gebhart/patrepeval huggingface dataset:
Long non-coding RNA-targeting therapeutics: discovery and development update (2023)

Extensive druggable target range of lncRNA combined with high specificity and accelerated development process of nucleic acid-based therapeutics open new prospects for treatment in areas of extreme unmet medical need, such as genetic diseases, aggressive cancers, protein deficiencies, and subsets of common diseases caused by known mutations. Although currently wide acceptance of lncRNA-targeting nucleic acid-based therapeutics is impeded by the need for parenteral or direct-to-CNS administration, development of less invasive techniques and orally available/BBB-penetrant nucleic acid-based therapeutics is showing early successes. Recently, mRNA-based COVID-19 vaccines have demonstrated clinical safety of all aspects of nucleic acid-based therapeutic technology, including multiple chemical modifications of nucleic acids and nanoparticle delivery. These trends position lncRNA-targeting drugs as significant players in the future of drug development, especially in the area of personalized medicine.
Modified Vaccinia Virus Ankara Protects Macaques against Respiratory Challenge with Monkeypox Virus (2005)

The use of classical smallpox vaccines based on vaccinia virus (VV) is associated with severe complications in both naive and immune individuals. Modified vaccinia virus Ankara (MVA), a highly attenuated replication-deficient strain of VV, has been proven to be safe in humans and immunocompromised animals, and its efficacy against smallpox is currently being addressed. Here we directly compare the efficacies of MVA alone and in combination with classical VV-based vaccines in a cynomolgus macaque monkeypox model. The MVA-based smallpox vaccine protected macaques against a lethal respiratory challenge with monkeypox virus and is therefore an important candidate for the protection of humans against smallpox.
Loss-of-Function Mutations in the Cardiac Calcium Channel Underlie a New Clinical Entity Characterized by ST-Segment Elevation, Short QT Intervals, and Sudden Cardiac Death (2007)

This is the first report of loss-of-function mutations in genes encoding the cardiac L-type calcium channel to be associated with a familial sudden cardiac death syndrome in which a Brugada syndrome phenotype is combined with shorter-than-normal QT intervals.
Chronic Obstructive Pulmonary Disease Quantification Using CT Texture Analysis and Densitometry: Results From the Danish Lung Cancer Screening Trial (2020)

<b>OBJECTIVE.</b> The purpose of this study is to establish whether texture analysis and densitometry are complementary quantitative measures of chronic obstructive pulmonary disease (COPD) in a lung cancer screening setting. <b>MATERIALS AND METHODS.</b> This was a retrospective study of data collected prospectively (in 2004-2010) in the Danish Lung Cancer Screening Trial. The texture score, relative area of emphysema, and percentile density were computed for 1915 baseline low-dose lung CT scans and were evaluated, both individually and in combination, for associations with lung function (i.e., forced expiratory volume in 1 second as a percentage of predicted normal [FEV<sub>1</sub>% predicted]), diagnosis of mild to severe COPD, and prediction of a rapid decline in lung function. Multivariate linear regression models with lung function as the outcome were compared using the likelihood ratio test or the Vuong test, and AUC values for diagnostic and prognostic capabilities were compared using the DeLong test. <b>RESULTS.</b> Texture showed a significantly stronger association with lung function (<i>p</i> < 0.001 vs densitometric measures), a significantly higher diagnostic AUC value (for COPD, 0.696; for Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade 1, 0.648; for GOLD grade 2, 0.768; and for GOLD grade 3, 0.944; <i>p</i> < 0.001 vs densitometric measures), and a higher but not significantly different association with lung function decline. In addition, only texture could predict a rapid decline in lung function (AUC value, 0.538; <i>p</i> < 0.05 vs random guessing). The combination of texture and both densitometric measures strengthened the association with lung function and decline in lung function (<i>p</i> < 0.001 and <i>p</i> < 0.05, respectively, vs texture) but did not improve diagnostic or prognostic performance. <b>CONCLUSION.</b> The present study highlights texture as a promising quantitative CT measure of COPD to use alongside, or even instead of, densitometric measures. Moreover, texture may allow early detection of COPD in subjects who undergo lung cancer screening.
Reconstruction of three‐dimensional linear structures in the breast from craniocaudal and mediolateral oblique mammographic views (2017)

