gebhart/patrepeval huggingface dataset:
The 2008 WHO classification of lymphomas: implications for clinical practice and translational research (2009)

The 4(th) edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues published in 2008 builds upon the success of the 2001 3(rd) edition; new entities are defined, and solutions for problematic categories are sought. Recent studies have drawn attention to the biological overlap between classical Hodgkin lymphoma (CHL) and diffuse large B-cell lymphomas (DLBCL). Similarly, there is a greater appreciation of the borderlands between Burkitt lymphoma and DLBCL. Strategies for the management of these borderline lesions are proposed. Additionally, age-specific and site-specific factors play an important role in the definition of several new entities, which also have biological underpinnings. Among the peripheral T-cell lymphomas (PTCL), more precise definitions were introduced for several entities, including anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, enteropathy-associated T-cell lymphoma, and subcutaneous panniculitis-like T-cell lymphoma. Several new variants of primary cutaneous T-cell lymphomas are proposed. Finally, the subclassification and categorization of the most common lymphoma subtypes, follicular lymphoma (FL) and DLBCL, were altered to enhance diagnostic accuracy and aid in clinical management. The 2008 WHO classification also draws attention to early events in lymphomagenesis. These lesions help delineate the earliest steps in neoplastic transformation and generally mandate a conservative therapeutic approach. The 2001 classification was rapidly adopted for clinical trials and successfully served as a common language for scientists comparing genetic and functional data. The modifications made in the 2008 classification are the result of this successful partnership among pathologists, clinicians, and biologists, but are only a stepping stone to the future.
Caveolin Scaffolding Region and the Membrane Binding Region of Src Form Lateral Membrane Domains (2002)

Formation of domains by the membrane binding motifs of caveolin and src were studied in large unilamellar vesicles using fluorescence digital imaging microscopy. Caveolin, a major structural protein of caveolae, contains a scaffolding region (residues 82-101) that contributes to the binding of the protein to the plasma membrane. A caveolin peptide (82-101) corresponding to this scaffolding region induced the formation of membrane domains enriched in the acidic lipids phosphatidylserine and phosphatidylinositol-4,5-bisphosphate. Cholesterol, another predominant component of caveolae, was also enriched in these domains. Caveolae also contain many different signaling molecules including src family tyrosine kinases. Src proteins bind to the plasma membrane via a N-terminal myristate chain and a cluster of basic residues that can interact electrostatically with negatively charged lipids. A peptide corresponding to the src membrane binding motifs (residues myr-2-19) sequestered acidic lipids into lateral membrane domains. Both the src and the caveolin peptides colocalized together with acidic lipids in the domains. Control experiments show the domains are not the result of vesicle aggregation. Two-photon fluorescence correlation spectroscopy experiments suggest diffusion in the domains was slower, but the domains were dynamic. Protein kinase C phosphorylated src in its N-terminal membrane binding region; however, the caveolin scaffolding peptide inhibited this activity. Consequently, protein-induced membrane domains may affect cell signaling by organizing signal transduction components within the membrane and changing reaction rates.
Review on Non-Volatile Memory with High-k Dielectrics: Flash for Generation Beyond 32 nm (2014)

Flash memory is the most widely used non-volatile memory device nowadays. In order to keep up with the demand for increased memory capacities, flash memory has been continuously scaled to smaller and smaller dimensions. The main benefits of down-scaling cell size and increasing integration are that they enable lower manufacturing cost as well as higher performance. Charge trapping memory is regarded as one of the most promising flash memory technologies as further down-scaling continues. In addition, more and more exploration is investigated with high<i>-k</i> dielectrics implemented in the charge trapping memory. The paper reviews the advanced research status concerning charge trapping memory with high<i>-k</i> dielectrics for the performance improvement. Application of high<i>-k</i> dielectric as charge trapping layer, blocking layer, and tunneling layer is comprehensively discussed accordingly.
Fragment-Based Drug Design:  How Big Is Too Big? (2006)

