gebhart/patrepeval huggingface dataset:
Recombinant Chimeric Yellow Fever-Dengue Type 2 Virus Is Immunogenic and Protective in Nonhuman Primates (2000)

A chimeric yellow fever (YF)-dengue type 2 (dengue-2) virus (ChimeriVax-D2) was constructed using a recombinant cDNA infectious clone of a YF vaccine strain (YF 17D) as a backbone into which we inserted the premembrane (prM) and envelope (E) genes of dengue-2 virus (strain PUO-218 from a case of dengue fever in Bangkok, Thailand). The chimeric virus was recovered from the supernatant of Vero cells transfected with RNA transcripts and amplified once in these cells to yield a titer of 6.3 log(10) PFU/ml. The ChimeriVax-D2 was not neurovirulent for 4-week-old outbred mice inoculated intracerebrally. This virus was evaluated in rhesus monkeys for its safety (induction of viremia) and protective efficacy (induction of anti-dengue-2 neutralizing antibodies and protection against challenge). In one experiment, groups of non-YF-immune monkeys received graded doses of ChimeriVax-D2; a control group received only the vaccine diluents. All monkeys (except the control group) developed a brief viremia and showed no signs of illness. Sixty-two days postimmunization, animals were challenged with 5.0 log(10) focus forming units (FFU) of a wild-type dengue-2 virus. No viremia (<1.7 log(10) FFU/ml) was detected in any vaccinated group, whereas all animals in the placebo control group developed viremia. All vaccinated monkeys developed neutralizing antibodies in a dose-dependent response. In another experiment, viremia and production of neutralizing antibodies were determined in YF-immune monkeys that received either ChimeriVax-D2 or a wild-type dengue-2 virus. Low viremia was detected in ChimeriVax-D2-inoculated monkeys, whereas all dengue-2-immunized animals became viremic. All of these animals were protected against challenge with a wild-type dengue-2 virus, whereas all YF-immune monkeys and nonimmune controls became viremic upon challenge. Genetic stability of ChimeriVax-D2 was assessed by continuous in vitro passage in VeroPM cells. The titer of ChimeriVax-D2, the attenuated phenotype for 4-week-old mice, and the sequence of the inserted prME genes were unchanged after 18 passages in Vero cells. The high replication efficiency, attenuation phenotype in mice and monkeys, immunogenicity and protective efficacy, and genomic stability of ChimeriVax-D2 justify it as a novel vaccine candidate to be evaluated in humans.
Mapping Health Data: Improved Privacy Protection With Donut Method Geomasking (2010)

A major challenge in mapping health data is protecting patient privacy while maintaining the spatial resolution necessary for spatial surveillance and outbreak identification. A new adaptive geomasking technique, referred to as the donut method, extends current methods of random displacement by ensuring a user-defined minimum level of geoprivacy. In donut method geomasking, each geocoded address is relocated in a random direction by at least a minimum distance, but less than a maximum distance. The authors compared the donut method with current methods of random perturbation and aggregation regarding measures of privacy protection and cluster detection performance by masking multiple disease field simulations under a range of parameters. Both the donut method and random perturbation performed better than aggregation in cluster detection measures. The performance of the donut method in geoprivacy measures was at least 42.7% higher and in cluster detection measures was less than 4.8% lower than that of random perturbation. Results show that the donut method provides a consistently higher level of privacy protection with a minimal decrease in cluster detection performance, especially in areas where the risk to individual geoprivacy is greatest.
Effects of ketotifen on symptoms and on bronchial mucosa in patients with atopic asthma (1997)