A three‐dimensional (3D) representation of the linear structures in a breast has been constructed by utilising information of the ridges in the craniocaudal (CC) and the mediolateral oblique (MLO) mammographic views of the breast. Blood vessels and ducts appear as ridges in the mammogram. The position and shape of the ridges in the breast are an indicator of malignancy. In the first stage of the proposed 3D reconstruction problem, an algorithm has been developed to find out which linear structure in the CC view and a linear structure in the MLO view correspond to the same 3D structure in the breast. The 3D view of the linear structures is constructed from the abovementioned correspondences. The positional error (per unit length of the reconstructed linear structure) between the manual reconstruction and the algorithmic reconstruction of a linear structure turns out to be better by 20% than a competing approach.
Evidence that the retroviral DNA integration process triggers an ATR-dependent DNA damage response (2003)

Caffeine is an efficient inhibitor of cellular DNA repair, likely through its effects on ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related) kinases. Here, we show that caffeine treatment causes a dose-dependent reduction in the total amount of HIV-1 and avian sarcoma virus retroviral vector DNA that is joined to host DNA in the population of infected cells and also in the number of transduced cells. These changes were observed at caffeine concentrations that had little or no effect on overall cell growth, synthesis, and nuclear import of the viral DNA, or the activities of the viral integrase in vitro. Substantial reductions in the amount of host-viral-joined DNA in the infected population, and in the number of transductants, were also observed in the presence of a dominant-negative form of the ATR protein, ATRkd. After infection, a significant fraction of these cells undergoes cell death. In contrast, retroviral transduction is not impeded in ATM-deficient cells, and addition of caffeine leads to the same reduction that was observed in ATM-proficient cells. These results suggest that activity of the ATR kinase, but not the ATM kinase, is required for successful completion of the viral DNA integration process and/or survival of transduced cells. Components of the cellular DNA damage repair response may represent potential targets for antiretroviral drug development.
First Total Synthesis of (–)-Merrillianin (2022)

The first total synthesis of (–)-merrillianin (1), which is a natural sesquiterpene with a tri- fused structure having a cyclopentane ring and five- and seven-membered lactone parts, is demonstrated. This asymmetric total synthesis enabled the absolute stereo structure determination of naturally occurring (–)-1.
High-Volume Arthroplasty Centers Demonstrate Higher Composite Quality Scores and Enhanced Value (2019)

Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.
SP347RISK AND CLINICAL OUTCOMES ASSOCIATED WITH CKD ANEMIA IN THE USA: A PREDICTIVE MACHINE LEARNING MODELING APPROACH USING NHANES (2019)

