AAG-stimulated tumor growth in bone. These data emphasize the importance of understanding the complex role played by Hsp90 in regulating signal transduction pathways in normal tissues as well as in cancer cells, and they demonstrate that drug-dependent modulation of the local tumor environment may profoundly affect the antitumor efficacy of Hsp90-directed therapy.
Syntheses of Conformationally Constricted Molecules as Potential NAALADase/PSMA Inhibitors (2004)

Two six-membered ring targeted analogues of PSMA inhibitors (4a and 4b) were designed on the basis of a computational analysis and synthesized. (E,Z)-Diene 10 was subjected to the nitroso Diels-Alder reaction to give the 1,4-trans six-membered ring adduct, 4a. The cis isomer 4b was derived from similar nitroso cycloaddition reactions with the corresponding (E,E)-diene and separately from cyclohexadiene. The IC(50) values of 4a and 4b in a NAALADase assay were found to be 0.9 and 0.1 microM, respectively. [reaction: see text]
The anatomy of the aging face: Volume loss and changes in 3-dimensional topography (2006)

Facial aging reflects the dynamic, cumulative effects of time on the skin, soft tissues, and deep structural components of the face, and is a complex synergy of skin textural changes and loss of facial volume. Many of the facial manifestations of aging reflect the combined effects of gravity, progressive bone resorption, decreased tissue elasticity, and redistribution of subcutaneous fullness. A convenient method for assessing the morphological effects of aging is to divide the face into the upper third (forehead and brows), middle third (midface and nose), and lower third (chin, jawline, and neck). The midface is an important factor in facial aesthetics because perceptions of facial attractiveness are largely founded on the synergy of the eyes, nose, lips, and cheek bones (central facial triangle). For aesthetic purposes, this area should be considered from a 3-dimensional rather than a 2-dimensional perspective, and restoration of a youthful 3-dimensional facial topography should be regarded as the primary goal in facial rejuvenation. Recent years have seen a significant increase in the number of nonsurgical procedures performed for facial rejuvenation. Patients seeking alternatives to surgical procedures include those who require restoration of lost facial volume, those who wish to enhance normal facial features, and those who want to correct facial asymmetry. Important factors in selecting a nonsurgical treatment option include the advantages of an immediate cosmetic result and a short recovery time.
Fabrication, Characterization, and Computational Modeling of a Piezoelectrically Actuated Microvalve for Liquid Flow Control (2006)

Liquid-compatible piezoelectric microvalves have been modeled, fabricated, and characterized. The microvalve was designed for proportional flow control of liquid propellant for integrated spacecraft micropropulsion. The microvalve consists of a custom-designed piezoelectric stack actuator bonded onto silicon valve components with the entire assembly contained within a stainless steel housing. The valve seat configuration includes narrow-edge seating rings and tensile-stressed silicon tethers that enable the normally closed and leak-tight operation. A concentric series of narrow rings simulates a "knife-edge" seal by greatly reducing the valve contact area, thereby increasing the seating pressure and consequently reducing leak. Leak testing of the microvalve, conducted using a Helium leak detector, showed a leak rate of approximately 3/spl times/10/sup -6/ scc/s for Helium gas. During operation, the valve flow rate was measured using an external Mass Flow Meter (MFM) with a measurement resolution of approximately 10/sup -2/ scc/s. The measured forward flow rate for deionized (DI) water is approximately 64 mg/min at an inlet pressure of 20 psi and an applied voltage of 50 V. The mechanical resonance frequency of the microvalve structure was measured at 11.1 kHz. The measured dynamic power consumption of the microvalve is approximately 60 mW when operated at 50 Hz. The measured static power consumption is approximately 2.5 mW at 20 V. Computational modeling of liquid flow within the piezoelectrically actuated microvalve has also been performed. The commercial computational fluid dynamics (CFD) code FLUENT was utilized for solving the continuity and momentum equations. The pressure drop between the inlet and outlet ports was determined as a function of the inlet mass flow rate, and a pressure drop coefficient was determined for each valve plate deflection value. The model-predicted values were compared to the experimental data, and confirmed the sensitivity of the results to the value of the deflection.
Transcriptional Instability during Evolving Sepsis May Limit Biomarker Based Risk Stratification (2013)

