gebhart/patrepeval huggingface dataset:
Clinical versus mechanical prediction: A meta-analysis. (2000)

The process of making judgments and decisions requires a method for combining data. To compare the accuracy of clinical and mechanical (formal, statistical) data-combination techniques, we performed a meta-analysis on studies of human health and behavior. On average, mechanical-prediction techniques were about 10% more accurate than clinical predictions. Depending on the specific analysis, mechanical prediction substantially outperformed clinical prediction in 33%-47% of studies examined. Although clinical predictions were often as accurate as mechanical predictions, in only a few studies (6%-16%) were they substantially more accurate. Superiority for mechanical-prediction techniques was consistent, regardless of the judgment task, type of judges, judges' amounts of experience, or the types of data being combined. Clinical predictions performed relatively less well when predictors included clinical interview data. These data indicate that mechanical predictions of human behaviors are equal or superior to clinical prediction methods for a wide range of circumstances.
Photochemistry of manganese porphyrins. Part 1.—Characterisation of some water soluble complexes (1979)

Manganese(III) forms many high spin d4 porphyrins, for which pyridyl, N-methylpyridyl, sulphonic acid and carboxylic acid and carboxylic acid functions act as water solubilising groups. Reduction with dithionite yields the corresponding manganese(II) porphyrin. Both oxidation states have been clearly identified by e.p.r. and magnetic susceptibility measurements. On the other hand, oxidation with persulphate gives an unstable manganese(III) porphyrin π-radical cation which appears to form a dimer in aqueous solution at pH ≈ 10. All the porphyrins undergo a series of acid/base transitions in alkaline solution due to axially coordinated water molecules. For manganese(III) porphyrins, there are two pK transitions, around 8.0 and 10.5, and electrophoresis has identified the total electronic charge of each of the acid/base forms.
ACC/AHA Release Updated Guideline on the Treatment of Blood Cholesterol to Reduce ASCVD Risk (2014)

The Blood Cholesterol Expert Panel from the American College of Cardiology (ACC) and the American Heart Association (AHA) issued an updated evidence-based guideline in 2013 that addresses the use of fixed doses of cholesterol-lowering drugs (statins) to reduce the risk of ASCVD in adults 21 years and older.
Kerr-gated picosecond Raman spectroscopy and Raman photon migration of equine bone tissue with 400-nm excitation (2004)

We show that Raman spectroscopy with visible lasers, even in the deep blue is possible with time-gated Raman spectroscopy. A 4 picosec time gate allows efficient fluorescence rejection, up to 1000X, and provides almost background-free Raman spectra with low incident laser power. The technology enables spectroscopy with better than 10X higher scattering efficiency than is possible with the NIR (785 nm and 830 nm) lasers that are conventionally used. Raman photon migration is shown to allow depth penetration. We show for the first time that Kerr-gated Raman spectra of bone tissue with blue laser excitation enables both fluorescence rejection and depth penetration.
Reclaiming the Brain (2014)

Software-defined networks (SDNs) have the potential to radically simplify the network management by providing a programmatic interface to a logically centralized controller. However, outsourcing the management to the software controller comes at a price, and good tradeoffs have to be found between the benefits of a fine-grained control and its costs.
Agonistic and antagonistic properties of CD40 mAb G28-5 are dependent on binding valency. (1994)

CD40 functional responses can be triggered by binding of mAb G28-5. Here we show that G28-5 induces partial CD40 responses and functions as a partial antagonist of natural CD40 ligand, gp39, by preventing gp39 binding. Fab fragments of G28-5 retain inhibitory activity but lose crosslinking-dependent stimulatory activity. The synergistic interaction of CD40 signals with PMA or CD20 show differential requirements for CD40 crosslinking and different sensitivity to cyclosporine A, suggesting that CD40 receptor may use different effector mechanisms for synergy with calcium-dependent CD20 signals or with calcium-independent signals from PMA. Activation of NF-kappa B occurred in RAJI cells by G28-5 or by gp39 treatment, and was CD40 crosslinking-dependent. These results suggest that activation of NF-kappa B is involved in some CD40 receptor signals and may be related to CD40 effects on stimulation or inhibition of apotosis.
Broad neutralization of SARS-related viruses by human monoclonal antibodies (2020)

