Miracle-dz/UniFAR-FTUs huggingface dataset:
Cyclin‐dependent kinase‐dependent phosphorylation of Lif1 and Sae2 controls imprecise nonhomologous end joining accompanied by double‐strand break resection

DNA double‐strand breaks (DSBs) are repaired by two distinct pathways, homologous recombination (HR) and nonhomologous end joining (NHEJ). NHEJ includes two pathways, that is, precise and imprecise end joining. We found that Lif1, a component of the DNA ligase IV complex in Saccharomyces cerevisiae, was phosphorylated by cyclin‐dependent kinase (CDK) at Ser261 during the S to G2 phase but not during G1 phase. This phosphorylation was required for efficient NHEJ in G2/M cells, rather than in G1 cells. It also promotes the stable binding of Lif1 protein to DSBs, specifically in G2/M‐arrested cells, which shows the resection of DSB ends. Thus, Lif1 phosphorylation plays a critical role in a certain type of imprecise NHEJ accompanied by DSB end resection and micro‐homology. Lif1 phosphorylation at Ser261 is probably involved in micro‐homology‐dependent end joining associated with producing single‐stranded DSB ends that are formed by Sae2 as early intermediates in the HR pathway. CDK‐dependent modification of the NHEJ pathway might make DSB ends compatible for NHEJ and thus prevent competition between HR and NHEJ in hierarchy on the choice of DSB repair pathways.
Prediction of the effect of building factors on the magnetic performance of electrical steels in automotive applications

Electrical steel is the predominant material used for the magnetic cores of electrical machines, such as the rotors and stators of electric motors. The cutting of electrical steel during the motor manufacturing process is detrimental to the magnetic properties and consequently the properties in operation will be different from those measured, on strips, by the steel manufacturer. The ability to predict the effect of the manufacturing processes on the magnetic performance would be of great benefit to the electrical machine designer. An enhanced system was developed to measure the local magnetic properties with the addition of being able to accurately map the properties of complex geometries in a time efficient manner. The local magnetic properties of 0.35 mm thick 2.4 % and 3.2 % silicon, punched non-oriented electrical steel rings with constant outer diameter and varying inner diameter were measured to explore and predict the effect of punching. The distinct contrast in flux density profile between the grades was attributed to spreading of residual stress from punching. The 3.2 % Si samples showed a degradation depth consistent between ring widths and extending 2.5 ± 0.5 mm from the edge, while the 2.4 % Si samples displayed a more gradual decrease. Original models were proposed to predict the increase in power loss and the flux density profile based on the residual stress distribution. This novel modelling approach, validated using FEM software, could accurately reproduce the flux density profile and showed good agreement with experimental results, within 5% for most data points. The integration of this four-parameter model into FEM packages could greatly aid the designers of EMs by improving the ability to accurately predict the flux density throughout a motor core, ultimately improving the efficiency of these machines.
Helicobacter pylori infection in elderly patients with peptic ulcer.

community-dwelling and institutionalized subjects in Aberdeen and the hospitalized subjects we studied is remarkable. However, this does not necessarily mean that the elderly population in Aberdeen is dehydrated, as dehydration can be best defined as a clinically important shortage of TBW compared with an individual’s optimal TBW. Absolute figures of TBW are subject to measurement errors (66% for TBW as measured with D2O [1]) and large between-population variability in body build and weight [3, 4]. It would be informative to compare TBW per kg body weight and TBW per kg fat-free mass of the subjects in Aberdeen with our subjects. However, we agree with Primrose et al. that their results and ours, and the differences between them, support our plea for wider use of subject-specific reference ranges not only in biochemical indices of dehydration, but also in data on body water compartments.
Sexual behaviour in Scottish prisons.

