Influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training on the plasma cytokine response to maximum sustainable voluntary ventilation

The influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training (IMT) on the cytokine response to maximum sustainable voluntary ventilation (MSVV) is unknown. Twelve healthy males were divided equally into an IMT or placebo (PLA) group, and before and after a 6-wk intervention they undertook, on separate days, 1h of (1) passive rest and (2) MSVV, whereby participants undertook volitional hyperpnea at rest that mimicked the breathing and respiratory muscle recruitment patterns commensurate with heavy cycling exercise. Plasma cytokines remained unchanged during passive rest. There was a main effect of time (P < 0.01) for plasma interleukin-1 (IL-1) and interleukin-6 (IL-6) concentrations and a strong trend (P = 0.067) for plasma interleukin-1 receptor antagonist concentration during MSVV. Plasma IL-6 concentration was reduced after IMT by 27 + 18% (main effect of intervention, P = 0.029), whereas there was no change after PLA (P = 0.753). There was no increase in a systemic marker of oxidative stress [DNA damage in peripheral blood mononuclear cells (PBMC)], and diaphragm fatigue was not related to the increases in plasma IL-1 and IL-6 concentrations. A dose-response relationship was observed between respiratory muscle work and minute ventilation and increases in plasma IL-6 concentration. In conclusion, increases in plasma IL-1 and IL-6 concentrations during MSVV were not due to diaphragm fatigue or DNA damage in PBMC. Increases in plasma IL-6 concentration during MSVV are attenuated following IMT, and the plasma IL-6 response is dependent upon the level of respiratory muscle work and minute ventilation

Spin and valley quantum Hall ferromagnetism in graphene

In a graphene Landau level (LL), strong Coulomb interactions and the fourfold spin/valley degeneracy lead to an approximate SU(4) isospin symmetry. At partial filling, exchange interactions can spontaneously break this symmetry, manifesting as additional integer quantum Hall plateaus outside the normal sequence. Here we report the observation of a large number of these quantum Hall isospin ferromagnetic (QHIFM) states, which we classify according to their real spin structure using temperature-dependent tilted field magnetotransport. The large measured activation gaps confirm the Coulomb origin of the broken symmetry states, but the order is strongly dependent on LL index. In the high energy LLs, the Zeeman effect is the dominant aligning field, leading to real spin ferromagnets with Skyrmionic excitations at half filling, whereas in the `relativistic' zero energy LL, lattice scale anisotropies drive the system to a spin unpolarized state, likely a charge- or spin-density wave.Comment: Supplementary information available at http://pico.phys.columbia.ed

Identification of novel subgroup a variants with enhanced receptor binding and replicative capacity in primary isolates of anaemogenic strains of feline leukaemia virus

&lt;b&gt;BACKGROUND:&lt;/b&gt; The development of anaemia in feline leukaemia virus (FeLV)-infected cats is associated with the emergence of a novel viral subgroup, FeLV-C. FeLV-C arises from the subgroup that is transmitted, FeLV-A, through alterations in the amino acid sequence of the receptor binding domain (RBD) of the envelope glycoprotein that result in a shift in the receptor usage and the cell tropism of the virus. The factors that influence the transition from subgroup A to subgroup C remain unclear, one possibility is that a selective pressure in the host drives the acquisition of mutations in the RBD, creating A/C intermediates with enhanced abilities to interact with the FeLV-C receptor, FLVCR. In order to understand further the emergence of FeLV-C in the infected cat, we examined primary isolates of FeLV-C for evidence of FeLV-A variants that bore mutations consistent with a gradual evolution from FeLV-A to FeLV-C.&lt;p&gt;&lt;/p&gt; &lt;b&gt;RESULTS:&lt;/b&gt; Within each isolate of FeLV-C, we identified variants that were ostensibly subgroup A by nucleic acid sequence comparisons, but which bore mutations in the RBD. One such mutation, N91D, was present in multiple isolates and when engineered into a molecular clone of the prototypic FeLV-A (Glasgow-1), enhanced replication was noted in feline cells. Expression of the N91D Env on murine leukaemia virus (MLV) pseudotypes enhanced viral entry mediated by the FeLV-A receptor THTR1 while soluble FeLV-A Env bearing the N91D mutation bound more efficiently to mouse or guinea pig cells bearing the FeLV-A and -C receptors. Long-term in vitro culture of variants bearing the N91D substitution in the presence of anti-FeLV gp70 antibodies did not result in the emergence of FeLV-C variants, suggesting that additional selective pressures in the infected cat may drive the subsequent evolution from subgroup A to subgroup C.&lt;p&gt;&lt;/p&gt; &lt;b&gt;CONCLUSIONS:&lt;/b&gt; Our data support a model in which variants of FeLV-A, bearing subtle differences in the RBD of Env, may be predisposed towards enhanced replication in vivo and subsequent conversion to FeLV-C. The selection pressures in vivo that drive the emergence of FeLV-C in a proportion of infected cats remain to be established