Broadly protective vaccines against known and preemergent human coronaviruses (HCoVs) are urgently needed. To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent severe acute respiratory syndrome (SARS) donor and identified 200 SARS coronavirus 2 (SARS-CoV-2) binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the non-neutralizing antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of preexisting memory B cells elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a target for the rational design of pan-sarbecovirus vaccines.
Monoclonal antibodies to human eosinophil plasma membrane antigens enhance the secretion of eosinophil cationic protein. (1986)

This study was done to examine the nature of the membrane constituents involved in the secretion of eosinophil cationic protein (ECP) from human blood eosinophils. Three mouse monoclonal antibodies were used, which showed greater binding to membrane antigens on activated, and light density eosinophils from patients with an eosinophilia, than on nonactivated or normal density eosinophils. All three antibodies (EoN4, EoN5 & EoN6) stimulated normal density human eosinophils to secrete ECP, either alone or in association with sepharose-C3b. The antibodies bound to at least two separate sites on the membrane, which were distinct from the receptors for immunoglobulins, C3b, and eosinophil activating factor. One combination of antibodies increased the amount of ECP which was secreted. The membrane antigen recognized by antibody EoN4 was a glycoprotein, molecular weight 75 kD. These findings showed that ECP secretion may be induced by a wider range of stimuli than has been previously recognized, and that the antigens recognized by these monoclonal antibodies may play an important role in the induction of eosinophil degranulation.
Blood Groups and HLA Antigens in Patients with Abdominal Aortic Aneurysms (1984)

Frequencies of blood groups (ABO, Rh, MNSs, P, Kell, Lewis and Duffy) and HLA antigens were studied in a series of patients from northern Sweden with abdominal aortic aneurysms. The following significant differences from the controls were found: a decreased frequency of the Rh-negative blood group and increased frequencies of the Kell-positive and MN blood groups. Previously reported associations with the ABO and Rh systems were not confirmed.
Folate Transport and the Modulation of Antifolate Sensitivity in a Methotrexate-Resistant Human Breast Cancer Cell Line (1991)

The mechanism of acquired methotrexate-resistance in an estrogen-receptor positive human breast cancer cell line (MTX(R)ZR-75-1) was studied. MTX(R) ZR-75-1 cells are 250-fold resistant to methotrexate when grown in the presence of 1 microM folinic acid and 2,400-fold resistant in the presence of 1 microM folic acid. This drug resistant cell line also showed collateral sensitivity (10-fold) to trimetrexate (TMQ), when grown in the presence of folinic acid. Using fluoresceinated methotrexate (F-MTX), FACS analysis indicated that there is no intracellular accumulation of methotrexate into MTX(R) ZR-75-1 cells, as determined by competition of F-MTX and methotrexate binding to dihydrofolate reductase. These characteristics strongly indicate that the mechanism of resistance involved down regulation of the reduced-folate transporter. To investigate this further, the transport kinetics of parental and MTX(R) ZR-75-1 cells were examined. Although the V(max) for methotrexate transport in wild-type (WT) ZR-75-1 breast cancer cells was 1-2 orders of magnitude lower than that in the well characterized leukemia cell lines, such as L1210 and CCRF-CEM cells, kinetic analysis indicated that transport of methotrexate into WT ZR-75-1 cells involved a mechanism that was similar if not identical to the reduced folate transporter. In contrast, no specific uptake of methotrexate was detected in MTX(R) ZR-75-1cells. Furthermore, neither cell line expressed detectable levels of folate binding protein, a binding protein with high affinity for folic acid as well as for reduced folates and antifolates. These results indicate that the level of expression of the reduced-folate carrier may be an important factor in determining the sensitivity of breast cancer cells as well as leukemia cells to antifolate compounds.
Multiwavelength networks and new approaches to packet switching (1989)

