gebhart/patrepeval huggingface dataset:
Prostate and Bone Fibroblasts Induce Human Prostate Cancer Growth in Vivo: Implications for Bidirectional Tumor-Stromal Cell Interaction in Prostate Carcinoma Growth and Metastasis (1992)

Prostate cancer selectively metastasizes to the axial skeleton to produce osteoblastic lesions, which suggests that bidirectional paracrine interactions exist between prostate cancer and bone cells. To evaluate the role of tumor-stromal cell interaction and stromal-specific growth factors in prostate cancer growth and dissemination, we coinoculated nontumorigenic human prostate cancer cells (LNCaP) and various tissue-specific fibroblasts subcutaneously in athymic mice. LNCaP tumors were induced most consistently by human bone fibroblasts (62%), followed by two prostate fibroblast cell lines (31% and 17%), but not by lung, kidney, or embryonic 3T3 fibroblasts. Carcinomas formed preferentially in male hosts, demonstrating in vivo androgen sensitivity. Immunohistochemical and biochemical techniques confirmed the human prostate component of these tumors and were paralleled by elevations in serum prostate specific antigen. In vitro mitogenic assays revealed a two-to three-fold bidirectional stimulation between LNCaP and bone or prostate fibroblast conditioned media, but not lung, kidney, or 3T3 fibroblast conditioned media. A novel method developed to deliver concentrated bone or prostate fibroblast conditioned media in vivo using a slowly absorbed matrix (gelfoam) also induced tumor formation, emphasizing the importance of fibroblast growth factors in LNCaP tumor formation. Northern analysis identified the stromal compartment as the primary source of extracellular matrix (collagen, fibronectin), while only LNCaP cells expressed transforming growth factor alpha. Although LNCaP and stromal cells express basic fibroblast growth factor (bFGF), the bidirectional paracrine-mediated mitogenic activity between these cells is not inhibited by anti-bFGF antibodies, suggesting that other undefined growth factors may be involved in stimulating LNCaP growth. These observations illustrate the importance of stromal-epithelial interaction in prostate tumor growth and suggest that extracellular matrix and paracrine-mediated growth factors play a role in prostate cancer growth and metastasis.
Understanding Climate Change Patterns with Multivariate Geovisualization (2009)

Climate change has been a challenging and urgent research problem for many related research fields. Climate change trends and patterns are complex, which may involve many factors and vary across space and time. However, most existing visualization and mapping approaches for climate data analysis are limited to one variable or one perspective at a time. For example, it is common to map the surface temperature anomaly at different locations or plot trends of time series. Although such approaches are useful in presenting information and knowledge, they have limited capability to support discovery and understanding of unknown complex patterns from data that span across multiple dimensions. This paper introduces the application of a multivariate geovisualization approach to explore and understand complex climate change patterns across multiple perspectives, including the geographic space, time, and multiple variables.
High-Capacity, Self-Assembled Metal–Oxide–Semiconductor Decoupling Capacitors (2004)

We combine nanometer-scale polymer self assembly with advanced semiconductor microfabrication to produce metal-oxide-semiconductor (MOS) capacitors with accumulation capacitance more than 400% higher than planar devices of the same lateral area. The self assembly technique achieves this degree of enhancement using only standard processing techniques, thereby obviating additional process complexity. These devices are suitable for use as on-chip power supply decoupling capacitors, particularly in high-performance silicon-on-insulator technology.
Autolysed antigen-extracted allogeneic bone for repair of diaphyseal bone defects in rabbits (1990)

Autolysed antigen-extracted allogeneic bone (AAA bone) was used to bridge a large osteoperiosteal gap in the diaphysis of the radius of 50 rabbits. Periodic observations of the graft were made clinically, radiologically and histologically every week up to fourteen weeks. The continuity of the radius was evaluated macroscopically and histologically. The AAA bones were progressively resorbed and replaced by the new bone. The bone remodelled to the mature tubular bone and did not undergo absorption during the experimental period. The AAA bone proceeded to be an osteoinductive and osteoconductive material. There were no appreciable histologic signs of immune or foreign body reaction.
[Classification of asthma based on genetics]. (1995)

