gebhart/patrepeval huggingface dataset:
A Novel Brain-Permeant Chemotherapeutic Agent for the Treatment of Brain Metastasis in Triple-Negative Breast Cancer (2021)

Development of metastases to central nervous system (CNS) is an increasing clinical issue following the diagnosis of advanced breast cancer. The propensity to metastasize to CNS varies by breast cancer subtype. Of the four breast cancer subtypes, triple-negative breast cancers (TNBC) have the highest rates of both parenchymal brain metastasis and leptomeningeal metastasis (LM). LM is rapidly fatal due to poor detection and limited therapeutic options. Therapy of TNBC brain metastasis and LM is challenged by multifocal brain metastasis and diffuse spread of LM, and must balance brain penetration, tumor cytotoxicity, and the avoidance of neurotoxicity. Thus, there is an urgent need for novel therapeutic options in TNBCs CNS metastasis. QBS10072S is a novel chemotherapeutic that leverages TNBC-specific defects in DNA repair and LAT1 (L-amino acid transporter type 1)-dependent transport into the brain. In our study, activity of QBS10072S was investigated <i>in vitro</i> with various cell lines including the human TNBC cell line MDA-MB-231 and its brain-tropic derivative MDA-MB-231-BR3. QBS10072S was preferentially toxic to TNBC cells. The efficacy of QBS10072S against brain metastasis and LM was tested using a model of brain metastasis based on the internal carotid injection of luciferase-expressing tumor cells into NuNu mice. The compound was well tolerated, delayed tumor growth and reduced leptomeningeal dissemination, resulting in significant extension of survival. Given that current treatments for LM are palliative with only few studies reporting a survival benefit, QBS10072S is planned to be investigated in clinical trials as a therapeutic for TNBC LM. SIGNIFICANCE: TNBC brain metastasis often involves dissemination into leptomeninges. Treatment options for TNBC leptomeningeal metastasis are limited and are mostly palliative. Our study demonstrates significant efficacy of the brain-penetrating agent QBS10072S against TNBC brain metastasis and leptomeningeal spread.
Omics and therapy – A basis for precision medicine (2012)

A founding premise of the human genome project was that knowledge of the spectrum of abnormalities that comprise cancers and other human diseases would lead to improved disease management by identifying molecular abnormalities that could guide disease detection and diagnosis, suggest new therapeutic strategies and be developed as markers to predict response to therapy. This project led to elucidation of a reference normal human genome sequence and normal polymorphisms therein against which sequences from diseased tissues can be compared to enable identification of causal abnormalities. It also stimulated development of an array of computational tools for genomic analysis and catalyzed public and private sector development of revolutionary tools for genome analysis that transformed analysis of whole genomes from an enterprise that required international teams and hundreds of millions of dollars to a process that can be carried out in core facilities for only a few thousand dollars per sample. Indeed, the $1000 genome is nearly upon us. Applications of these technologies to human cancers in international cancer genome projects are now revealing the spectra of abnormalities that comprise thousands of individual cancers. Analyses of these data are leading to the promised improvements in disease management. We review several aspects of cancer genomics with emphasis on aspects that are relevant to improving cancer therapy.
In-Network Linear Regression with Arbitrarily Split Data Matrices (2014)

In this paper, we address the problem of how a network of agents can collaboratively fit a linear model when each agent only ever has an arbitrary summand of the regression data. This problem generalizes previously studied data-matrix-splitting scenarios, allowing for some agents to have more measurements of some features than of others and even have measurements that other agents have. We present a variable-centric framework for distributed optimization in a network, and use this framework to develop a proximal algorithm, based on the Douglas-Rachford method, that solves the problem.
Control-Oriented modeling and validation of bicycle curve dynamics with focus on lateral tire parameters (2017)

