gebhart/patrepeval huggingface dataset:
Importance of immune monitoring approaches and the use of immune checkpoints for the treatment of diffuse intrinsic pontine glioma: From bench to clinic and vice versa (Review) (2018)

On the basis of immunological results, it is not in doubt that the immune system is able to recognize and eliminate transformed cells. A plethora of studies have investigated the immune system of patients with cancer and how it is prone to immunosuppression, due in part to the decrease in lymphocyte proliferation and cytotoxic activity. The series of experiments published following the demonstration by Dr Allison's group of the potential effect of anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) paved the way for a new perception in cancer immunotherapy: Immune checkpoints. Several T cell‑co-stimulatory molecules including cluster of differentiation (CD)28, inducible T cell co-stimulatory, 4-1BB, OX40, glucocorticoid-induced tumor necrosis factor receptor-related gene and CD27, and inhibitory molecules including T cell immunoglobulin and mucin domain-containing-3, programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), V-domain immunoglobulin suppressor of T cells activation, T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain, and B and T lymphocyte attenuator have been described in regulating T cell functions, and have been demonstrated to be essential targets in immunotherapy. In preclinical studies, glioblastoma multiforme, a high-grade glioma, the monotherapy targeting PD-1/PD-L1 and CTLA-4 resulted in increased survival times. An improved understanding of the pharmacodynamics and immune monitoring on glioma cancers, particularly in diffuse intrinsic pontine glioma (DIPG), an orphan type of cancer, is expected to have a major contribution to the development of novel therapeutic approaches. On the basis of the recent preclinical and clinical studies of glioma, but not of DIPG, the present review makes a claim for the importance of investigating the tumor microenvironment, the immune response and the use of immune checkpoints (agonists or antagonists) in preclinical/clinical DIPG samples by immune monitoring approaches and high-dimensional analysis. Evaluating the potential predictive and correlative biomarkers in preclinical and clinical studies may assist in answering certain crucial questions that may be useful to improve the clinical response in patients with DIPG.
A New Parallel Iterative Linear Solution Method for Large-Scale Reservoir Simulation (1991)

ABSTRACT Throughout the more than four decades of the existence of numerical reservoir simulation, computer hardware has been a strong driving force in the evolution of modeling capabilities. Advances in the architecture of computing platforms invariably stimulate advances in simulation technology. The principle underutilized hardware resource available today is the capability of many machines to perform concurrent or "parallel" processing. Within the family of algorithms comprising a reservoir simulator, numerical linear algebra is a long-standing bottleneck. Robust iterative linear solvers typically utilize recursive preconditioning methods and involve conjugate gradient-like computations such as dot products which are "fine" grained and are not ideally suited to the parallel processing environment. This paper will describe a robust, high-performance linear solver formulated specifically for parallel computers with shared memory and a relatively small number of sophisticated processors (e.g. IBM 3090-400S, CRAY Y-MP). In particular, this paper will address the parallel iterative solution of the pressure equation although the method can be adapted to the fully implicit case. A new preconditioning based on the application of domain decomposition to a variant of Nested Factorization is described. A new variation of the Generalized Conjugate Residual (GCR) method better suited to parallel computation is also presented. Even for a "small" waterflood model with two layers and 8,164 active cells, a speedup of 3.9 was experienced on a four processor CRAY Y-MP; 3.3 on an IBM 3090-400S. Larger models exhibit almost ideal performance. Results are presented for up to eight processors (CRAY Y-MP). These results confirm our view that the performance potential of the parallel processing environment can be realized by reservoir simulation.
Electrical, Morphological and Rheological Study of Melt‐Mixed Polystyrene/Copper Nanowire Nanocomposites (2008)

Abstract Polystyrene and copper nanowires were melt‐mixedat 200 °C and 50 rpm in 5 mL and 15 mL DSM co‐rotating conical micro‐compounders (DSM5 and DSM 15), respectively. The electrical, morphological and rheological properties of the resulting nanocomposites were studied. The electrical percolation of nanocomposites is between 1.0 and 2.0 vol.‐% for the composites prepared in DSM5 and above 2.0 vol.‐% for the composites prepared in DSM15. SEM micrographs show smaller copper nanowire agglomerates inside polystyrene from DSM15 than those from DSM5. However, TEM micrographs reveal that both single copper nanowires and nanowire bundles coexist in the polymer matrix for the samples prepared in both micro‐compounders. No obvious microstructure transition is detected by the dynamic rheological data at 200 °C. magnified image
Multicast communication facilities for distributed multimedia information systems (1989)