At Brixton HIV positive prisoners, who are segregated because of their infection, occupy better accommodation, which thus encourages prisoners to claim that they are positive for the virus. Retesting shows that some of them are indeed negative. Injecting drug use undoubtedly occurs in prisons, particularly among remand prisoners, and sharing of equipment is inevitable. Although cases of acute hepatitis B in prison have been recorded, so far there has been no evidence of acute HIV seroconversion illness. In an American custodial prison HIV testing on admission and release has not shown significant changes in seropositivity. , Long term prisoners are much less likely to abuse drugs. Identification of those prisoners infected with HIV, with guaranteed confidentiality, will permit targeted advice on reducing the risk of transmitting the virus and on maximising current health, including detoxification of drug users. Tests to evaluate the immune system will enable appropriate prophylaxis to be prescribed to those who are vulnerable to sudden life threatening opportunistic infections. Multidisciplinary committees should be established to plan, implement, and monitor systems for managing HIV infection in British prisons. Sensitive and effective handling will benefit public health in general and the prison population in particular, including staff.
Issues Related to Obtaining Intelligence Quotient-Matched Controls in Autism Research

Background: Intelligence Quotient (IQ) is considered to be an index of global cognitive functioning and has traditionally been used as a fulcral measure in case-control studies in neuro-developmental disorders such as autism. Aim: The aim is to highlight the issues of “matching for IQ” with controls in autism research. Materials and Methods: Percentile scores on the Coloured Progressive Matrices of 20 children with autism in the age range of 5 to 12 years have been graphically compared with 21 age matched typically developing children. Results and Conclusions: The percentile scores of the so-called high functioning children with autism from special schools were well below that of typically developing children. There are many challenges when using IQ in case-control studies of autism. Alternative approaches need to be considered.
Exploiting the Small-World Effect for Resource Finding in P2P Grids/Clouds

This paper presents a resource finding and allocation scheme for Grid-/Cloud-computing systems, called SWHYGRA (Small-World HYperspace-based Grid Resource Allocation). It models the overall system using a decentralized peer-to-peer approach organizing the nodes in an overlay network featuring specific convenient properties. SWHYGRA intends to exploit the small-world effect, by employing an algorithm aimed at building an overlay network whose structure mimics the small-world model. Such networks feature a high clustering degree coupled with a very low average path length, both being key characteristics for the SW-HYGRA approach. The former allows nodes with similar resource availability to be clustered; together with the latter, it permits a resource finding algorithm to reach a target node in a fast and efficient way.
Early commitment and robust differentiation in colonic crypts

Tissue stem cells produce a constant flux of differentiated cells with distinct proportions. Here, we show that stem cells in colonic crypts differentiate early to form precisely 1:3 ratio of secretory to absorptive cells. This precision is surprising, as there are only eight stem cells making irreversible fate decisions, and so large stochastic effects of this small pool should have yielded much larger noise in cell proportions. We use single molecule FISH, lineage‐tracing mice and simulations to identify the homeostatic mechanisms facilitating robust proportions. We find that Delta‐Notch lateral inhibition operates in a restricted spatial zone to reduce initial noise in cell proportions. Increased dwell time and dispersive migration of secretory cells further averages additional variability added during progenitor divisions and breaks up continuous patches of same‐fate cells. These noise‐reducing mechanisms resolve the trade‐off between early commitment and robust differentiation and ensure spatially uniform spread of secretory cells. Our findings may apply to other cases where small progenitor pools expand to give rise to precise tissue cell proportions.
Low levels of TGF-β1 enhance human umbilical cord-derived mesenchymal stem cell fibronectin production and extend survival time in a rat model of lipopolysaccharide-induced acute lung injury.

