gebhart/patrepeval huggingface dataset:
Transformation of cutaneous T cell lymphoma to large cell lymphoma. A clinicopathologic and immunologic study. (1988)

Some patients with cutaneous T cell lymphoma (CTCL) develop a high-grade, large-cell lymphoma associated with rapid deterioration of clinical status. This change in histologic appearance and clinical behavior of CTCL is similar to transformations of other hematopoietic and lymphoid neoplasms. From a group of 92 cases of CTCL, morphologic, immunologic and clinical features were studied in 17 cases of transformed CTCL. Transformation was noted, at presentation or subsequently, in either cutaneous or extracutaneous sites; remarkably, transformation was found at initial diagnosis of CTCL in 7 of 17 patients. T cell characteristics were maintained in all 17 cases of transformed CTCL; in 11 cases with complete phenotypes, there were 6 T-helper, 3 T-suppressor, and 2 aberrant T subtypes. The pre- and posttransformation phenotypes were similar in 3 of 7 cases tested over time (all T-helper); retention of T-suppressor phenotype was suggested in another case. T cell features were maintained in the other 3 cases, but the T subtypes were altered in 2 of these cases. Absent or diminished pan-T antigens (CD 5, CD 3, or UCHL1) were found in 9 of 17 cases. Leu-M1, Ki-1, or LN 2 antigens were expressed by transformed cells in 10 of 17 cases, often in patterns identical to Reed-Sternberg cells. Survival in patients with transformed CTCL was significantly shorter (median, 29 months) than in 44 CTCL patients without transformation (58 months, P = 0.015); survival after diagnosis of transformation was short (12 months). Patients with extracutaneous transformation had a shorter median survival after transformation (8 months) than those with transformation limited to skin (19 months). It is concluded that CTCL can transform morphologically to a large cell variant associated with aggressive behavior and shortened survival. Extracutaneous transformation apparently indicates a poorer prognosis than cutaneous transformation. Although transformed CTCL usually retains a T cell phenotype, some antigens are lost while other new antigens may be expressed. Recognition of transformed CTCL is facilitated by identification of the dysplastic cerebriform cell component, but often requires correlation of immunologic and clinical features.
High-Coherence Hybrid Superconducting Qubit (2010)

We report quantum coherence measurements of a superconducting qubit whose design is a hybrid of several existing types. Excellent coherence times are found: T2∼T1∼1.5 μs. The topology of the qubit is that of a traditional three-junction flux qubit, but it has a large shunting capacitance, and the ratio of the junction critical currents is chosen so that the qubit potential has a single-well form. The qubit has a sizable nonlinearity, but its sign is reversed compared with most other popular qubit designs. The qubit is read out dispersively using a high-Q resonator in a λ/2 configuration.
Identification of circulating antibodies to tumor‐associated proteins for combined use as markers of non‐small cell lung cancer (2004)

Currently only a limited number of tumor markers for non-small cell lung cancer (NSCLC) are available. Antibodies to tumor-associated proteins may expand the number of available tumor markers for lung cancer and be used together in a serum profile to enhance sensitivity and specificity. In this study, we isolated 57 tumor-associated proteins from two NSCLC cDNA T7 phage libraries using biopan enrichment techniques with NSCLC patient and normal sera. Sequence analysis showed that among the 57 phage-displayed proteins 45 have sequence identity with known or putative tumor-associated proteins. Immunochemical reactivity of patient sera with phage-expressed proteins showed enrichment on the number of immunogenic phage clones in the biopanning process and also confirmed that antibodies were present in patient sera but not in normal sera. Antibodies to five phage-expressed proteins were measured by enzyme-linked immunosorbent assay (ELISA) to validate the concept that combinations have greater predictive value than any single antibody alone. Logistic regression analysis showed that combined measurements of five antibodies was more predictive of disease than any single antibody alone, underscoring the importance of identifying multiple potential markers. The resulting antibody profiling is a feasible diagnostic strategy for NSCLC. An inventory of corresponding proteins may have significant relevance to tumor biology, novel drug development, and immunotherapies.
Extending ACID semantics to the file system (2007)

