Generation of continuous variable Einstein-Podolsky-Rosen entanglement via the Kerr nonlinearity in an optical fiber

We report on the generation of a continuous variable Einstein-Podolsky-Rosen (EPR) entanglement using an optical fiber interferometer. The Kerr nonlinearity in the fiber is exploited for the generation of two independent squeezed beams. These interfere at a beam splitter and EPR entanglement is obtained between the output beams. The correlation of the amplitude (phase) quadratures is measured to be 4.0±0.2 (4.0±0.4)dB below the quantum noise limit. The sum criterion for these squeezing variances 0.80±0.03<2 verifies the nonseparability of the state. The product of the inferred uncertainties for one beam (0.64±0.08) is well below the EPR limit of unity

Integrated Transcriptomic and Proteomic Analysis Reveals Role of the Hexosamine Biosynthetic Pathway in Invasion and Metastasis of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a major global cause of mortality. The epithelial-mesenchymal transition (EMT) transcription factor TWIST1 has been implicated in the invasion and metastasis of HCC, but the mechanism is unclear. My goal was to define a cancer cell autonomous mechanism of Twist1-induced metastasis in HCC. Integrated transcriptomic and proteomic analyses on primary liver tumors and lung metastases from a spontaneous Twist1-dependent metastasis mouse model of MYC-induced HCC identified the hexosamine biosynthetic pathway (HBP) as a cancer cell autonomous mechanism for EMT-mediated invasion and metastasis. I demonstrated that the hexosamine biosynthetic pathway is required and sufficient for invasion and metastasis in vitro in HCC cell lines, ex vivo in HCC tumor-derived organoids, and in vivo in a genetically engineered mouse model of metastatic HCC. Therefore, the HBP may be a potential therapeutic target for advanced HCC patients

Human urinary mutagenicity after wood smoke exposure during traditional temazcal use.

In Central America, the traditional temazcales or wood-fired steam baths, commonly used by many Native American populations, are often heated by wood fires with little ventilation, and this use results in high wood smoke exposure. Urinary mutagenicity has been previously employed as a non-invasive biomarker of human exposure to combustion emissions. This study examined the urinary mutagenicity in 19 indigenous Mayan families from the highlands of Guatemala who regularly use temazcales (N = 32), as well as control (unexposed) individuals from the same population (N = 9). Urine samples collected before and after temazcal exposure were enzymatically deconjugated and extracted using solid-phase extraction. The creatinine-adjusted mutagenic potency of urine extracts was assessed using the plate-incorporation version of the Salmonella mutagenicity assay with strain YG1041 in the presence of exogenous metabolic activation. The post-exposure mutagenic potency of urine extracts were, on average, 1.7-fold higher than pre-exposure samples (P &lt; 0.005) and also significantly more mutagenic than the control samples (P &lt; 0.05). Exhaled carbon monoxide (CO) was ~10 times higher following temazcal use (P &lt; 0.0001), and both CO level and time spent in temazcal were positively associated with urinary mutagenic potency (i.e. P &lt; 0.0001 and P = 0.01, respectively). Thus, the wood smoke exposure associated with temazcal use contributes to increased excretion of conjugated mutagenic metabolites. Moreover, urinary mutagenic potency is correlated with other metrics of exposure (i.e. exhaled CO, duration of exposure). Since urinary mutagenicity is a biomarker associated with genetic damage, temazcal use may therefore be expected to contribute to an increased risk of DNA damage and mutation, effects associated with the initiation of cancer

Sense-making, sensemaking and sense making:A systematic review and meta‐synthesis of literature in information science and education: An Annual Review of Information Science and Technology (ARIST) paper

