Miracle-dz/UniFAR-FTUs huggingface dataset:
Flagellar microtubule dynamics in Chlamydomonas: cytochalasin D induces periods of microtubule shortening and elongation; and colchicine induces disassembly of the distal, but not proximal, half of the flagellum

To study the mechanisms responsible for the regulation of flagellar length, we examined the effects of colchicine and Cytochalasin D (CD) on the growth and maintenance of Chlamydomonas flagella on motile wild type cells as well as on pf 18 cells, whose flagella lack the central microtubules and are immobile. CD had no effect on the regeneration of flagella after deflagellation but it induced fully assembled flagella to shorten at an average rate of 0.03 microns-min. Cells remained fully motile in CD and even stubby flagella continued to move, indicating that flagellar shortening did not selectively disrupt machinery necessary for motility. To observe the effects of the drug on individual cells, pf 18 cells were treated with CD and flagella on cells were monitored by direct observation over a 5-hour period. Flagella on control pf 18 cells maintained their initial lengths throughout the experiment but flagella on CD-treated cells exhibited periods of elongation, shortening, and regrowth suggestive of the dynamic behavior of cytoplasmic microtubules observed in vitro and in vitro. Cells behaved individually, with no two cells exhibiting the same flagellar behavior at any given time although both flagella on any single cell behaved identically. The rate of drug-induced flagellar shortening and elongation in pf 18 cells varied from 0.08 to 0.17 microns-min-1, with each event occurring over 10-60-min periods. Addition of colchicine to wild type and pf 18 cells induced flagella to shorten at an average rate of 0.06 microns-min-1 until the flagella reached an average of 73% of their initial length, after which they exhibited no further shortening or elongation. Cells treated with colchicine and CD exhibited nearly complete flagellar resorption, with little variation in flagellar length among cells. The effects of these drugs were reversible and flagella grew to normal stable lengths after drug removal. Taken together, these results show that the distal half to one-third of the Chlamydomonas flagellum is relatively unstable in the presence of colchicine but that the proximal half to two-thirds of the flagellum is stable to this drug. In contrast to colchicine, CD can induce nearly complete flagellar microtubule disassembly as well as flagellar assembly. Flagellar microtubules must, therefore, be inherently unstable, and flagellar length is stabilized by factors that are sensitive, either directly or indirectly, to the effects of CD.
Comparative Analysis of University of Auckland Diabetic Retinopathy Database

Diabetic retinopathy is a micro-vascular disease that affects the vision. People with diabetes are more likely to get affected by diabetic retinopathy. There are many screening techniques available to diagnose this pathology. Majority of this screening methods use the retinal image of the patient for the diagnosis. Recently many automatic retinal image analysis methods are being developed to automate the diagnosis of this pathology, thereby eliminating the need for a specialist ophthalmologist for such a screening. In order to evaluate the performance of any such automatic method, there is a need for a database of retinal images which could act as a reference for bench-marking the performance of the methods developed. In this paper, we discuss a new retinal image database known as University of Auckland Diabetic Retinopathy database (UoA-DR), prepared specifically for bench-marking the performance of various automatic systems developed for the diagnosis of diabetic retinopathy. This database consists of 200 retinal images mostly affected with diabetic retinopathy. This database also contains the manually segmented versions of various features obtained from these images which could act as a ground truth for algorithm's improvement to segment various features from retinal images automatically.
Effect of an antismoking advertisement on cinema patrons' perception of smoking and intention to smoke: a quasi-experimental study.

