Miracle-dz/UniFAR-FTUs huggingface dataset:
Lp82 calpain during rat lens maturation and cataract formation.

PURPOSE To measure changes in levels of Lp82 during maturation and selenite cataract formation in rat lens. Lp82 is a lens-specific, calcium-activated isozyme from the calpain family of cysteine proteases (EC 34.22.17). METHODS Competitive RT-PCR was used to assess Lp82 and m-calpain mRNA concentrations. Immunoblotting and ELISA after DEAE chromatography measured Lp82 and m-calpain protein levels. Casein zymography assessed proteolytic activities in regions and whole lenses from maturing rats. RESULTS Levels of Lp82 mRNA, protein, and caseinolytic activity decreased more rapidly during maturation of rat lens than for m-calpain. Unexpectedly, the water-insoluble fraction of rat lens contained enzymatically active Lp82. Selenite injection also caused major loss of Lp82 protein during cataract formation. CONCLUSIONS Lp82 is a proteolytic enzyme likely functioning in early lens development and maturation. The rapid loss of Lp82 activity during lens maturation is probably caused by three factors: autodegradation associated with the proteolysis of soluble and insoluble proteins occurring in the rat lens nucleus, association of Lp82 with the lens insoluble fraction, and loss of Lp82 mRNA. Lp82 may function early in lens maturation along with m-calpain, which then is predominant in the latter stages of maturation. Proteolysis in selenite cataract is partially caused by over-activation of Lp82.
A Hybrid Prediction Method for Bridging GPS Outages in High-Precision POS Application

Position and orientation system (POS) is a key technology widely used in remote sensing applications, which integrates inertial navigation system (INS) and GPS using a Kalman filter (KF) to provide high-accuracy position, velocity, and attitude information for remote sensing motion compensation. However, when GPS signal is blocked, the POS accuracy will decrease owing to the unbounded INS error accumulation. To improve the reliability and accuracy of POS, this paper proposes a hybrid prediction method for bridging GPS outages. This method uses radial basis function (RBF) neural network coupled with time series analysis to forecast the measurement update of KF, resulting in reliable performance during GPS outages. In verifying the proposed hybrid prediction method, a flight experiment was conducted in 2011, based on a high-precision Laser POS. Experimental results show that the proposed hybrid prediction method is more effective than two other methods (KF and RBF neural network).
Retaining and Supporting Mature Students in Higher Education

An increasing proportion of the United Kingdom's (UK) full-time undergraduate student population is mature. However, the reasons as to why these students leave higher education early are under-researched. Based upon research conducted in the North East of England, this article contributes to the closure of this gap as it highlights a number of issues that impact upon the retention of mature students. These issues include finance, a lack of preparedness for higher education and timetabling. The North East's six universities have responded to these issues by introducing systems of support that span the student lifecycle.
In vitro blood compatibility and bone mineralization aspects of polymeric scaffold laden with essential oil and metallic particles for bone tissue engineering

Abstract Bone tissue engineering scaffolds necessities appropriate physicochemical and mechanical properties to support its renewal. Electrospun scaffolds have been used unequivocally in bone tissue restoration. The main intention of this research is to develop electrospun polyurethane (PU) scaffold decorated with metallic particles and essential oil with advanced properties to make them as a putative candidate. The nanocomposite scaffold exhibited appropriate wettability and suitable fiber diameter compared to the polyurethane scaffold. Interaction of the added constituents with the polyurethane was corroborated through hydrogen bonding formation. Tensile strength of the composites was enhanced compared to the polyurethane scaffold. Thermal analysis depicted the lower weight loss of the composite scaffold than the pristine PU. Blood coagulation was significantly delayed and also the composite surface rendered safe interaction with red blood cells. In vitro toxicity testing using fibroblast cells portrayed the nontoxic behavior of the fabricated material. The above-said advanced properties of the composite scaffold can be warranted for bone tissue engineering application.
One step at a time: CYP2D6 guided tamoxifen treatment awaits convincing evidence of clinical validity.