Under the objective of modeling, simulating and controlling the dynamics of bicycles in dangerous situations, such as wheel slippage, an accurate tire model is essential. Especially the lateral tire behavior is crucial since it is fundamental for stability in both rectilinear and curve maneuvers. So far, various test bench measurements are available in literature that describe lateral tire forces and moments under different load, sideslip and camber angle. The most recent measurements that study the behavior of common bicycle tires that are still available on the market come to very different results, even for identical tires. Anyhow, test bench measurements almost always imply conditions that differ from field application of bicycles on actual road surface. The aim of this paper is to use lateral tire parameters extracted from literature and include them into a multibody model of lateral bicycle dynamics. The simulation result is then compared to measurements recorded in a realistic environment. Therefore a bicycle is equipped with sensors to provide a large set of relevant variables of lateral vehicle dynamics. The validation process identifies a set of tire parameters that allows good model accuracy. Also for different tires at different inflation pressure model validity can be shown using tire parameters extracted from test-bench measurements.
A novel fabrication method for semiconductor ring lasers that ensures optimal electrical pumping (2009)

Infrared semiconductor ring laser fabrication typically involves planarization of ridge waveguide device structures and deposition of metal electrodes for electrical pumping. Uniform planarization across large samples is difficult to achieve. This leads to inadequate electrical contact between portions of the ring resonator and the deposited metal electrode layer whereby the devices are not optimally pumped. This can lead to high threshold currents and device failure. The problem of inadequate electrical pumping on account of non-idea planarization has been addressed by utilizing a metallic etch mask instead of the commonly used photoresist 'soft' mask. The metallic mask remains intact after ridge etching and the other ensuing fabrication steps to form a continuous metallic cover above the entire device structure. This metallic cover ensures proper electrical contact between the ring resonator and the deposited metal electrode layer even when planarization imperfections render only certain portions of the resonator in proper electrical contact with the metal electrode layer. The proposed fabrication process has led to large diameter ring lasers with high yield and low threshold current levels. These devices are robust and exhibit stable operation over large current ranges in addition.
Ultrafiltration and Clearance Studies in Human Isolated Peritoneal Vascular Loops (1994)

Eight samples of human peritoneal tissue were obtained from patients undergoing hemicholectomy for cancer. An artery and a vein were cannulated and perfused with blood in vitro with a special circuit able to provide different perfusion pressures. Ultrafiltration and clearance studies were performed in these samples. Both ultrafiltration and small-solute clearances linearly correlated with the blood flow, demonstrating a strong dependence on this parameter. The peritoneal capillary showed a typical filtration pressure equilibrium with a constant filtration fraction at different blood flows. The results suggest that the blood flow may be a factor limiting the efficiency of peritoneal dialysis both in terms of mass transfer coefficients and maximal ultrafiltration rates.
Modulation of surface flow and vortex shedding of a circular cylinder in the subcritical regime by a self-excited vibrating rod (2006)

The surface flow, pressure distributions, and vortex-shedding properties of the circular cylinder flow in the subcritical regime modulated by a self-excited vibrating rod were experimentally studied in a closed-circuit wind tunnel for Reynolds numbers between $2\,{\times}\,10^4$ and $1.8\,{\times}\,10^5$ . The principle of galloping was employed to induce self-vibration of an elastic rod. The natural (uncontrolled) boundary layer showed significantly different flow patterns in two subranges of Reynolds number: $Re_D \,{&lt;}\,0.55\,{\times}\,10^5$ and $Re_D \,{&gt;}\, 0.55\,{\times}\,10^5$ . In the low-Reynolds-number subrange, the laminar separation mode , which was similar to the result reported by previous investigators, was observed. While in the high-Reynolds-number subrange, the separation bubble mode , which was rarely discussed previously, was found. The term separation bubble mode was used to denote the existence of secondary recirculation bubbles induced by the reattachment of separated boundary layers. The surface flow modulated by the vibrating rod presented complex variations in these two subranges. Depending on the position of the control rod, the separation bubble mode or the turbulent separation mode might appear because of the increase of the turbulence kinetic energy. Modulating the surface flow patterns could significantly influence the surface pressure distributions on the main cylinder and the vortex shedding in the wake. Forcing the boundary layer at the positions upstream of the natural separation point would drastically lower the values of the minimum pressure coefficient and the base pressure coefficient, and therefore increase the lift. The drag coefficient, however, would not be apparently decreased. The frequency of the vortex shedding in the wake could ‘lock’ to the rod vibration frequency if the position of the vibrating rod was properly adjusted.
Measurement of CuK-Shell and AgL-Shell Ionization Cross Sections by Low-Energy Positron Impact (2004)

