gebhart/patrepeval huggingface dataset:
Expression cDNA cloning of a novel oncogene with sequence similarity to regulators of small GTP-binding proteins. (1994)

We generated a cDNA expression library from a human mammary epithelial cell line for detection of novel oncogenes by focus formation assay in NIH3T3 cells. A morphologically unique focus was identified and the transforming plasmid was isolated. The transforming gene, designated TIM, encoded a predicted protein species of 60 kDa containing a Dbl-Homology (DH) motif. This motif is also present in other growth regulatory molecules including Bcr, Cdc24, Vav, Ras-grf, and Ect2 which have been implicated as regulators of small GTP-binding proteins. NIH3T3 cells transfected with TIM expression plasmid showed altered growth properties in vitro and were tumorigenic when injected into nude mice. The 6.5 kilobasepair (kb) transcript of the TIM gene was mainly expressed in kidney, liver, pancreas, lung, and placenta. By analysing a panel of human-hamster somatic cell hybrids, we localized the TIM gene to human chromosome 7.
Mesoscale Modelling of Compressive Behaviour of Concrete at High Strain Rate (2008)

As one of the most commonly used construction materials, concrete may be subjected to extreme dynamic loads such as blast loads and high velocity impact loads. Understanding the concrete material properties at high strain rate is essential for reliable prediction of concrete structure response to dynamic loads. Extensive experimental results have shown that the dynamic uniaxial compressive strength increased with the increase of the strain rate. However, this phenomenon is still under debate. Although many researchers attribute the increase of compressive strength as a material property, i.e., the strain rate effects on materials, some researchers argued that the increase of dynamic compressive strength is caused by the inertia confinement, or by friction constraint on the test specimen. In other words, the increase of the concrete material strength is a structural effect, instead of a material property. In the present study, mesoscale model is used to analyse the compressive behaviour of concrete at high strain rates. In the mesoscale model, the concrete sample is regarded as a three-phase composite consisting of coarse aggregate, mortar matrix and interfacial transaction zone (ITZ) between the aggregate and the mortar matrix. The coarse aggregate is assumed to be circular shape and the ITZ is modelled as a thin boundary around the aggregate. Different material models are used for the three phases to simulate the responses of concrete samples under compression at different strain rates. The strain rate effect on the compressive strength is analysed based on the numerical results and compared with test results. The failure process of concrete specimen, and the effect of the size and position of the aggregate on the crack pattern and the fragment distribution are also investigated.
Decoupled control techniques for dual flying capacitor bridge power supplies of large superconductive magnets (1987)

The dual flying capacitor (DFC) was developed in 1976 as a method of supplying efficient bilateral power to large superconductive magnets. This power supply concept uses a second superconductive coil for energy storage. Large reversable power demands of the load magnet are met by energy exchange between the storage and load coils, through the DFC bridge. This paper will show that the DFC circuit can be decomposed into two elementary single flying capacitor (SLC) circuits which can be controlled independently. The discovery of this decoupled control concept is the origin of several new control strategies which significantly improve the performance of DFC power supplies, microcomputer controllers containing the decoupled control algorithm were tested on a DFC system simulator. The results show that time optimal load coil current and voltage control is now achievable by a robust bang-bang control technique. Furthermore, load coil current ripple and voltage spectrum can be independently controlled, while following an arbitrary reference signal. The DFC bridge, with the decoupled controllers, is a high performance power supply candidate for superconductive magnets of fusion reactors, particle accelerators and other systems.
<i>patched</i> overexpression alters wing disc size and pattern: transcriptional and post-transcriptional effects on <i>hedgehog</i> targets (1995)

