gebhart/patrepeval huggingface dataset:
Abstract B35: Hyaluronan (HA) accumulation in tumors predicts response to pegylated rHuPH20 hyaluronidase (PEGPH20) in human tumors: A biomarker strategy. (2011)

Abstract Increasing evidence suggests that the tumor microenvironment (TME) is a potential source of novel anti-tumor targets. Extracellular matrix components in the TME include the matrix glycosaminoglycan, hyaluronan (HA), which accumulates in 20–30% of solid tumors. HA functions to increase water content of HA-rich stroma, thereby creating high tumor interstitial fluid pressure (IFP) characteristic of many tumors. Cells engineered to overexpress hyaluronan synthase form tumors more readily in mouse models, and HA accumulation has been associated with disease progression and poor prognosis in human cancers. Enzymatic degradation of HA with hyaluronidase can reduce IFP and facilitate delivery of anti-tumor agents. We have previously presented data that demonstrate the therapeutic potential of PEGPH20 in tumor xenografts derived from a spectrum of human malignancies. Here we highlight the utility of HA detection methods that use aggrecan-derived HA binding region (HABR). Accumulation of HA was measured in tumor tissues from 14 different xenografts and compared with anti-tumor activity of PEGPH20. When cell line-derived tumors were classified according to HABR staining intensity as HA+1,2,3 (low to high staining), the anti-tumor activity of PEGPH20 correlated with higher accumulation of HA in tumor specimens (r=0.8). To more rigorously test the hypothesis that HA-depletion is an effective candidate therapeutic approach for cancer, we utilized non-small cell lung cancer (SCC) patient tumor explants which were characterized for HA accumulation in advance of implantation into immunodeficient mice. Three SCC explants (HA+1,2,3) were treated with PEGPH20 and tumor growth was measured over a 2-week interval. Tumor growth inhibition corresponded to HA accumulation status, with the most dramatic reduction (97%; 4/10 regressions) observed in the HA+3 SCC explants. We have extended this work and detected tumor HA in pre- and post-treatment tumor biopsies collected from two patients enrolled in a Phase 1 study with PEGPH20. In both sets of specimens, a reduction in HA accumulation was demonstrated following PEGPH20 treatment. These results provide a rationale to assess tumor HA staining as a promising biomarker for clinical investigation with PEGPH20 for the treatment of solid tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B35.
THE PRIMARY EMPTY SELLA (1973)

From the Departments of Medicine, Radiology, and Physiology, Duke University Medical Center, Durham, N.C. 27710.
Data Clustering Using a Model Granular Magnet (1997)

We present a new approach to clustering, based on the physical properties of an inhomogeneous ferromagnet. No assumption is made regarding the underlying distribution of the data. We assign a Potts spin to each data point and introduce an interaction between neighboring points, whose strength is a decreasing function of the distance between the neighbors. This magnetic system exhibits three phases. At very low temperatures, it is completely ordered; all spins are aligned. At very high temperatures, the system does not exhibit any ordering, and in an intermediate regime, clusters of relatively strongly coupled spins become ordered, whereas different clusters remain uncorrelated. This intermediate phase is identified by a jump in the order parameters. The spin-spin correlation function is used to partition the spins and the corresponding data points into clusters. We demonstrate on three synthetic and three real data sets how the method works. Detailed comparison to the performance of other techniques clearly indicates the relative success of our method.
Targeting inflammatory pathways for the treatment of cardiovascular disease (2013)

This editorial refers to ‘Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis’[†][1], by S. Kaptoge et al ., on page 578 