Inner shell ionization cross sections by low-energy positron impact have been measured. Development of an x-ray detector with thin Si(Li) crystals has enabled the first measurements of the absolute cross sections for the positron impacts in the energy range below 30 keV. Threshold behavior of the measured cross sections for the Cu K shell and Ag L shell are compared with the theoretical results of Gryzinski and Kowalski [Phys. Lett. A 183, 196 (1993)]] and Khare and Wadehra [Can. J. Phys. 74, 376 (1996)]]. Good agreement has been found for the Cu K shell, while the experimental values for the Ag L shell were found to be smaller than the corresponding theoretical results.
Transgenic Tools and Animal Models of Mental Illness (2013)

Animal models of neuropsychiatric disorders are important to elucidate the pathophysiological mechanisms underlying these disorders as well as develop better treatment options. There has been tremendous progress made in the field of mouse genetics, and more recently in rats, to manipulate the genome in order to assess the impact of specific genetic manipulations on the animal. These approaches are particularly important as new genes are implicated in specific mental disorders allowing one to directly assess their relevance in a complete animal system. These genetic approaches in mice have also complemented and extended our understanding of pharmacological models of psychiatric diseases. This chapter will provide a brief overview of transgenic mice, knockout mice, as well as viral-mediated gene transfer approaches in neurobiology and provide select examples of how these approaches have contributed to our understanding of brain function with implications for molecular psychiatry.
Muscle membrane integrity in Duchenne muscular dystrophy: recent advances in copolymer-based muscle membrane stabilizers (2018)

The scientific premise, design, and structure-function analysis of chemical-based muscle membrane stabilizing block copolymers are reviewed here for applications in striated muscle membrane injury. Synthetic block copolymers have a rich history and wide array of applications from industry to biology. Potential for discovery is enabled by a large chemical space for block copolymers, including modifications in block copolymer mass, composition, and molecular architecture. Collectively, this presents an impressive chemical landscape to leverage distinct structure-function outcomes. Of particular relevance to biology and medicine, stabilization of damaged phospholipid membranes using amphiphilic block copolymers, classified as poloxamers or pluronics, has been the subject of increasing scientific inquiry. This review focuses on implementing block copolymers to protect fragile muscle membranes against mechanical stress. The review highlights interventions in Duchenne muscular dystrophy, a fatal disease of progressive muscle deterioration owing to marked instability of the striated muscle membrane. Biophysical and chemical engineering advances are presented that delineate and expand upon current understanding of copolymer-lipid membrane interactions and the mechanism of stabilization. The studies presented here serve to underscore the utility of copolymer discovery leading toward the therapeutic application of block copolymers in Duchenne muscular dystrophy and potentially other biomedical applications in which membrane integrity is compromised.
Link Budget Calculations (2016)

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Successful Placement of Openhole Plug in HT Conditions (2007)

Abstract This case history paper describes the use of a bottomhole kickoff assembly (BHKA) tool to place openhole plugs in a high-temperature well. The well was a 6 ½-in. diameter borehole with 52° deviation and 174°C (345°F) bottomhole static temperature (BHST). Depth was 5775 m (18,946 ft). Even though these extreme conditions were anticipated, they were discussed with the operator because two earlier attempts to achieve a kickoff had failed. In this successful kickoff operation, the BHKA was tagged 1 m (3.3 ft) below the calculated top of cement and was tested to 6 tons over the plug, using a 165-mm (6 1/2-in.) roller cone bit. Conditions for both the tool and cement slurry were extreme. Kickoff was successfully accomplished during the first 8 m (26 ft) of the BHKA plug; formation cuttings of 99% were reported.
Long-term anti-CD154 dosing in nephritic mice is required to maintain survival and inhibit mediators of renal fibrosis (2001)

