gebhart/patrepeval huggingface dataset:
Overexpression of Trigger Factor Prevents Aggregation of Recombinant Proteins in <i>Escherichia coli</i> (2000)

To examine the effects of overexpression of trigger factor (TF) on recombinant proteins produced in Escherichia coli, we constructed plasmids that permitted controlled expression of TF alone or together with the GroEL-GroES chaperones. The following three proteins that are prone to aggregation were tested as targets: mouse endostatin, human oxygen-regulated protein ORP150, and human lysozyme. The results revealed that TF overexpression had marked effects on the production of these proteins in soluble forms, presumably through facilitating correct folding. Whereas overexpression of TF alone was sufficient to prevent aggregation of endostatin, overexpression of TF together with GroEL-GroES was more effective for ORP150 and lysozyme, suggesting that TF and GroEL-GroES play synergistic roles in vivo. Although coexpression of the DnaK-DnaJ-GrpE chaperones was also effective for endostatin and ORP150, coexpression of TF and GroEL-GroES was more effective for lysozyme. These results attest to the usefulness of the present expression plasmids for improving protein production in E. coli.
50W CW visible laser source at 589nm obtained via frequency doubling of three coherently combined narrow-band Raman fibre amplifiers (2010)

We demonstrate the cascaded coherent collinear combination of a seed-split triplet of 1178nm high-power narrow-band (sub-1.5MHz) SBS-suppressed CW Raman fibre amplifiers via nested free-space constructive quasi-Mach-Zehnder interferometry, after analysing the combination of the first two amplifiers in detail. Near-unity combination and cascaded-combination efficiencies are obtained at all power levels up to a maximum P(1178) > 60W. Frequency doubling of this cascaded-combined output in an external resonant cavity yields P(589) > 50W with peak conversion efficiency eta(589) ~85%. We observe no significant differences between the SHG of a single, combined pair or triplet of amplifiers. Although the system represents a successful power scalability demonstrator for fibre-based Na-D(2a)-tuned mesospheric laser-guide-star systems, we emphasise its inherent wavelength versatility and consider its spectroscopic and near-diffraction-limited qualities equally well suited to other applications.
Determination of Hydrogen Solubility in Heavy Fractions of Crude Oils by a Modified Direct Method (2013)

The solubility of hydrogen in Venezuelan heavy coking gas oil (HCGO), Karamay atmospheric residue (KRAR), Liaohe atmospheric residue (LHAR), and Venezuelan atmospheric residue (VNAR) was measured at temperatures in the range 150 °C to 350 °C at pressures up to 11 MPa by a modified direct method. The measurement accuracy and reliability were examined by determining hydrogen solubility in toluene and n-heptane at temperatures of 25 °C, 50 °C and 100 °C, and results are in a good agreement with the data reported. The order of hydrogen solubility in the four feedstocks at the same experimental condition is VNAR < LHAR < KRAR < HCGO. The impact of oil properties, such as aromatic ring number and alkyl chain length, on hydrogen solubility was discussed. The results indicate that the condensed aromatics play a key role in the fractions of high boiling points. The hydrogen dissolving capacity in different derived oils with the same boiling range can be tentatively determined via analyzing the H/C atomic ratio of the oils.
A phase 2 study of berzosertib (M6620) in combination with carboplatin compared with docetaxel in combination with carboplatin in metastatic castration-resistant prostate cancer. (2021)