Mesenchymal stem cells (MSCs) are an attractive cellular source for cell‑based therapy, tissue engineering and regenerative medicine. However, the use of MSCs is limited by their low incorporation rate in the graft environment. The majority of cells are lost from the graft within 1 month, due to reduced microenvironment or local inflammation at the graft site. The extracellular matrix (ECM) may assist the survival and expansion of MSCs. The present study aimed to identify an effective approach to increase ECM expression levels by MSCs in order to enhance the therapeutic effect and survival rate of MSCs at the injury site. The concentration‑dependent effect of transforming growth factor (TGF)‑β1 on human umbilical cord (hUC)‑MSC proliferation and expression of ECM genes was investigated. MSCs were successfully isolated, cultured and expanded from hUC. A low concentration of TGF‑β1 (0.1 ng/ml) exhibited the optimal effect on hUC‑MSC proliferation and markedly stimulated the expression of ECM genes, particularly fibronectin (FN). Furthermore, treatment with TGF‑β1 caused no alteration in the immunophenotype and differentiation capacity of MSCs. In vivo experiments in rats demonstrated that intravenous injection of control UC-MSCs or TGF-β1-pre-treated UC-MSCs reduced the severity of lipopolysaccharide-induced lung injury, assessed using histology, measurements of the wet‑dry lung weight ratio, and neutrophil count and protein concentration in bronchoalveolar lavage fluid. However, the short‑term (48 h) therapeutic effects of untreated and TGF‑β1‑pre‑treated UC‑MSCs were similar. The survival of MSCs in damaged lungs, determined by Sry gene expression levels, were significantly increased in MSCs pre‑treated with TGF‑β1. In conclusion, pre‑treatment of MSCs with a low concentration of TGF‑β1 enhanced the expression of ECM components, particularly FN, thus, improving the survival and potential therapeutic benefits of MSCs. Pre‑treatment of MSCs with TGF‑β1 may prolong the effective therapy time and represent an efficient therapeutic approach for tissue repair.
Immunity to pathogenic free-living amoebae: role of humoral antibody

Pathogenic free-living amoebae are common in nature, but few clinical infections by these amoebae have been reported. This has prompted studies of host susceptibility factors in humans. A survey of normal human sera from three New Zealand Health Districts was made; antibodies to pathogenic free-living amoebae were found in all sera, with titers ranging from 1:5 to 1:20 for Naegleria spp. and from 1:20 to 1:80 for Acanthamoeba spp. The antibodies belonged mainly to immunoglobulin G and immunoglobulin M classes. The presence of a specific neutralizing factor against Acanthamoeba spp. but not Naegleria spp. was demonstrated. Possible protective mechanisms are discussed.
The Association of Vitamin D Deficiency and Insufficiency with Diabetic Nephropathy: Implications for Health Disparities

Objective: To evaluate the association between vitamin D deficiency and insufficiency with diabetic nephropathy across racial/ethnic groups. Methods: Cross-sectional analysis of the 2001 to 2006 National Health and Nutrition Examination Survey. A nationally representative sample of 1216 adults (≥20 years old) with diagnosed diabetes provides population estimates for >12.6 million individuals. Nephropathy was defined as urinary albumin-to-creatinine ratio ≥30 mg/g in a random spot urine sample. Serum 25-hydroxycalciferol vitamin D levels were characterized as <20 ng/mL vitamin D deficiency, 20 to 29 ng/mL vitamin D insufficiency, and ≥30 ng/mL normal vitamin D. Results: Overall, 30.7% of adults with diabetes have nephropathy, 48.9% have vitamin D deficiency and 36.6% have vitamin D insufficiency. Minorities are more likely to have nephropathy (non-Hispanic whites, 27.8%; non-Hispanic blacks, 36.2%; Hispanics 38.5%; P = .02) and vitamin D deficiency (non-Hispanic whites, 39.5%; non-Hispanic blacks, 80.4%; Hispanic, 59.0%; P < .01). Higher proportions of individuals with nephropathy have vitamin D deficiency than individuals without nephropathy (53.2% vs 47.0%; P = .03). Logistic regressions demonstrate vitamin D deficiency and insufficiency are associated with the presence of nephropathy after adjustment for race/ethnicity, age, sex, hypertension, high cholesterol, smoking status, and use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (odds ratio, 1.85; 95% CI, 1.06–3.23 for vitamin D deficiency; and odds ratio, 1.79; 95% CI, 1.12–2.85 for vitamin D insufficiency). Conclusions: There is a high prevalence of vitamin D deficiency and insufficiency in individuals with diabetes; minorities have the highest prevalences. Thus, evaluating vitamin D levels in people with diabetes may be warranted. There is an independent association between vitamin D deficiency and vitamin D insufficiency with the presence of nephropathy, even after adjustment for race/ethnicity and other variables. Further studies of this relationship may lead to new interventions that decrease health disparities in the progression of diabetic nephropathy.
Finite Element Analysis of Blanking Operation of Magnesium Alloy (AZ31) Sheet Using Ductile Fracture Criteria and Its Experimental Verification at Various Temperatures