Genetic factors may contribute to the development of bronchial asthma. However, results of traditional epidemiological studies have not clarified exactly which genes are involved. Recent advances in molecular genetics have resulted in the discovery of some candidate genes. Although there is still only a little information about the role of these genes in the development of asthma, we attempted to classify asthma based on genetics and here we present one example of such a classification. Classification of asthma based on genetics may be useful in screening for people susceptible to asthma and in developing prophylactic procedures. It may also enhance our understanding of the mechanisms of asthma and may promote the development of new therapeutic strategies.
Hemophilia A (1994)

The dramatic hemorrhages, the effect of the disease on history through its presence in Queen Victoria's descendants, and the devastating role of therapeutic concentrates in the transmission of the acquired immunodeficiency syndrome (AIDS) have made hemophilia A the object of great medical, scientific, and public interest. The commonest hereditary coagulation disorder and a disease without ethnic or geographic limitations, its incidence approaches 20 per 100,000 male births13. John Conrad Otto emphasized its inheritance as an X-linked disorder in his 1803 description of the disease in a New Hampshire family: “males only are subject to this strong affection . . . .
Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization (1989)

Human factor VIII(FVIII) inhibitors are pathologic, circulating antibodies that inactivate FVIII. We have examined the location of epitopes on the FVIII protein for inhibitors from hemophilia A and nonhemophilic individuals. The inhibitors were of type I or type II in the kinetics of their inactivation of FVIII. A cDNA clone of human FVIII was used to express defined FVIII protein fragments in Escherichia coli for immunoblotting with inhibitor plasma. An epitope for 18 heavy-chain inhibitors was localized to the aminoterminal 18.3 Kd of the A2 domain. Two of these inhibitors also recognized an epitope located between A1 and A2 domains. Similarly, an epitope for 23 light- chain inhibitors was localized to the C2 domain. Weaker epitopes for 13 of the same inhibitors within the C1 and C2 domains were also observed. Four of the 23 inhibitors in addition bound strongly to the A3 domain. Most inhibitors (22 of 23) were neutralized in vitro only by the FVIII fragments to which they bound on immunoblots; however, one inhibitor that was neutralized by a fragment containing the A1 domain did not bind to it on immunoblots. Conversely, 3 of 3 inhibitors that bound to the A3 domain and 5 of 15 that bound to the A2 domain were not neutralized by the corresponding fragments. The epitope specificity of an inhibitor did not depend on its source or type. Our results show that FVIII inhibitors bind to limited areas within the heavy and light chains of FVIII. Some inhibitor plasmas contain additional antibodies that may not be inhibitory.
Randomized Controlled Trial of Atomoxetine for Cognitive Dysfunction in Early Huntington Disease (2009)

Atomoxetine demonstrated no advantages over placebo for primary or secondary outcomes. Although atomoxetine was not effective at improving attention at this dose, its safety and tolerability were similar to other studies.
INDUCTIVE AND BAYESIAN LEARNING IN MEDICAL DIAGNOSIS (1993)

Abstract Although successful in medical diagnostic problems, inductive learning systems were not widely accepted in medical practice. In this paper two different approaches to machine learning in medical applications are compared: the system for inductive learning of decision trees Assistant, and the naive Bayesian classifier. Both methodologies were tested in four medical diagnostic problems: localization of primary tumor, prognostics of recurrence of breast cancer, diagnosis of thyroid diseases, and rheumatology. The accuracy of automatically acquired diagnostic knowledge from stored data records is compared, and the interpretation of the knowledge and the explanation ability of the classification process of each system is discussed. Surprisingly, the naive Bayesian classifier is superior to Assistant in classification accuracy and explanation ability, while the interpretation of the acquired knowledge seems to be equally valuable. In addition, two extensions to naive Bayesian classifier are briefly described: dealing with continuous attributes, and discovering the dependencies among attributes.
Magnetic resonance imaging in stage I endometrial carcinoma. (1990)