and safe therapeutic dose of BCD-131 upon repeated administration to 5D CKD patients. The hypothesis of the study was that the efficacy of BCD-131 is equivalent to Mircera. METHODS: The multicenter, randomized, open-label, comparative two-stage clinical study included 75 5D CKD patients with renal anemia, receiving epoetin alfa, epoetin beta or darbepoetin alfa for at least 3 months before signing the Informed Consent (IC) in a stable dose and Hb levels within 100-120 g/l for at least 2 weeks before signing the IC and at screening. On the stage 1 patients were included sequentially in the groups 1 and 2 to receive ascending doses of BCD-131: 1.05 mg/kgxCR (conversion ratio) and 1.7 mg/kgxCR, respectively; patients in group 3 received standard dose of Mircera. Drugs were administered SC once a month. The safety of each dose level of BCD-131 was established after each patient received 2 injections of the drug and completed the 2 weeks follow up period after the last injection. Both dose levels of BCD-131 were approved for the further investigation. BCD-131 dose 2.75 mg/kg was stated in the Protocol but wasn't studied because the dose level l.7 mg/kg demonstrated the sufficient PD effect. On the stage 2 patients were included additionally up to the number 25 in each group, patients continued treatment up to week 21. The main PD marker was reticulocytes count. The primary efficacy endpoint was the change in Hb level during the period of treatment. To establish the equivalence of the efficacy of BCD-131 and Mircera the 95% confidence interval (CI) for the difference in arithmetic mean values of the change in Hb level was calculated and compared with the equivalence margin of 10 g/l. RESULTS: Median Tmax of BCD-131 was 48.00-72.00 h. Cmax was 3036,00 [2311,00-4829,00] pg/ml and 3605,00 [2910,00-6679,00] hg/ml, median half-life was 9.87 days and 6.4 days in groups 1 and 2, respectively. The single injection of BCD-131 caused the rapid increase of reticulocytes count with a peak on the day 7. The PK and PD characteristics of BCD-131 in group 1 were comparable to those of Mircera. 65 patients completed the treatment according to the Protocol and were included in the efficacy analysis. There was a tendency of dose-dependence of severity and duration of the erythropoiesis stimulating effect. 75% of patients in group 1 maintained the target Hb level at the end of the study. In group 2 we observed an increase in the frequency of Hb elevation above target values. Thus the administration of BCD-131 in a dose 1.05 mg/kg provides more favorable therapeutic effect and allows stable maintaining of Hb level within the target range. The CI for the difference in arithmetic mean values of the change in Hb level between group 1 and group 3 (control) was [-8.87; 4.47] and fits the predefined equivalence limits [-10.00; 10.00]. CONCLUSIONS: In this clinical trial we determined the therapeutic dose of new ESA BCD-131. The efficacy and safety of the use of BCD-131 will be further investigated in phase III clinical trial.
Efficient Client-Transparent Fault Tolerance for Video Conferencing (2005)

As video conferencing plays an increasingly critical role in many business environments, there is a need to ensure highly reliable operation of the conferencing infrastructure. We present a scheme for adding fault tolerance to an existing video conferencing server. The scheme is client-transparent so that it can be used by the installed base of clients. While the scheme is based on replication, the associated overhead is negligible since the backup does not process the media streams. Most previous work on fault-tolerant network services focused on transaction-oriented services. Video conferencing is an interesting test-case for applying fault tolerance for other types of services since it combines critical conference state that must be protected with media streams where limited data losses are acceptable. Our implementation combines kernel modules with small changes to the server application to efficiently preserve both the reliable connections used for control messages and unreliable connections used for media transfer.
Progestin and Thrombin Regulate Tissue Factor Expression in Human Term Decidual Cells (2009)

In human term placental sections, DC-expressed TF exceeds that of other cell types at the maternal-fetal interface and is localized at the cell membranes in which it can bind to factor VII and meet the hemostatic demands of labor and delivery via thrombin formation. Unlike the general concept that TF is constitutive in cells that highly express it, MPA and thrombin significantly enhanced TF expression in term DC monolayers.
Proteome allocation is linked to transcriptional regulation through a modularized transcriptome (2023)

It has proved challenging to quantitatively relate the proteome to the transcriptome on a per-gene basis. Recent advances in data analytics have enabled a biologically meaningful modularization of the bacterial transcriptome. We thus investigated whether matched datasets of transcriptomes and proteomes from bacteria under diverse conditions could be modularized in the same way to reveal novel relationships between their compositions. We found that; 1) the modules of the proteome and the transcriptome are comprised of a similar list of gene products, 2) the modules in the proteome often represent combinations of modules from the transcriptome, 3) known transcriptional and post-translational regulation is reflected in differences between two sets of modules, allowing for knowledge-mapping when interpreting module functions, and 4) through statistical modeling, absolute proteome allocation can be inferred from the transcriptome alone. Quantitative and knowledge-based relationships can thus be found at the genome-scale between the proteome and transcriptome in bacteria.
Characterization of noncovalent protein-ligand complexes and associated enzyme intermediates of GlcNAc-6-O-sulfotransferase by electrospray ionization FT-ICR mass spectrometry (2004)