The CD154/CD40 pathway is required for the development and progression of disease in a variety of autoimmune model systems. We have demonstrated previously that long-term anti-CD154 treatment of nephritic (SWRxNZB)F1 mice prolonged survival and preserved kidney function. Herein we ask if long-term treatment is required and further characterize the protective effect on renal pathology by examining alpha-smooth muscle actin, collagen and TGF-beta1 expression in renal tissue. The effects of anti-CD154 on brain and heart inflammation are also examined. Three dosing strategies of anti-CD154 mAb were compared in SNF1 mice that exhibited moderate or severe nephritis: (1) weekly for 6 weeks; (2) monthly; (3) weekly for 6-12 weeks followed by monthly dosing. Proteinuria, serum anti-DNA, anti-CD154 pharmacokinetics and serum soluble CD154 analyses were performed. Anti-CD154 treatment of moderate disease increased survival across all regimens, although weekly followed by monthly maintenance dosing proved most efficacious. This regime also inhibited renal alpha-smooth muscle actin and collagen deposition. Only the most aggressive anti-CD154 treatment protocol increased survival in severely nephritic mice. Long-term anti-CD154 treatment significantly inhibits key mediators of kidney fibrosis and is required to maximize survival and renal function. Potential reasons for differential therapeutic efficacy in moderately vs severely nephritic mice are discussed.
Dynamic Searchable Encryption with Small Client Storage (2020)

We study the problem of dynamic searchable encryption (DSE) with forward-and-backward privacy. Many DSE schemes have been proposed recently but the most efficient ones have one limitation: they require maintaining one operation counter for each unique keyword, either stored locally at the client or stored encrypted at the server and accessed obliviously (e.g., with an oblivious map) during every operation. We propose three new schemes that overcome the above limitation and achieve constant permanent client storage with improved performance, both asymptotically and experimentally, compared to prior stateof-the-art works. In particular, our first two schemes adopt a "static-to-dynamic" transformation which eliminates the need for oblivious accesses during searches. Due to this, they are the first practical schemes with minimal client storage and non-interactive search. Our third scheme is the first quasi-optimal forward-andbackward DSE scheme with only a logarithmic overhead for retrieving the query result (independently of previous deletions). While it does require an oblivious access during search in order to keep permanent client storage minimal, its practical performance is up to four orders of magnitude better than the best existing scheme with quasi-optimal search.
Spongiacysteine, a Novel Cysteine Derivative from Marine Sponge Spongia sp. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Viable But Non-Culturable Cells Are Persister Cells (2017)

ABSTRACT Bacteria have two dormant phenotypes: the viable but non-culturable (VBNC) state and the persister state. Both resting stages arise without mutation and both have been linked to chronic infections; however, persister cells revive rapidly whereas the cell population called VBNC is reported to not resuscitate. Here we investigated the relatedness of the two stress-induced phenotypes at the single-cell level by using transmission electron microscopy and fluorescent microscopy to examine cell morphology and by quantifying cell resuscitation. Using the classic starvation conditions to create VBNC cells, we found that the majority of the remaining Escherichia coli population are spherical, have empty cytosol, and fail to resuscitate; however, some of the spherical cells under these classic VBNC-inducing conditions resuscitate immediately (most probably those with dense cytosol). Critically, all the culturable cells became persister cells within 14 days of starvation. We found that the persister cells initially are rodlike, have clear but limited membrane damage, can resuscitate immediately, and gradually become spherical by aging. After 24 h, only rod-shaped persister cells survive, and all the spherical cells lyse. Both cell populations formed under the VBNC-inducing conditions and the persister cells are metabolically inactive. Therefore, the bacterial population consists of dead cells and persister cells in the VBNC-inducing conditions; i.e., the non-lysed particles that do not resuscitate are dead, and the dormant cells that resuscitate are persister cells. Hence, “VBNC” and “persister” describe the same dormant phenotype.
The inhibition of Candida-albicans-secreted aspartic proteases by three different HIV protease inhibitors. (1999)

