Miracle-dz/UniFAR-FTUs huggingface dataset:
MAP-mediated nuclear delivery of a cargo protein

Radiolabeled cytochrome c (Cyt c), either as a free protein or as cell penetrating peptide (CPP)-conjugates, was tested for cellular uptake and nuclear transport in Human embryonic kidney293 (HEK293) cells and HeLa cells. Conjugation of Cyt c with either the amphipathic peptide model amphipathic peptide (MAP) or the cationic peptide oligoarginine via a disulfide linkage significantly increased the total internalization and nuclear localization of Cyt c in both cell lines, though to a greater extent following conjugation with MAP. The nuclear localization was also evaluated qualitatively by confocal laser scanning microscopy (CLSM). CLSM images depicted high amounts of colocalization of fluorescently labeled Cyt c-MAP and the nucleus in HEK293 cells. In addition, prevention of disulfide reduction at the cell surface, or comparison of reducible disulfide or non-reducible thioether MAP-conjugates, showed that maintenance of an intact conjugate using a stable linkage enhanced MAP-mediated nuclear delivery. Furthermore, nuclear transport of the MAP-cargo conjugate appears to be dependent on vesicle fusion events following internalization via endocytosis. The findings presented in this report demonstrate the MAP-mediated transport of a small protein such as Cyt c into the nuclear compartment, which can be used to improve current CPP-cargo delivery of macromolecules with nuclear biological functions.
Geographic Variation in Cardiovascular Inflammation among Healthy Women in the Women's Health Study

Background Geographic variation in traditional cardiovascular disease (CVD) risk factors has been observed among women in the US. It is not known whether state-level variation in cardiovascular inflammation exists or could be explained by traditional clinical risk factors and behavioral lifestyle factors. Methods and Results We used multilevel linear regression to estimate state-level variation in inflammatory biomarker patterns adjusted for clinical and lifestyle characteristics among 26,029 women free of CVD. Participants derived from the Women's Health Study, a national cohort of healthy middle-aged and older women. Inflammatory biomarker patterns (plasma levels of high-sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (sICAM-1), and fibrinogen) were compared to state-level patterns of traditional CVD risk factors and global risk scores. We found that all three inflammatory biomarkers exhibited significant state-level variation including hsCRP (lowest vs. highest state median 1.3 mg/L vs. 2.7 mg/L, unadjusted random effect estimate 1st to 99th percentile range for log hsCRP 0.52, p<.001), sICAM-1 (325 ng/ml vs. 366ng/ml, unadjusted random effect estimate 1st to 99th percentile range 0.44, p<.001), and fibrinogen (322 mg/dL vs. 367 mg/dL, unadjusted random effect estimate 1st to 99th percentile range 0.41, p = .001). Neither demographic, clinical or lifestyle characteristics explained away state-level effects in biomarker patterns. Southern and Appalachian states (Arkansas, West Virginia) had the highest inflammatory biomarker values. Regional geographic patterns of traditional CVD risk factors and risk scores did not completely overlap with biomarkers of inflammation. Conclusions There is state-level geographic variation in inflammatory biomarkers among otherwise healthy women that cannot be completely attributed to traditional clinical risk factors or lifestyle characteristics. Future research should aim to identify additional factors that may explain geographic variation in biomarkers of inflammation among healthy women.
Interferon-: A Key Factor in Autoimmune Disease ?

METHODS. Eleven patients with refractory uveitis, and 13 healthy individuals were enrolled. The number of circulating plasmacytoid dendritic cells (pDCs) and their capacity to produce IFNin culture on stimulation with synthetic oligodinucleotides containing the CpG-motif were studied. Peripheral blood CD4 T-cell phenotype and activation status were evaluated by flow cytometry at 0, 2, and 8 weeks after treatment for expression of CD69, CD62L, chemokine receptors (CCR4, CXCR3, and CCR5), and intracellular cytokines (TNF, IFN, and IL-10).
The evolution of the G matrix: selection or drift?

