Showing papers by "University of Medicine and Dentistry of New Jersey published in 2012"
TL;DR: In this paper, the authors estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010.
9,324 citations
TL;DR: A synthesis of the current status of mesenchymal stem cells is provided, which shows that there are bidirectional interactions between MSCs and inflammatory cells, which determine the outcome of MSC-mediated tissue repair processes.
519 citations
TL;DR: An approach to designing ideal protein structures stabilized by completely consistent local and non-local interactions is described, based on a set of rules relating secondary structure patterns to protein tertiary motifs, which make possible the design of funnel-shaped protein folding energy landscapes leading into the target folded state.
Abstract: Unlike random heteropolymers, natural proteins fold into unique ordered structures. Understanding how these are encoded in amino-acid sequences is complicated by energetically unfavourable non-ideal features--for example kinked α-helices, bulged β-strands, strained loops and buried polar groups--that arise in proteins from evolutionary selection for biological function or from neutral drift. Here we describe an approach to designing ideal protein structures stabilized by completely consistent local and non-local interactions. The approach is based on a set of rules relating secondary structure patterns to protein tertiary motifs, which make possible the design of funnel-shaped protein folding energy landscapes leading into the target folded state. Guided by these rules, we designed sequences predicted to fold into ideal protein structures consisting of α-helices, β-strands and minimal loops. Designs for five different topologies were found to be monomeric and very stable and to adopt structures in solution nearly identical to the computational models. These results illuminate how the folding funnels of natural proteins arise and provide the foundation for engineering a new generation of functional proteins free from natural evolution.
496 citations
TL;DR: This guideline focuses on long-term administration of antithrombotic drugs designed for primary and secondary prevention of cardiovascular disease, including two new antiplatelet therapies.
432 citations
TL;DR: It is demonstrated that SQ109 disrupts cell wall assembly, as evidenced by macromolecular incorporation assays and ultrastructural analyses and that MmpL3 is a transporter of mycobacterial TMM.
Abstract: SQ109, a 1,2-diamine related to ethambutol, is currently in clinical trials for the treatment of tuberculosis, but its mode of action remains unclear. Here, we demonstrate that SQ109 disrupts cell wall assembly, as evidenced by macromolecular incorporation assays and ultrastructural analyses. SQ109 interferes with the assembly of mycolic acids into the cell wall core of Mycobacterium tuberculosis, as bacilli exposed to SQ109 show immediate inhibition of trehalose dimycolate (TDM) production and fail to attach mycolates to the cell wall arabinogalactan. These effects were not due to inhibition of mycolate synthesis, since total mycolate levels were unaffected, but instead resulted in the accumulation of trehalose monomycolate (TMM), the precursor of TDM and cell wall mycolates. In vitro assays using purified enzymes showed that this was not due to inhibition of the secreted Ag85 mycolyltransferases. We were unable to achieve spontaneous generation of SQ109-resistant mutants; however, analogs of this compound that resulted in similar shutdown of TDM synthesis with concomitant TMM accumulation were used to spontaneously generate resistant mutants that were also cross-resistant to SQ109. Whole-genome sequencing of these mutants showed that these all had mutations in the essential mmpL3 gene, which encodes a transmembrane transporter. Our results suggest that MmpL3 is the target of SQ109 and that MmpL3 is a transporter of mycobacterial TMM.
429 citations
TL;DR: Proper M φ polarization is essential to effective wound healing, and distinct phenotypes, such as the angiogenic M2d Mφ, may be of critical importance to this process.
Abstract: Background: Macrophages (Mφs) participate in wound healing by coordinating inflammatory and angiogenic processes. Mφs respond to environmental cues by adopting either “classically” activated (M1) proinflammatory or “alternatively” activated (M2a, M2b, M2c, M2d) wound healing phenotypes. The Problem: Mφ polarization is essential for wound healing and aberrations in this process are linked to several pathologies. It is important to elucidate molecular mechanisms underlying Mφ polarization. Basic/Clinical Science Advances: Mφs are categorized as proinflammatory (M1) or anti-inflammatory/wound healing (M2). M1 Mφs are observed in initial tissue damage responses, are induced by exogenous pathogen-associated molecular patterns or endogenous damage-associated molecular patterns, and exhibit increased phagocytosis and pro-inflammatory cytokine production, facilitating innate immunity and wound debridement. M2 Mφs predominate later in repair, express vascular endothelial growth factor, transforming growth factor b...
