gebhart/patrepeval huggingface dataset:
Antiidiotypic antibody vaccine in murine Schistosomiasis mansoni comprising the internal image of antigen. (1989)

This study presents the characterization of an experimental immunotherapeutic approach for schistosomiasis utilizing antiidiotypic antibodies. Antiidiotype (31-3B6) was generated in rabbits using a protective murine monoclonal antibody 31-3B6 which recognizes a 68,000-D molecular mass glycoprotein present in extracts of Schistosomiasis mansoni adult worm homogenetics. Immunization of mice with antiidiotype (31-3B6) before S. mansoni cercariae infection resulted in protection levels ranging from 16 to 41% depending on the route of administration of antiidiotypic antibody and the use of adjuvant. Levels of protection as high as 25% could be obtained with a single injection of antiidiotype (31-3B6) without the use of adjuvant. Animals noted to be resistant to infection with S. mansoni cercariae were also noted to exhibit a humoral immune response that bound components of S. mansoni adult worm homogenetics. This induced antiantigen immune response was shown to bind to the surface of S. mansoni schistosoma by indirect immunofluorescence. Further characterization of the induced antiantigen response showed that a portion (3-32%) of the induced humoral immune response portrayed the binding specificities of the murine monoclonal antibody 31-3B6. The data indicate that antiidiotype antibodies generated utilizing defined monoclonal antibodies can act as surrogate antigens in the protection of infection in schistosomiasis.
Therapeutic potential of klotho–FGF23 fusion polypeptides: WO2009095372 (2010)

The molecular interaction of fibroblast growth factor 23 (FGF23) and klotho is essential for physiologic regulation of phosphate balance. In the absence of klotho, the FGF23 protein cannot exert its physiologic functions, as demonstrated by in vivo mouse genetic studies. Bioactive FGF23 protein loses its phosphate lowering effects in genetically modified mice with no klotho activity. The FGF23-klotho system not only affects phosphate homeostasis but can also influence parathyroid hormone (PTH) and vitamin D activities. Dysregulation of the FGF23-klotho system is noted in a number of human acquired and genetic diseases, including chronic kidney disease. Vitamin D is a strong inducer of both FGF23 and klotho expression, while FGF23 can suppress the renal expression of 1alpha(OH)ase to reduce 1,25(OH)(2)D activity. An understanding of the complex interactions of phosphate, vitamin D and PTH with the FGF23-klotho system has paved the way to explore the therapeutic benefits of modulating the FGF23-klotho system in diseases associated with abnormal mineral ion balance. The patent (WO2009095372) under discussion proposes using fusion polypeptides to manipulate the FGF23-klotho system.
Inhibition of Azoxymethane‐initiated Colon Tumor by Bovine Lactoferrin Administration in F344 Rats (1997)

The influence of bovine lactoferrin (bLF) on colon carcinogenesis was investigated in male F344 rats treated with azoxymethane (AOM). Following three weekly injections of AOM, the animals received 2 or 0.2% bLF for 36 weeks. No effects indicative of toxicity were noted, but significant reduction in both the incidence and number of adenocarcinomas of the large intestine was observed with both doses. Thus, the incidences of adenocarcinomas in the groups receiving 2% and 0.2% bLF were 15% and 25%, respectively, in contrast to the 57.5% control value (P < 0.01 and P < 0.05, respectively). The results indicate that bLF might find application for chemoprevention of colon cancer.
Relationship between cystic fibrosis respiratory tract bacterial communities and age, genotype, antibiotics and Pseudomonas aeruginosa (2010)

Polymicrobial bronchopulmonary infections in cystic fibrosis (CF) cause progressive lung damage and death. Although the arrival of Pseudomonas aeruginosa often heralds a more rapid rate of pulmonary decline, there is significant inter-individual variation in the rate of decline, the causes of which remain poorly understood. By coupling culture-independent methods with ecological analyses, we discovered correlations between bacterial community profiles and clinical disease markers in respiratory tracts of 45 children with CF. Bacterial community complexity was inversely correlated with patient age, presence of P. aeruginosa and antibiotic exposure, and was related to CF genotype. Strikingly, bacterial communities lacking P. aeruginosa were much more similar to each other than were those containing P. aeruginosa, regardless of antibiotic exposure. This suggests that community composition might be a better predictor of disease progression than the presence of P. aeruginosa alone and deserves further study.
Adaptive antennas: the calibration problem (2004)