The evolution of quantitative characters can be described by the equation Δ[zmacr ]=GP−1S where Δ[zmacr ] is the vector of mean responses, G is the matrix of additive genetic variances and covariances, P is the matrix of phenotypic variances and covariances and S is the vector of selection differentials. This equation can be used to predict changes in trait values or to retrospectively estimate the selection gradient and is thus a central equation of evolutionary quantitative genetics. Genetic variances and covariances will be reduced by stabilizing selection, directional selection and drift, and increased by mutation. Changes in trait values resulting from directional selection that are comparable with differences observed among species are readily obtainable in short geological time spans (<5000 generations) with selection intensities so small that they would have an insignificant effect on the G matrix (of course it is possible that such changes came about by strong selection over a few generations, followed by long periods of stasis; there is insufficient evidence to presently distinguish these two possibilities). On the other hand, observed effective population sizes are sufficiently small that considerable changes in G can be expected from drift alone. The action of drift can be distinguished from selection because the former produces a proportional change in G whereas the latter, in general, will not. A survey of studies examining variation in G suggests that the null hypothesis that most of the variation can be attributed to drift rather than selection cannot be rejected. However, more research on the predicted statistical distribution of G as a result of selection and/or drift is required and further development of statistical tests to distinguish these two forces needs to be made.
Evaluating Second Generation Open Government Data Infrastructures Using Value Models

Recently, a second generation of advanced open government data (OGD) infrastructures has emerged, influenced by the principles of the Web 2.0 paradigm, and oriented towards the elimination of the clear distinction between providers and consumers of such data, and the support of data 'pro-sumers'. This paper presents and validates a methodology for evaluating these advanced second generation of ODG infrastructures, which is based on the estimation of value models of them from users' ratings. This value model includes assessments of the various types of value generated by such an infrastructure, and also of the relations among them as well. This enables a deeper understanding of the whole value generation mechanism and a rational definition of improvement priorities. The proposed methodology has been used for the evaluation of an advanced second generation ODG e-Infrastructure developed in the European project ENGAGE.
Ultrasound assessment of lung aeration loss during a successful weaning trial predicts postextubation distress*

Objective:Postextubation distress after a successful spontaneous breathing trial is associated with increased morbidity and mortality. Predicting postextubation distress is therefore a major issue in critically ill patients. To assess whether lung derecruitment during spontaneous breathing trial assessed by lung ultrasound is predictive of postextubation distress. Design and Setting:Prospective study in two multidisciplinary intensive care units within University Hospital. Patients and Methods:One hundred patients were included in the study. Lung ultrasound, echocardiography, and plasma B-type natriuretic peptide levels were determined before and at the end of a 60-min spontaneous breathing trial and 4 hrs after extubation. To quantify lung aeration, a lung ultrasound score was calculated. Patients were followed up to hospital discharge. Measurements and Main Results:Fourteen patients failed the spontaneous breathing trial, 86 were extubated, 57 were definitively weaned (group 1), and 29 suffered from postextubation distress (group 2). Loss of lung aeration during the successful spontaneous breathing trial was observed only in group 2 patients: lung ultrasound scores increased from 15 [13;17] to 19 [16; 21] (p < .01). End-spontaneous breathing trial lung ultrasound scores were significantly higher in group 2 than in group 1 patients: 19 [16;21] vs. 10 [7;13], respectively (p < .001) and predicted postextubation distress with an area under the receiver operating characteristic curve of 0.86. Although significantly higher in group 2, B-type natriuretic peptide and echocardiography cardiac filling pressures were not clinically helpful in predicting postextubation distress. Conclusion:Lung ultrasound determination of aeration changes during a successful spontaneous breathing trial may accurately predict postextubation distress.
Biomarkers of Dose and Effect of Inhaled Ozone in Resting versus Exercising Human Subjects: Comparison with Resting Rats

