gebhart/patrepeval huggingface dataset:
Microbiological Factors Influencing the Outcome of Nosocomial Bloodstream Infections: A 6‐Year Validated, Population‐Based Model (1997)

All patients (n = 1,745) with nosocomial bloodstream infection identified between 1986 and 1991 at a single 900-bed tertiary care hospital were studied to identify microbiological factors independently associated with mortality due to the infection. Patients were identified by prospective, case-based surveillance and positive blood cultures. Mortality rates were examined for secular trends. Prognostic factors were determined with use of univariate and multivariate analyses, and both derivation and validation sets were used. A total of 1,745 patients developed nosocomial bloodstream infection. The 28-day crude mortality was 22%, and crude in-hospital mortality was 35%. Factors independently (all P < .05) associated with increased 28-day mortality rates were older age, longer length of hospital stay before bloodstream infection, and a diagnosis of cancer or disease of the digestive system. After adjustment for major confounders, Candida species were the only organisms independently influencing the outcome of nosocomial bloodstream infection (odds ratio [OR] for mortality = 1.84; 95% confidence interval [CI], 1.22-2.76; P = .0035). The two additional microbiological factors independently associated with increased mortality were pneumonia as a source of secondary infection (OR = 2.74; 95% CI, 1.87-4.00; P < .0001) and polymicrobial infection (OR = 1.68; 95% CI, 1.22-2.32; P = .0014). Our data suggest that microbiological factors independently affect the outcome of nosocomial bloodstream infection.
Antibody–Cytokine Fusion Proteins for the Therapy of Cancer (2004)

In recent years the development of tumor-specific recombinant antibodies fused to immuno-stimulatory cytokines such as interleukin-2 (IL-2), interleukin-12 (IL-12), and granulocyte/macrophage colony-stimulating factor (GM-CSF) has provided a promising novel approach to cancer immunotherapy. The combined properties of specific targeting of antibodies and the immune stimulation of cytokines results in high cytokine concentration in the tumor microenvironment, and as a consequence, in an improved tumoricidal activity of the antibody and/or in a secondary effective immune response against the tumor. In the present chapter we describe strategies for the construction, expression, and in vitro characterization of antibody-cytokine fusion proteins, with particular emphasis on antibody/IL-2 fusion proteins.
Multiplex selection technique (MuST): an approach to clone transcription factor binding sites. (1996)

We have used a multiplex selection approach to construct a library of DNA-protein interaction sites recognized by many of the DNA-binding proteins present in a cell type. An estimated minimum of two-thirds of the binding sites present in a library prepared from activated Jurkat T cells represent authentic transcription factor binding sites. We used the library for isolation of "optimal" binding site probes that facilitated cloning of a factor and to identify binding activities induced within 2 hr of activation of Jurkat cells. Since a large fraction of the oligonucleotides obtained appear to represent "optimal" binding sites for sequence-specific DNA-binding proteins, it is feasible to construct a catalog of consensus binding sites for DNA-binding proteins in a given cell type. Qualitative and quantitative comparisons of the catalogs of binding site sequences from various cell types could provide valuable insights into the process of differentiation acting at the level of transcriptional control.
The Relevance of Blood Cell-Vessel Wall Adhesive Interactions for Vascular Thrombotic Disease (1999)

Activation and signaling of circulating blood and vessel wall cells, as well as their direct adhesive interactions, are critical for the regulation of vascular homeostasis related to vasomotor responses, inflammation, hemostasis, and wound repair. Under conditions of stress, inflammation, or infection the targeting and anchoring of leukocytic cells to the vascular endothelium is mediated by specific pairs of adhesion receptors and their counter-ligands that may induce juxtacrine signaling resulting in the expression of prothrombotic agonists such as tissue factor. Concomitant action of inflammatory cytokines may down-regulate thromboprotective mechanisms of the endothelium. Through similar intercellular interactions, the platelets recruited to these inflamed sites may aggregate and modulate leukocyte function. In addition, leukocytes can influence coagulation by their ability to produce pro- and anticoagulant factors as well as by providing specific receptors (such as Mac-1 or EPR-1) that serve as direct molecular links between inflammation and hemostasis. The initiation and amplification of blood clotting reactions on the leukocyte surface has consequences on other vascular cell functions and involves (cytokine) activation and signaling pathways that contribute to pathophysiological aspects of inflammatory responses. As a consequence, the diverse cell-to-cell interactions, as well as different inflammatory mediators or bidirectional signaling pathways, appear to be promising targets for the treatment of thrombotic complications in the context of inflammation-dependent vascular diseases.
Targeting Syk as a treatment for allergic and autoimmune disorders (2004)

