Dynamics of an Intruder in Dense Granular Fluids

We investigate the dynamics of an intruder pulled by a constant force in a dense two-dimensional granular fluid by means of event-driven molecular dynamics simulations. In a first step, we show how a propagating momentum front develops and compactifies the system when reflected by the boundaries. To be closer to recent experiments \cite{candelier2010journey,candelier2009creep}, we then add a frictional force acting on each particle, proportional to the particle's velocity. We show how to implement frictional motion in an event-driven simulation. This allows us to carry out extensive numerical simulations aiming at the dependence of the intruder's velocity on packing fraction and pulling force. We identify a linear relation for small and a nonlinear regime for high pulling forces and investigate the dependence of these regimes on granular temperature

Reinforcement of poly-l-lactic acid electrospun membranes with strontium borosilicate bioactive glasses for bone tissue engineering

Herein, for the first time, we combined poly-l-lactic acid (PLLA) with a strontium borosilicate bioactive glass (BBG-Sr) using electrospinning to fabricate a composite bioactive PLLA membrane loaded with 10% (w/w) of BBG-Sr glass particles (PLLA-BBG-Sr). The composites were characterised by scanning electron microscopy (SEM) and microcomputer tomography (μ-CT), and the results showed that we successfully fabricated smooth and uniform fibres (1-3μm in width) with a homogeneous distribution of BBG-Sr microparticles (<45μm). Degradation studies (in phosphate buffered saline) demonstrated that the incorporation of BBG-Sr glass particles into the PLLA membranes increased their degradability and water uptake with a continuous release of cations. The addition of BBG-Sr glass particles enhanced the membrane's mechanical properties (69% higher Young modulus and 36% higher tensile strength). Furthermore, cellular in vitro evaluation using bone marrow-derived mesenchymal stem cells (BM-MSCs) demonstrated that PLLA-BBG-Sr membranes promoted the osteogenic differentiation of the cells as demonstrated by increased alkaline phosphatase activity and up-regulated osteogenic gene expression (Alpl, Sp7 and Bglap) in relation to PLLA alone. These results strongly suggest that the composite PLLA membranes reinforced with the BBG-Sr glass particles have potential as an effective biomaterial capable of promoting bone regeneration. STATEMENT OF SIGNIFICANCE: PLLA membranes were reinforced with 10% (w/w) of strontium-bioactive borosilicate glass microparticles, and their capacity to induce the osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) was evaluated. These membranes presented an increased: degradability, water uptake, Young modulus and tensile strength. We also demonstrated that these membranes are non-cytotoxic and promote the attachment of BM-MSCs. The addition of the glass microparticles into the PLLA membranes promoted the increase of ALP activity (under osteogenic conditions), as well as the BM-MSCs osteogenic differentiation as shown by the upregulation of Alpl, Sp7 and Bglap gene expression. Overall, we demonstrated that the reinforcement of PLLA with glass microparticles results in a biomaterial with the appropriate properties for the regeneration of bone tissue

CDM Accelerating Cosmology as an Alternative to LCDM model

A new accelerating cosmology driven only by baryons plus cold dark matter (CDM) is proposed in the framework of general relativity. In this model the present accelerating stage of the Universe is powered by the negative pressure describing the gravitationally-induced particle production of cold dark matter particles. This kind of scenario has only one free parameter and the differential equation governing the evolution of the scale factor is exactly the same of the $\Lambda$CDM model. For a spatially flat Universe, as predicted by inflation ($\Omega_{dm}+\Omega_{baryon}=1$), it is found that the effectively observed matter density parameter is $\Omega_{meff} = 1- \alpha$, where $\alpha$ is the constant parameter specifying the CDM particle creation rate. The supernovae test based on the Union data (2008) requires $\alpha\sim 0.71$ so that $\Omega_{meff} \sim 0.29$ as independently derived from weak gravitational lensing, the large scale structure and other complementary observations.Comment: 6 pages, 3 figure

