Miracle-dz/UniFAR-FTUs huggingface dataset:
The full-length E6 protein of human papillomavirus type 16 has transforming and trans-activating activities and cooperates with E7 to immortalize keratinocytes in culture

The wild-type E6 and E7 genes of human papillomavirus type 16 (HPV16) can cooperate to immortalize normal human keratinocytes in culture. The E6 open reading frame of HPV16 and other HPV types highly associated with cervical cancer has the potential of encoding both full-length E6 and two truncated E6* proteins, the latter being generated via splicing within the E6 open reading frame portion of the E6-E7 polycistronic transcript. Those types, such as HPV6, that are infrequently associated with cervical carcinoma lack the splice site and encode only a full-length E6. We have now found that, in addition to cooperating with E7 to immortalize keratinocytes, HPV16 E6 can induce anchorage-independent growth in NIH 3T3 cells and trans-activate the adenovirus E2 promoter. HPV6 E6 was also able to trans-activate the adenovirus E2 promoter, although it was inactive in both cell transformation assays. An HPV16 splice site mutant which expressed only the full-length HPV16 E6 was active in all three assays, indicating that the E6* proteins are not required for these activities. The plasmid which encodes the E6* proteins was inactive and did not potentiate the activity of the HPV16 splice site mutant. The mutation that prevented splicing in E6-E7 mRNA severely reduced the level of E7 protein and increased E6 protein. Taken together, the results suggest that the primary function of the splice within E6 is to facilitate the translation of E7 and reduce translation of full-length E6, rather than to generate biologically active E6* proteins.
Living at the Physiological Limits: Field and Maximum Metabolic Rates of the Common Shrew (Sorex araneus)

Shrews (genus Sorex, small insectivorous mammals) are well known for their extremely high basal metabolic rates (BMRs) even when corrected for their small body size. We measured energy expenditure of the common shrew (Sorex araneus) under natural conditions (field metabolic rate [FMR]) by doubly labeled water method to test whether FMR is proportional to high BMR in this species. The study was performed in summer in northeastern Poland. In addition to the FMR, we also measured maximum metabolic rates induced by cold exposure and by intense activity (MMRCOLD and MMRRUN, respectively) to evaluate the aerobic reserve (MMR − FMR) in S. araneus. This aerobic reserve was used as an indicator of the potential for metabolic constraints. The FMR averaged 2.31 ± 0.32 L CO2 d−1 (±SD) or 58.1 ± 8.0 kJ d−1 in 8.2‐g animals. This figure constituted 216%–258% of a value predicted for a “standard” mammal of the same body mass and was the highest mass‐specific field metabolic rate in mammals. Because of the high BMR level in S. araneus, the FMR to BMR ratio (2.4) was not far off mammalian standards (median value of 3.1). The rate of water efflux determined in S. araneus (20.2 mL H2O d−1 or 2.46 mL H2O g−1 d−1) exceeded all figures reported to date in other mammals and was apparently linked to the high FMR level and relatively high water content of shrews’ food. Maximal metabolic rates (MMRRUN of 18.1 ± 1.6 mL O2 g−1 h−1 and MMRCOLD of 23.5 ± 1.9 mL O2 g−1 h−1) were not high in proportion to BMR or FMR that resulted in relatively narrow aerobic reserve in S. araneus: 20% when calculated against the MMRRUN and 39% when compared with the MMRCOLD. Our study reveals that S. araneus has high energy costs of living and operates close to its physiological limits.
Malicious Applications Detection by Analyzing Manifest Files

With the rapid rise in the use of Android worldwide, the harm done due to malicious applications is increasing exponentially. Due to this the data of the Android users is not secure, and we need a system to detect the maliciousness of the applications being downloaded. The project being developed here is a solution to this problem as it detects whether an application is malicious or benign, this will not only provide data security but will also enhance the performance of the user's device. There are a number of systems like DroidMat and signature-based systems, already available in the market that detect malicious applications. But these systems detect that on the base of signatures and by parsing smali files which not only increases the processing time but also does not provide accurate results. The proposed system here that is Malicious applications detection using permissions retrieval detects whether an application is malicious or not based on the keywords present in the manifest file. This method does not affect the performance of the device in any way and gives us better throughput.
Exports in the European Union sub-models. Determinants and performances