The author shows how the bandwidth available through the use of multiwavelength optical-fiber technology can be used to achieve novel large-capacity switching systems to address anticipated switching bottlenecks. He does so by describing the features and network applications of a specific multiwavelength network, the Bellcore LAMBDANET packet switch. The discussion is then extended to a number of recent proposals for switching fabrics based on this new multiwavelength technology. The particular technologies he discusses are: the photonic knockout switch, a proposal similar to the concept of the LAMBDANET, but not requiring N receivers at each node; the FOX (fast optical cross-connect), an active wavelength routing approach; the ShuffleNet architecture; the HYPASS and BHYPASS switches; the coherent wavelength division lambda switch; and the Bellcore Star-Track multicast switch.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Binding and presentation of peptides derived from melanoma antigens MART-1 and glycoprotein-100 by HLA-A2 subtypes. Implications for peptide-based immunotherapy (1996)

Cellular immune responses to melanoma-associated Ags are the focus of ongoing studies aimed at developing immunotherapies for treatment of malignant melanoma. Melanoma predominantly affects Caucasians, a population in whom expression of HLA-A2 is prevalent. Among HLA-A2 subtypes, HLA-A*0201 is widely expressed, and HLA-A*0201-restricted, tumor-reactive CTL responses are well studied. We have observed in a group of melanoma patients an unexpectedly high frequency (approximately 20%) of non-HLA-A*0201 subtypes (*0202, *0204, and *0205), and little is known regarding antimelanoma response profiles in patients expressing such subtypes. We analyzed non-HLA-A*0201 peptide response profiles using HLA-A*0201-restricted epitopes from melanoma Ags MART-1/Melan A and glycoprotein 100. Most of these peptides bound to the majority of subtypes tested with 50% inhibitory concentrations less than 500 nM. Recognition of cells pulsed with different peptides (MART-1(27-35), G9(154), and G9(280) Flu M1(58-66)) and expressing different subtype molecules by HLA-A*0201-restricted CTL was limited to only a subset of non-HLA-A*0201 molecules, and the peptide/subtype complexes recognized varied among the effector populations tested. CTL responses elicited from PBL of patients and healthy donors expressing subtypes HLA-A*0202 and HLA-A*0205 suggested significant differences among HLA-A2 subtype function in the context of melanoma Ag presentation. These observations imply the necessity of subtyping patients considered for peptide-based protocols and highlight the need for further study of melanoma-directed cellular responses among patients expressing non-HLA-A*0201 subtypes.
Feature Selection for Unsupervised and Supervised Inference: The Emergence of Sparsity in a Weight-Based Approach (2005)

The problem of selecting a subset of relevant features in a potentially overwhelming quantity of data is classic and found in many branches of science. Examples in computer vision, text processing and more recently bio-informatics are abundant. In text classification tasks, for example, it is not uncommon to have 10 4 to 10 7 features of the size of the vocabulary containing word frequency counts, with the expectation that only a small fraction of them are relevant. Typical examples include the automatic sorting of URLs into a web directory and the detection of spam email. In this work we present a definition of “relevancy ” based on spectral properties of the Laplacian of the features ’ measurement matrix. The feature selection process is then based on a continuous ranking of the features defined by a least-squares optimization process. A remarkable property of the feature relevance function is that sparse solutions for the ranking values naturally emerge as a result of a “biased non-negativity ” of a key matrix in the process. As a result, a simple leastsquares optimization process converges onto a sparse solution, i.e., a selection of a subset of features which form a local maxima over the relevance function. The feature selection algorithm can be embedded in both unsupervised and supervised inference problems and empirical evidence show that the feature selections typically achieve high accuracy even when only a small fraction of the features are relevant. 1.
Chemotactic Properties of Angiopoietin-1 and -2, Ligands for the Endothelial-specific Receptor Tyrosine Kinase Tie2 (1998)