A typical Distributed Multimedia Information System (DMIS) is made up of clusters of workstations connected by local area networks. Such a system allows users to exchange information in the form of integrated documents containing text, graphics and voice. Recently, there have been proposals for such systems which support both store-and-forward (e.g. mail) and real-time material (e.g. conferencing). The efficiency of a DMIS relies heavily on the support of its underlying communication sub-system to transfer multimedia information. The different categories of data traffic required by a DMIS have different transmission requirements. These requirements range from unreliable real-time transmissions (for example, mouse-cursor coordinate data and real-time digitized voice) to reliable bulk data transfers. In this paper, the authors describe the design of a set of multicast communication facilities which fulfil these requirements. Their design is intended to be applied to a wide range of network environments and protocols.
Magnetic resonance imaging in the evaluation of treatment-related central nervous system damage (1986)

Neurologic and neuropsychologic treatment related sequelae are increasingly encountered in children with cancer, but conventional means of neurologic investigation are insensitive to the presence and extent of damage. Magnetic resonance imaging (MRI) has shown brain damage not demonstrable by other means of investigation. For this reason, 11 children with cancer and with nontumor-related neurologic dysfunction were studied on a 1.5 Tesla MRI unit. All had concurrent computed tomography (CT). MRI abnormalities were seen in all (100%) patients. In 10 of 11 patients, abnormalities were of greater extent on MRI than on CT. White matter changes were frequently seen on MRI without corresponding CT abnormality. Those patients with the most severe forms of neurologic compromise had the most extensive changes on MRI. Focal neurologic findings correlated well with regions of focal signal change. Milder forms of neurologic compromise occurred in patients with definite, but less extensive, periventricular and/or subcortical change on MRI. MRI is more sensitive than CT in demonstrating treatment-related neurologic damage in children with cancer, and the type of change seen on MRI seems to correlate well with the type and severity of neurologic dysfunction present.
Controllable Formation of Heterotrimetallic Coordination Compounds: Systematically Incorporating Lanthanide and Alkali Metal Ions into the Manganese 12-Metallacrown-4 Framework (2014)

The inclusion of Ln(III) ions into the 12-MC-4 framework generates the first heterotrimetallic complexes of this molecular class. The controllable and deliberate preparations of these compounds are demonstrated through 12 crystal structures of the Ln(III)M(I)(OAc)4[12-MCMn(III)(N)shi-4](H2O)4·6DMF complex, where OAc(-) is acetate, shi(3-) is salicylhydroximate, and DMF is N,N-dimethylformamide. Compounds 1-12 have M(I) as Na(I), and Ln(III) can be Pr(III) (1), Nd(III) (2), Sm(III) (3), Eu(III) (4), Gd(III) (5), Tb(III) (6), Dy(III) (7), Ho(III) (8), Er(III) (9), Tm(III) (10), Yb(III) (11), and Y(III) (12). An example with M(I) = K(I) and Ln(III) = Dy(III) is also reported (Dy(III)K(OAc)4[12-MCMn(III)(N)shi-4](DMF)4·DMF (14)). When La(III), Ce(III), or Lu(III) is used as the Ln(III) ions to prepare the Ln(III)Na(I)(OAc)4[12-MCMn(III)(N)shi-4] complex, the compound Na2(OAc)2[12-MCMn(III)(N)shi-4](DMF)6·2DMF·1.60H2O (13) results. For compounds 1-12, the identity of the Ln(III) ion affects the 12-MCMn(III)(N)shi-4 framework as the largest Ln(III), Pr(III), causes an expansion of the 12-MCMn(III)(N)shi-4 framework as demonstrated by the largest metallacrown cavity radius (0.58 Å for 1 to 0.54 Å for 11), and the Pr(III) causes the 12-MCMn(III)(N)shi-4 framework to be the most domed structure as evident in the largest average angle about the axial coordination of the ring Mn(III) ions (103.95° for 1 to 101.69° for 11). For 14, the substitution of K(I) for Na(I) does not significantly affect the 12-MCMn(III)(N)shi-4 framework as many of the structural parameters such as the metallacrown cavity radius (0.56 Å) fall within the range of compounds 1-12. However, the use of the larger K(I) ion does cause the 12-MCMn(III)(N)shi-4 framework to become more planar as evident in a smaller average angle about the axial coordination of the ring Mn(III) ions (101.35°) compared to the analogous Dy(III)/Na(I) (7) complex (102.40°). In addition to broadening the range of structures available through the metallacrown analogy, these complexes allow for the mixing and matching of a diverse range of metals that might permit the fine-tuning of molecular properties where one day they may be exploited as magnetic materials or luminescent agents.
Active suppression of major histocompatibility complex class II gene expression during differentiation from B cells to plasma cells. (1988)

