Enumerating Isolated Cliques in Temporal Networks

Isolation is a concept from the world of clique enumeration that is mostly used to model communities that do not have much contact to the outside world. Herein, a clique is considered isolated if it has few edges connecting it to the rest of the graph. Motivated by recent work on enumerating cliques in temporal networks, we lift the isolation concept to this setting. We discover that the addition of the time dimension leads to six distinct natural isolation concepts. Our main contribution is the development of fixed-parameter enumeration algorithms for five of these six clique types employing the parameter "degree of isolation". On the empirical side, we implement and test these algorithms on (temporal) social network data, obtaining encouraging preliminary results

In vitro culture with gemcitabine augments death receptor and NKG2D ligand expression on tumour cells

Much effort has been made to try to understand the relationship between chemotherapeutic treatment of cancer and the immune system. Whereas much of that focus has been on the direct effect of chemotherapy drugs on immune cells and the release of antigens and danger signals by malignant cells killed by chemotherapy, the effect of chemotherapy on cells surviving treatment has often been overlooked. In the present study, tumour cell lines: A549 (lung), HCT116 (colon) and MCF-7 (breast), were treated with various concentrations of the chemotherapeutic drugs cyclophosphamide, gemcitabine (GEM) and oxaliplatin (OXP) for 24 hours in vitro. In line with other reports, GEM and OXP upregulated expression of the death receptor CD95 (fas) on live cells even at sub-cytotoxic concentrations. Further investigation revealed that the increase in CD95 in response to GEM sensitised the cells to fas ligand treatment, was associated with increased phosphorylation of stress activated protein kinase/c-Jun N-terminal kinase and that other death receptors and activatory immune receptors were co-ordinately upregulated with CD95 in certain cell lines. The upregulation of death receptors and NKG2D ligands together on cells after chemotherapy suggest that although the cells have survived preliminary treatment with chemotherapy they may now be more susceptible to immune cell-mediated challenge. This re-enforces the idea that chemotherapy-immunotherapy combinations may be useful clinically and has implications for the make-up and scheduling of such treatments

Grey and white matter correlates of recent and remote autobiographical memory retrieval:Insights from the dementias

The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer's disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer's disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the contribution of discrete regions in mediating successful retrieval of distant versus recently experienced events

Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.

A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and "macaque versions" of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides

Role of Abl Kinase and the Wave2 Signaling Complex in HIV-1 Entry at a Post-Hemifusion Step

Entry of human immunodeficiency virus type 1 (HIV-1) commences with binding of the envelope glycoprotein (Env) to the receptor CD4, and one of two coreceptors, CXCR4 or CCR5. Env-mediated signaling through coreceptor results in Gαq-mediated Rac activation and actin cytoskeleton rearrangements necessary for fusion. Guanine nucleotide exchange factors (GEFs) activate Rac and regulate its downstream protein effectors. In this study we show that Env-induced Rac activation is mediated by the Rac GEF Tiam-1, which associates with the adaptor protein IRSp53 to link Rac to the Wave2 complex. Rac and the tyrosine kinase Abl then activate the Wave2 complex and promote Arp2/3-dependent actin polymerization. Env-mediated cell-cell fusion, virus-cell fusion and HIV-1 infection are dependent on Tiam-1, Abl, IRSp53, Wave2, and Arp3 as shown by attenuation of fusion and infection in cells expressing siRNA targeted to these signaling components. HIV-1 Env-dependent cell-cell fusion, virus-cell fusion and infection were also inhibited by Abl kinase inhibitors, imatinib, nilotinib, and dasatinib. Treatment of cells with Abl kinase inhibitors did not affect cell viability or surface expression of CD4 and CCR5. Similar results with inhibitors and siRNAs were obtained when Env-dependent cell-cell fusion, virus-cell fusion or infection was measured, and when cell lines or primary cells were the target. Using membrane curving agents and fluorescence microscopy, we showed that inhibition of Abl kinase activity arrests fusion at the hemifusion (lipid mixing) step, suggesting a role for Abl-mediated actin remodeling in pore formation and expansion. These results suggest a potential utility of Abl kinase inhibitors to treat HIV-1 infected patients

Models Analyses for Allelopathic Effects of Chicory at Equivalent Coupling of Nitrogen Supply and pH Level on F. arundinacea, T. repens and M. sativa

