Using neural networks for high-speed blood cell classification in a holographic-microscopy flow-cytometry system

High-throughput cell sorting with flow cytometers is an important tool in modern clinical cell studies. Most cytometers use biomarkers that selectively bind to the cell, but induce significant changes in morphology and inner cell processes leading sometimes to its death. This makes label-based cell sorting schemes unsuitable for further investigation. We propose a label-free technique that uses a digital inline holographic microscopy for cell imaging and an integrated, optical neural network for high-speed classification. The perspective of dense integration makes it attractive to ultrafast, large-scale cell sorting. Network simulations for a ternary classification task (monocytes/granulocytes/lymphocytes) resulted in 89% accuracy

Anisotropic valence-->core x-ray fluorescence from a [Rh(en)3][Mn(N)(CN)5]·H2O single crystal: Experimental results and density functional calculations

High resolution x-ray fluorescence spectra have been recorded for emission in different directions from a single crystal of the compound [Rh(en)3][Mn(N)(CN)5]·H2O. The spectra are interpreted by comparison with density functional theory (DFT) electronic structure calculations. The Kbeta[double-prime] line, which is strongly polarized along the Mn–N axis, can be viewed as an N(2s)-->Mn(1s) transition, and the angular dependence is understood within the dipole approximation. The so-called Kbeta2,5 region has numerous contributions but is dominated by Mn(4p) and C(2s)-->Mn(1s) transitions. Transition energy splittings are found in agreement with those of calculated occupied molecular orbitals to within 1 eV. Computed relative transition probabilities reproduce experimentally observed trends

Cognitive Change during the Life Course and Leukocyte Telomere Length in Late Middle-Aged Men

AbstractImportance: Cognitive skills are known to decline through the lifespan with large individual differences. The molecular mechanisms for this decline are incompletely understood. Although leukocyte telomere length provides an index of cellular age that predicts the incidence of age-related diseases, it is unclear whether there is an association between cognitive decline and leukocyte telomere length. Objective: To examine the association between changes in cognitive function during adult life and leukocyte telomere length after adjusting for confounding factors such as education, mental health and life style. Design, setting and participants: Two groups of men with negative (n=97) and positive (n=93) change in cognitive performance were selected from a birth cohort of 1985 Danish men born in 1953. Cognitive performance of each individual was assessed at age ~20 and ~56 years. Leukocyte telomere length at age ~58 was measured using qPCR. Linear regression models were used to investigate the association between cognitive function and leukocyte telomere length. Results: Men with negative change in cognitive performance during adult life had significantly shorter mean leukocyte telomere length than men with positive change in cognitive performance (unadjusted difference β= - 0.09, 95% CI -0.16 - -0.02, p= 0.02). This association remained significant after adjusting for smoking, alcohol consumption, leisure time activity, body mass index and cholesterol (adjusted difference β= -0.09, 95% CI -0.17 - -0.01, p= 0.02) but was nonsignificant after adjusting for smoking, alcohol consumption, leisure time activity, body mass index cholesterol, current cognitive function, depression and education (adjusted difference β= -0.07, 95% CI -0.16 - -0.01, p= 0.08). Conclusion and relevance: Preclinical cognitive changes may be associated with leukocyte telomere length

PT-Symmetric Electronics

We show both theoretically and experimentally that a pair of inductively coupled active LRC circuits (dimer), one with amplification and another with an equivalent amount of attenuation, display all the features which characterize a wide class of non-Hermitian systems which commute with the joint parity-time PT operator: typical normal modes, temporal evolution, and scattering processes. Utilizing a Liouvilian formulation, we can define an underlying PT-symmetric Hamiltonian, which provides important insight for understanding the behavior of the system. When the PT-dimer is coupled to transmission lines, the resulting scattering signal reveals novel features which reflect the PT-symmetry of the scattering target. Specifically we show that the device can show two different behaviors simultaneously, an amplifier or an absorber, depending on the direction and phase relation of the interrogating waves. Having an exact theory, and due to its relative experimental simplicity, PT-symmetric electronics offers new insights into the properties of PT-symmetric systems which are at the forefront of the research in mathematical physics and related fields.Comment: 17 pages, 7 figure

Structure formation in active networks

Structure formation and constant reorganization of the actin cytoskeleton are key requirements for the function of living cells. Here we show that a minimal reconstituted system consisting of actin filaments, crosslinking molecules and molecular-motor filaments exhibits a generic mechanism of structure formation, characterized by a broad distribution of cluster sizes. We demonstrate that the growth of the structures depends on the intricate balance between crosslinker-induced stabilization and simultaneous destabilization by molecular motors, a mechanism analogous to nucleation and growth in passive systems. We also show that the intricate interplay between force generation, coarsening and connectivity is responsible for the highly dynamic process of structure formation in this heterogeneous active gel, and that these competing mechanisms result in anomalous transport, reminiscent of intracellular dynamics