420 citations
TL;DR: These studies indicate that air pollution from these sources is a major preventable cause of increased incidence and exacerbation of respiratory disease and Physicians can help to reduce the risk of adverse respiratory effects of exposure to biomass and traffic air pollutants by promoting awareness and supporting individual and community-level interventions.
Abstract: Mounting evidence suggests that air pollution contributes to the large global burden of respiratory and allergic diseases, including asthma, chronic obstructive pulmonary disease, pneumonia, and possibly tuberculosis. Although associations between air pollution and respiratory disease are complex, recent epidemiologic studies have led to an increased recognition of the emerging importance of traffic-related air pollution in both developed and less-developed countries, as well as the continued importance of emissions from domestic fires burning biomass fuels, primarily in the less-developed world. Emissions from these sources lead to personal exposures to complex mixtures of air pollutants that change rapidly in space and time because of varying emission rates, distances from source, ventilation rates, and other factors. Although the high degree of variability in personal exposure to pollutants from these sources remains a challenge, newer methods for measuring and modeling these exposures are beginning to unravel complex associations with asthma and other respiratory tract diseases. These studies indicate that air pollution from these sources is a major preventable cause of increased incidence and exacerbation of respiratory disease. Physicians can help to reduce the risk of adverse respiratory effects of exposure to biomass and traffic air pollutants by promoting awareness and supporting individual and community-level interventions.
402 citations
Mayo Clinic1, Brown University2, University of Minnesota3, Johns Hopkins University4, University of North Carolina at Chapel Hill5, St Lukes Episcopal Hospital6, University of California, San Francisco7, Tufts University8, Good Hope Hospital9, University of Southern California10, University of Medicine and Dentistry of New Jersey11, University of Milan12, SUNY Downstate Medical Center13, Maimonides Medical Center14, Cornell University15, University of Manchester16
TL;DR: The Panel's recommendations build on those developed during the first and second Princeton Consensus Conferences, first emphasizing the use of exercise ability and stress testing to ensure that each man's cardiovascular health is consistent with the physical demands of sexual activity before prescribing treatment for ED, and second highlighting the link between ED and CVD, which may be asymptomatic and may benefit from cardiovascular risk reduction.
Abstract: The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative tradition dedicated to optimizing sexual function and preserving cardiovascular health. The third Princeton Consensus met November 8 to 10, 2010, and had 2 primary objectives. The first objective focused on the evaluation and management of cardiovascular risk in men with erectile dysfunction (ED) and no known cardiovascular disease (CVD), with particular emphasis on identification of men with ED who may require additional cardiologic work-up. The second objective focused on reevaluation and modification of previous recommendations for evaluation of cardiac risk associated with sexual activity in men with known CVD. The Panel's recommendations build on those developed during the first and second Princeton Consensus Conferences, first emphasizing the use of exercise ability and stress testing to ensure that each man's cardiovascular health is consistent with the physical demands of sexual activity before prescribing treatment for ED, and second highlighting the link between ED and CVD, which may be asymptomatic and may benefit from cardiovascular risk reduction.
384 citations
TL;DR: It is found that IL-17 initially contributed to inflammation and lung damage, whereas subsequent IL-4 receptor (IL-4R) signaling reduced elevations inIL-17 mRNA levels, enhanced the expression of insulin-like growth factor 1 and IL-10 and stimulated the development of M2 macrophages, all of which contributed to the rapid resolution of tissue damage.
