gebhart/patrepeval huggingface dataset:
Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis (1996)

Fourteen patients with multiple sclerosis were treated with the humanized monoclonal antibody CAMPATH-1H which targets the CD52 antigen present on all lymphocytes and some monocytes; four also received anti-CD4 antibody. Lymphopaenia developed rapidly and was sustained for at least 1 year. In 12 patients, the first infusion of antibody was characterized by significant exacerbation or re- awakening of pre-existing symptoms lasting several hours. These clinical effects of antibody treatment correlated with increased levels of circulating cytokines. Peak levels of tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma occurred at 2 h, whereas the rise in interleukin-6 (IL-6) was significantly delayed and peaked at 4 h after starting antibody treatment. There was a decline in CH50, indicating complement activation. The neurological symptoms could not be attributed directly to pyrexia and were not provoked (in one patient) by an artificial rise in temperature. In the remaining two patients, a single pre-treatment with intravenous methylprednisolone (500 mg) prevented both the transient increase in neurological symptoms and the cytokine release. Our results, involving 14 intensively studied patients treated with humanized monoclonal antibodies, suggested that soluble immune mediators contribute to symptom production in multiple sclerosis; the mechanism remains uncertain but, on the available evidence, we favour the interpretation that cytokines directly affect conduction through partially demyelinated pathways.
Costimulation through OX40 is crucial for induction of an alloreactive human T‐cell response (2003)

The alloreactive immune response is a series of events initiated by the interaction of T cells with allogeneic dendritic cells (DCs), involving alloantigen recognition and costimulatory signals. In this study, we investigated the role of OX40 in alloreactivity in vitro. We first demonstrated that anti-OX40 ligand (anti-OX40L) monoclonal antibody (mAb) could markedly suppress the mixed leucocyte reaction (MLR) of peripheral blood mononuclear cells (PBMC). To further define the contribution of the OX40/OX40L system to the MLR, we set up a co-culture system of CD4+ T cells and allogeneic monocyte-derived dendritic cells (DCs). After 2 days, OX40 expression was induced on CD4+ T cells and this induction was strongly inhibited by the addition of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4)-Fc fusion protein, suggesting that the expression of OX40 during alloreaction is dependent on CD28 signalling. Next we examined the effects of anti-OX40L mAb, CTLA-4-Fc fusion protein and anti-human leucocyte antigen (HLA)-DR mAb on the proliferative response of CD4+ T cells to allogeneic DCs. The proliferation of T cells was almost completely suppressed by anti-OX40L mAb, which was comparable with that of CTLA-4-Fc. Measurement of interleukin-2 (IL-2) production in the culture supernatants showed that suppression of a proliferative response was at least in part ascribed to reduced IL-2 production. Furthermore, purified OX40L- allogeneic DCs could induce considerable proliferation of CD4+ T cells, which was suppressed by anti-OX40L mAb. These results suggest that the OX40/OX40L system is crucial for induction of the allogeneic T-cell response and the OX40/OX40L system is subsequent to and dependent on CD28 signalling, but is crucial for the end outcome of the human alloreactive T-cell response.
Pressor effects of orexins injected intracisternally and to rostral ventrolateral medulla of anesthetized rats (2000)

Orexin A and B, two recently isolated hypothalamic peptides, have been reported to increase food consumption upon intracerebroventricular injections in rats. In addition to the hypothalamus, orexin A-immunoreactive fibers have been observed in several areas of the medulla that are associated with cardiovascular functions. The present study was undertaken to evaluate the hypothesis that orexins may influence cardiovascular response by interacting with neurons in the medulla. Intracisternal injections of orexins A (0.0056-7.0 nmol) or B (0.028-0.28 nmol) dose dependently increased mean arterial pressure (MAP) by 4-27 mmHg and heart rate (HR) by 26-80 beats/min in urethan-anesthetized rats, with orexin A being more effective in this regard. MAP and HR were not changed by intravenous injection of orexins at higher concentrations. Microinjection of orexin A (14 pmol/50.6 nl) to the rostral ventrolateral medulla, which was confirmed by histological examination, increased MAP and HR. Our results indicate that, in addition to a role in positive feeding behavior, orexins may enhance cardiovascular response via an action on medullary neurons.
Rapid leukocyte integrin activation by chemokines (2002)

