gebhart/patrepeval huggingface dataset:
Evolutionary multi-objective optimisation with a hybrid representation (2004)

For tackling multiobjective optimisation (MOO) problem, many methods are available in the field of evolutionary computation (EC). To use the proposed method(s), the choice of the representation should be considered first. In EC, often binary representation and real-valued representation are used. We propose a hybrid representation, composed of binary and real-valued representations for multi-objective optimisation problems. Several issues such as discretisation error in the binary representation, self-adaptation of strategy parameters and adaptive switching of representations are addressed. Experiments are conducted on five test functions using six different performance indices, which shows that the hybrid representation exhibits better and more stable performance than the single binary or real-valued representation.
Identification of G1 kinase activity for cdk6, a novel cyclin D partner. (1994)

A family of vertebrate cdc2-related kinases has been identified, and these kinases are candidates for roles in cell cycle regulation. Here, we show that the human PLSTIRE gene product is a novel cyclin-dependent kinase, cdk6. The cdk6 kinase is associated with cyclins D1, D2, and D3 in lysates of human cells and is activated by coexpression with D-type cyclins in Sf9 insect cells. Furthermore, we demonstrate that endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB, the product of the retinoblastoma tumor suppressor gene. The activation of cdk6 kinase occurs during mid-G1 in phytohemagglutinin-stimulated T cells, well prior to the activation of cdk2 kinase. This timing suggests that cdk6, and by analogy its homolog cdk4, links growth factor stimulation with the onset of cell cycle progression.
Photonic Glasses: A Step Beyond White Paint (2009)

Self-assembly techniques are widely used to grow ordered structures such as, for example, opal-based photonic crystals. Here, we report on photonic glasses, new disordered materials obtained via a modified self-assembling technique. These random materials are solid thin films which exhibit rich novel light diffusion properties originating from the optical properties of their building blocks. This novel material inaugurated a wide range of nanophotonic materials with fascinating applications, such as resonant random lasers or Anderson localization.
1,4,5,6-Tetrahydropyrrolo[3,4-c]pyrazoles:  Identification of a Potent Aurora Kinase Inhibitor with a Favorable Antitumor Kinase Inhibition Profile (2006)

The optimization of a series of 5-phenylacetyl 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives toward the inhibition of Aurora kinases led to the identification of compound 9d. This is a potent inhibitor of Aurora kinases that also shows low nanomolar potency against additional anticancer kinase targets. Based on its high antiproliferative activity on different cancer cell lines, favorable chemico-physical and pharmacokinetic properties, and high efficacy in in vivo tumor models, compound 9d was ultimately selected for further development.
Identification and elimination of replication-competent adeno-associated virus (AAV) that can arise by nonhomologous recombination during AAV vector production (1997)

Adeno-associated virus (AAV) vector preparations are often contaminated with variable amounts of replication-competent AAV (rcAAV), which may influence the behavior of these vectors both in cultured cells and in animals. A packaging plasmid/vector plasmid system containing no significant homology and lacking the wild-type AAV p5 promoter was constructed to eliminate the production of wild-type AAV by recombination. Still, rcAAV was detected in vector produced by cotransfection of these plasmids at large scale. Sequence analysis revealed that nonhomologous recombination was responsible for the generation of these novel rcAAVs. A new AAV packaging plasmid carrying separate rep and cap expression cassettes in opposite transcriptional orientations was constructed. AAV vector preparations produced by using this packaging construct did not contain rcAAV.
Ostial dimensional changes after pulmonary vein isolation: Pulsed field ablation vs radiofrequency ablation (2020)

This study indicates that unlike after RFA, the incidence and severity of PV narrowing/stenosis after PV isolation is virtually eliminated with PFA.
Antibacterial activity of medicinal plant extracts against periodontopathic bacteria (2003)