Abstract: Helminths induce potent T helper 2 (TH2)-type immune responses that can mediate worm expulsion, but the role of this response in controlling the acute tissue damage caused by migrating multicellular parasites through vital tissues remains uncertain. We used a helminth infection model in which parasitic nematode larvae migrate transiently through the lung, resulting in hemorrhage and inflammation. We found that IL-17 initially contributed to inflammation and lung damage, whereas subsequent IL-4 receptor (IL-4R) signaling reduced elevations in IL-17 mRNA levels, enhanced the expression of insulin-like growth factor 1 (IGF-1) and IL-10 and stimulated the development of M2 macrophages, all of which contributed to the rapid resolution of tissue damage. These studies indicate an essential role for TH2-type immune responses in mediating acute wound healing during helminth infection.
372 citations
TL;DR: It is shown that Mesenchymal stem cells can also enhance immune responses, and the dual effect on immune reactions was also observed in human MSCs, in which indoleamine 2,3-dioxygenase (IDO) acts as a switch.
Abstract: Mesenchymal stem cells (MSCs) have been employed successfully to treat various immune disorders in animal models and clinical settings. Our previous studies have shown that MSCs can become highly immunosuppressive upon stimulation by inflammatory cytokines, an effect exerted through the concerted action of chemokines and nitric oxide (NO). Here, we show that MSCs can also enhance immune responses. This immune-promoting effect occurred when proinflammatory cytokines were inadequate to elicit sufficient NO production. When inducible nitric oxide synthase (iNOS) production was inhibited or genetically ablated, MSCs strongly enhance T-cell proliferation in vitro and the delayed-type hypersensitivity response in vivo. Furthermore, iNOS−/− MSCs significantly inhibited melanoma growth. It is likely that in the absence of NO, chemokines act to promote immune responses. Indeed, in CCR5−/−CXCR3−/− mice, the immune-promoting effect of iNOS−/− MSCs is greatly diminished. Thus, NO acts as a switch in MSC-mediated immunomodulation. More importantly, the dual effect on immune reactions was also observed in human MSCs, in which indoleamine 2,3-dioxygenase (IDO) acts as a switch. This study provides novel information about the pathophysiological roles of MSCs.
355 citations
TL;DR: The current molecular epidemiology of CA-MRSA is reviewed with respect to genetic diversity, global distribution, and factors related to its emergence and spread.
TL;DR: It is proposed that adenosine receptor activation suppresses inflammation and promotes tissue restitution, in part, by promoting alternative macrophage activation.
Abstract: Adenosine has been implicated in suppressing the proinflammatory responses of classically activated macrophages induced by Th1 cytokines. Alternative macrophage activation is induced by the Th2 cytokines interleukin (IL)-4 and IL-13; however, the role of adenosine in governing alternative macrophage activation is unknown. We show here that adenosine treatment of IL-4- or IL-13-activated macrophages augments the expression of alternative macrophage markers arginase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and macrophage galactose-type C-type lectin-1. The stimulatory effect of adenosine required primarily A2B receptors because the nonselective adenosine receptor agonist 5′-N-ethylcarboxamidoadenosine (NECA) increased both arginase activity (EC50=261.8 nM) and TIMP-1 production (EC50=80.67 nM), and both pharmacologic and genetic blockade of A2B receptors prevented the effect of NECA. A2A receptors also contributed to the adenosine augmentation of IL-4-induced TIMP-1 release, as both adenosine and NECA were less efficacious in augmenting TIMP-1 release by A2A receptor-deficient than control macrophages. Of the transcription factors known to drive alternative macrophage activation, CCAAT-enhancer-binding protein β was required, while cAMP response element-binding protein and signal transducer and activator of transcription 6 were dispensable in mediating the effect of adenosine. We propose that adenosine receptor activation suppresses inflammation and promotes tissue restitution, in part, by promoting alternative macrophage activation.—Csoka, B., Selmeczy, Z., Koscso, B., Nemeth, Z. H., Pacher, P., Murray, P. J., Kepka-Lenhart, D., Morris S. M., Jr., Gause, W. C., Leibovich, S. J., Hasko, G. Adenosine promotes alternative macrophage activation via A2A and A2B receptors.