Constitutive expression of major histocompatibility complex class II genes is acquired very early in B-cell ontogeny and is maintained up to the B-cell blast stage. Terminal differentiation in plasma cells is, however, accompanied by a loss of class II gene expression. In B cells this gene system is under the control of several loci encoding transacting factors with activator function, one of which, the aIr-1 gene product, operates across species barriers. In this report human class II gene expression is shown to be extinguished in somatic cell hybrids between the human class II-positive B-cell line Raji and the mouse class II-negative plasmacytoma cell line P3-U1. Since all murine chromosomes are retained in these hybrids and no preferential segregation of a specific human chromosome is observed, the results are compatible with the presence of suppressor factors of mouse origin, operating across species barriers and inhibiting class II gene expression. Suppression seems to act at the level of transcription or accumulation of class II-specific mRNA, since no human, and very few murine, class II transcripts are detectable in the hybrids.
Automotive Service: Inspection, Maintenance, and Repair (2003)

Automotive Service: Inspection, Maintenance & Repair covers the fundamentals of operation and repair for all major systems of the modern automobile. This comprehensive text introduces the fundamentals of systems and progresses onto diagnosis and service with thousands of lavish, full-color illustrations, Shop Tips, Safety Notes, and review questions to aid in comprehension. Traditional and new topics have been integrated in a concise, easy-to-read format: OBD II, ABS, engine performance, safety, and shop tools. Structured around the eight ASE automotive test areas, this book helps users prepare for ASE certification.
Architectural support for SWAR text processing with parallel bit streams (2009)

Parallel bit stream algorithms exploit the SWAR (SIMD within a register) capabilities of commodity processors in high-performance text processing applications such as UTF-8 to UTF-16 transcoding, XML parsing, string search and regular expression matching. Direct architectural support for these algorithms in future SWAR instruction sets could further increase performance as well as simplifying the programming task. A set of simple SWAR instruction set extensions are proposed for this purpose based on the principle of systematic support for inductive doubling as an algorithmic technique. These extensions are shown to significantly reduce instruction count in core parallel bit stream algorithms, often providing a 3X or better improvement. The extensions are also shown to be useful for SWAR programming in other application areas, including providing a systematic treatment for horizontal operations. An implementation model for these extensions involves relatively simple circuitry added to the operand fetch components in a pipelined processor.
Restriction landmark genomic scanning (RLGS-M)-based genome-wide scanning of mouse liver tumors for alterations in DNA methylation status. (1997)

Restriction landmark genomic scanning for methylation (RLGS-M) was used to detect, and subsequently clone, genomic regions with alterations in DNA methylation associated with tumorigenesis. Use of a methylation-sensitive enzyme for the landmark cleavage allows analysis of changes in methylation patterns. In this study, we used RLGS-M to analyze SV40 T antigen-induced mouse liver tumors derived from interspecific F1 hybrids between Mus spretus (S) and C57BL/6 (B6). Because 575 S- and B6-specific RLGS loci/spots have been mapped, tumor-related alterations in the RLGS profile could be immediately localized to specific chromosomal regions. We previously found that the loss of contiguous loci/spots could be attributed primarily to DNA loss, whereas loss of solitary loci/spots could be attributed primarily to DNA methylation. In this study, we examined 30 mouse liver tumor samples for loss of the 507 mapped loci/spots. Fourteen solitary loci/spots found to be absent or reduced in more than 75% of tumor samples were cloned and subjected to DNA sequence analyses. Two loci were identified as alpha4 integrin and p16/CDKN2, genes reported to be involved in tumorigenesis. Thus, RLGS-M can detect alterations in the methylation status of known tumor suppressor genes and provide a method for detecting and subsequently cloning novel genomic regions that undergo alterations in methylation during tumorigenesis.
Fas Death Receptor Signaling Represses Monocyte Numbers and Macrophage Activation In Vivo (2004)