This study was performed to evaluate the antibacterial activity of Althaea officinalis L. roots, Arnica montana L. flowers, Calendula officinalis L. flowers, Hamamelis virginiana L. leaves, Illicium verum Hook. fruits and Melissa officinalis L. leaves, against anaerobic and facultative aerobic periodontal bacteria: Porphyromonas gingivalis, Prevotella spp., Fusobacterium nucleatum, Capnocytophaga gingivalis, Veilonella parvula, Eikenella corrodens, Peptostreptococcus micros and Actinomyces odontolyticus. The methanol extracts of H. virginiana and A. montana and, to a lesser extent, A. officinalis were shown to possess an inhibiting activity (MIC < or = 2048 mg/L) against many of the species tested. In comparison, M. officinalis and C. officinalis extracts had a lower inhibiting activity (MIC > or = 2048 mg/L) against all the tested species with the exception of Prevotella sp. Illicium verum methanol extract was not very active though it had a particular good activity against E. corrodens. The results suggest the use of the alcohol extracts of H. virginiana, A. montana and A. officinalis for topical medications in periodontal prophylactics.
Trajectories of postsurgical pain in children (2015)

Over 1 million children undergo inpatient surgery annually in the United States. Emerging research indicates that many children have longer-term problems with pain. However, limited data exist on the course of pain over time and the impact of pain recovery on long-term health outcomes. We sought to prospectively characterize children's postsurgical pain trajectories using repeated assessments over 12 months. In addition, we identified presurgical child and parent psychological risk factors associated with persistent pain and examined relationships between pain trajectories and long-term health outcomes. Sixty children aged 10 to 18 years undergoing major surgery and their parent/guardian were enrolled. Participants completed assessments at 5 time points: presurgery, inhospital, 2 weeks, 4 months, and 1 year postsurgery. Child and parent pain catastrophizing was assessed during the week before surgery. Children completed daily monitoring with an electronic pain diary and reported on pain characteristics, health-related quality of life, and activity limitations. Group-based longitudinal modeling revealed 2 distinct trajectories of postsurgical pain: early recovery (n = 49, 82%) and late recovery (n = 11, 18%). In a logistic regression model controlling for age and sex, parental pain catastrophizing before surgery significantly predicted membership in the late recovery group (odds ratio = 1.11, P = 0.03), whereas child catastrophizing and baseline pain did not (Ps < 0.05). In a multivariate regression controlling for age and sex, late pain recovery was significantly associated with poorer health-related quality of life (β = -10.7, P = 0.02) and greater activity limitations (β = 3.6, P = 0.04) at 1 year. Our findings suggest that preoperative interventions that modify parent behaviors and cognitions might be beneficial in this population.
Expression in CHO cells and pharmacokinetics and brain uptake in the Rhesus monkey of an IgG‐iduronate‐2‐sulfatase fusion protein (2011)

Sulfatases are potential therapeutic biopharmaceuticals, as mutations in sulfatase genes leads to inherited disease. Mucopolysaccharidosis (MPS) Type II is caused by mutations in the lysosomal enzyme, iduronate-2-sulfatase (IDS). MPS-II affects the brain and enzyme replacement therapy is ineffective for the brain, because IDS does not cross the blood-brain barrier (BBB). To deliver IDS across the human BBB, the sulfatase has been re-engineered as an IgG-sulfatase fusion protein with a genetically engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb part of the HIRMAb-IDS fusion protein acts as a molecular Trojan horse to ferry the fused IDS across the BBB. Chinese hamster ovary (CHO) cells were stably transfected to produce the HIRMAb-IDS fusion protein. The fusion protein was triaged to the lysosomal compartment of MPS-II fibroblasts based on confocal microscopy, and 300 ng/mL medium concentrations normalized IDS enzyme activity in the cells. The HIRMAb-IDS fusion protein was tritiated and injected intravenously into the adult Rhesus monkey at a low dose of 0.1 mg/kg. The IDS enzyme activity in plasma was elevated 10-fold above the endogenous level, and therapeutic plasma concentrations were generated in vivo. The uptake of the HIRMAb-IDS fusion protein in the brain was sufficiently high to produce therapeutic concentrations of IDS in the brain following IV administration of the fusion protein.
Antidiabetic thiazolidinediones inhibit leptin (ob) gene expression in 3T3-L1 adipocytes. (1996)