To determine the influence of exercise on pulmonary dose of inhaled pollutants, we compared biomarkers of inhaled ozone (O3) dose and toxic effect between exercise levels in humans, and between humans and rats. Resting human subjects were exposed to labeled O3 (18O3, 0.4 ppm, for 2 hours) and alveolar O3 dose measured as the concentration of excess 18O in cells and extracellular material of nasal, bronchial, and bronchoalveolar lavage fluid (BALF). We related O3 dose to effects (changes in BALF protein, LDH, IL-6, and antioxidant substances) measurable in the BALF. A parallel study of resting subjects examined lung function (FEV1) changes following O3. Subjects exposed while resting had 18O concentrations in BALF cells that were 1/5th of those of exercising subjects and directly proportional to the amount of O3 breathed during exposure. Quantitative measures of alveolar O3 dose and toxicity that were observed previously in exercising subjects were greatly reduced or non-observable in O3 exposed resting subjects. Resting rats and resting humans were found to have a similar alveolar O3 dose.
Attachment-related mental representations: introduction to the special issue

Bowlby's concept of mental working models of self, attachment figures, and the social world has been theoretically generative as a bridge between early relational experience and the beliefs and expectations that color later relationships. Contemporary attachment researchers, following his example, are applying new knowledge of children's conceptual development to their study of attachment-related mental representations in children and adults. The contributors to this special issue highlight recent advances in how the mental representations arising from attachment security should be conceptualized and studied, and identify a number of important directions for future work. This paper introduces the special issue by summarizing the major ideas of Bowlby and his followers concerning the nature and development of mental working models, points of theoretical clarity and uncertainty, and challenges in assessing these representations, as well as profiling each of the contributions to this issue.
Topological Entropy of Braids on the Torus

We present a fast method for computing the topological entropy of braids on the torus. This work is motivated by the need to analyze large braids when studying two‐dimensional flows via the braiding of a large number of particle trajectories. Our approach is a generalization of Moussafir’s technique for braids on the disk. Previous methods for computing topological entropy include the Bestvina–Handel train‐track algorithm and matrix representations of the braid group. However, the Bestvina–Handel algorithm is computationally intractable for large braid words, and matrix methods give only lower bounds, which are often poor for large braids. Our method is computationally fast and gives exponential convergence towards the exact entropy. As an illustration we apply our approach to the braiding of both periodic and aperiodic trajectories in the sine flow.
Racial differences in androgen receptor protein expression in men with clinically localized prostate cancer.

PURPOSE Black American men experience disproportionate mortality from prostate cancer (CaP) compared with white American men. Differences in outcome may stem from differences within the androgen axis. Since serum testosterone levels appear to be similar by race in men with CaP, we measured and compared androgen receptor (AR) protein expression in malignant and benign prostate tissue from black and white men who underwent radical prostatectomy for clinically localized CaP. MATERIALS AND METHODS Archived radical prostatectomy specimens obtained from 25 white and 25 black men had AR protein antigen retrieved and immunostained. AR protein expression from CaP and benign tissue was assessed by 2 methods. Automated digital color video image analysis was used to measure the percent area immunostained for AR protein and the intensity of expression (mean optical density). Visual scoring was performed to compare results with automated values. RESULTS In black compared with white men malignant nuclei were 27% more likely to immunostain for AR (p = 0.005) and in immunopositive nuclei AR protein expression was 81% greater (p = 0.002). Visual scoring of malignant nuclei revealed that AR immunostaining was significantly increased in black vs white men (171 +/- 40 vs 149 +/- 37, p = 0.048). In immunopositive benign nuclei AR protein expression was 22% greater in black than in white men (p = 0.027). Visual scoring of benign nuclei revealed 20% increased immunostaining in black vs white men, although this difference did not attain statistical significance (p = 0.065). Racial differences in AR protein expression were not explained by age, pathological grade or stage, although serum prostate specific antigen levels were higher in black men (9.7 +/- 7.5 vs 15.5 +/- 12.2 ng/ml, p = 0.049). CONCLUSIONS AR protein expression was 22% higher in the benign prostate and 81% higher in the CaP of black African compared with white men. CaP may occur at a younger age and progress more rapidly in black than in white men due to racial differences in androgenic stimulation of the prostate.
Clinical Relevance of Classification According to Weaning Difficulty