Ketotifen is marketed throughout the world as an antiallergy drug, but whether it affects infiltration of inflammatory cells into airway mucosa is not known. We studied the effects of ketotifen on symptoms, pulmonary function, and airway inflammation in 25 patients with atopic asthma. Patients took ketotifen (1 mg twice daily) or a matching placebo for 8 weeks in a double-blind, parallel-group study. Data recorded on diary cards were used for 2 weeks before treatment began, and they were used for the last 2 weeks of treatment to study asthma symptoms, use of beta 2-agonists, and peak expiratory flow (PEF). Pulmonary function tests, bronchial responsiveness to methacholine, and fiberoptic bronchoscopy were performed before and after treatment. Biopsy specimens were obtained by bronchoscopy. Specimens were stained immunohistochemically with monoclonal antibodies against stored eosinophil cationic protein (EG1), the secreted form of eosinophil cationic protein (EG2), mast-cell tryptase (AA1), neutrophil elastase (NP57), CD3, CD4, CD8, and CD25. The numbers of positively stained cells in the lamina propria were counted. Compared with the placebo, the ketotifen-treated group exhibited significant improvement of asthma symptoms (P < 0.05) and bronchial responsiveness (P < 0.05). This was accompanied by a reduction of EG2+ eosinophils (P < 0.05), CD3+ T cells (P < 0.001), CD4+ T cells (P < 0.01), and CD25+ activated T cells (P < 0.01) in the bronchial mucosa. These results suggested that the beneficial effects of ketotifen in bronchial asthma may result from consequent inhibition of activated eosinophils and T-cell recruitment into the airway. Moreover, ketotifen may relieve allergic inflammation in bronchial asthma.
Cooling Ingredients and Their Mechanism of Action (2009)

In Webster’s dictionary, we found the following descriptions: “revulsive”—(i) to pull away and (ii) an act or technique of turning or diverting a disease or blood from a diseased region in one part of the body to another (as by counterirritation); “rubefacient”—substance for external application that causes redness of the skin.
(S)-4,5-Dihydro-2-(2-hydroxy-4-hydroxyphenyl)-4-methyl-4-thiazolecarboxylic Acid Polyethers:  A Solution to Nephrotoxicity (2006)

Previous studies revealed that within a family of ligands the more lipophilic chelators have better iron-clearing efficiency. The larger the log P(app) value of the compound, the better the iron-clearing efficiency. What is also clear from the data is that although the relative effects of log P(app) changes are essentially the same through different families, there are differences in absolute value between families. However, there also exists a second, albeit somewhat more disturbing, relationship. In all sets of ligands, the most lipophilic chelator is always the most toxic. The current study focuses on designing ligands that balance the lipophilicity/toxicity problem while iron-clearing efficiency is maintained. Earlier studies with (S)-4,5-dihydro-2-(2-hydroxy-4-methoxyphenyl)-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(CH(3)O)-DADFT, 6] indicated that this methyl ether was a ligand with excellent iron-clearing efficiency in both rodents and primates; however, it was too toxic. On the basis of this finding, a less lipophilic, more water-soluble ligand than 6 was assembled, (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(HO)-DADFT-PE, 11], a polyether analogue, along with its ethyl and isopropyl esters. The parent polyether and its isopropyl and ethyl esters were all shown to be highly efficient iron chelators in both rodents and primates. A comparison of 11 in rodents with the desferrithiocin analogue (S)-4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(HO)-DADFT, 1] revealed the polyether to be more tolerable, achieving higher concentrations in the liver and significantly lower concentrations in the kidney. The lower renal drug levels are in keeping with the profound difference in the architectural changes seen in the kidney of rodents given 1 versus those treated with 11.
Cross‐linking of the T cell receptor complex with the subset‐specific differentiation antigen stimulates interleukin 2 receptor expression in human CD4 and CD8 T cells (1987)

