Miracle-dz/UniFAR-FTUs huggingface dataset:
Promoter Methylation of BRCA1, DAPK1 and RASSF1A is Associated with Increased Mortality among Indian Women with Breast Cancer

Background: Promoter methylation has been observed for several genes in association with cancer development and progression. Hypermethylation mediated-silencing of tumor suppressor genes (TSGs) may contribute to breast cancer pathogenesis. The present study was conducted to investigate the promoter methylation status of BRCA1, DAPK1 and RASSF1A genes in Indian women with breast cancer. Materials and Methods: Promoter methylation was evaluated in DNA extracted from mononuclear cells (MNCs) in peripheral blood samples of 60 histopathologically confirmed newly diagnosed, untreated cases of breast cancer as well as 60 age and sex matched healthy controls using MS-PCR. Association of promoter methylation with breast cancer-specific mortality was analyzed with Cox proportional hazards models. Kaplan-Meier survival analysis was performed for overall survival of the breast cancer patients. Results: We observed a significant increase of BRCA1, DAPK1 and RASSF1A promoter methylation levels by 51.7% (P <0.001), 55.0% (P <0.001) and 46.6% (P <0.001), respectively, when compared to healthy controls. A strong correlation was noted between hypermethylation of the tumor suppressor genes BRCA1 (P= 0.009), DAPK1 (P= 0.008) and RASSF1A (P= 0.02)) with early and advanced stages of breast cancer patients. We also found that breast cancer-specific mortality was significantly associated with promoter methylation of BRCA1 [HR and 95%CI:3.25 (1.448-7.317)] and DAPK1 [HR and 95%CI:2.32 (1.05-5.11)], whereas limited significant link was evident with RASSF1A [HR and 95%CI:1.54 (0.697-3.413]. Conclusion: Our results suggest that promoter methylation of BRCA1, DAPK1 and RASSF1A genes may be associated with disease progression and poor overall survival of Indian women with breast cancer.
Energy storage management for EV charging stations: Comparison between uncoordinated and statistical charging loads

Electricity price is essential factor in the deployment of electric vehicles (EVs) on large scale. In wholesale electricity market, EV charging stations(ECS) connected with suitably sized energy storage system (ESS) can save substantial amount of money by managing their time of utilisation (TOU). In this study, a real-time EV charging model at ECS along with ESS degradation model is considered to analyse effect of the ESS for TOU pricing benefits. The objective is to minimize the EVs charging cost. The proposed algorithm focuses on real-time energy management using combination of heuristic approach and deterministic approach. The algorithm analyses electricity pricing trend using historical and forecasted statistical data and controls the power imported from the grid, while feeding dynamic EV charging load. Significant amount of cost saving is seen in results due to deployment of ESS in utilizing TOU pricing benefits of wholesale electricity price.
Seed Production Affects Maternal Growth and Senescence in Arabidopsis1[OPEN]

Seed production in the monocarpic plant Arabidopsis thaliana promotes shoot senescence and suppresses shoot growth, affecting similar processes as apical dominance does. Correlative control (influence of one organ over another organ) of seeds over maternal growth is one of the most obvious phenotypic expressions of the trade-off between growth and reproduction. However, the underlying molecular mechanisms are largely unknown. Here, we characterize the physiological and molecular effects of correlative inhibition by seeds on Arabidopsis (Arabidopsis thaliana) inflorescences, i.e. global proliferative arrest (GPA) during which all maternal growth ceases upon the production of a given number of seeds. We observed transcriptional responses to growth- and branching-inhibitory hormones, and low mitotic activity in meristems upon GPA, but found that meristems retain their identity and proliferative potential. In shoot tissues, we detected the induction of stress- and senescence-related gene expression upon fruit production and GPA, and a drop in chlorophyll levels, suggestive of altered source-sink relationships between vegetative shoot and reproductive tissues. Levels of shoot reactive oxygen species, however, strongly decreased upon GPA, a phenomenon that is associated with bud dormancy in some perennials. Indeed, gene expression changes in arrested apical inflorescences after fruit removal resembled changes observed in axillary buds following release from apical dominance. This suggests that GPA represents a form of bud dormancy, and that dominance is gradually transferred from growing inflorescences to maturing seeds, allowing offspring control over maternal resources, simultaneously restricting offspring number. This would provide a mechanistic explanation for the constraint between offspring quality and quantity.
Interspecies diversity of chloride channel regulators, calcium-activated 3 genes

