Miracle-dz/UniFAR-FTUs huggingface dataset:
Depletion of B Cells by a Humanized Anti-CD20 Antibody PRO70769 in Macaca Fascicularis

PRO70769 is a humanized IgG1 monoclonal antibody against the CD20 molecule that is present on normal and malignant B cells. PRO70769 is being evaluated for treatment of B-cell-mediated diseases and is in a phase 1 trial for rheumatoid arthritis. As part of the preclinical toxicology evaluation, B-cell depletion profiles and safety of PRO70769 were assessed in cynomolgus monkeys. Animals were administered drug (IV) on days 1 and 15 with 10, 50, or 100 mg/kg PRO70769 and killed 2 weeks after the second dose and after a 3-month recovery period. In a parallel study, animals were not necropsied but instead were retreated with a second cycle of PRO70769 administered under an identical regimen. PRO70769 suppressed B cells in the blood to undetectable levels and significantly reduced B cells in lymphoid tissues. Splenic B cells were depleted to a greater extent compared with lymph node B cells. A second cycle of treatment resulted in a greater extent of depletion in lymphoid tissues compared with the depletion observed after one cycle of treatment; however, residual B cells in lymphoid tissues were still detectable, even at the highest dose. The rate of B-cell recovery in peripheral blood appeared similar between one and two cycles of treatment. Upon depletion there was a change in the profile of lymph node B-cell subsets. After recovery, B-cell subsets were reconstituted to normal levels. Depletion of CD20-expressing cells and lymphoid follicular atrophy were the only treatment-related effects.
Angiopoietin-1 upregulation by vascular endothelial growth factor in human retinal pigment epithelial cells.

PURPOSE To determine whether vascular endothelial growth factor (VEGF) regulates angiopoietin (Ang)-1 and -2 expression in retinal pigment epithelial (RPE) cells. METHODS Expression of VEGF, Ang1, and Ang2 in surgically removed human choroidal neovascular membranes (CNVMs) was analyzed by double-label confocal immunofluorescence microscopy. Total RNA was extracted from cultured human RPE cells treated with VEGF for mRNA analysis. Northern blot analysis was performed to examine the time course and dose response of Ang1 and Ang2 mRNA expression. mRNA stability and nuclear run-on analyses were performed. Secreted Ang1 and Ang2 protein levels in conditioned media from RPE cells were examined by Western blot analysis. RESULTS Ang1 and Ang2 immunostaining colocalized with VEGF-positive stromal cells in human CNVMS: Ang1 and Ang2 mRNAs were expressed by cultured serum-starved RPE cells. VEGF upregulated Ang1 mRNA in a time- and dose-dependent manner without a significant change in Ang2 mRNA. Ang1 and Ang2 mRNAs in RPE cells were as stable as that of S18. VEGF stimulation further increased the half-life of Ang1 mRNA, but did not alter its transcription rate. VEGF increased the amount of Ang1, but not Ang2, protein secreted into the medium. CONCLUSIONS The colocalization of Ang1 and Ang2 with VEGF in CNVM stromal cells and the upregulation of Ang1 expression by VEGF in cultured RPE cells suggest that VEGF may selectively modulate Ang expression during CNV.
Renewable Electricity Futures. Operational Analysis of the Western Interconnection at Very High Renewable Penetrations

The Renewable Electricity Futures Study (RE Futures)--an analysis of the costs and grid impacts of integrating large amounts of renewable electricity generation into the U.S. power system--examined renewable energy resources, technical issues regarding the integration of these resources into the grid, and the costs associated with high renewable penetration scenarios. These scenarios included up to 90% of annual generation from renewable sources, although most of the analysis was focused on 80% penetration scenarios. Hourly production cost modeling was performed to understand the operational impacts of high penetrations. One of the conclusions of RE Futures was that further work was necessary to understand whether the operation of the system was possible at sub-hourly time scales and during transient events. This study aimed to address part of this by modeling the operation of the power system at sub-hourly time scales using newer methodologies and updated data sets for transmission and generation infrastructure. The goal of this work was to perform a detailed, sub-hourly analysis of very high penetration scenarios for a single interconnection (the Western Interconnection). It focused on operational impacts, and it helps verify that the operational results from the capacity expansion models are useful. The primary conclusion of this studymore » is that sub-hourly operation of the grid is possible with renewable generation levels between 80% and 90%. « less
Impact of educational mailing on the blood pressure of primary care patients with mild hypertension