The aim of this paper is to identify the potential patterns within European Union submodels, knowing the social and economic performances that characterizes them. Also, based on an econometric model with panel data, covering the period of 2000 to 2013, we want to highlight the relation between sub-models’ exports competitiveness and their sensitivity to the fluctuations of several factors considered relevant in this study, such as: the share of tertiary education graduates, the unit labour cost and the investments.
Perceptions, Knowledge, and Satisfaction With Contralateral Prophylactic Mastectomy Among Young Women With Breast Cancer

UNLABELLED Chinese translation BACKGROUND Rates of contralateral prophylactic mastectomy (CPM) have increased dramatically, particularly among younger women with breast cancer, but little is known about how women approach the decision to have CPM. OBJECTIVE To examine preferences, knowledge, decision making, and experiences of young women with breast cancer who choose CPM. DESIGN Cross-sectional survey. SETTING 8 academic and community medical centers that enrolled 550 women diagnosed with breast cancer at age 40 years or younger between November 2006 and November 2010. PATIENTS 123 women without known bilateral breast cancer who reported having bilateral mastectomy. MEASUREMENTS A 1-time, 23-item survey that included items related to decision making, knowledge, risk perception, and breast cancer worry. RESULTS Most women indicated that desires to decrease their risk for contralateral breast cancer (98%) and improve survival (94%) were extremely or very important factors in their decision to have CPM. However, only 18% indicated that women with breast cancer who undergo CPM live longer than those who do not. BRCA1 or BRCA2 mutation carriers more accurately perceived their risk for contralateral breast cancer, whereas women without a known mutation substantially overestimated this risk. LIMITATIONS The survey, which was administered a median of 2 years after surgery, was not validated, and some questions might have been misinterpreted by respondents or subject to recall bias. Generalizability of the findings might be limited. CONCLUSION Despite knowing that CPM does not clearly improve survival, women who have the procedure do so, in part, to extend their lives. Many women overestimate their actual risk for cancer in the unaffected breast. Interventions aimed at improving risk communication in an effort to promote evidence-based decision making are warranted. PRIMARY FUNDING SOURCE Susan G. Komen for the Cure.
Bystander stimulation of activated CD4+ T cells of unrelated specificity following a booster vaccination with tetanus toxoid

Antigen‐specific CD4+ T cells are central to natural and vaccine‐induced immunity. An ongoing antigen‐specific T‐cell response can, however, influence surrounding T cells with unrelated antigen specificities. We previously observed this bystander effect in healthy human subjects following recall vaccination with tetanus toxoid (TT). Since this interplay could be important for maintenance of memory, we have moved to a mouse model for further analysis. We investigated whether boosting memory CD4+ T cells against TT in vivo would influence injected CD4+ TCR transgenic T cells (OT‐II) specific for an unrelated OVA peptide. If OT‐II cells were pre‐activated with OVA peptide in vitro, these cells showed a bystander proliferative response during the ongoing parallel TT‐specific response. Bystander proliferation was dependent on boosting of the TT‐specific memory response in the recipients, with no effect in naive mice. Bystander stimulation was also proportional to the strength of the TT‐specific memory T‐cell response. T cells activated in vitro displayed functional receptors for IL‐2 and IL‐7, suggesting these as potential mediators. This crosstalk between a stimulated CD4+ memory T‐cell response and CD4+ T cells activated by an unrelated antigen could be important in human subjects continually buffeted by environmental antigens.
Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer.