Recent advances in our understanding of allergic and autoimmune disorders have begun to translate into novel, effective and safe medicines for these common maladies. Examples include an anti-IgE monoclonal antibody recently approved for severe asthmatics and the TNF-alpha antagonists that have demonstrated their ability to suppress rheumatoid arthritis, Crohn's disease and other chronic inflammatory processes. However, protein therapies are difficult and expensive to develop, manufacture and administer. Clearly, there is also a need for small-molecule inhibitors of novel targets that have safe and effective characteristics. Syk is an intracellular protein tyrosine kinase that was discovered 15 years ago as a key mediator of immunoreceptor signalling in a host of inflammatory cells including B cells, mast cells, macrophages and neutrophils. These immunoreceptors, including Fc receptors and the B-cell receptor, are important for both allergic diseases and antibody-mediated autoimmune diseases and thus pharmacologically interfering with Syk could conceivably treat these disorders. In addition, as Syk is positioned upstream in the cell signalling pathway, therapies targeting Syk may be more advantageous relative to drugs that inhibit a single downstream event. Syk inhibition during an allergic or asthmatic response will block three mast cell functions: the release of preformed mediators such as histamine, the production of lipid mediators such as leukotrienes and prostaglandins and the secretion of cytokines. In contrast, commonly used antihistamines or leukotriene receptor antagonists target only a single mediator of this complex cascade. Despite its expression in platelets and other non-haematopoietic cells, the role of Syk in regulating vascular homeostasis and other housekeeping functions is minimal or masked by redundant Syk-independent pathways. This suggests that targeting Syk would be an optimal approach to effectively treat a multitude of chronic inflammatory diseases without undue toxicity.
Neovascular Glaucoma: Etiology, Diagnosis and Prognosis (2009)

Neovascular glaucoma (NVG) is a severe form of glaucoma with devastating visual outcome attributed to new blood vessels obstructing aqueous humor outflow, usually secondary to widespread posterior segment ischemia. Invasion of the anterior chamber by a fibrovascular membrane initially obstructs aqueous outflow in an open-angle fashion and later contracts to produce secondary synechial angle-closure glaucoma. The full blown picture of NVG is characterized by iris neovascularization, a closed anterior chamber angle, and extremely high intraocular pressure (IOP) with severe ocular pain and usually poor vision.
IL-12 Can Target Human Lung Adenocarcinoma Cells and Normal Bronchial Epithelial Cells Surrounding Tumor Lesions (2009)

This study demonstrates that IL-12 inhibits directly the growth of human lung adenocarcinoma and targets the adjacent NBEC. These novel anti-tumor activities of IL-12 add to the well known immune-modulatory properties of the cytokine and may provide a rational basis for the development of a clinical trial.
Tradeoff Characteristics Between Resistivity and Reliability for Scaled-Down Cu-Based Interconnects (2008)

We investigated tradeoff characteristics between resistivity and reliability for scaled-down Cu-based interconnects. A unique resistivity-measurement technique is proposed to detect influences due to impurity doping. Using this technique, we investigated the impacts of the impurity doping on three types of copper interconnects - cobalt-tungsten-phosphorous (CoWP) metal-cap interconnects, plasma-enhanced chemical-vapor-deposition self-aligned barrier interconnects, and CuAl alloy interconnects - and clarified the tradeoffs between the resistivity and the reliability. We found that the metal-cap interconnect shows not only high reliability but also outstanding efficiency with regard to the suppression of resistance increase due to impurity doping.
Distribution of an asialoglycoprotein receptor on rat hepatocyte cell surface. (1982)

