gebhart/patrepeval huggingface dataset:
Solution NMR Studies of a 42 KDa <i>Escherichia </i><i>C</i><i>oli</i> Maltose Binding Protein/β-Cyclodextrin Complex:  Chemical Shift Assignments and Analysis (1998)

The use of deuteration in concert with uniform 15N,13C-labeling has been critical for the chemical shift assignment of several proteins and protein complexes over 30 kDa. Unfortunately, deuteration reduces the number of interproton distance restraints available for structure determination, compromising the precision and accuracy of the NMR-derived structures determined from these samples. We have recently described an isotopic labeling strategy that addresses this problem by generating proteins labeled uniformly with 15N, 13C, and extensively with 2H with high levels of protonation at exchangeable sites and the methyl groups of Val, Leu, and Ile (δ1 only) (Gardner, K. H.; Kay, L. E. J. Am. Chem. Soc. 1997, 119, 7599−7600). This labeling pattern maintains the high efficiency of triple resonance methods while retaining sufficient protons to establish long-range NOEs between secondary structure elements. We demonstrate the utility of samples labeled in this manner by presenting the chemical shift assignments of one of the largest monomeric proteins assigned to date, the 370 residue Escherichia coli maltose binding protein in complex with β-cyclodextrin (42 kDa). The high level of Cα and Cβ deuteration provided by our labeling scheme enabled the collection of triple resonance data with high sensitivity and resolution, allowing assignment of over 95% of the backbone 15N, 13Cα, 1HN, and side chain 13Cβ nuclei. By using a combination of existing experiments and a new pulse scheme described here for correlating methyl chemical shifts with 13Cβ (Val), 13Cγ (Leu), or 13Cγ1 (Ile) carbons, over 98% of methyl 13C and 1H assignments from Val, Leu, and Ile (Cδ1 only) have been obtained. Analysis of the backbone chemical shifts and qualitative HN exchange data have confirmed that the MBP/β-cyclodextrin complex has a secondary structure similar to that previously observed in a 1.8 Å crystal structure.
Late onset Ito's nevus (2013)

Dermal melanocytoses include a variety of congenital and acquired melanocytic lesions characterised by the presence of multiple spindle-shaped dendritic melanocytes in the dermis. These lesions are commonly found in the skin of Asians, but they can also appear in Caucasians. The Mongolian spot, nevi of Ota and Ito are the most common morphological forms. We report a case of a 24-year-old Caucasian woman presented with a 10-months history of progressive darkening of the right side of her upper back. Cutaneous examination revealed a macular blue-grey hyperpigmentation of the right side of her upper back. Biopsy specimen from the macule showed multiple darkly pigmented, spindle-shaped dendritic melanocytes in the superficial dermis, interstitially arranged between collagen bundles. The diagnosis of nevus of Ito was established. Our patient is maintaining vigilance in dermatology consultation.
Protein Expression Systems: Why Soybean Seeds? (2011)

The global protein therapeutics market is approaching $100 billion in annual sales. Furthermore, the in vitro diagnostic market, which relies heavily on the use of recombinant proteins as analyte specific reagents, is approaching $50 billion in annual sales. Increases in each market sector are estimated to be 8% to 20% per year for the next decade. Therefore, the costs of protein-based therapeutics and diagnostics will continue to be a significant percentage of health care expenses for patients and for agricultural animals and pets. A platform technology, which produces recombinant proteins at greatly reduced costs, provides inherent advantages, and allows low-tech sustainability of product lines, represents a competitive innovation which could create significant wealth in this industry. The use of soybean-derived proteins has the potential to provide such advantages. Since the use of recombinant proteins is widespread in human and animal therapeutics and diagnostics, there are thousands of potential applications for such a platform technology. While no one technology is optimal for the expression of every transgenic protein (Brondyk, 2009), the research that we have performed to date demonstrates the utility and feasibility of commercial applications for proteins made in transgenic soybean seeds. Soybean seeds expressing transgenic proteins represent a novel, sustainable platform technology which overcomes some of the current limitations for producing recombinant proteins for diagnostics, therapeutics, and industrial applications. Advantages include low cost of glycoslyated protein production, greenhouse containment, highest protein/biomass ratio, marketable formulations which require no purification from soy, safety, accurate dosing, low cost of protein purification, low-tech sustainability of product lines, reduced risk of contamination, ease of scalability, minimal waste produced, as well as being a green technology. To our knowledge, no other protein expression technology compares. Despite the fact that the present protein therapeutic and diagnostic markets are growing rapidly, some applications continue to be limited by the current technologies employed (Brondyk, 2009). For example the cost of production and purification of certain recombinant proteins makes their use in particular applications non-profitable. Some proteins cannot be expressed by any current technology and require expensive purification from human or animal tissues. A platform technology which could alleviate these concerns would create significant opportunities for novel product development, or expanded applications for existing products. In short, there is a need for alternative technologies for expressing and purifying recombinant proteins which can advance their applications. We propose that
On Active Disturbance Rejection Control;Stability Analysis and Applications in Disturbance Decoupling Control (2009)

