Time- and angle-resolved photoemission spectroscopy with optimized high-harmonic pulses using frequency-doubled Ti:Sapphire lasers

Time- and angle-resolved photoemission spectroscopy (trARPES) using femtosecond extreme ultraviolet high harmonics has recently emerged as a powerful tool for investigating ultrafast quasiparticle dynamics in correlated-electron materials. However, the full potential of this approach has not yet been achieved because, to date, high harmonics generated by 800 nm wavelength Ti:Sapphire lasers required a trade-off between photon flux, energy and time resolution. Photoemission spectroscopy requires a quasi-monochromatic output, but dispersive optical elements that select a single harmonic can significantly reduce the photon flux and time resolution. Here we show that 400 nm driven high harmonic extreme-ultraviolet trARPES is superior to using 800 nm laser drivers since it eliminates the need for any spectral selection, thereby increasing photon flux and energy resolution to < 150 meV while preserving excellent time resolution of about 30 fs. © 2014 The Authors

Self-amplified photo-induced gap quenching in a correlated electron material.

Capturing the dynamic electronic band structure of a correlated material presents a powerful capability for uncovering the complex couplings between the electronic and structural degrees of freedom. When combined with ultrafast laser excitation, new phases of matter can result, since far-from-equilibrium excited states are instantaneously populated. Here, we elucidate a general relation between ultrafast non-equilibrium electron dynamics and the size of the characteristic energy gap in a correlated electron material. We show that carrier multiplication via impact ionization can be one of the most important processes in a gapped material, and that the speed of carrier multiplication critically depends on the size of the energy gap. In the case of the charge-density wave material 1T-TiSe2, our data indicate that carrier multiplication and gap dynamics mutually amplify each other, which explains-on a microscopic level-the extremely fast response of this material to ultrafast optical excitation

Escherichia coli phylogenetic group determination and its application in the identification of the major animal source of fecal contamination

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli </it>strains are commonly found in the gut microflora of warm-blooded animals. These strains can be assigned to one of the four main phylogenetic groups, A, B1, B2 and D, which can be divided into seven subgroups (A₀, A₁, B1, B2₂, B2₃, D₁and D₂), according to the combination of the three genetic markers <it>chuA</it>, <it>yjaA </it>and DNA fragment TspE4.C2. Distinct studies have demonstrated that these phylo-groups differ in the presence of virulence factors, ecological niches and life-history. Therefore, the aim of this work was to analyze the distribution of these <it>E. coli </it>phylo-groups in 94 human strains, 13 chicken strains, 50 cow strains, 16 goat strains, 39 pig strains and 29 sheep strains and to verify the potential of this analysis to investigate the source of fecal contamination.</p> <p>Results</p> <p>The results indicated that the distribution of phylogenetic groups, subgroups and genetic markers is non-random in the hosts analyzed. Strains from group B1 were present in all hosts analyzed but were more prevalent in cow, goat and sheep samples. Subgroup B2₃was only found in human samples. The diversity and the similarity indexes have indicated a similarity between the <it>E. coli </it>population structure of human and pig samples and among cow, goat and sheep samples. Correspondence analysis using contingence tables of subgroups, groups and genetic markers frequencies allowed the visualization of the differences among animal samples and the identification of the animal source of an external validation set. The classifier tools Binary logistic regression and Partial least square -- discriminant analysis, using the genetic markers profile of the strains, differentiated the herbivorous from the omnivorous strains, with an average error rate of 17%.</p> <p>Conclusions</p> <p>This is the first work, as far as we are aware, that identifies the major source of fecal contamination of a pool of strains instead of a unique strain. We concluded that the analysis of the <it>E. coli </it>population structure can be useful as a supplementary bacterial source tracking tool.</p

Quantification of the effects of an alpha-2 adrenergic agonist on reflex properties in spinal cord injury using a system identification technique

