gebhart/patrepeval huggingface dataset:
Isoform-Specific Phosphoinositide 3-Kinase Inhibitors Exert Distinct Effects in Solid Tumors (2010)

Therapeutic inhibitors are being developed against the phosphoinositide 3-kinase (PI3K) pathway, the deregulation of which drives tumor growth and survival in many cancers. There are eight PI3Ks in mammals divided into three classes. Class IA PI3Ks (p110alpha, p110beta, and p110delta) are critical for cell growth and survival, with the p110alpha isoform implicated as the most important in carcinomas. In this study, we examined the effects of small-molecule inhibitors of class IA PI3Ks to explore the contributions of different isoforms in cancer cells. Similar responses were seen in cancer cells with wild-type or activated mutant PI3K genes treated with p110alpha/delta or p110alpha/beta/delta inhibitors in cell viability assays. In contrast, PTEN-negative cell lines tended to be less responsive (4-fold overall) to an inhibitor of p110alpha/delta versus p110alpha/beta/delta. Combining a p110alpha/delta inhibitor with a p110beta inhibitor resulted in comparable potency to the p110alpha/beta/delta inhibitor. The disparity in efficacy was confirmed in vivo. Pharmacodynamic biomarker analysis revealed that an inhibitor with insufficient potency against the p110beta isoform was less effective at inhibiting the PI3K pathway in PTEN-negative tumor xenografts. Our results imply that patients with PTEN-negative tumors may preferentially benefit from treatment with a class I PI3K inhibitor that is capable of inhibiting the p110beta isoform.
Lentiviral Vectors and Protocols for Creation of Stable hESC Lines for Fluorescent Tracking and Drug Resistance Selection of Cardiomyocytes (2009)

The protocols, vectors and gene expression data comprise tools to enhance cardiomyocyte production for large-scale applications.
Antithrombogenic property of bone marrow mesenchymal stem cells in nanofibrous vascular grafts (2007)

Nanostructured biomaterials have tremendous potential for tissue engineering. However, the performance and integration of the nanomaterials in vivo are not well understood. A challenge in vascular tissue engineering is to develop optimal scaffolds and establish expandable cell sources for the construction of tissue-engineered vascular grafts that are nonthrombogenic and have long-term patency. Here, we used tissue-engineered vascular grafts as a model to demonstrate the potential of combining nanofibrous scaffolds and bone marrow mesenchymal stem cells (MSCs) for vascular tissue engineering. Biodegradable nanofibrous scaffolds with aligned nanofibers were used to mimic native collagen fibrils to guide cell organization in vascular grafts. The results from artery bypass experiments showed that nanofibrous scaffolds allowed efficient infiltration of vascular cells and matrix remodeling. Acellular grafts (without MSCs) resulted in significant intimal thickening, whereas cellular grafts (with MSCs) had excellent long-term patency and exhibited well organized layers of endothelial cells (ECs) and smooth muscle cells (SMCs), as in native arteries. Short-term experiments showed that nanofibrous scaffolds alone induced platelet adhesion and thrombus formation, which was suppressed by MSC seeding. In addition, MSCs, as ECs, resisted platelet adhesion in vitro, which depended on cell-surface heparan sulfate proteoglycans. These data, together with the observation on the short-term engraftment of MSCs, suggest that the long-term patency of cellular grafts may be attributed to the antithrombogenic property of MSCs. These results demonstrate several favorable characteristics of nanofibrous scaffolds, the excellent patency of small-diameter nanofibrous vascular grafts, and the unique antithrombogenic property of MSCs.
Nanobodies as novel agents for cancer therapy (2005)

Nanobodies are the smallest fragments of naturally occurring heavy-chain antibodies that have evolved to be fully functional in the absence of a light chain. As such, the cloning and selection of antigen-specific nanobodies obviate the need for construction and screening of large libraries, and for lengthy and unpredictable in vitro affinity maturation steps. The unique and well-characterised properties enable nanobodies to excel conventional therapeutic antibodies in terms of recognising uncommon or hidden epitopes, binding into cavities or active sites of protein targets, tailoring of half-life, drug format flexibility, low immunogenic potential and ease of manufacture. Moreover, the favourable biophysical and pharmacological properties of nanobodies, together with the ease of formatting them into multifunctional protein therapeutics, leaves them ideally placed as a new generation of antibody-based therapeutics. This review describes the state of the art on nanobodies and illustrates their potential as cancer therapeutic agents.
Expanded GAA repeats impede transcription elongation through theFXNgene and induce transcriptional silencing that is restricted to theFXNlocus (2015)