TL;DR: A review examines the commonalities in this growing subgroup of Burkholderia species and discusses their prospective biotechnological applications.
Abstract: The genus Burkholderia comprises more than 60 species isolated from a wide range of niches. Although they have been shown to be diverse and ubiquitously distributed, most studies have thus far focused on the pathogenic species due to their clinical importance. However, the increasing number of recently described Burkholderia species associated with plants or with the environment has highlighted the division of the genus into two main clusters, as suggested by phylogenetical analyses. The first cluster includes human, animal, and plant pathogens, such as Burkholderia glumae, Burkholderia pseudomallei, and Burkholderia mallei, as well as the 17 defined species of the Burkholderia cepacia complex, while the other, more recently established cluster comprises more than 30 non-pathogenic species, which in most cases have been found to be associated with plants, and thus might be considered to be potentially beneficial. Several species from the latter group share characteristics that are of use when associating with plants, such as a quorum sensing system, the presence of nitrogen fixation and/or nodulation genes, and the ability to degrade aromatic compounds. This review examines the commonalities in this growing subgroup of Burkholderia species and discusses their prospective biotechnological applications.
TL;DR: Child abuse and neglect affect long-term health status-increasing risk for diabetes, lung disease, malnutrition,nutrition, and vision problems-and support the need for early health care prevention.
Abstract: Objectives. We investigated whether abused and neglected children are at risk for negative physical health outcomes in adulthood.Methods. Using a prospective cohort design, we matched children (aged 0–11 years) with documented cases of physical and sexual abuse and neglect from a US Midwestern county during 1967 through 1971 with nonmaltreated children. Both groups completed a medical status examination (measured health outcomes and blood tests) and interview during 2003 through 2005 (mean age = 41.2 years).Results. After adjusting for age, gender, and race, child maltreatment predicted above normal hemoglobin, lower albumin levels, poor peak airflow, and vision problems in adulthood. Physical abuse predicted malnutrition, albumin, blood urea nitrogen, and hemoglobin A1C. Neglect predicted hemoglobin A1C, albumin, poor peak airflow, and oral health and vision problems, Sexual abuse predicted hepatitis C and oral health problems. Additional controls for childhood socioeconomic status, adult socioeconomic s...
TL;DR: These nonselection data provide the first prospective, blinded, clinical study directly measuring the predictive value of aneuploidy screening for clinical outcome, whereas implantation and delivery rates of euploid embryos are increased relative to the entire cohort of transferred embryos.
TL;DR: An understanding of the interaction between MSCs and the inflammatory microenvironment will provide critical information in revealing the precise in vivo mechanisms of MSC‐mediated therapeutic effects and designing more practical protocols for clinical use of these cells.
Abstract: Mesenchymal stem cells (MSCs) are emerging as a promising therapeutic approach of cell-based therapy for a wide range of autoimmune disorders and degenerative diseases. In preclinical and clinical studies, MSCs have been shown to be highly efficient in treating graft-versus-host disease, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, myocardial infarction, liver cirrhosis, inflammatory bowel disease, and other disorders. The underlying therapeutic mechanisms of MSCs include their homing efficiency to the tissue injury sites, their differentiation potential, their capability to produce a large amount of trophic factors, and their immunomodulatory effect. Because tissue damage sites are complicated milieus with distinct types of inflammatory cells and factors, available data have demonstrated that the properties of MSCs could be fundamentally influenced by the inflammatory elements. Thus, an understanding of the interaction between MSCs and the inflammatory microenvironment will provide critical information in revealing the precise in vivo mechanisms of MSC-mediated therapeutic effects and designing more practical protocols for clinical use of these cells.
TL;DR: The effects of virtual reality and interactive video gaming compared with an alternative intervention or no intervention on upper limb, lower limb, and global motor function after stroke were evaluated.