Much has been discussed about the proper physicochemical properties (e.g., molecular weight, hydrophobicity, etc.) that should be considered when utilizing fragment leads in drug design. However, little has been reported as to what emphasis, if any, should be placed on the potency of the resulting fragment leads. In this report, a retrospective analysis of 18 highly optimized inhibitors is described in which the compounds were systematically deconstructed until the minimal binding elements could be identified. An analysis of the potency changes that were observed as the leads were reduced in size indicate that a nearly linear relationship exists between molecular weight and binding affinity over the entire range of sizes and potencies represented in the dataset. On the basis of these observations, prediction maps can be constructed that enable critical and quantitative assessments of the process of lead identification and optimization. These data place well-defined limits on the ideal size and potency of fragment leads that are being considered for use in fragment-based drug design.
Oligosaccharides in Human Milk: Structural, Functional, and Metabolic Aspects (2000)

Research on human milk oligosaccharides (HMOs) has received much attention in recent years. However, it started about a century ago with the observation that oligosaccharides might be growth factors for a so-called bifidus flora in breast-fed infants and extends to the recent finding of cell adhesion molecules in human milk. The latter are involved in inflammatory events recognizing carbohydrate sequences that also can be found in human milk. The similarities between epithelial cell surface carbohydrates and oligosaccharides in human milk strengthen the idea that specific interactions of those oligosaccharides with pathogenic microorganisms do occur preventing the attachment of microbes to epithelial cells. HMOs may act as soluble receptors for different pathogens, thus increasing the resistance of breast-fed infants. However, we need to know more about the metabolism of oligosaccharides in the gastrointestinal tract. How far are oligosaccharides degraded by intestinal enzymes and does oligosaccharide processing (e.g. degradation, synthesis, and elongation of core structures) occur in intestinal epithelial cells? Further research on HMOs is certainly needed to increase our knowledge of infant nutrition as it is affected by complex oligosaccharides.
Inflammatory Exposure and Historical Changes in Human Life-Spans (2004)

Most explanations of the increase in life expectancy at older ages over history emphasize the importance of medical and public health factors of a particular historical period. We propose that the reduction in lifetime exposure to infectious diseases and other sources of inflammation--a cohort mechanism--has also made an important contribution to the historical decline in old-age mortality. Analysis of birth cohorts across the life-span since 1751 in Sweden reveals strong associations between early-age mortality and subsequent mortality in the same cohorts. We propose that a "cohort morbidity phenotype" represents inflammatory processes that persist from early age into adult life.
A tetrazolium-based colorimetric MTT assay to quantitate human monocyte mediated cytotoxicity against leukemic cells from cell lines and patients with acute myeloid leukemia (1994)

The MTT-colorimetric monocyte mediated cytotoxicity assay, based upon the ability of living cells to reduce 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) into formazan, was evaluated using leukemic cells from five representative human leukemic cell lines and from 28 patients with acute myeloid leukemia (AML). An excellent linearity between absorbance and leukemic cell number was observed up to 5 x 10(4) cells/well and 50 x 10(4) cells/well for all cell lines and patients samples tested, respectively, in a 96-wells microtiter culture system. A huge variability in the susceptibility of leukemic cells to purified and IFN-gamma-activated human monocytes could be observed at effector-to-target cell (E:T) ratios of 1. The mean signal-to-noise ratio of the MTT assay for monocyte-leukemic cell mixtures from patients was 2.69 +/- 0.39 at E:T 1. In conclusion, the MTT based monocyte mediated cytotoxicity assay should be useful for studying the susceptibility of a variety of leukemic cells from cell lines and from patients with AML to monocytes in a rapid, sensitive and semi-automated manner.
Spt5 and Spt6 are associated with active transcription and have characteristics of general elongation factors in D. melanogaster (2000)

The Spt4, Spt5, and Spt6 proteins are conserved throughout eukaryotes and are believed to play critical and related roles in transcription. They have a positive role in transcription elongation in Saccharomyces cerevisiae and in the activation of transcription by the HIV Tat protein in human cells. In contrast, a complex of Spt4 and Spt5 is required in vitro for the inhibition of RNA polymerase II (Pol II) elongation by the drug DRB, suggesting also a negative role in vivo. To learn more about the function of the Spt4/Spt5 complex and Spt6 in vivo, we have identified Drosophila homologs of Spt5 and Spt6 and characterized their localization on Drosophila polytene chromosomes. We find that Spt5 and Spt6 localize extensively with the phosphorylated, actively elongating form of Pol II, to transcriptionally active sites during salivary gland development and upon heat shock. Furthermore, Spt5 and Spt6 do not colocalize widely with the unphosphorylated, nonelongating form of Pol II. These results strongly suggest that Spt5 and Spt6 play closely related roles associated with active transcription in vivo.
Liens over property : construction law (2007)