OBJECTIVE: To assess the effectiveness of mailed hypertension educational materials.DESIGN: Prospective, randomized, controlled single-blind trial.SETTING: Primary care practice-based research network in which 9 clinics located in Portland, Oregon participated.PARTICIPANTS: Patients with mildly uncontrolled hypertension as defined as a last blood pressure of 140 to 159/90 to 99 mmHg from query of an electronic medical record database.INTERVENTIONS: Patients randomized to intervention were mailed 2 educational packets approximately 3 months apart. The first mailer included a letter from each patient’s primary care provider. The mailer included a booklet providing an overview of hypertension and lifestyle modification and a refrigerator magnet noting target blood pressure. The second mailing also included a letter from the patient’s primary care provider, a second educational booklet focused on medication compliance and home blood pressure monitoring, and a blood pressure logbook. The control group consisted of similar patients receiving usual care for hypertension.MEASUREMENTS AND MAIN RESULTS: Patients from each group were randomly selected for invitation to participate in a study visit to measure blood pressure and complete a survey (intervention n=162; control n=150). No significant difference was found in mean blood pressure between intervention and control patients (135/77 mmHg vs 137/77 mmHg; P=.229). Patients in the intervention arm scored higher on a hypertension knowledge quiz (7.48 ± 1.6 vs 7.06 ± 1.6; P=.019), and reported higher satisfaction with several aspects of their care. No significant difference was seen in the prevalence of home blood pressure monitoring ownership or use.CONCLUSIONS: In patients with mildly uncontrolled hypertension, educational mailers did not yield a significant decrease in blood pressure. However, significant improvement in patient knowledge, frequency of home monitoring, and satisfaction with care were demonstrated.
A comparative study on the use of digital panoramic and periapical radiographs to assess proximal bone height around dental implants.

OBJECTIVE The purpose of this study was to compare periapical radiographs (PA) and panoramic radiographs (PAN) in the measurement of proximal bone height around implants. METHOD AND MATERIALS Patients files that contained digital PAN and PA together with information on implant lengths and diameters were selected for this study. For each radiograph, the implant size served as reference for calibration. Proximal radiographic bone levels and the linear distance between the bone crest and implant shoulder were measured twice by one examiner. Paired t test was used to assess intra-examiner variability and differences between the two radiographic methods. Correlation was then assessed using Pearson correlation coefficient test. Significance level was determined at 5%. RESULTS For the PAN measurements, the median mesial distances from bone crest to implant shoulder were 0.53 and 0.56 mm (first and second sets, P = .53). Likewise, for distal measurements these readings were 0.92 and 0.86 mm respectively (P = .66). For PA measurements, the corresponding measurements were 0.33 and 0.44 mm (P = .48) and 0.99 and 0.99 mm (P = .42), respectively. When PAN and PA measurements were compared, no statistically significant differences were detected between the two radiographic modalities. A very high positive correlation (r > 0.91) was attained for the PAN - PA measurements (P < .0001). CONCLUSION PAN are potentially as reliable and reproducible as PA for the assessment of proximal bone height around dental implants.
A Mitochondrial Mutator System in Maize1[w]

The P2 line of maize (Zea mays) is characterized by mitochondrial genome destabilization, initiated by recessive nuclear mutations. These alleles alter copy number control of mitochondrial subgenomes and disrupt normal transfer of mitochondrial genomic components to progeny, resulting in differences in mitochondrial DNA profiles among sibling plants and between parents and progeny. The mitochondrial DNA changes are often associated with variably defective phenotypes, reflecting depletion of essential mitochondrial genes. The P2 nuclear genotype can be considered a natural mutagenesis system for maize mitochondria. It dramatically accelerates mitochondrial genomic divergence by increasing low copy-number subgenomes, by rapidly amplifying aberrant recombination products, and by causing the random loss of normal components of the mitochondrial genomes.
Association of atypical characteristics of benign breast lesions with subsequent risk of breast cancer