In the 15 years that have passed since C-reactive protein was linked to future cardiovascular events in otherwise healthy individuals,1 no alternative biomarker has proved to be a superior surrogate for vascular inflammation in the prediction of global cardiovascular risk. This observation is re-affirmed in population-based prospective cohort data from the Danish Research Center of Prevention and Health published by Kaptoge and colleagues in this issue of the European Heart Journal .2 In brief, in age- and gender-adjusted analyses, as well as in full multivariate models, basal levels of the ‘upstream’ pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-18, and tumour necrosis factor-α (TNF-α) were all associated with future vascular events in an approximately log-linear manner, as were levels of matrix metalloproteinase-9. However, and also consistent with prior work in this arena, the magnitudes of these effects were smaller than that associated with the ‘downstream’ inflammatory biomarker, C-reactive protein. Furthermore, among those study participants in whom direct comparison could be performed, only two biomarkers—downstream C-reactive protein (hazard ratio 1.69 per 1 SD higher baseline level) and upstream TNF-α (hazard ratio 1.32 per 1 SD higher baseline level)—remained statistically significant predictors of future vascular risk when simultaneously adjusting for the full panel of cytokines and chemokines.

The core question raised in the present analysis, however, does not relate to which inflammatory biomarker is best suited for clinical practice. That issue was addressed in a prior comprehensive meta-analysis from the Emerging Risk Factors Collaboration, in which the incremental utility of C-reactive protein for predicting vascular risk was found to be fully comparable in magnitude to that of total and high-density lipoprotein cholesterol.3 Rather, what the present …

 [1]: #fn-2
Pathophysiologic basis of contrast enhancement in breast tumors (1999)

While the diagnostic benefits of gadolinium (Gd)-chelate contrast agents are firmly established in magnetic resonance imaging (MRI) of tumors, the pathophysiologic basis of the enhancement observed and its histopathologic correlate remained vague. Tumor angiogenesis is fundamental for growth and metastasis and also of interest in new therapeutic concepts. By correlative analysis of a) histology; b) vascular density (CD31); and c) vascular permeability (vascular permeability factor/vascular endothelial growth factor [VPF/VEGF]), we found a) significantly (P < 0.001) faster exchange rates in malignant compared with benign breast lesions; b) distinct differences in enhancement characteristics between the histologic types (invasive ductal carcinoma, invasive lobular carcinoma, and ductal carcinoma in situ); and c) dependence of enhancement kinetics on the VPF/VEGF expression. The pathophysiologic basis for the differences in contrast enhancement patterns of tumors detectable by MRI is mainly due to vascular permeability, which leads to more characteristic differences than vascular density. MRI is able to subclassify malignant breast tumors due to their different angiogenetic properties.
Identification of Mutations Contributing to the Temperature-Sensitive, Cold-Adapted, and Attenuation Phenotypes of the Live-Attenuated Cold-Passage 45 ( cp 45) Human Parainfluenza Virus 3 Candidate Vaccine (1999)

The live-attenuated human parainfluenza virus 3 (PIV3) cold-passage 45 (cp45) candidate vaccine was shown previously to be safe, immunogenic, and phenotypically stable in seronegative human infants. Previous findings indicated that each of the three amino acid substitutions in the L polymerase protein of cp45 independently confers the temperature-sensitive (ts) and attenuation (att) phenotypes but not the cold-adaptation (ca) phenotype (29). cp45 contains 12 additional potentially important point mutations in other proteins (N, C, M, F, and hemagglutinin-neuraminidase [HN]) or in cis-acting sequences (the leader region and the transcription gene start [GS] signal of the N gene), and their contribution to these phenotypes was undefined. To further characterize the genetic basis for the ts, ca, and att phenotypes of this promising vaccine candidate, we constructed, using a reverse genetics system, a recombinant cp45 virus that contained all 15 cp45-specific mutations mentioned above, and found that it was essentially indistinguishable from the biologically derived cp45 on the basis of plaque size, level of temperature sensitivity, cold adaptation, level of replication in the upper and lower respiratory tract of hamsters, and ability to protect hamsters from subsequent wild-type PIV3 challenge. We then constructed recombinant viruses containing the cp45 mutations in individual proteins as well as several combinations of mutations. Analysis of these recombinant viruses revealed that multiple cp45 mutations distributed throughout the genome contribute to the ts, ca, and att phenotypes. In addition to the mutations in the L gene, at least one other mutation in the 3' N region (i.e., including the leader, N GS, and N coding changes) contributes to the ts phenotype. A recombinant virus containing all the cp45 mutations except those in L was more ts than cp45, illustrating the complex nature of this phenotype. The ca phenotype of cp45 also is a complex composite phenotype, reflecting contributions of at least three separate genetic elements, namely, mutations within the 3' N region, the L protein, and the C-M-F-HN region. The att phenotype is a composite of both ts and non-ts mutations. Attenuating ts mutations are located in the L protein, and non-ts attenuating mutations are located in the C and F proteins. The presence of multiple ts and non-ts attenuating mutations in cp45 likely contributes to the high level of attenuation and phenotypic stability of this promising vaccine candidate.
Sharing Visual Features for Multiclass and Multiview Object Detection (2007)