Abstract: Virtual reality and interactive video gaming have emerged as new treatment approaches in stroke rehabilitation. These approaches may be advantageous because they provide the opportunity to practice activities that are not or cannot be practiced within the clinical environment. Furthermore, virtual reality programs are often designed to be more interesting and enjoyable than traditional therapy tasks, thereby encouraging higher numbers of repetitions. The use of specialized virtual reality programs designed for rehabilitation is not yet commonplace in clinical settings. However, gaming consoles are ubiquitous.
The primary objective of this review was to evaluate the effects of virtual reality and interactive video gaming compared with an alternative intervention or no intervention on upper limb, lower limb, and global motor function after stroke. Secondary outcomes included activity limitation and adverse events. We also explored feasibility of the approach by examining recruitment rates.
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We searched the Cochrane Stroke Trials Register (March 2010), the …
Katholieke Universiteit Leuven1, Flanders Institute for Biotechnology2, University of Melbourne3, Peter MacCallum Cancer Centre4, National Institutes of Health5, International Agency for Research on Cancer6, University of Medicine and Dentistry of New Jersey7, Ghent University8, Monash University9, French Institute of Health and Medical Research10, University of California, Los Angeles11
TL;DR: It is shown that Mdm4 p53 binding protein homolog (MDM4), a negative regulator of p53, is upregulated in a substantial proportion (∼65%) of stage I–IV human melanomas and that melanocyte-specific MDM4 overexpression enhanced tumorigenesis in a mouse model of melanoma induced by the oncogene Nras.
Abstract: The inactivation of the p53 tumor suppressor pathway, which often occurs through mutations in TP53 (encoding tumor protein 53) is a common step in human cancer. However, in melanoma-a highly chemotherapy-resistant disease-TP53 mutations are rare, raising the possibility that this cancer uses alternative ways to overcome p53-mediated tumor suppression. Here we show that Mdm4 p53 binding protein homolog (MDM4), a negative regulator of p53, is upregulated in a substantial proportion (∼65%) of stage I-IV human melanomas and that melanocyte-specific Mdm4 overexpression enhanced tumorigenesis in a mouse model of melanoma induced by the oncogene Nras. MDM4 promotes the survival of human metastatic melanoma by antagonizing p53 proapoptotic function. Notably, inhibition of the MDM4-p53 interaction restored p53 function in melanoma cells, resulting in increased sensitivity to cytotoxic chemotherapy and to inhibitors of the BRAF (V600E) oncogene. Our results identify MDM4 as a key determinant of impaired p53 function in human melanoma and designate MDM4 as a promising target for antimelanoma combination therapy.
TL;DR: Canakinumab provided significant pain and inflammation relief and reduced the risk of new flares in these patients with acute gouty arthritis.
Abstract: Objectives Gouty arthritis patients for whom non-steroidal anti-inflammatory drugs and colchicine are inappropriate have limited treatment options. Canakinumab, an anti-interleukin-1β monoclonal antibody, may be an option for such patients. The authors assessed the efficacy/safety of one dose of canakinumab 150 mg (n=230) or triamcinolone acetonide (TA) 40 mg (n=226) at baseline and upon a new flare in frequently flaring patients contraindicated for, intolerant of, or unresponsive to non-steroidal anti-inflammatory drugs and/or colchicine. Core study co-primary endpoints were pain intensity 72 h postdose (0–100 mm visual analogue scale and time to first new flare. Methods Two 12-week randomised, multicentre, active-controlled, double-blind, parallel-group core studies with double-blind 12-week extensions (response in acute flare and in prevention of episodes of re-flare in gout (β-RELIEVED and β-RELIEVED-II)). Results 82.6% patients had comorbidities. Mean 72-h visual analogue scale pain score was lower with canakinumab (25.0 mm vs 35.7 mm; difference, −10.7 mm; 95% CI −15.4 to −6.0; p Conclusion Canakinumab provided significant pain and inflammation relief and reduced the risk of new flares in these patients with acute gouty arthritis.
TL;DR: Mechanistic studies reveal that NSC319726 restores WT structure and function to the p53(R175) mutant and is identified as a lead compound for p53-targeted drug development.
