High harmonic generation in a gas-filled hollow-core photonic crystal fiber

High harmonic generation (HHG) of intense infrared laser radiation (Ferray et al., J. Phys. B: At. Mol. Opt. Phys. 21:L31, 1988; McPherson et al., J. Opt. Soc. Am. B 4:595, 1987) enables coherent vacuum-UV (VUV) to soft-X-ray sources. In the usual setup, energetic femtosecond laser pulses are strongly focused into a gas jet, restricting the interaction length to the Rayleigh range of the focus. The average photon flux is limited by the low conversion efficiency and the low average power of the complex laser amplifier systems (Keller, Nature 424:831, 2003; Südmeyer et al., Nat. Photonics 2:599, 2008; Röser et al., Opt. Lett. 30:2754, 2005; Eidam et al., IEEE J. Sel. Top. Quantum Electron. 15:187, 2009) which typically operate at kilohertz repetition rates. This represents a severe limitation for many experiments using the harmonic radiation in fields such as metrology or high-resolution imaging. Driving HHG with novel high-power diode-pumped multi-megahertz laser systems has the potential to significantly increase the average photon flux. However, the higher average power comes at the expense of lower pulse energies because the repetition rate is increased by more than a thousand times, and efficient HHG is not possible in the usual geometry. So far, two promising techniques for HHG at lower pulse energies were developed: external build-up cavities (Gohle et al., Nature 436:234, 2005; Jones et al., Phys. Rev. Lett. 94:193, 2005) and resonant field enhancement in nanostructured targets (Kim et al., Nature 453:757, 2008). Here we present a third technique, which has advantages in terms of ease of HHG light extraction, transverse beam quality, and the possibility to substantially increase conversion efficiency by phase-matching (Paul et al., Nature 421:51, 2003; Ren et al., Opt. Express 16:17052, 2008; Serebryannikov et al., Phys. Rev. E (Stat. Nonlinear Soft Matter Phys.) 70:66611, 2004; Serebryannikov et al., Opt. Lett. 33:977, 2008; Zhang et al., Nat. Phys. 3:270, 2007). The interaction between the laser pulses and the gas occurs in a Kagome-type Hollow-Core Photonic Crystal Fiber (HC-PCF) (Benabid et al., Science 298:399, 2002), which reduces the detection threshold for HHG to only 200nJ. This novel type of fiber guides nearly all of the light in the hollow core (Couny et al., Science 318:1118, 2007), preventing damage even at intensities required for HHG. Our fiber guided 30-fs pulses with a pulse energy of more than 10μJ, which is more than five times higher than for any other photonic crystal fiber (Hensley et al., Conference on Lasers and Electro-Optics (CLEO), IEEE Press, New York, 2008

From red to white urine: a patient's nightmare with a rather benign outcome

<p>Abstract</p> <p>Background</p> <p>Chyluria is a medical condition with presence of chyle in the urine. The disease is most prevalent in endemic regions of Africa and the Indian subcontinent where it is mostly caused by parasitic infections, particularly lymphatic filariasis due to wucheria bancrofti. Non-parasitic chyluria, however, is a very rare finding.</p> <p>Case Presentation</p> <p>We report the case of a 48 year old woman who developed a lymphorenal fistula with chyluria following ureterrenoscopy with biopsies taken for urological work-up of persistent macrohematuria. Renal biopsy confirmed the diagnosis of benign familial hematuria due to thin basement nephropathy, a condition frequently associated with episodes of macrohematuria.</p> <p>Conclusions</p> <p>This case highlights a rare case of non-parasitic chyluria as a complication of urological work-up for macrohematuria of benign nature.</p

A simple electron time-of-flight spectrometer for ultrafast vacuum ultraviolet photoelectron spectroscopy of liquid solutions

We present a simple electron time of flight spectrometer for time resolved photoelectron spectroscopy of liquid samples using a vacuum ultraviolet (VUV) source produced by high-harmonic generation. The field free spectrometer coupled with the time-preserving monochromator for the VUV at the Artemis facility of the Rutherford Appleton Laboratory achieves an energy resolution of 0.65 eV at 40 eV with a sub 100 fs temporal resolution. A key feature of the design is a differentially pumped drift tube allowing a microliquid jet to be aligned and started at ambient atmosphere while preserving a pressure of 10−1 mbar at the micro channel plate detector. The pumping requirements for photoelectron (PE) spectroscopy in vacuum are presented while the instrument performance is demonstrated with PE spectra of salt solutions in water. The capability of the instrument for time resolved measurements is demonstrated by observing the ultrafast (50 fs) vibrational excitation of water leading to temporary proton transfer