Nonpolymorphic interactions between the T cell differentiation antigens CD4 or CD8 and major histocompatibility complex (MHC)-encoded molecules have been postulated to participate in antigen recognition of MHC-restricted T cells. This would imply simultaneous binding of CD4/8 and of the T cell receptor complex (Ti/CD3) to MHC molecules on the stimulator or target cell. In this report experimental evidence is provided that simultaneous binding by antibodies of Ti/CD3 and of CD4 or CD8 leads to the expression of interleukin 2 (IL 2) receptors in resting human T cells and to their subsequent proliferation in the presence of recombinant IL 2 (rIL 2). This could be shown by using a novel anti-CD3 monoclonal antibody (BMA 030) which alone only marginally stimulates highly purified human T cells even when applied in cross-linked form. However, human T cell subpopulations could be stimulated to grow in the presence of rIL 2 when BMA 030 was fixed to a solid support in combination with antibodies to either CD4 or CD8. In limiting dilution experiments, the frequencies of CD4 and CD8 T cells activated by the antibody combinations were similar to those activated by phytohemagglutinin in the presence of irradiated adherent cells. No stimulation was achieved if both or one antibody was applied in soluble form. In contrast, soluble antibodies inhibited activation by solid-phase antibodies. Taken together, cross-linking of Ti/CD3 with CD4/8 seems to be essential for T cell activation in cases of ligands that bind but do not activate T cells on their own--a situation that may reflect the interaction of T cell receptors with MHC-encoded molecules in association with antigen.
Privacy-Preserving Inference in Machine Learning Services Using Trusted Execution Environments (2019)

This work presents Origami, which provides privacy-preserving inference for large deep neural network (DNN) models through a combination of enclave execution, cryptographic blinding, interspersed with accelerator-based computation. Origami partitions the ML model into multiple partitions. The first partition receives the encrypted user input within an SGX enclave. The enclave decrypts the input and then applies cryptographic blinding to the input data and the model parameters. Cryptographic blinding is a technique that adds noise to obfuscate data. Origami sends the obfuscated data for computation to an untrusted GPU/CPU. The blinding and de-blinding factors are kept private by the SGX enclave, thereby preventing any adversary from denoising the data, when the computation is offloaded to a GPU/CPU. The computed output is returned to the enclave, which decodes the computation on noisy data using the unblinding factors privately stored within SGX. This process may be repeated for each DNN layer, as has been done in prior work Slalom. However, the overhead of blinding and unblinding the data is a limiting factor to scalability. Origami relies on the empirical observation that the feature maps after the first several layers can not be used, even by a powerful conditional GAN adversary to reconstruct input. Hence, Origami dynamically switches to executing the rest of the DNN layers directly on an accelerator without needing any further cryptographic blinding intervention to preserve privacy. We empirically demonstrate that using Origami, a conditional GAN adversary, even with an unlimited inference budget, cannot reconstruct the input. We implement and demonstrate the performance gains of Origami using the VGG-16 and VGG-19 models. Compared to running the entire VGG-19 model within SGX, Origami inference improves the performance of private inference from 11x while using Slalom to 15.1x.
A practical approach toward maximum likelihood sequence estimation for band-limited nonlinear channels (1983)

A receiver structure, called a maximum likelihood (pseudo MLSE), which approximates MLSE with a simple hardware configuration, was derived. By introducting a tentatively estimated sequence, the pseudo MLSE detects the received symbol by symbol, retaining the MLSE optimum decision property. The number of arithmetic operations required in one symbol duration is reduced from M^{L + 1} to (L + 1)M in an M -ary signaling case with channel memory length L . An adaptation algorithm for the variation in the channel characteristics was also developed. Pseudo MLSE application to quadrature phase shift keying (QPSK) for a band-limited nonlinear channel is described. The most practical application of pseudo MSLE, named the adaptive threshold detector with estimated sequence (ATDES), detects symbols with threshold detection and is suitable for high bit rate operation. For both the pseudo MLSE processor and ATDES, most of the hardware is occupied by a replica memory stored in the receiver. Performance in a typical nonlinear satellite channel model is evaluated by computer simulation. Simulation results show a 0.8 dB improvement by ATDES with 64 replica memories and 1.3 dB improvement by the pseudo MLSE processor with 3072 replica memories. The tentative estimation error effect is estimated to be less than 0.1 dB in the simulated satellite channel.
Simple Methods for Generating and Detecting Locus-Specific Mutations Induced with TALENs in the Zebrafish Genome (2012)