Direct ferritin immunoelectron microscopy was applied to visualize the distribution of the hepatocyte cell surface of the asialoglycoprotein receptor which is responsible for the rapid clearance of serum glycoproteins and lysosomal catabolism. For this purpose, rabbit antibody against the purified hepatic binding protein specific for asialoglycoproteins was prepared and coupled to ferritin by glutaraldehyde. The specific antibody conjugates were incubated with the hepatocytes, which were isolated from rat liver homogenate after fixation by glutaraldehyde perfusion. These cells preserved well the original polygonal shape and polarity, and it was easy to identify the sinusoidal, lateral, and bile canalicular faces. The surface density of the ferritin particles bound to the sinusoidal face was about four times higher than that of particles bound to the lateral face, while the bile canalicular face was hardly labeled and almost at the control level. Using the surface area of hepatocyte measured by morphometrical analyses, it was estimated that approximately 90% of bound ferritin particles were at the sinusoidal face, approximately 10% at the lateral face, and approximately 1% at the bile canalicular face. Nonhepatic cells such as endothelial and Kupffer cells had no receptor specific for asialoglycoproteins.
Determining the structure and functions of Government : program and functional reviews (2004)

This background paper presents an assessment of international approaches to, and experiences of undertaking program and functional reviews as part of an administrative reform program. The paper examines program and functional reviews drawn from twenty five examples from fourteen different countries. The first section of this paper provides an overview of international experience of, and approaches to program and functional reviews in government. The second section provides examples of the specific approaches and methodologies used in the most common types of program and functional reviews. The third section seeks to define an appropriate methodology for undertaking such reviews in Russia as part of the developing administrative reform program, taking account both of the context and needs in Russia, and of international experience in this area.
Cellular protein modulates effects of human immunodeficiency virus type 1 Rev (1994)

Replication of human immunodeficiency virus type 1 requires expression of the viral trans activator Rev. Rev binds to a highly structured RNA, the Rev response element, which is present in singly spliced and unspliced genomic viral RNAs. Although Rev helps to transport these transcripts from the nucleus to the cytoplasm, the mechanism(s) involved is not fully understood. Using the yeast two-hybrid system, we isolated a murine protein (YL2) that interacts with the basic domain of Rev, which is essential for the function of Rev in vivo and for the inhibitory splicing activity of Rev in vitro. YL2 has 92% identity to a human 32-kDa protein (p32), which copurifies with alternative splicing factor SF2/ASF. Furthermore, we found that whereas expression of YL2 greatly potentiated the activity of Rev, antisense YL2 transcripts blocked the effects of Rev in mammalian cells. YL2 also increased the activities of Rex on the Rex response element and of hybrid Rev proteins fused to Tat and the coat protein of bacteriophage MS2 on their respective RNAs. Thus, YL2 or p32 is a cellular protein that modulates the function of human immunodeficiency virus type 1 Rev.
FC‐53  Serologic allergy testing in horses with insect hypersensitivity (2004)

Serologic allergy testing (SAT) results in horses have not been consistent with manifestations of hypersensitivity or intradermal test (IDT) results. The purpose of this study was to determine whether the level of agreement between insect‐specific IgE values (as measured by a commercial polyclonal antihorse IgE‐based ELISA) and manifestation of disease or IDT was improved by shifting the positive/negative threshold from 200 (positive) to 150 (borderline) or by the utilization of insect type‐specific cut‐off points. The study included a population of 37 healthy horses and 40 Icelandic horses suffering from insect hypersensitivity. The study was conducted during the fall when affected horses showed acute clinical signs. IDT was performed as standard procedure using extracts of black ant, mosquito, horsefly, deerfly, housefly, and Culicoides variipennis. Insect‐specific IgE levels in horse sera were measured by an equine ELISA. Sensitivity and specificity was 98 and 3% (SAT versus insect hypersensitivity) and 97 and 4% (SAT versus IDT), respectively. A shift of the threshold value from 200 to 150 increased sensitivity, but did not improve the level of agreement between IDT and SAT (κ = 0.04, slight agreement). Circulating allergen‐specific IgE levels were not significantly different for the incidence and size of positive skin reactions or the onset and severity of insect hypersensitivity for any insect tested. Therefore, the utilisation of insect type‐specific cut‐off points did not increase the level of agreement between SAT and IDT or clinical data. Funding: Self‐funded.
Two-photon absorption and second hyperpolarizability measurements in diphenylbutadiene by degenerate four-wave mixing (1993)

