Expectation-Maximization Based Mixture-Model Exploiting Pathway Knowledge for Cancer Heterogeneity

Cancer cells are much more prone to mutations than normal cells, generating over time, more genetic variants of themselves within the tissue. Drugs designed for one variant might not work as intended for other variants. As such, effective drug design requires estimation of proportion of various cancer subpopulations. In this work, a mixture model based approach with expectation maximization is proposed for determination of cancer heterogeneity. We exploit the pathway knowledge collected by biologists over time to surpass the limitations of identifiability shown by mixture models. Also in cases where Expectation-Maximization converges to more than one solution, pathway knowledge is used to break the tie by defining an error metric. Finally, using experimental data, changes in composition of the mixture over time are estimated using the model. The approach can also be used to compare the effectiveness of different drugs on a heterogeneous cancer tissue by observing the response over time

Recurrence of Acute Page Kidney in a Renal Transplant Allograft.

Acute Page Kidney (APK) phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS). Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft

Recurrence of Acute Page Kidney in a Renal Transplant Allograft

Acute Page Kidney (APK) phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS). Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft

HLA-G Dimers in the Prolongation of Kidney Allograft Survival

Human leukocyte antigen-G (HLA-G) contributes to acceptance of allografts in solid organ/tissue transplantation. Most studies have determined that soluble HLA-G isoforms are systematically detected in serum/plasma of transplanted patients with significantly fewer episodes of acute and/or chronic rejection of allogeneic tissue/organ. Current models of the interactions of HLA-G and its specific receptors explain it as functioning in a monomeric form. However, in recent years, new data has revealed the ability of HLA-G to form disulfide-linked dimeric complexes with high preferential binding and functional activities. Limited data are available on the role of soluble HLA-G dimers in clinical pathological conditions. We describe here the presence of soluble HLA-G dimers in kidney transplant patients. Our study showed that a high level of HLA-G dimers in plasma and increased expression of the membrane-bound form of HLA-G on monocytes are associated with prolongation of kidney allograft survival. We also determined that the presence of soluble HLA-G dimers links to the lower levels of proinflammatory cytokines, suggesting a potential role of HLA-G dimers in controlling the accompanying inflammatory state

Comparative Metaproteomic Analysis on Consecutively Rehmannia glutinosa-Monocultured Rhizosphere Soil

National Natural Science Foundation of China [30772729, 30671220, 31070403]; Natural Science Foundation of Fujian province, China [2008J0051]Background: The consecutive monoculture for most of medicinal plants, such as Rehmannia glutinosa, results in a significant reduction in the yield and quality. There is an urgent need to study for the sustainable development of Chinese herbaceous medicine. Methodology/Principal Findings: Comparative metaproteomics of rhizosphere soil was developed and used to analyze the underlying mechanism of the consecutive monoculture problems of R. glutinosa. The 2D-gel patterns of protein spots for the soil samples showed a strong matrix dependency. Among the spots, 103 spots with high resolution and repeatability were randomly selected and successfully identified by MALDI TOF-TOF MS for a rhizosphere soil metaproteomic profile analysis. These proteins originating from plants and microorganisms play important roles in nutrient cycles and energy flow in rhizospheric soil ecosystem. They function in protein, nucleotide and secondary metabolisms, signal transduction and resistance. Comparative metaproteomics analysis revealed 33 differentially expressed protein spots in rhizosphere soil in response to increasing years of monoculture. Among them, plant proteins related to carbon and nitrogen metabolism and stress response, were mostly up-regulated except a down-regulated protein (glutathione S-transferase) involving detoxification. The phenylalanine ammonia-lyase was believed to participate in the phenylpropanoid metabolism as shown with a considerable increase in total phenolic acid content with increasing years of monoculture. Microbial proteins related to protein metabolism and cell wall biosynthesis, were up-regulated except a down-regulated protein (geranylgeranyl pyrophosphate synthase) functioning in diterpenoid synthesis. The results suggest that the consecutive monoculture of R. glutinosa changes the soil microbial ecology due to the exudates accumulation, as a result, the nutrient cycles are affected, leading to the retardation of plant growth and development. Conclusions/Significance: Our results demonstrated the interactions among plant, soil and microflora in the proteomic level are crucial for the productivity and quality of R. glutinosa in consecutive monoculture system

The Stock Market Evaluation of IPO-Firm Takeovers

We conduct an event study to assess the stock market evaluation of public takeover announcements. Unlike the majority of previous research, we specifically focus on acquisitions targeted at newly public IPO-firms and show that the stock market positively evaluates these M&As as R&D. However, bidders' abnormal announcement returns are significantly lower for takeovers directed at targets with critical intangible assets and innovative capabilities inalienably bound to their initial owners than for those that have internally accumulated respective resources and capabilities. We explain these findings with the acquirer's post-acquisition dependence on continued access to the IPO-firm founders' target-specific human capital. Our results contribute to literature in that they show that the stock market perceives these potential impediments to successful exploitation of acquired strategic resources and thus identify a potential cause for heretofore mostly inconsistent evidence on bidder abnormal returns in corporate takeovers found in previous research

Local cooling for relieving pain from perineal trauma sustained during childbirth (review)

BACKGROUND: Perineal trauma is common during childbirth and may be painful. Contemporary maternity practice includes offering women numerous forms of pain relief, including the local application of cooling treatments. OBJECTIVES: To evaluate the effectiveness and side effects of localised cooling treatments compared with no treatment, other forms of cooling treatments and non-cooling treatments. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2007), CINAHL (1982 to January 2007) and contacted experts in the field. SELECTION CRITERIA: Published and unpublished randomised and quasi-randomised trials (RCTs) that compared localised cooling treatment applied to the perineum with no treatment or other treatments applied to relieve pain related to perineal trauma sustained during childbirth. DATA COLLECTION AND ANALYSIS: At least two independent authors performed data extraction for each study. Analyses were performed on an intention-to-treat basis where data allowed. We sought additional information from the authors of three trials. MAIN RESULTS: Seven published RCTs were included, comparing local cooling treatments (ice packs, cold gel pads or cold/iced baths) with no treatment, hamamelis water (witch hazel), pulsed electromagnetic energy (PET), hydrocortisone/pramoxine foam [Epifoam] or warm baths. The RCTs reported on a total of 859 women. Ice packs provided improved pain relief 24 to 72 hours after birth compared with no treatment (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.41 to 0.91). Women preferred the utility of the gel pads compared with ice packs or no treatment, although no differences in pain relief were detected between the treatments. None of our comparisons of treatments resulted in differences detected in perineal oedema or bruising. Women reported more pain (RR 5.60, 95% CI 2.35 to 13.33) and used more additional analgesia (RR 4.00, 95% CI 1.44 to 11.13) following the application of ice packs compared with PET. AUTHORS' CONCLUSIONS: There is only limited evidence to support the effectiveness of local cooling treatments (ice packs, cold gel pads, cold/iced baths) applied to the perineum following childbirth to relieve pain