One main contribution of this dissertation is to analyze the stability characteristics of extended state observer (ESO) and active disturbance rejection control (ADRC).In particular, asymptotic stability of the dynamic system that describes the estimation error and the closed-loop system is established where the plant dynamics is completely known.In the face of large dynamic uncertainties, the estimation error, the closed-loop tracking error, and its up to the (n -1) st order derivatives are shown to be bounded.Furthermore, it is demonstrated that the error upper bounds, in general, monotonously decrease with the observer and control loop bandwidths.The second contribution is to develop a dynamic disturbance decoupling control strategy for square multivariable systems based on ADRC.The proposed method has been successfully applied to chemical process problems and micro-electro-mechanical systems gyroscopes.It is shown that a largely unknown square multivariable system can be readily decoupled by actively estimating and rejecting the effects of both the internal plant dynamics and external disturbances.By requiring little information on the plant model, the intention is to make the new decoupling approach practical.vi xi 13 The tracking error of CSTR. . . . . . . . . .
A hypertext electronic index based on the Grif structured document editor (1994)

This paper presents an electronic index service that was developed in the Grif editor by taking advantage of the hypertext facilities available in the system. Grif is a structured document editor based on the generic structure concept that supports both hierarchical structures and non-hierarchical links.
0.2‐Hz repetitive transcranial magnetic stimulation has no add‐on effects as compared to a realistic sham stimulation in Parkinson's disease (2002)

To study the efficacy of 0.2-Hz repetitive transcranial magnetic stimulation (rTMS) on Parkinson's disease (PD), 85 patients with PD were enrolled into three groups: 1). motor cortical, 2). occipital, and 3). sham stimulation. A round coil was centered over the vertex in motor cortical stimulation, and over the inion in occipital stimulation. In one session, 100 stimuli of 0.2-Hz rTMS at an intensity of 1.1 times active motor threshold (AMT) were given. In sham stimulation, electric currents were given with electrodes fixed on the head to mimic the sensation in real stimulation. Each session was carried out once a week for the first 8 weeks. The Unified Parkinson Disease Rating Scale (UPDRS), Hamilton Rating Scale for Depression (HRSD) and subjective score (visual analogue scale) were assessed. There were no significant differences in clinical features among the three groups. Total and motor score of UPDRS were improved to the same extent by rTMS over Cz, inion, and sham stimulation. HRSD was improved by rTMS over Cz and sham stimulation in the same manner. Subjective score was not significantly improved by any methods of stimulation. 0.2-Hz rTMS at an intensity of 1.1 x AMT has only a placebo effect on PD. Our realistic sham stimulation maneuver must produce powerful placebo effects as a real stimulation.
A phase I clinical study of VB4-845: Weekly intratumoral administration of an anti-EpCAM recombinant fusion protein in patients with squamous cell carcinoma of the head and neck (2008)

VB4-845 is a scFv-Pseudomonas exotoxin A fusion construct that targets epithelial cell adhesion molecule (EpCAM). A phase I trial was conducted to determine the maximum tolerated dose (MTD) of VB4-845 when administered as weekly intratumoral (IT) injections to patients with squamous cell carcinoma of the head and neck (SCCHN). Secondary objectives included the evaluation of the safety, tolerability, pharmacokinetic profile, and immunogenicity, and a preliminary assessment of tumor response. Twenty patients with advanced, recurrent SCCHN were treated weekly for four weeks in ascending dose cohorts of 100, 200, 330, 500, 700, and 930 microg. The MTD was established as 930 microg with a dose limiting toxicity of elevated liver enzymes in two of five patients. VB4-845 therapy was well tolerated with common treatment-related adverse events of injection site reactions, fever, gastrointestinal disorders, and elevated liver enzyme levels. All patients developed antibodies to VB4-845 by the end of the study, but only seven patients had neutralizing antibodies. Preliminary efficacy data found 87.5% of EpCAM-positive patients had a positive response to VB4-845 therapy. Noninjected dermal metastases were also resolved in one patient. VB4-845 IT therapy is safe and feasible and warrants further clinical evaluation for the treatment of SCCHN.
Equitable Quality Video Streaming (2009)