Adaptive antennas are recognized as a means of increasing the performance of communications systems. However, practical realization of such systems relies on suitable calibration of distortion effects caused by the circuitry and antenna structures. This work presents a detailed analysis of the classes of distortion that degrade the performance of adaptive antennas. This uses the results of an adaptive antenna testbed employing an eight-element circular array to illustrate the impact of temperature on performance. Design techniques that aid calibration are then described. In particular, digital downconversion, array design, harmonic sampling, sample clock dither, and clock management are discussed as a means of designing an adaptive array with the calibration problem in mind.
Prevention of Adenoviral Acute Respiratory Disease in Army Recruits: (1998)

Vaccination of Army recruits by any schedule was cost-saving due to the high level of prevented disease and averted hospitalizations. Even though a seasonally targeted program provided the greatest cost-savings, year-round vaccination must remain an option due to the potential for adenoviral ARD outbreaks in the low-risk period.
Synthetic oligonucleotide expressed by a recombinant vaccinia virus elicits therapeutic CTL. (1995)

P815A is a naturally occurring tumor rejection Ag of the methylcholanthrene-induced murine mastocytoma P815. The gene encoding the Ag P815A, designated P1A, is identical to that encoded in the normal genome of the DBA/2 mouse. A recombinant vaccinia virus (rVV) was constructed that expressed a synthetic oligonucleotide encoding the minimal determinant peptide of the tumor-associated Ag. Although the rVV recombinant expressing this mini-gene was recognized efficiently in vitro, it was an ineffective immunogen in vivo. The addition of an endoplasmic reticulum insertion signal sequence to the NH2 terminus of the minimal determinant resulted in a rVV that elicited CD8+ T cells that could lyse P815 mastocytoma cells in vitro and that were therapeutic in vivo. Recombinant viruses expressing synthetic oligonucleotide sequences preceded by the insertion signal sequences allow the expression of Ag directly into the endoplasmic reticulum, where binding to MHC class I molecules is most efficient. Vaccines based on synthetic oligonucleotides could be constructed with ease and rapidity but, most importantly, such constructs avoid the dangers associated with the expression of full length genes encoding TAA that are potentially oncogenic.
Advancement of opioid analgesia with controlled‐release oxycodone (2001)

Optimal pharmacologic management of pain requires selection of the appropriate analgesic drug, prescription of the appropriate dose, administration of the analgesic by the appropriate route, scheduling of the appropriate dosing interval, prevention of persistent pain and relief of breakthrough pain, aggressive titration of the dose of the analgesic, prevention, anticipation, and management of analgesic side-effects, use of appropriate co-analgesic drugs, and consideration of sequential trials of opioid analgesics. Controlled-release oxycodone (CRO) has the characteristics of an 'ideal' opioid analgesic drug: short half-life, long duration of action, predictable pharmacokinetics, absence of clinically active metabolites, rapid onset of action, easy titration, no ceiling dose, minimal adverse effects, and minimal associated stigma. CRO has been shown to be effective in the control of pain caused by cancer, osteoarthritis, post-herpetic neuralgia, major surgery, and degenerative spine disease.
Virtual reality: through the new looking glass (1993)

From the Publisher:
The revised edition of a 22,000-copy bestseller, much-praised as an authoritative, easy-to-understand overview of virtual reality. VR allows people to experience computer-generated worlds. Since the publication of the first edition of this book, VR has gone more mainstream. This edition covers the latest in VR applications, developments at VR companies, and up-to-the-minute information on Pentium-based VR systems.
Subfoveal Choroidal Neovascular Membranes in Age-Related Macular Degeneration (1986)