Multicomponent fractional quantum Hall effect in graphene

We report observation of the fractional quantum Hall effect (FQHE) in high mobility multi-terminal graphene devices, fabricated on a single crystal boron nitride substrate. We observe an unexpected hierarchy in the emergent FQHE states that may be explained by strongly interacting composite Fermions with full SU(4) symmetric underlying degrees of freedom. The FQHE gaps are measured from temperature dependent transport to be up 10 times larger than in any other semiconductor system. The remarkable strength and unusual hierarcy of the FQHE described here provides a unique opportunity to probe correlated behavior in the presence of expanded quantum degrees of freedom.Comment: 5 pages, 3 figure

Vertical Field Effect Transistor based on Graphene-WS2 Heterostructures for flexible and transparent electronics

The celebrated electronic properties of graphene have opened way for materials just one-atom-thick to be used in the post-silicon electronic era. An important milestone was the creation of heterostructures based on graphene and other two-dimensional (2D) crystals, which can be assembled in 3D stacks with atomic layer precision. These layered structures have already led to a range of fascinating physical phenomena, and also have been used in demonstrating a prototype field effect tunnelling transistor - a candidate for post-CMOS technology. The range of possible materials which could be incorporated into such stacks is very large. Indeed, there are many other materials where layers are linked by weak van der Waals forces, which can be exfoliated and combined together to create novel highly-tailored heterostructures. Here we describe a new generation of field effect vertical tunnelling transistors where 2D tungsten disulphide serves as an atomically thin barrier between two layers of either mechanically exfoliated or CVD-grown graphene. Our devices have unprecedented current modulation exceeding one million at room temperature and can also operate on transparent and flexible substrates

Long-term results after liver transplantation for primary hepatic epithelioid hemangioendothelioma

Background: Hepatic epithelioid hemangioendothelioma (PHEHE) is a multifocal, low-grade malignant neoplasia characterized by its epithelial-like appearance and vascular endothelial histogenesis. The outcome of 16 patients treated with orthotopic liver transplantation (OLT) is the subject of this report. Methods: A retrospective study of 16 patients with HEHE (7 men, 9 women) with ages ranging from 24 to 58 years (mean 37 ± 10.6 years). Follow-up intervals ranged from 1 to 15 years (median of 4.5 years). Results: Actual patient survival at 1, 3, and 5 years was 100, 87.5, and 71.3%, respectively. Disease-free survival at 1, 3, and 5 years was 81.3, 68.8, and 60.2%, respectively. The 90-day operative mortality was 0. Involvement of the hilar lymph nodes or vascular invasion did not affect survival. The 5-year survival of HEHE compares favorably with that of hepatocellular carcinoma at the same stage (stage 4A): 71.3 versus 9.8% (p=0.001) Conclusions: The long-term survival obtained in this series justifies OLT for these tumors even in the presence of limited extrahepatic disease. © 1995 The Society of Surgical Oncology, Inc

Liver Enzyme Abnormalities and Associated Risk Factors in HIV Patients on Efavirenz-Based HAART with or without Tuberculosis Co-Infection in Tanzania.