In this study, a GlcNAc-6-O-Sulfotransferase, NodST and its complexation with the substrate 3'-phosphoadenosine 5'-phosphosulfate (PAPS) and the inhibitor 3'-phosphoadenosine 5'-phosphate (PAP) were studied using Fourier transform ion cyclotron resonance (FTICR) mass spectrometry. In addition, using isotopically labeled substrate, we have successfully confirmed a sulfated enzyme intermediate, which was predicted by the MS kinetic measurement. It is also shown that information regarding solution binding affinities can be obtained using electrospray ionization (ESI)-FTICR mass spectrometry. The relative binding constants, Kd(PAPS)/Kd(PAP), derived from the solution and gas phase were very similar, which suggests that the binding domain of this particular enzyme system, given known structures of other sulfotransferases, may be preserved during the transmission of the complex from solution to the gas phase.
Design and development of a new two-DOF rotational optical image stabilizer (2011)

This work proposes design, optimization and validation of a new two degree-of-freedom (DOF) rotational optical image stabilizer (OIS) that is suitable for installing into a mobile-phone-camera. This OIS differs from the previous designs since it stabilizes the lens holder directly by two-DOF translational mechanisms that are actuated by voice coil motors (VCM). The work can be divided into three main parts: (1) designs of mechanism and genetic algorithm (GA) optimization of magnetic field, (2) establishments of the dynamic model and equation of motions (EOM) of a dual-axis rotational structure, and (3) realizations of a sliding mode control (SMC) controller with fine performance. The dynamic of the dual-axis rotational OIS system has been analyzed and the EOM has been derived. Based on the Lagrange's method, the motions of the OIS have been modeled through considering kinetic energy and electromagnetic torques. In the last part, the theory of SMC is applied, and the associated simulations are conducted. Based on the simulation results, the SMC controller is forged with the assistances from MATLAB pre-simulation and tested by a microprocessor module. After a series of experiments and verifications, the prototype of the novel OIS is finally accomplished with satisfactory performance of vibration reduction.
Mixture importance sampling and its application to the analysis of SRAM designs in the presence of rare failure events (2006)

In this paper, we propose a novel methodology for statistical SRAM design and analysis. It relies on an efficient form of importance sampling, mixture importance sampling. The method is comprehensive, computationally efficient and the results are in excellent agreement with those obtained via standard Monte Carlo techniques. All this comes at significant gains in speed and accuracy, with speedup of more than 100X compared to regular Monte Carlo. To the best of our knowledge, this is the first time such a methodology is applied to the analysis of SRAM designs.
Ultrasonic investigation of the normal-incommensurate-commensurate phase transitions in Rb2ZnCl4and K2ZnCl4 (1981)

Abstract An ultrasonic attenuation has been measured near the normal-incommensurate phase transition point of Rb2ZnCl4. Elastic relaxation times have been estimated both above and below the transition point. An anomaly of the shear stiffness c55 of K2ZnCl4 around the incommensurate-commensurate transition point is also reported.
Diurnal changes in core body temperature, day/night locomotor activity patterns, and actigraphy-generated behavioral sleep in aged canines with varying levels of cognitive dysfunction (2016)

Core body temperature (CBT) rhythm, locomotor activity, and actigraphy-sleep were evaluated in geriatric dogs with cognitive dysfunction. Dogs (<i>n</i>=33; 9-16 yrs) performed a spatial working memory task and divided into three memory groups: Low, Moderate, and High, with subsequent evaluation of learning and attention. Rectal CBT was recorded 6 times over a 17.5 h period and Actiwatch® activity monitoring system for 5 days while housed indoors with 12 h light/dark schedule. Rhythm of daily activity data was evaluated using the traditional cosinor analysis and generation of non-parametric measures of interdaily stability, intradaily variability, and relative amplitude. CBT differed with time (F (5, 130)=11.36, <i>p</i><0.001), and was the highest at 19:00C. CBT at 19:00 was positively related (<i>p</i><0.01) to memory (<i>r</i>(31)<i>=</i>0.50) and 3-domain cognitive performance index (memory, learning, attention; <i>r</i>(31)<i>=</i>0.39). Total daytime or night-time activity did not differ between memory groups, but hourly counts at 8:00 were positively related (<i>p</i><0.05) to memory (<i>r</i>(31)<i>=</i>0.52), learning (<i>r</i>(31)<i>=</i>0.36), and 3-domain cognitive performance index (<i>r</i>(31)<i>=</i>0.53). There were no significant differences between age or memory groups for any circadian rhythm measures. Daytime naps were inversely related to memory accuracy (<i>r</i>(31)<i>=</i>-0.39; <i>p</i><0.05) and BT at 15:00 <i>(r</i>(30)<i>=</i>-0.51; <i>p</i><0.01). Lower peak BT and inc<i>r</i>eased napping may predict some aspects of cognitive performance of working memory, learning, and/or attention processes in these geriatric dogs, but minimal diurnal rhythm disruption of locomotor activity is observed when these cognitive processes decline.
Appendix: Physical Constants (2005)