An organization's data is often its most valuable asset, but today's file systems provide few facilities to ensure its safety. Databases, on the other hand, have long provided transactions. Transactions are useful because they provide atomicity, consistency, isolation, and durability (ACID). Many applications could make use of these semantics, but databases have a wide variety of nonstandard interfaces. For example, applications like mail servers currently perform elaborate error handling to ensure atomicity and consistency, because it is easier than using a DBMS. A transaction-oriented programming model eliminates complex error-handling code because failed operations can simply be aborted without side effects. We have designed a file system that exports ACID transactions to user-level applications, while preserving the ubiquitous and convenient POSIX interface. In our prototype ACID file system, called Amino, updated applications can protect arbitrary sequences of system calls within a transaction. Unmodified applications operate without any changes, but each system call is transaction protected. We also built a recoverable memory library with support for nested transactions to allow applications to keep their in-memory data structures consistent with the file system. Our performance evaluation shows that ACID semantics can be added to applications with acceptable overheads. When Amino adds atomicity, consistency, and isolation functionality to an application, it performs close to Ext3. Amino achieves durability up to 46% faster than Ext3, thanks to improved locality.
Isolation of Monomeric Human VHS by a Phage Selection (2005)

Human V(H) domains are promising molecules in applications involving antibodies, in particular, immunotherapy because of their human origin. However, they are, in general, prone to aggregation. Therefore, various strategies have been employed to acquire monomeric human V(H)s. We had previously discovered that filamentous phages displaying engineered monomeric V(H) domains gave rise to significantly larger plaques on bacterial lawns than phages displaying wild type V(H)s with aggregation tendencies. Using plaque size as the selection criterion and a phage-displayed naïve human V(H) library we identified 15 V(H)s that were monomeric. Additionally, the V(H)s demonstrated good expression yields, good refolding properties following thermal denaturation, resistance to aggregation during long incubation at 37 degrees C, and to trypsin at 37 degrees C. These 15 V(H)s should serve as good scaffolds for developing immunotherapeutics, and the selection method employed here should have general utility for isolating proteins with desirable biophysical properties.
β2 Integrins Are Involved in Cytokine Responses to Whole Gram-Positive Bacteria (2000)

Proinflammatory cytokines have an important pathophysiologic role in septic shock. CD14 is involved in cytokine responses to a number of purified bacterial products, including LPS. However, little is known of monocyte receptors involved in cytokine responses to whole bacteria. To identify these receptors, human monocytes were pretreated with different mAbs and TNF-alpha was measured in culture supernatants after stimulation with whole heat-killed bacteria. Human serum and anti-CD14 Abs significantly increased and decreased, respectively, TNF-alpha responses to the Gram-negative Escherichia coli. However, neither treatment influenced responses to any of the Gram-positive bacteria tested, including group A and B streptococci, Listeria monocytogenes, and Staphylococcus aureus. Complement receptor type III (CR3 or CD18/CD11b) Abs prevented TNF-alpha release induced by heat-killed group A or B streptococci. In contrast, the same Abs had no effects when monocytes were stimulated with L. monocytogenes or S. aureus. Using either of the latter bacteria, significant inhibition of TNF-alpha release was produced by Abs to CD11c, one of the subunits of CR4. To confirm these blocking Ab data, IL-6 release was measured in CR3-, CR4-, or CD14-transfected Chinese hamster ovary cells after bacterial stimulation. Accordingly, streptococci triggered moderate IL-6 production (p < 0.05) in CR3 but not CD14 or CR4 transfectants. In contrast, L. monocytogenes and S. aureus induced IL-6 release in CR4 but not CR3 or CD14 transfectants. Collectively our data indicate that beta 2 integrins, such as CR3 and CR4, may be involved in cytokine responses to Gram-positive bacteria. Moreover, CD14 may play a more important role in responses to whole Gram-negative bacteria relative to Gram-positive ones.
ZASP: A New Z-band Alternatively Spliced PDZ-motif Protein (1999)