Friedreich's ataxia (FRDA) is a severe neurodegenerative disease caused by homozygous expansion of the guanine-adenine-adenine (GAA) repeats in intron 1 of the FXN gene leading to transcriptional repression of frataxin expression. Post-translational histone modifications that typify heterochromatin are enriched in the vicinity of the repeats, whereas active chromatin marks in this region are underrepresented in FRDA samples. Yet, the immediate effect of the expanded repeats on transcription progression through FXN and their long-range effect on the surrounding genomic context are two critical questions that remain unanswered in the molecular pathogenesis of FRDA. To address these questions, we conducted next-generation RNA sequencing of a large cohort of FRDA and control primary fibroblasts. This comprehensive analysis revealed that the GAA-induced silencing effect does not influence expression of neighboring genes upstream or downstream of FXN. Furthermore, no long-range silencing effects were detected across a large portion of chromosome 9. Additionally, results of chromatin immunoprecipitation studies confirmed that histone modifications associated with repressed transcription are confined to the FXN locus. Finally, deep sequencing of FXN pre-mRNA molecules revealed a pronounced defect in the transcription elongation rate in FRDA cells when compared with controls. These results indicate that approaches aimed to reactivate frataxin expression should simultaneously address deficits in transcription initiation and elongation at the FXN locus.
The regenerative dialysis (REDY) sorbent system (1998)

SUMMARY: The concept of regenerating the spent hemodialysate instead of discarding it was first suggested by A. Johnson in 1966. Drs M. Maxwell and A. Gordon felt that development of the concept could provide information on uremic toxins and lead to a wearable artificial kidney. Suitable sorbents consisting of zirconium phosphate, hydrated zirconium oxide and carbon combined with urease were placed in a cartridge by Dr. L. Marantz. Uremic dogs were successfully maintained using this cartridge to regenerate the hemodialysate. After completion of human studies the system was placed on the market in 1973. Three major problems occurred in the first year of marketing: 1. Displacement of the urease by the liquid in the Cordis‐Dow dialysers. 2. Deafness after use with an unrinsed dialyser. 3. Inactivation of the urease by copper in the water supply. They were resolved by emptying the Cordis‐Dow dialyser, rinsing all dialyser before use and adding a scavenger layer to the cartridge. At first the major market for the REDY System was the home market. However, as this market shrank the major market became dialysis of the acute renal failure patient. After it was found that the eluant from the cartridge sometimes contained aluminium, the alumina in the zirconium layers was removed and the present cartridge no longed contributes aluminium to the dialysate but also can be used to remove aluminium from hemodialysate. Attempts have been made to use the system to develop a wearable kidney.
Identification and regional localization of DNA markers on chromosome 7 for the cloning of the cystic fibrosis gene. (1988)

To facilitate mapping of the cystic fibrosis locus (CF) and to isolate the corresponding gene, we have screened a flow-sorted chromosome 7-specific library for additional DNA markers in the 7q31-q32 region. Unique ("single-copy") DNA segments were selected from the library and used in hybridization analysis with a panel of somatic cell hybrids containing various portions of human chromosome 7 and patient cell lines with deletion of this chromosome. A total of 258 chromosome 7-specific single-copy DNA segments were identified, and most of them localized to subregions. Fifty three of these corresponded to DNA sequences in the 7q31-q32 region. Family and physical mapping studies showed that two of the DNA markers, D7S122 and D7S340, are in close linkage with CF. The data also showed that D7S122 and D7S340 map between MET and D7S8, the two genetic markers known to be on opposite sides of CF. The study thus reaffirms the general strategy in approaching a disease locus on the basis of chromosome location.
Reversal of physiological stress-induced resistance to topoisomerase II inhibitors using an inducible phosphorylation site-deficient mutant of I kappa B alpha. (2001)