A prospective study was conducted on 50 consecutive patients with stage I endometrial cancer who had primary surgical treatment. The purpose of the study was to assess the value of magnetic resonance imaging (MRI) for accurate staging of early disease and determination of myometrial invasion. Features identified by MRI were correlated with surgical pathology. Preliminary MRI results provided additional valuable information. All but one of 18 patients with histologically proven deep myometrial invasion were predicted preoperatively by MRI. Of 17 patients with detached fragments of malignant tissue in the endocervical curettage (ECC) but with results inconclusive for actual cervical invasion, MRI revealed all three patients with true cervical tissue involvement. Magnetic resonance imaging detected all six patients with gross extrauterine spread and also precisely measured uterine enlargement by myomata. The extent and location of tumor growth in the uterus could be mapped out in the majority of cases. Based on these findings, a pretreatment MRI scan of the pelvis in presumably stage I endometrial carcinoma resulted in an advance in staging in 18% of the patients, and accurately predicted deep myometrial invasion in 94% of the cases. Inclusion of MRI in the routine work-up in stage I endometrial carcinoma should be considered for proper clinical staging, particularly in patients with a positive but nondiagnostic ECC, uterine papillary serous carcinoma, or grade 3 tumor.
Separate and combined effects of ephedrine and caffeine on protein and lipid deposition in finishing pigs (1995)

Abstract Two experiments were conducted to examine the effects of dietary inclusion of an ephedrine (Eph)/caffeine (Caf) mixture on finishing (55 to 100 kg live weight) castrated male pigs. The first experiment was conducted as a dose-response study and showed that the mixture had an optimal effect on performance and carcass composition at a dietary inclusion level of approximately 56/560 mg/kg of Eph and Caf, respectively. In the second experiment, interactions between the compounds were studied by dietary inclusion of Eph (56 mg/kg) and Caf (560 mg/kg) separately or as a mixture (56/560 mg/kg). The mixture reduced food intake by 0·12 and improved the food: gain ratio by 0·08. Muscle protein deposition rate was increased proportionately by 0·25, lipid accretion rate was decreased proportionately by 0·27, and gross energetic efficiency of energy deposition decreased proportionately by 0·09. This resulted in a changed proportional carcass composition towards more muscle (0·08) and less fat (0·21) after treatment with the mixture. The reduction in food intake was sustained due to an interaction over the first 3 weeks of treatment changing to additive effects by the compounds. The increased muscle protein deposition rate after feeding the mixture was entirely due to Eph, while the decreased gross energetic efficiency of energy deposition was caused by Caf. On the other hand, both compounds contributed almost equally to the decrease in lipid accretion rate. These results show that an Eph/Caf mixture markedly improves performance and body composition in finishing castrated pigs.
Human immunodeficiency virus type 1 Vif- mutant particles from restrictive cells: role of Vif in correct particle assembly and infectivity (1995)

Disruption of the vif gene of human immunodeficiency virus (HIV) type 1 affects virus infectivity to various degrees, depending on the T-cell line used. We have concentrated our studies on true phenotypic Vif- mutant particles produced from CEMx174 or H9 cells. In a single round of infection, Vif- virus is approximately 25 (from CEMx174 cells) to 100 (from H9 cells) times less infectious than wild-type virus produced from these cells or than the Vif- mutant produced from HeLa cells. Vif- virions recovered from restrictive cells, but not from permissive cells, are abnormal both in terms of morphology and viral protein content. Notably, they contain much reduced quantities of envelope proteins and altered quantities of Gag and Pol proteins. Although wild-type and Vif- virions from restrictive cells contain similar quantities of viral RNA, no viral DNA synthesis was detectable after acute infection of target cells with phenotypically Vif- virions. To examine the possible role of Vif in viral entry, attempts were made to rescue the Vif- defect in H9 cells by pseudotyping Vif+ and Vif- HIV particles with amphotropic murine leukemia virus envelope. Vif- particles produced in the presence of HIV envelope could not be propagated when pseudotyped. In contrast, when only the murine leukemia virus envelope was present, significant propagation of Vif- HIV particles could be detected. These results demonstrate that Vif is required for proper assembly of the viral particle and for efficient HIV Env-mediated infection of target cells.
PEA3 Is Necessary for Optimal Epidermal Growth Factor Receptor–Stimulated Matrix Metalloproteinase Expression and Invasion of Ovarian Tumor Cells (2007)

Elevated expression of the epidermal growth factor (EGF) receptor (EGFR) is detected in human ovarian tumors and is associated with decreased recurrence-free and overall survival. EGFR activation affects tumor progression in part by promoting tumor invasion through the induction of prometastatic matrix metalloproteinases (MMP). PEA3, an ETS family transcription factor, is elevated in advanced and metastatic ovarian cancer and regulates MMPs in various cell types, therefore, we investigated whether PEA3 is required for the EGFR-dependent induction of MMP mRNA. MMP-9 and MMP-14 mRNA levels were selectively increased in response to EGFR activity in ovarian tumor cells. EGFR activation resulted in nuclear accumulation of PEA3 and direct binding of PEA3, but not the related protein ETS-1, to the endogenous MMP-9 and MMP-14 promoters. Furthermore, PEA3 overexpression was sufficient to induce MMP-9 and MMP-14 mRNA, tumor cell migration, and invasion, suggesting that PEA3 is an important contributor to the metastatic phenotype. Additionally, inhibition of PEA3 expression via short interfering RNA reduced the EGF induction of MMP-9 and MMP-14 gene expression by 92% and 50%, respectively, and impaired EGF-stimulated tumor cell invasion. These results suggest that PEA3 is regulated by EGFR and that the elevated PEA3 expression detected in human ovarian cancer may divert cells to a more invasive phenotype by regulating MMP-9 and MMP-14.
Recombinant human erythropoietin trial in thalassemia intermedia (1996)

It has been shown that high doses of human recombinant erythropoietin (r epo) increase haemoglobin levels by augmentation of F-cells, and Hb-F production in animal models and in human trials. In this study, r epo was used in patients with beta thalassemia intermedia. Our purpose was to improve haemoglobin levels by at least 2 g and maintain an average level between 10 and 12 g/dl. Ten patients aged 6-29 years (mean 14 +/- 7.6 years) with thalassemia intermedia were treated with r epo. It was given subcutaneously in rising doses from 500 to 1000 U/kg three times weekly for 3 months. During r epo therapy eight cases (80 per cent) showed an increase in haemoglobin, haematocrit, and reticulocyte levels, and an increase of at least 2 g of haemoglobin was obtained. Blood transfusion was not needed during the study except in one case. Five cases (50 per cent) improved life quality with therapy. Hb levels of all patients returned to baseline values over 1 or 2 months after r epo was discontinued. There was no significant change in absolute Hb-F, F-cells, and ferritin levels during treatment. Generally, the drug was well tolerated. No patient had hypertension. Recombinant erythropoietin seems to be an effective treatment for anaemia of beta-thalassemia intermedia, but longer term randomized trials are needed especially in patients with beta thalassemia major.
The tail at scale (2013)

Software techniques that tolerate latency variability are vital to building responsive large-scale Web services.
Balancing Request Denial Probability and Latency in an Agent-Based VPN Architecture (2010)

Agent-based virtual private networks architecture (ABVA) refers to the environment where a third-party provider runs and administers remote access virtual private network (VPN) service for organizations that do not want to maintain their own in-house VPN servers. In this paper, we consider the problem of optimally connecting users of an organization to VPN server locations in an ABVA environment so that request denial probability and latency are balanced. A user request needs a certain bandwidth between the user and the VPN server. The VPN server may deny requests when the bandwidth is insufficient (capacity limitation). At the same time, the latency perceived by a user from its current location to a VPN server is an important consideration. We present a number of schemes regarding how VPN servers are to be selected and the number of servers to be tried so that request denial probability is minimized without unduly affecting latency. These schemes are studied on a number of different topologies. For our study, we consider Poisson and non-Poisson arrival of requests under both finite and infinite population models to understand the impact on the entire system. We found that the arrival processes have a significant and consistent impact on the request denial probability and the impact on the latency is dependent on the traffic load in the infinite model. In the finite model, arrival processes have an inconsistent impact to the request denial probability. As to the latency in the finite model, arrivals that have a squared co-efficient of variation less than one is consistently largest, followed by the Poisson case, then the case that the squared co-efficient of variation is more than one. Finally, a strength of this work is the comparison of infinite and finite models; we found that a mismatch between the infinite and the finite model is dependent both on the number of users in the system and the load.
Development and Installation of an Extended Reach Multilateral Junction (2009)

