Learning Temporal Transformations From Time-Lapse Videos

Based on life-long observations of physical, chemical, and biologic phenomena in the natural world, humans can often easily picture in their minds what an object will look like in the future. But, what about computers? In this paper, we learn computational models of object transformations from time-lapse videos. In particular, we explore the use of generative models to create depictions of objects at future times. These models explore several different prediction tasks: generating a future state given a single depiction of an object, generating a future state given two depictions of an object at different times, and generating future states recursively in a recurrent framework. We provide both qualitative and quantitative evaluations of the generated results, and also conduct a human evaluation to compare variations of our models.Comment: ECCV201

Record linkage research and informed consent: who consents?

BACKGROUND: Linking computerized health insurance records with routinely collected survey data is becoming increasingly popular in health services research. However, if consent is not universal, the requirement of written informed consent may introduce a number of research biases. The participants of a national health survey in Taiwan were asked to have their questionnaire results linked to their national health insurance records. This study compares those who consented with those who refused. METHODS: A national representative sample (n = 14,611 adults) of the general adult population aged 20 years or older who participated in the Taiwan National Health Interview Survey (NHIS) and who provided complete survey information were used in this study. At the end of the survey, the respondents were asked if they would give permission to access their National Health Insurance records. Information given by the interviewees in the survey was used to analyze who was more likely to consent to linkage and who wasn't. RESULTS: Of the 14,611 NHIS participants, 12,911 (88%) gave consent, and 1,700 (12%) denied consent. The elderly, the illiterate, those with a lower income, and the suburban area residents were significantly more likely to deny consent. The aborigines were significantly less likely to refuse. No discrepancy in gender and self-reported health was found between individuals who consented and those who refused. CONCLUSION: This study is the first population-based study in assessing the consent pattern in a general Asian population. Consistent with people in Western societies, in Taiwan, a typical Asian society, a high percentage of adults gave consent for their health insurance records and questionnaire results to be linked. Consenters differed significantly from non-consenters in important aspects such as age, ethnicity, and educational background. Consequently, having a high consent rate (88%) may not fully eliminate the possibility of selection bias. Researchers should take this source of bias into consideration in their study design and investigate any potential impact of this source of bias on their results

Viral non-coding RNA inhibits HNF4α expression in HCV associated hepatocellular carcinoma

BACKGROUND: Hepatitis C virus (HCV) infection is an established cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC); however, it is unclear if the virus plays a direct role in the development of HCC. Hepatocyte nuclear factor 4α (HNF4α) is critical determinant of epithelial architecture and hepatic development; depletion of HNF4α is correlated with oncogenic transformation. We explored the viral role in the inhibition of HNF4α expression, and consequent induction of tumor-promoting genes in HCV infection-associated HCC. METHODS: Western blot analysis was used to monitor the changes in expression levels of oncogenic proteins in liver tissues from HCV-infected humanized mice. The mechanism of HNF4α depletion was studied in HCV-infected human hepatocyte cultures in vitro. Targeting of HNF4α expression by viral non-coding RNA was examined by inhibition of Luciferase HNF4α 3’-UTR reporter. Modulation of invasive properties of HCV-infected cells was examined by Matrigel cell migration assay. RESULTS: Results show inhibition of HNF4α expression by targeting of HNF4α 3’-UTR by HCV-derived small non-coding RNA, vmr11. Vmr11 enhances the invasive properties of HCV-infected cells. Loss of HNF4α in HCV-infected liver tumors of humanized mice correlates with the induction of epithelial to mesenchymal transition (EMT) genes. CONCLUSIONS: We show depletion of HNF4α in liver tumors of HCV-infected humanized mice by HCV derived small non-coding RNA (vmr11) and resultant induction of EMT genes, which are critical determinants of tumor progression. These results suggest a direct viral role in the development of hepatocellular carcinoma

Community-acquired Klebsiella pneumoniae meningitis in an alcoholic patient with an infected pancreatic pseudocyst; a case report and review of literature

