gebhart/patrepeval huggingface dataset:
Peroxidase-Catalyzed Oligomerization of Ferulic Acid Esters (2008)

Valuable information about possible types of linkages, reaction mechanisms, and sequences for oxidative coupling of phenolic compounds in planta is available from in vitro model systems. Ferulate oligomers were generated in a system using ethyl ferulate, peroxidase, and hydrogen peroxide under various conditions. A molar ferulate/H2O2 ratio of 1:1, an ethanol level of 30% in an aqueous sodium phosphate buffer (pH 6.0), and a reaction time of 10 min were considered to be ideal to produce maximal proportions of ferulate trimers and tetramers from ethyl ferulate as starting material. The dominant trimer and tetramer were each isolated from the reaction mixture and identified as 8-O-4/8-5(cyclic)-dehydrotriferulic acid triethyl ester and 8-5(cyclic)/4-O-5/8-5(cyclic)-dehydrotetraferulic acid tetraethyl ester. The structure of the 8-O-4/8-5(cyclic)-dehydrotriferulic acid triethyl ester revealed that a third ferulate unit is bound to a preformed 8-O-4-diferulate dimer, a surprising reaction sequence considering the dominance of 8-5-coupled dimers among dehydrodiferulates in H2O2/peroxidase-based model reactions. As 4-O-5-coupling is not favored in the dimerization process of ferulates, the main tetramer isolated in this study is probably formed by 4-O-5-coupling of two preformed 8-5(cyclic)-diferulates, a logical step in analogy with reactions occurring in lignin biosynthesis.
JAK2 V617F Mutation Identifies a Biologically Distinct Subtype of Essential Thrombocythemia Which Resembles Polycythemia Vera. (2005)

Abstract An acquired V617F mutation in JAK2 occurs in most patients with polycythemia vera (PV) but only half of those with essential thrombocythemia (ET) and idiopathic myelofibrosis. It is not known whether mutation-bearing patients are biologically distinct from those lacking the mutation, or why the same mutation is associated with different phenotypes. Two sensitive PCR-based methods were used to assess the JAK2 mutation status of 806 patients with ET, including 776 from the MRC PT-1 trial and two other prospective studies. The combined cohort provides a unique resource for studying ET, particularly in view of its large size, centralized review of end-points and comprehensive follow-up. The involvement of a large number of secondary and tertiary centers, together with the inclusion of patients in all risk categories, suggest the results are of general relevance. JAK2 mutation status divided the cohort into two distinct subgroups. Mutation-positive patients (53.4%) displayed multiple features resembling PV, with significantly increased hemoglobin levels (p&amp;lt;0.0001), neutrophil counts (p&amp;lt;0.0001), bone marrow erythropoiesis (p=0.001) and granulopoiesis (p=0.005). They suffered more venous thromboses in the year before diagnosis (p=0.04) and during follow-up (p=0.06), together with a higher incidence of polycythemic transformation (p=0.01). To explore the resemblance between V617F-positive ET and PV further, we analysed factors that might constrain erythropoiesis. Compared to mutation-negative patients with ET, mutation-positive patients had lower serum epo (p&amp;lt;0.0001), lower ferritin (p=0.01), and were more likely to be microcytic (p&amp;lt;0.0001). V617F-positive patients were more sensitive to hydroxyurea, requiring lower doses to control platelet count than V617F-negative patients (p&amp;lt;0.0001), a pattern not seen with anagrelide. Despite lower doses of hydroxyurea, V617F-positive patients had greater reductions in hemoglobin, platelet and white cell counts than V617F-negative patients, with no analogous differences noted between V617F-positive and negative patients randomized to anagrelide (p=0.004, p=0.04, p=0.0003 for platelet count, Hb and WCC). Mutation-negative patients did exhibit many clinical and laboratory features characteristic of a myeloproliferative disorder, including cytogenetic abnormalities, hypercellular bone marrow, abnormal megakaryocyte morphology, PRV1 over-expression, growth of epo-independent erythroid colonies, and a risk of myelofibrotic or leukemic transformation. JAK2 mutation status defines two biologically distinct subgroups of ET with differences in presentation, outcome and response to therapy. Our results suggest a model in which V617F-positive ET and PV form a continuum, with the degree of erythrocytosis determined by physiological or genetic modifiers, including iron stores, epo homeostasis, gender and V617F-homozygosity. This concept has major implications for the classification, diagnosis and management of MPDs.
The absence of SIR2alpha protein has no effect on global gene silencing in mouse embryonic stem cells. (2003)