Lack of leptin (ob) protein causes obesity in mice. The leptin gene product is important for normal regulation of appetite and metabolic rate and is produced exclusively by adipocytes. Leptin mRNA was induced during the adipose conversion of 3T3-L1 cells, which are useful for studying adipocyte differentiation and function under controlled conditions. We studied leptin regulation by antidiabetic thiazolidinedione compounds, which are ligands for the adipocyte-specific nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) that regulates the transcription of other adipocyte-specific genes. Remarkably, leptin gene expression was dramatically repressed within a few hours after thiazolidinedione treatment. The ED50 for inhibition of leptin expression by the thiazolidinedione BRL49653 was between 5 and 50 nM, similar to its Kd for binding to PPARgamma. The relatively weak, nonthiazolidinedione PPAR activator WY 14,643 also inhibited leptin expression, but was approximately 1000 times less potent than BRL49653. These results indicate that antidiabetic thiazolidinediones down-regulate leptin gene expression with potencies that correlate with their abilities to bind and activate PPARgamma.
Interleukin-6 is associated with acute concussion in military combat personnel (2020)

Reported here is a significant elevation of IL-6 levels in concussed military personnel less than 8 h following injury. Future studies may examine acute and chronic neurological symptomology associated with inflammatory cytokine levels, distinguish individuals at high risk for developing neurological complications, and identify underlying biological pathways to mitigate inflammation and improve outcomes.
Behavioral synthesis for FPGA-based computing (2002)

We describe how a behavioral synthesis system can be used to create designs for FPGA-based computing systems directly from a specification of the desired algorithm. This higher level of specification reduces design times and design errors. Our target hardware is called the Rasa Board and is composed of three Xilinx FPGAs interconnected with Aptix Field Programmable Interconnect Chips. We address two significant challenges in this research effort: the synthesis of multiple FPGA designs, and the improvement of the design through designer interaction.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Overexpression of hypoxia-inducible factor 1alpha is associated with an unfavorable prognosis in lymph node-positive breast cancer. (2002)

This study shows that HIF-1alpha is an independent prognostic factor for an unfavorable prognosis in patients with lymph node-positive breast cancer. Our results indicate that patients with advanced-stage breast cancers might profit from future therapies targeting HIF-1alpha.
Demonstration of isoelectric focusing on an etched quartz chip with UV absorption imaging detection† (1999)

The feasibility of isoelectric focusing (IEF) performed on-chip was demonstrated for the first time via absorption imaging detection. Microchannels on a quartz chip were fabricated using photolithography and a chemical etching process. The separation channels were 40 mm long, 100 µm wide and 10 µm deep, and were coated with linear polyacrylamide to reduce electroosmotic flow. A quartz chip cartridge for IEF was assembled in which two pieces of hollow fiber were glued to the two ends of the separation channel to isolate the electrolytes from the samples. Low molecular mass pI markers and myoglobin were selected as model samples which were mixed with 4% carrier ampholyte solution. Samples were injected into the channel via the connection capillary by pressure. A voltage of 3 kV was applied to perform IEF. The IEF current decreased from about 13.4 to 1.3 µA. The focused zones were monitored in real time by absorption imaging detection at 280 nm. The detection limit was about 0.3 µg ml–1 or 24 pg for pI marker 6.6, and 30 µg ml–1 or 2.4 ng for myoglobin with an optical pathlength of 10 µm. Good reproducibility and resolution were obtained for linear polyacrylamide coated channels. The total analysis time was less than 10 min. This imaged chip IEF provides a fast separation technique with quantitative ability and the potential for increasing throughput.
Photoreceptors and Regulation of Flowering Time (2000)

One of the most important environmental factors affecting flowering time is the daily duration of light, the photoperiod, which was first discovered by Garner and Allard in the 1920s ([Thomas and Vince-Prue, 1997][1], and refs. therein). Plants in which flowering occurs or is accelerated in short
Role of Sphingosine-1-phosphate Phosphatase 1 in Epidermal Growth Factor-induced Chemotaxis (2004)