We report a case of a 49-year-old male with a history of chronic alcoholism and evidence of a pancreatic pseudocyst on CT scanning. He presented with a 3-days history of fever, loss of appetite and upper abdominal pain. Blood cultures grew Klebsiella pneumoniae and he improved clinically with a seven-day course of intravenous co-amoxiclav and metronidazole. Two weeks later he was readmitted to hospital with impaired consciousness and septic shock, and died three days later in intensive care. Post mortem examination revealed bacterial meningitis and an infected pancreatic pseudocyst. Klebsiella pneumoniae was isolated from the pancreas and meninges

Pemetrexed pharmacokinetics and pharmacodynamics in a phase I/II study of doublet chemotherapy with vinorelbine: implications for further optimisation of pemetrexed schedules

The purpose of this study was to investigate the utility of plasma pharmacokinetic and pharmacodynamic measures including plasma deoxynucleosides, homocysteine and methylmalonic acid concentrations in understanding the time course and extent of the inhibition of thymidylate synthase (TS) by pemetrexed in the context of a phase I/II combination study with vinorelbine. Eighteen patients received supplementation with folic acid and Vitamin B12 1 week before beginning treatment with pemetrexed and vinorelbine administered in a dose-escalating manner on a 21-day cycle. Heparinised blood samples were collected from consenting patients in the first cycle for pharmacokinetic analyses and in the first two cycles for determination of plasma thymidine, deoxyuridine, homocysteine and methylmalonic acid concentrations. These values were correlated with response and toxicity. Plasma deoxyuridine was used as a measure of TS inhibition, and concentrations of deoxyuridine were significantly elevated relative to baseline on days 1 (P<0.01), 2 (P<0.001) and 3 (P<0.05) after treatment at all pemetrexed dose levels (400–700 mg m−2). The magnitude of deoxyuridine elevation correlated with pemetrexed area under the plasma concentration–time curve (AUC) (r2=0.23, P<0.05). However, deoxyuridine concentrations returned to baseline between 8 and 15 days after treatment with pemetrexed, suggesting that inhibition of TS was not durable. Pemetrexed AUC correlated with the percentage decline (relative to baseline) in both platelets (r2=0.58, P<0.001) and leucocytes (r2=0.26, P<0.05) at day 8. Baseline homocysteine was also significantly correlated with these measures of haematological toxicity (r2=0.37, P<0.01 and r2=0.39, P<0.01, respectively). In addition, there was a significant reduction of plasma homocysteine on days 8 (P<0.005) and 15 (P<0.05) in cycle 1 compared to baseline values. The results suggest that the TS inhibitory effects of pemetrexed are short-lived and make the case for a more frequent schedule of administration such as every 2 weeks. The lack of protracted TS inhibition may be due to concomitant vitamin administration, and this may be the mechanism by which vitamins prevent life-threatening toxicity from pemetrexed. Baseline homocysteine concentration remains a predictive marker for haematological toxicity even following folate supplementation

CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines.

INTRODUCTION: Metastasis is a complex process involving loss of adhesion, migration, invasion and proliferation of cancer cells. Cell adhesion molecules play a pivotal role in this phenomenon by regulating cell-cell and cell-matrix interactions. CD146 (MCAM) is associated with an advanced tumor stage in melanoma, prostate cancer and ovarian cancer. Studies of CD146 expression and function in breast cancer remain scarce except for a report concluding that CD146 could act as a tumor suppressor in breast carcinogenesis. METHODS: To resolve these apparent discrepancies in the role of CD146 in tumor cells, we looked at the association of CD146 expression with histoclinical features in human primary breast cancers using DNA and tissue microarrays. By flow cytometry, we characterized CD146 expression on different breast cancer cell lines. Using siRNA or shRNA technology, we studied functional consequences of CD146 downmodulation of MDA-MB-231 cells in migration assays. Wild-type, mock-transfected and downmodulated transfected cells were profiled using whole-genome DNA microarrays to identify genes whose expression was modified by CD146 downregulation. RESULTS: Microarray studies revealed the association of higher levels of CD146 with histoclinical features that belong to the basal cluster of human tumors. Expression of CD146 protein on epithelial cells was detected in a small subset of cancers with histoclinical features of basal tumors. CD146+ cell lines displayed a mesenchymal phenotype. Downmodulation of CD146 expression in the MDA-MB-231 cell line resulted in downmodulation of vimentin, as well as of a set of genes that include both genes associated with a poor prognosis in a variety of cancers and genes known to promote cell motility. In vitro functional assays revealed decreased migration abilities associated with decreased CD146 expression. CONCLUSIONS: In addition to its expression in the vascular compartment, CD146 is expressed on a subset of epithelial cells in malignant breast. CD146 may directly or indirectly contribute to tumor aggressiveness by promoting malignant cell motility. Changes in molecular signatures following downmodulation of CD146 expression suggest that CD146 downmodulation is associated with the reversal of several biological characteristics associated with epithelial to mesenchymal transition, and the phenomenon associated with the metastatic process.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Low-Energy Probes of a Warped Extra Dimension

