Optimal softening for force calculations in collisionless N-body simulations

In N-body simulations the force calculated between particles representing a given mass distribution is usually softened, to diminish the effect of graininess. In this paper we study the effect of such a smoothing, with the aim of finding an optimal value of the softening parameter. As already shown by Merritt (1996), for too small a softening the estimates of the forces will be too noisy, while for too large a softening the force estimates are systematically misrepresented. In between there is an optimal softening, for which the forces in the configuration approach best the true forces. The value of this optimal softening depends both on the mass distribution and on the number of particles used to represent it. For higher number of particles the optimal softening is smaller. More concentrated mass distributions necessitate smaller softening, but the softened forces are never as good an approximation of the true forces as for not centrally concentrated configurations. We give good estimates of the optimal softening for homogeneous spheres, Plummer spheres, and Dehnen spheres. We also give a rough estimate of this quantity for other mass distributions, based on the harmonic mean distance to the $k$th neighbour ($k$ = 1, .., 12), the mean being taken over all particles in the configuration. Comparing homogeneous Ferrers ellipsoids of different shapes we show that the axial ratios do not influence the value of the optimal softening. Finally we compare two different types of softening, a spline softening (Hernquist & Katz 1989) and a generalisation of the standard Plummer softening to higher values of the exponent. We find that the spline softening fares roughly as well as the higher powers of the power-law softening and both give a better representation of the forces than the standard Plummer softening.Comment: 16 pages Latex, 19 figures, accepted for publication in MNRAS, corrected typos, minor changes mainly in sec.

Identification of meat spoilage gene biomarkers in Pseudomonas putida using gene profiling

While current food science research mainly focuses on microbial changes in food products that lead to foodborne illnesses, meat spoilage remains as an unsolved problem for the meat industry. This can result in important economic losses, food waste and loss of consumer confidence in the meat market. Gram-negative bacteria involved in meat spoilage are aerobes or facultative anaerobes. These represent the group with the greatest meat spoilage potential, where Pseudomonas tend to dominate the microbial consortium under refrigeration and aerobic conditions. Identifying stress response genes under different environmental conditions can help researchers gain an understanding of how Pseudomonas adapts to current packaging and storage conditions. We examined the gene expression profile of Pseudomonas putida KT2440, which plays an important role in the spoilage of meat products. Gene expression profiles were evaluated to select the most differentially expressed genes at different temperatures (30 °C and 10 °C) and decreasing glucose concentrations, in order to identify key genes actively involved with the spoilage process. A total of 739 and 1269 were found to be differentially expressed at 30 °C and 10 °C respectively; of which 430 and 568 genes were overexpressed, and 309 and 701 genes were repressed at 30 °C and 10 °C respectively

Novel approaches for food safety management and communication

The current safety and quality controls in the food chain are lacking or inadequately applied and fail to prevent microbial and/or chemical contamination of food products, which leads to reduced confidence among consumers. On the other hand to meet market demands food business operators (producers, retailers, resellers) and regulators need to develop and apply structured quality and safety assurance systems based on thorough risk analysis and prevention, through monitoring, recording and controlling of critical parameters covering the entire product's life cycle. However the production, supply, and processing sectors of the food chain are fragmented and this lack of cohesion results in a failure to adopt new and innovative technologies, products and processes. The potential of using information technologies, for example, data storage, communication, cloud, in tandem with data science, for example, data mining, pattern recognition, uncertainty modelling, artificial intelligence, etc., through the whole food chain including processing within the food industry, retailers and even consumers, will provide stakeholders with novel tools regarding the implementation of a more efficient food safety management system

Journey of Trail From Bench to Bedside and Its Potential Role in Immuno-Oncology

Induction of apoptosis in cancer cells has increasingly been the focus of many therapeutic approaches in oncology field. Since its identification as a TNF family member, TRAIL (TNF-related apoptosis-inducing ligand) paved a new path in apoptosis inducing cancer therapies. Its selective ability to activate extrinsic and intrinsic cell death pathways in cancer cells only, independently from p53 mutations responsible for conventional therapeutics resistance, spotted TRAIL as a potent cancer apoptotic agent. Many recombinant preparations of TRAIL and death receptor targeting monoclonal antibodies have been developed and being tested pre-clinically and clinically both as a single agent and in combinations. Of note, the monoclonal antibodies were not the only type of antibodies developed to target TRAIL receptors. Recent technology has brought forth several single chain variable domains (scFv) designs fused recombinantly to TRAIL as well. Also, it is becoming progressively more understandable that field of nanotechnology has revolutionized cancer diagnosis and therapy. The recent breakthroughs in materials science and protein engineering have helped considerably in strategically loading drugs into nanoparticles or conjugating drugs to their surface. In this review we aim to comprehensively highlight the molecular knowledge of TRAIL in the context of its pathway, receptors and resistance factors. We also aim to review the clinical trials that have been done using TRAIL based therapies and to review various scFv designs, the arsenal of nano-carriers and molecules available to selectively target tumor cells with TRAIL