The yeast sir2 gene plays a central role in mediating gene silencing and DNA repair in this organism. The mouse sir2alpha gene is closely related to its yeast homologue and encodes a nuclear protein expressed at particularly high levels in embryonic stem (ES) cells. We used homologous recombination to create ES cells null for sir2alpha and found that these cells did not have elevated levels of acetylated histones and did not ectopically express silent genes. Unlike yeast sir2 mutants, our sir2alpha null ES cells had normal sensitivity to insults such as ionizing radiation and heat shock, and they were able to silence invading retroviruses normally. These sir2alpha null cells were able to differentiate in culture normally. Our results failed to provide evidence that the mammalian SIR2alpha protein plays a role in gene silencing and suggest that the physiological substrate(s) for the SIR2alpha deacetylase may be nuclear proteins other than histones.
Micropatterning of Organic Electronic Devices by Cold-Welding (2000)

A simple and general postdeposition electrode patterning technique for active organic electronic devices is demonstrated and is applied to patterning the metal cathodes of organic light-emitting devices. Selective lift-off of the metal cathode layer is achieved by pressing a prepatterned, metal-coated silicon stamp on the unpatterned device layers. Under pressure, the metal coating on the stamp cold-welds to the metal cathode coating the underlying organic films. Subsequent separation of the stamp from the substrate results in removal of the cathode metal in the regions contacted by the stamp, resulting in submicrometer feature definition. A 17x17 passive matrix display, with a pixel size of 440 micrometers by 320 micrometers, was fabricated with this process. Cold-welding followed by lift-off of the cathode metal allows simple, cost-effective, and high-throughput large-area fabrication of organic electronic devices.
The human REV1 gene codes for a DNA template-dependent dCMP transferase (1999)

DNA is frequently damaged by various physical and chemical agents. DNA damage can lead to mutations during replication. In the yeast Saccharomyces cerevisiae, the damage-induced mutagenesis pathway requires the Rev1 protein. We have isolated a human cDNA homologous to the yeast REV1 gene. The human REV1 cDNA consists of 4255 bp and codes for a protein of 1251 amino acid residues with a calculated molecular weight of 138 248 Da. The human REV1 gene is localized between 2q11.1 and 2q11.2. We show that the human REV1 protein is a dCMP transferase that specifically inserts a dCMP residue opposite a DNA template G. In addition, the human REV1 transferase is able to efficiently and specifically insert a dCMP opposite a DNA template apurinic/apyrimidinic (AP) site or a uracil residue. These results suggest that the REV1 transferase may play a critical role during mutagenic translesion DNA synthesis bypassing a template AP site in human cells. Consistent with its role as a fundamental mutagenic protein, the REV1 gene is ubiquitously expressed in various human tissues.
Fast Wavenet Generation Algorithm (2016)

This paper presents an efficient implementation of the Wavenet generation process called Fast Wavenet. Compared to a naive implementation that has complexity O(2^L) (L denotes the number of layers in the network), our proposed approach removes redundant convolution operations by caching previous calculations, thereby reducing the complexity to O(L) time. Timing experiments show significant advantages of our fast implementation over a naive one. While this method is presented for Wavenet, the same scheme can be applied anytime one wants to perform autoregressive generation or online prediction using a model with dilated convolution layers. The code for our method is publicly available.
Intravenous synthetic peptide MBP8298 delayed disease progression in an HLA Class II‐defined cohort of patients with progressive multiple sclerosis: results of a 24‐month double‐blind placebo‐controlled clinical trial and 5 years of follow‐up treatment (2006)