Physiological stress conditions associated with the tumor microenvironment play a role in resistance to anticancer therapy. In this study, treatment of EMT6 mouse mammary tumor cells with hypoxia or the chemical stress agents brefeldin A (BFA) or okadaic acid (OA) causes the development of resistance to the topoisomerase II inhibitor etoposide. The mechanism of physiological stress-induced drug resistance may involve the activation of stress-responsive proteins and transcription factors. Our previous work shows that treatment with BFA or OA causes activation of the nuclear transcription factor NF-kappa B. Pretreatment with the proteasome inhibitor carbobenzyoxyl-leucinyl-leucinyl-leucinal inhibits stress-induced NF-kappa B activation and reverses BFA-induced drug resistance. To test whether NF-kappa B specifically mediates stress-induced drug resistance, an inducible phosphorylation site-deficient mutant of I kappa B alpha (I kappa B alpha M, S32/36A) was introduced into EMT6 cells. In this study, we show that I kappa B alpha M expression inhibits stress-induced NF-kappa B activation and prevents BFA-, hypoxia-, and OA-induced resistance to etoposide. These results indicate that NF-kappa B activation mediates both chemical and physiological drug resistance to etoposide. Furthermore, they imply that coadministration of agents that inhibit NF-kappa B may enhance the efficacy of topoisomerase II inhibitors in clinical cancer chemotherapy.
Fuzzy Feedback Linearizing Controller and Its Equivalence With the Fuzzy Nonlinear Internal Model Control Structure (2007)

Fuzzy Feedback Linearizing Controller and Its Equivalence With the Fuzzy Nonlinear Internal Model Control Structure This paper examines the inverse control problem of nonlinear systems with stable dynamics using a fuzzy modeling approach. Indeed, based on the ability of fuzzy systems to approximate any nonlinear mapping, the nonlinear system is represented by a Takagi-Sugeno ( TS ) fuzzy system, which is then inverted for designing a fuzzy controller. As an application of the proposed inverse control methodology, two popular control structures, namely, feedback linearization and Nonlinear Internal Model Control (NIMC) are investigated. Moreover, the paper points out that, under some conditions, both of the control structures are equivalent and naturally implement a Smith predictor in the presence of time delays.
Suppression of Human Cytotoxic T Lymphocyte Responses by Adherent Peripheral Blood Leukocytes (1988)

Cytotoxic T lymphocyte (CTL) responses to HLA alloantigens are unexpectedly weak compared to the CTL response to influenza virus. Allogeneic CTL activity was increased dramatically by removal of a Leu M3+ cell with adherence properties. The Leu M3+-enriched population was capable of suppressing the allogeneic-CTL response. Precultured cells suppressed both allogeneic and influenza-specific CTL responses. Inactivation of suppression was achieved by addition of influenza virus to the cultures in which suppressor activity was generated. A high proportion of asymptomatic HIV-seropositive and AIDS patients, as well as one high-risk group appear to have lost suppressor-cell activity. These findings are discussed with respect to the possible role of this suppressor system in transplantation immunology and the T cell-immune abnormalities observed in development of AIDS.
Proximity based IoT device authentication (2017)

Internet of Things (IoT) devices are largely embedded devices which lack a sophisticated user interface, e.g., touch screen, keyboard, etc. As a consequence, traditional Pre-Shared Key (PSK) based authentication for mobile devices becomes difficult to apply. For example, according to our study on home automation devices which leverage smartphone for PSK input, the current process does not protect against active impersonating attack and also leaks the Wi-Fi password to eavesdroppers, i.e., currently these IoT devices can be exploited to enter into critical infrastructures, e.g., home networks. Motivated by this real-world security vulnerability, in this paper we propose a novel proximity-based mechanism for IoT device authentication, called Move2Auth, for the purpose of enhancing IoT device security. In Move2Auth, we require user to hold smartphone and perform one of two hand-gestures (moving towards and away, and rotating) in front of IoT device. By combining (1) large RSS-variation and (2) matching between RSS-trace and smartphone sensor-trace, Move2Auth can reliably detect proximity and authenticate IoT device accordingly. Based on our implementation on Samsung Galaxy smartphone and commodity Wi-Fi adapter, we prove Move2Auth can protect against powerful active attack, i.e., the false-positive rate is consistently lower than 0.5%.
PAST: PALEONTOLOGICAL STATISTICAL SOFTWARE PACKAGE FOR EDUCATION AND DATA ANALYSIS (2001)