AIMS To assess the effect of an antismoking advertisement under real-world conditions. Design Quasi-experimental study. SETTING/PARTICIPANTS Multiplex cinema in Kiel, Germany; 4073 patrons were surveyed after having viewed a movie. Some 4005 patrons were > or = 10 years old (28.7% between 10 and 17 years). A total of 654 subjects (16.3%) were smokers. INTERVENTION In the intervention condition (weeks 1 and 3), a 30-second antismoking advertisement-accentuating long-term health consequences of smoking and promoting cessation-was shown prior to all movies; in the control condition (weeks 2 and 4) no such spot was shown. MAIN OUTCOME MEASURES (i) Awareness of smoking in the movie, (ii) approval of smoking in the movie, (iii) attitude towards smoking, (iv) intention to smoke in the future and (v) desire to smoke among smokers. Findings Patrons who were exposed to the antismoking advertisement were more likely to be female, but did not differ with respect to smoking status. After controlling for gender differences, patrons exposed to the antismoking advertisement had (i) higher awareness of smoking in the movies, (ii) lower levels of approval of smoking in the movies, and (iii) a more negative attitude towards smoking in general compared with those not exposed. Among smokers, smoking in the movies increased urge to smoke, but there was no interaction between smoking in the movies and experimental condition. CONCLUSIONS Study results suggest that placing an antismoking advertisement before movies can affect attitudes towards smoking, bolstering evidence in support of such policies.
Sensitivity to pertuzumab (2C4) in ovarian cancer models: cross-talk with estrogen receptor signaling

Pertuzumab (Omnitarg, rhuMab 2C4) is a humanized monoclonal antibody, which inhibits HER2 dimerization. Because it has shown some clinical activity in ovarian cancer, this study sought to identify predictors of response to this agent in a model of ovarian cancer. A panel of 13 ovarian cancer cell lines was treated with heregulin β1 (HRGβ1) or transforming growth factor-α, and cell proliferation was assessed. Both agents increased cell number in the majority of cell lines studied, the response to both being similar (r = 0.83; P = 0.0004, Pearson test). HRGβ1 stimulation could be partially reversed by pertuzumab in 6 of 13 cell lines, with complete reversal in PE04 and PE06 cells. Addition of pertuzumab to transforming growth factor-α−stimulated cells produced growth inhibition in 3 of 13 cell lines (PE01, PE04, and PE06). The magnitude of HRGβ1-driven growth stimulation correlated significantly with an increase in extracellular signal-regulated kinase 2 (P = 0.037) but not Akt (P = 0.99) phosphorylation. Such HRGβ1-driven phosphorylation of extracellular signal-regulated kinase 1/2 and Akt could be reduced with pertuzumab, accompanied by changes in cell cycle distribution. In cell lines responsive to pertuzumab, HRGβ1-enhanced phosphorylation of HER2 (Tyr877) was reduced. Estrogen-stimulated changes in growth, cell cycle distribution, and signaling were reversed by pertuzumab, indicating cross-talk between HER2 and estrogen signaling. These data indicate that there is a subset of ovarian cancer cell lines sensitive to pertuzumab and suggest possible predictors of response to identify patients who could benefit from this therapy. Furthermore, we have identified an interaction between HER2 and estrogen signaling in this disease. [Mol Cancer Ther 2007;6(1):93–100]
Scattering From Inhomogeneous Dielectric Cylinders With Finite Length

The electromagnetic scattering by a dielectric cylinder of finite length is important in many applications, particularly for microwave remote sensing of vegetated terrain. Yet, not only a unified analytical solution is still elusive in providing the scattering cross sections but also other important aspects, such as the phase of the scattering amplitude function, energy conservation, and reciprocity relation, have been scantly touched in the literature. The treatment of a dielectric inhomogeneous cylinder of finite length brings forth new challenges. Taking on such challenges is the focus of this paper. The main plan of attack is to extend the virtual partition method, which is a T-matrix-based semi-analytical model, that we have previously proposed to treat scattering from a homogeneous dielectric cylinder of finite length, to the inhomogeneous cases. The effectiveness of the proposed method is validated numerically, including: 1) high-fidelity prediction of the copolarized and cross-polarized cross sections for arbitrary bistatic scattering configuration; 2) high-fidelity predictions of the phase of the scattering amplitude function; 3) verification of energy conservation; and 4) verification of the reciprocity theorem.
Fusion Algorithm Design Based on Adaptive SCKF and Integral Correction for Side-Slip Angle Observation