The zebrafish is a powerful experimental system for uncovering gene function in vertebrate organisms. Nevertheless, studies in the zebrafish have been limited by the approaches available for eliminating gene function. Here we present simple and efficient methods for inducing, detecting, and recovering mutations at virtually any locus in the zebrafish. Briefly, double-strand DNA breaks are induced at a locus of interest by synthetic nucleases, called TALENs. Subsequent host repair of the DNA lesions leads to the generation of insertion and deletion mutations at the targeted locus. To detect the induced DNA sequence alterations at targeted loci, genomes are examined using High Resolution Melt Analysis, an efficient and sensitive method for detecting the presence of newly arising sequence polymorphisms. As the DNA binding specificity of a TALEN is determined by a custom designed array of DNA recognition modules, each of which interacts with a single target nucleotide, TALENs with very high target sequence specificities can be easily generated. Using freely accessible reagents and Web-based software, and a very simple cloning strategy, a TALEN that uniquely recognizes a specific pre-determined locus in the zebrafish genome can be generated within days. Here we develop and test the activity of four TALENs directed at different target genes. Using the experimental approach described here, every embryo injected with RNA encoding a TALEN will acquire targeted mutations. Multiple independently arising mutations are produced in each growing embryo, and up to 50% of the host genomes may acquire a targeted mutation. Upon reaching adulthood, approximately 90% of these animals transmit targeted mutations to their progeny. Results presented here indicate the TALENs are highly sequence-specific and produce minimal off-target effects. In all, it takes about two weeks to create a target-specific TALEN and generate growing embryos that harbor an array of germ line mutations at a pre-specified locus.
A role for FGF-8 in the dorsoventral patterning of the zebrafish gastrula (1997)

Signals released from Spemann's organizer, together with ventralizing factors such as BMPs, are necessary to pattern the dorsoventral axis of the vertebrate embryo. We report that a member of the FGF family, fgf-8, not secreted by the axial mesoderm but expressed in a dorsoventral gradient at the margin of the zebrafish gastrula, also contributes to the establishment of the dorsoventral axis of the embryo. Ectopic expression of FGF-8 leads to the expansion of dorsolateral derivatives at the expense of ventral and posterior domains. Moreover, FGF-8 displays some organizer properties as it induces the formation of a partial secondary axis in the absence of factors released from Spemann's organizer territory. Analysis of its interaction with the ventralizing factors, BMPs, reveals that overexpression of FGF-8 inhibits the expression of these factors in the ventral part of the embryo as early as blastula stage, suggesting that FGF-8 acts upstream of BMP2 and BMP4. We conclude that FGF-8 is involved in defining dorsoventral identity and is an important organizing factor responsible for specification of mesodermal and ectodermal dorsolateral territories of the zebrafish gastrula.
Inside the Classroom (and Out): How We Learn through Folklore (2008)

Inside the Classroom (and Out): How We Learn through Folklore. Edited by Kennedi L. Untiedt. Publications of the Texas Society LXII. (Denton: University of North Texas Press, 2005. Pp. xiv + 322, preface, photographs, illustrations, index. $29.95cloth) The twenty-five essays in this collection are linked, for the most part, by a focus on how folklore plays a fundamental role in the learning process in many areas (viii) . Their original dates of composition are not in every case given, but they seem to range from the 1960s to the present day. The articles themselves are a hodgepodge, ranging from scholarly to amateur, from analytic to anecdotal, from classroom pedagogy to undigested collections of texts to nostalgic recollections of Texas schools in the early twentieth century. Perhaps a quarter of the essays have litde apparent relationship to the stated theme of die book, although several of them (including those by Rodenberger and Pinkerton) are effective and moving memoirs of early twentieth century Texas teachers. The book as a whole does not have a clear audience - teachers? folklorists? members of the Texas Society? What the essays do have in common is Texas. Some will hold litde interest for non-Texans. The book is divided into five sections. The Early Years includes two brief and very basic essays/lectures by Mody Boatright and Cynthia Savage on defining folklore, brief articles on the use of folklore in daycare centers and on Boy Scout folklore, an article on using Fauldess Starch pamphlets from the early twentieth as a source for children's folklore, and Barbara Morgan-Fleming's essay Folklore in Schools: Connections Between and Education, a stimulating and useful ethnography of a fifth grade classroom. Morgan-Fleming applies concepts of emergence, framing and linguistic competence to focus on the oral improvisational nature of teaching, in ways that can be direcdy used by teachers to create tradition and community in the classroom. It is the best essay in the book. Part Two, The High School Years, includes a very brief account of a survey of folk medicine beliefs among high school students, collections of folklore related to yearbooks and cheerleaders, and a short piece on perceptions of high school football coaches. Part Three, A Tribute to Paul Patterson, is dedicated to a recendy deceased teacher, storyteller and cowboy poet, derived from a special session at the 1990 Texas Society meeting. A touching tribute to an obviously beloved individual, it bears litde relationship to the rest of the book. Part Four, College Years, includes brief articles on campus ghost stories and on the history of female participation in campus rodeos, a one-page article on black-eyed peas, and a pair of anecdotal memoirs about early Texas educators, and is perhaps the book's greatest disappointment. …
BAK and BAX deletion using zinc‐finger nucleases yields apoptosis‐resistant CHO cells (2009)