TL;DR: It is demonstrated that, in an inflammatory environment, tumor-resident MSCs promote tumor growth by recruiting monocytes/macrophages.
TL;DR: Compared with guideline-based usual care, exercise training resulted in a modest reduction in depressive symptoms, although the clinical significance of this improvement is unknown.
Abstract: Context Depression is common in patients with cardiac disease, especially in patients with heart failure, and is associated with increased risk of adverse health outcomes. Some evidence suggests that aerobic exercise may reduce depressive symptoms, but to our knowledge the effects of exercise on depression in patients with heart failure have not been evaluated. Objective To determine whether exercise training will result in greater improvements in depressive symptoms compared with usual care among patients with heart failure. Design, Setting, and Participants Multicenter, randomized controlled trial involving 2322 stable patients treated for heart failure at 82 medical clinical centers in the United States, Canada, and France. Patients who had a left ventricular ejection fraction of 35% or lower, had New York Heart Association class I to IV heart failure, and had completed the Beck Depression Inventory II (BDI-II) score were randomized (1:1) between April 2003 and February 2007. Depressive scores ranged from 0 to 59; scores of 14 or higher are considered clinically significant. Interventions Participants were randomized either to supervised aerobic exercise (goal of 90 min/wk for months 1-3 followed by home exercise with a goal of ≥120 min/wk for months 4-12) or to education and usual guideline-based heart failure care. Main Outcome Measures Composite of death or hospitalization due to any cause and scores on the BDI-II at months 3 and 12. Results Over a median follow-up period of 30 months, 789 patients (68%) died or were hospitalized in the usual care group compared with 759 (66%) in the aerobic exercise group (hazard ratio [HR], 0.89; 95% CI, 0.81 to 0.99; P = .03). The median BDI-II score at study entry was 8, with 28% of the sample having BDI-II scores of 14 or higher. Compared with usual care, aerobic exercise resulted in lower mean BDI-II scores at 3 months (aerobic exercise, 8.95; 95% CI, 8.61 to 9.29 vs usual care, 9.70; 95% CI, 9.34 to 10.06; difference, −0.76; 95% CI,−1.22 to −0.29; P = .002) and at 12 months (aerobic exercise, 8.86; 95% CI, 8.67 to 9.24 vs usual care, 9.54; 95% CI, 9.15 to 9.92; difference, −0.68; 95% CI, −1.20 to −0.16; P = .01). Conclusions Compared with guideline-based usual care, exercise training resulted in a modest reduction in depressive symptoms, although the clinical significance of this improvement is unknown. Trial Registration clinicaltrials.gov Identifier: NCT00047437
TL;DR: A meta-analysis of randomized controlled trials using statins that reported ICH found no significant difference in incidence of ICH observed in the active treatment group versus control, and a significant reduction in all stroke and all-cause mortality was observed with statin therapy.
Abstract: Background and Purpose—Statin therapy decreases the risk of ischemic stroke. An increased risk of intracerebral hemorrhage (ICH) has been observed in some studies. To investigate this issue, we performed a meta-analysis of randomized controlled trials using statins that reported ICH. Methods—We performed a literature search of Medline, Web of Science, and The Cochrane Library through January 25, 2012, and identified additional randomized controlled trials by reviewing reference lists of retrieved studies and prior meta-analyses. All randomized controlled trials of statin therapy that reported ICH or hemorrhagic stroke were included. The primary outcome variable was ICH. Thirty-one randomized controlled trials were included. All analyses used random effects models and heterogeneity was not observed in any of the analyses. Results—A total of 91 588 subjects were included in the active group and 91 215 in the control group. There was no significant difference in incidence of ICH observed in the active treatm...
TL;DR: It is shown that the transcription factor Elf5, a key regulator of mammary gland alveologenesis, controls EMT in both mammary glands development and metastasis and that Elf5 suppresses EMT by directly repressing the transcription of Snail2, a master regulator of Mammary stem cells and a known inducer of EMT.