Chemokines control selective targeting of circulating leukocytes to the microvasculature by triggering inside-out signal transduction pathways leading to integrin-dependent adhesion. Integrin activation by chemokines is very rapid, is downmodulated within minutes and appears to involve both enhanced heterodimer lateral mobility on the plasma membrane, facilitating encounters with dispersed ligand, as well as induction of a high-affinity state. These two modalities of integrin activation by chemokines involve distinct signaling pathways in the cell, yet complement each other functionally, allowing binding of rolling cells under conditions of low as well as high ligand density. Recent data show that chemokines generate both pro- and anti-adhesive intracellular signaling events, whose equilibrium is likely to be relevant to the kinetics of adhesion and de-adhesion, and to cell movement during diapedesis and chemotaxis. Importantly, chemokines utilize different signaling mechanisms to modulate the activity of distinct integrin subtypes. These recent advances suggest that chemokines may regulate adhesive responses of immune cells based not only on patterns of chemokine receptor expression, but also on variable signaling pathways that can modulate the pro-adhesive responses of leukocytes as a function of their differentiated state, and of the local microenvironment.
The microenvironment in human myeloid malignancies: emerging concepts and therapeutic implications (2017)

Similar to their healthy counterpart, malignant hematopoietic stem cells in myeloid malignancies, such as myeloproliferative neoplasms, myelodysplastic syndromes, and acute myeloid leukemia, reside in a highly complex and dynamic cellular microenvironment in the bone marrow. This environment provides key regulatory signals for and tightly controls cardinal features of hematopoietic stem cells (HSCs), including self-renewal, quiescence, differentiation, and migration. These features are essential to maintaining cellular homeostasis and blood regeneration throughout life. A large number of studies have extensively addressed the composition of the bone marrow niche in mouse models, as well as the cellular and molecular communication modalities at play under both normal and pathogenic situations. Although instrumental to interrogating the complex composition of the HSC niche and dissecting the niche remodeling processes that appear to actively contribute to leukemogenesis, these models may not fully recapitulate the human system due to immunophenotypic, architectural, and functional inter-species variability. This review summarizes several aspects related to the human hematopoietic niche: (1) its anatomical structure, composition, and function in normal hematopoiesis; (2) its alteration and functional relevance in the context of chronic and acute myeloid malignancies; (3) age-related niche changes and their suspected impact on hematopoiesis; (4) ongoing efforts to develop new models to study niche-leukemic cell interaction in human myeloid malignancies; and finally, (5) how the knowledge gained into leukemic stem cell (LSC) niche dependencies might be exploited to devise novel therapeutic strategies that aim at disrupting essential niche-LSC interactions or improve the regenerative ability of the disease-associated hematopoietic niche.
Managing 21st Century Business and Technology Innovation: Core Banking Transformation with System z (2007)

The article discusses two of the biggest challenges facing the banking sector - shrinking banking share due to the emergence of nonbanks and the commodization of banking products. Some case studies of how IBM transforms a company's core banking system detailing improvements are highlighted.
Dynamics of arthropod filiform hairs. I. Mathematical modelling of the hair and air motions (1993)