A retrospective case‐control study was carried out to determine to what degree atypical changes in the mammary duct system are associated with increased risk of developing breast cancer. A previously developed grading system was used by one of us (MMB) to describe the morphological atypicality in a series of benign breast lesions. Our primary finding is that a woman with some degree of ductular atypia in a benign lesion is subject to a risk of developing breast cancer 5 times that of a woman with no evidence of atypical changes. The implications of this finding regarding treatment require further study.
Interaction between the antibiotic spiramycin and a ribosomal complex active in peptide bond formation.

The inhibition of peptide bond formation by spiramycin was studied in an in vitro system derived from Escherichia coli. Peptide bonds are formed between puromycin (S) and Ac-Phe-tRNA, which is a component of complex C, i.e., of the [Ac-Phe-tRNA-70S ribosome-poly(U)] complex, according to the puromycin reaction: C+S (Ks)<==>CS (k3)==>C'+P [Synetos, D. , & Coutsogeorgopoulos, C. (1987) Biochim. Biophys. Acta 923, 275-285]. It is shown that spiramycin (A) reacts with complex C and forms the spiramycin complex C*A, which is inactive toward puromycin. C*A is the tightest complex formed between complex C and any of a number of antibiotics, such as chloramphenicol, blasticidin S, lincomycin, or sparsomycin. C*A remains stable following gel chromatography on Sephadex G-200 and sucrose gradient ultracentrifugation. Detailed kinetic study suggests that C*A is formed in a variation of a two-step mechanism in which the initial encounter complex CA is kinetically insignificant and C*A is the product of a conformational change of complex CA according to the equation, C+A (kassoc)<==>(kdissoc) C*A. The rate constants of this reaction (spiramycin reaction) are kassoc = 3.0 x 10(4) M-1 s-1 and kdissoc = 5.0 x 10(-5) s-1. Such values allow the classification of spiramycin as a slow-binding, slowly reversible inhibitor; they also lead to the calculation of an apparent overall dissociation constant equal to 1.8 nM for the C*A complex. Furthermore, they render spiramycin a useful tool in the study of antibiotic action on protein synthesis in vitro. Thus, the spiramycin reaction, in conjunction with the puromycin reaction, is applied (i) to detect a strong preincubation effect exerted by chloramphenicol and lincomycin (this effect constitutes further evidence that these two antibiotics combine with complex C as slow-binding inhibitors) and (ii) to determine the rate constant for the regeneration (k7 = 2.0 x 10(-3) s-1) of complex C from the sparsomycin complex C*I [Theocharis, D. A. , & Coutsogeorgopoulos, C. (1992) Biochemistry 31, 5861-5868] according to the equation, C+I (Ki)<==>CI (k6)<==>(k7) C*I. The determination of k7 enables us to calculate the apparent association rate constant of sparsomycin, (k7/Ki') = 1.0 x 10(5) M-1 s-1, where Ki' = Ki(k7/k6 + k7). It is also shown that Ac-Phe-tRNA bound to the sparsomycin complex C*I is protected against attack by hydroxylamine. (ABSTRACT TRUNCATED AT 400 WORDS)
Non-characteristic harmonics and DC side capacitor calculation in VSC connected to a distribution system with unbalanced voltage

This paper presents a model of typical three-phase, three-wire and two-level PWM controlled voltage-source converters (VSC) suitable to investigate the non-characteristic harmonic generation at dc- and ac-side of the converter under sinusoidal unbalanced voltage condition, e.g., third order current harmonic component of positive-sequence in the VSC ac-side current. The proposed model, based on instantaneous power as well as switching functions concepts, permits to evaluate the oscillating voltage that appears on the VSC dc-side. The effect of the negative-sequence voltage component is considered on the dc capacitance calculation which consequently enables to size the dc capacitor accurately in order to keep the dc voltage ripple under pre-defined limits. The model also shows the exact dc-side voltage ripple due to the VSC ac-side negative-sequence voltage component. The dc capacitor size and the non-characteristic harmonics obtained based on the proposed model are assessed using time-domain simulation in the PSCAD program.
Identifying an important change estimate for the Multiple Sclerosis Walking Scale-12 (MSWS-12v1) for interpreting clinical trial results