Biochar-based wastewater treatment to combat antimicrobial resistance

Antimicrobial resistance (AMR) is driven in part by environmental reservoirs of antimicrobial-resistant organisms and genes, as well as antimicrobials themselves, which drive resistance via selective pressure. According to the UN, 80% of all wastewater flows into the environment untreated. When wastewater is treated, treatment plants can act as hotspots of horizontal gene transfer from resistant to non-resistant organisms. There is therefore an urgent need to filter wastewater from sources rich in resistant bacteria and antimicrobials, like hospitals and pharmaceutical plants, before they reach environmental reservoirs where resistance can spread. Biochars produced from waste lignocellulosic biomass are ideal for this purpose, as they are highly adsorbent, affordable, and sustainable, with morphologies and surface chemistries that are tunable by choice of production conditions. Here, we link peak pyrolysis temperatures and alkaline pretreatment of walnut shell biochars to their filtration performance, showing these materials are suitable for in-line filtration of wastewater to combat AMR

Role of Nanotechnology and Gene Delivery Systems in TRAIL-Based Therapies

Since its identification as a member of the tumour necrosis factor (TNF) family, TRAIL (TNF-related apoptosis-inducing ligand) has emerged as a new avenue in apoptosis-inducing cancer therapies. Its ability to circumvent the chemoresistance of conventional therapeutics and to interact with cancer stem cells (CSCs) self-renewal pathways, amplified its potential as a cancer apoptotic agent. Many recombinant preparations of this death ligand and monoclonal antibodies targeting its death receptors have been tested in monotherapy and combinational clinical trials. Gene therapy is a new approach for cancer treatment which implies viral or non-viral functional transgene induction of apoptosis in cancer cells or repair of the underlying genetic abnormality on a molecular level. The role of this approach in overcoming the traditional barriers of radiation and chemotherapeutics systemic toxicity, risk of recurrence, and metastasis made it a promising platform for cancer treatment. The recent first Food Drug Administration (FDA) approved oncolytic herpes virus for melanoma treatment brings forth the potency of the cancer gene therapy approach in the future. Many gene delivery systems have been studied for intratumoural TRAIL gene delivery alone or in combination with chemotherapeutic agents to produce synergistic cancer cytotoxicity. However, there still remain many obstacles to be conquered for this different gene delivery systems. Nanomedicine on the other hand offers a new frontier for clinical trials and biomedical research. The FDA approved nanodrugs motivates horizon exploration for other nanoscale designed particles\u27 implications in gene delivery. In this review we aim to highlight the molecular role of TRAIL in apoptosis and interaction with cancer stem cells (CSCs) self-renewal pathways. Finally, we also aim to discuss the different roles of gene delivery systems, mesenchymal cells, and nanotechnology designs in TRAIL gene delivery

Clinical Evaluation of a New Approach for IOL Power Calculation in Keratoconus

Purpose: To obtain an expression of the adjusted IOL power (PIOLadj) in keratoconus eyes associated with minimal errors in IOL power calculation. Materials and methods: This retrospective study included a total of 25 eyes of 25 patients with ages ranging from 20 years to 76 years. The following IOLs were implanted: Acrysof IQ Toric, Acrysof SA60AT in 9 eyes, Sensar in 3 eyes, Tecnis 1 in 4 eyes, and Tecnis Toric in 2 eyes. The PIOLadj is based on Gauss equations, using adjusted keratometric index (nkadj) specific to keratoconus eyes. From this nkadj, an adjusted keratometric corneal power is calculated (Pkadj). The PIOLadj calculation was performed after estimating the effective lens position (ELP) using a mathematical expression obtained by multiple regression analysis (named ELPadj). Comparison between the PIOLadj and the real intraocular power implanted in each patient (PIOLreal) was carried out. Results: No significant differences between PIOLreal and PIOLadj were found. However, differences could be clinically relevant up to of 2.54 D as PIOLreal increases. But, in the range of PIOLreal between 0 and 20 D, differences were lower than 1.5 D, being most of them below 1 D. Conclusion: A new formula of IOL power calculation (PIOLadj) based on the use of an adjusted keratometric power (Pkadj) that considers a variable keratometric index due to the influence of the posterior corneal surface (nkadj) and adjusted effective lens position (ELPadj) is useful for estimating IOL power in low-to-moderate keratoconus, with more limitation in the most advanced keratoconus.David P Piñero is supported by the Spanish Ministry of Economy, Industry, and Competitiveness within the program Ramón y Cajal, RYC-2016-20471