Sense‐making, sensemaking, and sense making are terms used in different disciplines. Similarities of usage seem unclear. (1) to examine the concepts used in different approaches to sense‐making/sensemaking/sense making; (2) to identify, classify and synthesize recent studies relevant to information science, as well as similar group on sensemaking in education research; (3) to reflect on future directions for sense‐making/sensemaking methodology in information science. The objectives were to retrieve, examine, classify and perform meta‐synthesis on sense‐making/sensemaking studies in both information science and education research. The review used systematic review principles, with selection criteria for case studies for examination in both information science and education sets. The final meta‐synthesis used a meta‐ethnographic approach, together with findings of recent overviews on organizational sensemaking, and other information science reviews. Qualitative sense‐making studies in information science often used Dervin's SMM (sense‐making methodology) and studies in organizations and education frequently used Weick's organizational sensemaking. Different mixed methods approaches were identified. Sense‐making is actively used in research and practice in information science and knowledge management. Using a coherent sense‐making methodology helps and dialogic principles are useful in planning, data collection and analysis. Individual and collective sense‐making are important to information science

Splice variants of DOMINO control Drosophila circadian behavior and pacemaker neuron maintenance.

Circadian clocks control daily rhythms in behavior and physiology. In Drosophila, the small ventral lateral neurons (sLNvs) expressing PIGMENT DISPERSING FACTOR (PDF) are the master pacemaker neurons generating locomotor rhythms. Despite the importance of sLNvs and PDF in circadian behavior, little is known about factors that control sLNvs maintenance and PDF accumulation. Here, we identify the Drosophila SWI2/SNF2 protein DOMINO (DOM) as a key regulator of circadian behavior. Depletion of DOM in circadian neurons eliminates morning anticipatory activity under light dark cycle and impairs behavioral rhythmicity in constant darkness. Interestingly, the two major splice variants of DOM, DOM-A and DOM-B have distinct circadian functions. DOM-A depletion mainly leads to arrhythmic behavior, while DOM-B knockdown lengthens circadian period without affecting the circadian rhythmicity. Both DOM-A and DOM-B bind to the promoter regions of key pacemaker genes period and timeless, and regulate their protein expression. However, we identify that only DOM-A is required for the maintenance of sLNvs and transcription of pdf. Lastly, constitutive activation of PDF-receptor signaling rescued the arrhythmia and period lengthening of DOM downregulation. Taken together, our findings reveal that two splice variants of DOM play distinct roles in circadian rhythms through regulating abundance of pacemaker proteins and sLNvs maintenance

Protein diversification through post-translational modifications, alternative splicing, and gene duplication

Proteins provide the basis for cellular function. Having multiple versions of the same protein within a single organism provides a way of regulating its activity or developing novel functions. Post-translational modifications of proteins, by means of adding/removing chemical groups to amino acids, allow for a well-regulated and controlled way of generating functionally distinct protein species. Alternative splicing is another method with which organisms possibly generate new isoforms. Additionally, gene duplication events throughout evolution generate multiple paralogs of the same genes, resulting in multiple versions of the same protein within an organism. In this review, we discuss recent advancements in the study of these three methods of protein diversification and provide illustrative examples of how they affect protein structure and function

Impact of an interdisciplinary patient care model and routine screening on clinical outcomes in patients with hepatitis C

Testing for hepatitis C in hospital emergency departments (ED) and linkage to care to clinics have been reported to provide the most opportunity for screening patients and facilitating continuum of care. Treatment model initiatives have expanded to include telehealth services and open treatment capacity to non-physician providers, such as pharmacists. This study’s objective is to assess the impact of implementing automated routine screening for hepatitis C virus (HCV) and a clinical pharmacist into the interdisciplinary care model on HCV diagnosis and treatment outcomes.     This retrospective cohort study compared outcomes in a pre-intervention and post-intervention group. Patients were screened and diagnosed with HCV at Jersey City Medical Center (JCMC) and completed linkage to care at JCMC Center for Comprehensive Care. Interventions were the implementation of automated routine HCV screening in the ED and addition of a clinical pharmacist to the interdisciplinary patient care model. Primary Endpoints analyzed the number of patients who have achieved sustained virologic response after 12 weeks of treatment (SVR12) and patients who have completed treatment with no reported record of SVR12. Secondary Endpoints analyzed the number of patients lost to follow-up, appointment type, time spent in appointments, and clinical pharmacist specialist interventions. Data was collected as categorical variables and chi-squared tests assessed if there were differences between the two samples.     Data was collected from 46 patients in the pre-intervention group and 37 patients in the post-intervention group. Patients consisted of mostly males. Ages ranged from 27 to 83 years old. Race and ethnicities included Black, White, Asian, and Other.     This study’s results show the positive impact on implementation of routine screening, telehealth services, and an interdisciplinary team approach to HCV diagnosis and management. Given the timeframe, it also shows the potential positive impact on these interventions during a global pandemic. 