We have investigated two-photon absorption (TPA) in diphenylbutadiene at 532 nm using degenerate four-wave mixing (DFWM) of nanosecond laser pulses. We present a theory which describes the development of double-peaked phase conjugate pulses produced in DFWM due to TPA-induced gratings superimposed on the usual electronic third-order processes. Our analysis suggests a novel technique for measuring both the real and imaginary parts of the third-order susceptibility of a molecular solution, hence leading to a determination of the TPA cross section σ2 and second hyperpolarizability γ of the solute molecules. Applying this experimental technique to diphenylbutadiene in chloroform, we obtain σ2=(40±8)×10−50 cm−4 s/photon–molecule and ‖γ‖=(420±80)×10−36 esu for this diphenyl polyene. We show that these values are in agreement with related measurements in diphenylbutadiene, and that they are consistent with a two-photon resonance near 39 500 cm−1. The DFWM measurement technique we describe is very sensitive and should be applicable for measuring the two-photon spectra of a variety of molecules.
Assessment of ≥50% and <50% Intracranial Stenoses by Transcranial Color-Coded Duplex Sonography (1999)

TCCS may reliably assess >/=50% and <50% basal cerebral artery narrowing and prove useful for noninvasive management of patients with symptomatic intracranial stenoses.
Normalization of Mineral Ion Homeostasis by Dietary Means Prevents Hyperparathyroidism, Rickets, and Osteomalacia, But Not Alopecia in Vitamin D Receptor-Ablated Mice (1998)

1,25-Dihydroxyvitamin D3 plays a major role in intestinal calcium transport. To determine what phenotypic abnormalities observed in vitamin D receptor (VDR)-ablated mice are secondary to impaired intestinal calcium absorption rather than receptor deficiency, mineral ion levels were normalized by dietary means. VDR-ablated mice and control littermates were fed a diet that has been shown to prevent secondary hyperparathyroidism in vitamin D-deficient rats. This diet normalized growth and random serum ionized calcium levels in the VDR-ablated mice. The correction of ionized calcium levels prevented the development of parathyroid hyperplasia and the increases in PTH messenger RNA synthesis and in serum PTH levels. VDR-ablated animals fed this diet did not develop rickets or osteomalacia. However, alopecia was still observed in the VDR-ablated mice with normal mineral ions, suggesting that the VDR is required for normal hair growth. This study demonstrates that normalization of mineral ion homeostasis can prevent the development of hyperparathyroidism, osteomalacia, and rickets in the absence of the genomic actions of 1,25-dihydroxyvitamin D3.
The Anterior cruciate ligament : current and future concepts (1993)

Part 1 Structure: anatomy of the ACL sensory role of the ACL. Part 2 Function: ACL function in the normal knee tensile properties of the ACL as function of age mechanical and viscoelastic properties of ACL and ACL fascicles knee motions and their relations to ACL function estimation of ACL loads in situ - indirect non-contact methods measurement of ACL loads - direct methods the measurement of ACL strain in vivo joint kinematics in muscle stabilized knees ACL forces in activity ligament restraints in ACL deficient knees functional evaluation of normal and ACL deficient knee using gait analysis techniques. Part 3 Injury, healing repair, reconstruction: cell biology of ligament and ligament healing adhesion macromolecules of the ligament - the molecular glues in wound healing molecular signals in ligament healing collagen ultrastructure in the normal ACL and ACL graft collagen remodelling in ACL reconstruction (Goat model) biomechanical properties of normal and healing ligaments. Part 4 ACL reconstruction and substitutes (biologic): the use of knee laxity testers for determination of anterior posterior stability of the knee - their pitfalls in practice selecting patients for ACL surgery mechanics of ACL reconstruction acute repair of anterior cruciate ligament tears autograft reconstruction of the ACL - placement, tensioning and preconditioning, patella tendon, semitendinosus ACL reconstruction allograft reconstruction of the ACL - fresh frozen, freeze dried, fresh and cryopreserved augmentation prosthetic replacement for the ACL complications - patellar entrapment following ACL injury, cyclops lesions, loss of motion following ACL reconstruction.
Predicting Financial Crime: Augmenting the Predictive Policing Arsenal (2017)