Crossover and self-averaging in the two-dimensional site-diluted Ising model

Using the newly proposed probability-changing cluster (PCC) Monte Carlo algorithm, we simulate the two-dimensional (2D) site-diluted Ising model. Since we can tune the critical point of each random sample automatically with the PCC algorithm, we succeed in studying the sample-dependent $T_c(L)$ and the sample average of physical quantities at each $T_c(L)$ systematically. Using the finite-size scaling (FSS) analysis for $T_c(L)$, we discuss the importance of corrections to FSS both in the strong-dilution and weak-dilution regions. The critical phenomena of the 2D site-diluted Ising model are shown to be controlled by the pure fixed point. The crossover from the percolation fixed point to the pure Ising fixed point with the system size is explicitly demonstrated by the study of the Binder parameter. We also study the distribution of critical temperature $T_c(L)$. Its variance shows the power-law $L$ dependence, $L^{-n}$, and the estimate of the exponent $n$ is consistent with the prediction of Aharony and Harris [Phys. Rev. Lett. {\bf 77}, 3700 (1996)]. Calculating the relative variance of critical magnetization at the sample-dependent $T_c(L)$, we show that the 2D site-diluted Ising model exhibits weak self-averaging.Comment: 6 pages including 6 eps figures, RevTeX, to appear in Phys. Rev.

HER2-Enriched Subtype and ERBB2 Expression in HER2-Positive Breast Cancer Treated with Dual HER2 Blockade

Background: Identification of HER2-positive breast cancers with high anti-HER2 sensitivity could help de-escalate chemotherapy. Here, we tested a clinically applicable RNA-based assay that combines ERBB2 and the HER2-enriched (HER2-E) intrinsic subtype in HER2-positive disease treated with dual HER2-blockade without chemotherapy. Methods: A research-based PAM50 assay was applied in 422 HER2-positive tumors from five II-III clinical trials (SOLTI-PAMELA, TBCRC023, TBCRC006, PER-ELISA, EGF104090). In SOLTI-PAMELA, TBCRC023, TBCRC006, and PER-ELISA, all patients had early disease and were treated with neoadjuvant lapatinib or pertuzumab plus trastuzumab for 12-24 weeks. Primary outcome was pathological complete response (pCR). In EGF104900, 296 women with advanced disease were randomized to receive either lapatinib alone or lapatinib plus trastuzumab. Progression-free survival (PFS), overall response rate (ORR), and overall survival (OS) were evaluated. Results: A total of 305 patients with early and 117 patients with advanced HER2-positive disease were analyzed. In early disease, HER2-E represented 83.8% and 44.7% of ERBB2-high and ERBB2-low tumors, respectively. Following lapatinib and trastuzumab, the HER2-E and ERBB2 (HER2-E/ERBB2)-high group showed a higher pCR rate compared to the rest (44.5%, 95% confidence interval [CI] = 35.4% to 53.9% vs 11.6%, 95% CI = 6.9% to 18.0%; adjusted odds ratio [OR] = 6.05, 95% CI = 3.10 to 11.80, P <. 001). Similar findings were observed with neoadjuvant trastuzumab and pertuzumab (pCR rate of 66.7% in HER2-E/ERBB2-high, 95% CI = 22.3% to 95.7% vs 14.7% in others, 95% CI = 4.9% to 31.1%; adjusted OR = 11.60, 95% CI = 1.66 to 81.10, P =. 01). In the advanced setting, the HER2-E/ERBB2-high group was independently associated with longer PFS (hazard ratio [HR] = 0.52, 95% CI = 0.35 to 0.79, P <. 001); higher ORR (16.3%, 95% CI = 8.9% to 26.2% vs 3.7%, 95% CI = 0.8% to 10.3%, P =. 02); and longer OS (HR = 0.66, 95% CI = 0.44 to 0.97, P =. 01). Conclusions: Combining HER2-E subtype and ERBB2 mRNA into a single assay identifies tumors with high responsiveness to HER2-targeted therapy. This biomarker could help de-escalate chemotherapy in approximately 40% of patients with HER2-positive breast cancer

Measurement of the D+ and Ds+ decays into K+K-K+

We present the first clear observation of the doubly Cabibbo suppressed decay D+ --> K-K+K+ and the first observation of the singly Cabibbo suppressed decay Ds+ --> K-K+K+. These signals have been obtained by analyzing the high statistics sample of photoproduced charm particles of the FOCUS(E831) experiment at Fermilab. We measure the following relative branching ratios: Gamma(D+ --> K-K+K+)/Gamma(D+ --> K-pi+pi+) = (9.49 +/- 2.17(statistical) +/- 0.22(systematic))x10^-4 and Gamma(Ds+ --> K-K+K+)/Gamma(Ds+ --> K-K+pi+) = (8.95 +/- 2.12(statistical) +2.24(syst.) -2.31(syst.))x10^-3.Comment: 10 pages, 8 figure