Vehicle side-slip angle is crucial for various vehicle active safety applications, but measuring it directly needs expensive measurement instruments and the vehicle nonlinear dynamics, parameters uncertainty, and sensor noise cause difficulties in its observation. Therefore, the accurate, affordable side-slip angle estimator is essential. Thus, a novel adaptive square-root cubature Kalman filter (ASCKF)-based estimator with the integral correction fusion is proposed. First, the square-root cubature Kalman filter (SCKF) parameters can be adjusted adaptively based on the vehicle dynamics states. Then, considering the unknown colored noises of sensors, the integral estimation is corrected by the damping item and zero-point-reset method and the integral value can compensate the estimation error caused by the vehicle nonlinear dynamics. Therefore, the accurate side-slip angle can be estimated by the adaptive fusion of the estimation and integral values. The simulation results and real-vehicle tests show that the proposed ASCKF-based fusion algorithm has better performance than both the traditional SCKF and ASCKF.
Macropinocytosis: a pathway to protozoan infection

Among the various endocytic mechanisms in mammalian cells, macropinocytosis involves internalization of large amounts of plasma membrane together with extracellular medium, leading to macropinosome formation. These structures are formed when plasma membrane ruffles are assembled after actin filament rearrangement. In dendritic cells, macropinocytosis has been reported to play a role in antigen presentation. Several intracellular pathogens are internalized by host cells via multiple endocytic pathways and macropinocytosis has been described as an important entry site for various organisms. Some bacteria, such as Legionella pneumophila, as well as various viruses, use this pathway to penetrate and subvert host cells. Some protozoa, which are larger than bacteria and virus, can also use this pathway to invade host cells. As macropinocytosis is characterized by the formation of large uncoated vacuoles and is triggered by various signaling pathways, which is similar to what occurs during the formation of the majority of parasitophorous vacuoles, it is believed that this phenomenon may be more widely used by parasites than is currently appreciated. Here we review protozoa host cell invasion via macropinocytosis.
[The Environmental Burden of Disease Concept].

GOAL OF THE STUDY Environmental risk factors are of great importance for public health with a considerable but often unused potential for prevention. However, knowledge about the complex associations between the environment and health effects is limited for some risk factors. A concept, which is using the existing evidence on associations between the impact of environmental factors and health effects, is the environmental burden of disease (EBD) concept. The aim of this article is to present the quantification method of the EBD concept and to discuss the advantages and its points of criticism. METHODS The EBD concept combines morbidity and mortality data in a single measure (Disability-Adjusted Life Year, DALY) to enable a comparative description of the burden of disease. Life years are used as measurement unit. The environmental share of the total DALYs is quantified by using the attributable fraction. RESULTS Despite its increasing application especially in the international context, the method is still criticized, because by summarizing the complex construct of health in one single measurement unit, much important information about quality of life is lost. A further criticism refers to partly arbitrarily set social value choices. Additionally, missing or insufficient data can limit the quality and validity of EBD estimations. CONCLUSION A scientific discourse is needed to decide to what extent the EBD approach can and should be used in Germany.
Effects of Vitamin D Supplementation on Blood Pressure

Objective: Inconsistent findings from epidemiological studies have continued the controversy over the role of oral vitamin D supplementation in reducing blood pressure in normotensive or hypertensive populations. Methods: We performed a literature search up to December 2009, with no restrictions. Only double-blind randomized controlled trials (RCTs) of oral vitamin D supplementation in normotensive or hypertensive individuals with blood pressure measurements were included. Results: From 244 retrieved papers, four RCTs involving 429 participants met our inclusion criteria for this meta-analysis. Vitamin D supplementation reduced systolic blood pressure (SBP) by 2.44 mm Hg (weighted mean difference [WMD]: −2.44, 95% confidence interval [CI]: −4.86, −0.02), but not diastolic blood pressure (DBP) (WMD: −0.02, 95% CI: −4.04, 4.01) compared with calcium or placebo. Subgroup analysis suggested that the change of blood pressure did not vary markedly across the dose of vitamin D supplementation, study length, or intervention. Conclusions: Oral vitamin D supplementation may lead to a reduction in systolic blood pressure but not diastolic blood pressure. Given the small number of trials and small but statistically significant reduction in systolic blood pressure from this meta-analysis, further studies are required to confirm the magnitude of the effect of vitamin D on blood pressure reduction and define the optimum dose, dosing interval, and type of vitamin D to administer.
Effects of BMS-986094, a Guanosine Nucleotide Analogue, on Mitochondrial DNA Synthesis and Function.

