An Ultrahigh-throughput Microfluidic Platform for Single-cell Genome Sequencing.

Sequencing technologies have undergone a paradigm shift from bulk to single-cell resolution in response to an evolving understanding of the role of cellular heterogeneity in biological systems. However, single-cell sequencing of large populations has been hampered by limitations in processing genomes for sequencing. In this paper, we describe a method for single-cell genome sequencing (SiC-seq) which uses droplet microfluidics to isolate, amplify, and barcode the genomes of single cells. Cell encapsulation in microgels allows the compartmentalized purification and tagmentation of DNA, while a microfluidic merger efficiently pairs each genome with a unique single-cell oligonucleotide barcode, allowing >50,000 single cells to be sequenced per run. The sequencing data is demultiplexed by barcode, generating groups of reads originating from single cells. As a high-throughput and low-bias method of single-cell sequencing, SiC-seq will enable a broader range of genomic studies targeted at diverse cell populations

Ovarian Carcinoma‐Associated Mesenchymal Stem Cells Arise from Tissue‐Specific Normal Stroma

Carcinoma‐associated mesenchymal stem cells (CA‐MSCs) are critical stromal progenitor cells within the tumor microenvironment (TME). We previously demonstrated that CA‐MSCs differentially express bone morphogenetic protein family members, promote tumor cell growth, increase cancer “stemness,” and chemotherapy resistance. Here, we use RNA sequencing of normal omental MSCs and ovarian CA‐MSCs to demonstrate global changes in CA‐MSC gene expression. Using these expression profiles, we create a unique predictive algorithm to classify CA‐MSCs. Our classifier accurately distinguishes normal omental, ovary, and bone marrow MSCs from ovarian cancer CA‐MSCs. Suggesting broad applicability, the model correctly classifies pancreatic and endometrial cancer CA‐MSCs and distinguishes cancer associated fibroblasts from CA‐MSCs. Using this classifier, we definitively demonstrate ovarian CA‐MSCs arise from tumor mediated reprograming of local tissue MSCs. Although cancer cells alone cannot induce a CA‐MSC phenotype, the in vivo ovarian TME can reprogram omental or ovary MSCs to protumorigenic CA‐MSCs (classifier score of >0.96). In vitro studies suggest that both tumor secreted factors and hypoxia are critical to induce the CA‐MSC phenotype. Interestingly, although the breast cancer TME can reprogram bone marrow MSCs into CA‐MSCs, the ovarian TME cannot, demonstrating for the first time that tumor mediated CA‐MSC conversion is tissue and cancer type dependent. Together these findings (a) provide a critical tool to define CA‐MSCs and (b) highlight cancer cell influence on distinct normal tissues providing powerful insights into the mechanisms underlying cancer specific metastatic niche formation. Stem Cells 2019;37:257–269Ovarian cancer reprograms normal tissue derived mesenchymal stem cells (MSCs) into ovarian cancer promoting carcinoma‐associated mesenchymal stem cells (CA‐MSCs) in a tissue specific manner. Ovarian cancer cells convert ovary and omental MSCs into CA‐MSCs but fail to reprogram bone marrow (BM)‐MSCs whereas breast cancer cells convert BM‐MSCs into breast cancer supporting CA‐MSCs.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147827/1/stem2932_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147827/2/stem2932.pd

X-ray and Optical Study of Low Core Density Globular Clusters NGC6144 and E3

We report on the Chandra X-ray Observatory and Hubble Space Telescope observation of two low core density globular clusters, NGC6144 and E3. By comparing the number of X-ray sources inside the half-mass radius to those outside, we found 6 X-ray sources within the half-mass radius of NGC6144, among which 4 are expected to be background sources; 3 X-ray sources are also found within the half-mass radius of E3, of which 3 is expected to be background source. Therefore, we cannot exclude that all our sources are background sources. However, combining the results from X-ray and optical observations, we found that 1-2 sources in NGC6144 and 1 source in E3 are likely to be cataclysmic variables and that 1 source in NGC6144 is an active binary, based on the X-ray and optical properties. The number of faint X-ray sources in NGC6144 and E3 found with Chandra and HST is higher than a prediction based on collision frequency, but is closer to that based on mass. Our observations strongly suggest that the compact binary systems in NGC6144 and E3 are primordial in origin.Comment: 28 pages, 9 figures, 6 tables, Accepted for publication in Ap

Laser-polarization-dependent photoelectron angular distributions from polar molecules

Photoelectron angular distributions (PADs) of oriented polar molecules in response to different polarized lasers are systematically investigated. It is found that the PADs of polar CO molecules show three distinct styles excited by linearly, elliptically and circularly polarized lasers respectively. In the case of elliptical polarization, a deep suppression is observed along the major axis and the distribution concentrates approximately along the minor axis. Additionally, it is also found that the concentrated distributions rotate clockwise as the ellipticity increases. Our investigation presents a method to manipulate the motion and angular distribution of photoelectrons by varying the polarization of the exciting pulses, and also implies the possibility to control the processes in laser-molecule interactions in future work.Comment: 12 pages and 7 figure