This is the first study of its kind detailing extensive expression changes in children during the evolution of sepsis. This highlights a limitation of static or single time point biomarker estimation. Serial estimations or more comprehensive network approaches may be required to optimize risk stratification in complex, time-critical conditions such as evolving sepsis.
Characterization and molecular cloning of a Cu/Zn superoxide dismutase from the human parasite Onchocerca volvulus (1991)

Evidence suggests that the helminth antioxidant enzyme superoxide dismutase (SOD) may play a role in parasite's defense against the cellular immune mechanisms of the host. In order to investigate this for the human parasite Onchocerca volvulus, the enzyme activity was characterized, the release of SOD by the parasite was examined, and a complete cDNA encoding the O. volvulus SOD was identified. The SOD activity in adult O. volvulus was found to be 8.1 +/- 4.2 U/mg of protein. A Cu/Zn-containing enzyme was demonstrated by its sensitivity towards cyanide, azide, and hydrogen peroxide. Isoelectric focusing, combined with an enzyme activity assay, revealed two activities at pI 6.8 and 7.6, with both activities inhibited by KCN. Adult parasites, maintained in vitro, released SOD into the culture medium, which was detected by enzyme activity. In parallel, lactate production was measured to ensure the viability of the parasite. Oligonucleotides (based upon conserved sequences in the SOD genes of other organisms) and the polymerase chain reaction were used to identify a portion of the SOD gene from O. volvulus genomic DNA. A cDNA library was constructed in lambda unizapII and screened with the genomic polymerase chain reaction fragment. A complete cDNA encoding the Cu/Zn SOD was identified, and its nucleotide sequence was determined. Southern blot hybridization experiments indicated that the Cu/Zn SOD is encoded by a single-copy gene with at least one intron.
Electrochemically Controlled Swelling and Mechanical Properties of a Polymer Nanocomposite (2009)

We present the layer-by-layer assembly of an electroactive polymer nanocomposite thin film containing cationic linear poly(ethyleneimine) (LPEI) and 68 vol % anionic Prussian Blue (PB) nanoparticles, which allow for electrochemical control over film thickness and mechanical properties. Electrochemical reduction of the PB doubles the negative charge on the particles, causing an influx of water and ions from solution to maintain electroneutrality in the film; concomitant swelling and increased elastic compliance of the film result. Reversible swelling upon reduction is on the order of 2-10%, as measured via spectroscopic ellipsometry and electrochemical atomic force microscopy. Reversible changes in the Young's elastic modulus of the hydrated composite film upon reduction are on the order of 50% (from 3.40 to 1.75 GPa) as measured with in situ nanoindentation, and a qualitative increase in viscous contributions to energy dissipation upon redox is indicated by electrochemical quartz crystal microbalance. Electrochemical stimuli maintain a mild operating environment and can be applied rapidly, reversibly, and locally. We maintain that electrochemical control over the swelling and mechanical behavior of polymer nanocomposites could have important implications for responsive coatings of nanoscale devices, including mechanically tunable surfaces to modulate behavior of adherent cells.
Partial shape recognition: a landmark-based approach (2003)

A technique to guide landmark matching known as hopping dynamic programming is described. The location of the model in the scene is estimated with a least-squares fit. A heuristic measure is then computed to decide if the model is in the scene. The shape features of an object are the landmarks associated with the object. The landmarks of an object are defined as the points of interest of the object that have important shape attributes. Examples of landmarks are corners, holes, protrusions, and high-curvature points.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Reverse and forward engineering of frequency control in power networks (2014)

We reverse-engineer the frequency dynamics with general primary frequency control and show that it is a distributed algorithm to solve a well-defined optimization problem. We further investigate the role of deadband in control, and show that if the aggregated uncontrolled load deviation is nonzero the frequencies will be synchronized, and if however it is zero the frequencies may oscillate but within the deadband. The optimization model does not only provide a way to characterize the equilibrium and establish the convergence of the frequency dynamics, but also suggests a principled way to engineer frequency control. By leveraging the optimization problem and insights from reverse engineering, we propose a distributed realtime frequency control scheme that does not only maintain the frequency to the nominal value but also achieves economic efficiency. This is drastically different from the current hierarchical control approach that addresses frequency regulation and economic efficiency at different timescales and with centralized control, and is what is needed for future power system to cope with rapid and large fluctuations in supply/demand and manage a huge number of control points. This work presents a step towards developing a new foundation - network dynamics as optimization algorithms - for distributed realtime control and optimization of future power networks.
Individually addressable vertically aligned carbon nanofiber-based electrochemical probes (2002)