<p>Abstract</p> <p>Background</p> <p>Despite numerous investigations, the impact of tizanidine, an anti-spastic medication, on changes in reflex and muscle mechanical properties in spasticity remains unclear. This study was designed to help us understand the mechanisms of action of tizanidine on spasticity in spinal cord injured subjects with incomplete injury, by quantifying the effects of a single dose of tizanidine on ankle muscle intrinsic and reflex components.</p> <p>Methods</p> <p>A series of perturbations was applied to the spastic ankle joint of twenty-one spinal cord injured subjects, and the resulting torques were recorded. A parallel-cascade system identification method was used to separate intrinsic and reflex torques, and to identify the contribution of these components to dynamic ankle stiffness at different ankle positions, while subjects remained relaxed.</p> <p>Results</p> <p>Following administration of a single oral dose of Tizanidine, stretch evoked joint torque at the ankle decreased significantly (p < 0.001) The peak-torque was reduced between 15% and 60% among the spinal cord injured subjects, and the average reduction was 25%. Using systems identification techniques, we found that this reduced torque could be attributed largely to a reduced reflex response, without measurable change in the muscle contribution. Reflex stiffness decreased significantly across a range of joint angles (p < 0.001) after using tizanidine. In contrast, there were no significant changes in intrinsic muscle stiffness after the administration of tizanidine.</p> <p>Conclusions</p> <p>Our findings demonstrate that tizanidine acts to reduce reflex mechanical responses substantially, without inducing comparable changes in intrinsic muscle properties in individuals with spinal cord injury. Thus, the pre-post difference in joint mechanical properties can be attributed to reflex changes alone. From a practical standpoint, use of a single "test" dose of Tizanidine may help clinicians decide whether the drug can helpful in controlling symptoms in particular subjects.</p

Treatment of Branch Retinal Vein Occlusion induced Macular Edema with Bevacizumab

BACKGROUND: Branch retinal vein occlusion is a frequent cause of visual loss with currently insufficient treatment options. We evaluate the effect of Bevacizumab (Avastin) treatment in patients with macular edema induced by branch retinal vein occlusion. METHODS: Retrospective analysis of 32 eyes in 32 patients with fluorescein angiography proven branch retinal vein occlusion, macular edema and Bevacizumab treatment. Outcome measures were best corrected visual acuity in logMAR and central retinal thickness in OCT. RESULTS: Visual acuity was significantly better 4 to 6 weeks after Bevacizumab treatment compared to visual acuity prior to treatment (before 0.7 +/- 0.3 and after 0.5 +/- 0.3; mean +/- standard deviation; p < 0.01, paired t-test). Gain in visual acuity was accompanied by a significant decrease in retinal thickness (454 +/- 117 to 305 +/- 129 microm, p < 0.01, paired t-test). Follow up (170, 27 - 418 days; median, range) shows that improvement for both visual acuity and retinal thickness last for several months after Bevacizumab use. CONCLUSION: We present evidence that intravitreal Bevacizumab is an effective and lasting treatment for macular edema after branch retinal vein occlusion

Symptoms and quality of life in late stage Parkinson syndromes: a longitudinal community study of predictive factors

BACKGROUND Palliative care is increasingly offered earlier in the cancer trajectory but rarely in Idiopathic Parkinson's Disease(IPD), Progressive Supranuclear Palsy(PSP) or Multiple System Atrophy(MSA). There is little longitudinal data of people with late stage disease to understand levels of need. We aimed to determine how symptoms and quality of life of these patients change over time; and what demographic and clinical factors predicted changes. METHODS We recruited 82 patients into a longitudinal study, consenting patients with a diagnosis of IPD, MSA or PSP, stages 3-5 Hoehn and Yahr(H&Y). At baseline and then on up to 3 occasions over one year, we collected self-reported demographic, clinical, symptom, palliative and quality of life data, using Parkinson's specific and generic validated scales, including the Palliative care Outcome Scale (POS). We tested for predictors using multivariable analysis, adjusting for confounders. FINDINGS Over two thirds of patients had severe disability, over one third being wheelchair-bound/bedridden. Symptoms were highly prevalent in all conditions - mean (SD) of 10.6(4.0) symptoms. More than 50% of the MSA and PSP patients died over the year. Over the year, half of the patients showed either an upward (worsening, 24/60) or fluctuant (8/60) trajectory for POS and symptoms. The strongest predictors of higher levels of symptoms at the end of follow-up were initial scores on POS (AOR 1.30; 95%CI:1.05-1.60) and being male (AOR 5.18; 95% CI 1.17 to 22.92), both were more predictive than initial H&Y scores. INTERPRETATION The findings point to profound and complex mix of non-motor and motor symptoms in patients with late stage IPD, MSA and PSP. Symptoms are not resolved and half of the patients deteriorate. Palliative problems are predictive of future symptoms, suggesting that an early palliative assessment might help screen for those in need of earlier intervention