Video streaming has frequently been deployed using constant bit rate video encoding and transmission as these are easily implemented and network provisioning, although requiring admission control, is straightforward. However, it is sub-optimal for both the user, who experiences time varying quality, and the network operator, who can not fully utilize the network during periods of low usage and is faced with admission control and session refusal at busy times. Instead we propose an equitable quality scheme in which the available network bandwidth is divided between the concurrent sessions so that the same quality is delivered in each. We show that we can increase average quality (mean opinion score) by 0.74, or alternatively increase the number of sessions that can be supported at the same average overall quality by 80%.
Structure-Function Analysis of Plasma Cholesteryl Ester Transfer Protein by Protease Digestion and Expression of cDNA Fragments in Escherichia coli (1989)

In an attempt to define an active domain of the protein, fragments of cholesteryl ester transfer protein (CETP) were obtained by limited digestion of the native, plasma-derived protein with trypsin, chymotrypsin, or Staphylococcus aureus V8 protease or by expression of CETP cDNA restriction fragments in Escherichia coli. Although digestion of native CETP with these proteases resulted in extensive fragmentation of the protein and loss of the intact 74-kDa molecule as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, CE transfer activity was unaffected (trypsin or chymotrypsin treatment) or only partially lost (V8 protease treatment). Analysis by molecular sieve chromatography showed that the CE transfer-active product of this proteolysis consisted of polypeptide fragments which remained associated, retaining the native molecular weight of CETP. These proteolyzed complexes were resistant to dissociation by dithiothreitol, 8 M urea, or delipidating agents. As shown by CE transfer activity, native CETP was found to possess a stable conformation which remained unchanged in buffers containing up to 4.5 M urea, or following exposure to even higher (8 M) urea concentrations. CETP polypeptides from bacterially expressed cDNA fragments were found to be catalytically inactive although they contained the epitope for an inhibitory anti-CETP monoclonal antibody and had emulsion binding properties similar to native CETP. Selected synthetic CETP peptides (including the peptide containing the inhibitory monoclonal antibody epitope) were also devoid of CE transfer activity. Thus, no evidence was found for an independently active subunit of the CETP. Together, the results indicate that the CETP possesses a distinct and highly stable tertiary structure which is required for CE transfer catalytic activity.
Late expression of a beta chemokine homolog by murine cytomegalovirus (1997)

A gene (HJ1) present in murine cytomegalovirus (MCMV) encodes an open reading frame (ORF) whose predicted amino acid sequence shows homology to the beta (or C-C) class of chemotactic cytokines known as chemokines. The region of homology is located in the carboxyl-terminal portion of the 116-amino-acid ORF. A 0.9-kb RNA transcript corresponding to the HJ1 gene is expressed in MCMV-infected fibroblasts and macrophages as a member of the late kinetic class of virally encoded transcripts. A transcriptional start site is located between the third and fourth methionine residues in the ORF, predicting a primary amino acid structure, starting at the fourth methionine residue, which includes a possible signal peptide as well as conserved cysteine residues typical for mammalian beta chemokines. The RNA transcript is polyadenylated, suggesting that it can undergo translation within the cytoplasm of an MCMV-infected cell. We speculate that expression of the chemokine homolog at late times in the MCMV replication cycle plays a role in MCMV pathogenesis, possibly by action as a chemotactic agonist or antagonist or by alteration of the activation or differentiation state of a susceptible cell such as a macrophage.
Brain-Chip Interfaces: The Present and The Future (2011)

Brain-chip-interfaces (BCHIs) are hybrid entities where chips and nerve cells establish a close physical interaction allowing the transfer of information in one or both directions. Typical examples are represented by multi-site-recording chips interfaced to cultured neurons or implanted in the brain to record or stimulate neuronal excitation. We provide an overview on recent achievements in the field of BCHIs leading to enhancement of signals transmission from nerve cells to chip or from chip to nerve cells, either in terms of signal-to-noise ratio or of spatiotemporal resolution. Micro-nail shaped microelectrodes engulfed by neurons in culture establish a tight electrical coupling with the cells and allow for high signal-to-noise ratio recording. Oxide-insulated chips, featuring large-scale and high-resolution arrays of stimulation and recording elements, represent a promising technology for high spatiotemporal resolution interfacing, as recently demonstrated by recordings obtained from hippocampal slices and brain cortex in implanted animals. Although most BCHIs deal with electrical signals, chemical signaling has also to be considered and some new advances in this direction are reported. Finally, we present and discuss important challenges for design and fabrication of new generations of BCHIs.
Insulin: Inducer of Pyruvate Kinase (1965)

The hepatic pyruvate kinase activity markedly decreased when rats were made diabetic by alloxan injection. Insulin treatment induced new synthesis of pyruvate kinase which was prevented by injection of ethionine and actinomycin D. The evidence indicated that the increased pyruvate kinase activity induced by inisulin entails at a certain stage a stimulation of the synthesis of certain RNA species relevant to the production of this enzyme.
Max-min fair collision-free scheduling for wireless sensor networks (2005)