We consider the problem of detecting a large number of different classes of objects in cluttered scenes. Traditional approaches require applying a battery of different classifiers to the image, at multiple locations and scales. This can be slow and can require a lot of training data since each classifier requires the computation of many different image features. In particular, for independently trained detectors, the (runtime) computational complexity and the (training-time) sample complexity scale linearly with the number of classes to be detected. We present a multitask learning procedure, based on boosted decision stumps, that reduces the computational and sample complexity by finding common features that can be shared across the classes (and/or views). The detectors for each class are trained jointly, rather than independently. For a given performance level, the total number of features required and, therefore, the runtime cost of the classifier, is observed to scale approximately logarithmically with the number of classes. The features selected by joint training are generic edge-like features, whereas the features chosen by training each class separately tend to be more object-specific. The generic features generalize better and considerably reduce the computational cost of multiclass object detection.
Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation (2010)

End-stage liver disease caused by chronic hepatitis C virus (HCV) infection is a leading cause for liver transplantation (LT). Due to viral evasion from host immune responses and the absence of preventive antiviral strategies, reinfection of the graft is universal. The mechanisms by which the virus evades host immunity to reinfect the liver graft are unknown. In a longitudinal analysis of six HCV-infected patients undergoing LT, we demonstrate that HCV variants reinfecting the liver graft were characterized by efficient entry and poor neutralization by antibodies present in pretransplant serum compared with variants not detected after transplantation. Monoclonal antibodies directed against HCV envelope glycoproteins or a cellular entry factor efficiently cross-neutralized infection of human hepatocytes by patient-derived viral isolates that were resistant to autologous host-neutralizing responses. These findings provide significant insights into the molecular mechanisms of viral evasion during HCV reinfection and suggest that viral entry is a viable target for prevention of HCV reinfection of the liver graft.
1D Tellurium Nanostructures: Photothermally Assisted Morphology‐Controlled Synthesis and Applications in Preparing Functional Nanoscale Materials (2007)

Abstract A facile visible‐light‐assisted solution‐phase approach has been successfully developed to synthesize trigonal Te 1D nanostructures. By varying the relative amount of H 2 TeO 3 and water‐soluble polymers, wirelike, beltlike, tubular Te, and Te nanoparticle‐joined 1D aggregates, as well as a novel thorny 1D assembly of Te nanothreads can be synthesized on a large scale. The diameter of the Te nanowires can be modulated by controlling the nucleation and growth process through modulation of the pH value of the reaction mixture. It is believed that the light irradiation and thermal effect play a significant role in this photothermally assisted technique. We have shown that the Te nanowires can be used as a template to prepare Pt–Te nanochains, where the composition of Pt in the Pt–Te 1D products can be modulated by adjusting the ratio of the Te nanowires and Pt salts. Preliminary optical investigations reveal that blue–violet emission of Te nanowires can be enhanced by the formation of defects or dislocations in the Te region through the galvanic replacement reaction between Te nanowires and H 2 PtCl 6 . In addition, we demonstrate that Te 1D nanostructures can be utilized to prepare Te at carbon‐rich nanocables and carbonaceous nanotubes. Te–Pt at carbon‐rich nanocables can also be fabricated using Te–Pt nanochains as the template. These Pt–Te nanochains and carbonaceous nanostructures are expected to find wide applications in electrochemistry, catalysis, fuel cells, sensors, and other fields. Furthermore, the successful preparation of Te 1D nanostructures with abundant shapes, Pt–Te nanochains, and their carbonaceous composite nanomaterials will offer great opportunities to explore the dependence of novel properties of nanomaterials on their morphology and composition, regulate the photoconductivity of semiconductors, and also be essential for the manufacture of potential optoelectronic devices.
Fluorene-based polymer gain media for solid-state laser emission across the full visible spectrum (2003)