PDZ motifs are modular protein-protein interaction domains, consisting of 80-120 amino acid residues, whose function appears to be the direction of intracellular proteins to multiprotein complexes. In skeletal muscle, there are a few known PDZ-domain proteins, which include neuronal nitric oxide synthase and syntrophin, both of which are components of the dystrophin complex, and actinin-associated LIM protein, which binds to the spectrin-like repeats of alpha-actinin-2. Here, we report the identification and characterization of a new skeletal muscle protein containing a PDZ domain that binds to the COOH-terminal region of alpha-actinin-2. This novel 31-kD protein is specifically expressed in heart and skeletal muscle. Using antibodies produced to a fragment of the protein, we can show its location in the sarcomere at the level of the Z-band by immunoelectron microscopy. At least two proteins, 32 kD and 78 kD, can be detected by Western blot analysis of both heart and skeletal muscle, suggesting the existence of alternative forms of the protein. In fact, several forms were found that appear to be the result of alternative splicing. The transcript coding for this Z-band alternatively spliced PDZ motif (ZASP) protein maps on chromosome 10q22.3-10q23.2, near the locus for infantile-onset spinocerebellar ataxia.
Dyna-Style Planning with Linear Function Approximation and Prioritized Sweeping (2012)

We consider the problem of efficiently learning optimal control policies and value functions over large state spaces in an online setting in which estimates must be available after each interaction with the world. This paper develops an explicitly model-based approach extending the Dyna architecture to linear function approximation. Dynastyle planning proceeds by generating imaginary experience from the world model and then applying model-free reinforcement learning algorithms to the imagined state transitions. Our main results are to prove that linear Dyna-style planning converges to a unique solution independent of the generating distribution, under natural conditions. In the policy evaluation setting, we prove that the limit point is the least-squares (LSTD) solution. An implication of our results is that prioritized-sweeping can be soundly extended to the linear approximation case, backing up to preceding features rather than to preceding states. We introduce two versions of prioritized sweeping with linear Dyna and briefly illustrate their performance empirically on the Mountain Car and Boyan Chain problems.
Insulin, ketone bodies, and mitochondrial energy transduction (1995)

Addition of insulin or a physiological ratio of ketone bodies to buffer with 10 mM glucose increased efficiency (hydraulic work/energy from O2 consumed) of working rat heart by 25%, and the two in combination increased efficiency by 36%. These additions increased the content of acetyl CoA by 9- to 18-fold, increased the contents of metabolites of the first third of the tricarboxylic acid (TCA) cycle 2- to 5-fold, and decreased succinate, oxaloacetate, and aspartate 2- to 3-fold. Succinyl CoA, fumarate, and malate were essentially unchanged. The changes in content of TCA metabolites resulted from a reduction of the free mitochondrial NAD couple by 2- to 10-fold and oxidation of the mitochondrial coenzyme Q couple by 2- to 4-fold. Cytosolic pH, measured using 31P-NMR spectra, was invariant at about 7.0. The total intracellular bicarbonate indicated an increase in mitochondrial pH from 7.1 with glucose to 7.2, 7.5 and 7.4 with insulin, ketones, and the combination, respectively. The decrease in Eh7 of the mitochondrial NAD couple, Eh7NAD+/NADH, from -280 to -300 mV and the increase in Eh7 of the coenzyme Q couple, Eh7Q/QH2, from -4 to +12 mV was equivalent to an increase from -53 kJ to -60 kJ/2 mol e in the reaction catalyzed by the mitochondrial NADH dehydrogenase multienzyme complex (EC 1.6.5.3). The increase in the redox energy of the mitochondrial cofactor couples paralleled the increase in the free energy of cytosolic ATP hydrolysis, delta GATP. The potential of the mitochondrial relative to the cytosolic phases, Emito/cyto, calculated from delta GATP and delta pH on the assumption of a 4 H+ transfer for each ATP synthesized, was -143 mV during perfusion with glucose or glucose plus insulin, and decreased to -120 mV on addition of ketones. Viewed in this light, the moderate ketosis characteristic of prolonged fasting or type II diabetes appears to be an elegant compensation for the defects in mitochondrial energy transduction associated with acute insulin deficiency or mitochondrial senescence.
The case for geographical push-caching (2002)

Most wide-area caching schemes are client initiated. Decisions on when and where to cache information are made without the benefit of the server's global knowledge of the situation. We believe that the server should play a role in making these caching decisions, and we propose geographical push-caching as a way of bringing the server back into the loop. The World Wide Web is an excellent example of a wide-area system that will benefit from geographical push-caching, and we present an architecture that allows a Web server to autonomously replicate HTML pages.
Melatonin in Circadian Sleep Disorders in the Blind (1999)