BACKGROUND Although tumor-infiltrating T cells have been documented in ovarian carcinoma, a clear association with clinical outcome has not been established. METHODS We performed immunohistochemical analysis of 186 frozen specimens from advanced-stage ovarian carcinomas to assess the distribution of tumor-infiltrating T cells and conducted outcome analyses. Molecular analyses were performed in some tumors by real-time polymerase chain reaction. RESULTS CD3+ tumor-infiltrating T cells were detected within tumor-cell islets (intratumoral T cells) in 102 of the 186 tumors (54.8 percent); they were undetectable in 72 tumors (38.7 percent); the remaining 12 tumors (6.5 percent) could not be evaluated. There were significant differences in the distributions of progression-free survival and overall survival according to the presence or absence of intratumoral T cells (P<0.001 for both comparisons). The five-year overall survival rate was 38.0 percent among patients whose tumors contained T cells and 4.5 percent among patients whose tumors contained no T cells in islets. Significant differences in the distributions of progression-free survival and overall survival according to the presence or absence of intratumoral T cells (P<0.001 for both comparisons) were also seen among 74 patients with a complete clinical response after debulking and platinum-based chemotherapy: the five-year overall survival rate was 73.9 percent among patients whose tumors contained T cells and 11.9 percent among patients whose tumors contained no T cells in islets. The presence of intratumoral T cells independently correlated with delayed recurrence or delayed death in multivariate analysis and was associated with increased expression of interferon-gamma, interleukin-2, and lymphocyte-attracting chemokines within the tumor. The absence of intratumoral T cells was associated with increased levels of vascular endothelial growth factor. CONCLUSIONS The presence of intratumoral T cells correlates with improved clinical outcome in advanced ovarian carcinoma.
Risk factors for depression among elderly community subjects: a systematic review and meta-analysis.

OBJECTIVE The goal of this study was to determine risk factors for depression among elderly community subjects. METHOD MEDLINE and PsycINFO were searched for potentially relevant articles published from January 1966 to June 2001 and from January 1967 to June 2001, respectively. The bibliographies of relevant articles were searched for additional references. Twenty studies met the following six inclusion criteria: original research reported in an English or French publication, study group of community residents, age of subjects 50 years or more, prospective study design, examination of at least one risk factor, and use of an acceptable definition of depression. The validity of studies was assessed according to the four primary criteria for risk factor studies described by the Evidence-Based Medicine Working Group. Information about group size at baseline and follow-up, age, proportion of men, depression criteria, exclusion criteria at baseline, length of follow-up, number of incident cases of depression, and risk factors was abstracted from each report. RESULTS Follow-up of the inception cohort was incomplete in most studies. In the qualitative meta-analysis, risk factors identified by both univariate and multivariate techniques in at least two studies each were disability, new medical illness, poor health status, prior depression, poor self-perceived health, and bereavement. In the quantitative meta-analysis, bereavement, sleep disturbance, disability, prior depression, and female gender were significant risk factors. CONCLUSIONS Despite the methodologic limitations of the studies and this meta-analysis, bereavement, sleep disturbance, disability, prior depression, and female gender appear to be important risk factors for depression among elderly community subjects.
Tolerance to COX‐2 inhibitors in children with hypersensitivity to nonsteroidal anti‐inflammatory drugs

Hypersensitivity to nonsteroidal anti‐inflammatory drugs (NSAIDs) can affect children, with the mechanism proposed being inhibition of the cyclooxygenase enzyme‐1 (COX‐1). In these patients nonchemically related NSAIDs, including COX‐2 inhibitors, can induce the reaction, hampering treatment of fever and inflammatory processes.
Increased Coral Larval Supply Enhances Recruitment for Coral and Fish Habitat Restoration

Loss of foundation reef-corals is eroding the viability of reef communities and ecosystem function in many regions globally. Coral populations are naturally resilient but when breeding corals decline, larval supply becomes limiting and natural recruitment is insufficient for maintaining or restoring depleted populations. Passive management approaches are important but in some regions they are proving inadequate for protecting reefs, therefore active additional intervention and effective coral restoration techniques are needed. Coral spawning events produce trillions of embryos that can be used for mass larval rearing and settlement on degraded but recoverable reef areas. We supplied 4.6 million Acropora tenuis larvae contained in fine mesh enclosures in situ on three degraded reef plots in the northwestern Philippines during a five day settlement period to initiate restoration. Initial mean larval settlement was very high (210.2 ± 86.4 spat per tile) on natural coral skeleton settlement tiles in the larval-enhanced plots, whereas no larvae settled on tiles in control plots. High mortality occurred during early post-settlement life stages as expected, however, juvenile coral survivorship stabilised once colonies had grown into visible-sized recruits on the reef by 10 months. Most recruits survived and grew rapidly, resulting in significantly increased rates of coral recruitment and density in larval-enhanced plots. After two years growth, mean colony size reached 11.1 ± 0.61 cm mean diameter, and colonies larger than 13 cm mean diameter were gravid and spawned, the fastest growth to reproductive size recorded for broadcast spawning corals. After three years, mean colony size reached 17 ± 1.7 cm mean diameter, with a mean density of 5.7 ± 1.25 colonies per m–2, and most colonies were sexually reproductive. Coral cover increased significantly in larval plots compared with control plots, primarily from A. tenuis recruitment and growth. Total production cost for each of the 220 colonies within the restored breeding population after three years was United States $17.80 per colony. A small but significant increase in fish abundance occurred in larval plots in 2018, with higher abundance of pomacentrids and corallivore chaetodontids coinciding with growth of A. tenuis colonies. In addition, innovative techniques for capturing coral spawn slicks and larval culture in pools in situ were successfully developed that can be scaled-up for mass production of larvae on reefs in future. These results confirm that enhancing larval supply significantly increases settlement and coral recruitment on reefs, enabling rapid re-establishment of breeding coral populations and enhancing fish abundance, even on degraded reef areas.
Cellular Origin(s) of Congenital Diaphragmatic Hernia