Alllelopathic potential of chicory was investigated by evaluating its effect on seed germination, soluble sugar, malondialdehyde (MDA) and the chlorophyll content of three target plants species (Festuca arundinacea, Trifolium repens and Medicago sativa). The secretion of allelochemicals was regulated by keeping the donor plant (chicory) separate from the three target plant species and using different pH and nitrogen levels. Leachates from donor pots with different pH levels and nitrogen concentrations continuously irrigated the target pots containing the seedlings. The allelopathic effects of the chicory at equivalent coupling of nitrogen supply and pH level on the three target plants species were explored via models analyses. The results suggested a positive effect of nitrogen supply and pH level on allelochemical secretion from chicory plants. The nitrogen supply and pH level were located at a rectangular area defined by 149 to 168 mg/l nitrogen supply combining 4.95 to 7.0 pH value and point located at nitrogen supply 177 mg/l, pH 6.33 when they were in equivalent coupling effects; whereas the inhibitory effects of equivalent coupling nitrogen supply and pH level were located at rectangular area defined by 125 to 131 mg/l nitrogen supply combining 6.71 to 6.88 pH value and two points respectively located at nitrogen supply 180 mg/l with pH 6.38 and nitrogen supply 166 mg/l with pH 7.59. Aqueous extracts of chicory fleshy roots and leaves accompanied by treatment at different sand pH values and nitrogen concentrations influenced germination, seedling growth, soluble sugar, MDA and chlorophyll of F. arundinacea, T. repens and M. sativa. Additionally, we determined the phenolics contents of root and leaf aqueous extracts, which were 0.104% and 0.044% on average, respectively

Rules for Growth: Promoting Innovation and Growth Through Legal Reform

The United States economy is struggling to recover from its worst economic downturn since the Great Depression. After several huge doses of conventional macroeconomic stimulus - deficit-spending and monetary stimulus - policymakers are understandably eager to find innovative no-cost ways of sustaining growth both in the short and long runs. In response to this challenge, the Kauffman Foundation convened a number of America’s leading legal scholars and social scientists during the summer of 2010 to present and discuss their ideas for changing legal rules and policies to promote innovation and accelerate U.S. economic growth. This meeting led to the publication of Rules for Growth: Promoting Innovation and Growth Through Legal Reform, a comprehensive and groundbreaking volume of essays prescribing a new set of growth-promoting policies for policymakers, legal scholars, economists, and business men and women. Some of the top Rules include: • Reforming U.S. immigration laws so that more high-skilled immigrants can launch businesses in the United States. • Improving university technology licensing practices so university-generated innovation is more quickly and efficiently commercialized. • Moving away from taxes on income that penalize risk-taking, innovation, and employment while shifting toward a more consumption-based tax system that encourages saving that funds investment. In addition, the research tax credit should be redesigned and made permanent. • Overhauling local zoning rules to facilitate the formation of innovative companies. • Urging judges to take a more expansive view of flexible business contracts that are increasingly used by innovative firms. • Urging antitrust enforcers and courts to define markets more in global terms to reflect contemporary realities, resist antitrust enforcement from countries with less sound antitrust regimes, and prohibit industry trade protection and subsidies. • Reforming the intellectual property system to allow for a post-grant opposition process and address the large patent application backlog by allowing applicants to pay for more rapid patent reviews. • Authorizing corporate entities to form digitally and use software as a means for setting out agreements and bylaws governing corporate activities. The collective essays in the book propose a new way of thinking about the legal system that should be of interest to policymakers and academic scholars alike. Moreover, the ideas presented here, if embodied in law, would augment a sustained increase in U.S. economic growth, improving living standards for U.S. residents and for many in the rest of the world

Epidemiological and clinical features, response to HAART, and survival in HIV-infected patients diagnosed at the age of 50 or more

BACKGROUND: Over the last years, the mean age of subjects with HIV infection and AIDS is increasing. Moreover, some epidemiological and clinical differences between younger and older HIV-infected individuals have been observed. However, since introduction of HAART therapy, there are controversial results regarding their response to HAART. The aim of the present study is to evaluate epidemiological and clinical features, response to HAART, and survival in elderly HIV-infected patients with regard to younger HIV-infected patients. METHODS: A prospective cohort study (1998–2003) was performed on patients from Sabadell Hospital, in Northeast of Spain. The cohort includes newly attended HIV-infected patients since January 1, 1998. For the purpose of this analysis, data was censured at December 31, 2003. Taking into account age at time of diagnosis, it was considered 36 HIV-positive people aged 50 years or more (Group 1, G1) and 419 HIV-positive people aged 13–40 years (Group 2, G2). Epidemiological, clinical, biological and therapy data are recorded. Statistical analysis was performed using Chi-squared test and Fisher exact test, Mann-Whitney U test, Kaplan-Meier, Log Rank test, and Two-Way ANOVA from random factors. RESULTS: G1 showed higher proportion of men than G2. The most common risk factors in G1 were heterosexual transmission (P = 0.01) and having sex with men or women (P < 0.001). G1 and G2 show parallel profiles through the time regarding immunological response (P = 0.989) and virological response (P = 0.074). However, older people showed lower CD4 cell counts at first clinic visit (P < 0.001) and, eventually, they did not achieve the same counts as G2. G1 presented faster progression to AIDS (P < 0.001) and shorter survival (P < 0.001). CONCLUSION: Older patients have different epidemiological features. Their immunological and virological responses are good. However, older patients do not achieve the same CD4 cell counts likely due to they have lower counts at first clinic visit. Thus, it is essential physicians know older HIV-infected patients features to consider the possibility of HIV infection in these patients with the aim of treatment would not be delayed