In this paper we present the fabrication and initial testing results of high aspect ratio vertically aligned carbon nanofiber (VACNF)-based electrochemical probes. Electron beam lithography was used to define the catalytic growth sites of the VACNFs. Following catalyst deposition, VACNF were grown using a plasma enhanced chemical vapor deposition process. Photolithography was performed to realize interconnect structures. These probes were passivated with a thin layer of SiO2, which was then removed from the tips of the VACNF, rendering them electrochemically active. We have investigated the functionality of completed devices using cyclic voltammetry (CV) of ruthenium hexammine trichloride, a highly reversible, outer sphere redox system. The faradaic current obtained during CV potential sweeps shows clear oxidation and reduction peaks at magnitudes that correspond well with the geometry of these nanoscale electrochemical probes. Due to the size and the site-specific directed synthesis of the VACNFs, these probes are ideally suited for characterizing electrochemical phenomena with an unprecedented degree of spatial resolution.
An Adaptive Reliability Analysis Using Path Testing for Complex Component-Based Software Systems (2011)

With the growing size and complexity of software applications, traditional software reliability methods are insufficient to analyze inter-component interactions of modular software systems. The number of test cases may be extremely large for this application; therefore, it is hard for us to extensively test each software component given resource limitations. In this paper, we propose an adaptive framework of incorporating path testing into reliability estimation for modular software systems. Three estimated methods based on common program structures, namely, sequence, branch, and loop structures, are proposed to calculate the path reliability. Consequently, the derived path reliabilities can be applied to the estimates of software reliability. Some experiments are performed based on two real systems. In addition, the accuracy and correlation with respect to the experiments are investigated by simulation and sensitivity analysis. Experimental results show that the path reliability has a high correlation to the actual software reliability. For software with loop structures, a smaller loop number can be assigned to derive an acceptable estimation of path reliability. Further, the sensitivity analysis can be used to identify critical modules and paths for resource allocation. It can be concluded that the proposed methods are useful and helpful for estimating software reliability and can be adaptively used in the early stages of software development.
Ionic interactions in biological and physical systems: a variational treatment (2012)

Chemistry is about chemical reactions. Chemistry is about electrons changing their configurations as atoms and molecules react. Chemistry has for more than a century studied reactions as if they occurred in ideal conditions of infinitely dilute solutions. But most reactions occur in salt solutions that are not ideal. In those solutions everything (charged) interacts with everything else (charged) through the electric field, which is short and long range extending to the boundaries of the system. Mathematics has recently been developed to deal with interacting systems of this sort. The variational theory of complex fluids has spawned the theory of liquid crystals (or vice versa). In my view, ionic solutions should be viewed as complex fluids, particularly in the biological and engineering context. In both biology and electrochemistry ionic solutions are mixtures highly concentrated (to approximately 10 M) where they are most important, near electrodes, nucleic ids, proteins, active sites of enzymes, and ionic channels. Ca2+ is always involved in biological solutions because the concentration (really free energy per mole) of Ca2+ in a particular location is the signal that controls many biological functions. Such interacting systems are not simple fluids, and it is no wonder that analysis of interactions, such as the Hofmeister series, rooted in that tradition has not succeeded as one would hope. Here, we present a variational treatment of ard spheres in a frictional dielectric with the hope that such a treatment of an lectrolyte as a complex fluid will be productive. The theory automatically extends to spatially nonuniform boundary conditions and the nonequilibrium systems and flows they produce. The theory is unavoidably self-consistent since differential equations are derived (not assumed) from models of (Helmholtz free) nergy and dissipation of the electrolyte. The origin of the Hofmeister series is (in my view) an inverse problem that becomes well posed when enough data from disjoint experimental traditions are interpreted with a self-consistent theory.