Role of High-Mobility Group Box-1 in Liver Pathogenesis

High-mobility group box 1 (HMGB1) is a highly abundant DNA-binding protein that can relocate to the cytosol or undergo extracellular release during cellular stress or death. HMGB1 has a functional versatility depending on its cellular location. While intracellular HMGB1 is important for DNA structure maintenance, gene expression, and autophagy induction, extracellular HMGB1 acts as a damage-associated molecular pattern (DAMP) molecule to alert the host of damage by triggering immune responses. The biological function of HMGB1 is mediated by multiple receptors, including the receptor for advanced glycation end products (RAGE) and Toll-like receptors (TLRs), which are expressed in different hepatic cells. Activation of HMGB1 and downstream signaling pathways are contributing factors in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), and drug-induced liver injury (DILI), each of which involves sterile inflammation, liver fibrosis, ductular reaction, and hepatic tumorigenesis. In this review, we will discuss the critical role of HMGB1 in these pathogenic contexts and propose HMGB1 as a bona fide and targetable DAMP in the setting of common liver diseases

Terahertz quantum Hall effect for spin-split heavy-hole gases in strained Ge quantum wells

Spin-split heavy-hole gases in strained germanium quantum wells were characterized by polarisation-resolved terahertz time-domain spectroscopy. Effective masses, carrier densities, g-factors, transport lifetimes, mobilities and Rashba spin-splitting energies were evaluated, giving quantitative insights into the influence of strain. The Rashba coefficient was found to lower for samples with higher biaxial compressive strain, while heavy-hole mobilities were enhanced to over $1.5\times {10}^{6}$ cm2 V−1 s−1 at 3 K. This high mobility enabled the observation of the optical quantum Hall effect at terahertz frequencies for spin-split two-dimensional heavy-holes, evidenced as plateaux in the transverse magnetoconductivity at even and odd filling factors

Observation of negative differential conductance in a reverse-biased Ni/Ge Schottky diode

We report the experimental observation of negative differential conductance in a Ni/Ge Schottky diode. With the aid of theoretical models and numerical simulation we show that, at reverse bias, electons tunnel into the high electric field of the depletion region. This scatters the electrons into the upper valley of the Ge conduction band, which has a lower mobility. The observed negative differential conductance is hence attributed to the transferred-electron effect. This shows that Schottky contacts can be used to create hot electrons for transferred-electron devices

Strong correlation between mobility and magnetoresistance in Weyl and Dirac semimetals

The discovery of Weyl and Dirac fermions in solid systems is a recent major breakthrough in the field of condensed matter physics. These materials exhibit extraordinary properties in terms of carrier mobility and magnetoresistance (MR). These two quantities are highly dependent in the Weyl semimetal transition monopnictide family, i.e. NbP, TaP, NbAs, and TaAs. Furthermore, the gathered mobility and MR (or slope of MR) at 2 K in 9 T of other well-known Weyl and Dirac semimetals follow a relation similar to the right turn symbol, i.e. the MR increases rapidly with mobility; thereafter it begins to saturate after reaching a value of 10(3). This suggests a nonlinear dependency. Nevertheless, for materials possessing high carrier mobility, it is valid to expect high MR

Detecting Traffic Conditions Model Based On Clustering Nodes Situations In VANET

In the last decade, cooperative vehicular network has been one of the most studied areas for developing the intelligent transportation systems (ITS). It is considered as an important approach to share the periodic traffic situations over vehicular ad hoc networks (VANETs) to improve efficiency and safety over the road. However, there are a number of issues in exchanging traffic data over high mobility of VANET, such as broadcast storms, hidden nodes and network instability. This paper proposes a new model to detect the traffic conditions using clustering traffic situations that are gathered from the nodes (vehicles) in VANET. The model designs new principles of multi-level clustering to detect the traffic condition for road users. Our model (a) divides the situations of vehicles into clusters, (b) designs a set of metrics to get the correlations among vehicles and (c) detects the traffic condition in certain areas. These metrics are simulated using the network simulator environment (NS-3) to study the effectiveness of the model