A comprehensive, but simple-to-use software package for executing a range of standard numerical analysis and operations used in quantitative paleontology has been developed. The program, called PAST (PAleontological STatistics), runs on standard Windows computers and is available free of charge. PAST integrates spreadsheet-type data entry with univariate and multivariate statistics, curve fitting, timeseries analysis, data plotting, and simple phylogenetic analysis. Many of the functions are specific to paleontology and ecology, and these functions are not found in standard, more extensive, statistical packages. PAST also includes fourteen case studies (data files and exercises) illustrating use of the program for paleontological problems, making it a complete educational package for courses in quantitative methods.
Model based, sensor directed remediation of underground storage tanks (2002)

Experimental investigations into the application of intelligent robot control technology to the problem of removing waste stored in tanks are described, with particular attention paid to the computing and software environment. Intelligent system control is achieved through the integration of extensive geometric and kinematic world models with real-time sensor-based control. All operator interactions with the system are through fully animated, graphical representations, which validate all operator commands before execution to provide for safe operation. Sensing is used to add information to the robot system's world model and to allow sensor-based servocontrol during selected operations. The results of a first critical features test are reported, and the potential for applying advanced intelligent control concepts to the removal of waste in storage tanks is discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Heat shock induces the release of fibroblast growth factor 1 from NIH 3T3 cells. (1992)

Fibroblast growth factor 1 (FGF-1) is a potent angiogenic and neurotrophic factor whose structure lacks a classical signal sequence for secretion. Although the initiation of these biological activities involves the interaction between FGF-1 and cell surface receptors, the mechanism responsible for the regulation of FGF-1 secretion is unknown. We report that murine NIH 3T3 cells transfected with a synthetic gene encoding FGF-1 secrete FGF-1 into their conditioned medium in response to heat shock. The form of FGF-1 released by NIH 3T3 cells in response to increased temperature (42 degrees C, 2 hr) in vitro is not biologically active and does not associate with either heparin or the extracellular NIH 3T3 monolayer matrix. However, it was possible to derive biologically active FGF-1 from the conditioned medium of heat-shocked NIH 3T3 cell transfectants by ammonium sulfate fractionation. The form of FGF-1 exposed by ammonium sulfate fractionation is similar in size to cytosolic FGF-1 and can bind and be eluted from immobilized heparin similarly to the recombinant human FGF-1 polypeptide. Further, the release of FGF-1 by NIH 3T3 cell transfectants in response to heat shock is reduced significantly by both actinomycin D and cycloheximide. These data indicate that increased temperature may upregulate the expression of a factor responsible for the secretion of FGF-1 as a biologically inactive complex that requires an activation step to exhibit the biological activity of the extracellular polypeptide mitogen.
The Effect of Steroids on Radiation-Induced Lung Disease in the Rat (1993)

We have used a model of bilateral radiation-induced lung disease in the rat to study the effects of corticosteroids. This model is characterized by interstitial edema at 2 weeks after radiotherapy followed by florid alveolitis with an alveolar protein leak which peaks at 4 weeks. Mast cell density peaks at 7 weeks, and there is a progressive increase in lung collagen (fibrosis) from 5 to 20 weeks. Intraperitoneal corticosteroids or saline were given at the time of irradiation or sham irradiation (protocol 1), every second day during weeks 3 and 4 (protocol 2), or three times weekly during weeks 3 to 8 (protocol 3). In protocol 1, steroids protected the lung from interstitial edema at 2 weeks, delayed the alveolitis without reducing its intensity, and significantly reduced the alveolar protein leak. However, radiation fibrosis was not reduced at 20 weeks. Longer steroid administration (protocol 2) suppressed the alveolar protein leak and delayed and significantly reduced the severity of the inflammatory cell response. Although the tissue mast cell and fibrotic responses were suppressed during and for at least 3 weeks after steroids, the ultimate fibrotic reaction was the same in both irradiated groups. In protocol 3, steroids suppressed the alveolitis and delayed the rise in tissue mast cell density, but did not affect the fibrotic response at 20 weeks. These studies suggest that steroids can suppress the alveolitis provided they are used throughout the period of alveolitis. Although they also delay the tissue mast cell response to radiation, the ultimate fibrosis is not altered. This provides further evidence for the dissociation of alveolitis and fibrosis after lung irradiation and has potential implications for management of radiation-induced lung disease in humans.
Serologic cross-reactions among Ehrlichia equi, Ehrlichia phagocytophila, and human granulocytic Ehrlichia (1995)

