Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrated self‐organization of transitional ER and early Golgi compartments

COPII coated vesicles bud from an ER domain termed the transitional ER (tER), but the mechanism that clusters COPII vesicles at tER sites is unknown. tER sites are closely associated with early Golgi or pre‐Golgi structures, suggesting that the clustering of nascent COPII vesicles could be achieved by tethering to adjacent membranes. This model challenges the prevailing view that COPII vesicles are clustered by a scaffolding protein at the ER surface. Although Sec16 was proposed to serve as such a scaffolding protein, recent data suggest that rather than organizing COPII into higher‐order structures, Sec16 acts at the level of individual COPII vesicles to regulate COPII turnover. A plausible synthesis is that tER sites are created by tethering to Golgi membranes and are regulated by Sec16. Meanwhile, the COPII vesicles that bud from tER sites are thought to nucleate new Golgi cisternae. Thus, an integrated self‐organization process may generate tER‐Golgi units.
Physiotherapists utilizing diagnostic ultrasound in shoulder clinics. How useful do patients find immediate feedback from the scan as part of the management of their problem?

AIMS Physiotherapists are beginning to utilize diagnostic ultrasound imaging in upper limb/shoulder clinics. The aim of the present study was to receive feedback on the views of the patients concerning the usefulness of the information obtained immediately from the scan in the management of their problem. METHODS A questionnaire was offered to all patients attending a physiotherapist-led upper limb/shoulder clinic who underwent ultrasound imaging as part of a shoulder assessment over a 6-month period. A total of 103 patients completed a questionnaire for analysis. RESULTS Patients rated the ultrasound scan to be of benefit in all aspects. Regarding the ability to understand their shoulder problem better and in feeling reassured about their problem, 97% of patients either strongly agreed or agreed that this was the case. Concerning the capability of managing their problem, 89% of patients strongly agreed or agreed that they felt more able to do this. In total, 96% of patients evaluated the ultrasound scan to be of very high/high value to them. CONCLUSION Patients highly rate the information gained from ultrasound imaging in a physiotherapy-led upper limb/shoulder clinic and felt that it assisted them in the understanding, reassurance and management of their problem.
Automatic cancer detection and localization on prostatectomy histopathology images

Automatic localization of cancer on whole-slide histology images from radical prostatectomy specimens would support quantitative, graphical pathology reporting and research studies validating in vivo imaging against gold-standard histopathology. There is an unmet need for such a system that is robust to staining variability, is sufficiently fast and parallelizable as to be integrated into the clinical pathology workflow, and is validated using whole-slide images. We developed and validated such a system, with tuning occurring on an 8-patient data set and cross-validation occurring on a separate 41-patient data set comprising 703,745 480μm × 480μm sub-images from 166 whole-slide images. Our system computes tissue component maps from pixel data using a technique that is robust to staining variability, showing the loci of nuclei, luminal areas, and areas containing other tissue including stroma. Our system then computes first- and second-order texture features from the tissue component maps and uses machine learning techniques to classify each sub-image on the slide as cancer or non-cancer. The system was validated against expert-drawn contours that were verified by a genitourinary pathologist. We used leave-one-patient-out, 5-fold, and 2-fold cross-validation to measure performance with three different classifiers. The best performing support vector machine classifier yielded an area under the receiver operating characteristic curve of 0.95 from leave-one-out cross-validation. The system demonstrated potential for practically useful computation speeds, with further optimization and parallelization of the implementation. Upon successful multi-centre validation, this system has the potential to enable quantitative surgical pathology reporting and accelerate imaging validation studies using histopathologic reference standards.
Assessing Biodiversity in Boreal Forests with UAV-Based Photogrammetric Point Clouds and Hyperspectral Imaging

Forests are the most diverse terrestrial ecosystems and their biological diversity includes trees, but also other plants, animals, and micro-organisms. One-third of the forested land is in boreal zone; therefore, changes in biological diversity in boreal forests can shape biodiversity, even at global scale. Several forest attributes, including size variability, amount of dead wood, and tree species richness, can be applied in assessing biodiversity of a forest ecosystem. Remote sensing offers complimentary tool for traditional field measurements in mapping and monitoring forest biodiversity. Recent development of small unmanned aerial vehicles (UAVs) enable the detailed characterization of forest ecosystems through providing data with high spatial but also temporal resolution at reasonable costs. The objective here is to deepen the knowledge about assessment of plot-level biodiversity indicators in boreal forests with hyperspectral imagery and photogrammetric point clouds from a UAV. We applied individual tree crown approach (ITC) and semi-individual tree crown approach (semi-ITC) in estimating plot-level biodiversity indicators. Structural metrics from the photogrammetric point clouds were used together with either spectral features or vegetation indices derived from hyperspectral imagery. Biodiversity indicators like the amount of dead wood and species richness were mainly underestimated with UAV-based hyperspectral imagery and photogrammetric point clouds. Indicators of structural variability (i.e., standard deviation in diameter-at-breast height and tree height) were the most accurately estimated biodiversity indicators with relative RMSE between 24.4% and 29.3% with semi-ITC. The largest relative errors occurred for predicting deciduous trees (especially aspen and alder), partly due to their small amount within the study area. Thus, especially the structural diversity was reliably predicted by integrating the three-dimensional and spectral datasets of UAV-based point clouds and hyperspectral imaging, and can therefore be further utilized in ecological studies, such as biodiversity monitoring.
The mutagenesis of a type IV secretion system locus of Piscirickettsia salmonis leads to the attenuation of the pathogen in Atlantic salmon, Salmo salar.