We report a study of the optical gain properties of three polyfluorenes with chemically tuned emission characteristics that span 400–800 nm. We demonstrate low threshold light amplification in the blue, green, and red spectral ranges via amplified spontaneous emission (ASE) in optically pumped planar asymmetric waveguides. Gain and loss measurements at the peak ASE wavelengths show large net gains, 22⩽g⩽66 cm−1, and low losses, 15⩾α⩾3 cm−1. Our findings establish fluorene-based polymers as an attractive family of materials for use in tuneable solid-state lasers that emit at wavelengths across the whole visible spectrum.
Cellular therapy and myocardial tissue engineering: the role of adult stem and progenitor cells (2006)

Acquired cardiovascular diseases and complex congenital heart diseases are leading causes of morbidity and mortality. Cellular therapy and tissue engineering are emerging as promising alternative approaches to treat cardiovascular diseases. Cellular therapy involves isolating cells and delivering the cells to the site of cardiac injury to restore blood flow and contractility to previously infarcted, scarred or dysfunctional heart. Myocardial tissue engineering, engineered heart tissue by seeding cells in three-dimensional matrices of biodegradable polymers or cell sheet engineering without artificial scaffolds to form new myocardial constructs. Questions are common to both these approaches, such as the best cell source and optimal conditions for therapeutic application. The capabilities of stem cells for pluripotency and long-term self-renewal make it an ideal source for myocardial tissue engineering and cell therapy. We review the current understanding of postnatal adult stem and progenitor cells in cellular therapy and myocardial tissue engineering from a surgical view point, and highlight the latest advances in these exciting fields.
An area efficient high turn ratio monolithic transformer for silicon RFIC (2008)

A novel way of manufacturing an on-chip transformer that produces high inductance ratio (L <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Sec</inf> /L <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Pri</inf> ≫ 30) with excellent area efficiency is presented. This technique uses an electrical all-round coupling effect of a conductor A (Primary Coil), having large effective width, and a densely routed conductor B (Secondary Coil). Thus, a high turn ratio monolithic transformer, using minimum die size, is realizable on silicon. The coil having the dense routing can also be doubled up as a monolithic RF choke on silicon. In this work, area efficiency is compared between various type of existing transformer structures (i.e. Interleaved and Stacked transformer), based on unit inductance. The method presented is fully compatible to all the foundry standard CMOS processes.
Effect of Tacticity on the Structure of Poly(1‐octadecene) (2004)

Abstract Summary: A sample of poly(1‐octadecene), synthesized with a highly active heterogeneous Ziegler‐Natta catalyst, has been fractioned with heptane, giving soluble and insoluble fractions. Both fractions and the original polymer have been characterized by size exclusion chromatography, solution and solid‐state 13 C NMR, DSC and X‐ray diffraction. The results show that the fractionation occurs on the basis of both molecular mass and tacticity differences, with the atactic content concentrated in the lower molecular mass chains. Thus, the soluble fraction, having a lower average molecular mass than the original sample, consists predominantly of atactic chains, whereas the insoluble fraction is mainly isotactic. The analysis of the solid‐state structure reveals that both atactic and isotactic fractions are able to crystallize, although their crystalline structures are different. The NMR and X‐ray data together support the “most probable” structure for the isotactic polymer advanced by Turner‐Jones. That structure is characterized by an orthorhombic crystal form, where a) the backbone crystallizes in a quaternary helical conformation, b) the sidechains are packed in a way analogous to orthorhombic polyethylene, and c) successive sidechains are conformationally inequivalent. Support for points b) and c) are respectively found in the chemical shift of the sidechains and in the splittings observed for backbone carbons and for some sidechain carbons located near the points of attachment. In addition, there is evidence that the mobility of sidechain sites at points near both the bonded and free ends are not uniform from chain to chain. On the other hand, the crystal form for the atactic polymer shows only sidechain order with some support for the notion that this order approximates the disordered hexagonal rotator phase of the alkanes. X‐ray diffractograms of the three poly(1‐octadecene) samples. magnified image X‐ray diffractograms of the three poly(1‐octadecene) samples.
Epitope specificities and quantitative and serologic aspects of monoclonal complement (C3c and C3d) antibodies (1987)