Sphingosine-1-phosphate (S1P) is the ligand for a family of specific G protein-coupled receptors that regulate a wide variety of cellular functions, including cytoskeletal rearrangements and cell motility. Because of the pivotal role of S1P, its levels are low and tightly regulated in a spatial-temporal manner through its synthesis catalyzed by sphingosine kinases and degradation by an S1P lyase and specific S1P phosphatases (SPP). Surprisingly, down-regulation of SPP-1 enhanced migration toward epidermal growth factor (EGF); conversely, overexpression of SPP-1, which is localized in the endoplasmic reticulum, attenuated migration toward EGF. To determine whether the inhibitory effect on EGF-induced migration was because of decreased S1P or increased ceramide as a consequence of acylation of increased sphingosine by ceramide synthase, we used fumonisin B1, a specific inhibitor of ceramide synthase. Although fumonisin B1 blocked ceramide production and increased sphingosine, it did not reverse the negative effect of SPP-1 expression on EGF- or S1P-induced chemotaxis. EGF activated the epidermal growth factor receptor to the same extent in SPP-1-expressing cells, yet ERK1/2 activation was impaired. In agreement, PD98059, an inhibitor of the ERK-activating enzyme MEK, decreased EGF-stimulated migration. We next examined the possibility that intracellularly generated S1P might be involved in activating a G protein-coupled S1P receptor important for EGF-directed migration. Treatment with pertussis toxin to inactivate Galpha(i) suppressed EGF-induced migration. Moreover, expression of regulator of G protein signaling 3, which inhibits S1P receptor signaling and completely prevented ERK1/2 activation mediated by S1P receptors, not only reduced migration toward S1P but also markedly reduced migration toward EGF. Collectively, these results suggest that metabolism of S1P by SPP-1 is important for EGF-directed cell migration.
Covalent Modification of the Regulatory Domain Irreversibly Stimulates Cystic Fibrosis Transmembrane Conductance Regulator (1997)

The cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel is regulated by three cytosolic domains, the regulatory domain (R domain) and two nucleotide binding domains. To learn more about how the cytosolic domains regulate channel activity, we used chemical modification to probe their structure. When we applied the sulfhydryl-modifying reagent N-ethylmaleimide (NEM) and other N-substituted maleimides to the cytosolic domains, we found that they rapidly and irreversibly stimulated channel activity. CFTR contains 14 intracellular cysteine residues that might be targets for NEM modification. We identified one, Cys832, that was essential for the response. Cys832 is located in the R domain. Single channel studies showed that NEM stimulated CFTR by increasing the duration of bursts of activity and by shortening the closed interval between bursts. At the single channel level, CFTR in which Cys832 was mutated to alanine behaved identically to wild-type CFTR, except that it failed to respond to NEM. Additional studies showed that NEM modification increased the potency of ATP-mediated stimulation. Previous work has shown that modification of the R domain by phosphorylation, which introduces negative charge, or replacement of multiple serines by negatively charged aspartates stimulates the channel. Our current data show that covalent modification of the R domain with a neutral, hydrophobic adduct at a site that is not phosphorylated can also stimulate CFTR. This finding suggests that an alteration in the conformation of the R domain may be a key feature that regulates channel activity.
Anti-CD40 monoclonal antibodies or CD4+ T cell clones and IL-4 induce IgG4 and IgE switching in purified human B cells via different signaling pathways (1991)

IL-4 induces IgE and IgG4 synthesis, but in addition to IL-4, a second signal provided by CD4+ T cells is required. Here we demonstrate that the signal provided by CD4+ T cells can be replaced by anti-CD40 mAb. Highly purified surface (sIgM+) human B cells cultured with soluble anti-CD40 mAb in the presence of IL-4 produced IgM, total IgG, IgG4, and relatively high levels of IgE, indicating that production of these isotypes represented H chain switching and was not the result of a selective outgrowth of isotype committed B cells. No IgA was produced in these cultures. However, the T cell signal was different from the signal provided by anti-CD40 mAb, because in contrast to CD4+ T cells, anti-CD40 mAb failed to induce germ-line epsilon transcripts. However, anti-CD40 mAb strongly enhanced germ-line epsilon mRNA expression induced by IL-4. In addition, IFN-gamma, IFN-alpha, and anti-CD23 mAb, which block IL-4-induced IgE production by PBMC, or B cells cocultured with CD4+ T cell clones, failed to inhibit IgG4 and IgE synthesis induced by anti-CD40 mAb. Finally, anti-CD40 mAb and CD4+ T cell clones had strong synergistic effects on IgG4 and IgE synthesis. These results indicate that different B cell activation pathways can result in IgG4 and IgE switching in the presence of IL-4.
Thermodynamics and Kinetics of the Li/FeF3 Reaction by Electrochemical Analysis (2012)