Angiopoietin-1 and its putative natural antagonist, angiopoietin-2, were recently isolated, and the critical role of angiopoietin-1 in embryogenic angiogenesis was demonstrated by targeted gene disruption. Specific biological effects of angiopoietin-1, however, have yet to be defined. In this study we demonstrate that angiopoietin-1, but not angiopoietin-2, is chemotactic for endothelial cells. In contrast, angiopoietin-1 as well as angiopoietin-2 exhibit no proliferative effect on endothelial cells. Excess soluble Tie2, but not Tie1 receptor, abolish the chemotactic response of endothelial cells toward angiopoietin-1. Angiopoietin-2 dose-dependently blocks directed migration toward angiopoietin-1, consistent with the role of angiopoietin-2 as a naturally occurring inhibitor of angiopoietin-1. Fibroblasts stably transfected with Tie2 receptor exhibit chemotactic responses for both angiopoietin-1 and angiopoietin-2. Fibroblasts stably expressing a transfected chimeric receptor consisting of the ectodomain of TrkC fused to the cytoplasmic domain of Tie2 also exhibit a chemotactic response to neurotrophin 3 (NT-3), a specific ligand for TrkC. Endothelial cells are shown to express angiopoietin-2 mRNA and protein, indicating the potential for autocrine activation of angiopoietin/Tie2. Finally, the demonstration that Tie2 as well as angiopoietin-1 are expressed in normal human arteries and veins suggests that the role of angiopoietin/Tie2 may extend beyond embryonic angiogenesis to maintaining integrity of the adult vasculature.
Preculture of PBMCs at high cell density increases sensitivity of T-cell responses, revealing cytokine release by CD28 superagonist TGN1412 (2011)

Human volunteers receiving TGN1412, a humanized CD28-specific monoclonal antibody, experienced a life-threatening cytokine release syndrome during a recent trial. Preclinical tests using human PBMCs had failed to announce the rapid release of TNF, IFN-γ, and other toxic cytokines in response to this CD28 "superagonist" (CD28SA). CD28SA activate T-lymphocytes by ligating CD28 without overt engagement of the TCR. They do, however, depend on "tonic" TCR signals, which they amplify. Here we show that short-term preculture of PBMCs at high, but not at low, cell density results in massive cytokine release during subsequent stimulation with soluble TGN1412. Restoration of reactivity was cell-contact dependent, involved functional maturation of both monocytes and T cells, was sensitive to blockade by HLA-specific mAb, and was associated with TCR polarization and tyrosine phosphorylation. CD4 effector memory T cells were identified as the main source of proinflammatory cytokines. Importantly, responses to other T-cell activating agents, including microbial antigens, were also enhanced if PBMCs were first allowed to interact under tissue-like conditions. We provide a protocol, which strongly improves reactivity of circulating T cells to soluble stimulants, thereby allowing for more reliable preclinical testing of both activating and inhibitory immunomodulatory drugs.
A bulge structure in HIV-1 TAR RNA is required for Tat binding and Tat-mediated trans-activation. (1990)

The Tat protein of human immunodeficiency virus type 1 (HIV-1) trans-activates viral gene expression and is obligatory for virus replication. Tat function is mediated through a sequence termed TAR that comprises part of the 5'-noncoding region of all HIV-1 mRNAs. This region forms a stable stem-loop structure in vitro. Recent evidence indicates that Tat binds directly to the TAR RNA sequence, and this binding is independent of the nucleotide sequence in the loop but dependent on the integrity of the upper stem. We used the electrophoretic mobility-shift assay to identify the sequence and structure specificity of this interaction and its correlation with Tat trans-activation. We show that a 3-nucleotide bulge structure (positions +23 to +25) in TAR RNA is important for both Tat interaction with TAR RNA and Tat-mediated trans-activation of gene expression. Single base substitutions at position +23 that impair Tat-mediated trans-activation in vivo also reduce binding of Tat to TAR in vitro, suggesting that the first uridine residue in the bulge is the critical base for both functions. In contrast, mutations in the loop (positions +31 to +34) and the stem (positions +9 to +12 and +49 to +52), which reduce Tat-mediated trans-activation, had no effect on Tat binding. We also show that a Tat peptide that includes the basic region required for nucleolar localization binds to TAR RNA with the same specificity as the full-length protein. We conclude that Tat binding to TAR is necessary but not sufficient by itself to account for trans-activation.
On the Reduction of Entropy Coding Complexity via Symbol Grouping: I - Redundancy Analysis and Optimal Alphabet Partition (2004)