We determined the visual prognosis of 94 eyes in 92 patients having age-related macular degeneration, a discrete choroidal neovascular membrane directly under the center of the foveal avascular zone (subfoveal), and an initial visual acuity of 20/100 or better. Of the patients who were reexamined 24 months following their initial presentation, 77% had lost at least four lines of vision and 64% had lost at least six lines. Estimation of visual loss using a conservative assessment procedure showed four-line visual loss in 65% of the patients and six-line loss in 50%. In general, the better the visual acuity at the initial examination, the more likely the patient was to have a smaller choroidal neovascular membrane. These results suggest that it may be reasonable to consider a randomized clinical trial of laser photocoagulation for this group of patients with a relatively poor visual prognosis.
Synthesis, Structure, and Reactivity of Enediyne Macrocycles (1996)

The reaction of bis-propargyl bromide enediyne 4 with weakly basic nucleophiles allows the facile synthesis of acyclic and macrocyclic enediynes. Depending on the bis-nucleophile employed, 12- to 16-membered enediyne macrocycles were obtained. The thermal stability of the new cyclic enediynes was investigated by differential scanning calorimetry. Upon coordination of the macrocycle 5c with Hg(O(2)CCF(3))(2), a drop of the enediyne cyclization temperature of nearly 100 K was observed.
Modification of Gene Expression in Ripening Fruit (1991)

Fruit ripening is a coordinated series of biochemical changes that renders the fruit attractive to eat. The fruit may soften, develop colour, change starch or acid into sugar, become flavoursome, produce more ethylene, increase in sensitivity to ethylene, and respire more rapidly. This syndrome is under contemporary genetic control as illustrated by mutants with fruit that develop normally but lack the ability to ripen, or are deficient or modified in an aspect of ripening. Molecular analysis has revealed changes in gene expression in ripening avocado, tomato, pear and apple fruits. Genes encoding β-1, 4-glucanase (avocado), polygalacturonase (tomato) and trypsin inhibitor (tomato) are among those whose expression increases through ripening. To modify the softening of tomato fruits, antisense constructs with constitutive promoters have been used to reduce the apparent expression of the polygalacturonase gene. The experiments confirmed a role for polygalacturonase in fruit softening but a need for other inputs was also indicated. In experiments using chimaeric genes, the coding sequence of polygalacturonase linked to a fruit-specific and ethylene-sensitive promoter was introduced into the rin tomato genome. Rin plants have fruit which do not ripen or accumulate polygalacturonase. The transformed rin fruit accumulated polygalacturonase but did not ripen or soften. This experiment confirms conclusions drawn from the use of antisense constructs that polygalacturonase action is not the sole determinant of texture changes in ripening tomatoes. Ethylene has a key role throughout ripening. The molecular biology of ethylene production and perception is gradually unfolding. A cDNA for ACC synthase for zucchini, a small gene family whose expression correlated with Ethylene Forming Enzyme (EFE) activity, and a consensus sequence in promoters that are ethylene sensitive have all been described. There is accumulating evidence that some of these sequences and the polygalacturonase sequence are conserved between species, and this will be useful in extending the presently available information.
Splanchnic ischemia and gut mucosal injury in sepsis and the multiple organ dysfunction syndrome. (1996)

The incidence of multiple organ failure syndrome (MOFS) has increased dramatically in most intensive care units (ICU) in the United States and is now the leading cause of death after sepsis, trauma, and burns (1). Despite advances in resuscitation, availability of potent antibiotics, and modern techniques of organ support (2), the survival of critically ill patients with MOFS has not significantly improved since the syndrome was first described over 2 decades ago (3). In the ICU, the monitoring and management of critically ill patients with MOFS has relied, in large part, on readily available measurements of global hemodynamics and oxygen transport. Given the increased understanding of the special role of splanchnic hypoperfusion in the pathophysiology of sepsis and MOFS (4-5), investigators have focused more recently on regional blood flow and oxygen metabolism in these patients (6). In this article, we first present a clinical overview of sepsis and MOFS. Current concepts of the pathogenesis and pathophysiology of MOFS are discussed, with particular emphasis on the roles of splanchnic ischemia and gut barrier failure in the development of both sepsis and the maintenance of the systemic inflammatory response that leads to MOFS. Alterations in both global and regional oxygen transport in septic shock are described to emphasize the limitations of global monitoring in the assessment of splanchnic tissue oxygenation. The role of gastric tonometry in the monitoring of splanchnic oxygenation and its utility in critically ill patients is then analyzed. In addition, the effects and clinical implications of commonly used vasoactive agents on intestinal oxygenation are discussed. Finally, novel therapeutic strategies based on the "gut-origin hypothesis" of MOFS are reviewed.
Monocyte Chemoattractant Protein-1 and Macrophage Inflammatory Protein-1α as Possible Biomarkers for the Chronic Pelvic Pain Syndrome (2008)