Background: Severe forms of oropharyngeal candidiasis due to Candida albicans are commonly observed in AIDS patients. However, the incidence of this disease has declined after the introduction of combination therapy using HIV aspartic protease inhibitors. Aspartic proteases secreted by C. albicans (Saps), which are enzymes involved in virulence, have similarities with the HIV aspartic protease. Objective: The aim of this study was to investigate the effect of three different HIV aspartic protease inhibitors, ritonavir, saquinavir and indinavir, on the activity of different C. albicans Saps. Methods: The activity of 6 Sap isoenzymes was measured in the presence and the absence of different HIV aspartic protease inhibitors using resorufin-labeled casein as a substrate. Results: Three different Saps involved in adherence of C. albicans, Sap1, Sap2 and Sap3, were inhibited by ritonavir, saquinavir and indinavir at concentrations achievable in the serum of patients (for ritonavir). Conclusion : Direct Sap inhibition by aspartic protease inhibitors could contribute to the markedly reduced incidence of oropharyngeal candidiasis observed in individuals receiving anti-HIV combination therapy. The development of specific aspartic protease inhibitors might be of interest for the treatment of mucosal candidiasis in both HIV and non-HIV patients.
Rapid nonlinear speaker adaptation for large-vocabulary continuous speech recognition (2012)

Recently, kernel eigenvoices were revisited using kernel representations of distributions for rapid nonlinear speaker adaptation. These representations reassure the validity of the adapted distribution functions and enable expectation-maximisation training. Though gains have been shown in terms of word error rate for rapid speaker adaptation, this approach leads to an increase in decoding cost as the number of likelihood evaluations is amplified. The present paper addresses this issue by providing a coherent framework for systematic probabilistic approaches aimed at reducing the recognition cost and yet yielding equally powerful adapted models. The common denominator of such approaches is the use of probabilistic criteria, such as Kullback-Leibler divergence. However, in the general case, the resulting adapted models have full covariance matrices. In order to overcome this issue, the use of predictive semi-tied transforms to yield diagonal covariances for decoding is investigated in this paper. Experimental results are presented on a large-vocabulary conversational telephone task.
Investigation of the Impact of Pad Surface Texture from Different Pad Conditioners on the CMP Performance (2020)

Chemical mechanical polishing (CMP) is a common method for planarization/polishing materials during integrated circuits (IC) fabrication. Pad conditioning is a critical component of a CMP process. Herein, the impact of surface textures created by different types of pad conditioners (PC) such as coarse, mid-coarse, and fine PC on the solid pads are studied. Additional surface texture parameters such as surface height distribution, skewness, Dale Void Volume are used to determine an optimum surface texture that gives desired CMP performance such as material removal rate and within-wafer non-uniformity. It was determined that an optimum surface texture on a solid CMP pad can be obtained with a mid-coarse disk. It is further demonstrated that by the addition of porosity to the pads, it is possible to recreate an optimum surface texture and desired CMP performance, similar to that obtained with a mid-coarse disk and a solid pad. Tribological mechanisms of the different pad and PC combinations are presented using the coefficient of friction. It is concluded that porous pad and fine PC pairing can tackle the issues of slurry transport limitations, lack of asperity contact, and process stability over pad life.
Characterizing Cas9 Protospacer-Adjacent Motifs with High-Throughput Sequencing of Library Depletion Experiments (2016)

This protocol outlines a general approach for characterizing the protospacer-adjacent motifs (PAMs) of Cas9 orthologs. It uses a three-plasmid system: One plasmid carries Cas9 and its tracrRNA, a second targeting vector contains the spacer and repeat, and the third plasmid encodes the targeted sequence (as the protospacer) with varying PAM sequences. It leverages the Cas9 nuclease activity to cleave and destroy plasmids that bear a compatible PAM. The level of depletion of a library of targeted plasmids after Cas9-mediated selection can then be assessed by deep sequencing to reveal candidate PAMs for downstream validation.