De Broglie Wavelength of a Nonlocal Four-Photon

Superposition is one of the most distinct features of quantum theory and has been demonstrated in numerous realizations of Young's classical double-slit interference experiment and its analogues. However, quantum entanglement - a significant coherent superposition in multiparticle systems - yields phenomena that are much richer and more interesting than anything that can be seen in a one-particle system. Among them, one important type of multi-particle experiments uses path-entangled number-states, which exhibit pure higher-order interference and allow novel applications in metrology and imaging such as quantum interferometry and spectroscopy with phase sensitivity at the Heisenberg limit or quantum lithography beyond the classical diffraction limit. Up to now, in optical implementations of such schemes lower-order interference effects would always decrease the overall performance at higher particle numbers. They have thus been limited to two photons. We overcome this limitation and demonstrate a linear-optics-based four-photon interferometer. Observation of a four-particle mode-entangled state is confirmed by interference fringes with a periodicity of one quarter of the single-photon wavelength. This scheme can readily be extended to arbitrary photon numbers and thus represents an important step towards realizable applications with entanglement-enhanced performance.Comment: 19 pages, 4 figures, submitted on November 18, 200

Super-resolving phase measurements with a multi-photon entangled state

Using a linear optical elements and post-selection, we construct an entangled polarization state of three photons in the same spatial mode. This state is analogous to a ``photon-number path entangled state'' and can be used for super-resolving interferometry. Measuring a birefringent phase shift, we demonstrate two- and three-fold improvements in phase resolution.Comment: 4 pages, 3 figure

General framework for estimating the ultimate precision limit in noisy quantum-enhanced metrology

The estimation of parameters characterizing dynamical processes is central to science and technology. The estimation error changes with the number N of resources employed in the experiment (which could quantify, for instance, the number of probes or the probing energy). Typically, it scales as 1/N^(1/2). Quantum strategies may improve the precision, for noiseless processes, by an extra factor 1/N^(1/2). For noisy processes, it is not known in general if and when this improvement can be achieved. Here we propose a general framework for obtaining attainable and useful lower bounds for the ultimate limit of precision in noisy systems. We apply this bound to lossy optical interferometry and atomic spectroscopy in the presence of dephasing, showing that it captures the main features of the transition from the 1/N to the 1/N^(1/2) behaviour as N increases, independently of the initial state of the probes, and even with use of adaptive feedback.Comment: Published in Nature Physics. This is the revised submitted version. The supplementary material can be found at http://www.nature.com/nphys/journal/v7/n5/extref/nphys1958-s1.pd

Regulation of RasGRP1 Function in T Cell Development and Activation by Its Unique Tail Domain

The Ras-guanyl nucleotide exchange factor RasGRP1 plays a critical role in T cell receptor-mediated Erk activation. Previous studies have emphasized the importance of RasGRP1 in the positive selection of thymocytes, activation of T cells, and control of autoimmunity. RasGRP1 consists of a number of well-characterized domains, which it shares with its other family members; however, RasGRP1 also contains an ∼200 residue-long tail domain, the function of which is unknown. To elucidate the physiological role of this domain, we generated knock-in mice expressing RasGRP1 without the tail domain. Further analysis of these knock-in mice showed that thymocytes lacking the tail domain of RasGRP1 underwent aberrant thymic selection and, following TCR stimulation, were unable to activate Erk. Furthermore, the deletion of the tail domain led to enhanced CD4+ T cell expansion in aged mice, as well as the production of autoantibodies. Mechanistically, the tail-deleted form of RasGRP1 was not able to traffic to the cell membrane following stimulation, indicating a potential reason for its inability to activate Erk. While the DAG-binding C1 domain of RasGRP1 has long been recognized as an important factor mediating Erk activation, we have revealed the physiological relevance of the tail domain in RasGRP1 function and control of Erk signaling

Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis

The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving a frequency of TARDBP mutations in non-SOD1 FALS of 5% and SALS of 0.4%. Analysis of clinical data identified that patients had typical ALS, with limb or bulbar onset, and showed considerable variation in age of onset and rapidity of disease course. However, all cases had an absence of clinically overt cognitive dysfunction

Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations.

Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses

Mindfulness-based interventions for young offenders: a scoping review

Youth offending is a problem worldwide. Young people in the criminal justice system have frequently experienced adverse childhood circumstances, mental health problems, difficulties regulating emotions and poor quality of life. Mindfulness-based interventions can help people manage problems resulting from these experiences, but their usefulness for youth offending populations is not clear. This review evaluated existing evidence for mindfulness-based interventions among such populations. To be included, each study used an intervention with at least one of the three core components of mindfulness-based stress reduction (breath awareness, body awareness, mindful movement) that was delivered to young people in prison or community rehabilitation programs. No restrictions were placed on methods used. Thirteen studies were included: three randomized controlled trials, one controlled trial, three pre-post study designs, three mixed-methods approaches and three qualitative studies. Pooled numbers (n = 842) comprised 99% males aged between 14 and 23. Interventions varied so it was not possible to identify an optimal approach in terms of content, dose or intensity. Studies found some improvement in various measures of mental health, self-regulation, problematic behaviour, substance use, quality of life and criminal propensity. In those studies measuring mindfulness, changes did not reach statistical significance. Qualitative studies reported participants feeling less stressed, better able to concentrate, manage emotions and behaviour, improved social skills and that the interventions were acceptable. Generally low study quality limits the generalizability of these findings. Greater clarity on intervention components and robust mixed-methods evaluation would improve clarity of reporting and better guide future youth offending prevention programs

Genetic polymorphisms in the matrix metalloproteinase 12 gene (MMP12) and breast cancer risk and survival: the Shanghai Breast Cancer Study

INTRODUCTION: Matrix metalloproteinase 12 (MMP12) is a proteolytic enzyme responsible for cleavage of plasminogen to angiotensin, which has an angiostatic effect. Using data from a population-based case–control study conducted among Chinese women in Shanghai, we evaluated the association of breast cancer risk and survival with two common polymorphisms in the MMP12 gene: A-82G in the promoter region and A1082G in exon, resulting in an amino acid change of asparagine to serine. METHODS: Included in the study were 1,129 cases and 1,229 age-frequency-matched population controls. Breast cancer patients were followed up to determine the intervals of overall survival and disease-free survival. RESULTS: The frequencies of the G allele in the A-82G and A1082G polymorphism among controls were 0.029 and 0.107, respectively. There were no associations between MMP12 polymorphisms and breast cancer risk. Patients with the AG or GG genotype of the A1082G polymorphism showed poorer overall survival (though the difference was not statistically significant) than patients with the AA genotype (hazard ratio 1.36, 95% CI 0.92 to 2.00). CONCLUSION: This result suggests that MMP12 A1082G polymorphism may be related to prognosis in breast cancer patients. Additional studies with larger sample sizes are warranted

Resuscitation of Severe Uncontrolled Hemorrhage 7.5% Sodium Chloride/6% Dextran 70 vs 0.9% Sodium Chloride

Objectives: Resuscitation studies of hypertonic saline using controlled and uncontrolled hemorrhage models yield conflicting results with regard to efficacy. These disparate results reflect the use of models and resuscitation regimens that are not comparable between studies. This study evaluated the effects of comparable and clinically relevant resuscitation regimens of 7.5% sodium chloride/6% dextran 70 (HSD) and 0.9% sodium chloride (NS) in a near-fatal uncontrolled hemorrhage model. Methods: Thirty-six swine (14.2 to 21.4 kg) with 4-mm aortic tears were bled to a pulse pressure of 5 mm Hg (40-45 mL/kg). The animals were resuscitated with either NS or HSD administered in volumes that provided equivalent sodium loads at similar rates. Group II (n = 12) was resuscitated with 80 mL/kg of NS at a rate of 4 mL/kg/min. Group III (n = 12) received 9.6 mL/kg of HSD at a rate of 0.48 mL/kg/min. In both groups, crystalloid resuscitation was followed by shed blood infusion (30 mL/kg) at a rate of 2 mL/kg/min. Group I (controls; n = 12) were not resuscitated. Results: One-hour mortality was significantly greater in group I (92%) as compared with group II (33%) and group III (33%) (Fisher's exact test; p = 0.004). Intraperitoneal hemorrhage was significantly greater in group II (34 ± 20 mL/kg) and group III (31 ± 13 mL/kg) as compared with group I (5 ± 2 mL/kg) (ANOVA; p < 0.05). There was no significant difference in hemodynamic parameters between groups II and III. Conclusion: In this model of severe uncontrolled hemorrhage, resuscitation with HSD or NS, administered in volumes that provided equivalent sodium loads at similar rates, had similar effects on mortality, hemodynamic parameters, and hemorrhage from the injury site.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73625/1/j.1553-2712.2000.tb02060.x.pd