Monocyte chemoattractant protein 1 and macrophage inflammatory protein-1alpha within the prostatic fluid in both chronic pelvic pain syndrome subtypes provide candidate future biomarkers for chronic pelvic pain syndrome. In addition, macrophage inflammatory protein-1alpha increase in expressed prostatic secretions provides a new marker for clinical pain in chronic pelvic pain syndrome patients. Given these findings prostatic dysfunction likely has a role in the pathophysiology of this syndrome. These chemokines may serve as effective diagnostic markers and modulators against the chemokines could provide an attractive treatment strategy in individuals with chronic pelvic pain syndrome.
Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1 (1991)

Murine IgM monoclonal antibody STRO-1 identifies a cell surface antigen expressed by stromal elements in human bone marrow (BM). STRO-1 binds to approximately 10% of BM mononuclear cells, greater than 95% of which are nucleated erythroid precursors, but does not react with committed progenitor cells (colony-forming unit granulocyte-macrophage [CFU-GM], erythroid bursts [BFU-E], and mixed colonies [CFU-Mix]). Fibroblast colony-forming cells (CFU-F) are present exclusively in the STRO-1+ population. Dual-color cell sorting using STRO-1 in combination with antibody to glycophorin A yields a population approximately 100-fold enriched in CFU-F in the STRO-1+/glycophorin A- population. When plated under long-term BM culture (LTBMC) conditions, STRO-1+ cells generate adherent cell layers containing multiple stromal cell types, including adipocytes, smooth muscle cells, and fibroblastic elements. STRO-1+ cells isolated from LTBMC at later times retain the capacity to generate adherent layers with a cellular composition identical to that of the parent cultures. The STRO-1-selected adherent layers are able to support the generation of clonogenic cells and mature hematopoietic cells from a population of CD34+ cells highly enriched in so-called long-term culture-initiating cells. We conclude that antibody STRO-1 binds to BM stromal elements with the capacity to transfer the hematopoietic microenvironment in vitro.
Targeted Sequencing of Cancer-Related Genes in Colorectal Cancer Using Next-Generation Sequencing (2013)

Recent advance in sequencing technology has enabled comprehensive profiling of genetic alterations in cancer. We have established a targeted sequencing platform using next-generation sequencing (NGS) technology for clinical use, which can provide mutation and copy number variation data. NGS was performed with paired-end library enriched with exons of 183 cancer-related genes. Normal and tumor tissue pairs of 60 colorectal adenocarcinomas were used to test feasibility. Somatic mutation and copy number alteration were analyzed. A total of 526 somatic non-synonymous sequence variations were found in 113 genes. Among these, 278 single nucleotide variations were 232 different somatic point mutations. 216 SNV were 79 known single nucleotide polymorphisms in the dbSNP. 32 indels were 28 different indel mutations. Median number of mutated gene per tumor was 4 (range 0-23). Copy number gain (>X2 fold) was found in 65 genes in 40 patients, whereas copy number loss (<X0.5 fold) was found in 103 genes in 39 patients. The most frequently altered genes (mutation and/or copy number alteration) were APC in 35 patients (58%), TP53 in 34 (57%), and KRAS in 24 (40%). Altered gene list revealed ErbB signaling pathway as the most commonly involved pathway (25 patients, 42%). Targeted sequencing platform using NGS technology is feasible for clinical use and provides comprehensive genetic alteration data.
Evidence for Thiol-Dependent Production of Oxygen Radicals by 4-Methyl-5-pyrazinyl-3H-1,2-dithiole-3-thione (Oltipraz) and 3H-1,2-Dithiole-3-thione:  Possible Relevance to the Anticarcinogenic Properties of 1,2-Dithiole-3-thiones (1997)