OBJECTIVE: To evaluate the clinical relevance of the weaning from mechanical ventilation classification system derived from the 2005 international consensus conference, in patients who receive mechanical ventilation for more than 48 hours, and evaluate its correlation with prognosis. METHODS: We conducted a retrospective cohort study in a 12-bed intensive care unit (ICU) in a teaching hospital. We included patients who required > 48 hours of mechanical ventilation and who passed a spontaneous breathing trial (SBT). Weaning and sedation were monitored according to standardized protocol-directed procedures. We collected data on physiological characteristics, mechanical ventilation duration, ICU and hospital stay, and mortality from the medical records database. We assessed one-year mortality with a prospective, standardized method. Multivariate logistic regression was performed to evaluate the association between weaning categories and outcome. RESULTS: We included 329 ventilation episodes, in which 115 patients passed at least one SBT. Thirty-four patients (30%) succeeded in their first SBT (simple weaning group), 47 patients (40%) succeeded in their 2nd or 3rd SBT or in less than 7 days of weaning (the difficult weaning group), and 34 patients (30%) required more than 3 SBTs or more than 7 days of weaning (the prolonged weaning group). There were significant differences in ICU and hospital mortality between the simple, difficult, and prolonged-weaning groups. Prolonged weaning was an independent risk factor for longer ICU stay (odds ratio 15.11, 95% CI 1.61–141.91, P = .01) and hospital mortality (odds ratio 3.66, 95% CI 0.99–13.51). However, the weaning process did not impact one-year mortality (odds ratio 2.61, 95% CI 0.82–8.35). CONCLUSIONS: The new weaning classification system is clinically relevant and correlates to ICU and hospital mortality, but not to one-year mortality.
Prostaglandins and sepsis: still a fascinating topic despite almost 40 years of research.

northover and subramanian([31][1]) reported in 1962 that treating dogs with aspirin, a prototypical nonsteroidal anti-inflammatory drug (NSAID), ameliorated the development of arterial hypotension after the injection of lipopolysaccharide (LPS). Subsequent to this early report, many other
High-Brightness Quantum Well Tapered Lasers

High-power quantum well lasers with high brightness in the spectral range between 650 nm and 1080 nm will be presented. Improved layer structures with a narrow vertical far-field divergence down to angles of 15deg (full-width at half-maximum) were developed. For these layer structures, optimized tapered lasers were processed to achieve laterally a nearly diffraction-limited beam quality with beam propagation factors smaller than 2. Depending on the emission wavelength, the tapered devices reach an output power up to 12 W and a brightness of 1 GWmiddotcm-2middotsr-1.
Two Structural Results for Low Degree Polynomials and Applications

In this paper, two structural results concerning low degree polynomials over finite fields are given. The first states that over any finite field F, for any polynomial f on n variables with degree d > log(n)/10, there exists a subspace of F^n with dimension at least d n^(1/(d-1)) on which f is constant. This result is shown to be tight. Stated differently, a degree d polynomial cannot compute an affine disperser for dimension smaller than the stated dimension. Using a recursive argument, we obtain our second structural result, showing that any degree d polynomial f induces a partition of F^n to affine subspaces of dimension n^(1/(d-1)! ), such that f is constant on each part. We extend both structural results to more than one polynomial. We further prove an analog of the first structural result to sparse polynomials (with no restriction on the degree) and to functions that are close to low degree polynomials. We also consider the algorithmic aspect of the two structural results. Our structural results have various applications, two of which are: * Dvir [CC 2012] introduced the notion of extractors for varieties, and gave explicit constructions of such extractors over large fields. We show that over any finite field any affine extractor is also an extractor for varieties with related parameters. Our reduction also holds for dispersers, and we conclude that Shaltiel's affine disperser [FOCS 2011] is a disperser for varieties over the binary field. * Ben-Sasson and Kopparty [SIAM J. C 2012] proved that any degree 3 affine disperser over a prime field is also an affine extractor with related parameters. Using our structural results, and based on the work of Kaufman and Lovett [FOCS 2008] and Haramaty and Shpilka [STOC 2010], we generalize this result to any constant degree.
The aging HIV/AIDS population: Fragile social networks

