The microscopic environment inside a metazoan organism is highly crowded. Whether individual cells can tailor their behavior to the limited space remains unclear. In this study, we found that cells ...measure the degree of spatial confinement by using their largest and stiffest organelle, the nucleus. Cell confinement below a resting nucleus size deforms the nucleus, which expands and stretches its envelope. This activates signaling to the actomyosin cortex via nuclear envelope stretch-sensitive proteins, up-regulating cell contractility. We established that the tailored contractile response constitutes a nuclear ruler-based signaling pathway involved in migratory cell behaviors. Cells rely on the nuclear ruler to modulate the motive force that enables their passage through restrictive pores in complex three-dimensional environments, a process relevant to cancer cell invasion, immune responses, and embryonic development.
Yebes 40m radio telescope is the main and largest observing instrument at Yebes Observatory and it is devoted to Very Long Baseline Interferometry (VLBI) and single dish observations since 2010. It ...has been covering frequency bands between 2 GHz and 90 GHz in discontinuous and narrow windows in most of the cases, to match the current needs of the European VLBI Network (EVN) and the Global Millimeter VLBI Array (GMVA).
Nanocosmos project, a European Union funded synergy grant, opened the possibility to increase the instantaneous frequency coverage to observe many molecular transitions with single tunnings in single dish mode. This reduces the observing time and maximises the output from the telescope.
We present the technical specifications of the recently installed 31.5 - 50GHz (Q band) and 72 - 90.5 GHz (W band) receivers along with the main characteristics of the telescope at these frequency ranges. We have observed IRC+10216, CRL 2688 and CRL 618, which harbour a rich molecular chemistry, to demonstrate the capabilities of the new instrumentation for spectral observations in single dish mode.
The results show the high sensitivity of the telescope in the Q band. The spectrum of IRC+10126 offers a signal to noise ratio never seen before for this source in this band. On the other hand, the spectrum normalised by the continuum flux towards CRL 618 in the W band demonstrates that the 40 m radio telescope produces comparable results to those from the IRAM 30 m radio telescope, although with a smaller sensitivity. The new receivers fulfil one of the main goals of Nanocosmos and open the possibility to study the spectrum of different astrophysical media with unprecedented sensitivity.
To examine the associations of physical fitness (i.e. cardiorespiratory fitness, muscular strength, and speed/agility) with psychological distress and psychological well-being in overweight/obese ...pre-adolescent children.
110 overweight/obese children (10.0±1.1years old, 61 boys) from the ActiveBrains project (http://profith.ugr.es/activebrains) participated in this cross-sectional study.
Physical fitness was evaluated by the ALPHA battery test. Cardiorespiratory fitness was additionally evaluated by a maximal incremental treadmill. Stress was assessed by the Children’s Daily Stress Inventory, anxiety by the State-Trait Anxiety Inventory, depression by the Children Depression Inventory, positive affect and negative affect by the Positive and Negative Affect Scale for Children, happiness by the Subjective Happiness Scale, optimism by the Life Orientation Test, and self-esteem by the Rosenberg Self-Esteem questionnaire. Linear regression adjusted for sex and peak height velocity was used to examine associations.
Absolute upper-body muscular strength was negatively associated with stress and negative affect (β=−0.246, p=0.047; β=−0.329, p=0.010, respectively). Furthermore, absolute lower-body muscular strength was negatively associated with negative affect (β=−0.301, p=0.029). Cardiorespiratory fitness, expressed by the last completed lap, and relative upper-body muscular strength were positively associated with optimism (β=0.220, p=0.042; β=0.240, p=0.017, respectively). Finally, absolute upper-body muscular strength was positively associated with self-esteem (β=0.362, p=0.003) independently of sex and weight status (p for interactions >0.3), and absolute lower-body muscular strength was also positively associated with self-esteem (β=0.352, p=0.008).
Muscular strength was associated with psychological distress (i.e. stress and negative affect) and psychological well-being (i.e. optimism and self-esteem) as well as cardiorespiratory fitness was associated with optimism. Therefore, increased levels of physical fitness, specifically muscular strength, could have significant benefits for overweight/obese children psychological health.
Abstract Background Retrospective analyses were performed in patients with metastatic renal cell carcinoma (mRCC) to characterise the objective response (OR) rate to sunitinib and differentiate ...pretreatment features and outcomes of patients with early (response by ⩽12 weeks) versus late response, and responders versus non-responders. Methods Data were pooled from 1059 patients in six trials. Median progression-free survival (PFS) and overall survival (OS) were estimated by Brookmeyer and Crowley method and compared between groups by log-rank test. Baseline characteristics were compared by Fisher-exact, t -, or Wilcoxon rank-sum tests. Associations between characteristics and survival were investigated by Cox proportional regression analysis. Results 398 patients (38%) had confirmed OR (12 complete responses); 26%, 61%, 79% and 86% responded by 6, 12, 18 and 24 weeks, respectively. Median (range) time to tumour response (TTR) was 10.6 (2.7–94.4) weeks and was similar in treatment-naïve and cytokine-refractory patients. Median response duration in early and late responders was 52.0 and 55.0 weeks, respectively. Median PFS in early versus late responders was 13.8 versus 20.2 months ( P = 0.001); however, median OS did not significantly differ (37.8 versus 40.8 months; P = 0.144). Early responders had more lung metastases ( P < 0.01), but baseline characteristics were otherwise mostly similar. Median PFS (16.3 versus 5.3 months) and OS (40.1 versus 14.5 months) were longer in responders versus non-responders (both P < 0.001); responders had more favourable prognostic factors. Conclusions OR occurred in 38% of sunitinib-treated mRCC patients. Sixty-one percent of responses occurred by 12 weeks of therapy, and responders had favourable pretreatment features and significantly longer survival.
