Resource dedication problem in a multi-project environment

There can be different approaches to the management of resources within the context of multi-project scheduling problems. In general, approaches to multiproject scheduling problems consider the resources as a pool shared by all projects. On the other hand, when projects are distributed geographically or sharing resources between projects is not preferred, then this resource sharing policy may not be feasible. In such cases, the resources must be dedicated to individual projects throughout the project durations. This multi-project problem environment is defined here as the resource dedication problem (RDP). RDP is defined as the optimal dedication of resource capacities to different projects within the overall limits of the resources and with the objective of minimizing a predetermined objective function. The projects involved are multi-mode resource constrained project scheduling problems with finish to start zero time lag and non-preemptive activities and limited renewable and nonrenewable resources. Here, the characterization of RDP, its mathematical formulation and two different solution methodologies are presented. The first solution approach is a genetic algorithm employing a new improvement move called combinatorial auction for RDP, which is based on preferences of projects for resources. Two different methods for calculating the projects’ preferences based on linear and Lagrangian relaxation are proposed. The second solution approach is a Lagrangian relaxation based heuristic employing subgradient optimization. Numerical studies demonstrate that the proposed approaches are powerful methods for solving this problem

How to manage the transplant question in myelofibrosis

Allogeneic stem cell transplantation remains the only curative therapy for myelofibrosis. Despite advances in transplant, the morbidity and the mortality of the procedure necessitate careful patient selection. In this manuscript, we describe the new prognostic scoring system to help select appropriate patients for transplant and less aggressive therapies. We explore the advances in non-transplant therapy, such as with investigational agents. We review the blossoming literature on results of myeloablative, reduced intensity and alternative donor transplantation. Finally, we make recommendations for which patients are most likely to benefit from transplantation

Swallowing, nutrition and patient-rated functional outcomes at 6 months following two non-surgical treatments for T1-T3 oropharyngeal cancer

Altered fractionation radiotherapy with concomitant boost (AFRT-CB) may be considered an alternative treatment for patients not appropriate for chemoradiation (CRT). As functional outcomes following AFRT-CB have been minimally reported, this exploratory paper describes the outcomes of patients managed with AFRT-CB or CRT at 6 months post-treatment

Topical vitamin A treatment of recalcitrant common warts

<p>Abstract</p> <p>Background</p> <p>Common warts (<it>verruca vulgaris</it>) are benign epithelial proliferations associated with human papillomavirus (HPV) infection. Salicylic acid and cryotherapy are the most frequent treatments for common warts, but can be painful and cause scarring, and have high failure and recrudescence rates. Topical vitamin A has been shown to be a successful treatment of common warts in prior informal studies.</p> <p>Case</p> <p>The subject is a healthy, physically-active 30 old female with a 9 year history of common warts on the back of the right hand. The warts resisted treatment with salicylic acid, apple cider vinegar and an over-the-counter blend of essential oils marketed for the treatment of warts. Daily topical application of natural vitamin A derived from fish liver oil (25,000 IU) led to replacement of all the warts with normal skin. Most of the smaller warts had been replaced by 70 days. A large wart on the middle knuckle required 6 months of vitamin A treatment to resolve completely.</p> <p>Conclusion</p> <p>Retinoids should be further investigated in controlled studies to determine their effectiveness in treating common warts and the broad range of other benign and cancerous lesions induced by HPVs.</p

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Long-term functional outcomes and the patient perspective following altered fractionation with concomitant boost for oropharyngeal cancer