Over 1 billion monocytes are produced daily, with a small percentage differentiating into macrophages, suggesting that excess monocytes are deleted through a tightly regulated process. Although the in vivo mechanism governing monocyte/macrophage homeostasis is unknown, deletion of monocytes in culture is mediated by the Fas death pathway and is blocked by M-CSF. To determine the in vivo significance of Fas in monocyte development, mice lacking Fas (lpr/lpr) and mice deficient in Fas and M-CSF were examined. Compared with congenic control C57BL/6 (B6) mice, lpr/lpr mice displayed increased numbers of circulating monocytes. The lack of Fas in M-CSF-deficient mice resulted in an enhanced percentage, but not total numbers, of monocytes. Fas deficiency led to an increase in myeloid bone marrow progenitor potential only in M-CSF-intact mice. Although lpr/lpr and B6 mice had similar numbers of tissue macrophages, the loss of Fas in M-CSF-deficient mice was sufficient to increase the number of macrophages in a subset of tissues. Additionally, after stimulation with thioglycolate, lpr/lpr and B6 mice showed equivalent numbers of peritoneal macrophages. However, Fas-deficient peritoneal macrophages displayed a marked increase in spontaneous and LPS-induced proinflammatory molecule production. Moreover, Fas-deficient mice showed enhanced systemic inflammatory arthritis associated with up-regulation of IL-1beta and CCL2 secretion, elevated numbers of inflammatory monocytes, and increased numbers of tissue macrophages. Collectively, these data suggest that Fas may be required for maintaining circulating monocytes and for suppressing macrophage activation and recruitment that are stimulus dependent.
Feedforward neural network with a specialized architecture for estimation of the temperature influence on the electric load (2008)

The problem of temperature-load relationship revealing is considered. A specialized architecture of a feedforward neural network is proposed that provides separation of temperature influence from other factors and its analysis in an explicit form. The proposed approach is illustrated by computational experiments with data from two locations with different climatic conditions.
Cross-document Event Extraction and Tracking: Task, Evaluation, Techniques and Challenges (2009)

This paper proposes a new task of cross-document event extraction and tracking and its evaluation metrics. We identify important person entities which are frequently involved in events as ‘centroid entities’. Then we link the events involving the same centroid entity along a time line. We also present a system performing this task and our current approaches to address the main research challenges. We demonstrate that global inference from background knowledge and cross-document event aggregation are crucial to enhance the performance. This new task defines several extensions to the traditional single-document Information Extraction paradigm beyond ‘slot filling’.
Loss of tau rescues inflammation-mediated neurodegeneration (2015)

Neuroinflammation is one of the neuropathological hallmarks of Alzheimer's disease (AD) and related tauopathies. Activated microglia spatially coexist with microtubule-associated protein tau (Mapt or tau)-burdened neurons in the brains of human AD and non-AD tauopathies. Numerous studies have suggested that neuroinflammation precedes tau pathology and that induction or blockage of neuroinflammation via lipopolysaccharide (LPS) or anti-inflammatory compounds (such as FK506) accelerate or block tau pathology, respectively in several animal models of tauopathy. We have previously demonstrated that microglia-mediated neuroinflammation via deficiency of the microglia-specific chemokine (fractalkine) receptor, CX3CR1, promotes tau pathology and neurodegeneration in a mouse model of LPS-induced systemic inflammation. Here, we demonstrate that tau mediates the neurotoxic effects of LPS in Cx3cr1 (-/-) mice. First, Mapt (+/+) neurons displayed elevated levels of Annexin V (A5) and TUNEL (markers of neurodegeneration) when co-cultured with LPS-treated Cx3cr1 (-/-)microglia, which is rescued in Mapt (-/-) neurons. Second, a neuronal population positive for phospho-S199 (AT8) tau in the dentate gyrus is also positive for activated or cleaved caspase (CC3) in the LPS-treated Cx3cr1 (-/-) mice. Third, genetic deficiency for tau in Cx3cr1 (-/-) mice resulted in reduced microglial activation, altered expression of inflammatory genes and a significant reduction in the number of neurons positive for CC3 compared to Cx3cr1 (-/-)mice. Finally, Cx3cr1 (-/-)mice exposed to LPS displayed a lack of inhibition in an open field exploratory behavioral test, which is rescued by tau deficiency. Taken together, our results suggest that pathological alterations in tau mediate inflammation-induced neurotoxicity and that deficiency of Mapt is neuroprotective. Thus, therapeutic approaches toward either reducing tau levels or blocking neuroinflammatory pathways may serve as a potential strategy in treating tauopathies.
Differential Effects of Interleukin-6 and -10 on Skeletal Muscle and Liver Insulin Action In Vivo (2004)