The membrane protein, Patched, plays a critical role in patterning embryonic and imaginal tissues in Drosophila. patched constitutively inactivates the transcription of target genes such as wingless, decapentaplegic, and patched itself. The secreted protein, Hedgehog, induces transcription of target genes by opposing the Patched signaling pathway. Using the Gal4 UAS system we have overexpressed patched in wing imaginal discs and found that high Patched levels, expressed in either normal or ectopic patterns, result in loss of wing vein patterning in both compartments centering at the anterior/posterior border. In addition, patched inhibits the formation of the mechanosensory neurons, the campaniform sensilla, in the wing blade. The patched wing vein phenotype is modulated by mutations in hedgehog and cubitus interruptus (ci). Patched overexpression inhibits transcription of patched and decapentaplegic and post-transcriptionally decreases the amount of Ci protein at the anterior/posterior boundary. In hedgehogMrt wing discs, which express ectopic hedgehog, Ci levels are correspondingly elevated, suggesting that hedgehog relieves patched repression of Ci accumulation. Protein kinase A also regulates Ci; protein kinase A mutant clones in the anterior compartment have increased levels of Ci protein. Thus patched influences wing disc patterning by decreasing Ci protein levels and inactivating hedgehog target genes in the anterior compartment.
ChemInform Abstract: Displacement Reactions of 2,3‐Dichloro‐6‐nitroquinoxaline: Synthesis of s‐Triazolo[3,4‐a]quinoxaline. (1986)

Abstract The reaction of the dichloro compound (I) with N‐methylpiperazine (II) yields, depending on the reaction temp., the mono‐derivative (IIIa) or the bis‐derivative (IIIb).
WNT pathway inhibitor pyrvinium pamoate inhibits the self-renewal and metastasis of breast cancer stem cells (2016)

Acquisition of chemoresistance and metastatic phenotype are the major causes of breast cancer treatment failure and cancer-related mortality. Recently, a plethora of experimental and clinical studies points toward a central role of cancer stem cells (CSCs) in the chemoresistance and metastasis. In the present study, we demonstrated that pyrvinium pamoate (PP), an anthelmintic drug, inhibited proliferation of different subtypes of breast cancer cells (luminal: MCF-7, claudin-low: MDA-MB‑231, basal-like: MDA-MB‑468 and Her-2 enriched: SkBr-3) as a novel WNT pathway inhibitor. Additionally, PP was also shown to inhibit self-renewal of breast cancer stem cells (BCSCs) and decrease both CD44+CD24-/low and ALDH-positive BCSCs content in a panel of breast cancer cell lines. Besides, the metastatic potential and expression of EMT markers (such as N-cadherin, vimentin, Snail) were also found suppressed by PP. By using a xenograft model, we next tested the efficacy of PP on tumorigenicity of MDA-MB‑231, one of the most aggressive breast cancer cell lines, and we observed PP significantly delayed tumor growth in vivo. Moreover, in-depth analysis revealed that PP caused inhibition of WNT pathway activity and stemness regulator expression including NANOG, SOX2 and OCT4, which were inherently upregulated in the BCSCs as compared with the bulk of cells within the tumor. Collectively, our findings provide direct evidence for PP serving as a promising high-yield agent targeting BCSCs and cancer heterogeneity. Therefore, strategies combining PP with standard chemotherapy drugs which fail to eliminate the BCSCs hold promise to overcome BCSCs associated treatment resistance and achieve a better therapeutic outcome.
Interaction Mechanisms between Polyamines and IRK1 Inward Rectifier K+ Channels (2003)