This study focuses on modeling and analyzing sheet blanking process of Magnesium alloy sheet (AZ31) using finite element method at various temperatures. The computational analysis is then compared with the results obtained through the experimental setup. In the finite element model fracture initiation and the shape of the blanked edge are influenced by the value of critical damage criteria (C). The value of critical criteria is determined and compared using the ductile fracture criteria proposed by various researchers by varying various process parameters and temperature. The effect of temperature and process parameters on the geometry of the blanked edge including burr, fracture zone, shear surface and rollover has been investigated. Moreover, numerical predictions were compared with the experimental results.
Prevalence of Tibiofemoral Osteoarthritis 15 Years after Nonoperative Treatment of Anterior Cruciate Ligament Injury

Background The occurrence of osteoarthritis (OA), associated meniscal injuries, meniscectomy, and patient-related measures for patients treated nonoperatively after anterior cruciate ligament (ACL) injuries have not been well described in the literature in terms of natural history. Hypothesis Patients with ACL injury can achieve a low occurrence of tibiofemoral OA and good knee function when treated without ACL reconstruction. Study Design Cohort study (prognosis); Level of evidence, 2. Methods One hundred consecutive patients with an acute, complete ACL injury were observed for 15 years. All patients were primarily treated with activity modification and without ACL reconstruction. To achieve improved functional stability, supervised physical therapy was initiated early after injury. The patients were examined using anteroposterior weightbearing radiography. The Knee injury and Osteoarthritis Outcome Score (KOOS) was used to quantify knee-related symptoms and knee function. Results Seventy-nine patients consented to radiographic examination and 93 completed the KOOS questionnaire. Thirteen patients (16%), all of whom were among the 35 patients whose knees were meniscectomized, developed radiographic tibiofemoral OA. In contrast, none of the remaining nonmeniscectomized and radiographed knees developed OA (n = 44) (P < .0001). Sixty-three patients (68%) had an asymptomatic knee. Twenty-two patients (23%) had undergone ACL reconstruction with a mean time of 4 years after injury. Conclusion The study had a favorable long-term outcome regarding incidence of radiographic knee OA, knee function and symptoms, and need for ACL reconstruction. Although risk factors for posttraumatic OA are multifactorial, the primary risk factor that stood out in this study was if a meniscectomy had been performed. Early activity modification and neuromuscular knee rehabilitation might also have been related to the low prevalence of radiographic knee OA. In patients with ACL injury willing to moderate activity level to avoid reinjury, initial treatment without ACL reconstruction should be considered.
Detection of large above-ground biomass variability in lowland forest ecosystems by airborne LiDAR