The builder's lien is a right of retention which the contractor acquires over the building or structure which it has constructed and for which it has not received payment. It is without doubt the most powerful tool the contractor has to ensure payment. The lien in itself can never constitute a cause of action as it is a form of tacit security, which provides the contractor with a defence against the vindicatory action of the owner of the property.
An auralization system for real time room acoustics simulation (2009)

A real time room acoustics auralization system for arbitrarily shaped rooms is presented. The system is based on an accelerated image source method and a time-dependent radiosity method for the computation of the complete binaural room impulse response. The auralization module is implemented as a wide band frequency dependence system. Elements such as wall and air absorption, source and receiver directivities are taken into account. The system permits the auralization of suitable audio signals by including the direct sound, the early specular and diffuse reflections as well as the reverberant tail of the room response. Accelerating techniques and algorithmic improvements are used in this system allowing real time auralization through binaural technology. RESUMEN Neste artigo e apresentado um sistema para a simulacao e auralizacao em tempo real da acustica de salas. O modulo de calculo do sistema baseia-se num metodo das imagens acelerado e num metodo de radiosidade hierarquica dependente do tempo para a computacao da resposta binaural de um dado espaco fechado, de geometria arbitraria. O modulo de auralizacao utiliza uma implementacao espectral de banda larga. As directividades da fonte e receptor sao consideradas, bem como a absorcao das paredes e a atenuacao no ar. O sistema permite a auralizacao de sinais sonoros anecoicos gravados tendo em conta o sinal directo, as primeiras reflexoes, especulares e difusas, bem como a cauda reverberante da resposta da sala em simulacao. Varias tecnicas de aceleracao e de optimizacao dos algoritmos sao utilizadas neste sistema permitindo a auralizacao em tempo real atraves da tecnologia binaural.
Intestinal fibrosis is reduced by early elimination of inflammation in a mouse model of IBD: Impact of a “Top-Down” approach to intestinal fibrosis in mice (2011)

This study demonstrates that intestinal fibrosis develops despite removal of an inflammatory stimulus and elimination of inflammation. Early intervention ameliorates but does not abolish subsequent fibrosis, suggesting that fibrosis, once initiated, is self-propagating, suggesting that a very early top-down interventional approach may have the most impact on fibrostenosing disease.
Dipeptidyl Peptidase IV Inhibition Reduces the Degradation and Clearance of GIP and Potentiates Its Insulinotropic and Antihyperglycemic Effects in Anesthetized Pigs (2001)

Glucose-dependent insulinotropic peptide (GIP) is known to be degraded by dipeptidyl peptidase IV (DPP IV), forming an inactive metabolite, but the extent of the enzyme's role in regulating the biological activity of GIP in vivo is still largely unknown. In nonfasted anesthetized pigs given an intravenous infusion of GIP, the intact peptide (determined by a novel NH(2)-terminally directed radioimmunoassay) accounts for only 14.5 +/- 2.5% of total immunoreactivity. This is increased (to 40.9 +/- 0.9%, P < 0.0001) by coadministration of valine-pyrrolidide (a specific DPP IV inhibitor) at a dose that completely inhibits plasma DPP IV activity. The plasma t(1/2) of intact GIP is prolonged by the inhibitor (from 3.3 +/- 0.3 to 8.1 +/- 0.6 min; P < 0.001), whereas the t(1/2) for COOH-terminal immunoreactivity is unaffected (13.2 +/- 0.5 and 11.5 +/- 0.8 min, pre- and postinhibitor). Measurement of arteriovenous concentration differences revealed that the liver, kidney, and extremities are the main sites of removal of exogenous intact GIP (organ extractions, 28.0 +/- 2.2, 26.3 +/- 5.7, and 21.8 +/- 3.0%, respectively). These organ extractions are reduced (P < 0.02) but not eliminated (kidney and extremities) by valine-pyrrolidide (to 6.5 +/- 4.6, 14.1 +/- 3.1, and 13.9 +/- 2.4%, respectively). Valine-pyrrolidide potentiates the insulinotropic effect of GIP (P < 0.02), resulting in an enhanced glucose disappearance rate (k, from 8.0 +/- 0.5 to 15.5 +/- 2.2%/min; P < 0.01) and a reduction in the glucose excursion after an intravenous glucose load (area under the curve, from 133 +/- 23 to 75 +/- 9 min. mmol/l; P < 0.05). These results suggest that DPP IV plays an important role in GIP metabolism but is not the sole enzyme responsible for its NH(2)-terminal degradation. Nevertheless, DPP IV inhibition increases the proportion of intact peptide sufficiently to enhance its insulinotropic and antihyperglycemic effects.
The Role of the Adenosinergic Pathway in Immunosuppression Mediated by Human Regulatory T Cells (Treg) (2011)