Workflow Modifications and Addition of MALDI-TOF Technology Significantly Improved Turn-Around-Time to Identification of Common Urine Pathogens

Background: In order to improve the identification of common aerobic urine cultures as well as antimicrobial susceptibility testing (AST) setup at an Academic Medical Center, work-flow modifications and MALDI-TOF technology were incorporated. Previously, the majority of species identification was achieved with conventional identification/antimicrobial susceptibility combo panels. All urine cultures, regardless of laboratory receipt time, were previously read once per day on 1st shift. Methods: The initial workflow modification involved addition of a 2nd shift urine culture reading. Urine specimens received from 8:00 AM to 4:00 PM were read on 1st shift, while urine specimens received from 4:00 PM to 8:00 AM were read on 2nd shift. Additionally, urine cultures were sorted into categories: no growth (NG) at 24 hours, no growth at \u3c24 hours, single colonies of growth, multiple colonies of growth, and potential contaminants. No growth cultures were signed out at 24 hours. No growth cultures at \u3c 24 hours were reincubated to be read on subsequent shift. Cultures with growth were set aside as either single colony types or multiple colony types. Cultures of probable contaminants were signed out. Once cultures were sorted, the isolated colonies underwent MALDI-TOF analysis (Bruker) and antimicrobial susceptibility testing (AST) as appropriate. Individual technologists setup the MALDITOF target plate map and spotted the associated target plate. AST was setup at the same time. The MALDI-TOF was then operated by a central technologist and results reported by the original technologist reading the culture. Results: Retrospective pre-workflow (September-November 2013) and post-workflow (May, June, October 2014) modification turn-around-times were compared for 16 commonly isolated pathogens. These pathogens consisted of common urine pathogens as noted in Table 1. Staphylococcus aureus was previously identified in our laboratory by a positive coagulase test and not included in this analysis. The average turn-around-times, standard deviations and the p-values for each organism are indicated in Table 1. Conclusion: Converting from conventional identification methods to MALDI-TOF, in conjunction with workflow modifications such as a 2nd culture reading, notably improved urine culture turn-around-time for identification and AST

Cytokinesis Monitoring during Development Rapid Pole-to-Pole Shuttling of a Signaling Protein by Localized Kinase and Phosphatase in Caulobacter

AbstractFor successful generation of different cell types by asymmetric cell division, cell differentiation should be initiated only after completion of division. Here, we describe a control mechanism by which Caulobacter couples the initiation of a developmental program to the completion of cytokinesis. Genetic evidence indicates that localization of the signaling protein DivK at the flagellated pole prevents premature initiation of development. Photobleaching and FRET experiments show that polar localization of DivK is dynamic with rapid pole-to-pole shuttling of diffusible DivK generated by the localized activities of PleC phosphatase and DivJ kinase at opposite poles. This shuttling is interrupted upon completion of cytokinesis by the segregation of PleC and DivJ to different daughter cells, resulting in disruption of DivK localization at the flagellated pole and subsequent initiation of development in the flagellated progeny. Thus, dynamic polar localization of a diffusible protein provides a control mechanism that monitors cytokinesis to regulate development