Financial crime is a rampant but hidden threat. In spite of this, predictive policing systems disproportionately target "street crime" rather than white collar crime. This paper presents the White Collar Crime Early Warning System (WCCEWS), a white collar crime predictive model that uses random forest classifiers to identify high risk zones for incidents of financial crime.
Labelled Oligonucleotides as Radiopharmaceuticals: Pitfalls, Problems and Perspectives (2002)

The labelling of single-stranded oligonucleotides with a positron or single-photon emitter can result in valuable radiopharmaceuticals with promising applications for: (i) Imaging of specific mRNAs, i.e. visualisation of the expression of specific genes in vivo (ii) Monitoring of antisense chemotherapy, i.e. measuring the efficiency of efforts to block the expression of specific genes; (iii) Gene radiotherapy, i.e. the targeting of radiation damage to specific DNA sequences in order to destroy tumours; (iv) Imaging of protein targets by the use of aptamer oligonucleotides, i.e. oligonucleotide ligands obtained by in vitro evolution of selection-amplification steps, or selected for their interaction with nucleic acid-binding proteins; (v) Pre-targeting strategies based on the specificity of complementary sequence hybridisation. Nevertheless, oligonucleotides are intrinsically poor pharmaceuticals because of their large size, low stability, poor membrane passage and a number of undesirable and sometimes unpredictable side effects. As an alternative to the inherently unstable phosphodiester DNAs, chemically modified oligonucleotides such as phosphorothioate, methylphosphonate and peptide nucleic acid oligomers have been developed, and some are in clinical trials for the chemotherapy of several types of tumours. Imaging techniques could be useful in the development of such therapies. In addition, the potential of targeting virtually any disease or physiological process, by changing only the sequence of the oligomer, could provide a means to identify serious diseases in a very early stage, and be a highly specific modality to diagnose and differentiate various cancers. This has stimulated efforts to develop such radiopharmaceuticals in many laboratories, and encouraging results have been reported using technetium-99m, indium-111, carbon-11, fluorine-18, bromine-76 and iodine-125 labelled oligonucleotides.
Antigen recognition by H-2-restricted T cells. I. Cell-free antigen processing. (1983)

We examined the ability of a set of cloned chicken ovalbumin (cOVA)-specific, Id-restricted, T cell hybridomas to produce interleukin-2 in response to cOVA presented by the Ia+ B cell lymphoma line, A20-2J. Although viable A20-2J cells presented native, denatured, and fragmented cOVA more or less equally well, A20-2J cells that were glutaraldehyde-fixed could present only enzymatically or chemically fragmented cOVA. These results suggest that antigen fragmentation may be both necessary and sufficient to define accessory cell processing of soluble antigens so that they may be recognized in association with I-region molecules by T cells.
Probing the Link among Genomic Cargo, Contact Mechanics, and Nanoindentation in Recombinant Adeno-Associated Virus 2 (2017)

Recombinant adeno-associated virus (AAV) is a promising gene therapy vector. To make progress in this direction, the relationship between the characteristics of the genomic cargo and the capsid stability must be understood in detail. The goal of this study is to determine the role of the packaged vector genome in the response of AAV particles to mechanical compression and adhesion to a substrate. Specifically, we used atomic force microscopy to compare the mechanical properties of empty AAV serotype 2 (AAV2) capsids and AAV2 vectors packaging single-stranded DNA or self-complementary DNA. We found that all species underwent partial deformation upon adsorption from buffer on an atomically flat graphite surface. Upon adsorption, a preferred orientation toward the twofold symmetry axis on the capsid, relative to the substrate, was observed. The magnitude of the bias depended on the cargo type, indicating that the interfacial properties may be influenced by cargo. All particles showed a significant relative strain before rupture. Different from interfacial interactions, which were clearly cargo-dependent, the elastic response to directional stress was largely dominated by the capsid properties. Nevertheless, small differences between particles laden with different cargo were measurable; scAAV vectors were the most resilient to external compression. We also show how elastic constant and rupture force data sets can be analyzed according a multivariate conditional probability approach to determine the genome content on the basis of a database of mechanical properties acquired from nanoindentation assays. Implications for understanding how recombinant AAV capsid-genome interactions can affect vector stability and effectiveness of gene therapy applications are discussed.