Detection of meat adulteration using spectroscopy-based sensors

Minced meat is a vulnerable to adulteration food commodity because species- and/or tissue-specific morphological characteristics cannot be easily identified. Hence, the economically motivated adulteration of minced meat is rather likely to be practiced. The objective of this work was to assess the potential of spectroscopy-based sensors in detecting fraudulent minced meat substitution, specifically of (i) beef with bovine offal and (ii) pork with chicken (and vice versa) both in fresh and frozen-thawed samples. For each case, meat pieces were minced and mixed so that different levels of adulteration with a 25% increment were achieved while two categories of pure meat also were considered. From each level of adulteration, six different samples were prepared. In total, 120 samples were subjected to visible (Vis) and fluorescence (Fluo) spectra and multispectral image (MSI) acquisition. Support Vector Machine classification models were developed and evaluated. The MSI-based models outperformed the ones based on the other sensors with accuracy scores varying from 87% to 100%. The Vis-based models followed in terms of accuracy with attained scores varying from 57% to 97% while the lowest performance was demonstrated by the Fluo-based models. Overall, spectroscopic data hold a considerable potential for the detection and quantification of minced meat adulteration, which, however, appears to be sensor-specific

A Phase III Trial of Tirasemtiv as a Potential Treatment for Amyotrophic Lateral Sclerosis

Objective: To assess the efficacy of tirasemtiv, a fast skeletal muscle troponin activator, vs. placebo in patients with amyotrophic lateral sclerosis. Methods: VITALITY-ALS (NCT02496767) was a multinational, double-blind, randomized, placebo-controlled clinical trial. Participants tolerating 2 weeks of open-label tirasemtiv (125 mg twice daily) were randomized 3:2:2:2 to placebo or one of three target tirasemtiv dose levels, using an escalating dosage protocol lasting 28 days. The primary outcome measure was changed in slow vital capacity (SVC) at 24 weeks. Secondary endpoints included a change in muscle strength and time to respiratory milestones of disease progression. Results: Of 744 participants, 565 tolerated open-label tirasemtiv and received randomized treatment. By 24 weeks, 23 (12.2%) placebo-treated participants discontinued study treatment vs. 129 (34.2%) randomized to tirasemtiv. SVC declined by 14.4% (95% CI: ˆ’16.8, ˆ’11.9) in the placebo group and 13.4% (95% CI: ˆ’15.3, ˆ’11.6) in the tirasemtiv group (p = 0.56). Secondary endpoints did not show significant differences. However, participants who tolerated tirasemtiv at their randomized dose showed a numeric trend toward a dose-related slowing of decline in SVC (p = 0.11). Dizziness, fatigue, nausea, weight loss, and insomnia occurred more frequently on tirasemtiv. Serious adverse events were similar across groups. Conclusions: Tirasemtiv did not alter the decline of SVC or significantly impact secondary outcome measures. Poor tolerability of tirasemtiv may have contributed to this result. However, participants tolerating their intended dose exhibited a trend toward treatment benefit on SVC, suggesting the underlying mechanism of action may still hold promise, as is being tested with a different fast skeletal muscle troponin activator (NCT03160898)

How common is truly benign MS in a UK population?

Objectives The prevalence and definition of benign multiple sclerosis (BMS) remain controversial. Most definitions are based on the Expanded Disability Status Scale (EDSS), not encompassing the wider impact of disease. The explanation for favourable outcomes remains unclear. We aim to provide a detailed characterisation of patients with low EDSS scores at long disease durations. Methods We screened a population-based registry containing 3062 people with MS to identify individuals with unlimited walking ability at disease durations >15 years. A representative cohort underwent detailed clinical assessment and classified as having BMS according to EDSS score <3, no significant fatigue, mood disturbance, cognitive impairment or disrupted employment, and had not received a disease-modifying therapy. We determined patient-reported perceptions of MS status and made comparisons with EDSS-based definitions. Results Of 1049 patients with disease duration of >15 years, 200 (19.1%) had most recent EDSS score <4.0. Detailed contemporary clinical assessment of a representative sample of 60 of these patients revealed 48 (80%) had an EDSS score of <4.0, 35 (58%) <3.0 and 16 (27%) <2.0. Only nine (15%) fulfilled our criteria for BMS; impaired cognition (57%) and effects on employment (52%) the most common causes for exclusion. Meanwhile, 33/60 (69%) patients considered their disease benign. Population frequency for BMS was estimated at 2.9% (95% CI 2.0 to 4.1). Conclusions Comprehensive assessment reveals a small minority of people with MS who appear genuinely benign after 15 years. Study of such individuals may uncover insights about disease pathogenesis. However, discrepancy between patient perception and clinician perception of BMS undermines use of the term ‘benign’ in clinical settings