The circulating level of the inflammatory cytokine interleukin (IL)-6 is elevated in various insulin-resistant states including type 2 diabetes, obesity, cancer, and HIV-associated lipodystrophy. To determine the role of IL-6 in the development of insulin resistance, we examined the effects of IL-6 treatment on whole-body insulin action and glucose metabolism in vivo during hyperinsulinemic-euglycemic clamps in awake mice. Pretreatment of IL-6 blunted insulin's ability to suppress hepatic glucose production and insulin-stimulated insulin receptor substrate (IRS)-2-associated phosphatidylinositol (PI) 3-kinase activity in liver. Acute IL-6 treatment also reduced insulin-stimulated glucose uptake in skeletal muscle, and this was associated with defects in insulin-stimulated IRS-1-associated PI 3-kinase activity and increases in fatty acyl-CoA levels in skeletal muscle. In contrast, we found that co-treatment of IL-10, a predominantly anti-inflammatory cytokine, prevented IL-6-induced defects in hepatic insulin action and signaling activity. Additionally, IL-10 co-treatment protected skeletal muscle from IL-6 and lipid-induced defects in insulin action and signaling activity, and these effects were associated with decreases in intramuscular fatty acyl-CoA levels. This is the first study to demonstrate that inflammatory cytokines IL-6 and IL-10 alter hepatic and skeletal muscle insulin action in vivo, and the mechanism may involve cytokine-induced alteration in intracellular fat contents. These findings implicate an important role of inflammatory cytokines in the pathogenesis of insulin resistance.
Tuning the differentiation of periosteum using biochemical and mechanical stimulation (2009)

High prevalence of osteoarthritis and poor intrinsic healing capacity of articular cartilage create a demand for cell-based cartilage repair strategies. It is possible to tissue engineer cartilage with almost native proteoglycan content, but collagen reaches only 15% to 35% of the native content. It is generally believed that the application of mechanical loading during culturing increases collagen content, and therewith mechanical properties. We hypothesize that sliding of an indenter over a construct would induce tensile strains (Fig 2A) that stimulate collagen synthesis, and consequently increase the mechanical properties of neo-formed cartilage.
Depth of interaction decoding of a continuous crystal detector module (2007)

We present a clustering method to extract the depth of interaction (DOI) information from an 8 mm thick crystal version of our continuous miniature crystal element (cMiCE) small animal PET detector. This clustering method, based on the maximum-likelihood (ML) method, can effectively build look-up tables (LUT) for different DOI regions. Combined with our statistics-based positioning (SBP) method, which uses a LUT searching algorithm based on the ML method and two-dimensional mean-variance LUTs of light responses from each photomultiplier channel with respect to different gamma ray interaction positions, the position of interaction and DOI can be estimated simultaneously. Data simulated using DETECT2000 were used to help validate our approach. An experiment using our cMiCE detector was designed to evaluate the performance. Two and four DOI region clustering were applied to the simulated data. Two DOI regions were used for the experimental data. The misclassification rate for simulated data is about 3.5% for two DOI regions and 10.2% for four DOI regions. For the experimental data, the rate is estimated to be approximately 25%. By using multi-DOI LUTs, we also observed improvement of the detector spatial resolution, especially for the corner region of the crystal. These results show that our ML clustering method is a consistent and reliable way to characterize DOI in a continuous crystal detector without requiring any modifications to the crystal or detector front end electronics. The ability to characterize the depth-dependent light response function from measured data is a major step forward in developing practical detectors with DOI positioning capability.