5034 Background: Alterations in DNA damage repair (DDR) genes are common in metastatic castration-resistant prostate cancer (mCRPC), and are implicated in responses to carboplatin [carbo], PARP inhibitors and immunotherapeutics. Inhibitors of the ATR kinase, which is involved in the DDR response, have been demonstrated to have synergistic activity with platinum compounds in preclinical models. We therefore conducted a phase 2 study of the ATR inhibitor berzosertib [berzo]+carbo vs. docetaxel [doce]+carbo in mCRPC. Methods: Patients (pts) previously treated with at least one secondary hormonal therapy and taxane underwent mandatory pre-treatment biopsy and were randomized 1:1 to receive Arm A (doce 60 mg/m2 day 1 + carbo AUC 4 day 1) or Arm B (berzo 90 mg/m2 days 2,9 + carbo AUC 5 day 1) every 21 days. Pts randomized to Arm A who were not candidates for doce received carbo AUC 5 monotherapy. Stratification factors were 1) prior PARP inhibitor (yes vs. no) and 2) evaluable disease by RECIST 1.1 (yes vs. no). Pts on Arm A crossed over to Arm B (berzo+carbo) at the earlier of PSA or radiographic progression. The primary endpoint was overall response rate (ORR; PSA reduction by ≥ 50% or radiographic response by RECIST 1.1). Secondary endpoints included time to PSA progression, radiographic PFS (rPFS), PFS by PCWG3 criteria, and adverse events (AEs) in each arm. Planned enrollment was 136 pts (for 130 to be treated), with interim analysis for futility after 65 pts were treated. Results: 73 pts were randomized between 6/2019 and 7/2020; 34 pts were treated on Arm A (26 carbo+doce; 8 carbo alone) and 31 on Arm B. Median number of prior systemic therapies (excluding ADT, 5α-reductase inhibitors, 1st generation antiandrogens) was 4 (range 2-8). Median treatment duration was 3 cycles, and 4 pts in each arm discontinued for AEs. Grade 3 or higher treatment-related AEs (TrAE) were seen in 13(38%) pts in Arm A and 21(68%) in Arm B. Pts in Arm B had greater frequency of grade 3-4 thrombocytopenia (8[26%] vs. 3[9%]). 1 pt in Arm B had grade 5 sepsis attributed to study treatment. ORR was 15% in Arm A (5/34; 5/26[19%] in pts who received carbo+doce) and 0% in Arm B (0/31). 14 pts in Arm A crossed over, with no subsequent responses seen. Median rPFS was 2.1(95% CI:2.0,3.2) mo in Arm A and 2.4(1.9,4.2) mo in Arm B. At planned interim analysis, trial enrollment and crossover to Arm B were halted due to futility. Conclusions: Carbo+berzo led to fewer overall responses and a higher rate of grade 3 or higher TrAEs compared to carbo+doce. All responses seen were in pts who received carbo+doce despite requirement for prior progression on taxane, suggesting that this combination is favored over carbo+berzo or carbo monotherapy in a heavily pre-treated biomarker-unselected population. Extensive genetic and molecular studies for DDR assessment from tissue and cfDNA are in progress. Clinical trial information: NCT03517969.
Bacterial Membranes as Predictors of Antimicrobial Potency (2008)

A wide range of chemical structures having antimicrobial activity have been studied in an effort to treat the increasing emergence of bacteria that are resistant to traditional antibiotics. These agents have varying degrees of toxicity against different bacterial species. We demonstrate, using members of a novel class of antimicrobial agents, the oligomers of acyllysine, that one cause for the difference in species selectivity is the ability to induce the clustering of anionic lipids, resulting in their segregation into domains. This phenomenon occurs only in bacterial membranes composed of both anionic and zwitterionic lipids and not with bacteria whose membrane lipids are largely anionic. As a consequence it can be predicted which bacterial species will be most affected by antimicrobial agents that function principally by this mechanism. This finding allows for the design of new antibiotics with selective toxicity against different groups of bacteria.
Cloning and expression of the Hpal restriction-modification genes (1992)

The genes from Haemophilus parainfluenzae encoding the HpaI restriction-modification system were cloned and expressed in Escherichia coli. From the DNA sequence, we predicted the HpaI endonuclease (R.HpaI) to have 254 amino acid residues (Mr 29,630) and the HpaI methyltransferase (M.HpaI) to have 314 amino acid residues (37,390). The R.HpaI and M.HpaI genes overlapped by 16 base pairs on the chromosomal DNA. The genes had the same orientation. The clone, named E. coli HB101-HPA2, overproduced R.HpaI. R.HpaI activity from the clone was 100-fold that from H. parainfluenzae. The amino acid sequence of M.HpaI was compared with those of other type II methyltransferases.
Three-Level Switching Cell for Low Voltage/High-Current DC–DC Converters (2007)