Assessment of sleep patterns in blind people demonstrates a high prevalence of sleep disorders. Our studies have shown that subjects with no conscious light perception (NPL) have a higher occurrence and more severe sleep disorders than those with some degree of light perception (LP). A detailed study of 49 blind individuals showed that those with NPL are likely to have free-running (FR) circadian rhythms (aMT6s, cortisol) including sleep. Non-24-hour (or FR) sleep-wake disorder, characterised by periods of good and bad sleep is a condition that may benefit from melatonin treatment. Melatonin has been administered to NPL subjects with FR circadian rhythms and compared with placebo (or the no-treatment baseline) sleep parameters improved. The results suggest that prior knowledge of the subject's type of circadian rhythm, and timing of treatment in relation to the individual's circadian phase, may improve the efficacy of melatonin.
Biosensor Measurement of the Binding of Insulin-like Growth Factors I and II and Their Analogues to the Insulin-like Growth Factor-binding Protein-3 (1996)

Most insulin-like growth factor (IGF) molecules in the circulation are found in a 150-kDa complex containing IGF-binding protein-3 (IGFBP-3) and an acid-labile subunit, which does not itself bind IGF. Affinities (Kd values) between 0.03 and 0.5 nM have been reported for IGF-I/IGFBP-3 binding, but no kinetic data are available. In this study we measured the high affinity binding of unlabeled IGFs and IGF analogues to recombinant unglycosylated IGFBP-3, using a BIAcoretrade mark instrument (Pharmacia Biosensor AB). IGF-I binding showed fast association and slow non-first-order dissociation kinetics, and an equilibrium Kd of 0.23 nM. IGF-II had similar kinetics with slightly higher affinity. Analogues with mutations in the first 3 amino acids of the B-region (des(1-3) IGF-I and long IGF-I) showed 25 and 50 times lower affinity than IGF-I. Replacement of residues 28-37 by Gly-Gly-Gly-Gly or deletion of residues 29-41 in the C-region had little effect on the kinetic parameters, contrasting with the markedly impaired binding of these analogues to the IGF-I receptor. Swapping of the disulfide bridges in IGF-I and the C-region mutants decreased the affinity dramatically for IGFBP-3, primarily by decreasing the association rate. Insulin had approximately 1000 times lower affinity than IGF-I.
A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA) (2006)

MicroRNAs represent a class of short (approximately 22 nt), noncoding regulatory RNAs involved in development, differentiation, and metabolism. We describe a novel microarray platform for genome-wide profiling of mature miRNAs (miChip) using locked nucleic acid (LNA)-modified capture probes. The biophysical properties of LNA were exploited to design probe sets for uniform, high-affinity hybridizations yielding highly accurate signals able to discriminate between single nucleotide differences and, hence, between closely related miRNA family members. The superior detection sensitivity eliminates the need for RNA size selection and/or amplification. MiChip will greatly simplify miRNA expression profiling of biological and clinical samples.
An intercomparison of results from three trajectory models (2001)

Abstract Three three‐dimensional trajectory models (LAGRANTO, TRAJKS and FLEXTRA), all driven with analysis wind fields from the European Centre for Medium‐Range Weather Forecasts, are intercompared. The comparison has three parts: first, a case study of strong ascent in a warm conveyor belt is performed; second, a large set of back trajectories from the tropopause region over Europe and the mid‐latitude Atlantic Ocean is investigated; third, a set of low‐level trajectories is compared. The intercomparison shows that all three models have been implemented correctly. The degree of model accordance depends on the interpolation methods used. Deviations between the results from a single model using different interpolation schemes are of the same magnitude as the deviations of different models. If all models use linear spatial interpolation, their respective trajectories closely agree with each other, with deviations of 2% or less for the average distance between the starting and the ending positions in the free atmosphere after 48 h. Close to the surface, where the differences in the model formulations are largest, average horizontal position deviations may be up to 10%. Compared with other sources of errors, such as inaccuracies in the wind fields or insufficient temporal and spatial resolution of the data set, these differences are much smaller. Non‐linear spatial interpolation leads to stronger vertical motions than linear interpolation and, in the case study, enhanced the quality of the results. Copyright © 2001 Royal Meteorological Society
TLB Shootdown Mitigation for Low-Power Many-Core Servers with L1 Virtual Caches (2017)