Book DOI: 10.1049/SBRA017E Chapter DOI: 10.1049/SBRA017E_appendix ISBN: 9781891121401 e-ISBN: 9781613531440
The UK silicon photonics project (2010)

The project is a consortium based activity involving researchers from the UK institutions of the Universities of Surrey, St. Andrews, Leeds, Warwick, and Southampton, as well as the commercial research institution QinetiQ. The aims of the project are to progress the state of the art in Silicon Photonics, in the areas of waveguides, modulators, couplers, detectors, Raman processes, and integration with electronics. Thus the field is vast, and impossible to cover comprehensively in one project, nor indeed in one paper. The programme is run on a truly collaborative basis, with members from each institution running one or more work packages within the project, each co-ordinating work from their own plus other institutions. To date, the most well developed work has emerged from the activity on basic waveguides and their characteristics, the modulator activity, optical filters, and work on Raman Amplifiers. This work will be the main focus of this paper, but an attempt will be made to update the audience on the remaining activities within the project. By the nature of the project, much of the work is medium term, and hence some activities are not expected to yield viable results until at least next year, hence the concentration on some activities rather than all activities at this stage.
IgA and/or IgG subclass deficiency in children with recurrent respiratory infections and its relationship with chronic pulmonary damage. (2005)

Most patients with IgA and/or IgG subclass deficiency are asymptomatic but some may suffer from frequent mainly respiratory infections. The aim of our study was to determine the frequency of IgA and/or IgG subclass deficiencies and the rate of chronic pulmonary damage secondary to recurrent pulmonary infections in these children. Serum IgA and IgG subclass levels were measured in 225 children aged 6 months to 6 years with recurrent sinopulmonary infections (44 with recurrent upper respiratory tract infections, 100 with recurrent pulmonary infections and 81 with recurrent bronchiolitis). In order to determine chronic pulmonary damage due to recurrent infections in patients with recurrent pulmonary infections CT scans of thorax were also obtained. The overall frequency of antibody defects was found to be 19.1%. IgA deficiency was observed in 9.3%, IgG subclass deficiency in 8.4% and IgA + IgG subclass deficiency in 1.4%. The prevalance of IgA and/or IgG subclass deficiency was 25% in patients with recurrent upper respiratory tract infections, 22% in patients with recurrent pulmonary infections and 12.3% in patients with recurrent bronchiolitis (p>0.05). Chronic pulmonary damage in lungs was determined radiologically in 17 of 100 cases with recurrent pulmonary infection. In IgG subclass deficiencies sequel changes, although not statistically significant, were observed five times more frequently than that of IgA deficiencies. CT scans revealed pulmonary sequels in 5 of the 22 (22.7%) patients with recurrent pulmonary infections and immunodeficiency (bronchiectasis in 2 patients with IgG3 deficiency, fibrotic changes in one with IgA deficiency and in one with IgG3 deficiency, bronchiolitis obliterans in one with IgG2 + IgG3 deficiency). On the other hand, pulmonary sequels were observed in 12 patients (15.4%) with normal immunoglobulin levels. Eight of them were bronchiolitis obliterans, 2 of them were atelectasia and 1 of them was bronchiectasia. We therefore suggest that determination of antibody levels and evaluation of pulmonary alterations is crucial in patients with recurrent sinopulmonary infections since the deficiency of antibodies is associated with a greater pulmonary damage.