A Non-parametric Approach to the D+ to K*0bar mu+ nu Form Factors

Using a large sample of D+ -> K- pi+ mu+ nu decays collected by the FOCUS photoproduction experiment at Fermilab, we present the first measurements of the helicity basis form factors free from the assumption of spectroscopic pole dominance. We also present the first information on the form factor that controls the s-wave interference discussed in a previous paper by the FOCUS collaboration. We find reasonable agreement with the usual assumption of spectroscopic pole dominance and measured form factor ratios.Comment: 14 pages, 5 figures, and 2 tables. We updated the previous version by changing some words, removing one plot, and adding two tables. These changes are mostly stylisti

Search for Λc+→pK+π−\Lambda_c^+ \to p K^+ \pi^- and Ds+→K+K+π−D_s^+ \to K^+ K^+ \pi^- Using Genetic Programming Event Selection

We apply a genetic programming technique to search for the double Cabibbo suppressed decays $\Lambda_c^+ \to p K^+ \pi^-$ and $D_s^+ \to K^+ K^+ \pi^-$. We normalize these decays to their Cabibbo favored partners and find $\text{BR}($\Lambda_c^+ \to p K^+ \pi^-$)/\text{BR}($\Lambda_c^+ \to p K^- \pi^+$) = (0.05 \pm 0.26 \pm 0.02)$ and $\text{BR}($D_s^+ \to K^+ K^+ \pi^-$)/\text{BR}($D_s^+ \to K^+ K^- \pi^+$) = (0.52\pm 0.17\pm 0.11)$ where the first errors are statistical and the second are systematic. Expressed as 90% confidence levels (CL), we find $< 0.46$ and $< 0.78$ respectively. This is the first successful use of genetic programming in a high energy physics data analysis.Comment: 10 page

Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group

Next-generation sequencing (NGS) allows sequencing of a high number of nucleotides in a short time frame at an affordable cost. While this technology has been widely implemented, there are no recommendations from scientific societies about its use in oncology practice. The European Society for Medical Oncology (ESMO) is proposing three levels of recommendations for the use of NGS. Based on the current evidence, ESMO recommends routine use of NGS on tumour samples in advanced non-squamous non-small-cell lung cancer (NSCLC), prostate cancers, ovarian cancers and cholangiocarcinoma. In these tumours, large multigene panels could be used if they add acceptable extra cost compared with small panels. In colon cancers, NGS could be an alternative to PCR. In addition, based on the KN158 trial and considering that patients with endometrial and small-cell lung cancers should have broad access to anti-programmed cell death 1 (anti-PD1) antibodies, it is recommended to test tumour mutational burden (TMB) in cervical cancers, well- and moderately-differentiated neuroendocrine tumours, salivary cancers, thyroid cancers and vulvar cancers, as TMB-high predicted response to pembrolizumab in these cancers. Outside the indications of multigene panels, and considering that the use of large panels of genes could lead to few clinically meaningful responders, ESMO acknowledges that a patient and a doctor could decide together to order a large panel of genes, pending no extra cost for the public health care system and if the patient is informed about the low likelihood of benefit. ESMO recommends that the use of off-label drugs matched to genomics is done only if an access programme and a procedure of decision has been developed at the national or regional level. Finally, ESMO recommends that clinical research centres develop multigene sequencing as a tool to screen patients eligible for clinical trials and to accelerate drug development, and prospectively capture the data that could further inform how to optimise the use of this technology

Measurement of the relative branching ratio BR(\Xi_c^+ \to p^+ K^-\pi^+)\BR(\Xi_c^+ \to \Xi^- \pi^+ \pi^+)

We report the observation of the Cabibbo suppressed decay \Xi_c^+ \to p K^-\pi^+ using data collected with the FOCUS spectrometer during the 1996--97 Fermilab fixed target run. We find a \Xi_c^+ signal peak of 202\pm35 events. We have measured the relative branching ratios BR(\Xi^+_c\to p K^-\pi^+)/BR(\Xi^+_c\to\Xi^-\pi^+\pi^+)= 0.234 \pm 0.047 \pm 0.022 and BR(\Xi^+_c\to p \bar{K}^*(892)^0)/BR(\Xi^+_c\to p K^-\pi^+)= 0.54 \pm 0.09 \pm 0.05 .Comment: 9 pages, 4 figure