Structural efficiency of percolation landscapes in flow networks

Complex networks characterized by global transport processes rely on the presence of directed paths from input to output nodes and edges, which organize in characteristic linked components. The analysis of such network-spanning structures in the framework of percolation theory, and in particular the key role of edge interfaces bridging the communication between core and periphery, allow us to shed light on the structural properties of real and theoretical flow networks, and to define criteria and quantities to characterize their efficiency at the interplay between structure and functionality. In particular, it is possible to assess that an optimal flow network should look like a "hairy ball", so to minimize bottleneck effects and the sensitivity to failures. Moreover, the thorough analysis of two real networks, the Internet customer-provider set of relationships at the autonomous system level and the nervous system of the worm Caenorhabditis elegans --that have been shaped by very different dynamics and in very different time-scales--, reveals that whereas biological evolution has selected a structure close to the optimal layout, market competition does not necessarily tend toward the most customer efficient architecture.Comment: 8 pages, 5 figure

Co-evolution of density and topology in a simple model of city formation

We study the influence that population density and the road network have on each others' growth and evolution. We use a simple model of formation and evolution of city roads which reproduces the most important empirical features of street networks in cities. Within this framework, we explicitely introduce the topology of the road network and analyze how it evolves and interact with the evolution of population density. We show that accessibility issues -pushing individuals to get closer to high centrality nodes- lead to high density regions and the appearance of densely populated centers. In particular, this model reproduces the empirical fact that the density profile decreases exponentially from a core district. In this simplified model, the size of the core district depends on the relative importance of transportation and rent costs.Comment: 13 pages, 13 figure

Impact of the interval between coronary angiography and off-pump coronary bypass surgery on postoperative renal function

BACKGROUND: Postoperative acute kidney injury (AKI) is a significant complication after coronary artery bypass surgery. Prior coronary angiography increases the likelihood of AKI due to the use of a radiocontrast dye. This study examined the effect of coronary angiography on the postoperative renal function after off-pump coronary artery bypass surgery (OPCAB). METHODS: The records of 110 patients who required OPCAB were reviewed. These patients also had at least two of the following conditions: chronic kidney disease, hypertension, diabetes mellitus, emergency surgery, congestive heart failure, age >75 years, hematocrit /=50% or >/=0.3 mg/dl within 48 hours. RESULTS: The postoperative changes in the SCr, cystatin C and eGFR were similar in the two groups. The incidence of AKI and renal replacement therapy were similar in the two groups. CONCLUSIONS: Coronary angiography performed within two days of OPCAB does not affect the postoperative renal functionope

Versatile Sarcosine Biosensing Schemes Utilizing Layer-by-Layer Construction of Carbon Nanotube-Chitosan Composite Films

Layer-by-layer composite films of carbon nanotubes (CNTs) within a chitosan matrix with sarcosine oxidase enzyme and capped with Nafion have been developed and optimized as a versatile 1st generation amperometric sarcosine biosensing platform that operates successfully both as an isolated sarcosine sensor as well as a functional component within a creatinine sensor. Accurate measurement of sarcosine in urine and creatinine in blood may help with early diagnosis of diseases such as prostate cancer and renal failure, respectively. In this study, each material within the film is systematically optimized toward sarcosine sensitivity, including a critical evaluation of different CNTs effect on sensing performance. Films featuring carboxylic acid–modified single–walled carbon nanotubes and strategic enzyme doping were shown to be most effective sarcosine sensing platforms, exhibiting excellent sensitivity (~0.5 μA/mM), a linear response (≤ 0.75 mM), fast response time (8 s), low limits of detection (~6 μM), as well as both continuous use stability (7 days) and effective shelf life (\u3e 12 days). Operation of the sarcosine sensor was demonstrated in a urine matrix, detecting sarcosine at physiologically relevant concentrations and successfully quantifying sarcosine-spiked urine samples with high percent recovery and low relative error. The sarcosine sensing platform was also adapted to a 1st generation creatinine biosensing scheme in which the sarcosine enzymatic reaction is critical to a trienzymatic cascade event. The creatinine sensor yielded sensitivity of ~0.6 μA/mM, similar sensing performance parameters to the sarcosine sensor, and was effectively operated in blood serum at physiologically relevant creatinine concentrations. The demonstrated functionality of these sensors in their respective biological fluids at physiological concentrations of the analyte species suggests potential clinical application as diagnostic tools

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721

Outcomes in hepatitis C virus–infected recipients of living donor vs. deceased donor liver transplantation

In this retrospective study of hepatitis C virus (HCV)–infected transplant recipients in the 9-center Adult to Adult Living Donor Liver Transplantation Cohort Study, graft and patient survival and the development of advanced fibrosis were compared among 181 living donor liver transplant (LDLT) recipients and 94 deceased donor liver transplant (DDLT) recipients. Overall 3-year graft and patient survival were 68% and 74% in LDLT, and 80% and 82% in DDLT, respectively. Graft survival, but not patient survival, was significantly lower for LDLT compared to DDLT ( P = 0.04 and P = 0.20, respectively). Further analyses demonstrated lower graft and patient survival among the first 20 LDLT cases at each center (LDLT 20; P = 0.002 and P = 0.002, respectively) and DDLT recipients ( P 20 and DDLT were not significantly different ( P = 0.66 and P = 0.74, respectively). Overall, 3-year graft survival for DDLT, LDLT >20, and LDLT 20 were not significantly different. Important predictors of graft loss in HCV-infected patients were limited LDLT experience, pretransplant HCC, and higher MELD at transplantation. Liver Transpl 13:122–129, 2007. © 2006 AASLD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55915/1/20995_ftp.pd