HMGB1-Induced Cross Talk between PTEN and miRs 221/222 in Thyroid Cancer

High mobility group box 1 (HMGB1) is an ubiquitous protein that plays different roles in the nucleus, cytoplasm and extra-cellular space. It is an important DAMP molecule that allows communication between damaged or tumor cells and the immune system. Tumor cells exploit HMGB1’s ability to activate intracellular pathways that lead to cell growth and migration. Papillary thyroid cancer is a well differentiated tumor and is often used to study relationships between cells and the inflammatory microenvironment as the latter is characterized by high levels of inflammatory cells and cytokines. Anaplastic thyroid cancer is one of the most lethal human cancers in which many microRNAs and tumor suppressor genes are de-regulated. Up-regulation of microRNAs 221 and 222 has been shown to induce the malignant phenotype in many human cancers via inhibition of PTEN expression. In this study we suggest that extracellular HMGB1 interaction with RAGE enhances expression of oncogenic cluster miR221/222 that in turn inhibits tumor suppressor gene PTEN in two cell lines derived from human thyroid anaplastic and papillary cancers. The newly identified pathway HMGB1/RAGE/miR 221/222 may represent an effective way of tumor escape from immune surveillance that could be used to develop new therapeutic strategies against anaplastic tumors

Host defense responses to infection by Mycobacterium tuberculosis. Induction of IRF-1 and a serine protease inhibitor.

Alveolar macrophages and newly recruited monocytes are targets of infection by Mycobacterium tuberculosis. Therefore, we examined the expression of interferon regulatory factor 1 (IRF-1), which plays an important role in host defense against M. tuberculosis, in undifferentiated and differentiated cells. Infection induced IRF-1 in both. IRF-1 from undifferentiated, uninfected monocytic cell lines was modified during extraction to produce specific species that were apparently smaller than intact IRF-1. After infection by M. tuberculosis or differentiation, intact IRF-1 was recovered. Subcellular fractions were assayed for the ability to modify IRF-1 or inhibit its modification. A serine protease on the cytoplasmic surface of an organelle or vesicle in the "lysosomal/mitochondrial" fraction from undifferentiated cells was responsible for the modification of IRF-1. Thus, the simplest explanation of the modification is cleavage of IRF-1 by the serine protease. Recovery of intact IRF-1 correlated with induction of a serine protease inhibitor that was able to significantly reduce the modification of IRF-1. The inhibitor was present in the cytoplasm of M. tuberculosis-infected or -differentiated cells. It is likely that induction of both IRF-1 and the serine protease inhibitor in response to infection by M. tuberculosis represent host defense mechanisms

Disruption and aberrant expression of HMGA2 as a consequence of diverse chromosomal translocations in myeloid malignancies

Chromosomal translocations that target HMGA2 at chromosome band 12q14 are seen in a variety of malignancies, notably lipoma, pleomorphic salivary adenoma and uterine leiomyoma. Although some HMGA2 fusion genes have been reported, several lines of evidence suggest that the critical pathogenic event is the expression of truncated HMGA2 isoforms. We report here the involvement of HMGA2 in six patients with myeloid neoplasia, dysplastic features and translocations or an inversion involving chromosome bands 12q13-15 and either 7p12, 8q22, 11q23, 12p11, 14q31 or 20q11. Breaks within or very close to HMGA2 were found in all six cases by molecular cytogenetic analysis, leading to overexpression of this gene as assessed by RT-PCR. Truncated transcripts consisting of HMGA2 exons 1-2 or exons 1-3 spliced to intron-derived sequences were identified in two patients, but were not seen in controls. These findings suggest that abnormalities of HMGA2 play an important and previously unsuspected role in myelodysplasia

Control of threshold voltage in E-mode and D-mode GaN-on-Si metal-insulator-semiconductor heterostructure field effect transistors by in-situ fluorine doping of atomic layer deposition Al2O3 gate dielectrics

We report the modification and control of threshold voltage in enhancement and depletion mode AlGaN/GaN metal-insulator-semiconductor heterostructure field effect transistors through the use of in-situ fluorine doping of atomic layer deposition Al2O3. Uniform distribution of F ions throughout the oxide thickness are achievable, with a doping level of up to 5.5 × 1019 cm−3 as quantified by secondary ion mass spectrometry. This fluorine doping level reduces capacitive hysteretic effects when exploited in GaN metal-oxide-semiconductor capacitors. The fluorine doping and forming gas anneal also induces an average positive threshold voltage shift of between 0.75 and 1.36 V in both enhancement mode and depletion mode GaN-based transistors compared with the undoped gate oxide via a reduction of positive fixed charge in the gate oxide from +4.67 × 1012 cm−2 to −6.60 × 1012 cm−2. The application of this process in GaN based power transistors advances the realisation of normally off, high power, high speed devices