1,2-Dithiole-3-thiones are an important class of anticarcinogens that selectively induce cellular production of chemoprotective phase II detoxification enzymes. It is important to identify chemical properties of anticarcinogens that are responsible for this enzyme induction. Previously, the ability of 1,2-dithiole-3-thiones to induce phase II enzymes has been attributed to their electrophilic character. We report here that the anticarcinogenic 1,2-dithiole-3-thiones, oltipraz (4-methyl-5-pyrazinyl-3H-1,2-dithiole-3-thione, 1) and 3H-1,2-dithiole-3-thione (2), in conjunction with thiols, including the biological thiol glutathione, mediate the conversion of molecular oxygen to reactive oxygen radicals. Using a plasmid-based assay that monitors DNA cleavage, we find that 1 and 2, at micromolar concentrations, efficiently cleave DNA and that this cleavage can be suppressed by removal of molecular oxygen, addition of radical scavenging agents (mannitol, methanol, ethanol, and dimethyl sulfoxide), chelators of adventitious trace metals, and the peroxide-destroying enzyme catalase. Taken together, our data suggest that, in these reactions, molecular oxygen is converted to a peroxide species that undergoes a trace metal-catalyzed, Fenton-type reaction to generate oxygen radicals that cleave DNA. Reactive oxygen species are known to be capable of modulating gene expression in mammalian cells; thus, our studies indicate that oxygen radical production by 1,2-dithiole-3-thiones should be considered as a second chemical property, in addition to electrophilicity, that may play a role in the induction of protective phase II enzymes by this promising class of anticarcinogens.
On The Security Of Querying Encrypted Data (2012)

Data security is a serious concern when we migrate data to a cloud DBMS. Database encryption, where sensitive columns are encrypted before they are stored in the cloud, has been proposed as a mechanism to address such data security concerns.The intuitive expectation is that an adversary cannot “learn” anything about the encrypted columns, since she does not have access to the encryption key. However, it turns out that the act of query processing over encrypted data can reveal information that in the worst case can undermine the very purpose of encryption. In this paper, we argue that such information disclosure should not be handled in an ad hoc manner; in particular, query processing over encrypted data requires: 1) a precise contract (in the form of a security model) that specifies what information is permitted to be disclosed during query processing and 2) a query engine that is carefully engineered to meet the contract efficiently. We believe these are important building blocks in designing a “secure” database-as-a-service paradigm. In this paper, we develop a security model for query processing over encrypted data and take the first steps in understanding the space of secure query processing.
Manipulating the germline: its impact on the study of carcinogenesis (2000)

the need for relatively large-scale breeding programmes and CF10 3US, UK the difficulty in identifying subtle or recessive phenotypes.
Factor VIII gene variants and inhibitor risk in African American hemophilia A patients (2015)

African American hemophilia A (HA) patients experience a higher incidence of neutralizing anti-factor VIII (FVIII) antibodies ("inhibitors") vis-à-vis white patients. Nonsynonymous single-nucleotide polymorphisms (ns-SNPs) in the F8 gene encoding FVIII-H484, FVIII-E1241, and FVIII-V2238 are more prevalent in African Americans. This study tested the hypothesis that immune responses to these sites provoke inhibitors. Blood samples were obtained from 174 African American and 198 white HA subjects and their F8 gene sequences determined. Major histocompatibility complex class II binding and T-cell recognition of polymorphic sequences were evaluated using quantitative binding assays and HLA-DRB1 tetramers. Peptides corresponding to 4 common ns-SNPs showed limited binding to 11 HLA-DRB1 proteins. CD4 T cells from 22 subjects treated with FVIII products having sequences at residues FVIII-484, 1241, and 2238 differing from those of putative proteins encoded by their F8 genes did not show high-avidity tetramer binding, whereas positive-control staining of tetanus-specific CD4 T cells was routinely successful. African Americans with an intron-22 inversion mutation showed a 2-3 times-higher inhibitor incidence than whites with the same mutation (odds ratio = 2.3 [1.1-5.0, P = .04]), but this did not correlate with any of the ns-SNPs. We conclude that immune responses to "sequence-mismatched" FVIII products are unlikely to contribute appreciably to the inhibitor incidence in African Americans.