Congenital diaphragmatic hernia (CDH) is a structural birth defect characterized by a diaphragmatic defect, lung hypoplasia and structural vascular defects. In spite of recent developments, the pathogenesis of CDH is still poorly understood. CDH is a complex congenital disorder with multifactorial etiology consisting of genetic, cellular and mechanical factors. This review explores the cellular origin of CDH pathogenesis in the diaphragm and lungs and describes recent developments in basic and translational CDH research.
Direct synthesis of general Chebyshev bandpass filters with a frequency variant complex load

This paper presents a direct approach to the synthesis of a general Chebyshev coupled resonator filter with a frequency variant complex load. The new approach is based on the power wave renormalization of admittance parameters of a matched filter with a complex load to unitary load. When the port reference is changed from a complex load to a real load, a set of new expressions of admittance parameters can be obtained for the same filter. By introducing a piece of dispersive transmission line to the original matched filter, the poles of the original admittance parameters are retained, which greatly facilitates the extraction of the new admittance parameters, and consequently the synthesis of the coupling matrix. The approach is applicable to the synthesis of an optimal channel filter of a diplexer and a multiplexer, where the load presented at a port of the filter is a frequency variant complex load in a wide frequency range.
Effect of macrophage-derived mouse ApoE, human ApoE3-Leiden, and human ApoE2 (Arg158-->Cys) on cholesterol levels and atherosclerosis in ApoE-deficient mice.

The effect of monocyte/macrophage-derived wild-type mouse apolipoprotein E (apoE), human apoE3-Leiden, and human apoE2 on serum cholesterol levels and the development of atherosclerosis in apoE-deficient (apoe-/-) mice was investigated by using bone marrow transplantation (BMT). At 4 weeks after BMT, murine apoe+/+ bone marrow reduced serum cholesterol levels by 87% in apoe-/- mice, whereas macrophage-derived human apoE3-Leiden and human apoE2 induced a maximal, transient reduction of 35% and 48%, respectively. At 4 months after BMT, atherosclerosis was 23-fold (P<0.001) reduced in apoe+/+-->apoe-/- mice, whereas no significant reduction in apoE3-Leiden.apoe-/--->apoe-/- and apoE2.apoe-/--->apoe-/- mice could be demonstrated. A highly significant decrease in serum cholesterol levels (78% reduction) and atherosclerosis (21-fold, P<0. 001) was found in apoE3-Leiden.apoe-/- animals expressing high levels of apoE in multiple tissues, whereas apoE2 was ineffective even at high concentrations. Furthermore, in contrast to apoE-deficient macrophages, cholesterol efflux from apoE2 or apoE3-Leiden macrophages was not impaired. In conclusion, apoE3-Leiden as well as apoE2 are less effective in reducing cholesterol levels and atherosclerosis in apoe-/- animals, compared with apoe+/+, with apoE2<apoE3-Leiden<apoe+/+, irrespective of the observed adequate efflux of cholesterol from macrophages expressing apoE2 and apoE3-Leiden, indicating that normalization of cholesterol efflux by macrophages is not accompanied by measurable effects on lesion growth.
Evaluation of a Method for Determining Binaural Sensitivity to Temporal Fine Structure (TFS-AF Test) for Older Listeners With Normal and Impaired Low-Frequency Hearing