New three-level switching cell converter topologies are proposed for transformer isolated low voltage/high current output dc-dc conversion. When compared with corresponding conventional converters without the three-level switching cell, the proposed converters operate with smaller current ripple and reduced voltage stresses. Alternatively, the current ripple size can be kept the same and the filter inductor value can be reduced for higher slew rate. First, the operation principles of these converters are described. Then converter design, control implementation and applications are presented. The capacitor charge balance problem is also addressed. Circuit simulations and experiments verify the basic operation of the new converters and their efficiency improvement.
Snoring: analysis, measurement, clinical implications and applications (1996)

Snoring was described in literature even before medicine. Common definitions do not consider acoustic measurements of snoring. In this paper we discuss the main pathophysiological aspects of snoring and the snoring-sleep relationship as the generating mechanisms. Snoring can be analysed and measured by the following methods: 1) Leq-Equivalent Continuous Sound Level, which only quantifies noisiness, annoyance, and damage to the partner's and snorer's hearing; 2) Power Spectrum, with frequency values, formantic structure data and typical shape, which can help to distinguish simple snoring from heavy snoring with obstructive sleep apnoea syndrome (OSAS); 3) Linear Prediction Code (LPC) method, which can define the cross-sectional area (CSA) of the upper airways and which locates sites of obstruction. Simulated snoring analysis with LPC and with simultaneous fluoroscopy permits the definition of CSA and the identification of three snoring patterns: nasal, oral and oronasal. Snoring is an important sign of sleep-related breathing disorders (SRBD), of the upper airway resistance syndrome (UARS), and of the OSAS. Snoring is a symptom of nasal obstruction and is associated with cardiovascular diseases and nocturnal asthma as a trigger or causative factor; however, its acoustic features in these disorders are not well-defined. Home monitoring of snoring is very useful for epidemiology and is mandatory, together with heart rate and arterial oxygen saturation (Sa,O2), to screen SRBD.
Mutagenesis of Bordetella pertussis with transposon Tn5tac1: conditional expression of virulence-associated genes (1990)

The Tn5tac1 transposon contains a strong outward-facing promoter, Ptac, a lacI repressor gene, and a selectable Kanr gene. Transcription from Ptac is repressed by the lacI protein unless an inducer (isopropyl-beta-D-thiogalactopyranoside [IPTG]) is present. Thus, Tn5tac1 generates insertion mutations in Escherichia coli with conditional phenotypes because it is polar on distal gene expression when IPTG is absent and directs transcription of these genes when the inducer is present. To test the usefulness of Tn5tac1 in Bordetella pertussis, a nonenteric gram-negative bacterial pathogen, we chose the bifunctional adenylate cyclase-hemolysin determinant as an easily scored marker to monitor insertional mutagenesis. Tn5tac1 delivered to B. pertussis on conjugal suicide plasmids resulted in Kanr exconjugants at a frequency of 10(-3) per donor cell, and nonhemolytic (Hly-) mutants were found among the Kanr colonies at a frequency of about 1%. Of eight independent Kanr Hly- mutants, two were conditional and exhibited an Hly+ phenotype only in the presence of IPTG. Using a new quantitative assay for adenylate cyclase based on high-pressure liquid chromatography, we found that enzymatic activity in these two strains was specifically induced at least 500-fold in a dose-dependent fashion over the range of 0 to 125 microM IPTG. These data show that Ptac serves as a promoter, lacI is expressed and is functional, and IPTG can induce Ptac transcription in B. pertussis. Adenylate cyclase expression in whole cells, culture supernatants, and cell extracts from these strains depended upon IPTG, suggesting that the insertions do not merely alter secretion of adenylate cyclase-hemolysin. Other virulence determinants under control of the vir locus are expressed normally, implying that these Tn5tac1 insertions specifically regulate adenylate cyclase-hemolysin expression. We conclude that Tn5tac1 insertion mutations permit sensitive, exogenous control over the expression of genes of interest, providing a useful tool for studying virulence and other important traits of diverse bacterial species.
Crosstalk between Gi and Gq/Gs pathways in airway smooth muscle regulates bronchial contractility and relaxation (2007)

Receptor-mediated airway smooth muscle (ASM) contraction via G(alphaq), and relaxation via G(alphas), underlie the bronchospastic features of asthma and its treatment. Asthma models show increased ASM G(alphai) expression, considered the basis for the proasthmatic phenotypes of enhanced bronchial hyperreactivity to contraction mediated by M(3)-muscarinic receptors and diminished relaxation mediated by beta(2)-adrenergic receptors (beta(2)ARs). A causal effect between G(i) expression and phenotype has not been established, nor have mechanisms whereby G(i) modulates G(q)/G(s) signaling. To delineate isolated effects of altered G(i), transgenic mice were generated overexpressing G(alphai2) or a G(alphai2) peptide inhibitor in ASM. Unexpectedly, G(alphai2) overexpression decreased contractility to methacholine, while G(alphai2) inhibition enhanced contraction. These opposite phenotypes resulted from different crosstalk loci within the G(q) signaling network: decreased phospholipase C and increased PKCalpha, respectively. G(alphai2) overexpression decreased beta(2)AR-mediated airway relaxation, while G(alphai2) inhibition increased this response, consistent with physiologically relevant coupling of this receptor to both G(s) and G(i). IL-13 transgenic mice (a model of asthma), which developed increased ASM G(alphai), displayed marked increases in airway hyperresponsiveness when G(alphai) function was inhibited. Increased G(alphai) in asthma is therefore a double-edged sword: a compensatory event mitigating against bronchial hyperreactivity, but a mechanism that evokes beta-agonist resistance. By selective intervention within these multipronged signaling modules, advantageous G(s)/G(q) activities could provide new asthma therapies.
REDUCTION OF ADHERENCE OF STRICTLY ANAEROBIC BACTERIA ON FLUORINE-DOPED TITANIUM (2018)

In the past decades, titanium-based biomaterials have been broadly used in maxillofacial and periodontology surgery. The main aetiological agents related to complications in this procedures are Por...
<title>Series of CCD cameras for low-light-level applications</title> (1996)

We describe a series of five CCD cameras designed by Gordian for low light-level applications. The first device is a low-cost non-imaging astronomical autoguiding tracker based on the Texas Instruments TC255 CCD chip and an MC6811 microcontroller. Mounting off-axis, it provides standardized tracking-motor signals for any telescope with a dual-axis drive corrector, automatically compensating for the mechanical peculiarities of the drive, set- up factors, and pointing errors. The tracker can guide to +/- 1 arcsec on an 8th magnitude star when used with an 8' aperture, f/10 telescope. The basic autoguider design has been extended to produce self-contained 8-bit and 16-bit imaging cameras with autoguiding functionality. Images are buffered in PSRAM, then relayed to a host PC via an RS-232 serial connection. The addition of regulated thermoelectric cooling reduces CCD thermal noise and alleviates dark current saturation. Gordian has also designed two high-resolution cameras based on the Kodak KAF-0400 and KAF-1600 CCDs. The cameras produce 16-bit images with 768 X 512 pixels or 1536 X 1024 pixels, respectively. Pixel size is 9 micrometers square. The camera head contains the CCD, thermoelectric cooling mechanism, analog electronics, and a custom-designed electromechanical shutter based on Flexinol<SUP>TM</SUP> actuator wire. A separate base unit houses a Motorola 68306 microprocessor and associated electronics for telescope control and on-board image processing. A stepper-motor based filter wheel can be attached directly to the camera head. The camera communicates with a personal computer via SCSI or serial connection. Software for the host PC provides additional control options, data storage, and image processing capability.
Costless: Optimizing Cost of Serverless Computing through Function Fusion and Placement (2018)

Serverless computing has recently experienced significant adoption by several applications, especially Internet of Things (IoT) applications. In serverless computing, rather than deploying and managing dedicated virtual machines, users are able to deploy individual functions, and pay only for the time that their code is actually executing. However, since serverless platforms are relatively new, they have a completely different pricing model that depends on the memory, duration, and the number of executions of a sequence/workflow of functions. In this paper we present an algorithm that optimizes the price of serverless applications in AWS Lambda. We first describe the factors affecting price of serverless applications which include: (1) fusing a sequence of functions, (2) splitting functions across edge and cloud resources, and (3) allocating the memory for each function. We then present an efficient algorithm to explore different function fusion-placement solutions and find the solution that optimizes the application's price while keeping the latency under a certain threshold. Our results on image processing workflows show that the algorithm can find solutions optimizing the price by more than 35%-57% with only 5%-15% increase in latency. We also show that our algorithm can find non-trivial memory configurations that reduce both latency and price.
Recent advances in cartilage tissue engineering (2014)