Power efficiency has become one of the most important design constraints for high-performance systems. In this paper, we revisit the design of low-power virtually-addressed caches. While virtually-addressed caches enable significant power savings by obviating the need for Translation Lookaside Buffer (TLB) lookups, they suffer from several challenging design issues that curtail their widespread commercial adoption. We focus on one of these challenges-cache flushes due to virtual page remappings. We use detailed studies on an ARM many-core server to show that this problem degrades performance by up to 25 percent for a mix of multi-programmed and multi-threaded workloads. Interestingly, we observe that many of these flushes are spurious, and caused by an indiscriminate invalidation broadcast on ARM architecture. In response, we propose a low-overhead and readily implementable hardware mechanism using bloom filters to reduce spurious invalidations and mitigate their ill effects.
Comparative glycomics of connective tissue glycosaminoglycans (2008)

Homeostasis of connective joint tissues depends on the maintenance of an extracellular matrix, consisting of an integrated assembly of collagens, glycoproteins, proteoglycans, and glycosaminoglycans (GAGs). Isomeric chondroitin sulfate (CS) glycoforms differing in position and degree of sulfation and uronic acid epimerization play specific and distinct functional roles during development and disease onset. This work profiles the CS epitopes expressed by different joint tissues as a function of age and osteoarthritis. GAGs were extracted from joint tissues (cartilage, tendon, ligment, muscle, and synovium) and partially depolymerized using chondroitinase enzymes. The oligosaccharide products were differentially stable isotope labeled by reductive amination using 2-anthranilic acid-d(0) or -d(4) and subjected to amide-hydrophilic interaction chromatography (HILIC) online LC-MS/MS. The analysis presented herein enables simultaneous profiling of the expression of nonreducing end, linker region, and Delta-unsaturated interior oligosaccharide domains of the CS chains among the different joint tissues. The results provide important new information on the changes to the expression of CS GAG chains during disease and development.
Terahertz pulse propagation in a plastic photonic crystal fiber (2002)

Guided-wave single-mode propagation of subpicosecond terahertz (THz) pulses in a plastic photonic crystal fiber has been experimentally demonstrated. The plastic photonic crystal fiber is fabricated from high-density polyethylene tubes and filaments. The fabricated fiber exhibits the low loss and relatively low dispersive propagation of THz pulses within the experimental bandwidth of 0.1–3 THz.
Ascorbic Acid Enhances Endothelial Nitric-oxide Synthase Activity by Increasing Intracellular Tetrahydrobiopterin (2000)

Ascorbic acid enhances NO bioactivity in patients with vascular disease through unclear mechanism(s). We investigated the role of intracellular ascorbic acid in endothelium-derived NO bioactivity. Incubation of porcine aortic endothelial cells (PAECs) with ascorbic acid produced time- and dose-dependent intracellular ascorbic acid accumulation that enhanced NO bioactivity by 70% measured as A23187-induced cGMP accumulation. This effect was due to enhanced NO production because ascorbate stimulated both PAEC nitrogen oxide (NO(2)(-) + NO(3)(-)) production and l-arginine to l-citrulline conversion by 59 and 72%, respectively, without altering the cGMP response to authentic NO. Ascorbic acid also stimulated the catalytic activity of eNOS derived from either PAEC membrane fractions or baculovirus-infected Sf9 cells. Ascorbic acid enhanced bovine eNOS V(max) by approximately 50% without altering the K(m) for l-arginine. The effect of ascorbate was tetrahydrobiopterin (BH(4))-dependent, because ascorbate was ineffective with BH(4) concentrations >10 microm or in PAECs treated with sepiapterin to increase intracellular BH(4). The effect of ascorbic acid was also specific because A23187-stimulated cGMP accumulation in PAECs was insensitive to intracellular glutathione manipulation and only ascorbic acid, not glutathione, increased the intracellular concentration of BH(4). These data suggest that ascorbic acid enhances NO bioactivity in a BH(4)-dependent manner by increasing intracellular BH(4) content.