Quantification of tropical forest above-ground biomass (AGB) over large areas as input for Reduced Emissions from Deforestation and forest Degradation (REDD+) projects and climate change models is challenging. This is the first study which attempts to estimate AGB and its variability across large areas of tropical lowland forests in Central Kalimantan (Indonesia) through correlating airborne light detection and ranging (LiDAR) to forest inventory data. Two LiDAR height metrics were analysed, and regression models could be improved through the use of LiDAR point densities as input ( R 2 = 0.88; n = 52). Surveying with a LiDAR point density per square metre of about 4 resulted in the best cost / benefit ratio. We estimated AGB for 600 km of LiDAR tracks and showed that there exists a considerable variability of up to 140% within the same forest type due to varying environmental conditions. Impact from logging operations and the associated AGB losses dating back more than 10 yr could be assessed by LiDAR but not by multispectral satellite imagery. Comparison with a Landsat classification for a 1 million ha study area where AGB values were based on site-specific field inventory data, regional literature estimates, and default values by the Intergovernmental Panel on Climate Change (IPCC) showed an overestimation of 43%, 102%, and 137%, respectively. The results show that AGB overestimation may lead to wrong greenhouse gas (GHG) emission estimates due to deforestation in climate models. For REDD+ projects this leads to inaccurate carbon stock estimates and consequently to significantly wrong REDD+ based compensation payments.
Chemosensory guidance cues in a turbulent chemical odor plume

The characteristics of chemical odor plumes released into a turbulent open channel flow are evaluated in the context of chemical plume tracking. The objective is to assess the availability and usefulness of chemosensory cues to animals, such as benthic crustaceans, attempting to orient in the plume. Releasing fluorescent dye into the fully developed turbulent boundary layer of a large laboratory‐scale flume created turbulent odor plumes. Flow visualization of odor fields created with varying release velocity, release distance from the bed, and nozzle diameter indicated that chemosensory cues in plumes depend on the release characteristics as well as the ambient flow conditions. Thus, to understand animal behavior, it is important to quantify the plume release properties and characteristics. We chose to quantify concentration fields for the case of isokinetic release using the planar laser‐induced fluorescence technique. These measurements indicate that the time‐averaged concentration converges far too slowly to be useful to a foraging animal. Similarly, resolving the rise slope of a concentration burst requires sampling rates unattainable by animals, and the spatial variation of rise slope is too mild to follow without lengthy sampling periods. In addition, only mild variation with distance from the source is observed in the concentration burst magnitude and duration. Thus, the time‐averaged concentration, rise slope, and burst shape all appear to have limited usefulness for plume orientation for animals known to orient effectively to these types of odor sources.
Recombinant CPE fused to tumor necrosis factor targets human ovarian cancer cells expressing the claudin-3 and claudin-4 receptors

Using gene expression profiling, others and we have recently found that claudin-3 (CLDN3) and claudin-4 (CLDN4) are two of the most highly and consistently up-regulated genes in ovarian carcinomas. Because these tight junction proteins are the naturally occurring receptors for Clostridium perfringens enterotoxin (CPE), in this study, we used the COOH-terminal 30 amino acids of the CPE (CPE290-319), a fragment that is known to retain full binding affinity but have no cytolytic effect, to target tumor necrosis factor (TNF) to ovarian cancers. We constructed a pET32-based vector that expressed the fusion protein, designated here as CPE290-319-TNF, in which CPE290-319 was fused to TNF at its NH2-terminal end. Western blotting confirmed presence of both CPE290-319 and TNF in the fusion protein. The TNF component in CPE290-319-TNF was 5-fold less potent than free TNF as determined by a standard L-929 TNF bioassay. However, the CPE290-319-TNF was >6.7-fold more cytotoxic than free TNF to 2008 human ovarian cancer cells, which express both CLDN3 and CLDN4 receptors. shRNAi-mediated knockdown of either CLDN3 or CLDN4 expression in 2008 markedly attenuated the cytotoxic effects of CPE290-319-TNF. The fusion construct was efficiently delivered into target cells and located in both cytosol and vesicular compartments as assessed by immunofluorescent staining. We conclude that CPE290-319 effectively targeted TNF to ovarian cancer cells and is an attractive targeting moiety for development of CPE-based toxins for therapy of ovarian carcinomas that overexpress CLDN3 and CLDN4. [Mol Cancer Ther 2009;8(7):1906–15]