MBP8298 is a synthetic peptide with a sequence corresponding to amino acid residues 82-98 of human myelin basic protein (DENPVVHFFKNIVTPRT). It represents the immunodominant target for both B cells and T cells in multiple sclerosis (MS) patients with HLA haplotype DR2. Its administration in accordance with the principle of high dose tolerance results in long-term suppression of anti-myelin basic protein (MBP) autoantibody levels in the cerebrospinal fluid (CSF) of a large fraction of progressive MS patients. MBP8298 was evaluated in a 24-month placebo-controlled double-blinded Phase II clinical trial in 32 patients with progressive MS. The objective was to assess the clinical efficacy of 500 mg of MBP8298 administered intravenously every 6 months, as measured by changes in Expanded Disability Status Scale (EDSS) scores. Contingency analysis for all patients at 24 months showed no significant difference between MBP8298 and placebo-treatments (n = 32, P = 0.29). Contingency analysis in an HLA Class II defined subgroup showed a statistically significant benefit of MBP8298 treatment compared with placebo in patients with HLA haplotypes DR2 and/or DR4 (n = 20, P = 0.01). Long-term follow-up treatment and assessment of patients in this responder group showed a median time to progression of 78 months for MBP8298 treated patients compared with 18 months for placebo-treatment (Kaplan-Meier analysis, P = 0.004; relative rate of progression = 0.23). Anti-MBP autoantibody levels in the CSF of most MBP8298 treated patients were suppressed, but antibody suppression was not predictive of clinical benefit. Anti-MBP autoantibodies that reappeared in the CSF of one patient at 36 months, whilst under treatment with MBP8298, were not reactive with the MBP8298 peptide in vitro. The identification of a responder subgroup (62.5% of the patients in this study) enables a more efficient design of a large confirmatory clinical trial of MBP8298. The probability that patients with other less common HLA-DR haplotypes will respond to this treatment should not be ignored.
Two Proteins Modulating Transendothelial Migration of Leukocytes Recognize Novel Carboxylated Glycans on Endothelial Cells (2001)

We recently showed that a class of novel carboxylated N:-glycans was constitutively expressed on endothelial cells. Activated, but not resting, neutrophils expressed binding sites for the novel glycans. We also showed that a mAb against these novel glycans (mAbGB3.1) inhibited leukocyte extravasation in a murine model of peritoneal inflammation. To identify molecules that mediated these interactions, we isolated binding proteins from bovine lung by their differential affinity for carboxylated or neutralized glycans. Two leukocyte calcium-binding proteins that bound in a carboxylate-dependent manner were identified as S100A8 and annexin I. An intact N terminus of annexin I and heteromeric assembly of S100A8 with S100A9 (another member of the S100 family) appeared necessary for this interaction. A mAb to S100A9 blocked neutrophil binding to immobilized carboxylated glycans. Purified human S100A8/A9 complex and recombinant human annexin I showed carboxylate-dependent binding to immobilized bovine lung carboxylated glycans and recognized a subset of mannose-labeled endothelial glycoproteins immunoprecipitated by mAbGB3.1. Saturable binding of S100A8/A9 complex to endothelial cells was also blocked by mAbGB3.1. These results suggest that the carboxylated glycans play important roles in leukocyte trafficking by interacting with proteins known to modulate extravasation.
Activating mutations in the extracellular domain of the fibroblast growth factor receptor 2 function by disruption of the disulfide bond in the third immunoglobulin-like domain (1998)

Multiple human skeletal and craniosynostosis disorders, including Crouzon, Pfeiffer, Jackson-Weiss, and Apert syndromes, result from numerous point mutations in the extracellular region of fibroblast growth factor receptor 2 (FGFR2). Many of these mutations create a free cysteine residue that potentially leads to abnormal disulfide bond formation and receptor activation; however, for noncysteine mutations, the mechanism of receptor activation remains unclear. We examined the effect of two of these mutations, W290G and T341P, on receptor dimerization and activation. These mutations resulted in cellular transformation when expressed as FGFR2/Neu chimeric receptors. Additionally, in full-length FGFR2, the mutations induced receptor dimerization and elevated levels of tyrosine kinase activity. Interestingly, transformation by the chimeric receptors, dimerization, and enhanced kinase activity were all abolished if either the W290G or the T341P mutation was expressed in conjunction with mutations that eliminate the disulfide bond in the third immunoglobulin-like domain (Ig-3). These results demonstrate a requirement for the Ig-3 cysteine residues in the activation of FGFR2 by noncysteine mutations. Molecular modeling also reveals that noncysteine mutations may activate FGFR2 by altering the conformation of the Ig-3 domain near the disulfide bond, preventing the formation of an intramolecular bond. This allows the unbonded cysteine residues to participate in intermolecular disulfide bonding, resulting in constitutive activation of the receptor.
Video-Based Monitoring of Pedestrian Movements at Signalized Intersections (2008)