Background The 12-question Multiple Sclerosis Walking Scale (MSWS-12v1) is a widely-used patient-reported outcome (PRO) measure of walking ability in multiple sclerosis (MS). Objective To estimate the magnitude of an important change in MSWS-12v1 scores for the interpretation of meaningful subject-level improvements across a 6-month trial of MS patients with walking disability. Methods MOBILE was a 6-month exploratory study assessing fampridine’s effect on walking ability in 132 people with MS. Three PRO measures assessed walking ability: MSWS-12v1, EuroQol 5-Dimension-5 Level (EQ-5D-5L) mobility question, and a patient global impression of change (PGIC) in overall walking ability. Pre-specified anchor- and distribution-based analyses estimated the MSWS-12v1 change scores representing an important change for participants. Results were triangulated to propose a single best value indicating meaningful improvement. Results Using baseline to week 2 through week 24 change scores, anchor-based analyses demonstrated mean and median improvements of 5.2–6.6 (PGIC) and 9.7–13.4 (EQ-5D-5L mobility) points on the MSWS-12v1, indicating meaningful improvements. The distribution-based estimate was 6.8 points. Triangulation across the results suggested an 8-point reduction in MSWS-12v1 score represents an important subject-level change in these participants. Conclusion In similar MS clinical trials, an 8-point improvement on the MSWS-12v1 is a reasonable estimate of meaningful improvement in walking ability.
Labour Subjectivities for the New World of Work: A Critique of Government Policy on the Integration of Entrepreneurialism in the University Curriculum.

International debates on the aims and purposes of entrepreneurship education in universities are examined in this paper through the prism of a policy critique of recent English higher education initiatives. The Department of Business, Innovation and Skills (BIS) policy to integrate rather than ‘add on’ enterprise education throughout university courses has been widely implemented. In contrast to the debates about enterprise policy by authors in social psychology, business studies, secondary school education and entrepreneurship, which question the claims of enterprise rhetoric and examine the practicalities of forming start-up companies, policy to integrate entrepreneurship into the curriculum has remained largely uncontested in UK universities. It is argued that policy to integrate enterprise into the humanities and social sciences produces three critical gaps; a limited scope for social theory, ahistorical analysis and the absence of demand-side economics. This critique of BIS policy is set within the wider context of the neo-liberal reconfiguration of the institutional relations between the university, the state and the market that erode university autonomy in the UK and on an international scale.
Predictors of Vertigo in Patients With Untreated Vestibular Schwannoma

Objectives Previous studies have shown that vertigo is the most powerful negative predictor of quality of life in patients with vestibular schwannomas, but the variability in vertigo symptom severity is still poorly understood. We wanted to find out whether vertigo could be related to objective parameters such as tumor size, location, vestibular nerve function, hearing, and postural stability in patients with untreated vestibular schwannomas. Study Design Baseline data from prospective cohort study. Setting Tertiary referral center. Patients Four hundred thirty-four consecutive patients with unilateral VS diagnosed on MRI. Mean age 56 years (range 16–84 yr). Fifty-three percent women. Intervention Diagnostic, with a medical history, otolaryngological examination, pure-tone and speech audiometry, MRI, posturography, and videonystagmography with bithermal caloric tests. Main Outcome Measure Dizziness measured on a 100-mm visual analog scale (VAS). Secondary outcome measures were canal paresis and postural imbalance (static and dynamic posturography). Results Three hundred three patients (70%) completed the VAS. Severe dizziness, defined as VAS 75 or greater, was reported by 9% of the patients. Larger tumors were associated with higher risk of postural instability and canal paresis. Moderate to severe dizziness was associated with postural imbalance and canal paresis, and possibly with small to medium-sized tumors. Postural instability was related to tumor size and canal paresis when measured by dynamic, but not with static, posturography. Conclusion A minority of VS patients experience severe vestibular symptoms related to canal paresis and postural instability. A curvilinear relationship is hypothesized between tumor size and dizziness.
Probabilistic Electrical Power Generation Modeling Using Decimal to Binary Conversion