Rectification of macroscopic current through inward-rectifier K+ (Kir) channels reflects strong voltage dependence of channel block by intracellular cations such as polyamines. The voltage dependence results primarily from the movement of K+ ions across the transmembrane electric field, which accompanies the binding-unbinding of a blocker. Residues D172, E224, and E299 in IRK1 are critical for high-affinity binding of blockers. D172 appears to be located somewhat internal to the narrow K+ selectivity filter, whereas E224 and E299 form a ring at a more intracellular site. Using a series of alkyl-bis-amines of varying length as calibration, we investigated how the acidic residues in IRK1 interact with amine groups in the natural polyamines (putrescine, spermidine, and spermine) that cause rectification in cells. To block the pore, the leading amine of bis-amines of increasing length penetrates ever deeper into the pore toward D172, while the trailing amine in every bis-amine binds near a more intracellular site and interacts with E224 and E299. The leading amine in nonamethylene-bis-amine (bis-C9) makes the closest approach to D172, displacing the maximal number of K+ ions and exhibiting the strongest voltage dependence. Cells do not synthesize bis-amines longer than putrescine (bis-C4) but generate the polyamines spermidine and spermine by attaching an amino-propyl group to one or both ends of putrescine. Voltage dependence of channel block by the tetra-amine spermine is comparable to that of block by the bis-amines bis-C9 (shorter) or bis-C12 (equally long), but spermine binds to IRK1 with much higher affinity than either bis-amine does. Thus, counterintuitively, the multiple amines in spermine primarily confer the high affinity but not the strong voltage dependence of channel block. Tetravalent spermine achieves a stronger interaction with the pore by effectively behaving like a pair of tethered divalent cations, two amine groups in its leading half interacting primarily with D172, whereas the other two in the trailing half interact primarily with E224 and E299. Thus, nature has optimized not only the blocker but also, in a complementary manner, the channel for producing rapid, high-affinity, and strongly voltage-dependent channel block, giving rise to exceedingly sharp rectification.
Improvements to keyboard optimization with integer programming (2014)

Keyboard optimization is concerned with the design of keyboards for different terminals, languages, user groups, and tasks. Previous work in HCI has used random search based methods, such as simulated annealing. These "black box" approaches are convenient, because good solutions are found quickly and no assumption must be made about the objective function. This paper contributes by developing integer programming (IP) as a complementary approach. To this end, we present IP formulations for the letter assignment problem and solve them by branch-and-bound. Although computationally expensive, we show that IP offers two strong benefits. First, its structured non-random search approach improves the out- comes. Second, it guarantees bounds, which increases the designer's confidence over the quality of results. We report improvements to three keyboard optimization cases.
An Evolutionary Approach to Synthetic Biology: Zen and the Art of Creating Life (1993)

Our concepts of biology, evolution, and complexity are constrained by having observed only a single instance of life, life on earth. A truly comparative biology is needed to extend these concepts. Because we cannot observe life on other planets, we are left with the alternative of creating Artificial Life forms on earth. I will discuss the approach of inoculating evolution by natural selection into the medium of the digital computer. This is not a physical/chemical medium; it is a logical/informational medium. Thus, these new instances of evolution are not subject to the same physical laws as organic evolution (e.g., the laws of thermodynamics) and exist in what amounts to another universe, governed by the “physical laws” of the logic of the computer. This exercise gives us a broader perspective on what evolution is and what it does.An evolutionary approach to synthetic biology consists of inoculating the process of evolution by natural selection into an artificial medium. Evolution is then allowed to find the natural forms of living organisms in the artificial medium. These are not models of life, but independent instances of life. This essay is intended to communicate a way of thinking about synthetic biology that leads to a particular approach: to understand and respect the natural form of the artificial medium, to facilitate the process of evolution in generating forms that are adapted to the medium, and to let evolution find forms and processes that naturally exploit the possibilities inherent in the medium. Examples are cited of synthetic biology embedded in the computational medium, where in addition to being an exercise in experimental comparative evolutionary biology, it is also a possible means of harnessing the evolutionary process for the production of complex computer software.
Control-structure interaction (1992)

The feasibility of using conventional proportional-integral-derivative (PID) control and an alternative optimal control to perform the pointing and tracking functions of the Space Station solar dynamic power module is investigated. A very large state model of six rigid body modes and 272 flexible modes is used in conjunction with classical linear-quadratic-Gaussian (LQG) optimal control to produce a full-order controller that satisfies the requirements. The results are compared with a classically designed PID controller that was implemented for a much smaller (six rigid body, 40 flexible modes) model. The conventional control design approach is shown to be very much influenced by the order reduction of the plant model, i.e. the number of retained elastic modes from the full-order model, suggesting that for a complex, large space structure, such as the Space Station Freedom solar dynamic module, application of conventional control system design methods may not be adequate. The use of LQG control is recommended, and method for solving the large matrix. Riccati equation that arises from the optimal formulation is provided.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Encephalocele of the middle ear (1986)