Abstract
In light of the growing interest in the Hayward black hole solution, a detailed study on the corresponding lapse function and its roots is presented. The lapse function is expressed in terms ...of the classical Schwarzschild radius
r
s
and the Hayward’s parameter
l
. Both of these quantities are used as thermodynamic variables to find related thermodynamic quantities. In this context, the variable
l
is associated with a canonical conjugate variable
F
H
, and a free energy Ξ. Moreover, a second order phase transition is found to appears at
l
≈ 0.333
r
s
.
The motion of massless particles on the background of a toroidal topological black hole is analyzed in the context of conformal Weyl gravity. Null geodesics, in terms of the Jacobi elliptic ...functions, are found analytically. In addition, the Sagnac effect in this space-time is characterized, and we find a strong condition in the theory’s parameters that is required for its existence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified ...exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data.
PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W for 24 months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9 weeks, survival every 2 months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) ≥50% and ≥1%; pembrolizumab doses were pooled in this analysis.
At date cut-off of 24 March 2017, median follow-up was 31 months (range 23–41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 95% confidence interval (CI): 0.57, 0.77. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS ≥50%. For TPS ≥50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS ≥1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS ≥50%, PFS HRs were similar across archival 0.63 (95% CI: 0.45, 0.89) and newly collected samples 0.53 (95% CI: 0.38, 0.72). In patients with TPS ≥1%, PFS HRs were similar across archival 0.82 (95% CI: 0.66, 1.02) and newly collected samples 0.83 (95% CI: 0.68, 1.02).
Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples.
ClinicalTrials.gov: NCT01905657.
We report direct-detection constraints on light dark matter particles interacting with electrons. The results are based on a method that exploits the extremely low levels of leakage current of the ...DAMIC detector at SNOLAB of 2–6×10−22 A cm−2. We evaluate the charge distribution of pixels that collect <10e− for contributions beyond the leakage current that may be attributed to dark matter interactions. Constraints are placed on so-far unexplored parameter space for dark matter masses between 0.6 and 100 MeV c−2. We also present new constraints on hidden-photon dark matter with masses in the range 1.2–30 eV c−2.
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease. HCM is a highly complex and heterogeneous disease regarding not only the number of associated mutations but also ...the severity of phenotype, symptom burden, and the risk of complications, such as heart failure and sudden death. The penetrance is incomplete and it is age and gender dependent. It is accepted as a disease of the sarcomere. Sixty percent of HCM cases carry mutations in 1 of 8 sarcomere protein genes, mainly non‐sense MYBPC3 and missense MYH7 variants. Young patients with severe phenotype and other clinical features are included in proposed scores for prediction of high positive genetic result. The number of genes reported as disease‐causing has increased in the last few years, in some cases without robust evidence. Currently available in silico tools are not always useful for differentiation between benign and deleterious variants. There is enough information on genotype‐phenotype correlations to start understanding the mechanisms of the disease. Genetic and environmental modifiers have been explored with some interesting insights from miRNA studies with potential as biomarkers and therapeutic agents. There is an additional value of genetic testing in HCM for prognosis. Knowledge about genetics and functional studies are the basis of near future therapies.
Submicron aerosol was analyzed during the MILAGRO field campaign in March 2006 at the T0 urban supersite in Mexico City with a High-Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS) ...and complementary instrumentation. Mass concentrations, diurnal cycles, and size distributions of inorganic and organic species are similar to results from the CENICA supersite in April 2003 with organic aerosol (OA) comprising about half of the fine PM mass. Positive Matrix Factorization (PMF) analysis of the high resolution OA spectra identified three major components: chemically-reduced urban primary emissions (hydrocarbon-like OA, HOA), oxygenated OA (OOA, mostly secondary OA or SOA), and biomass burning OA (BBOA) that correlates with levoglucosan and acetonitrile. BBOA includes several very large plumes from regional fires and likely also some refuse burning. A fourth OA component is a small local nitrogen-containing reduced OA component (LOA) which accounts for 9% of the OA mass but one third of the organic nitrogen, likely as amines. OOA accounts for almost half of the OA on average, consistent with previous observations. OA apportionment results from PMF-AMS are compared to the PM2.5 chemical mass balance of organic molecular markers (CMB-OMM, from GC/MS analysis of filters). Results from both methods are overall consistent. Both assign the major components of OA to primary urban, biomass burning/woodsmoke, and secondary sources at similar magnitudes. The 2006 Mexico City emissions inventory underestimates the urban primary PM2.5 emissions by a factor of ~4, and it is ~16 times lower than afternoon concentrations when secondary species are included. Additionally, the forest fire contribution is at least an order-of-magnitude larger than in the inventory.
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