Piscirickettsiosis is a threatening infectious disease for the salmon industry, due to it being responsible for significant economic losses. The control of outbreaks also poses considerable environmental challenges. Despite Piscirickettsia salmonis having been discovered as the aetiological agent of the disease more than 25 years ago, its pathogenicity remains poorly understood. Among virulence factors identified so far, type four secretion systems (T4SS) seem to play a key role during the infection caused by the bacterium. We report here the genetic manipulation of P. salmonis by means of the transference of plasmid DNA in mating assays. An insertion cassette was engineered for targeting the icmB gene, which encodes a putative T4SS-ATPase and is carried by one of the chromosomal T4SS clusters found within the genome of P. salmonis PM15972A1, a virulent representative of the EM-90-like strain. The molecular characterization of the resulting mutant strain demonstrated that the insertion interrupted the target gene. Further in vitro testing of the icmB mutant showed a dramatic drop in infectivity as tested in CHSE-214 cells, which is in agreement with its attenuated behaviour observed in vivo. Altogether, our results demonstrate that, similar to other facultative intracellular pathogens, P. salmonis' virulence relies on an intact T4SS.
Electrochemical oxygen transfer during direct current arc welding

The electrochemical transfer of oxygen was investigated for electrode negative and electrode positive polarities in the submerged arc, shielded metal arc and gas tungsten arc welding processes. Analysis of the welds showed that electrochemical reactions as well as thermochemical reactions are significant in altering the oxygen content of the weld metal. The oxygen transfer in the submerged and shielded metal arc welding processes is strongly influenced by electrochemical reactions at the slag/metal interface, and oxygen transfer in gas tungsten arc welding is strongly influenced by electrochemical reactions at the plasma/metal interface. The electrochemical oxygen reactions at the slag/metal interface include oxygen pickup at the anode and oxygen refining at the cathode. Electrochemical oxygen reactions at the plasma/metal interface include the refining of oxygen at the anode and pickup at the cathode. Electrochemical reactions have the greatest influence on weld metal chemistry at high welding currents and at slow weld travel speeds.
Structural Biology of the TNFα Antagonists Used in the Treatment of Rheumatoid Arthritis

The binding of the tumor necrosis factor α (TNFα) to its cognate receptor initiates many immune and inflammatory processes. The drugs, etanercept (Enbrel®), infliximab (Remicade®), adalimumab (Humira®), certolizumab-pegol (Cimzia®), and golimumab (Simponi®), are anti-TNFα agents. These drugs block TNFα from interacting with its receptors and have enabled the development of breakthrough therapies for the treatment of several autoimmune inflammatory diseases, including rheumatoid arthritis, Crohn’s disease, and psoriatic arthritis. In this review, we describe the latest works on the structural characterization of TNFα–TNFα antagonist interactions related to their therapeutic efficacy at the atomic level. A comprehensive comparison of the interactions of the TNFα blockers would provide a better understanding of the molecular mechanisms by which they neutralize TNFα. In addition, an enhanced understanding of the higher order complex structures and quinary structures of the TNFα antagonists can support the development of better biologics with the improved pharmacokinetic properties. Accumulation of these structural studies can provide a basis for the improvement of therapeutic agents against TNFα for the treatment of rheumatoid arthritis and other autoimmune inflammatory diseases in which TNFα plays an important role in pathogenesis.
A prospective genome-wide study of prostate cancer metastases reveals association of wnt pathway activation and increased cell cycle proliferation with primary resistance to abiraterone acetate–prednisone