With no long-term data available in published research to date, this study presents details of the swallowing outcomes as well as barriers to and facilitators of oral intake and weight maintenance at 2 years after altered fractionation radiotherapy with concomitant boost (AFRT-CB). Twelve patients with T1-T3 oropharyngeal cancer who received AFRT-CB were assessed at baseline, 6 months, and 2 years post-treatment for levels of dysphagia and salivary toxicity, food and fluid tolerance, functional swallowing outcomes, patient-reported function, and weight. At 2 years, participants were also interviewed to explore barriers and facilitators of oral intake. Outcomes were significantly worse at 2 years when compared to baseline for late toxicity, functional swallowing, and patient-rated physical aspects of swallowing. Most patients (83%) tolerated a full diet pretreatment, but the rate fell to 42% (remainder tolerated soft diets) at 2 years. Multiple barriers to oral intake that impacted on activity and participation levels were identified. Participants lost 11 kg from baseline to 2 years, which was not regained between 6 months and 2 years. Global, social, and emotional domains of patient-reported function returned to pretreatment levels. At 2 years post AFRT-CB, worsening salivary and dysphagia toxicity, declining functional swallowing, and multiple reported ongoing barriers to oral intake had a negative impact on participants' activity and participation levels relating to eating. These ongoing deficits contributed to significant deterioration in physical swallowing functioning determined by the MDADI. In contrast, patients perceived their broader functioning had improved at 2 years, suggesting long-term adjustment to ongoing swallowing deficits

SMAR1 binds to T(C/G) repeatvand inhibits tumor progression by regulating miR-371-373 cluster

Chromatin architecture and dynamics are regulated by various histone and non-histone proteins. The matrix attachment region binding proteins (MARBPs) play a central role in chromatin organization and function through numerous regulatory proteins. In the present study, we demonstrate that nuclear matrix protein SMAR1 orchestrates global gene regulation as determined by massively parallel ChIPsequencing. The study revealed that SMAR1 binds to T(C/G) repeat and targets genes involved in diverse biological pathways. We observe that SMAR1 binds and targets distinctly different genes based on the availability of p53. Our data suggest that SMAR1 binds and regulates one of the imperative microRNA clusters in cancer and metastasis, miR-371-373. It negatively regulates miR-371-373 transcription as confirmed by SMAR1 overexpression and knockdown studies. Further, deletion studies indicate that a ~200 bp region in the miR-371-373 promoter is necessary for SMAR1 binding and transcriptional repression. Recruitment of HDAC1/mSin3A complex by SMAR1, concomitant with alteration of histone marks results in downregulation of the miRNA cluster. The regulation of miR-371-373 by SMAR1 inhibits breast cancer tumorigenesis and metastasis as determined by in vivo experiments. Overall, our study highlights the binding of SMAR1 to T(C/G) repeat and its role in cancer through miR-371-37

Tumor Suppressor Protein p53 Recruits Human Sin3B/HDAC1 Complex for Down-Regulation of Its Target Promoters in Response to Genotoxic Stress

Master regulator protein p53, popularly known as the “guardian of genome” is the hub for regulation of diverse cellular pathways. Depending on the cell type and severity of DNA damage, p53 protein mediates cell cycle arrest or apoptosis, besides activating DNA repair, which is apparently achieved by regulation of its target genes, as well as direct interaction with other proteins. p53 is known to repress target genes via multiple mechanisms one of which is via recruitment of chromatin remodelling Sin3/HDAC1/2 complex. Sin3 proteins (Sin3A and Sin3B) regulate gene expression at the chromatin-level by serving as an anchor onto which the core Sin3/HDAC complex is assembled. The Sin3/HDAC co-repressor complex can be recruited by a large number of DNA-binding transcription factors. Sin3A has been closely linked to p53 while Sin3B is considered to be a close associate of E2Fs. The theme of this study was to establish the role of Sin3B in p53-mediated gene repression. We demonstrate a direct protein-protein interaction between human p53 and Sin3B (hSin3B). Amino acids 1–399 of hSin3B protein are involved in its interaction with N-terminal region (amino acids 1–108) of p53. Genotoxic stress induced by Adriamycin treatment increases the levels of hSin3B that is recruited to the promoters of p53-target genes (HSPA8, MAD1 and CRYZ). More importantly recruitment of hSin3B and repression of the three p53-target promoters upon Adriamycin treatment were observed only in p53+/+ cell lines. Additionally an increased tri-methylation of the H3K9 residue at the promoters of HSPA8 and CRYZ was also observed following Adriamycin treatment. The present study highlights for the first time the essential role of Sin3B as an important associate of p53 in mediating the cellular responses to stress and in the transcriptional repression of genes encoding for heat shock proteins or proteins involved in regulation of cell cycle and apoptosis