Modulation of Neutrophil Function by a Secreted Mucinase of Escherichia coli O157∶H7

Escherichia coli O157∶H7 is a human enteric pathogen that causes hemorrhagic colitis which can progress to hemolytic uremic syndrome, a severe kidney disease with immune involvement. During infection, E. coli O157∶H7 secretes StcE, a metalloprotease that promotes the formation of attaching and effacing lesions and inhibits the complement cascade via cleavage of mucin-type glycoproteins. We found that StcE cleaved the mucin-like, immune cell-restricted glycoproteins CD43 and CD45 on the neutrophil surface and altered neutrophil function. Treatment of human neutrophils with StcE led to increased respiratory burst production and increased cell adhesion. StcE-treated neutrophils exhibited an elongated morphology with defective rear detachment and impaired migration, suggesting that removal of the anti-adhesive capability of CD43 by StcE impairs rear release. Use of zebrafish embryos to model neutrophil migration revealed that StcE induced neutrophil retention in the fin after tissue wounding, suggesting that StcE modulates neutrophil-mediated inflammation in vivo. Neutrophils are crucial innate effectors of the antibacterial immune response and can contribute to severe complications caused by infection with E. coli O157∶H7. Our data suggest that the StcE mucinase can play an immunomodulatory role by directly altering neutrophil function during infection. StcE may contribute to inflammation and tissue destruction by mediating inappropriate neutrophil adhesion and activation

The porin and the permeating antibiotic: A selective diffusion barrier in gram-negative bacteria

Gram-negative bacteria are responsible for a large proportion of antibiotic resistant bacterial diseases. These bacteria have a complex cell envelope that comprises an outer membrane and an inner membrane that delimit the periplasm. The outer membrane contains various protein channels, called porins, which are involved in the influx of various compounds, including several classes of antibiotics. Bacterial adaptation to reduce influx through porins is an increasing problem worldwide that contributes, together with efflux systems, to the emergence and dissemination of antibiotic resistance. An exciting challenge is to decipher the genetic and molecular basis of membrane impermeability as a bacterial resistance mechanism. This Review outlines the bacterial response towards antibiotic stress on altered membrane permeability and discusses recent advances in molecular approaches that are improving our knowledge of the physico-chemical parameters that govern the translocation of antibiotics through porin channel

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

What parathyroid hormone levels should we aim for in children with stage 5 chronic kidney disease; what is the evidence?

The bone disease that occurs as a result of chronic kidney disease (CKD) is not only debilitating but also linked to poor growth and cardiovascular disease. It is suspected that abnormal bone turnover is the main culprit for these poor outcomes. Plasma parathyroid hormone (PTH) levels are used as a surrogate marker of bone turnover, and there is a small number of studies in children that have attempted to identify the range of PTH levels that correlates with normal bone histology. It is clear that high PTH levels are associated with high bone turnover, although the range is wide. However, the ability of PTH levels to distinguish between low and normal bone turnover is less clear. This is an important issue, because current guidelines for calcium and phosphate management are based upon there being an “optimum” range for PTH. This editorial takes a critical look at the evidence upon which these recommendations are based