We analyze the technique for reducing the complexity of entropy coding that consists in the a priori grouping of the source alphabet symbols, and in the decomposition of the coding process in two stages: first coding the number of the symbol's group with a more complex method, followed by coding the symbol's rank inside its group using a less complex method, or simply using its binary representation. This technique proved to be quite effective, yielding great reductions in complexity with reasonably small losses in compression, even when the groups are designed with empiric methods. It is widely used in practice and it is an important part in standards like MPEG and JPEG. However, the theory to explain its effectiveness and optimization had not been sufficiently developed. In this work, we provide a theoretica l analysis of the properties of these methods in general circumstances. Next, we study the problem of finding optimal source alphabet partitions. We demonstrate a necessary optimality condition that eliminates most of the possible solutions, and guarantees that a more constrained version of the problem, which can be solved via dynamic programming, provides the optimal solutions. In addition, we show that the data used by the dynamic programming optimization has properties similar to the Monge matrices, allowing the use of much more efficient solution methods.
Association of CBFA2 mutation with decreased platelet PKC-θ and impaired receptor-mediated activation of GPIIb-IIIa and pleckstrin phosphorylation: proteins regulated by CBFA2 play a role in GPIIb-IIIa activation (2003)

The mechanisms by which agonists activate glycoprotein (GP) IIb-IIIa function remain unclear. We have reported data on a patient with thrombocytopenia and impaired receptor-mediated aggregation, phosphorylation of pleckstrin (a protein kinase C [PKC] substrate), and activation of the GPIIb-IIIa complex. Abnormalities in hematopoietic transcription factors have been associated with thrombocytopenia and platelet dysfunction. To define the molecular mechanisms, we amplified from patient platelet RNA exons 3 to 6 of core-binding factor A2 (CBFA2) cDNA, which encompasses the DNA-binding Runt domain; a 13-nucleotide (nt) deletion was found (796-808 nt). The gDNA revealed a heterozygous mutation (G>T) in intron 3 at the splice acceptor site for exon 4, leading to a frameshift with premature termination in the Runt domain. On immunoblotting, platelet CBFA2, PKC-, albumin, and IgG were decreased, but pleckstrin, PKC-alpha, -betaI, -betaII, -eta, -epsilon, -delta, and -zeta, and fibrinogen were normal. Our conclusions are that (1) CBFA2 mutation is associated with not only thrombocytopenia, but also impaired platelet protein phosphorylation and GPIIb-IIIa activation; (2) proteins regulated by CBFA2 are required for inside-out signal transduction-dependent activation of GPIIb-IIIa; and (3) we have documented the first deficiency of a human PKC isozyme (PKC-), suggesting a major role of this isozyme in platelet production and function.
T-Cell Recognition of Human Melanoma Antigens (1993)

The adoptive transfer of tumor-infiltrating lymphocytes (TILs) with interleukin-2 (IL-2) has antitumor activity in some patients with metastatic melanoma. We have analyzed molecular mechanisms of TIL recognition of human melanoma. Some cultured TILs specifically lysed autologous and some allogeneic melanomas sharing a variety of class I major histocompatibility complex (MHC) molecules. HLA-A2-restricted melanoma-specific TILs lysed many HLA-A2+ melanoma cell lines from different patients but failed to lyse HLA-A2- melanoma and HLA-A2+ nonmelanoma cell lines. However, these TILs were capable of lysing many naturally HLA-A2- melanomas after introduction of the HLA-A2.1 gene by vaccinia virus. These results indicate that shared melanoma antigens (Ag) are expressed in melanomas regardless of their human leukocyte antigen types. In order to identify these shared melanoma Ags, we have tested some known proteins expressed in melanoma. Expression of tyrosinase or HMB45 Ag correlated with lysis of TILs. We are also attempting to isolate antigenic peptides by high performance liquid chromatography separation and genes encoding melanoma Ag by cDNA expression cloning. The T-cell component of the antimelanoma response was also analyzed by determining the genetic structure of the T-cell receptor (TCR) used by melanoma TILs. However, we did not observe common TCR variable region usage by different melanoma TILs. We could establish melanoma cell clones and lines resistant to TIL lysis due to the absence of or defects in the expression of Ag, MHC, or beta 2-microglobulin molecules. These data indicate multiple mechanisms for melanoma escape from T-cell immunosurveillance.(ABSTRACT TRUNCATED AT 250 WORDS)