Inverse Magnetoresistance of Molecular Junctions

We present calculations of spin-dependent electron transport through single organic molecules bridging pairs of iron nanocontacts. We predict the magnetoresistance of these systems to switch from positive to negative with increasing applied bias for both conducting and insulating molecules. This novel inverse magnetoresistance phenomenon is robust, does not depend on the presence of impurities, and is unique to molecular and atomic nanoscale magnetic junctions. Its physical origin is identified and its relevance to experiment and to potential technological applications is discussed.Comment: 5 pages, 3 figures; published version Phys. Rev.

Report of Objective Clinical Responses of Cancer Patients to Pharmaceutical-grade Synthetic Cannabidiol.

BACKGROUND/AIM: Cannabinoids are widely used in the management of pain, nausea and cachexia in cancer patients. However, there has been no objective clinical evidence of any anticancer activity yet. The aim of this study was to assess the effects of pharmaceutical-grade synthetic cannabidiol on a range of cancer patients. PATIENTS AND METHODS: We analysed the data routinely collected, as part of our treatment program, in 119 cancer patients over a four-year period. RESULTS: Clinical responses were seen in 92% of the 119 cases with solid tumours including a reduction in circulating tumour cells in many cases and in other cases, a reduction in tumour size, as shown by repeat scans. No side-effects of any kind were observed when using pharmaceutical grade synthetic cannabidiol. CONCLUSION: Pharmaceutical-grade synthetic cannabidiol is a candidate for treating breast cancer and glioma patients

Enhanced effect of checkpoint inhibitors when given after or together with IMM-101: significant responses in four advanced melanoma patients with no additional major toxicity

Background The use of checkpoint inhibitors (ipilimumab, pembrolizumab, nivolumab) has revolutionised the treatment of metastatic melanoma. However still more than the half the patients do not respond to single-agent immunotherapy. This has led to the development of combining these agents in an attempt to enhance the anti-cancer activity. More than 300 different studies with 15 different drug doses are currently ongoing. Combining different checkpoint inhibitors (CPIs) does indeed lead to an increase in response rate, but this is associated with significant toxicity. IMM-101 is a heat killed Mycobacterium preparation which induces marked immune modulation and little systemic toxicity. It has been reported as having activity in melanoma as single agent and in pancreatic cancer in combination with gemcitabine, the latter in a randomised study. Methods Here we report the effect of adding CPIs to 3 patients who had previously been on IMM-101, either as a trial or a named patient programme and a patient who received the IMM-101 together with nivolumab. Results All 4 patients had rapid and very good responses, three of them maintained over 18 months with no significant additional toxicity. Conclusions The rapid and complete clinical responses seen in these patients may suggest that IMM-101 is activating a complementary pathway which is synergistic with CPI treatment

Theoretical Study of Spin-dependent Electron Transport in Atomic Fe Nanocontacts

We present theoretical predictions of spintronic transport phenomena that should be observable in ferromagnetic Fe nanocontacts bridged by chains of Fe atoms. We develop appropriate model Hamiltonians based on semi-empirical considerations and the known electronic structure of bulk Fe derived from ab initio density functional calculations. Our model is shown to provide a satisfactory description of the surface properties of Fe nano-clusters as well as bulk properties. Lippmann-Schwinger and Green's function techniques are used together with Landauer theory to predict the current, magneto-resistance, and spin polarization of the current in Fe nanocontacts bridged by atomic chains under applied bias. Unusual device characteristics are predicted including negative magneto-resistance and spin polarization of the current, as well as spin polarization of the current for anti-parallel magnetization of the Fe nanocontacts under moderate applied bias. We explore the effects that stretching the atomic chain has on the magneto-resistance and spin polarization and predict a cross-over regime in which the spin polarization of the current for parallel magnetization of the contacts switches from negative to positive. We find resonant transmission due to dangling bond formation on tip atoms as the chain is stretched through its breaking point to play an important role in spin-dependent transport in this regime. The physical mechanisms underlying the predicted phenomena are discussed.Comment: 13 pages, 6 figures, Accepted for publication in Physical Review

Culture and the remembering of trauma

This research investigated the influence of culture and posttraumatic stress disorder (PTSD) on global autobiographical remembering (Study 1a) and on the phenomenological properties (Study 1b) and memory-content variables (Study 1c) of trauma-specific autobiographical remembering. Australian, British, and Iranian trauma survivors with and without PTSD completed the Autobiographical Memory Test, Self-Defining Memory Task, and Autobiographical Memory Questionnaire and provided trauma- and negative-memory narratives. We found that there were pan-cultural deficits and distortions in the global autobiographical remembering of participants with PTSD (Study 1a). In addition, the presence of PTSD moderated the usual effect of culture on the phenomenological properties of the trauma memory (Study 1b). Finally, participants with PTSD, regardless of cultural background, had significantly fewer expressions of autonomy and self-determination in their autobiographical remembering than did those without PTSD (Study 1c). The findings suggest that pan-culturally, individuals with PTSD have similar disruptions and distortions in their autobiographical remembering

Supernatants from lymphocytes stimulated with Bacillus Calmette-Guerin can modify the antigenicity of tumours and stimulate allogeneic T-cell responses

BACKGROUND: Reduced expression of class 1 human leucocyte antigens (HLA1) is often a mechanism by which tumours evade surveillance by the host immune system. This is often associated with an immune function that is unable to mount appropriate responses against disease, which can result in a state that favours carcinogenesis. METHODS: In the current study, we have explored the effects of Bacillus Calmette-Guerin (BCG) on the cytokine output of leucocytes, which is a key determinant in generating antitumour action, and have also assessed the effect of these cytokine cocktails on HLA1 expression in solid tumour cell lines. RESULTS: BCG potently activated a broad range of leucocytes, and also enhanced the production of cytokines that were Th(1)-predominant. Supernatants from BCG-treated leucocytes significantly increased the expression of HLA1 on the surface of cancer cell lines, which correlated with increased cytolytic T-cell activity. We also showed that the increased HLA1 expression was associated with activation of intracellular signalling pathways, which was triggered by the increases in the Th(1)-cytokines interferon-γ and tumour necrosis factor-α, as counteracting their effects negated the enhancement. CONCLUSION: These studies reaffirm the role of BCG as a putative immunotherapy through their cytokine-modifying effects on leucocytes and their capacity to enhance tumour visibility

Modulation of the virus-receptor interaction by mutations in the V5 loop of feline immunodeficiency virus (FIV) following in vivo escape from neutralising antibody

<b>BACKGROUND:</b> In the acute phase of infection with feline immunodeficiency virus (FIV), the virus targets activated CD4+ T cells by utilising CD134 (OX40) as a primary attachment receptor and CXCR4 as a co-receptor. The nature of the virus-receptor interaction varies between isolates; strains such as GL8 and CPGammer recognise a "complex" determinant on CD134 formed by cysteine-rich domains (CRDs) 1 and 2 of the molecule while strains such as PPR and B2542 require a more "simple" determinant comprising CRD1 only for infection. These differences in receptor recognition manifest as variations in sensitivity to receptor antagonists. In this study, we ask whether the nature of the virus-receptor interaction evolves in vivo.<p></p> <b>RESULTS:</b> Following infection with a homogeneous viral population derived from a pathogenic molecular clone, a quasispecies emerged comprising variants with distinct sensitivities to neutralising antibody and displaying evidence of conversion from a "complex" to a "simple" interaction with CD134. Escape from neutralising antibody was mediated primarily by length and sequence polymorphisms in the V5 region of Env, and these alterations in V5 modulated the virus-receptor interaction as indicated by altered sensitivities to antagonism by both anti-CD134 antibody and soluble CD134.<p></p> <b>CONCLUSIONS:</b> The FIV-receptor interaction evolves under the selective pressure of the host humoral immune response, and the V5 loop contributes to the virus-receptor interaction. Our data are consistent with a model whereby viruses with distinct biological properties are present in early versus late infection and with a shift from a "complex" to a "simple" interaction with CD134 with time post-infection.<p></p&gt