Approximately 80% of breast tumors are estrogen-receptor positive (ER+), relying on estrogenic signaling to stimulate cellular replication and tumor growth. These tumors are relatively indolent, sensitive to endocrine therapy and resistant to chemotherapy. Tamoxifen is a selective estrogen receptor modulator (SERM) that antagonizes ER in the cancer cell. The addition of 5 years of tamoxifen to local therapy (i.e., surgery and radiation) provides a survival benefit in the nonmetastatic breast cancer setting in preand post-menopausal patients with ER+ tumors [1]. Tamoxifen is a relatively weak antiestrogen in comparison to its active metabolites, particularly endoxifen. Two parallel pathways bioactivate tamoxifen to endoxifen through several overlapping cytochrome P450 (CYP) enzymes; the rate limiting step is catalyzed by the highly polymorphic CYP2D6 enzyme. CYP2D6 genotype can be translated into predicted metabolic activity phenotypes: poor metabolizer (PM), intermediate metabolizer (IM), extensive metabolizer (EM), ultrarapid metabolizer (UM) [2], which are strongly predictive of endoxifen concentration during tamoxifen treatment [3]. Many pharmacogenetic studies have investigated a putative association between low activity CYP2D6 genotype and inferior efficacy from tamoxifen treatment, with highly discordant results [4]. Most are typical pharmaco genetic discovery studies performed retro spectively in small, heterogeneous cohorts with limited patient, disease and outcome information, which are highly susceptible to false positive and negative findings. Validation of a true pharmacogenetic association, demonstration of so-called ‘clinical validity’, should be conducted in prospective clinical studies that are larger, have more homogeneous patients and treatment and systematically collect outcomes data. In the case of CYP2D6 and tamoxifen, validation attempts in the Breast International Group 1–98 (BIG 1–98), Arimidex, Tamoxifen, Alone or in Combination (ATAC) and Austrian Breast & Colo rectal Cancer Study Group (ABCSG) eight clinical trials have been similarly discordant [5–7], with only the ABCSG8 study detecting a significant pharmacogenetic association. The International Tamoxifen Pharmacogenetics Consortium (ITPC) conducted a patient-level meta-analysis of the association between CYP2D6 genotype and invasive disease free survival (IDFS) in patients receiving tamoxifen treatment. After applying strict inclusion criteria to 4973 patients, the ITPC reported a statistically significant increase in IDFS (hazard ratio [HR]: 1.25; 95% CI: One step at a time: CYP2D6 guided tamoxifen treatment awaits convincing evidence of clinical validity
Effects of imidazole derivatives on cytochromes P450 from human hepatocytes in primary culture

The expression of several forms of cytochrome P450 including P450 1A2, 2D6, 2E1, and 3A was investigated in human hepatocytes maintained in primary culture for 96 h in the absence or presence of 50 μm of various imidazole derivatives. These included ketoconazole, clotrimazole, miconazole, fluconazole, secnidazole and metronidazole. In addition, the typical inducers rifampicin and β‐naphthoflavone were used for comparison. Western and Northern blot analysis of microsomes and RNA prepared from these cultures as well as de novo synthesis experiments revealed that, among the imidazole derivatives tested, only clotrimazole was a strong rifampicin‐like inducer of P450 3A. The expression of the other forms of P450 tested was not affected by the treatments. Analysis of the inhibition of 13 monoxygenase activities, including ethoxyresorufin and phenacetin O‐deethylases, coumarin 7α‐, lauric acid 11‐ and 12‐, mephenytoin 4‐, debrisoquin 4‐, and aniline hydroxylases, benzphetamine, aminopyrine, mephenytoin and erythromycin demethylases, and cyclosporin oxidase (representative of 10 different forms of P450 in human liver microsomes) revealed that ketoconazole was a strong and selective in vitro inhibitor of P450 3A (cyclosporin oxidase) with a Ki < 1 μm. Clotrimazole and miconazole were also strong inhibitors of P450 3A‐mediated activities in contrast to the other imidazole derivatives. —Maurice, M. ; Pichard, L. ; Daujat, M. ; Fabre, I. ; Joyeux, H. ; Domergue, J.; Maurel, P. Effects of imidazole derivatives on cytochromes P450 from human hepatocytes in primary culture. FASEB J. 6: 752‐758; 1992.
Effects of Cyclic Compressive Loading on Chondrogenesis of Rabbit Bone‐Marrow Derived Mesenchymal Stem Cells

