Space efficient opposed-anvil high-pressure cell and its application to optical and NMR measurements up to 9 GPa

We have developed a new type of opposed-anvil high pressure cell with substantially improved space efficiency. The clamp cell and the gasket are made of non-magnetic Ni-Cr-Al alloy. Non-magnetic tungsten carbide (NMWC) is used for the anvils. The assembled cell with the dimension \phi 29mm \times 41mm is capable of generating pressure up to 9 GPa over a relatively large volume of 7 mm3. Our cell is particularly suitable for those experiments which require large sample space to achieve good signal-to-noise ratio, such as the nuclear magnetic resonance (NMR) experiment. Argon is used as the pressure transmitting medium to obtain good hydrostaticity. The pressure was calibrated in situ by measuring the fluorescence from ruby through a transparent moissanite (6H-SiC) window. We have measured the pressure and temperature dependences of the 63Cu nuclear-quadrupole-resonance (NQR) frequency of Cu2O, the in-plane Knight shift of metallic tin, and the Knight shift of platinum. These quantities can be used as reliable manometers to determine the pressure values in situ during the NMR/NQR experiments up to 9 GPa.Comment: 9 pages, 5 figures, 3 tables, accepted for publication in J. Phys. Soc. Jp

Simple Metals at High Pressure

In this lecture we review high-pressure phase transition sequences exhibited by simple elements, looking at the examples of the main group I, II, IV, V, and VI elements. General trends are established by analyzing the changes in coordination number on compression. Experimentally found phase transitions and crystal structures are discussed with a brief description of the present theoretical picture.Comment: 22 pages, 4 figures, lecture notes for the lecture given at the Erice course on High-Pressure Crystallography in June 2009, Sicily, Ital

Cytokine Gene Polymorphisms across Tuberculosis Clinical Spectrum in Pakistani Patients

BACKGROUND: Pakistan ranks 7(th) globally in terms of tuberculosis (TB) disease burden (incidence 181/100000 pop./yr; prevalence of 329/pop./yr). Reports from different populations show variable associations of TB susceptibility and severity with cytokine gene polymorphisms. Tuberculosis clinical severity is multi-factorial and cytokines play a pivotal role in the modulation of disease severity. We have recently reported that the ratio of two key cytokines (IFNgamma and IL10) show significant correlation with the severity spectrum of tuberculosis. The objective of the current study was to analyze the frequency of cytokine gene polymorphisms linked to high and low responder phenotypes (IFNgamma +874 T(hi)-->A(lo) and IL10 -1082 G(lo)-->A(hi)) in tuberculosis patients. METHODS AND FINDINGS: STUDY GROUPS WERE STRATIFIED ACCORDING TO DISEASE SITE AS WELL AS DISEASE SEVERITY: Pulmonary N = 111 (Minimal, PMN = 19; Moderate, PMD = 63; Advance, PAD = 29); Extra-pulmonary N = 67 (Disseminated DTB = 20, Localized LTB = 47) and compared with healthy controls (TBNA = 188). Genotype analyses were carried out using amplification refractory mutation system-PCR (ARMS-PCR) and stimulated whole blood (WB) culture assay was used for assessing cytokine profiles. Our results suggest that the IFNgamma +874 TT genotype and T allele was overrepresented in PMN (p = 0.01) and PMD (p = 0.02). IFNgamma +874 TT in combination with IL10 GG(lo) genotypes showed the highest association (chi(2) = 6.66, OR = 6.06, 95% CI = 1.31-28.07, p = 0.01). IFNgamma AA(lo) on the other hand in combination with IL10 GG(lo) increased the risk of PAD (OR = 5.26; p = 0.005) and DTB (OR = 3.59; p = 0.045). CONCLUSION: These findings are consistent with the role of IL10 in reducing collateral tissue damage and the protective role of IFNgamma in limiting disease in the lung

Direct Enhancement of Nuclear Singlet Order by Dynamic Nuclear Polarization

Hyperpolarized singlet order is available immediately after dissolution DNP, avoiding need for additional preparation steps. We demonstrate this procedure on a sample of [1,2–13C2]pyruvic aci

Role of genetic polymorphisms in tumour angiogenesis

Angiogenesis plays a crucial role in the development, growth and spread of solid tumours. Pro- and anti-angiogenic factors are abnormally expressed in tumours, influencing tumour angiogenesis, growth and progression. Polymorphisms in genes encoding angiogenic factors or their receptors may alter protein expression and/or activity. This article reviews the literature to determine the possible role of angiogenesis-related polymorphisms in cancer. Further research studies in this potentially crucial area of tumour biology are proposed

Dysregulated Expression of Both the Costimulatory CD28 and Inhibitory CTLA-4 Molecules in PB T Cells of Advanced Cervical Cancer Patients Suggests Systemic Immunosuppression Related to Disease Progression

Cervical cancer (CC) occurs more frequently in women who are immunosuppressed, suggesting that both local and systemic immune abnormalities may be involved in the evolution of the disease. Costimulatory CD28 and inhibitory CTLA-4 molecules expressed in T cells play a key role in the balanced immune responses. There has been demonstrated a relation between CD28, CTLA-4, and IFN genes in susceptibility to CC, suggesting their importance in CC development. Therefore, we assessed the pattern of CD28 and CTLA-4 expression in T cells from PB of CC patients with advanced CC (stages III and IV according to FIGO) compared to controls. We also examined the ability of PBMCs to secrete IFN-gamma. We found lower frequencies of freshly isolated and ex vivo stimulated CD4 + CD28+ and CD8 + CD28+ T cells in CC patients than in controls. Loss of CD28 expression was more pronounced in the CD8+ T subset. Markedly increased proportions of CTLA-4+ T cells in CC patients before and after culture compared to controls were also observed. In addition, patients’ T cells exhibited abnormal kinetics of surface CTLA-4 expression, with the peak at 24 h of stimulation, which was in contrast to corresponding normal T cells, revealing maximum CTLA-4 expression at 72 h of stimulation. Of note, markedly higher IFN-gamma concentrations were shown in supernatants of stimulated PBMCs from CC patients. Conclusions: Our report shows the dysregulated CD28 and CTLA-4 expression in PB T cells of CC patients, which may lead to impaired function of these lymphocytes and systemic immunosuppression related to disease progression

Association of the Gene Polymorphisms IFN-γ +874, IL-13 −1055 and IL-4 −590 with Patterns of Reinfection with Schistosoma mansoni

Approximately 200 million people have schistosomiasis in parts of Africa, South America, the Middle East, the Caribbean and Asia. Several studies of multiple treatments and reinfections indicate that some people develop resistance to reinfection. Of all the immunologic findings associated with such studies, the most consistent observation is that resistance (usually defined as lower levels of infection upon reinfection) correlates with high IgE and low IgG4 antibodies against schistosome antigens. Our studies test whether single nucleotide polymorphisms residing in the gene or promoter regions of cytokines pivotal in controlling production of these antibody isotypes are different amongst those that develop resistance to reinfection as opposed to those that do not. Through genotyping of these polymorphisms in a cohort of occupationally exposed car washers, we found that men with certain genotypic patterns of polymorphisms in IL-4, IFN-γ, and IL-13 were significantly more likely to be resistant to reinfection than those with different patterns. These data provide initial insights into the potential genetic foundation of propensities of people to develop resistance to reinfection by schistosomes, and offer a basis for further molecular studies of how these polymorphisms might work at the transcriptional and gene product level in cells stimulated by schistosome antigens

Strategies for the hyperpolarization of acetonitrile and related Ligands by SABRE

(Chemical Equation Presented) We report on a strategy for using SABRE (signal amplification by reversible exchange) for polarizing 1H and 13C nuclei of weakly interacting ligands which possess biologically relevant and nonaromatic motifs. We first demonstrate this via the polarization of acetonitrile, using Ir(IMes)(COD)Cl as the catalyst precursor, and confirm that the route to hyperpolarization transfer is via the J-coupling network. We extend this work to the polarization of propionitrile, benzylnitrile, benzonitrile, and trans-3-hexenedinitrile in order to assess its generality. In the 1H NMR spectrum, the signal for acetonitrile is enhanced 8-fold over its thermal counterpart when [Ir(H)2(IMes)(MeCN)3]+ is the catalyst. Upon addition of pyridine or pyridine-d5, the active catalyst changes to [Ir(H)2(IMes)- (py)2(MeCN)]+ and the resulting acetonitrile 1H signal enhancement increases to 20- and 60-fold, respectively. In 13C NMR studies, polarization transfers optimally to the quaternary 13C nucleus of MeCN while the methyl 13C is hardly polarized. Transfer to 13C is shown to occur first via the 1H - 1H coupling between the hydrides and the methyl protons and then via either the 2J or 1J couplings to the respective 13Cs, of which the 2J route is more efficient. These experimental results are rationalized through a theoretical treatment which shows excellent agreement with experiment. In the case of MeCN, longitudinal two-spin orders between pairs of 1H nuclei in the three-spin methyl group are created. Two-spin order states, between the 1H and 13C nuclei, are also created, and their existence is confirmed for Me13CN in both the 1H and 13C NMR spectra using the Only Parahydrogen Spectroscopy protocol