A case of congenital encephalocele of the middle ear presenting as a conductive hearing loss is reported. In retrospect it is possible that CT scanning with metrizimide contrast studies may have been helpful in establishing the diagnosis (Cooper and Kassel, 1982). However, it is stressed that even in the absence of radiological abnormality of the temporal bone, surgical exploration of the middle cranial fossa should be undertaken.
Severe vitamin D deficiency is associated with worsened outcomes in surgical patients with ventilated-associated pneumonia (2012)

Matthews, Leslie Ray MD, FACS; Wilson, Kenneth MD, FACS; Ahmed, Yusuf MD, MPH; Griggs, Diane NP, Ed Childs, MD, FACS; Danner, Omar MD, FACS Author Information
Acromegaly and gastrointestinal cancer (1991)

A cohort of 1041 men who were discharged from the hospital with a diagnosis of acromegaly were examined for subsequent cancer. With a mean follow-up time of 8.3 years, an increased rate of cancers of the digestive organs was observed (27 cases; standard incidence ratio [SIR], 2.0; 95% confidence interval [CI], 1.3 to 2.9). Rates were elevated for cancers of the esophagus (7 cases; SIR, 3.1), stomach (4 cases; SIR, 2.5), and colon (13 cases; SIR, 3.1). The increased risk of colon cancer in acromegaly is consistent with previous clinical reports and suggests opportunities for etiologic research and early cancer detection. It would seem prudent to also evaluate this risk in current research on the use of growth hormone in older individuals to increase muscle mass and reduce body fat.
Final results of E2603: A double-blind, randomized phase III trial comparing carboplatin (C)/paclitaxel (P) with or without sorafenib (S) in metastatic melanoma. (2010)

8511 Background: Systemic treatment of metastatic melanoma has not advanced for decades, prompting investigation of novel approaches. Sorafenib is a kinase inhibitor active against RAF and VEGFR tyrosine kinases, amongst others. The discovery of BRAF mutations in 60% of melanoma prompted investigation of the combination of S/C/P following promising results in a large, uncontrolled phase II trial in metastatic melanoma. Methods: Our primary objective was to determine whether S/C/P improves overall survival (OS) compared to C/P in chemotherapy- naïve metastatic melanoma pts. Pts were not prescreened for BRAF mutations. All pts received C AUC 6 IV q 21d and P 225 mg/m2 IV q21d with random assignment to S 400 mg BID days 2-19 every 21d or placebo. 800 patients were needed to provide 90% power to detect a 22.5% improvement in hazard ratio (HR) for OS. Interim analyses were conducted preserving the overall type I error rate of 0.05 (two-sided), and monitoring for early stopping in favor of the null hypothesis using Jennison-Turnbull repeated confidence interval. PFS, RR, and toxicity were secondary endpoints. Potential predictive genetic and immunohistologic correlates are under study. Results: 823 pts (411 C/P, 409 S/C/P, 3% ineligible) were accrued over 34 months. After the third interim analysis, 75% of the events required for final analysis had transpired. The study had crossed the futility boundary, and was unblinded. The log-rank test HR, stratifying by AJCC stage, ECOG PS and prior therapy, was 1.0 (p = 0.878). The median OS for the S/C/P group is 11.1 months (95% CI and 10.3-12.3) and for the C/P group is 11.3 mos. (95% CI 9.7-12.3). Median PFS was 4.9 for S/C/P and 4.1 for C/P (p = 0.12). RR was 18% for S/C/P and 16% for C/P (p = 0.48). 78% of patients in C/P arm and 84% in the S/C/P arm had grade 3 or higher toxicities (p = 0.032), with significantly increased rash, hand-foot syndrome, neuropathy, and thrombocytopenia. Conclusions: S/C/P does not improve overall survival in combination with C/P for chemotherapy-naïve pts with metastatic melanoma. This study also establishes RR and PFS for the C/P combination chemotherapy regimen in first-line therapy of metastatic melanoma. No significant financial relationships to disclose.
Privacy-preserving distributed mining of association rules on horizontally partitioned data (2010)