The objective of this study was to examine the effects of cyclic compressive loading on chondrogenic differentiation of rabbit bone‐marrow mesenchymal stem cells (BM‐MSCs) in agarose cultures. Rabbit BM‐MSCs were obtained from the tibias and femurs of New Zealand white rabbits. After the chondrogenic potential of BM‐MSCs was verified by pellet cultures, cell‐agarose constructs were made by suspending BM‐MSCs in 2% agarose (107 cells/ml) for a cyclic, unconfined compression test performed in a custom‐made bioreactor. Specimens were divided into four groups: control; transforming growth factor (TGF‐β) (with TGF‐β1 treatment); loading (with stimulation of cyclic, unconfined compressive loading); and TGF‐β loading (with TGF‐β1 treatment and loading stimulation) groups. In the loading experiment, specimens were subjected to sinusoidal loading with a 10% strain magnitude at a frequency of 1 Hz for 4 hours a day. Experiments were conducted for 3, 7, and 14 consecutive days. While the experimental groups (TGF‐β, loading, and TGF‐β loading) exhibited significantly higher levels of expressions of chondrogenic markers (collagen II and aggrecan) at three time periods, there were no differences among the experimental groups after an extra 5‐day culture. This suggests that compressive loading alone induces chondrogenic differentiation of rabbit BM‐MSCs as effectively as TGF‐β or TGF‐β plus loading treatment. Moreover, both the compressive loading and the TGF‐β1 treatment were found to promote the TGF‐β1 gene expression of rabbit BM‐MSCs. These findings suggest that cyclic compressive loading can promote the chondrogenesis of rabbit BM‐MSCs by inducing the synthesis of TGF‐β1, which can stimulate the BM‐MSCs to differentiate into chondrocytes.
Omnivory of an Insular Lizard: Sources of Variation in the Diet of Podarcis lilfordi (Squamata, Lacertidae)

Through 17 years and from a sample of 7,790 faecal pellets and 26,346 prey items, we studied the diet of the Balearic lizard Podarcis lilfordi in Aire Island (Menorca, Balearic Islands, Spain). We analysed the diet in terms of prey frequencies, as well as by their volume and biomass contributions. The diet of the Balearic lizard was extremely variable through the years, months and areas under study. The dominance of small clumped prey, particularly ants, was confirmed. However, the main contribution by volume corresponded to beetles, with a relevant role for Diplopoda and terrestrial Isopoda during some months and at particular areas of the island. Several prey items were probably captured at the base of shrubs, under stones or inside rock crevices. Therefore, our estimations of electivity would only be reliable for epigeal and flying prey. The capacity of the Balearic lizard to include marine subsidies in its diet, such as coastal crustaceans, is noteworthy. Also, its consumption of carrion from carcasses of gulls and rabbits and leftovers from human visitors is remarkable. Juvenile conspecifics can also be a sporadic food resource, especially during the second half of summer, whereas the consumption of vegetal matter is constant for each whole year. The shifts of vegetal exploitation among areas of the island and months take place according to availability of different plant species at each area or during a given period. Thus, lizards are able to conduct a thorough monitoring of plant phenology, exploiting a large variety of plant species. Omnivory does not imply the indiscriminate inclusion of any edible food in its diet. Rather, the inclusion of several food items means the adoption of a wide range of foraging behaviours adapted to the exploitation of each food resource.
Alveolar Macrophages and Lung Dendritic Cells Sense RNA and Drive Mucosal IgA Responses

The mechanisms regulating systemic and mucosal IgA responses in the respiratory tract are incompletely understood. Using virus-like particles loaded with single-stranded RNA as a ligand for TLR7, we found that systemic vs mucosal IgA responses in mice were differently regulated. Systemic IgA responses following s.c. immunization were T cell independent and did not require TACI or TGFβ, whereas mucosal IgA production was dependent on Th cells, TACI, and TGFβ. Strikingly, both responses required TLR7 signaling, but systemic IgA depended upon TLR7 signaling directly to B cells whereas mucosal IgA required TLR7 signaling to lung dendritic cells and alveolar macrophages. Our data show that IgA switching is controlled differently according to the cell type receiving TLR signals. This knowledge should facilitate the development of IgA-inducing vaccines.
Mortality among substance-using mothers in California: a 10-year prospective study.