Anoxic and metabolic stresses in large-scale cell culture during biopharmaceutical production can induce apoptosis. Strategies designed to ameliorate the problem of apoptosis in cell culture have focused on mRNA knockdown of pro-apoptotic proteins and over-expression of anti-apoptotic ones. Apoptosis in cell culture involves mitochondrial permeabilization by the pro-apoptotic Bak and Bax proteins; activity of either protein is sufficient to permit apoptosis. We demonstrate here the complete and permanent elimination of both the Bak and Bax proteins in combination in Chinese hamster ovary (CHO) cells using zinc-finger nuclease-mediated gene disruption. Zinc-finger nuclease cleavage of BAX and BAK followed by inaccurate DNA repair resulted in knockout of both genes. Cells lacking Bax and Bak grow normally but fail to activate caspases in response to apoptotic stimuli. When grown using scale-down systems under conditions that mimic growth in large-scale bioreactors they are significantly more resistant to apoptosis induced by starvation, staurosporine, and sodium butyrate. When grown under starvation conditions, BAX- and BAK-deleted cells produce two- to fivefold more IgG than wild-type CHO cells. Under normal growth conditions in suspension culture in shake flasks, double-knockout cultures achieve equal or higher cell densities than unmodified wild-type cultures and reach viable cell densities relevant for large-scale industrial protein production.
Biological Markers in DCIS and Risk of Breast Recurrence: A Systematic Review (2011)

Understanding of the biology and clinical behavior of ductal carcinoma in situ (DCIS) is currently inadequate. The aim of this comprehensive review was to identify important molecular biological markers associated with DCIS and candidate markers associated with increased risk of ipsilateral recurrence after diagnosis of DCIS. A comprehensive systematic review was performed to identify studies published in the past 10 years that investigated biological markers in DCIS. To be included in this review, studies that investigated the rate of biological expression of markers had to report on at least 30 patients; studies that analyzed the recurrence risk associated with biomarker expression had to report on at least 50 patients. There were 6,252 patients altogether in our review. Biological markers evaluated included steroid receptors, proliferation markers, cell cycle regulation and apoptotic markers, angiogenesis-related proteins, epidermal growth factor receptor family receptors, extracellular matrix-related proteins, and COX-2. Although the studies in this review provide valuable preliminary information regarding the expression and prognostic significance of biomarkers in DCIS, common limitations of published studies (case-series, cohort, and case-control studies) were that they were limited to small patient cohorts in which the extent of surgery and use of radiotherapy or endocrine therapy varied from patient to patient, and variable methods of determining biomarker expression. These constraints made it difficult to interpret the absolute effect of expression of various biomarkers on risk of local recurrence. No prospective validation studies were identified. As the study of biomarkers are in their relative infancy in DCIS compared with invasive breast cancer, key significant prognostic and predictive markers associated with invasive breast cancer have not been adequately studied in DCIS. There is a critical need for prospective analyses of novel and other known breast cancer molecular markers in large cohorts of patient with DCIS to differentiate indolent from aggressive DCIS and better tailor the need and extent of current therapies.