Theory and experiment of entanglement in a quasi-phase-matched two-crystal source

We report new results regarding a source of polarization entangled photon-pairs created by the process of spontaneous parametric downconversion in two orthogonally oriented, periodically poled, bulk KTiOPO4 crystals (PPKTP). The source emits light colinearly at the non-degenerate wavelengths of 810 nm and 1550 nm, and is optimized for single-mode optical fiber collection and long-distance quantum communication. The configuration favors long crystals, which promote a high photon-pair production rate at a narrow bandwidth, together with a high pair-probability in fibers. The quality of entanglement is limited by chromatic dispersion, which we analyze by determining the output state. We find that such a decoherence effect is strongly material dependent, providing for long crystals an upper bound on the visibility of the coincidence fringes of 41% for KTiOPO4, and zero for LiNbO3. The best obtained raw visibility, when canceling decoherence with an extra piece of crystal, was 91 \pm 0.2%, including background counts. We confirm by a violation of the CHSH-inequality (S = 2.679 \pm 0.004 at 55 s^{-1/2} standard deviations) and by complete quantum state tomography that the fibers carry high-quality entangled pairs at a maximum rate of 55 x 10^3 s^{-1}THz^{-1}mW^{-1}.Comment: 12 pages, 10 figures, REVTeX

Perturbed CD8+ T cell TIGIT/CD226/PVR axis despite early initiation of antiretroviral treatment in HIV infected individuals.

HIV-specific CD8+ T cells demonstrate an exhausted phenotype associated with increased expression of inhibitory receptors, decreased functional capacity, and a skewed transcriptional profile, which are only partially restored by antiretroviral treatment (ART). Expression levels of the inhibitory receptor, T cell immunoglobulin and ITIM domain (TIGIT), the co-stimulatory receptor CD226 and their ligand PVR are altered in viral infections and cancer. However, the extent to which the TIGIT/CD226/PVR-axis is affected by HIV-infection has not been characterized. Here, we report that TIGIT expression increased over time despite early initiation of ART. HIV-specific CD8+ T cells were almost exclusively TIGIT+, had an inverse expression of the transcription factors T-bet and Eomes and co-expressed PD-1, CD160 and 2B4. HIV-specific TIGIThi cells were negatively correlated with polyfunctionality and displayed a diminished expression of CD226. Furthermore, expression of PVR was increased on CD4+ T cells, especially T follicular helper (Tfh) cells, in HIV-infected lymph nodes. These results depict a skewing of the TIGIT/CD226 axis from CD226 co-stimulation towards TIGIT-mediated inhibition of CD8+ T cells, despite early ART. These findings highlight the importance of the TIGIT/CD226/PVR axis as an immune checkpoint barrier that could hinder future "cure" strategies requiring potent HIV-specific CD8+ T cells

Unintended weight loss in the elderly living at home: the aged in homecare project (Adhoc)

Objective: To describe associations between unintended weight loss (UWL) and characteristics of nutritional status. Design: A comparative cross-sectional assessment study at 11 sites in Europe. The target population was a stratified random sample of 4,455 recipients of home care (405 in each random sample from 11 urban areas) aged 65 years and older. Measurements: the Resident Assessment Instrument for Home Care, version 2.0. Epidemiological and medical characteristics of clients and service utilisation were recorded in a standardized, comparative manner. UWL was defined as information of 5% or more weight loss in the last 30 days (or 10% or more in the last 180 days). Results: The final sample consisted of 4,010 persons; 74% were female. The mean ages were 80.9 ± 7.5 years (males) and 82.8 ± 7.3 years (females). No associations were found between single diagnoses and UWL, except for cancer. Cancer patients were excluded from further analyses. Persons with a Cognitive Performance Scale value (CPS) > 3 (impaired) had increased risk of UWL (OR = 2.0) compared with those scoring < 3 (less impaired). Only in the oldest group did we find a significant association between UWL and reduction in ADL and IADL functions, comparing those who scored 3 or less with those who scored more than 3 (disabled). A binary logistic regression model explained 26% of UWL: less than one meal/day, reduced appetite, malnutrition, reduced social activity, experiencing a flare-up of a recurrent or chronic problem, and hospitalisation were important indicators. Conclusion: We recommend a regular comprehensive assessment in home care to identify clients with potential risk factors for weight loss and malnutrition, in particular those discharged from hospital, and those with physical dependency or cognitive problems. This study may provide incentives to create tailored preventive strategies

Home care needs of extremely obese elderly european women

Objective: To examine the health and needs of extremely obese women aged over 65 years receiving home care in Europe. Study design: A cross-sectional assessment study based on the Aged in Home Care (AdHOC) project recruited 2974 women aged 65 or over who were receiving home care at 11 sites in European countries. Extreme obesity was defined as ‘Obesity of such a degree as to interfere with normal activities, including respiration’. Main outcome measures: Resident Assessment Instrument for Home Care (RAI-HC version 2.0); Activity of Daily Living Scale; Instrumental Activity of Daily Living Scale; the Minimum Data Set Cognitive Performance Scale; and a health profile. Results: One hundred and twenty women (4.0%) were extremely obese. They were younger than their thinner counterparts, with a median age of 78.3 versus 83.3 years, and they more often had multiple health complaints and needed more help with mobility outside the home. The extremely obese had received home care longer than the non-extremely obese (median 28.7 versus 36.6 months). Extremely obese women also needed more help with personal care than the other group and, due to lower age, they were less cognitively impaired. Conclusions: Extreme obesity is a problem that increasingly affects home care of elderly women

UV-induced ligand exchange in MHC class I protein crystals

High-throughput structure determination of protein−ligand complexes is central in drug development and structural proteomics. To facilitate such high-throughput structure determination we designed an induced replacement strategy. Crystals of a protein complex bound to a photosensitive ligand are exposed to UV light, inducing the departure of the bound ligand, allowing a new ligand to soak in. We exemplify the approach for a class of protein complexes that is especially recalcitrant to high-throughput strategies: the MHC class I proteins. We developed a UV-sensitive, “conditional”, peptide ligand whose UV-induced cleavage in the crystals leads to the exchange of the low-affinity lytic fragments for full-length peptides introduced in the crystallant solution. This “in crystallo” exchange is monitored by the loss of seleno-methionine anomalous diffraction signal of the conditional peptide compared to the signal of labeled MHC β2m subunit. This method has the potential to facilitate high-throughput crystallography in various protein families

Class I major histocompatibility complexes loaded by a periodate trigger

Class I major histocompatibility complexes (MHCs) present peptide ligands on the cell surface for recognition by appropriate cytotoxic T cells. The unstable nature of unliganded MHC necessitates the production of recombinant class I complexes through in vitro refolding reactions in the presence of an added excess of peptides. This strategy is not amenable to high-throughput production of vast collections of class I complexes. To address this issue, we recently designed photocaged MHC ligands that can be cleaved by a UV light trigger in the MHC bound state under conditions that do not affect the integrity of the MHC structure. The results obtained with photocaged MHC ligands demonstrate that conditional MHC ligands can form a generally applicable concept for the creation of defined peptide−MHCs. However, the use of UV exposure to mediate ligand exchange is unsuited for a number of applications, due to the lack of UV penetration through cell culture systems and due to the transfer of heat upon UV irradiation, which can induce evaporation. To overcome these limitations, here, we provide proof-of-concept for the generation of defined peptide−MHCs by chemical trigger-induced ligand exchange. The crystal structure of the MHC with the novel chemosensitive ligand showcases that the ligand occupies the expected binding site, in a conformation where the hydroxyl groups should be reactive to periodate. We proceed to validate this technology by producing peptide−MHCs that can be used for T cell detection. The methodology that we describe here should allow loading of MHCs with defined peptides in cell culture devices, thereby permitting antigen-specific T cell expansion and purification for cell therapy. In addition, this technology will be useful to develop miniaturized assay systems for performing high-throughput screens for natural and unnatural MHC ligands

Validity and reliability of Resource Utilization Groups (RUG-III) in Finnish long-term care facilities

Resource Utilization Groups, Version III (RUG-III) is a case-mix system developed in the USA for classification of long-term care residents. This paper examines the validity and reliability of an adapted 22-group version of RUG-III (RUG-III/22) for use in long-term care facilities in Finland. Finnish cost weights for RUG-III/22 groups are calculated and different methods for their computation are evaluated. The study sample (1,964 residents) was collected in 1995 - 96 from ten long-term care facilities in Finland. RUG-III/22 alone explained 38.2% of the variance of total patient-specific (nursing + auxiliary staff) per diem cost. Resource use within RUG groups was relatively homogeneous. Other predictors of resource use included age, gender and length of stay. RUG-III/22 also met the standard for good reliability (i.e. a kappa value of 0.6 or higher) for crucial classification items, such as activities of daily living and high correlation between assessments based on relative cost.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68924/2/10.1177_14034948990270030201.pd

Highly Efficient Source for Indistinguishable Photons of Controlled Shape

We demonstrate a straightforward implementation of a push-button like single-photon source which is based on a strongly coupled atom-cavity system. The device operates intermittently for periods of up to 100 microseconds, with single-photon repetition rates of 1.0 MHz and an efficiency of 60 %. Atoms are loaded into the cavity using an atomic fountain, with the upper turning point near the cavity's mode centre. This ensures long interaction times without any disturbances induced by trapping potentials. The latter is the key to reaching deterministic efficiencies as high as obtained in probabalistic photon-heralding schemes. The price to pay is the random loading of atoms into the cavity and the resulting intermittency. However, for all practical purposes, this has a negligible impact