Background Genomic aberrations have been identified in metastatic castration-resistant prostate cancer (mCRPC), but molecular predictors of resistance to abiraterone acetate/prednisone (AA/P) treatment are not known. Patients and methods In a prospective clinical trial, mCRPC patients underwent whole-exome sequencing (n = 82) and RNA sequencing (n = 75) of metastatic biopsies before initiating AA/P with the objective of identifying genomic alterations associated with resistance to AA/P. Primary resistance was determined at 12 weeks of treatment using criteria for progression that included serum prostate-specific antigen measurement, bone and computerized tomography imaging and symptom assessments. Acquired resistance was determined using the end point of time to treatment change (TTTC), defined as time from enrollment until change in treatment from progressive disease. Associations of genomic and transcriptomic alterations with primary resistance were determined using logistic regression, Fisher's exact test, single and multivariate analyses. Cox regression models were utilized for determining association of genomic and transcriptomic alterations with TTTC. Results At 12 weeks, 32 patients in the cohort had progressed (nonresponders). Median study follow-up was 32.1 months by which time 58 patients had switched treatments due to progression. Median TTTC was 10.1 months (interquartile range: 4.4-24.1). Genes in the Wnt/β-catenin pathway were more frequently mutated and negative regulators of Wnt/β-catenin signaling were more frequently deleted or displayed reduced mRNA expression in nonresponders. Additionally, mRNA expression of cell cycle regulatory genes was increased in nonresponders. In multivariate models, increased cell cycle proliferation scores (≥ 50) were associated with shorter TTTC (hazard ratio = 2.11, 95% confidence interval: 1.17-3.80; P = 0.01). Conclusions Wnt/β-catenin pathway activation and increased cell cycle progression scores can serve as molecular markers for predicting resistance to AA/P therapy.
Characterization of Nano-sized ZnO Electrodes with Curcumin- derived Natural Dye Extract for DSSC Application

Zinc oxide (ZnO) powder was first prepared by hydrothermal synthesis at low temperature. X-ray diffraction (XRD) investigation was carried out to examine the structural properties of ZnO powder. ZnO colloidal solution was deposited onto ITO/glass by rolling. After air drying, annealing in O2, atmospheric ambient was performed at 300 C and 400 C for 1 h. As the surface treatment, sintered ZnO film was immersed in 0.1 M HCl, washed with DIW and dried at room temperature. The Curcumin, a yellow-orange dye found in turmeric root, was used as a photosensitizer and was carefully prepared to avoid colour fading. Next, the ZnO film was dipped in dye solution for 15 h. High performance carbon counter electrode was prepared and used as a counter electrode. Two glass slides were offset and two binder clips were used to hold the electrodes together. Photovoltaic response of ZnO cell was measured and it was expected to utilize the DSSC application. The conversion efficiency of DSSC at 400oC (0.129%) was found to be larger than that of the cell at 300oC (0.117%).
Full-Body Musculoskeletal Model for Muscle-Driven Simulation of Human Gait

Objective: Musculoskeletal models provide a noninvasive means to study human movement and predict the effects of interventions on gait. Our goal was to create an open-source 3-D musculoskeletal model with high-fidelity representations of the lower limb musculature of healthy young individuals that can be used to generate accurate simulations of gait. Methods: Our model includes bony geometry for the full body, 37 degrees of freedom to define joint kinematics, Hill-type models of 80 muscle-tendon units actuating the lower limbs, and 17 ideal torque actuators driving the upper body. The model's musculotendon parameters are derived from previous anatomical measurements of 21 cadaver specimens and magnetic resonance images of 24 young healthy subjects. We tested the model by evaluating its computational time and accuracy of simulations of healthy walking and running. Results: Generating muscle-driven simulations of normal walking and running took approximately 10 minutes on a typical desktop computer. The differences between our muscle-generated and inverse dynamics joint moments were within 3% (RMSE) of the peak inverse dynamics joint moments in both walking and running, and our simulated muscle activity showed qualitative agreement with salient features from experimental electromyography data. Conclusion: These results suggest that our model is suitable for generating muscle-driven simulations of healthy gait. We encourage other researchers to further validate and apply the model to study other motions of the lower extremity. Significance: The model is implemented in the open-source software platform OpenSim. The model and data used to create and test the simulations are freely available at https://simtk.org/home/full_body/, allowing others to reproduce these results and create their own simulations.
An Extended Nomenclature for Mammalian V-ATPase Subunit Genes and Splice Variants