Abstract This study is concerned with the mathematical modelling of the motion of arthropod filiform hairs in general, and of spider trichobothria specifically, in oscillating air flows. Analysis of the behaviour of hair motion is based on numerical calculations of the equation for conservation of hair angular momentum. In this equation the air-induced drag and virtual mass forces driving the hair about the point of attachment to the substrate are both significant and require a correct prescription of the air velocity. Two biologically significant cases are considered. In one the air oscillates parallel to the axis of the cylindrical substrate supporting the hair. In the other the air oscillates normal to that axis. It is shown that the relative orientation between the respective directions of the air motion and the substrate axis has a marked effect on the magnitudes of hair displacement, velocity and acceleration but not on the resonance frequency of the hair. It is also shown that the variation of velocity with distance from the substrate depends on the value of the parameter ResSts, the product of the Reynolds number and the Strouhal number characterizing the motion of air past the substrate. In the case of air motion parallel to the substrate axis the analytical result derived by Stokes (1851), for a fluid oscillating along a flat surface of infinite extent, applies if ResSts &amp;gt;10 or, equivalently, if fD2/v&amp;gt;20/n where f is the air oscillation frequency, D the substrate diameter and v the kinematic viscosity of the air. In contrast, in the case of air motion perpendicular to the substrate axis Stokes’ (1851) analysis never applies due to a substrate curvature dependence of the velocity profile for all biologically significant values of ResSts. Present theoretical considerations point to a new method for simultaneously determining R, the damping constant, and S, the torsional restoring constant of a filiform hair from measurements of the phase difference between hair displacement and air velocity as a function of the air oscillation frequency. For the filiform hairs of crickets we find from the data available that S = 0(10-11) N m rad-1 and R = 0(10-13) N m rad-1. All major qualitative aspects of known hair motion in response to air motion are correctly predicted by the numerical model.
JNJ-28312141, a novel orally active colony-stimulating factor-1 receptor/FMS-related receptor tyrosine kinase-3 receptor tyrosine kinase inhibitor with potential utility in solid tumors, bone metastases, and acute myeloid leukemia (2009)

There is increasing evidence that tumor-associated macrophages promote the malignancy of some cancers. Colony-stimulating factor-1 (CSF-1) is expressed by many tumors and is a growth factor for macrophages and mediates osteoclast differentiation. Herein, we report the efficacy of a novel orally active CSF-1 receptor (CSF-1R) kinase inhibitor, JNJ-28312141, in proof of concept studies of solid tumor growth and tumor-induced bone erosion. H460 lung adenocarcinoma cells did not express CSF-1R and were not growth inhibited by JNJ-28312141 in vitro. Nevertheless, daily p.o. administration of JNJ-28312141 caused dose-dependent suppression of H460 tumor growth in nude mice that correlated with marked reductions in F4/80(+) tumor-associated macrophages and with increased plasma CSF-1, a possible biomarker of CSF-1R inhibition. Furthermore, the tumor microvasculature was reduced in JNJ-28312141-treated mice, consistent with a role for macrophages in tumor angiogenesis. In separate studies, JNJ-28312141 was compared with zoledronate in a model in which MRMT-1 mammary carcinoma cells inoculated into the tibias of rats led to severe cortical and trabecular bone lesions. Both agents reduced tumor growth and preserved bone. However, JNJ-28312141 reduced the number of tumor-associated osteoclasts superior to zoledronate. JNJ-28312141 exhibited additional activity against FMS-related receptor tyrosine kinase-3 (FLT3). To more fully define the therapeutic potential of this new agent, JNJ-28312141 was evaluated in a FLT3-dependent acute myeloid leukemia tumor xenograft model and caused tumor regression. In summary, this novel CSF-1R/FLT3 inhibitor represents a new agent with potential therapeutic activity in acute myeloid leukemia and in settings where CSF-1-dependent macrophages and osteoclasts contribute to tumor growth and skeletal events.
Contrast-induced nephropathy: how it develops, how to prevent it. (2006)

No current treatment can reverse or ameliorate contrast-induced nephropathy once it occurs, but prophylaxis is possible. Many preventive measures have failed to show benefits in well-designed, prospective, randomized, double-blinded trials. This review will focus only on the prophylactic strategies that have possible or proven value.
A prospective, longitudinal study of the renin–angiotensin system, prostacyclin and thromboxane in the first trimester of normal human pregnancy: association with birthweight (2005)