Welcome to the WIT Press eLibrary - the home of the Transactions of the Wessex Institute collection, providing on-line access to papers presented at the Institute's prestigious international conferences and from its State-of-the-Art in Science & Engineering publications.
Fully Integrated Single Photon Avalanche Diode Detector in Standard CMOS 0.18- $\mu$m Technology (2008)

Avalanche photodiodes (APDs) operating in Geiger mode can detect weak optical signals at high speed. The implementation of APD systems in a CMOS technology makes it possible to integrate the photodetector and its peripheral circuits on the same chip. In this paper, we have fabricated APDs of different sizes and their driving circuits in a commercial 0.18-mum CMOS technology. The APDs are theoretically analyzed, measured, and the results are interpreted. Excellent breakdown performance is measured for the 10 and 20 m APDs at 10.2 V. The APD system is compared to the previous implementations in standard CMOS. Our APD has a 5.5% peak probability of detection of a photon at an excess bias of 2 V, and a 30 ns dead time, which is better than the previously reported results.
European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts) * Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR) (2012)

C-reactive protein CURE Clopidogrel in Unstable Angina to Prevent Recurrent Events CVD cardiovascular disease DALYs disability-adjusted life years DBP diastolic blood
A Study of Infantile Motor Neuron Disease with Neurofilament and Ubiquitin Immunocytochemistry* (1989)

We report a patient with infantile motor neuron disease who had pathologic findings consistent with multisystem degeneration. Although the muscle showed denervation atrophy and spinal anterior horn cells showed either atrophy or ballooning degeneration consistent with lower motor neuron disease, the infant was hypertonic and spastic. Degenerative changes were also detected in the dorsal root ganglia, cerebellum, and thalamus. Immunohistochemical studies showed a paucity of neurofilament (NF) staining in the corticospinal tract and accumulation of phosphorylated NF in ballooned neurons. Antibodies to ubiquitin immunostained ballooned neurons in the dorsal root ganglia, anterior horns, and thalamus. Accumulation of ubiquitinated and phosphorylated NF epitopes in degenerating neurons suggest that basic abnormalities in the neuronal cytoskeleton may be instrumental in the pathogenesis of this disorder.
Direct Conversion of Cyclohexane into Adipic Acid with Molecular Oxygen Catalyzed by <i>N</i>-Hydroxyphthalimide Combined with Mn(acac)<sub>2</sub> and Co(OAc)<sub>2</sub> (1998)

Direct conversion of cyclohexane into adipic acid was achieved by the use of the radical catalyst, N-hydroxyphthalimide (NHPI), in the presence of a small amount of a transition metal. For instance, cyclohexane could be converted into adipic acid in 73% selectivity at 73% conversion under atmospheric oxygen (1 atm) in the presence of NHPI (10 mol %) and Mn(acac)2 (1 mol %) at 100 °C for 20 h. ESR measurements show that the formation of phthalimide N-oxyl generated from NHPI with O2 was assisted by Co(II) species. Thus, the oxidation of cyclohexane to adipic acid was found to be enhanced by the addition of a small amount of Co(OAc)2 to the NHPI/Mn(acac)2 system. The NHPI-catalyzed oxidation of cyclohexane provides an attractive direct method which has long been desired in the chemical industry for the manufacturing of adipic acid. The present oxidation seems to be the first practical environmentally friendly process, in which nitric acid is not used as the oxidant, for the production of adipic acid from cyclohexane.
Properties of the Glycoprotein Laccase Immobilized by Two Methods. (1975)

Laccase (p-diphenol:oxygen oxidoreductase; EC 1.10.3.2) from Neurospora crassa has been immobilized by two different procedures: (1) Covalent attachment to Sepharose 4B activated with cyanogen bromide, and (2) Adsorption to Concanavalin A-Sepharose via the carbohydrate moiety. Except for small changes in the Michaelis-Menten constants, no differences were noted in the enzymological properties of the immobilized enzymes when compared to free enzyme. The carbohydrate moiety of laccase involved in the interaction with Concanavalin A does not appear to be closely associated with the active center since binding to the lectin has no effect on the enzymological parameters investigated.