Heat Conductance of the Quantum Hall Bulk

The Quantum Hall Effect (QHE) is the prototypical realization of a topological state of matter. It emerges from a subtle interplay between topology, interactions, and disorder. The disorder enables the formation of localized states in the bulk that stabilize the quantum Hall states with respect to the magnetic field and carrier density. Still, the details of the localized states and their contribution to transport remain beyond the reach of most experimental techniques. Here, we describe an extensive study of the bulk's heat conductance. Using a novel 'multi-terminal' device, we separate the longitudinal thermal conductance (due to bulk's contribution) $\kappa_{xx}T$ from the two-terminal value $\kappa_{2T}T$, by eliminating the contribution of the edge modes. We find that when the field is tuned away from the conductance plateau center, the electronic states of the bulk conduct heat efficiently while the bulk remains electrically insulating. For fragile fractional states, such as the non-Abelian $\nu=5/2$, we observe a finite $\kappa_{xx}T$ throughout the plateau. We identify the localized states as the cause of the finite $\kappa_{xx}T$ and propose a theoretical model which qualitatively explains our findings.Comment: 26 pages 9 figure

Human cytomegalovirus long noncoding RNA4.9 regulates viral DNA replication

Viruses are known for their extremely compact genomes composed almost entirely of protein-coding genes. Nonetheless, four long noncoding RNAs (lncRNAs) are encoded by human cytomegalovirus (HCMV). Although these RNAs accumulate to high levels during lytic infection, their functions remain largely unknown. Here, we show that HCMV-encoded lncRNA4.9 localizes to the viral nuclear replication compartment, and that its depletion restricts viral DNA replication and viral growth. RNA4.9 is transcribed from the HCMV origin of replication (oriLyt) and forms an RNA-DNA hybrid (R-loop) through its G+C-rich 5’ end, which may be important for the initiation of viral DNA replication. Furthermore, targeting the RNA4.9 promoter with CRISPR-Cas9 or genetic relocalization of oriLyt leads to reduced levels of the viral single-stranded DNA-binding protein (ssDBP), suggesting that the levels of ssDBP are coupled to the oriLyt activity. We further identified a similar, oriLyt-embedded, G+C-rich lncRNA in murine cytomegalovirus (MCMV). These results indicate that HCMV RNA4.9 plays an important role in regulating viral DNA replication, that the levels of ssDBP are coupled to the oriLyt activity, and that these regulatory features may be conserved among betaherpesviruses

Syncytiotrophoblast Microvesicles Released from Pre-Eclampsia Placentae Exhibit Increased Tissue Factor Activity

Background: Pre-eclampsia is a complication of pregnancy associated with activation of coagulation. It is caused by the placenta, which sheds increased amounts of syncytiotrophoblast microvesicles (STBM) into the maternal circulation. We hypothesized that STBM could contribute to the haemostatic activation observed in pre-eclampsia. Methodology/Principal Findings: STBM were collected by perfusion of the maternal side of placentae from healthy pregnant women and women with pre-eclampsia at caesarean section. Calibrated automated thrombography was used to assess thrombin generation triggered by STBM-borne tissue factor in platelet poor plasma (PPP). No thrombin was detected in PPP alone but the addition of STBM initiated thrombin generation in 14/16 cases. Pre-eclampsia STBM significantly shortened the lag time (LagT, P = 0.01) and time to peak thrombin generation (TTP, P = 0.005) when compared to normal STBM. Blockade of tissue factor eliminated thrombin generation, while inhibition of tissue factor pathway inhibitor significantly shortened LagT (p = 0.01) and TTP (P,0.0001), with a concomitant increase in endogenous thrombin potential. Conclusions/Significance: STBM triggered thrombin generation in normal plasma in a tissue factor dependent manner, indicating that TF activity is expressed by STBM. This is more pronounced in STBM shed from pre-eclampsia placentae. As more STBM are shed in pre-eclampsia these observations give insight into the disordered haemostasis observed in thi

A clinical evaluation of an ex vivo organ culture system to predict patient response to cancer therapy

IntroductionEx vivo organ cultures (EVOC) were recently optimized to sustain cancer tissue for 5 days with its complete microenvironment. We examined the ability of an EVOC platform to predict patient response to cancer therapy.MethodsA multicenter, prospective, single-arm observational trial. Samples were obtained from patients with newly diagnosed bladder cancer who underwent transurethral resection of bladder tumor and from core needle biopsies of patients with metastatic cancer. The tumors were cut into 250 μM slices and cultured within 24 h, then incubated for 96 h with vehicle or intended to treat drug. The cultures were then fixed and stained to analyze their morphology and cell viability. Each EVOC was given a score based on cell viability, level of damage, and Ki67 proliferation, and the scores were correlated with the patients’ clinical response assessed by pathology or Response Evaluation Criteria in Solid Tumors (RECIST).ResultsThe cancer tissue and microenvironment, including endothelial and immune cells, were preserved at high viability with continued cell division for 5 days, demonstrating active cell signaling dynamics. A total of 34 cancer samples were tested by the platform and were correlated with clinical results. A higher EVOC score was correlated with better clinical response. The EVOC system showed a predictive specificity of 77.7% (7/9, 95% CI 0.4–0.97) and a sensitivity of 96% (24/25, 95% CI 0.80–0.99).ConclusionEVOC cultured for 5 days showed high sensitivity and specificity for predicting clinical response to therapy among patients with muscle-invasive bladder cancer and other solid tumors

The microrelations of urban governance: dynamics of patronage and partnership

The classic urban ecological paradigm envisioned the articulation of the social organization of neighborhoods with that of the city as a whole. This article offers novel empirical evidence in support of this proposi- tion. We analyze the microrelations of governance across two key urban domains, politics and nonprofit organizations, and identify the district- based politician as a key actor linking neighborhood-based and citywide forms of social organization. Using data of contracts allocated by city council members to nonprofits in New York City, analysis of the social network system linking these two types of actors shows two distinct re- lational dynamics: a patronage dynamic characterized by exclusive and long-lasting relationships between a council member and his/her local constituency and a partnership dynamic characterized by citywide rela- tionships that are short-lived and fostered by organizational differentia- tion and embeddedness. Furthermore, politicians and nonprofits differ- ently accommodate the copresence of these two models of resource allocation