Angiotensinogen is known to be rate-limiting in pregnancy. Its association with birthweight may be through effects on early plasma volume expansion and may have implications for intrauterine growth restriction and pre-eclampsia.
Current evidence on surgery, systemic methotrexate and expectant management in the treatment of tubal ectopic pregnancy: a systematic review and meta-analysis (2008)

This meta-analysis shows that laparoscopic surgery is the most cost-effective treatment for tubal EP. Systemic MTX is a good alternative in selected patients with low serum hCG concentrations.
Intravenous Immunoglobulins: In-Depth Review of Excipients and Acute Kidney Injury Risk (2013)

It is recommended that the choice of IVIG should be guided by the patient's medical history, present comorbidities and concomitant medications. Prospective studies with inclusion of creatinine values, as well as rigorous reporting of cases in the literature and/or via pharmacovigilance systems, are imperative to better define patient profiles.
SYNTHESIS AND BIOLOGICAL ACTIVITY OF 4′-C-HYDROXYMETHYL-2′-FLUORO- D-ARABINOFURANOSYLPURINE NUCLEOSIDES (2001)

A series of 4'-C-hydroxymethyl-2'-fluoro-D-arabinofuranosylpurine nucleosides was prepared and evaluated for cytotoxicity. The details of a convenient synthesis of the carbohydrate precursor 4-C-hydroxymethyl-3,5-di-O-benzoyl-2-fluoro-alpha-D-arabinofuranosyl bromide (13) are presented. Proof of the structure and configuration at all chiral centers of the sugars and the nucleosides were obtained by proton NMR. All five target nucleosides were evaluated for cytotoxicity in human tumor cell lines. The 4'-C-hydroxymethyl clofarabine analogue (16beta) showed slight cytotoxicity in CCRF-CEM leukemia cells.
Optical models for direct volume rendering (1995)

This tutorial survey paper reviews several different models for light interaction with volume densities of absorbing, glowing, reflecting, and/or scattering material. They are, in order of increasing realism, absorption only, emission only, emission and absorption combined, single scattering of external illumination without shadows, single scattering with shadows, and multiple scattering. For each model the paper provides the physical assumptions, describes the applications for which it is appropriate, derives the differential or integral equations for light transport, presents calculation methods for solving them, and shows output images for a data set representing a cloud. Special attention is given to calculation methods for the multiple scattering model.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The role of Schlemm's canal in aqueous outflow from the human eye. (1983)

A mathematical model of Schlemm's canal is developed to simulate collapse of the canal and its effect on resistance to flow through the aqueous outflow network. Schlemm's canal is modeled as a porous, compliant channel that is held open by the trabecular meshwork. The trabecular meshwork is modeled as a series of linear springs that allow the inner wall of Schlemm's canal to deform in proportion to the local pressure drop across it. Based on comparisons between the model and results in the literature, the following tentative conclusions are reached: (1) Most of the resistance in the aqueous outflow network occurs in the inner wall of Schlemm's canal. (2) Glaucoma is not caused by a weakening of the trabecular meshwork and a resultant collapse of Schlemm's canal alone. Instead, glaucoma probably results from an increased flow resistance of the inner wall of the canal.
Code transformations for energy-efficient device management (2004)

Energy conservation without performance degradation is an important goal for battery-operated computers, such as laptops and hand-held assistants. We study application-supported device management for optimizing energy and performance. In particular, we consider application transformations that increase device idle times and inform the operating system about the length of each upcoming, period of idleness. We use modeling and experimentation to assess the potential energy and performance benefits of this type of application support for a laptop disk. Furthermore, we propose and evaluate a compiler framework for performing the transformations automatically. Our main modeling results show that the transformations are potentially beneficial. However, our experimental results with six real laptop applications demonstrate that, unless applications are transformed, they cannot accrue any of the predicted benefits. In addition, they show that our compiler can produce almost the same performance and energy results as hand-modifying applications. Overall, we find that the transformations can reduce disk energy consumption from 55 percent to 89 percent with degradation in performance of at most 8 percent.
Centromeres were derived from telomeres during the evolution of the eukaryotic chromosome (2007)

The centromere is the DNA region of the eukaryotic chromosome that determines kinetochore formation and sister chromatid cohesion. Centromeres interact with spindle microtubules to ensure the segregation of chromatids during mitosis and of homologous chromosomes in meiosis. The origin of centromeres, therefore, is inseparable from the evolution of cytoskeletal components that distribute chromosomes to offspring cells. Although the origin of the nucleus has been debated, no explanation for the evolutionary appearance of centromeres is available. We propose an evolutionary scenario: The centromeres originated from telomeres. The breakage of the ancestral circular genophore activated the transposition of retroelements at DNA ends that allowed the formation of telomeres by a recombination-dependent replication mechanism. Afterward, the modification of the tubulin-based cytoskeleton that allowed specific subtelomeric repeats to be recognized as new cargo gave rise to the first centromere. This switch from actin-based genophore partition to a tubulin-based mechanism generated a transition period during which both types of cytoskeleton contributed to fidelity of chromosome segregation. During the transition, pseudodicentric chromosomes increased the tendency toward chromosomal breakage and instability. This instability generated multiple telocentric chromosomes that eventually evolved into metacentric or holocentric chromosomes.
Advances in silicon photonics (2005)

Silicon photonics based on silicon-on-insulator (SOI) has recently attracted a great deal of attention since it offers an opportunity for low cost solutions for various applications ranging from telecommunications to chip-to-chip interconnects. As single crystal silicon exhibits no linear electro-optic effect, design and fabrication of a high-speed silicon optical modulator with bandwidth exceeding 1 GHz are very challenging. In this presentation we will review the recent demonstration of a fast (GHz) silicon optical modulator based on a metal-oxide-semiconductor (MOS) capacitor. We will present the device design, fabrication, and characterization. We will also discuss the modulation bandwidth and phase efficiency scaling for higher speed applications. Finally, we will give an overview of recent development in other silicon photonics related topics and challenges.
Letter to the Editor (1996)

Twenty-three patients with recurrent breast cancer participating in a Phase III trial evaluating radiotherapy (XRT) with or without hyperthermia (HT) were included in a parallel study of heat shock protein (hsp) expression. The patients had core biopsies and/or fine needle aspirates (FNA) performed on their tumours, before and after treatment. These were analysed for hsp content using immunohistochemical staining with a monoclonal antibody to the inducible form of hsp 70. The proportion of samples containing identifiable cancer cells was greater for the core biopsy specimens (80%) than with FNA (60%). Staining intensity was analysed using either the majority score, i.e. the staining intensity (on a relative scale from 0 to 3) for the largest proportion of tumour cells, or the arithmetic score, which is the sum of the product of percentage of tumour cells and their staining intensity. The staining intensity for hsp's after treatment correlated inversely with the probability of attaining a complete response (CR). Specifically, the median and maximum scores for the biopsy specimens were significantly inversely related to the probability of attaining CR. The results suggest that this technique may be useful in predicting for thermotolerance development, though more data is needed to confirm the utility of the technique. Results from this study corroborate data from other clinical studies which suggest that tumours with elevated hsp levels may demonstrate resistant biologic behaviour.
Electrical properties of Athabasca Oil Sands (1979)

The results of a series of laboratory measurements of the electrical properties of samples of oil sand from the Athabasca deposit in northeastern Alberta are reported. The electrical conductivity and relative dielectric constant of the samples have been determined over a frequency range extending from 50–10 9 Hz. The measurements were performed on samples with a wide range of moisture content and over a temperature range from about 3–150 °C. A discussion of the methods and apparatus used is included.Sufficient data have been collected to permit correlation of the electrical properties of oil sand with density, moisture content, and temperature, and hence to indicate how the laboratory results can be extended to estimate in situ conductivities and dielectric constants. The results of these correlations, which are presented in graphical form, are of fundamental importance in any realistic assessment of the viability of electromagnetically heating large in situ deposits of oil sand.