Pedestrian and cyclist crossing characteristics are important for the design of urban intersections and signalized crossings. Parameters such as waiting time, crossing time, and arrival rate are key variables for describing pedestrian characteristics and improving crossing designs and signal timing plans. Manually collecting such data is often extremely labor intensive. Therefore, an automated computer-vision-based approach is introduced for collecting these parameters in real time with ordinary video cameras. Broadly defined pedestrian objects, including bicyclists and other nonmotorized modes, are extracted by means of the background subtraction technique and tracked through an inherent cost characteristic function in conjunction with an α-β-filter. The waiting-zone concept introduced helps provide robust pedestrian tracking initialization and parameter extraction. The proposed approach is implemented in a pedestrian tracking (PedTrack) system by using Microsoft Visual C++. Tested with real video data from three study sites, this system was proved to be effective and about 80% of pedestrian crossing events were successfully detected. PedTrack shows the potential to be a great data collection tool for nonmotorized object movements at intersections.
Building a Distributed Block Storage System for Cloud Infrastructure (2010)

The development of cloud infrastructures has stimulated interest in virtualized block storage systems, exemplified by Amazon Elastic Block Store (EBS), Eucalyptusâ€™ EBS implementation, and the Virtual Block Store (VBS) system. Compared with other solutions, VBS is designed for flexibility, and can be extended to support various Virtual Machine Managers and Cloud platforms. However, due to its single-volume-server architecture, VBS has the problem of single point of failure and low scalability. This paper presents our latest improvements to VBS for solving these problems, including a new distributed architecture based on the Lustre file system, new workflows, better reliability and scalability, and read-only volume sharing. We call this improved implementation VBS-Lustre. Preliminary tests show that VBS-Lustre can provide both better throughput and higher scalability in multiple attachment scenarios than VBS. VBS-Lustre could potentially be applied to solve some challenges for current cluster file systems, such as metadata management and small file access.
An introduction to quantum error correction and fault-tolerant quantum computation (2010)

Quantum states are very delicate, so it is likely some sort of quantum error correction will be necessary to build reliable quantum computers. The theory of quantum error-correcting codes has some close ties to and some striking differences from the theory of classical error-correcting codes. Many quantum codes can be described in terms of the stabilizer of the codewords. The stabilizer is a finite Abelian group, and allows a straightforward characterization of the error-correcting properties of the code. The stabilizer formalism for quantum codes also illustrates the relationships to classical coding theory, particularly classical codes over GF(4), the finite field with four elements. To build a quantum computer which behaves correctly in the presence of errors, we also need a theory of fault-tolerant quantum computation, instructing us how to perform quantum gates on qubits which are encoded in a quantum error-correcting code. The threshold theorem states that it is possible to create a quantum computer to perform an arbitrary quantum computation provided the error rate per physical gate or time step is below some constant threshold value.
Within-night variation in respiratory effort preceding apnea termination and EEG delta power in sleep apnea (1998)

We studied the within-night variability of the maximum esophageal pressure deflection before apnea termination (DPmax) in nine patients with severe obstructive sleep apnea as an index of the arousal threshold and the mean electroencephalogram (EEG) delta power for each 30 s as an index of the timing of sleep cycles. Periodicity in the time variation of delta power and DPmax was analyzed by determining their power spectral density and their relationship determined by cross correlation. DPmax and delta power varied cyclically and in phase with a major periodicity (major peak in power spectral density) of 117.6 +/- 8.8 (SE) min. The correlation between the values of DPmax and delta power was significant (P < 0.001) in each subject (mean r = 0.47 +/- 0.03), and the coherence between DPmax and delta power at their dominant frequency was high. Within cycles of non-rapid-eye-movement sleep, DPmax and delta power increased, reaching peak values on average at or after midcycle. These findings suggest that the arousal threshold to airway occlusion in patients with obstructive sleep apnea varies cyclically during the night synchronous to the underlying cycles of sleep.
Hybrid gene synthesis: its application to the assembly of DNA sequences encoding the human parathyroid hormones and analogues (1986)