Tumor-induced dysfunction of immune cells is a common problem in cancer. Tumors induce immune suppression by many different mechanisms, including accumulation of regulatory T cells (Treg). Adaptive Treg (Tr1) generated in the tumor microenvironment express CD39 and CD73 ectonucleotidases, produce adenosine and are COX2+PGE2+. Adenosine and PGE2 produced by Tr1 or tumor cells bind to their respective receptors on the surface of T effector cells (Teff) and cooperate in up-regulating cytosolic 3'5'-cAMP levels utilizing adenylyl cyclase isoform 7 (AC-7). In Teff, increased cAMP mediates suppression of anti-tumor functions. Treg, in contrast to Teff, seem to require high cAMP levels for mediating suppression. This differential requirement of Treg and Teff for cAMP offers an opportunity for pharmacologic interventions using selected inhibitors of the adenosine/PGE2 pathways. Blocking of adenosine/PGE2 production by Tr1 or blocking binding of these factors to their receptors on T cells or inhibition of cAMP synthesis in Teff all represent novel therapeutic strategies that used in combination with conventional therapies could restore anti-tumor functions of Teff . At the same time, these inhibitors could disarm Tr1 cells by depriving them of the factors promoting their generation and activity or by down-regulating 3'5'-cAMP levels. Thus, the pharmacologic control of Treg-Teff interactions offers a novel strategy for restoration of anti-tumor Teff functions and silencing of Treg. Used in conjunction with anti-cancer drugs or with immune therapies, this strategy has a potential to improve therapeutic effects by preventing or reversing tumor-induced immune suppression.
Targeted deletion of B2-kinin receptors protects against the development of diabetic nephropathy (2007)

Diabetic nephropathy (DN), the leading cause of end-stage renal failure, is clinically manifested by albuminuria and a progressive decline in glomerular filtration rate. The factors and mechanisms that contribute to progression of DN are still undefined. To address the contribution of B(2)-kinin receptors (B2KR) to the development of DN, we studied B2KR knockout mice (B2KR(-/-)) and their wild-type littermates (B2KR(+/+)). Diabetes was induced by daily injections of streptozotocin (50 mg/kg body wt) for 3-5 days. A total of 48 mice divided into 4 groups were used: group 1, wild-type control (B2KR(+/+) C); group 2, wild-type diabetic (B2KR(+/+) D); group 3, B2KR knockout control (B2KR(-/-) C); and group 4, B2KR knockout diabetic (B2KR(-/-) D). Glucose levels and albumin excretion rate (AER) were measured at predetermined intervals. Half of the mice were killed at 3 mo, and the remaining half, at 6 mo. Plasma glucose levels were markedly elevated in both B2KR(+/+) D and B2KR(-/-) D groups of mice compared with their controls. Diabetic B2KR(-/-) mice displayed reduced AER as well as reduced glomerular and tubular injury compared with diabetic B2KR(+/+) mice. The renoprotection conferred by deletion of B2KR was associated with increased renal expression of B(1)-kinin and angiotensin II AT(2) receptors and decreased expression of connective tissue growth factor. At a cellular level, our findings demonstrate that bradykinin downregulates the expression of AT(2) receptors in mesangial cells. These findings provide the first evidence that targeted deletion of B2KR protects against the development of DN.
A 118-mW Pulse-Based Radar SoC in 55-nm CMOS for Non-Contact Human Vital Signs Detection (2017)