Homology in the 16S rDNAs shows that the agent of human granulocytic ehrlichiosis (HGE) is closely related to the veterinary pathogens Erlichia equi and Erlichia phagocytophila. After HGE, patients develop antibodies reactive with E. equi and E. phagocytophila; thus, we hypothesized that these species are closely related and share significant antigenicity. Antisera from humans, horses, dogs, and cattle were tested by indirect fluorescent-antibody assay (IFA) for antibodies reactive with E. equi and other ehrlichiae and tested by immunoblot to identify the specific reactions with E. equi. All convalescent-phase sera from human patients with HGE and from animals infected or immunized with E. equi or E. phagocytophila had antibodies reactive with E. equi by IFA; no reactions with Ehrlichia chaffeensis occurred with these sera, and only one horse naturally infected with E. equi had a serologic reaction against Ehrlichia sennetsu. Human and animal sera obtained after infection or immunization with other Ehrlichia, Rickettsia, and Bartonella species did not react with E. equi by IFA. E. equi immunoblots revealed as many as 19 bands with equine anti-E. equi serum. All HGE agent, E. equi, and E. phagocytophila antisera tested reacted with a 44-kDa antigen of E. equi, while other anti-Ehrlichia spp. sera reacted with this antigen rarely or not at all. HGE agent, E. equi, and E. phagocytophila antisera but not other sera also reacted occasionally with 25-, 42-, and 100-kDa antigens. Most sera reacted with antigens between approximately 56 and 75 kDa, probably heat shock proteins. The HGE agent, E. equi, and E. phagocytophila share significant antigenicity by IFA and immunoblot. Coupled with the nearly identical nucleotide sequences of 16S rRNA genes, these data indicate that E. equi, E. phagocytophila, and the human granulocytic ehrlichia are closely related or identical species.
Porous Silicon: From Luminescence to LEDs (1997)

Silicon is at the heart of the microelectronics revolution. Its dominance over other semiconductors is intimately tied to its superior materials and processing properties and to the tremendous base of technology that has developed around it. Another semiconductor is not likely to displace silicon as the material of choice in electronic applications. Silicon, however, is an extremely inefficient light emitter, and for this reason has not enjoyed the same level of dominance in optical applications.
Cellular markers that distinguish the phases of hemangioma during infancy and childhood. (1994)

Hemangiomas, localized tumors of blood vessels, appear in approximately 10-12% of Caucasian infants. These lesions are characterized by a rapid proliferation of capillaries for the first year (proliferating phase), followed by slow, inevitable, regression of the tumor over the ensuing 1-5 yr (involuting phase), and continual improvement until 6-12 yr of age (involuted phase). To delineate the clinically observed growth phases of hemangiomas at a cellular level, we undertook an immunohistochemical analysis using nine independent markers. The proliferating phase was defined by high expression of proliferating cell nuclear antigen, type IV collagenase, and vascular endothelial growth factor. Elevated expression of the tissue inhibitor of metalloproteinase, TIMP 1, an inhibitor of new blood vessel formation, was observed exclusively in the involuting phase. High expression of basic fibroblast growth factor (bFGF) and urokinase was present in the proliferating and involuting phases. There was coexpression of bFGF and endothelial phenotypic markers CD31 and von Willebrand factor in the proliferating phase. These results provide an objective basis for staging hemangiomas and may be used to evaluate pharmacological agents, such as corticosteroids and interferon alfa-2a, which accelerate regression of hemangiomas. By contrast, vascular malformations do not express proliferating cell nuclear antigen, vascular endothelial growth factor, bFGF, type IV collagenase, and urokinase. These data demonstrate immunohistochemical differences between proliferating hemangiomas and vascular malformations which reflect the biological distinctions between these vascular lesions.