An exactly solvable quantum-lattice model with a tunable degree of nonlocality

An array of N subsequent Laguerre polynomials is interpreted as an eigenvector of a non-Hermitian tridiagonal Hamiltonian $H$ with real spectrum or, better said, of an exactly solvable N-site-lattice cryptohermitian Hamiltonian whose spectrum is known as equal to the set of zeros of the N-th Laguerre polynomial. The two key problems (viz., the one of the ambiguity and the one of the closed-form construction of all of the eligible inner products which make $H$ Hermitian in the respective {\em ad hoc} Hilbert spaces) are discussed. Then, for illustration, the first four simplest, $k-$parametric definitions of inner products with $k=0,k=1,k=2$ and $k=3$ are explicitly displayed. In mathematical terms these alternative inner products may be perceived as alternative Hermitian conjugations of the initial N-plet of Laguerre polynomials. In physical terms the parameter $k$ may be interpreted as a measure of the "smearing of the lattice coordinates" in the model.Comment: 35 p

Chronic psychosocial and financial burden accelerates 5-year telomere shortening: findings from the Coronary Artery Risk Development in Young Adults Study.

Leukocyte telomere length, a marker of immune system function, is sensitive to exposures such as psychosocial stressors and health-maintaining behaviors. Past research has determined that stress experienced in adulthood is associated with shorter telomere length, but is limited to mostly cross-sectional reports. We test whether repeated reports of chronic psychosocial and financial burden is associated with telomere length change over a 5-year period (years 15 and 20) from 969 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a longitudinal, population-based cohort, ages 18-30 at time of recruitment in 1985. We further examine whether multisystem resiliency, comprised of social connections, health-maintaining behaviors, and psychological resources, mitigates the effects of repeated burden on telomere attrition over 5 years. Our results indicate that adults with high chronic burden do not show decreased telomere length over the 5-year period. However, these effects do vary by level of resiliency, as regression results revealed a significant interaction between chronic burden and multisystem resiliency. For individuals with high repeated chronic burden and low multisystem resiliency (1 SD below the mean), there was a significant 5-year shortening in telomere length, whereas no significant relationships between chronic burden and attrition were evident for those at moderate and higher levels of resiliency. These effects apply similarly across the three components of resiliency. Results imply that interventions should focus on establishing strong social connections, psychological resources, and health-maintaining behaviors when attempting to ameliorate stress-related decline in telomere length among at-risk individuals

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Electrical manipulation of spin states in a single electrostatically gated transition-metal complex

We demonstrate an electrically controlled high-spin (S=5/2) to low-spin (S=1/2) transition in a three-terminal device incorporating a single Mn2+ ion coordinated by two terpyridine ligands. By adjusting the gate-voltage we reduce the terpyridine moiety and thereby strengthen the ligand-field on the Mn-atom. Adding a single electron thus stabilizes the low-spin configuration and the corresponding sequential tunnelling current is suppressed by spin-blockade. From low-temperature inelastic cotunneling spectroscopy, we infer the magnetic excitation spectrum of the molecule and uncover also a strongly gate-dependent singlet-triplet splitting on the low-spin side. The measured bias-spectroscopy is shown to be consistent with an exact diagonalization of the Mn-complex, and an interpretation of the data is given in terms of a simplified effective model.Comment: Will appear soon in Nanoletter

Cancer incidence in persons with type 1 diabetes : a five-country study of 9,000 cancers in type 1 diabetic individuals

An excess cancer incidence of 20-25% has been identified among persons with diabetes, most of whom have type 2 diabetes. We aimed to describe the association between type 1 diabetes and cancer incidence. Persons with type 1 diabetes were identified from five nationwide diabetes registers: Australia (2000-2008), Denmark (1995-2014), Finland (1972-2012), Scotland (1995-2012) and Sweden (1987-2012). Linkage to national cancer registries provided the numbers of incident cancers in people with type 1 diabetes and in the general population. We used Poisson models with adjustment for age and date of follow up to estimate hazard ratios for total and site-specific cancers. A total of 9,149 cancers occurred among persons with type 1 diabetes in 3.9 million person-years. The median age at cancer diagnosis was 51.1 years (interquartile range 43.5-59.5). The hazard ratios (HRs) (95% CIs) associated with type 1 diabetes for all cancers combined were 1.01 (0.98, 1.04) among men and 1.07 (1.04, 1.10) among women. HRs were increased for cancer of the stomach (men, HR 1.23 [1.04, 1.46]; women, HR 1.78 [1.49, 2.13]), liver (men, HR 2.00 [1.67, 2.40]; women, HR 1.55 [1.14, 2.10]), pancreas (men, HR 1.53 [1.30, 1.79]; women, HR 1.25 [1.02,1.53]), endometrium (HR 1.42 [1.27, 1.58]) and kidney (men, HR 1.30 [1.12, 1.49]; women, HR 1.47 [1.23, 1.77]). Reduced HRs were found for cancer of the prostate (HR 0.56 [0.51, 0.61]) and breast (HR 0.90 [0.85, 0.94]). HRs declined with increasing diabetes duration. Type 1 diabetes was associated with differences in the risk of several common cancers; the strength of these associations varied with the duration of diabetes.Peer reviewe