BMS-986094, the prodrug of a guanosine nucleotide analogue (2'-C-methylguanosine), was withdrawn from clinical trials due to serious safety issues. Nonclinical investigative studies were conducted as a follow up to evaluate the potential for BMS-986094-related mitochondrial-toxicity. In vitro, BMS-986094 was applied to human hepatoma cells (HepG2 and Huh-7) or cardiomyocytes (hiPSCM) up to 19 days to assess mitochondrial DNA content and specific gene expression. There were no mitochondrial DNA changes at concentrations ≤10 µM. Transcriptional effects, such as reductions in Huh-7 MT-ND1 and MT-ND5 mRNA content and hiPSCM MT-ND1, MT-COXII, and POLRMT protein expression levels, occurred only at cytotoxic concentrations (≥10 µM) suggesting these transcriptional effects were a consequence of the observed toxicity. Additionally, BMS-986094 has a selective weak affinity for inhibition of RNA polymerases as opposed to DNA polymerases. In vivo, BMS-986094 was given orally to cynomolgus monkeys for 3 weeks or 1 month at doses of 15 or 30 mg/kg/day. Samples of heart and kidney were collected for assessment of mitochondrial respiration, mitochondrial DNA content, and levels of high energy substrates. Although pronounced cardiac and renal toxicities were observed in some monkeys at 30 mg/kg/day treated for 3-4 weeks, there were no changes in mitochondrial DNA content or ATP/GTP levels. Collectively, these data suggest that BMS-986094 is not a direct mitochondrial toxicant.
Multi‐parametric cytometry from a complex cellular sample: Improvements and limits of manual versus computational‐based interactive analyses

The wide possibilities opened by the developments of multi‐parametric cytometry are limited by the inadequacy of the classical methods of analysis to the multi‐dimensional characteristics of the data. While new computational tools seemed ideally adapted and were applied successfully, their adoption is still low among the flow cytometrists. In the purpose to integrate unsupervised computational tools for the management of multi‐stained samples, we investigated their advantages and limits by comparison to manual gating on a typical sample analyzed in immunomonitoring routine. A single tube of PBMC, containing 11 populations characterized by different sizes and stained with 9 fluorescent markers, was used. We investigated the impact of the strategy choice on manual gating variability, an undocumented pitfall of the analysis process, and we identified rules to optimize it. While assessing automatic gating as an alternate, we introduced the Multi‐Experiment Viewer software (MeV) and validated it for merging clusters and annotating interactively populations. This procedure allowed the finding of both targeted and unexpected populations. However, the careful examination of computed clusters in standard dot plots revealed some heterogeneity, often below 10%, that was overcome by increasing the number of clusters to be computed. MeV facilitated the identification of populations by displaying both the MFI and the marker signature of the dataset simultaneously. The procedure described here appears fully adapted to manage homogeneously high number of multi‐stained samples and allows improving multi‐parametric analyses in a way close to the classic approach. © 2016 International Society for Advancement of Cytometry
Carotid Web (Intimal Fibromuscular Dysplasia) Has High Stroke Recurrence Risk and Is Amenable to Stenting