The ability to process binaural temporal fine structure (TFS) information was assessed using the TFS-AF test (where AF stands for adaptive frequency) for 26 listeners aged 60 years or more with normal or elevated low-frequency audiometric thresholds. The test estimates the highest frequency at which a fixed interaural phase difference (IPD) of ϕ (varied here between 30° and 180°) can be discriminated from an IPD of 0°, with higher thresholds indicating better performance. A sensation level of 30 dB was used. All listeners were able to perform the task reliably, giving thresholds well above the lowest allowed frequency of 30 Hz. The duration of a run averaged 5 min. Repeated testing of the normal-hearing listeners showed no significant practice effects. Thresholds varied markedly across listeners, but their ranking was fairly consistent across values of ϕ. Thresholds decreased (worsened) with decreasing ϕ and were lower than for a group of young listeners tested in an earlier study. There were weak to moderate, negative correlations between TFS-AF thresholds and audiometric thresholds at low frequencies (125–1000 Hz) but not at high frequencies (4000–8000 Hz). In conclusion, the TFS-AF test yielded a graded measure of binaural TFS sensitivity for all listeners. This contrasts with the TFS-LF (low-frequency) test, which measures the smallest detectable shift in IPD for a fixed frequency. The absence of practice effects and a reasonably short administration time make the TFS-AF test a good candidate for the assessment of sensitivity to changes in binaural TFS for older listeners without or with hearing loss.
Persistent Brain Abnormalities in Antiretroviral-Naive HIV Patients 3 Months after Haart

Background Proton magnetic resonance spectroscopy (1H-MRS) and neuropsychological tests may be useful for monitoring the effectiveness of highly active antiretroviral therapy (HAART) in HIV-associated brain injury. We aimed to evaluate whether brain abnormalities will improve 3 months after HAART. Method Thirty-three HIV patients naive to antiretroviral medications were evaluated before and 3 months after HAART using 1H-MRS and neuropsychological tests; results were compared with those of 26 seronegative control subjects. Results Despite significant improvement in CD4 counts, and suppression of plasma and cerebrospinal fluid (CSF) viral loads, elevated brain metabolites (choline compounds and myoinositol in the frontal lobes) and neuropsychological tests abnormalities (including the computerized tests [CalCAP®]) persisted after 3 months of HAART. In the basal ganglia, choline and myoinositol became elevated only after treatment. No interaction effect was observed between the number of CSF-penetrating drugs (one vs two) and changes (baseline vs 3 months) in any of the brain metabolites, cognitive performance or CSF viral load. Conclusions The persistent brain abnormalities suggest ongoing repair or reactive inflammatory processes in the brain after 3 months of HAART. Regimens with two CSF-penetrating antiretroviral medications do not appear to be more effective than those with one CSF-penetrating drug in treating HIV brain injury at 3 months.
Downregulation of connexin 26 in human lung cancer is related to promoter methylation

Cell‐Cell communication via gap junctions plays a key role in carcinogenesis and in growth control. One of the gap junction proteins, Connexin 26 (Cx26) was considered as tumor suppressor in various cancers. In our study, the expression of Cx26 was analyzed in human lung cancer. The reduced mRNA expression was observed in 17 lung cancer cell lines examined by Northern blot analysis and RT‐PCR. In 138 primary carcinomas comprising all subtypes analyzed by immunohistochemistry, 85 cases (62%) exhibited no expression of Cx26, whereas in other 53 cases the Cx26 staining was positive (38%). Additionally, an association between Cx26 protein expression and higher grading of tumors was found in whole tumor samples (p =0.028) but no statistically significant correlations could be observed with tumor stage, tumor size and node status. In squamous cell carcinoma, tumors with higher stage and grading were linked to higher expression of Cx26 (p = 0.015 and 0.017, respectively). To explore the mechanism responsible for the downregulation of Cx26, we treated 2 lung cancer cell lines H2170 and H226 with the demethylation agent 5‐aza‐2′‐deoxycytidine and found the reexpression of Cx26 mRNA. Methylation status of these 2 cell lines was further analyzed by PCR amplification of bisulfite modified DNA and sequencing. A heterogeneous methylation pattern turned out. Our results suggest the inactivation of Cx26 in lung cancer may be explained by promoter methylation.