Twenty-two monoclonal antibodies to human C3c and ten to C3d were obtained by hybridization after the immunization of mice with complement-coated human red cells and/or purified human complement components. C3c antibodies were variable in their agglutination reactions with cells coated with C3 by antibody in vitro; more consistent and potent reactions with these cells were observed with anti-C3d, and all anti-C3d reacted with red cells coated with C3 in vivo. Immunoradiometric assays were used to estimate antibody concentration, affinity, and epitope specificity. The antibody content in ascitic fluids varied from less than 0.1 mg per ml to 5.6 mg per ml. The estimated values of antibody affinities for Sepharose-coupled C3 ranged from 2.8 X 10(6) l per M to 5.0 X 10(8) l per M; on average, IgM antibodies had higher affinities than IgG antibodies. Competitive binding assays showed that the monoclonal antibodies recognized at least seven different epitopes, four on the C3c and three on the C3d fragment of C3. When the results of serologic and quantitative assays were compared, no convincing relationship was found between serologic performance and epitope specificity, antibody concentration, or affinity. IgM antibodies generally gave higher agglutination scores than IgG antibodies, and Ig class was the only useful predictor of serologic efficacy.
Neural mechanisms underlying melodic perception and memory for pitch (1994)

The neural correlates of music perception were studied by measuring cerebral blood flow (CBF) changes with positron emission tomography (PET). Twelve volunteers were scanned using the bolus water method under four separate conditions: (1) listening to a sequence of noise bursts, (2) listening to unfamiliar tonal melodies, (3) comparing the pitch of the first two notes of the same set of melodies, and (4) comparing the pitch of the first and last notes of the melodies. The latter two conditions were designed to investigate short-term pitch retention under low or high memory load, respectively. Subtraction of the obtained PET images, superimposed on matched MRI scans, provides anatomical localization of CBF changes associated with specific cognitive functions. Listening to melodies, relative to acoustically matched noise sequences, resulted in CBF increases in the right superior temporal and right occipital cortices. Pitch judgments of the first two notes of each melody, relative to passive listening to the same stimuli, resulted in right frontal-lobe activation. Analysis of the high memory load condition relative to passive listening revealed the participation of a number of cortical and subcortical regions, notably in the right frontal and right temporal lobes, as well as in parietal and insular cortex. Both pitch judgment conditions also revealed CBF decreases within the left primary auditory cortex. We conclude that specialized neural systems in the right superior temporal cortex participate in perceptual analysis of melodies; pitch comparisons are effected via a neural network that includes right prefrontal cortex, but active retention of pitch involves the interaction of right temporal and frontal cortices.
Soft Errors in Advanced Computer Systems (2005)

As the dimensions and operating voltages of computer electronics shrink to satisfy consumers' insatiable demand for higher density, greater functionality, and lower power consumption, sensitivity to radiation increases dramatically. In terrestrial applications, the predominant radiation issue is the soft error, whereby a single radiation event causes a data bit stored in a device to be corrupted until new data is written to that device. This article comprehensively analyzes soft-error sensitivity in modern systems and shows it to be application dependent. The discussion covers ground-level radiation mechanisms that have the most serious impact on circuit operation along with the effect of technology scaling on soft-error rates in memory and logic.