Bypassing any intermediate steps of purification and gene assembly, several synthetic oligonucleotides constituting a DNA duplex with a small base-mismatching region were phosphorylated, annealed, and ligated directly into a linearized plasmid vector. After transformation in bacteria, the two plasmid strands individually yielded two different plasmids bearing altered versions of the same gene. Via this approach, DNA coding sequences of the human parathyroid hormone and analogues were synthesized and cloned in Escherichia coli.
Transcriptional Profiling Analysis of the Global Regulator NorG, a GntR-Like Protein of Staphylococcus aureus (2011)

The GntR-like protein NorG has been shown to affect Staphylococcus aureus genes involved in resistance to quinolones and β-lactams, such as those encoding the NorB and AbcA transporters. To identify the target genes regulated by NorG, we carried out transcriptional-profiling assays using S. aureus RN6390 and its isogenic norG::cat mutant. Our data showed that NorG positively affected the transcription of global regulators mgrA, arlS, and sarZ. The three putative drug efflux pump genes most positively affected by NorG were the NorB efflux pump (5.1-fold), the MmpL-like protein SACOL2566 (5.2-fold), and the BcrA-like drug transporter SACOL2525 (5.7-fold) genes. The S. aureus predicted MmpL protein showed 53% homology with the MmpL lipid transporter of Mycobacterium tuberculosis, and the putative SACOL2525 protein showed 87% homology with the bacitracin drug transporter BcrA of Staphylococcus hominis. Two pump genes most negatively affected by NorG were the NorC (4-fold) and AbcA (6-fold) genes. Other categories of genes, such as those participating in amino acid, inorganic ion, or nucleotide transporters and metabolism, were also affected by NorG. Real-time reverse transcription (RT)-PCR assays for mgrA, arlS, sarZ, norB, norC, abcA, mmpL, and bcrA-like were carried out to verify microarray data and showed the same level of up- or downregulation by NorG. The norG mutant showed a 2-fold increase in resistance to norfloxacin and rhodamine, both substrates of the NorC transporter, which is consistent with the resistance phenotype conferred by overexpression of norC on a plasmid. These data indicate that NorG has broad regulatory function in S. aureus.
Immediate and midterm follow-up results of using an electrodetachable, fully retrievable SOLO stent system in the endovascular coil occlusion of wide-necked cerebral aneurysms (2007)

The fully retrievable self-expandible SOLO stent is a feasible, secure, and effective system with a high radial force and ease of delivery in treating wide-necked intracranial aneurysms in combination with coil embolization.
Membrane distal cytokine binding domain of LIFR interacts with soluble CNTFR in vitro (2002)

Ciliary neurotrophic factor (CNTF) is a member of the gp130 family of cytokines. The functional receptor complex of CNTF is composed of the CNTF receptor alpha (CNTFR), gp130 and the leukemia inhibitory factor receptor (LIFR). Three regions on CNTF have been identified as binding sites for its receptors. The ligand-receptor interactions are mediated through the cytokine binding domains (CBDs) and/or the immunoglobulin-like domains of the receptors. However, in the case of CNTF, the precise nature of the protein-protein contacts in the signaling complex has not yet been resolved. In this study, we provide the first demonstration that the membrane distal CBD (CBD1) of LIFR associates in vitro with soluble CNTFR in the absence of CNTF. Moreover, purified CBD1 partially blocks CNTF signaling, but not that of interleukin-6 or LIF, in human embryonal carcinoma cell line Ntera/D1 cells. These data raise the possibility that LIFR has the capability to form a ligand-free complex with CNTFR.
Updated Clinical Classification of Pulmonary Hypertension (2012)

The fourth World Symposium on Pulmonary Hypertension and the conjoint ERS/ESC guidelines revise previous classifications of pulmonary hypertension (PH) in order to accurately reflect information published over the past 5 years. PH has been defined as an increase in mean pulmonary arterial pressure (mPAP) ≧25 mm Hg at rest as assessed by right heart catheterization. No definition for PH on exercise was considered. PH was defined as precapillary when pulmonary capillary wedge pressure was ≤15 mm Hg associated with a normal or reduced cardiac output. In Group 1 (PAH), the term familial PAH has been replaced by heritable PAH, including sporadic idiopathic PAH with germline mutations and familial cases. Pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis have been individualized and designated as clinical Group 1’. Group 2 ‘pulmonary hypertension due to left heart diseases’ has been divided into three subgroups: systolic dysfunction, diastolic dysfunction, and valvular disease. Group 3 includes only chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms.