Folding model study of the elastic α+α\alpha + \alpha scattering at low energies

The folding model analysis of the elastic $\alpha + \alpha$ scattering at the incident energies below the reaction threshold of 34.7 MeV (in the lab system) has been done using the well-tested density dependent versions of the M3Y interaction and realistic choices for the $^4$He density. Because the absorption is negligible at the energies below the reaction threshold, we were able to probe the $\alpha + \alpha$ optical potential at low energies quite unambiguously and found that the $\alpha + \alpha$ overlap density used to construct the density dependence of the M3Y interaction is strongly distorted by the Pauli blocking. This result gives possible explanation of a long-standing inconsistency of the double-folding model in its study of the elastic $\alpha + \alpha$ and $\alpha$-nucleus scattering at low energies using the same realistic density dependent M3Y interaction

Hexa Histidine–Tagged Recombinant Human Cytoglobin Deactivates Hepatic Stellate Cells and Inhibits Liver Fibrosis by Scavenging Reactive Oxygen Species

BACKGROUND & AIMS: Anti-fibrotic therapy remains an unmet medical need in human chronic liver disease. We report the anti-fibrotic properties of cytoglobin (CYGB), a respiratory protein expressed in hepatic stellate cells (HSCs), the main cell type involved in liver fibrosis. APPROACH & RESULTS: Cygb-deficient mice which had bile duct ligation (BDL)-induced liver cholestasis or choline-deficient L-amino acid-defined (CDAA) diet-induced steatohepatitis significantly exacerbated liver damage, fibrosis and reactive oxygen species (ROS) formation. All these manifestations were attenuated in Cygb-overexpressing mice. We produced 6His-tagged recombinant human CYGB (His-CYGB), traced its bio-distribution and assessed its function in HSCs or in mice with advanced liver cirrhosis using thioacetamide (TAA) or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). In cultured HSCs, extracellular His-CYGB was endocytosed and accumulated in endosomes via clathrin-mediated pathway. His-CYGB significantly impeded ROS formation spontaneously or in the presence of ROS inducers in HSCs, thus leading to the attenuation of collagen type I alpha 1 production and alpha-smooth muscle actin expression. Replacement the iron centre of the heme group with cobalt nullified the effect of His-CYGB. In addition, His-CYGB induced interferon-β secretion by HSCs which partly contributed to its anti-fibrotic function. Momelotinib incompletely reversed the effect of His-CYGB. Intravenously injected His-CYGB markedly suppressed liver inflammation, fibrosis and oxidative cell damage in TAA- or DDC-administered mice without adverse effects. RNA-seq analysis revealed the downregulation of inflammation and fibrosis-related genes and the upregulation of antioxidant genes in both cell culture and liver tissues. The injected His-CYGB predominantly localised to HSCs but not to macrophages, suggesting specific targeting effects. His-CYGB exhibited no toxicity in humanised liver chimeric PXB mice. CONCLUSIONS: His-CYGB could have anti-fibrotic clinical applications for human chronic liver diseases

Sources of Multidrug Resistance in Patients With Previous Isoniazid-Resistant Tuberculosis Identified Using Whole Genome Sequencing: A Longitudinal Cohort Study

Background Meta-analysis of patients with isoniazid-resistant tuberculosis given standard first-line anti-tuberculosis treatment indicated an increased risk of multi-drug resistant tuberculosis (MDR-TB) emerging (8%), compared to drug-sensitive tuberculosis (0.3%). Here we use whole genome sequencing (WGS) to investigate whether treatment of patients with pre-existing isoniazid resistant disease with first-line anti-tuberculosis therapy risks selecting for rifampicin resistance, and hence MDR-TB. Methods Patients with isoniazid-resistant pulmonary TB were recruited and followed up for 24 months. Drug-susceptibility testing was performed by Microscopic observation drug-susceptibility assay (MODS), Mycobacterial Growth Indicator Tube (MGIT) and by WGS on isolates at first presentation and in the case of re-presentation. Where MDR-TB was diagnosed, WGS was used to determine the genomic relatedness between initial and subsequent isolates. De novo emergence of MDR-TB was assumed where the genomic distance was five or fewer single nucleotide polymorphisms (SNPs) whereas reinfection with a different MDR-TB strain was assumed where the distance was 10 or more SNPs. Results 239 patients with isoniazid-resistant pulmonary tuberculosis were recruited. Fourteen (14/239, 5.9%) patients were diagnosed with a second episode of tuberculosis that was multi-drug resistant. Six (6/239, 2.5%) were identified as having evolved MDR-TB de novo and six as having been re-infected with a different strain. In two cases the genomic distance was between 5-10 SNPs and therefore indeterminate. Conclusions In isoniazid-resistant TB, de novo emergence and reinfection of MDR-TB strains equally contributed to MDR development. Early diagnosis and optimal treatment of isoniazid resistant TB are urgently needed to avert the de novo emergence of MDR-TB during treatment

Cancer cells produce liver metastasis via gap formation in sinusoidal endothelial cells through proinflammatory paracrine mechanisms

Intracellular gap (iGap) formation in liver sinusoidal endothelial cells (LSECs) is caused by the destruction of fenestrae and appears under pathological conditions; nevertheless, their role in metastasis of cancer cells to the liver remained unexplored. We elucidated that hepatotoxin-damaged and fibrotic livers gave rise to LSECs-iGap formation, which was positively correlated with increased numbers of metastatic liver foci after intrasplenic injection of Hepa1-6 cells. Hepa1-6 cells induced interleukin-23-dependent tumor necrosis factor-α (TNF-α) secretion by LSECs and triggered LSECs-iGap formation, toward which their processes protruded to transmigrate into the liver parenchyma. TNF-α triggered depolymerization of F-actin and induced matrix metalloproteinase 9 (MMP9), intracellular adhesion molecule 1, and CXCL expression in LSECs. Blocking MMP9 activity by doxycycline or an MMP2/9 inhibitor eliminated LSECs-iGap formation and attenuated liver metastasis of Hepa1-6 cells. Overall, this study revealed that cancer cells induced LSEC-iGap formation via proinflammatory paracrine mechanisms and proposed MMP9 as a favorable target for blocking cancer cell metastasis to the liver

Virulence of Mycobacterium tuberculosis Clinical Isolates Is Associated With Sputum Pre-treatment Bacterial Load, Lineage, Survival in Macrophages, and Cytokine Response

It is uncertain whether differences in Mycobacterium tuberculosis (Mtb) virulence defined in vitro influence clinical tuberculosis pathogenesis, transmission, and mortality. We primarily used a macrophage lysis model to characterize the virulence of Mtb isolates collected from 153 Vietnamese adults with pulmonary tuberculosis. The virulence phenotypes were then investigated for their relationship with sputum bacterial load, bacterial lineages, bacterial growth, and cytokine responses in macrophages. Over 6 days of infection, 34 isolates (22.2%) showed low virulence (< 5% macrophages lysed), 46 isolates (30.1%) showed high virulence (≥90% lysis of macrophages), and 73 isolates (47.7%) were of intermediate virulence (5–90% macrophages lysed). Highly virulent isolates were associated with an increased bacterial load in patients' sputum before anti-tuberculosis therapy (P = 0.02). Isolate-dependent virulence phenotype was consistent in both THP-1 and human monocyte-derived macrophages. High virulence isolates survived better and replicated in macrophages one hundred fold faster than those with low virulence. Macrophages infected with high virulence isolates produced lower concentrations of TNF-α and IL-6 (P = 0.002 and 0.0005, respectively), but higher concentration of IL-1β (P = 5.1 × 10−5) compared to those infected with low virulence isolates. High virulence was strongly associated with East Asian/Beijing lineage [P = 0.002, Odd ratio (OR) = 4.32, 95% confident intervals (CI) 1.68–11.13]. The association between virulence phenotypes, bacterial growth, and proinflammatory cytokines in macrophages suggest the suppression of certain proinflammatory cytokines (TNF-α and IL-6) but not IL-1β allows better intracellular survival of highly virulent Mtb. This could result in rapid macrophage lysis and higher bacterial load in sputum of patients infected with high virulence isolates, which may contribute to the pathogenesis and success of the Beijing lineage

Nonresonant Three-body Decays of D and B Mesons

Nonresonant three-body decays of D and B mesons are studied. It is pointed out that if heavy meson chiral perturbation theory (HMChPT) is applied to the heavy-light strong and weak vertices and assumed to be valid over the whole kinematic region, then the predicted decay rates for nonresonant charmless 3-body B decays will be too large and especially B^- --> pi^- K^+ K^- greatly exceeds the current experimental limit. This can be understood as chiral symmetry has been applied there twice beyond its region of validity. If HMChPT is applied only to the strong vertex and the weak transition is accounted for by the form factors, the dominant B^* pole contribution to the tree-dominated direct three-body B decays will become small and the branching ratio will be of order 10^{-6}. The decay modes B^- --> (K^- h^+ h^-)_{NR} and bar{B}^0 --> (bar{K}^0 h^+h^-)_{NR} for h = pi, K are penguin dominated. We apply HMChPT in two different cases to study the direct 3-body D decays and compare the results with experiment. Theoretical uncertainties are discussed.Comment: 24 pages, 2 figures. New experimental results of direct 3-body D decays as Reported at ICHEP2002 are included. To appear in Phys. Re

Impact of perception and assessment of consumers on willingness to pay for upgraded fresh pork: An experimental study in Vietnam

Traditional pork shops play an essential role in delivering pork, the most popular food in Vietnam, to consumers. Studies have shown the need for investment in training and equipment to improve the safety of pork sold at traditional shops. However, it remains unclear how consumers perceived improvement to the hygiene in pork shops and if they are ready to pay premium prices for safer products. This study used an experimental approach to determine consumers' perception and assessment of improved pork shops and their willingness to pay (WTP) for pork products. A total of 152 respondents in two provinces in Vietnam joined in a Becker–DeGroot–Marschak (BDM) mechanism experiment to collect data on WTP for pork from typical and upgraded pork shops. A questionnaire was used to record consumers' perceptions and assessments of the pork shops and products. Overall, consumers were willing to pay 20% more for upgraded fresh pork than for what is currently available on the market. Consumers trusted in the effectiveness of the upgraded intervention and the quality of pork at the pork shop, which increased their WTP for the upgraded pork. Concerns about contaminated pork had a negative impact on the WTP for typical pork, while the high frequency of pork consumption and the existence of elderly family members led to higher WTP for both products. The findings indicate the potential economic benefit of upgrading pork shops, which would be an important driver to motivate sellers to improve food safety

Helicobacter pylori infection and gastroduodenal diseases in Vietnam: a cross-sectional, hospital-based study

<p>Abstract</p> <p>Background</p> <p>The rate of <it>H. pylori </it>infection in Vietnam is reportedly high, but the spectrum of <it>H. pylori</it>-associated gastroduodenal diseases has not been systematically investigated. Moreover, despite the similarities of ethnicity and diet, the age-standardized incidence rate of gastric cancer in the northern city of Hanoi is higher than that in the southern city of Ho Chi Minh, but the reason for this phenomenon is unknown. The virulence of Vietnamese <it>H. pylori </it>has also not been investigated in detail.</p> <p>Methods</p> <p>Individuals undergoing esophagogastroduodenoscopy were randomly recruited. <it>H. pylori </it>infection status was determined based on the combined results of culture, histology, immunohistochemistry, rapid urine test and serum ELISA. Peptic ulcer (PU) and gastroesophageal reflux disease was diagnosed by endoscopy, and chronic gastritis was determined histologically. <it>H. pylori </it>virulence factors were investigated by PCR and sequencing.</p> <p>Results</p> <p>Among the examined patients, 65.6% were infected with <it>H. pylori</it>. The prevalence of infection was significantly higher in those over 40 years of age than in those aged ≤40. Chronic gastritis was present in all <it>H. pylori</it>-infected individuals, 83.1% of whom had active gastritis, and 85.3% and 14.7% had atrophy and intestinal metaplasia, respectively. PU was present in 21% of infected patients, whereas its incidence was very low in non-infected individuals. The prevalence of PU was significantly higher in Hanoi than in Ho Chi Minh. The prevalence of <it>vacA m1</it>, which has been identified as an independent risk factor for PU in Vietnam, was significantly higher among <it>H. pylori </it>isolates from Hanoi than among those from Ho Chi Minh.</p> <p>Conclusions</p> <p><it>H. pylori </it>infection is common in Vietnam and is strongly associated with PU, active gastritis, atrophy and intestinal metaplasia. <it>vacA m1 </it>is associated with an increased risk for PU and might contribute to the difference in the prevalence of PU and gastric cancer between Hanoi and Ho Chi Minh.</p