Abstract: Kang and colleagues show that the transcription factor Elf5 controls the epithelial–mesenchymal transition (EMT) during development and in metastasis, by repressing the expression of Snail2/Slug, a key EMT-inducing factor.
TL;DR: Inactivation of Rheb protects CMs during ED through activation of autophagy, and mTORC1 may represent therapeutic targets to reduce myocardial damage during ischemia, particularly in obese patients.
Abstract: Background—Rheb is a GTP-binding protein that promotes cell survival and mediates the cellular response to energy deprivation (ED). The role of Rheb in the regulation of cell survival during ED has...
TL;DR: Data indicate that the widely touted “innovation crisis” in pharmaceuticals is a myth, and current incentives that reward companies for developing large numbers of new drugs with few clinical advantages over existing ones are a myth.
Abstract: Data indicate that the widely touted “innovation crisis” in pharmaceuticals is a myth. The real innovation crisis, say Donald Light and Joel Lexchin , stems from current incentives that reward companies for developing large numbers of new drugs with few clinical advantages over existing ones
TL;DR: In this article, the effect of statins in decreasing cardiovascular events in women and men was evaluated with random effects meta-analyses and the results showed that statin therapy is associated with significant decreases in cardiovascular events and in all-cause mortality.
TL;DR: This paper proposes a novel algorithm that can reliably separate touching cells in hematoxylin-stained breast TMA specimens that have been acquired using a standard RGB camera and compares the pixel-wise accuracy provided by human experts with that produced by the new automated segmentation algorithm.
Abstract: Automated image analysis of histopathology specimens could potentially provide support for early detection and improved characterization of breast cancer. Automated segmentation of the cells comprising imaged tissue microarrays (TMAs) is a prerequisite for any subsequent quantitative analysis. Unfortunately, crowding and overlapping of cells present significant challenges for most traditional segmentation algorithms. In this paper, we propose a novel algorithm that can reliably separate touching cells in hematoxylin-stained breast TMA specimens that have been acquired using a standard RGB camera. The algorithm is composed of two steps. It begins with a fast, reliable object center localization approach that utilizes single-path voting followed by mean-shift clustering. Next, the contour of each cell is obtained using a level set algorithm based on an interactive model. We compared the experimental results with those reported in the most current literature. Finally, performance was evaluated by comparing the pixel-wise accuracy provided by human experts with that produced by the new automated segmentation algorithm. The method was systematically tested on 234 image patches exhibiting dense overlap and containing more than 2200 cells. It was also tested on whole slide images including blood smears and TMAs containing thousands of cells. Since the voting step of the seed detection algorithm is well suited for parallelization, a parallel version of the algorithm was implemented using graphic processing units (GPU) that resulted in significant speedup over the C/C++ implementation.
TL;DR: Group-based comprehensive risk reduction was found to be an effective strategy to reduce adolescent pregnancy, HIV, and STIs and no conclusions could be drawn on the effectiveness of group-based abstinence education.
TL;DR: The canonical functions of the components of the eEF1 complex in translation elongation are discussed as well as the secondary interactions they have with other cellular factors outside of the translational apparatus.
Abstract: The vast majority of proteins are believed to have one specific function. Throughout the course of evolution, however, some proteins have acquired additional functions to meet the demands of a complex cellular milieu. In some cases, changes in RNA or protein processing allow the cell to make the most of what is already encoded in the genome to produce slightly different forms. The eukaryotic elongation factor 1 (eEF1) complex subunits, however, have acquired such moonlighting functions without alternative forms. In this article, we discuss the canonical functions of the components of the eEF1 complex in translation elongation as well as the secondary interactions they have with other cellular factors outside of the translational apparatus. The eEF1 complex itself changes in composition as the complexity of eukaryotic organisms increases. Members of the complex are also subject to phosphorylation, a potential modulator of both canonical and non-canonical functions. Although alternative functions of the eEF1A subunit have been widely reported, recent studies are shedding light on additional functions of the eEF1B subunits. A thorough understanding of these alternate functions of eEF1 is essential for appreciating their biological relevance.