We investigate a natural realization of a light Abelian hidden sector in an extended Randall-Sundrum (RS) model. In addition to the usual RS bulk we consider a second warped space containing a bulk U(1)_x gauge theory with a characteristic IR scale of order a GeV. This Abelian hidden sector can couple to the standard model via gauge kinetic mixing on a common UV brane. We show that if such a coupling induces significant mixing between the lightest U(1)_x gauge mode and the standard model photon and Z, it can also induce significant mixing with the heavier U(1)_x Kaluza-Klein (KK) modes. As a result it might be possible to probe several KK modes in upcoming fixed-target experiments and meson factories, thereby offering a new way to investigate the structure of an extra spacetime dimension.Comment: 26 pages, 1 figure, added references, corrected minor typos, same as journal versio

Production of Virus-Derived Ping-Pong-Dependent piRNA-like Small RNAs in the Mosquito Soma

The natural maintenance cycles of many mosquito-borne pathogens require establishment of persistent non-lethal infections in the invertebrate host. The mechanism by which this occurs is not well understood, but we have previously shown that an antiviral response directed by small interfering RNAs (siRNAs) is important in modulating the pathogenesis of alphavirus infections in the mosquito. However, we report here that infection of mosquitoes with an alphavirus also triggers the production of another class of virus-derived small RNAs that exhibit many similarities to ping-pong-dependent piwi-interacting RNAs (piRNAs). However, unlike ping-pong-dependent piRNAs that have been described previously from repetitive elements or piRNA clusters, our work suggests production in the soma. We also present evidence that suggests virus-derived piRNA-like small RNAs are capable of modulating the pathogenesis of alphavirus infections in dicer-2 null mutant mosquito cell lines defective in viral siRNA production. Overall, our results suggest that a non-canonical piRNA pathway is present in the soma of vector mosquitoes and may be acting redundantly to the siRNA pathway to target alphavirus replication

Enterovirus 71 3C Protease Cleaves a Novel Target CstF-64 and Inhibits Cellular Polyadenylation

Identification of novel cellular proteins as substrates to viral proteases would provide a new insight into the mechanism of cell–virus interplay. Eight nuclear proteins as potential targets for enterovirus 71 (EV71) 3C protease (3Cpro) cleavages were identified by 2D electrophoresis and MALDI-TOF analysis. Of these proteins, CstF-64, which is a critical factor for 3′ pre-mRNA processing in a cell nucleus, was selected for further study. A time-course study to monitor the expression levels of CstF-64 in EV71-infected cells also revealed that the reduction of CstF-64 during virus infection was correlated with the production of viral 3Cpro. CstF-64 was cleaved in vitro by 3Cpro but neither by mutant 3Cpro (in which the catalytic site was inactivated) nor by another EV71 protease 2Apro. Serial mutagenesis was performed in CstF-64, revealing that the 3Cpro cleavage sites are located at position 251 in the N-terminal P/G-rich domain and at multiple positions close to the C-terminus of CstF-64 (around position 500). An accumulation of unprocessed pre-mRNA and the depression of mature mRNA were observed in EV71-infected cells. An in vitro assay revealed the inhibition of the 3′-end pre-mRNA processing and polyadenylation in 3Cpro-treated nuclear extract, and this impairment was rescued by adding purified recombinant CstF-64 protein. In summing up the above results, we suggest that 3Cpro cleavage inactivates CstF-64 and impairs the host cell polyadenylation in vitro, as well as in virus-infected cells. This finding is, to our knowledge, the first to demonstrate that a picornavirus protein affects the polyadenylation of host mRNA