Abstract A multitude of extended reach technologies have been utilized in the West Sak field on the North Slope of Alaska to reduce surface impact in a remote and environmentally sensitive area. Significant to the shallow heavy oil West Sak development is the use of multilateral horizontal wells with a junction providing mechanical support and both through-tubing lateral isolation and re-entry capabilities. However, as extended reach drilling capabilities evolved to routinely reach departure to true vertical depth ratios in excess of five to one, multilateral junction technology did not evolve at the same pace. A new multilateral junction was designed to match current extended reach drilling capabilities and replace existing multilateral equipment which was utilized beyond its intended limit incurring both installation and production risk. The newly designed junction allows lateral liners to overcome drag limitations by rotating the liner and junction to setting depth in one trip and includes several positive indicators to ensure a successful installation. This paper discusses the evolution of multilateral wells in the West Sak development, the limitations of multilateral junctions when utilized in extended reach wells, the development and testing of a new multilateral junction, and several successful field installations. Operation highlights during the completion phase of a multilateral well with a lateral departure to true vertical depth ratio in excess of six to one are included. Existing tools such as oil based mud lubricants and thorough torque and drag prediction were combined with the new junction for a successful completion which progressed the application for multilateral junctions in extended reach wells
High frequencies in African and non-African populations of independent mutations in the mannose binding protein gene (1992)

We have previously identified, in three British families having an index child with frequent infections, a point mutation (GGC-->GAC) in codon 54 of exon 1 of the gene for the human lectin mannose binding protein (MBP). This was associated with low serum levels of this complement activating protein and would be anticipated to impair opsonization of mannose rich microorganisms. We now report a second point mutation (GGA-->GAA) in Gambians from West Africa, involving codon 57 of exon 1. By substituting carboxylic acids for axial glycines in the translated proteins both mutations would be expected to disrupt the secondary structure of the collagenous triple helix of the 96 kDa MBP subunits. In the Gambians the codon 57 mutation was studied by PCR, sequence analysis and restriction analysis and found to be remarkably common (frequency of the mutant gene 0.29 in adults and 0.23 in newborns) whereas the codon 54 mutation was very rare (frequency 0.003). However, the codon 54 mutation was frequent in both a British Caucasian and a Hong Kong Chinese population (frequency of the mutant gene 0.17 and 0.11 respectively). It was predicted that both homozygous and heterozygous individuals would have profoundly reduced serum levels of the protein and this was confirmed by immunoassay as was the reduced capacity of such sera to activate complement through the MBP initiated classical pathway. Our data indicate that the two mutations have arisen independently since the divergence of African and non African populations and both have attained high frequencies.
Structural elements of the cholesterol-dependent cytolysins that are responsible for their cholesterol-sensitive membrane interactions (2007)

The pore-forming mechanism of the cholesterol-dependent cytolysins (CDCs) exhibits an absolute requirement for membrane cholesterol. The structural elements of the CDCs that mediate this interaction are not well understood. Three short hydrophobic loops (L1-L3) and a highly conserved undecapeptide sequence at the tip of domain 4 of the CDC structure are known to anchor the CDC to the membrane. It has been thought that the undecapeptide directly mediates the interaction of the CDCs with a cholesterol-rich cell surface. Herein we show that the L1-L3 loops, not the undecapeptide, are responsible for mediating the specific interaction of the CDCs with cholesterol-rich membranes. The membrane insertion of the undecapeptide was uncoupled from membrane binding by the covalent modification of the undecapeptide cysteine thiol. Modification of the cysteine prevented prepore to pore conversion, but did not affect membrane binding, thus demonstrating that undecapeptide membrane insertion follows that of the L1-L3 loops. These studies provide an example of a structural motif that specifically mediates the interaction of a bacterial toxin with a cholesterol-rich membrane.