The vacuolar-type H+-ATPase (V-ATPase) is a multisubunit proton pump that is involved in both intra- and extracellular acidification processes throughout the body. Multiple homologs and splice variants of V-ATPase subunits are thought to explain its varied spatial and temporal expression pattern in different cell types. Recently subunit nomenclature was standardized with a total of 22 subunit variants identified. However this standardization did not accommodate the existence of splice variants and is therefore incomplete. Thus, we propose here an extension of subunit nomenclature along with a literature and sequence database scan for additional V-ATPase subunits. An additional 17 variants were pulled from a literature search while 4 uncharacterized potential subunit variants were found in sequence databases. These findings have been integrated with the current V-ATPase knowledge base to create a new V-ATPase subunit catalogue. It is envisioned this catalogue will form a new platform on which future studies into tissue- and organelle-specific V-ATPase expression, localization and function can be based.
Position Control for Magnetic Rodless Cylinders With Strong Static Friction

An adaptive extended state observer (AESO) based robust controller is proposed for precise position tracking control of a magnetic rodless cylinder with strong static friction. The AESO with dynamic gains is utilized to estimate the static friction and nonlinearities. Precise and robust control is achieved by the proposed controller that integrates the advantages of a sliding-mode controller and a linear active disturbance rejection controller. Experimental results show that both response rate and position accuracy are significantly improved by the proposed method in this paper.
Effects of Estradiol on Histological Parameters and Secretory Ability of Pituitary Mammotrophs in Ovariectomized Female Rats

Objective Estrogen replacement therapy remains current as a therapeutic approach to treat menopausal symptoms and may significantly affect hormone-producing cells in the female pituitaries. The aim of this study was to examine the histological parameters of pituitary mammotrophs and prolactin secretion after chronic estradiol treatment in ovariectomized adult female rats, reflecting premature menopause. Materials and Methods In this experimental study, adult female Wistar rats were divided into non-ovariectomized (C), ovariectomized (OVX) and estradiol-treated ovariectomized (OVX+E) groups. Estradiol dipropionate [0.625 mg/kg body mass per day] was administered for four weeks, while the C and OVX groups received vehicle alone. Mammotrophs were identified by the peroxidase-antiperoxidase (PAP) immunohistochemical procedure, while prolactin concentrations were measured by the non-isotopic two-step assay (Delfia) method. Comparison of the differences between groups was performed using one-way analysis of variance (ANOVA) and Tukay (honest significant difference) HSD test. Results Ovariectomy caused significant (P<0.05) decreases in mammotroph optical density (OD), volume density (VV) and number per mm2 by 29, 27 and 34%, respectively, in comparison with the C females. In the OVX+E group, significant (P<0.05) increases in OD, cell volume, VVand number of mammotrophs per mm2 by 181, 15%, 5.8-fold and 5.2-fold, respectively, were observed when compared to OVX animals. The serum prolactin concentration in OVX females was significantly (P<0.05) decreased by 14% in comparison to the C group, while in OVX+E females, prolactin levels were significantly (P<0.05) increased by 53% compared to the OVX controls. Conclusion Estradiol supplementation in ovariectomized females is followed by stimulatory histological and secretory changes of the mammotrophs. These results could serve as indicators of possible prolactinome development upon estradiol application in premature menopausal subjects.
On the Effectiveness of Source Code Transformations for Binary Obfuscation

Obfuscation is gaining momentum as a protection mechanism for the intellectual property contained within or encapsulated by software. Usually, one of the following three directions is followed: source code obfuscation is achieved through source code transformations, Java bytecode obfuscation through transformations on the bytecode, and binary obfuscation through binary rewriting. In this paper, we study the effectiveness of source code transformations for binary obfuscation. The transformations applied by several existing source code obfuscators are empirically shown to have no impact on the stripped binary after compilation. Subsequently, we study which source code transformations are robust enough to percolate through the compiler into
Inhibition of Escherichia coli O157:H7 on stainless steel using Pseudomonas veronii biofilms

We produced a Pseudomonas veronii biofilm on the surface of a stainless steel that is inhibitory to Escherichia coli O157:H7. Pseudomonas veronii strain KACC 81051BP, isolated from lettuce, readily formed biofilm on the surface of stainless steel coupons (SSCs) immersed in tryptic soy broth at 25°C. Cells showed significantly (P ≤ 0·05) enhanced tolerance to desiccation stress (43% relative humidity (RH)) and retained antimicrobial activity against E. coli O157:H7. The number of E. coli O157:H7 (control; 4·1 ± 0·1 log CFU per coupon) on sterile SSCs decreased to 2·7 ± 0·2 log CFU per coupon after exposure to 43% RH at 25°C for 48 h, while the population of E. coli O157:H7 (4·1 ± 0·0 log CFU per coupon) on SSCs containing P. veronii biofilm decreased to below the theoretical detection limit (1·5 log CFU per coupon) within 24 h. The antimicrobial biofilm produced on stainless steel may have application in preventing cross‐contamination by E. coli O157:H7 on other abiotic surfaces in food‐contact environments.