Social support becomes an increasingly critical resource for people as they age. In New York City, 25% of all people living with HIV/AIDS are over age 50, and 64% are over age 40. This study sample (n = 160) reflects current HIV/AIDS epidemiology, with 34% females and 89% people of color. This study provides a detailed profile of this growing, aging cohort and their social networks. Our study finds this growing group of aging adults is isolated from informal networks due to the stigma of HIV/AIDS and ageism. Typically, partners and family members are key sources of informal support, but only 1/3 of respondents had a partner and 71% lived alone. This group relies heavily on friends, many of whom are also HIV-positive. Participants were in primary care and many (86%) utilized Medicaid. The fragile networks of these older adults will be challenged by age-related comorbidities. Without traditional caregivers, these aging adults with HIV/AIDS will have an immense impact on healthcare delivery and community-based programs.
Population and seasonal distribution of Procamallanus daccai in Eutropiichthys vacha in Kaptai Lake, Chittagong, Bangladesh

Abstract The population and seasonal distribution of Procamallanus daccai (Nematoda: Procamallanidae) in Eutropiichthys vacha (Siluridae) from the Kaptai Lake were studied for a period of 20 months during 1986–1987. A total of 208 fish were necropsied and 5652 worms were recovered, of which 2392 were from 87 infected male fish and 3260 were from 89 infected female fish. Prevalence values varied from 50% to 95%. The intensity and abundance of nematodes fluctuated over the study period and are statistically significant (F=14.87, P<0.0001), and showed a seasonal preference for the summer period (F=33.39, P<0.05). The mean intensity was the highest in the smallest size group at 66.3±12.7 which gradually decreased to 4±1.89 in the largest size group. No significant differences were found between parasites from male and female hosts, except in the summer. Male parasites were less abundant in the population. Female worms were grouped into immature, maturing and gravid and all these stages were present throughout the year. The highest occurrence of both immature and gravid P. daccai was found during the months of February to April each year. Peak recruitment seems to occur during this period due to the presence of high quantities of immature worms.
Diagnostic Power of Optic Disc Morphology, Peripapillary Retinal Nerve Fiber Layer Thickness, and Macular Inner Retinal Layer Thickness in Glaucoma Diagnosis With Fourier-domain Optical Coherence Tomography

PurposeTo evaluate the capability of the optic disc, peripapillary retinal nerve fiber layer (P-RNFL), macular inner retinal layer (M-IRL) parameters, and their combination obtained by Fourier-domain optical coherent tomography (OCT) in differentiating a glaucoma suspect from perimetric glaucoma. MethodsTwo hundred and twenty eyes from 220 patients were enrolled in this study. The optic disc morphology, P-RNFL, and M-IRL were assessed by the Fourier-domain OCT (RTVue OCT, Model RT100, Optovue, Fremont, CA). A linear discriminant function was generated by stepwise linear discriminant analysis on the basis of OCT parameters and demographic factors. The diagnostic power of these parameters was evaluated with receiver operating characteristic (ROC) curve analysis. The diagnostic power in the clinically relevant range (specificity ≥80%) was presented as the partial area under the ROC curve (partial AROC). ResultsThe individual OCT parameter with the largest AROC and partial AROC in the high specificity (≥80%) range were cup/disc vertical ratio (AROC=0.854 and partial AROC=0.142) for the optic disc parameters, average thickness (AROC=0.919 and partial AROC=0.147) for P-RNFL parameters, inferior hemisphere thickness (AROC=0.871 and partial AROC=0.138) for M-IRL parameters, respectively. The linear discriminant function further enhanced the ability in detecting perimetric glaucoma (AROC=0.970 and partial AROC=0.172). ConclusionsAverage P-RNFL thickness is the optimal individual OCT parameter to detect perimetric glaucoma. Simultaneous evaluation on disc morphology, P-RNFL, and M-IRL thickness can improve the diagnostic accuracy in diagnosing glaucoma.