Background and Purpose— Carotid webs have been increasingly recognized as a cause of recurrent stroke, but evidence remains scarce. We aim to report the clinical outcomes and first series of carotid stenting in a cohort of patients with strokes from symptomatic carotid webs. Methods— Prospective and consecutive data of patients <65 years old with cryptogenic stroke admitted within September 2014 to May 2017. Carotid web was defined by a shelf-like/linear filling defect in the posterior internal carotid artery bulb by computed tomographic angiography. Results— Twenty-four patients were identified (91.6% strokes/8.4% transient ischemic attacks [TIAs]). Median age was 46 (41–59) years, 61% were female, and 75% were black. Median National Institutes of Health Stroke Scale score was 10.5 (3.0–16.0) and ASPECTS (Alberta Stroke Program Early CT Score) was 8 (7–8). There were no parenchymal hemorrhages, and 96% of patients were independent at 3 months. All webs caused <50% stenosis. In patients with bilateral webs (58%), median ipsilateral web length was larger than contralateral (3.1 [3.0–4.5] mm versus 2.6 [1.85–2.9] mm; P=0.01), respectively. Twenty-nine percent of patients had thrombus superimposed on the symptomatic carotid web. A recurrent stroke/TIA involving the territory of the previously symptomatic web occurred in 7 (32%; 6 strokes/1 TIA) patients: 3 <1 week, 2 1 year of follow-up. Two recurrences occurred on dual antiplatelet therapy, 3 on antiplatelet monotherapy, 1 within 24 hours of thrombolysis, and 1 off antithrombotics. Median follow-up was 12.2 (8.0–18.0) months. Sixteen (66%) patients were stented at a median 12.2 (7.0–18.7) days after stroke with no periprocedural complications. No recurrent strokes/TIAs occurred in stented individuals (median follow-up of 4 [2.4–12.0] months). Conclusions— Carotid web is associated with high recurrent stroke/TIA risk, despite antithrombotic use, and is amenable to carotid stenting.
Cache-emulated register file: An integrated on-chip memory architecture for high performance GPGPUs

The on-chip memory design is critical to the GPGPU performance because it serves between the massive threads and the huge external memory as a low-latency and high-throughput data communication point. However, the existing on-chip memory hierarchy is inherited from the conventional CPU architecture and is oftentimes sub-optimal to the SIMT (single instruction, multiple threads) execution. In this study, we surpass the traditional memory hierarchy design and reform the on-chip memory into an integrated architecture with the cache-emulated register file (RF) capability tailored for high performance GPGPU computing. With the lightweight support from ISA, compiler and the modified microarchitecture, this integrated architecture can dynamically emulate a variable-sized RF and a cache in a uniform way. Evaluation results demonstrate that this novel architecture can deliver better performance and energy efficiency with smaller on-chip memory size. For example, it can gain an average of 50% performance improvement for the cache-sensitive applications.
Levels, Trends and Correlates of Abortion in Tehran, Iran: 2009-2014.

CONTEXT Accurate, up-to-date information on abortion incidence is lacking for Iran, where abortion is illegal. METHODS Data from 2,934 currently married women aged 15-49 who completed the 2009 Tehran Survey of Fertility (TSF) and 3,012 such women who completed the 2014 TSF were used to estimate levels of and trends in abortion and related measures. Analyses also examined characteristics of abortions, abortion recipients and providers, as well as trends in women's reasons for having an abortion. RESULTS Between 2009 and 2014, the proportion of married women who reported having ever had an abortion decreased from 8.3% to 5.6%. Declines also occurred in the general abortion rate (from 6.6 to 5.4 abortions per 1,000 women), the total abortion rate (from 0.18 to 0.17 abortions per married woman) and the annual number of abortions (from 10,656 to 8,734); however, the proportion of pregnancies that were terminated was stable (8.7-8.8%). The proportion of terminations obtained for nonmedical reasons rose from 68% to 81%. In 2014, abortion rates were elevated among women who were more educated, wealthier, employed, urban migrants or not highly religious, and among those who had no more than one child. The most commonly used providers were midwives (40%) and obstetricians (32%). Half of abortions resulted from withdrawal failure, but only one-fourth of withdrawal users switched to a modern contraceptive method after an abortion. CONCLUSIONS Some subgroups of women had an elevated risk of abortion and may benefit from measures that increase couples' effective use of contraceptives.