We report a direct-RF pulse-based radar System on Chip (SoC) with applications in vital signs monitoring and occupancy detection. The transmitter complies with FCC, ETSI, and KCC regulatory masks with -10 dB bandwidths of 1.4 and 1.5 GHz centered at 7.29 and 8.748 GHz. The receiver samples the reflected signal at 23.328 GS/s, covering a 9.9-m consecutive range. The measured front-end noise figure is 6.3 dB with 14.7-dB gain at 7.29 GHz. Chest movements from breathing and heartbeats in a human subject were detected at 9 and 5 m, respectively. All required power management and clock functions are integrated on-chip. The SoC was implemented in 55-nm CMOS. In active mode, the system consumes 118 mW from a 1.8-V power supply.
Gap junctions and connexins: potential contributors to the immunological synapse (2002)

Gap junctional communication is a widespread mechanism for metabolic coupling of adjoining cells. In the immune system, evidence has built up showing that lymphocytes possess the protein building blocks of gap junctions, the connexins. The most widespread is connexin 43, but connexin 40 is also present in secondary lymphoid organs. Inhibitors of gap junctional communication, especially the highly specific connexin mimetic peptides, have been shown to decrease the secretion of immunoglobulins and cytokines by T and B lymphocyte cocultures, indicating that connexins may play a fundamental role in lymphocyte physiology. Traditionally, connexins function when assembled into gap junction-intercellular channels. However, the possibility is now arising that gap junction hemichannels, previously viewed as plasma membrane precursors of gap junctions, are also involved in the release from cells of small metabolites, e.g., adenosine 5'-triphosphate and nicotinamide adenine dinucleotide(+), and this opens up a second, possible paracrine function for connexins detected in lymphocytes. The increasing structural and functional evidence points to a potential role that lymphocyte gap junctional intercellular communication may play within the complex signaling components of the immunological synapse.
Selective value prediction (1999)

Value Prediction is a relatively new technique to increase instruction-level parallelism by breaking true data dependence chains. A value prediction architecture produces values, which may be later consumed by instructions that execute speculatively using the predicted value.This paper examines selective techniques for using value prediction in the presence of predictor capacity constraints and reasonable misprediction penalties. We examine prediction and confidence mechanisms in light of these constraints, and we minimize capacity conflicts through instruction filtering. The latter technique filters which instructions put values into the value prediction table. We examine filtering techniques based on instruction type, as well as giving priority to instructions belonging to the longest data dependence path in the processor's active instruction window. We apply filtering both to the producers of predicted values and the consumers. In addition, we examine the benefit of using different confidence levels for instructions using predicted values on the longest dependence path.
An antibody-interleukin 2 fusion protein overcomes tumor heterogeneity by induction of a cellular immune response. (1996)

Antibody-based therapies for cancer rely on the expression of defined antigens on neoplastic cells. However, most tumors display heterogeneity in the expression of such antigens. We demonstrate here that antibody-targeted interleukin 2 delivery overcomes this problem by induction of a host immune response. Immunohistochemical analysis demonstrated that the antibody-interleukin 2 fusion protein-induced eradication of established tumors is mediated by host immune cells, particularly CD8+ T cells. Because of this cellular immune response, antibody-directed interleukin 2 therapy is capable to address established metastases displaying substantial heterogeneity in expression of the targeted antigen. This effector mechanism further enables the induction of partial regressions of large subcutaneous tumors that exceeded more than 5% of the body weight. These observations indicate that antibody-directed cytokine delivery offers an effective new tool for cancer therapy.
SARS-CoV-2 Neutralizing Antibody Responses Are More Robust in Patients with Severe Disease (2020)

We studied plasma antibody responses of 35 patients about 1 month after SARS-CoV-2 infection. Titers of antibodies binding to the viral nucleocapsid and spike proteins were significantly higher in patients with severe disease. Likewise, mean antibody neutralization titers against SARS-CoV-2 pseudovirus and live virus were higher in the sicker patients, by ~5-fold and ~7-fold, respectively. These findings have important implications for those pursuing plasma therapy, isolation of neutralizing monoclonal antibodies, and determinants of immunity.