FeF3 is a promising cathode material for lithium batteries with a very high energy density due to its complete reduction to a mixture of LiF and Fe. The material is not yet practical due to a greater than 1 V hysteresis during charge and discharge. Previous work has suggested that this hysteresis might be intrinsic due to different reaction pathways. We employ galvanostatic intermittent titration (GITT), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) to study the reaction thermodynamics and kinetics. GITT experiments, when the electrode is allowed to rest for 72 h following a discharge or charge step, show that the hysteresis is 280 mV, in contrast to >1 V observed previously with slow rate charge and discharge experiments. CV results obtained in different potential ranges indicate that the apparent hysteresis is mostly due to the large overpotential needed to overcome the energy barrier for the nucleation of the LiF/Fe composite phases. EIS results are consistent with the formation of the nanocomposite. Further, EIS results indicate that extended rest of the electrode under open circuit appears to result in coalescence of the Fe nanoparticles, which reduces the Fe/LiF interfacial area. This hypothesis is also consistent with our observation that the charge–discharge overpotentials at high rates are smaller than what the Ohmic law would dictate. On the basis of these results, a reaction mechanism for the reaction is presented. The mechanism also points to potential approaches to mitigate the hysteresis through nanoengineering of the material.
Diphtheria toxin. Site and configuration of ADP-ribosylation of diphthamide in elongation factor 2. (1981)

Diphtheria toxin inactivates protein synthesis elongation factor 2 by catalyzing the ADP-ribosylation of a novel derivative of histidine, diphthamide, in the protein (Van Ness, B. G., Howard, J. B., and Bodley, J. W. (1980) J. Biol. Chem. 255, 10710-10716). In this report, we describe experiments involving nuclear Overhauser enhancement NMR spectroscopy which were undertaken to elucidate the site of ADP-ribosylation of diphthamide and the configuration of the glycosidic bond formed by the toxin. The essential result of these experiments is that, in ribosyl-diphthamide obtained by enzymatic digestion of ADP-ribosyl-elongation factor-2, the H-5 imidazole proton is near the R-4 proton of ribose. This result and others are consistent with the interpretation that diphtheria toxin covalently attaches ADP-ribose to the imidazole N-1 of diphthamide via an alpha-glycosidic linkage.
Age-related activation of the tyrosine kinase receptor protooncogenes RET and NTRK1 in papillary thyroid carcinoma (1996)

Oncogenic rearrangements of RET and NTRK1 proto-oncogenes are frequently detected in papillary thyroid carcinomas. Several studies have shown an association between ionizing radiation and development of this tumor type. In addition in vitro irradiation of tumor cell lines induced rearrangements of RET similar to those observed in human papillary thyroid carcinomas. These two observations could be related to the reported increased incidence of papillary thyroid carcinomas in children living in contaminated areas around Chernobyl, given that it has been demonstrated that about 60% of them presents a RET oncogenic activation. However, this high frequency of RET positivity in radiation exposed children does not rule out the possibility that age could also play a role in the development of RET positive tumors. To assess this possibility we looked for a relationship between the presence of RET and NTRK1 oncogenic rearrangements and age at surgery in a sample of 92 consecutive patients. Our results show that, in papillary thyroid carcinoma, the frequency of RET and NTRK1 activation is significantly higher in the group of patients aged 4-30 years, thas supporting the concept that age could be contributing to this thyroid specific carcinogenic process.
A new view of the EM algorithm that justifies incremental and other variants (1993)

We present a new view of the EM algorithm for maximum likelihood estimation in situations with unobserved variables. In this view, both the E and the M steps of the algorithm are seen as maximizing a joint function of the model parameters and of the distribution over unobserved variables. From this perspective, it is easy to justify an incremental variant of the algorithm in which the distribution for only one of the unobserved variables is recalculated in each E step. This variant is shown empirically to give faster convergence in a mixture estimation problem. A wide range of other variant algorithms are also seen to be possible. Some key words: EM algorithm, incremental algorithms, free energy, mixtures Submitted to Biometrika 1 Introduction The Expectation-Maximization (EM) algorithm finds maximum likelihood parameter estimates in problems where some variables were unobserved. Its widespread applicability was first discussed by Dempster, Laird, and Rubin (1977). The EM algorithm ...