Members of the chloride channel regulators, calcium-activated (CLCA) family, have been implicated in diverse biomedical conditions, including chronic inflammatory airway diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis, the activation of macrophages, and the growth and metastatic spread of tumor cells. Several observations, however, could not be repeated across species boundaries and increasing evidence suggests that select CLCA genes are particularly prone to dynamic species-specific evolvements. Here, we systematically characterized structural and expressional differences of the CLCA3 gene across mammalian species, revealing a spectrum of gene duplications, e.g., in mice and cows, and of gene silencing via diverse chromosomal modifications in pigs and many primates, including humans. In contrast, expression of a canonical CLCA3 protein from a single functional gene seems to be evolutionarily retained in carnivores, rabbits, guinea pigs, and horses. As an accepted asthma model, we chose the cat to establish the tissue and cellular expression pattern of the CLCA3 protein which was primarily found in mucin-producing cells of the respiratory tract and in stratified epithelia of the esophagus. Our results suggest that, among developmental differences in other CLCA genes, the CLCA3 gene possesses a particularly high dynamic evolutionary diversity with pivotal consequences for humans and other primates that seem to lack a CLCA3 protein. Our data also help to explain previous contradictory results on CLCA3 obtained from different species and warrant caution in extrapolating data from animal models in conditions where CLCA3 may be involved.
miR-202 inhibits the progression of human cervical cancer through inhibition of cyclin D1

The human cervical cancer (CC) acts as the most common one of women tumors. However, the pathological changes and molecular alterations of CC are not clear. It has been reported that miR-202 takes part in the development and progression of different tumors. The present study aims to detect the expression of miR-202 in 100 cases of CC tissues and cells, and then we continued to investigate the potential mechanisms of miR-202 in CC cells. In this work, we found that the expression of miR-202 is obviously decreased in both CC cell lines and tissues, and negatively related with the expression of cyclin D1 in SiHa, HeLa and Caski cells. In-vitro assay revealed that the ectopic expression of miR-202 suppressed the proliferation, migration and invasion of SiHa and HeLa cells. Additionally, the over-expression of miR-202 extremely affected the expression of cyclin D1 protein. Notably, the over-expression of cyclin D1 in SiHa and HeLa cells with miR-202 mimics attenuated the inhibitory effects of miR-202 on cell proliferation, migration and invasion. In conclusion, our study identified that miR-202 plays an important role in regulating cell proliferation, migration and invasion of CC by directly targeting cyclin D1, thus miR-202 may represent a potential therapeutic target for patients with cervical cancer.
Co-existence of BRAF and NRAS driver mutations in the same melanoma cells results in heterogeneity of targeted therapy resistance

Acquired chemotherapeutic resistance of cancer cells can result from a Darwinistic evolution process in which heterogeneity plays an important role. In order to understand the impact of genetic heterogeneity on acquired resistance and second line therapy selection in metastatic melanoma, we sequenced the exomes of 27 lesions which were collected from 3 metastatic melanoma patients treated with targeted or non-targeted inhibitors. Furthermore, we tested the impact of a second NRAS mutation in 7 BRAF inhibitor resistant early passage cell cultures on the selection of second line therapies. We observed a rapid monophyletic evolution of melanoma subpopulations in response to targeted therapy that was not observed in non-targeted therapy. We observed the acquisition of NRAS mutations in the BRAF mutated patient treated with a BRAF inhibitor in 1 of 5 of his post-resistant samples. In an additional cohort of 5 BRAF-inhibitor treated patients we detected 7 NRAS mutations in 18 post-resistant samples. No NRAS mutations were detected in pre-resistant samples. By sequencing 65 single cell clones we prove that NRAS mutations co-occur with BRAF mutations in single cells. The double mutated cells revealed a heterogeneous response to MEK, ERK, PI3K, AKT and multi RTK - inhibitors. We conclude that BRAF and NRAS co-mutations are not mutually exclusive. However, the sole finding of double mutated cells in a resistant tumor is not sufficient to determine follow-up therapy. In order to target the large pool of heterogeneous cells in a patient, we think combinational therapy targeting different pathways will be necessary.
Study of association between pre-senile cataracts and rs11615 of ERCC1, rs13181 of ERCC2, and rs25487 of XRCC1 polymorphisms in a Spanish population