To investigate the timing, incidence, clinical presentation, pharmacokinetics and pharmacogenetic predictors for antiretroviral and anti-tuberculosis drug induced liver injury (DILI) in HIV patients with or without TB co-infection. A total of 473 treatment naïve HIV patients (253 HIV only and 220 with HIV-TB co-infection) were enrolled prospectively. Plasma efavirenz concentration and CYP2B6*6, CYP3A5*3, *6 and *7, ABCB1 3435C/T and SLCO1B1 genotypes were determined. Demographic, clinical and laboratory data were collected at baseline and up to 48 weeks of antiretroviral therapy. DILI case definition was according to Council for International Organizations of Medical Sciences (CIOMS). Incidence of DILI and identification of predictors was evaluated using Cox Proportional Hazards Model. The overall incidence of DILI was 7.8% (8.3 per 1000 person-week), being non-significantly higher among patients receiving concomitant anti-TB and HAART (10.0%, 10.7 per 1000 person-week) than those receiving HAART alone (5.9%, 6.3 per 1000 person-week). Frequency of CYP2B6*6 allele (p = 0.03) and CYP2B6*6/*6 genotype (p = 0.06) was significantly higher in patients with DILI than those without. Multivariate cox regression model indicated that CYP2B6*6/*6 genotype and anti-HCV IgG antibody positive as significant predictors of DILI. Median time to DILI was 2 weeks after HAART initiation and no DILI onset was observed after 12 weeks. No severe DILI was seen and the gain in CD4 was similar in patients with or without DILI. Antiretroviral and anti-tuberculosis DILI does occur in our setting, presenting early following HAART initiation. DILI seen is mild, transient and may not require treatment interruption. There is good tolerance to HAART and anti-TB with similar immunological outcomes. Genetic make-up mainly CYP2B6 genotype influences the development of efavirenz based HAART liver injury in Tanzanians

Quantum Hall effect and Landau level crossing of Dirac fermions in trilayer graphene

We investigate electronic transport in high mobility (\textgreater 100,000 cm$^2$/V$\cdot$s) trilayer graphene devices on hexagonal boron nitride, which enables the observation of Shubnikov-de Haas oscillations and an unconventional quantum Hall effect. The massless and massive characters of the TLG subbands lead to a set of Landau level crossings, whose magnetic field and filling factor coordinates enable the direct determination of the Slonczewski-Weiss-McClure (SWMcC) parameters used to describe the peculiar electronic structure of trilayer graphene. Moreover, at high magnetic fields, the degenerate crossing points split into manifolds indicating the existence of broken-symmetry quantum Hall states.Comment: Supplementary Information at http://jarilloherrero.mit.edu/wp-content/uploads/2011/04/Supplementary_Taychatanapat.pd

Multisensory information facilitates reaction speed by enlarging activity difference between superior colliculus hemispheres in rats

Animals can make faster behavioral responses to multisensory stimuli than to unisensory stimuli. The superior colliculus (SC), which receives multiple inputs from different sensory modalities, is considered to be involved in the initiation of motor responses. However, the mechanism by which multisensory information facilitates motor responses is not yet understood. Here, we demonstrate that multisensory information modulates competition among SC neurons to elicit faster responses. We conducted multiunit recordings from the SC of rats performing a two-alternative spatial discrimination task using auditory and/or visual stimuli. We found that a large population of SC neurons showed direction-selective activity before the onset of movement in response to the stimuli irrespective of stimulation modality. Trial-by-trial correlation analysis showed that the premovement activity of many SC neurons increased with faster reaction speed for the contraversive movement, whereas the premovement activity of another population of neurons decreased with faster reaction speed for the ipsiversive movement. When visual and auditory stimuli were presented simultaneously, the premovement activity of a population of neurons for the contraversive movement was enhanced, whereas the premovement activity of another population of neurons for the ipsiversive movement was depressed. Unilateral inactivation of SC using muscimol prolonged reaction times of contraversive movements, but it shortened those of ipsiversive movements. These findings suggest that the difference in activity between the SC hemispheres regulates the reaction speed of motor responses, and multisensory information enlarges the activity difference resulting in faster responses

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics