Thermal design issues and performance of microcalorimeter arrays at sub-Kelvin temperatures

We have produced 5/spl times/5 pixel arrays of microcalorimeters using bulk micromachining. Analysis of our data provides the thermal conductivity parameters of Si/sub x/N/sub y/ 1 /spl mu/m thick membranes at 100 mK. Moreover we find that the thermal transport at 100 mK in Si beams, with dimensions 1.25 mm /spl times/ 0.35mm /spl times/ 35/spl mu/m (length /spl times/ height /spl times/ width) is dominated by ballistic phonons with a mean free path of 110 /spl mu/m. These thermal parameters can be used for modelling future 32 /spl times/ 32 pixel arrays. In addition we operated three pixels in a 5 /spl times/ 5 array of microcalorimeters and find that the pixel to pixel reproducibility is very good. When used as an X-ray microcalorimeter individual pixels have a thermal decay time of 200 /spl mu/s is and their energy resolution is between 6 and 7 eV for 5.89 keV X-ray photons

Radiative ballistic phonon transport in silicon-nitride membranes at low temperatures

We studied the phonon transport in free-standing 1 µm thick silicon-nitride membranes at temperatures around 100 mK. By varying the geometry of the membranes and the dimensions of the heater element, we are able to distinguish between radiative and diffuse phonon transport. The data indicate that the transport is radiative ballistic with a lower limit to a phonon mean-free path of about 1 mm and that the probability for specular reflection from the surface is at least 0.99. The tested silicon-nitride membranes were grown on Si(100), Si(110), and polycrystalline-Si and the transport properties show no dependency on the substrat

Safety of the Combination of PERC and YEARS Rules in Patients With Low Clinical Probability of Pulmonary Embolism: A Retrospective Analysis of Two Large European Cohorts

BACKGROUND: This study aimed to determine the failure rate of a combination of the PERC and the YEARS rules for the diagnosis of pulmonary embolism (PE) in the emergency department (ED). METHODS: We performed a retrospective analysis of two European cohorts of emergency patients with low gestalt clinical probability of PE (PROPER and PERCEPIC). All patients we included were managed using a conventional strategy (D-dimer test, followed, if positive, by computed tomographic pulmonary angiogram (CTPA). We tested a diagnostic strategy that combined PERC and YEARS to rule out PE. The primary endpoint was a thromboembolic event diagnosed in the ED or at 3-months follow-up. Secondary endpoints included a thromboembolic event at baseline in the ED and a CTPA in the ED. Ninety-five percent confidence intervals (CIs) of proportions were calculated with the use of Wilson\u27s continuity correction. RESULTS: We analyzed 1,951 patients (mean ± SD age = 47 ± 18 years, 56% women) with an overall proportion of patients with PE of 3.5%. Both PERC and YEARS strategies were associated with 11 missed PE in the ED: failure rate 0.57 (95% CI = 0.32-1.02). At 3-month follow-up, the overall failure rate was 0.83% (95% CI = 0.51-1.35). Among the 503 patients who underwent a CTPA (26%), the use of the PERC-YEARS combination would have ruled out PE without CTPA in 249 patients (50% [95%CI = 45%-54%], absolute reduction 13% (95% CI = 11%-14%]). CONCLUSION: The combination of PERC then YEARS was associated with a low risk of PE diagnostic failure and would have resulted in a relative reduction of almost half of CTPA

Microarray evidence of glutaminyl cyclase gene expression in melanoma: implications for tumor antigen specific immunotherapy

BACKGROUND: In recent years encouraging progress has been made in developing vaccine treatments for cancer, particularly with melanoma. However, the overall rate of clinically significant results has remained low. The present research used microarray datasets from previous investigations to examine gene expression patterns in cancer cell lines with the goal of better understanding the tumor microenvironment. METHODS: Principal Components Analyses with Promax rotational transformations were carried out with 90 cancer cell lines from 3 microarray datasets, which had been made available on the internet as supplementary information from prior publications. RESULTS: In each of the analyses a well defined melanoma component was identified that contained a gene coding for the enzyme, glutaminyl cyclase, which was as highly expressed as genes from a variety of well established biomarkers for melanoma, such as MAGE-3 and MART-1, which have frequently been used in clinical trials of melanoma vaccines. CONCLUSION: Since glutaminyl cyclase converts glutamine and glutamic acid into a pyroglutamic form, it may interfere with the tumor destructive process of vaccines using peptides having glutamine or glutamic acid at their N-terminals. Finding ways of inhibiting the activity of glutaminyl cyclase in the tumor microenvironment may help to increase the effectiveness of some melanoma vaccines

MAGE-C2/CT10 Protein Expression Is an Independent Predictor of Recurrence in Prostate Cancer

The cancer-testis (CT) family of antigens is expressed in a variety of malignant neoplasms. In most cases, no CT antigen is found in normal tissues, except in testis, making them ideal targets for cancer immunotherapy. A comprehensive analysis of CT antigen expression has not yet been reported in prostate cancer. MAGE-C2/CT-10 is a novel CT antigen. The objective of this study was to analyze extent and prognostic significance of MAGE-C2/CT10 protein expression in prostate cancer. 348 prostate carcinomas from consecutive radical prostatectomies, 29 castration-refractory prostate cancer, 46 metastases, and 45 benign hyperplasias were immunohistochemically analyzed for MAGE-C2/CT10 expression using tissue microarrays. Nuclear MAGE-C2/CT10 expression was identified in only 3.3% primary prostate carcinomas. MAGE-C2/CT10 protein expression was significantly more frequent in metastatic (16.3% positivity) and castration-resistant prostate cancer (17% positivity; p<0.001). Nuclear MAGE-C2/CT10 expression was identified as predictor of biochemical recurrence after radical prostatectomy (p = 0.015), which was independent of preoperative PSA, Gleason score, tumor stage, and surgical margin status in multivariate analysis (p<0.05). MAGE-C2/CT10 expression in prostate cancer correlates with the degree of malignancy and indicates a higher risk for biochemical recurrence after radical prostatectomy. Further, the results suggest MAGE-C2/CT10 as a potential target for adjuvant and palliative immunotherapy in patients with prostate cancer

Preferential Amplification of CD8 Effector-T Cells after Transcutaneous Application of an Inactivated Influenza Vaccine: A Randomized Phase I Trial

Background: Current conventional vaccination approaches do not induce potent CD8 T-cell responses for fighting mostly variable viral diseases such as influenza, avian influenza viruses or HIV. Following our recent study on vaccine penetration by targeting of vaccine to human hair follicular ducts surrounded by Langerhans cells, we tested in the first randomized Phase-Ia trial based on hair follicle penetration (namely transcutaneous route) the induction of virus-specific CD8 T cell responses. Methods and Findings: We chose the inactivated influenza vaccine – a conventional licensed tetanus/influenza (TETAGRIP®) vaccine – to compare the safety and immunogenicity of transcutaneous (TC) versus IM immunization in two randomized controlled, multi-center Phase I trials including 24 healthy-volunteers and 12 HIV-infected patients. Vaccination was performed by application of inactivated influenza vaccine according to a standard protocol allowing the opening of the hair duct for the TC route or needle-injection for the IM route. We demonstrated that the safety of the two routes was similar. We showed the superiority of TC application, but not the IM route, to induce a significant increase in influenza-specific CD8 cytokine-producing cells in healthy-volunteers and in HIV-infected patients. However, these routes did not differ significantly for the induction of influenza-specific CD4 responses, and neutralizing antibodies were induced only by the IM route. The CD8 cell response is thus the major immune response observed after TC vaccination. Conclusions: This Phase Ia clinical trial (Manon05) testing an anti-influenza vaccine demonstrated that vaccines designed for antibody induction by the IM route, generate vaccine-specific CD8 T cells when administered transcutaneously. These results underline the necessity of adapting vaccination strategies to control complex infectious diseases when CD8 cellular responses are crucial. Our work opens up a key area for the development of preventive and therapeutic vaccines for diseases in which CD8 cells play a crucial role

Long-range transport in an assembly of ZnO quantum dots : the effects of quantum confinement, Coulomb repulsion and structural disorder

We have studied the storage and long-range transport of electrons in a porous assembly of weakly coupled ZnO quantum dots permeated with an aqueous and a propylene carbonate electrolyte solution. The number of electrons per ZnO quantum dot is controlled by the electrochemical potential of the assembly; the charge of the electrons is compensated by ions present in the pores. We show with optical and electrical measurements that the injected electrons occupy the S, P, and D type conduction electron levels of the quantum dots; electron storage in surface states is not important. With this method of three-dimensional charge compensation, up to ten electrons per quantum-dot can be stored if the assembly is permeated with an aqueous electrolyte. The screening of the electron charge is less effective in the case of an assembly permeated with a propylene carbonate electrolyte solution. Long-range electron transport is studied with a transistor set-up. In the case of ZnO assemblies permeated with an aqueous electrolyte, two quantum regimes are observed corresponding to multiple tunnelling between the S orbitals (at a low occupation) and P orbitals (at a higher occupation). In a ZnO quantum-dot assembly permeated with a propylene carbonate electrolyte solution, there is a strong overlap between these two regimes

Optical transitions in few-electron artificial atoms strongly confined in ZnO nanocrystals

We have studied the optical transitions in artificial atoms consisting of one to ten electrons occupying the conduction levels in ZnO nanocrystals. We analyzed near IR absorption spectra of assemblies of weakly coupled ZnO nanocrystals for a gradually increasing electron number and found four allowed dipole transitions with oscillator strengths in quantitative agreement with tight-binding theory. Furthermore, this spectroscopy provides the single-particle energy separation between the conduction levels of the ZnO quantum dots