ABSTRACT Background: The purpose of this study was to attempt to determine if the presence of certain polymorphisms in the DNA repair genes (ERCC1, ERCC2, and XRCC1) is associated with pre-senile cataract development. Materials and methods: We performed a retrospective study over three groups of patients. The first group with pre-senile cataract was formed by 72 patients younger than 55 years with cataract surgery. The second group with senile cataract was formed by 101 patients older than 55 years with cataract surgery. And the third group, without cataract, was formed by 42 subjects older than 55 years without lens opacities. We analyzed the presence of SNP rs11615 from ERCC1, rs13181 from ERCC2, and rs25487 from XRCC1 and the relationship between risk factors such as smoking, alcohol intake, hypertension, and diabetes. Results: The comparison of the genotype distribution in ERCC1 and ERCC2 did not show any statistically significant association in any of our analyses (p > 0.05). The comparison of the genotype distribution in XRCC1 within the different groups did not show any statistically significant associations (p > 0.05), except for the comparison between the pre-senile cataract group and the group without cataract, where an increased risk of developing pre-senile cataract for the genotype Gln/Gln (p = 0.029; OR = 1.02–40.67) in recessive inheritance models was observed when adjusting for risk factors. Conclusions: Allelic variants in ERCC1 and ERCC2 are not associated with an increased risk of developing pre-senile cataract. The presence of Gln/Gln in XRCC1 in the pre-senile cataract group with regard to the group without cataract is associated with a major risk of developing pre-senile cataract.
Multigene phylogeny reveals eusociality evolved twice in vespid wasps

Eusocial wasps of the family Vespidae are thought to have derived their social behavior from a common ancestor that had a rudimentary caste-containing social system. In support of this behavioral scenario, the leading phylogenetic hypothesis of Vespidae places the eusocial wasps (subfamilies Stenogastrinae, Polistinae, and Vespinae) as a derived monophyletic clade, thus implying a single origin of eusocial behavior. This perspective has shaped the investigation and interpretation of vespid social evolution for more than two decades. Here we report a phylogeny of Vespidae based on data from four nuclear gene fragments (18S and 28S ribosomal DNA, abdominal-A and RNA polymerase II) and representatives from all six extant subfamilies. In contrast to the current phylogenetic perspective, our results indicate two independent origins of vespid eusociality, once in the clade Polistinae+Vespinae and once in the Stenogastrinae. The stenogastrines appear as an early diverging clade distantly related to the vespines and polistines and thus evolved their distinctive form of social behavior from a different ancestor than that of Polistinae+Vespinae. These results support earlier views based on life history and behavior and have important implications for interpreting transitional stages in vespid social evolution.
The Anomalous Influence of Spectral Resolution on Pulsed THz Time Domain Spectroscopy under Real Conditions

We have studied the spectral resolution influence on the accuracy of the substance detection and identification at using a broadband THz pulse measured under real conditions (at a distance of more than 3 m from a THz emitter in ambient air with a relative humidity of about 50%). We show that increasing spectral resolution leads to manifestation of small-scale perturbations (random fluctuations) in the signal spectrum caused by the influence of the environment or the sample structure. Decreasing the spectral resolution allows us to exclude from consideration this small-scale modulation of the signal as well as to detect the water vapor absorption frequencies. This fact is important in practice because it allows us to increase the signal processing rate. In order to increase the detection reliability, it is advisable to decrease the spectral resolution up to values of not more than 40% of the corresponding spectral line bandwidth. The method of spectral dynamics analysis together with the integral correlation criteria is used for the substance detection and identification. Neutral substances such as chocolate and cookies are used as the samples in the physical experiment.
Multi-template homology-based structural model of L-2-haloacid dehalogenase (DehL) from Rhizobium sp. RC1

Dehalogenases are of high interest due to their potential applications in bioremediation and in synthesis of various industrial products. DehL is an L-2-haloacid dehalogenase (EC 3.8.1.2) that catalyses the cleavage of halide ion from L-2-halocarboxylic acid to produce D-2-hydroxycarboxylic acid. Although DehL utilises the same substrates as the other L-2-haloacid dehalogenases, its deduced amino acid sequence is substantially different (<25%) from those of the rest L-2-haloacid dehalogenases. To date, the 3D structure of DehL is not available. This limits the detailed understanding of the enzyme’s reaction mechanism. The present work predicted the first homology-based model of DehL and defined its active site. The monomeric unit of the DehL constitutes α/β structure that is organised into two distinct structural domains: main and subdomains. Despite the sequence disparity between the DehL and other L-2-haloacid dehalogenases, its structural model share similar fold as the experimentally solved L-DEX and DehlB structures. The findings of the present work will play a crucial role in elucidating the molecular details of the DehL functional mechanism.
Recent Improvement in the Long-term Survival of Breast Cancer Patients by Age and Stage in Japan