When the data rates in sensor networks are comparable to the available channel bandwidth, traditional randomized access schemes face the problem of energy inefficiency and reduced throughput due to increased MAC collisions as well as the problem of unfair data delivery. We argue that under such conditions it is preferable to focus on techniques for scheduled access. We present a linear programming formulation and corresponding distributed TDMA-based scheduling algorithms to provide max-min fair collision-free bandwidth allocation to all sources. We evaluate the performance of the proposed scheduled flow technique using the Tossim/Nido network simulator for the Berkeley Mote/TinyOS platform. Our results show that under high data rate conditions, the proposed scheme significantly outperforms randomized access based schemes in terms of key metrics such as fairness, energy efficiency, throughput, and delay.
Antifungal Susceptibility of<i>Candida</i>Biofilms: Unique Efficacy of Amphotericin B Lipid Formulations and Echinocandins (2002)

Biofilms, likely the predominant mode of device-related microbial infection, exhibit resistance to antimicrobial agents. Evidence suggests that Candida biofilms have dramatically reduced susceptibility to antifungal drugs. We examined antifungal susceptibilities of Candida albicans and Candida parapsilosis biofilms grown on a bioprosthetic model. In addition to conventional agents, we determined if new antifungal agents (triazoles, amphotericin B lipid formulations, and echinocandins) have activities against Candida biofilms. We also explored effects of preincubation of C. albicans cells with subinhibitory concentrations (sub-MICs) of drugs to see if they could modify subsequent biofilm formation. Finally, we used confocal scanning laser microscopy (CSLM) to image planktonic- and biofilm-exposed blastospores to examine drug effects on cell structure. Candida biofilms were formed on silicone elastomer and quantified by tetrazolium and dry weight (DW) assays. Susceptibility testing of fluconazole, nystatin, chlorhexidine, terbenafine, amphotericin B (AMB), and the triazoles voriconazole (VRC) and ravuconazole revealed resistance in all Candida isolates examined when grown as biofilms, compared to planktonic forms. In contrast, lipid formulations of AMB (liposomal AMB and AMB lipid complex [ABLC]) and echinocandins (caspofungin [Casp] and micafungin) showed activity against Candida biofilms. Preincubation of C. albicans cells with sub-MIC levels of antifungals decreased the ability of cells to subsequently form biofilm (measured by DW; P < 0.0005). CSLM analysis of planktonic and biofilm-associated blastospores showed treatment with VRC, Casp, and ABLC resulted in morphological alterations, which differed with each agent. In conclusion, our data show that Candida biofilms show unique susceptibilities to echinocandins and AMB lipid formulations.
A novel fuzzy classification to enhance software regression testing (2013)

An effective system regression testing for consecutive releases of very large software systems, such as modern telecommunications systems, depends considerably on the selection of test cases for execution. Classification models can classify, early in the test planning phase, those test cases that are likely to detect faults in the upcoming regression test. Due to the high uncertainties in regression test, classification models based on fuzzy logic are very useful. Recently, methods have been proposed for automatically generating fuzzy if-then rules by applying complicated rule generation procedures to numerical data. In this research, we introduce and demonstrate a new rule-based fuzzy classification (RBFC) modeling approach as a method for identifying high effective test cases. The modeling approach, based on test case metrics and the proposed rule generation technique, is applied to extracting fuzzy rules from numerical data. In addition, it also provides a convenient way to modify rules according to the costs of different misclassification errors. We illustrate our modeling technique with a case study of large-scale industrial software systems and the results showed that test effectiveness and efficiency was significantly improved.
Value Based BTB Indexing for indirect jump prediction (2010)

History-based branch direction predictors for conditional branches are shown to be highly accurate. Indirect branches however, are hard to predict as they may have multiple targets corresponding to a single indirect branch instruction. We propose the Value Based BTB Indexing (VBBI), a correlation-based target address prediction scheme for indirect jump instructions. For each static hard-to-predict indirect jump instruction, the compiler identifies a `hint instruction', whose output value strongly correlates with the target address of the indirect jump instruction. At run time, multiple target addresses of the indirect jump instruction are stored and subsequently accessed from the BTB at different indices computed using the jump instruction PC and the hint instruction output values. In case the hint instruction has not finished its execution when the jump instruction is fetched, a second and more accurate target address prediction is made when the hint instruction output is available, thus reducing the jump misprediction penalty. We compare our design to the regular BTB design and the best previously proposed indirect jump predictor, the tagged target cache (TTC). Our evaluation shows that the VBBI scheme improves the indirect jump target prediction accuracy by 48% and 18%, compared with the baseline BTB and TTC designs, respectively. This results in average performance improvement of 16.4% over the baseline BTB scheme, and 13% improvement over the TTC predictor. Out of this performance improvement 2% is contributed by target prediction overriding which is accurate 96% of the time.