Abstract—Data mining can extract important knowledge from large data collections—but sometimes these collections are split among various parties. Privacy concerns may prevent the parties from directly sharing the data and some types of information about the data. This paper addresses secure mining of association rules over horizontally partitioned data. The methods incorporate cryptographic techniques to minimize the information shared, while adding little overhead to the mining task. Index Terms—Data mining, security, privacy. æ
Gaussian multiple access channels for radar and communications spectrum sharing (2016)

This paper develops the fundamental performance bounds for a radar operating in the presence of communication interference. To do so, we recast radar as a communication problem with the radar waveform acting as a convolutional encoder, which allows for the description of the achievable information-theoretic limits of the radar problem. While information theory has been applied to communications and radar, there has been little work on applying information theory to systems that explicitly combine sensing and communications. The new viewpoint presented in this paper, which does not require new mathematics, allows one to recast the problem of a radar operating in the presence of communication interference as a Gaussian multiple access channel problem. The derived bounds describe the fundamental limits on the amount of information the radar can obtain about the scattering environment in the presence of communications interference.
Computational identification of evolutionarily conserved exons (2004)

Phylogenetic hidden Markov models (phylo-HMMs) have recently been proposed as a means for addressing a multi-species version of the ab initio gene prediction problem. These models allow sequence divergence, a phylogeny, patterns of substitution, and base composition all to be considered simultaneously, in a single unified probabilistic model. Here, we apply phylo-HMMs to a restricted version of the gene prediction problem in which individual exons are sought that are evolutionarily conserved across a diverse set of species. We discuss two new methods for improving prediction performance: (1) the use of context-dependent phylogenetic models, which capture phenomena such as a strong CpG effect in noncoding regions and a preference for synonymous rather than nonsynonymous substitutions in coding regions; and (2) a novel strategy for incorporating insertions and deletion (indels) into the state-transition structure of the model, which captures the different characteristic patterns of alignment gaps in coding and noncoding regions. We also discuss the technique, previously used in pairwise gene predictors, of explicitly modeling conserved noncoding sequence to help reduce false positive predictions. These methods have been incorporated into an exon prediction program called ExoniPhy, and tested with two large data sets. Experimental results indicate that all three methods produce significant improvements in prediction performance. In combination, they lead to prediction accuracy comparable to that of some of the best available gene predictors, despite several limitations of our current models.
Light weight security for parallel access to multiple mirror sites (2002)

The mirror sites approach has been proposed previously for reducing the access delay and providing load balancing in network servers. In the mirror site approach a file, such as a multimedia book, is replicated and dispersed over multiple servers and can be requested in parallel. However, to limit the bandwidth waste, each server maintains not the entire file but only a portion of it. Current solutions to provide parallel access to multiple servers are based on breaking the file into b "pieces" using forward error correction (FEC) codes or their variants. In such techniques any k/spl les/b pieces are necessary and sufficient to construct the file. Thus, protection of the file from unauthorized access has to be based on encryption. As a result, as the degree of parallelism increases a trade off occurs between the security overhead and access delay. In this work, we propose new file dispersal and access control protocols to reduce the security overhead significantly. Our protocols are based on the combinatorial techniques which break a file into small pieces in a similar way to FEC code. Thus, at least k pieces are necessary to construct the file. However, in contrast with the previous approaches, not every k pieces are sufficient. Capitalizing on this property this work presents secure dispersal and access protocols that aim to minimize the overhead at the servers.
The non- <i>H pylori</i> helicobacters: their expanding role in gastrointestinal and systemic diseases (2002)

The number of species in the genus Helicobacter has rapidly expanded over the past decade. The genus now includes at least 24 formally named species as well as numerous other helicobacters awaiting formal naming. This review highlights the expanding role that other helicobacters, although not as well known as H pylori, play in gastrointestinal and systemic disease in humans.