AIMS To examine mortality rates and causes of death among a cohort of substance-using mothers and to identify risk factors that predict mortality. DESIGN, SETTING, PARTICIPANTS This is a prospective study of a cohort of 4447 substance-using mothers (pregnant or parenting) who were enrolled during 2000-02 in 40 drug abuse treatment programs across California. METHODS All mothers were assessed at baseline using the Addiction Severity Index. Mortality data were obtained from the National Death Index and causes of death were coded using ICD-10. Standardized mortality ratios (SMR) were calculated relative to women in the general population adjusted for age. Proportional hazard (Cox) regression was used to identify risk factors predicting death. RESULTS At the end of 2010, 194 deaths were confirmed, corresponding to a crude mortality rate of 4.47 per 1000 person-years and SMR of 8.4 (95% confidence interval: 7.2-9.6). Drug overdose (28.8%), cardiovascular disease (10%), and alcohol or drug disorders (8.9%) were the leading causes of death. Baseline factors associated with higher mortality included older age, being white (relative to African American or Hispanic), heroin, alcohol, cocaine or marijuana (relative to methamphetamine) as the primary drug problem, drug injection and greater severity of employment, medical/health and psychiatric problems. CONCLUSIONS Substance-using mothers have 8.4 times the mortality than that observed among US women of similar age. Greater severity of employment, medical/health and psychiatric problems contributed to the elevated mortality.
Cystic artery: An anatomic morphological study and its clinical significance

Background Cystic artery is one of the arteries which is of utmost surgical importance, as it originates from the vast range of blood vessels, associated to the coeliac trunk and superior mesenteric artery and its relation to the biliary ducts is variable. Cystic artery is not only difficult to visualize, but difficult to approach during the surgery. This study was undertaken to study the anatomy of arterial variations of cystic artery in the specimens of liver and gallbladder by exploring the extrahepatic duct system, and in addition the relations of cystic artery in the Calot's triangle were also studied and observed. Materials and Methods The study was conducted on 50 human liver specimens with intact gallbladder and extrahepatic duct system, collected from the Department of Anatomy over a period of 5 years. The specimens obtained were fixed in 10% formalin and were finely dissected. The specimens were observed for parameters like the origin of the cystic artery, its length and diameter, mode and level of termination, relation to the Calot's triangle, and the extrahepatic duct system. Results Origin of the cystic artery was normal in 92% of cases and variations were seen in approximately 8% cases. The most common origin of the cystic artery was from the right hepatic artery, which was in 92% of the cases. In the present study, in 97% cases the cystic artery terminated by dividing into the superficial and deep branches. In the rest, the artery continued as a superficial branch, the deep branch being replaced by the accessory cystic artery. In 64% cases, the cystic artery was seen within the Calot's triangle, and in 36% of cases, it was outside the Calot's triangle. In 67% cases, the cystic artery was medial to the cystic duct, in approximately 63% cases the cystic artery was lateral to the common hepatic duct, and in 30% of the cases the cystic artery passed anterior to the cystic duct. Incidence of accessory cystic arteries in the present study was approximately 4%.
Temporomandibular disorders after whiplash injury: a controlled, prospective study.

AIMS Whiplash injury to the neck is often considered a significant risk factor for development of temporomandibular disorders (TMD), and has been proposed to produce internal derangements of the temporomandibular joint (TMJ). Few studies, however, have examined TMD-related pain in acute whiplash patients compared with a matched control group. The aim of the present study was to assess pain and sensorimotor function in the craniofacial region in an unselected group of patients sustaining a motor vehicle accident involving a rear collision. METHODS Prospectively, 19 acute whiplash patients exposed to a motor vehicle accident involving a rear collision participated in a study of TMD. The control group consisted of 20 age- and gender-matched ankle-injury patients. Participants were seen within 4 weeks and again at 6 months post-injury. The masticatory system was examined in accordance with the research diagnostic criteria. Participants underwent structured interviews, filled out the McGill Pain Questionnaire (MPQ), and had their masticatory system examined by a trained dentist, blinded to their diagnosis. Pain detection threshold (PDT) to pressure stimuli, and maximal voluntary occlusal force (MVOF) were obtained at each visit. RESULTS One whiplash patient and 1 ankle-injury patient had jaw pain at the first visit. Palpation scores of the TMJ and the summated palpation scores only tended to be higher in patients sustaining a whiplash injury than in ankle-injury controls at the first visit. However, MPQ, TMD symptoms and signs, MVOF and PDT were not significantly different in whiplash-injury and ankle-injury patients after 4 weeks and 6 months. CONCLUSION TMD pain after whiplash injury and ankle injury is rare, suggesting that whiplash injury is not a major risk factor for the development of TMD problems. Further studies are needed to identify which other factors may contribute to TMD pain.
Corporate governance structure and product market competition