Generation system reliability assessment is an important task which can be performed using deterministic or probabilistic techniques. The probabilistic approaches have significant advantages over the deterministic methods. However, more complicated modeling is required by the probabilistic approaches. Power generation model is a basic requirement for this assessment. One form of the generation models is the well known capacity outage probability table (COPT). Different analytical techniques have been used to construct the COPT. These approaches require considerable mathematical modeling of the generating units. The unit’s models are combined to build the COPT which will add more burdens on the process of creating the COPT. Decimal to Binary Conversion (DBC) technique is widely and commonly applied in electronic systems and computing This paper proposes a novel utilization of the DBC to create the COPT without engaging in analytical modeling or time consuming simulations. The simple binary representation , “0 ” and “1 ” is used to model the states o f generating units. The proposed technique is proven to be an effective approach to build the generation model. Keywords—Decimal to Binary, generation, reliability.
10SENT: A stable sentiment analysis method based on the combination of off‐the‐shelf approaches

Sentiment analysis has become a very important tool for analysis of social media data. There are several methods developed, covering distinct aspects of the problem and disparate strategies. However, no single technique fits well in all cases or for all data sources. Supervised approaches may be able to adapt to specific situations, but require manually labeled training, which is very cumbersome and expensive to acquire, mainly for a new application. In this context, we propose to combine several popular and effective state‐of‐the‐practice sentiment analysis methods by means of an unsupervised bootstrapped strategy. One of our main goals is to reduce the large variability (low stability) of the unsupervised methods across different domains. The experimental results demonstrate that our combined method (aka, 10SENT) improves the effectiveness of the classification task, considering thirteen different data sets. Also, it tackles the key problem of cross‐domain low stability and produces the best (or close to best) results in almost all considered contexts, without any additional costs (e.g., manual labeling). Finally, we also investigate a transfer learning approach for sentiment analysis to gather additional (unsupervised) information for the proposed approach, and we show the potential of this technique to improve our results.
Comparison of Levator Ani Muscle Avulsion Injury After Forceps-Assisted and Vacuum-Assisted Vaginal Childbirth

OBJECTIVE: Using three-dimensional transperineal ultrasonography, we compared the prevalence of levator ani muscle injury after forceps with vacuum-assisted vaginal delivery. METHODS: This was a retrospective cohort study. Women who experienced at least one forceps delivery (across all deliveries) were compared with women who had at least one vacuum birth. On average, participants were 10 years from the index delivery. Three-dimensional transperineal ultrasound volumes were captured as cine loops at rest with Valsalva and with pelvic floor muscle contraction. The primary outcome was levator ani muscle avulsion. Secondary outcomes included hiatal diameter and area. Prevalence of pelvic floor disorders was also compared between the two delivery groups. RESULTS: Among 45 participants in the forceps group and 28 participants in the vacuum group, there were no differences between groups in maternal age at first delivery, parity, body mass index, birth weight, episiotomy, or duration of second stage. History of anal sphincter laceration was more common in the forceps group. The prevalence of levator ani muscle avulsion was significantly higher after forceps compared with vacuum delivery (22/45 [49%] compared with 5/28 [18%], P=.012, prevalence ratio 2.74, 95% confidence interval [CI] 1.17–6.40, odds ratio 4.40 [95% CI 1.42–13.62]). Controlling for delivery type, levator ani muscle avulsion was associated with symptoms of prolapse (P=.036), although objective evidence of prolapse was not significantly different between groups (P=.20). CONCLUSION: Ten years after delivery, the prevalence of levator avulsion is almost tripled after forceps compared with vacuum-assisted vaginal delivery. LEVEL OF EVIDENCE: II