Optimal feedback control for dynamic systems with state constraints: An exact penalty approach

In this paper, we consider a class of nonlinear dynamic systems with terminal state and continuous inequality constraints. Our aim is to design an optimal feedback controller that minimizes total system cost and ensures satisfaction of all constraints. We first formulate this problem as a semi-infinite optimization problem. We then show that by using a new exact penalty approach, this semi-infinite optimization problem can be converted into a sequence of nonlinear programming problems, each of which can be solved using standard gradient-based optimization methods.We conclude the paper by discussing applications of our work to glider control

Feasibility investigation of direct laser cutting process of metal foam with high pore density

To avoid damage to the pore structure of metal foam, a laser cutting process for efficiently and directly cutting metal foam into regular shapes is proposed. After analyzing the proposed laser cutting process, its effects when applied to three different types of metal material (copper, ferroalloy, and nickel) and two levels of pore density, namely 90 and 110 pores per inch (PPI), were investigated. The results show that metal foam with a good surface quality can be obtained without damaging the pore structure by using the proposed laser cutting process. Of the three metal types considered, the highest material removal rate (MRR) and material oxidation rate (MOR) were observed for ferroalloy foam. Of the two pore densities, metal foam of 90 PPI showed a larger material removal rate than metal foam of 110 PPI. The MRR and MOR increased with an increase in the laser output power and decrease in the scanning speed. Using a central composite experimental design method, optimized processing parameters of 26 W laser output power and 475 mm/s scanning speed were adopted to cut the metal foam with a high pore density

Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in Hepatocellular Carcinoma: the PLANET study

Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for Hepatocellular Carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across TNM stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas

RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations altering this enzyme have not previously been linked to any pathology in humans, which is a testament to its indispensable role in cell biology. On the basis of a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II (ref. 1), hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors show dysregulation of key meningeal identity genes including WNT6 and ZIC1/ZIC4. In addition to mutations in POLR2A, NF2, SMARCB1, TRAF7, KLF4, AKT1, PIK3CA, and SMO4 we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features

Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature

Treating metastatic osteosarcoma (OS) remains a challenge in oncology. Current treatment strategies target the primary tumour rather than metastases and have a limited efficacy in the treatment of metastatic disease. Metastatic cells have specific features that render them less sensitive to therapy and targeting these features might enhance the efficacy of current treatment. A detailed study of the biological characteristics and behaviour of metastatic OS cells may provide a rational basis for innovative treatment strategies. The aim of this review is to give an overview of the biological changes in metastatic OS cells and the preclinical and clinical efforts targeting the different steps in OS metastases and how these contribute to designing a metastasis directed treatment for OS

Revisiting the Myths of Protein Interior: Studying Proteins with Mass-Fractal Hydrophobicity-Fractal and Polarizability-Fractal Dimensions

A robust marker to describe mass, hydrophobicity and polarizability distribution holds the key to deciphering structural and folding constraints within proteins. Since each of these distributions is inhomogeneous in nature, the construct should be sensitive in describing the patterns therein. We show, for the first time, that the hydrophobicity and polarizability distributions in protein interior follow fractal scaling. It is found that (barring ‘all-α’) all the major structural classes of proteins have an amount of unused hydrophobicity left in them. This amount of untapped hydrophobicity is observed to be greater in thermophilic proteins, than that in their (structurally aligned) mesophilic counterparts. ‘All-β’(thermophilic, mesophilic alike) proteins are found to have maximum amount of unused hydrophobicity, while ‘all-α’ proteins have been found to have minimum polarizability. A non-trivial dependency is observed between dielectric constant and hydrophobicity distributions within (α+β) and ‘all-α’ proteins, whereas absolutely no dependency is found between them in the ‘all-β’ class. This study proves that proteins are not as optimally packed as they are supposed to be. It is also proved that origin of α-helices are possibly not hydrophobic but electrostatic; whereas β-sheets are predominantly hydrophobic in nature. Significance of this study lies in protein engineering studies; because it quantifies the extent of packing that ensures protein functionality. It shows that myths regarding protein interior organization might obfuscate our knowledge of actual reality. However, if the later is studied with a robust marker of strong mathematical basis, unknown correlations can still be unearthed; which help us to understand the nature of hydrophobicity, causality behind protein folding, and the importance of anisotropic electrostatics in stabilizing a highly complex structure named ‘proteins’

A water-based training program that include perturbation exercises to improve stepping responses in older adults: study protocol for a randomized controlled cross-over trial

<p>Abstract</p> <p>Background</p> <p>Gait and balance impairments may increase the risk of falls, the leading cause of accidental death in the elderly population. Fall-related injuries constitute a serious public health problem associated with high costs for society as well as human suffering. A rapid step is the most important protective postural strategy, acting to recover equilibrium and prevent a fall from initiating. It can arise from large perturbations, but also frequently as a consequence of volitional movements. We propose to use a novel water-based training program which includes specific perturbation exercises that will target the stepping responses that could potentially have a profound effect in reducing risk of falling. We describe the water-based balance training program and a study protocol to evaluate its efficacy (Trial registration number #NCT00708136).</p> <p>Methods/Design</p> <p>The proposed water-based training program involves use of unpredictable, multi-directional perturbations in a group setting to evoke compensatory and volitional stepping responses. Perturbations are made by pushing slightly the subjects and by water turbulence, in 24 training sessions conducted over 12 weeks. Concurrent cognitive tasks during movement tasks are included. Principles of physical training and exercise including awareness, continuity, motivation, overload, periodicity, progression and specificity were used in the development of this novel program. Specific goals are to increase the speed of stepping responses and improve the postural control mechanism and physical functioning. A prospective, randomized, cross-over trial with concealed allocation, assessor blinding and intention-to-treat analysis will be performed to evaluate the efficacy of the water-based training program. A total of 36 community-dwelling adults (age 65–88) with no recent history of instability or falling will be assigned to either the perturbation-based training or a control group (no training). Voluntary step reaction times and postural stability using stabiliogram diffusion analysis will be tested before and after the 12 weeks of training.</p> <p>Discussion</p> <p>This study will determine whether a water-based balance training program that includes perturbation exercises, in a group setting, can improve speed of voluntary stepping responses and improve balance control. Results will help guide the development of more cost-effective interventions that can prevent the occurrence of falls in the elderly.</p

Search for neutral MSSM Higgs bosons decaying to a pair of tau leptons in pp collisions

Peer reviewe

Measurement of prompt J/ψ pair production in pp collisions at √s = 7 Tev

Peer reviewe