Abstract This article assesses the effects of the competitive structure of a product market on a firm’s corporate governance structure. Our model demonstrates that shareholders strategically determine the corporate governance structure, including the manager’s stock ownership and his controlling power over the firm, in order to maximize their utility in the product market competition. We find that the manager’s stock ownership is lower and his controlling power over the firm is higher when the firm’s product is more profitable or when competition within the product market is more severe. The inefficiency of the wealth transfer from shareholders to the manager also affects the corporate governance structure.
New insights into the biology and ecology of the insect vectors of apple proliferation for the development of sustainable control strategies

Apple proliferation (AP) is a phytoplasma-caused disease widespread in many European regions, and represents a serious problem in Italian apple orchards. The etiological agent, ‘Candidatus Phytoplasma mali’, causes symptoms suggesting profound disorders in the normal balance of hormones in infected plants: witches’ brooms, enlarged stipules, early leaf reddening in autumn. The fruits of infected trees, which are smaller and have altered organoleptic properties, cannot be commercialized. Valsugana (Trentino, Italy), a representative applegrowing area with high incidence of AP, was chosen as model region to study and to monitor the evolution and spread of AP during three years. To reach this goal, the distribution of infected plants was mapped along the valley and the populations of the psyllid vectors (Cacopsylla picta and Cacopsylla melanoneura) were monitored. The final aims were drawing a picture of the disease spread to help advisors to optimize the current control strategies and to have the information necessary to correlate the presence of psyllid vectors and symptomatic trees, building new knowledge on their biology and ecology. To limit AP spread, a national strategy was established, in which uprooting of diseased trees and control of vector populations are compulsory. After a three-year survey, thanks to the phytosanitary measures adopted in the area, the percentage of apple plants drastically decreased. Regarding the psyllid vectors, C. melanoneura showed higher population levels compared to C. picta in both conventional and untreated orchards, but the percentages of infected individuals were higher in the latter species.
Performance analysis of broadcasting schemes in mobile ad hoc networks

Numerous broadcasting schemes have been proposed to alleviate the broadcast storm problem in high-density ad hoc networks. Little work has been done to model and analyze these schemes. We consider the popular counter-based and distance-based schemes in a unit-disk network model. Through the rigorous theoretic analysis, we achieve statistic results that reveal the relations between network parameters and the performance of these schemes. We also expect these results to be further useful to the development of mathematical models for other ad hoc broadcasting schemes.
A Satellite Assessment of Environmental Controls of Phytoplankton Community Size Structure

Phytoplankton play a key role as the base of the marine food web and a crucial component in the Earth's carbon cycle. There have been a few regional studies that have utilized satellite‐estimated phytoplankton functional type products in conjunction with other environmental metrics. Here we expand to a global perspective and ask, what are the physical drivers of phytoplankton composition variability? Using a variety of satellite‐observed ocean color products and physical properties spanning 1997–2015, we characterize spatial and temporal variability in phytoplankton community size structure in relation to satellite‐based physical drivers. We consider the relationships globally and by major thermal regimes (cold and warm), dominant size distribution, and chlorophyll concentration variability. Globally, euphotic depth is the most important parameter driving phytoplankton size variability and also over the majority of the high‐latitude ocean and the central gyres. In all other regions, size variability is driven by a balance of light and mode of nutrient delivery. We investigated the relationship between size composition and chlorophyll concentration and the physical drivers through correlation analysis. Changes in size composition over time are regionally varying and explained by temporal shifts in the varying physical conditions. These changes in phytoplankton size composition and the varying underlying physical drivers will ultimately impact carbon export and food web processes in our changing ocean.