Background Recent improvements in 5-year survival of breast cancer have been reported in Japan and other countries. Though the number of long-term breast cancer survivors has been increasing, recent improvements in 10-year survival have not been reported. Moreover, the degree of improvement according to age and disease stage remains unclear. Methods We calculated long-term survival using data on breast cancer diagnosed from 1993 through 2006 from six prefectural population-based cancer registries in Japan. The recent increase in 10-year relative survival was assessed by comparing the results of period analysis in 2002–2006 with the results of cohort analysis in 1993–1997. We also conducted stratified analyses by age group (15–34, 35–49, 50–69, and 70–99 years) and disease stage (localized, regional, and distant). Results A total of 63,348 patients were analysed. Ten-year relative survival improved by 2.4% (76.9% vs 79.3%) from 1993 through 2006. By age and stage, 10-year relative survival clearly improved in the age 35–49 years (+2.9%; 78.1% vs 81.0%), 50–69 years (+2.8%; 75.2% vs 78.0%) and regional disease (+3.4%; 64.9% vs 68.3%). In contrast, the degree of improvement was small in the age 15–34 years (+0.1%; 68.2% vs 68.3%), 70–99 years (+1.0%; 87.6% vs 88.6%), localized disease (+1.1%; 92.6% vs 93.7%) and distant metastasis (+0.9%; 13.8% vs 14.7%). Conclusions These population-based cancer registry data show that 10-year relative survival improved 2.4% over this period in Japan. By age and stage, improvement in the age 15–34 years and distant metastasis was very small, which suggests the need for new therapeutic strategies in these patients.
Perceptions of Coronary Heart Disease Risk in African American Women With Type 2 Diabetes

Purpose The purpose of this study was to explore the perceptions of coronary heart disease (CHD) risk in a group of southern African American women with type 2 diabetes (T2DM). Methods Semistructured interviews were conducted in participants’ homes or setting of choice. The interviews were conducted with 6 participants from a larger study of 48 women who were stratified into levels of low, medium, and high perception of CHD risk, with 2 participants in each group. The interviews were analyzed using NVivo software; both investigators recoded and analyzed the data. Results African American women with T2DM do not believe they are at risk for CHD unless they are told specifically by their primary health care provider that they have heart disease. The African American women in the study expressed that managing their diabetes to prevent heart disease can be overwhelming. Participants identified faith beliefs called not claiming the illness as a reason they did not perceive themselves at risk for CHD. Conclusions Not claiming an illness may influence health and preventive behaviors. Many African American women with T2DM may not claim their illness. Diabetes educators should acknowledge and address women’s beliefs to create an appropriate plan of care.
Encapsulated galanin‐producing cells attenuate focal epileptic seizures in the hippocampus

Encapsulated cell biodelivery (ECB) is a relatively safe approach, since the devices can be removed in the event of adverse effects. The main objectives of the present study were to evaluate whether ECB could be a viable alternative of cell therapy for epilepsy. We therefore developed a human cell line producing galanin, a neuropeptide that has been shown to exert inhibitory effects on seizures, most likely acting via decreasing glutamate release from excitatory synapses. To explore whether ECB of genetically modified galanin‐producing human cell line could provide seizure‐suppressant effects, and test possible translational prospect for clinical application, we implanted ECB devices bilaterally into the hippocampus of rats subjected to rapid kindling, a model for recurrent temporal lobe seizures.
Emotion and vantage point in autobiographical memory

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The consequences of ignoring measurement invariance for path coefficients in structural equation models

We report a Monte Carlo study examining the effects of two strategies for handling measurement non-invariance – modeling and ignoring non-invariant items – on structural regression coefficients between latent variables measured with item response theory models for categorical indicators. These strategies were examined across four levels and three types of non-invariance – non-invariant loadings, non-invariant thresholds, and combined non-invariance on loadings and thresholds – in simple, partial, mediated and moderated regression models where the non-invariant latent variable occupied predictor, mediator, and criterion positions in the structural regression models. When non-invariance is ignored in the latent predictor, the focal group regression parameters are biased in the opposite direction to the difference in loadings and thresholds relative to the referent group (i.e., lower loadings and thresholds for the focal group lead to overestimated regression parameters). With criterion non-invariance, the focal group regression parameters are biased in the same direction as the difference in loadings and thresholds relative to the referent group. While unacceptable levels of parameter bias were confined to the focal group, bias occurred at considerably lower levels of ignored non-invariance than was previously recognized in referent and focal groups.
Reliability potential of silicone molding compounds for LED application

As the development of light emitting devices (LEDs), integrate circuits (ICs) and concentration photovoltaic (CPV) modules towards higher density, packaging materials are facing the challenges of withstand with heat generation and high energy. Epoxy molding compound (EMC) is the latest technology for LED and solar cell package to replace PPA and PCT. However, it is well known that the thermal and radiation resistance of epoxy is limited. Recently, silicone based composites are attracting attention as ideal materials because they are insensible to high energy density and good resistance to UV light and heat. Epoxy and silicone both have reliability issues during long-term service at high temperature and high energy. Thermal and radiation degradation of reflector materials will largely affect their reflectance and their contribution to a higher light output and energy efficiency. Therefore, it is very essential to evaluate reliability performance of SMC and EMC based reflecting materials. Aging under multip.