Key Role of the GITR/GITRLigand Pathway in the Development of Murine Autoimmune Diabetes: A Potential Therapeutic Target

BACKGROUND: The cross-talk between pathogenic T lymphocytes and regulatory T cells (Tregs) plays a major role in the progression of autoimmune diseases. Our objective is to identify molecules and/or pathways involved in this interaction and representing potential targets for innovative therapies. Glucocorticoid-induced tumor necrosis factor receptor (GITR) and its ligand are key players in the T effector/Treg interaction. GITR is expressed at low levels on resting T cells and is significantly up-regulated upon activation. Constitutive high expression of GITR is detected only on Tregs. GITR interacts with its ligand mainly expressed on antigen presenting cells and endothelial cells. It has been suggested that GITR triggering activates effector T lymphocytes while inhibiting Tregs thus contributing to the amplification of immune responses. In this study, we examined the role of GITR/GITRLigand interaction in the progression of autoimmune diabetes. METHODS AND FINDINGS: Treatment of 10-day-old non-obese diabetic (NOD) mice, which spontaneously develop diabetes, with an agonistic GITR-specific antibody induced a significant acceleration of disease onset (80% at 12 weeks of age). This activity was not due to a decline in the numbers or functional capacity of CD4(+)CD25(+)Foxp3(+) Tregs but rather to a major activation of 'diabetogenic' T cells. This conclusion was supported by results showing that anti-GITR antibody exacerbates diabetes also in CD28(-/-) NOD mice, which lack Tregs. In addition, treatment of NOD mice, infused with the diabetogenic CD4(+)BDC2.5 T cell clone, with GITR-specific antibody substantially increased their migration, proliferation and activation within the pancreatic islets and draining lymph nodes. As a mirror image, blockade of the GITR/GITRLigand pathway using a neutralizing GITRLigand-specific antibody significantly protected from diabetes even at late stages of disease progression. Experiments using the BDC2.5 T cell transfer model suggested that the GITRLigand antibody acted by limiting the homing and proliferation of pathogenic T cells in pancreatic lymph nodes. CONCLUSION: GITR triggering plays an important costimulatory role on diabetogenic T cells contributing to the development of autoimmune responses. Therefore, blockade of the GITR/GITRLigand pathway appears as a novel promising clinically oriented strategy as GITRLigand-specific antibody applied at an advanced stage of disease progression can prevent overt diabetes

Neglected Tropical Diseases and the Millennium Development Goals-why the "other diseases" matter: reality versus rhetoric

Since 2004 there has been an increased recognition of the importance of Neglected Tropical Diseases (NTDs) as impediments to development. These diseases are caused by a variety of infectious agents - viruses, bacteria and parasites - which cause a diversity of clinical conditions throughout the tropics. The World Health Organisation (WHO) has defined seventeen of these conditions as core NTDs. The objectives for the control, elimination or eradication of these conditions have been defined in World Health Assembly resolutions whilst the strategies for the control or elimination of individual diseases have been defined in various WHO documents. Since 2005 there has been a drive for the expanded control of these diseases through an integrated approach of mass drug administration referred to as Preventive Chemotherapy via community-based distribution systems and through schools. This has been made possible by donations from major pharmaceutical companies of quality and efficacious drugs which have a proven track record of safety. As a result of the increased commitment of endemic countries, bilateral donors and non-governmental development organisations, there has been a considerable expansion of mass drug administration. In particular, programmes targeting lymphatic filariasis, onchocerciasis, schistosomiasis, trachoma and soil transmitted helminth infections have expanded to treat 887. 8 million people in 2009. There has been significant progress towards guinea worm eradication, and the control of leprosy and human African trypanosomiasis. This paper responds to what the authors believe are inappropriate criticisms of these programmes and counters accusations of the motives of partners made in recently published papers. We provide a detailed response and update the information on the numbers of global treatments undertaken for NTDs and list the success stories to date

Apoptosis of CD4+CD25high T Cells in Type 1 Diabetes May Be Partially Mediated by IL-2 Deprivation

from T1D subjects. in T1D may be caught up in a relatively deficient cytokine milieu. function in subjects predisposed to T1D

Early over expression of messenger RNA for multiple genes, including insulin, in the Pancreatic Lymph Nodes of NOD mice is associated with Islet Autoimmunity

<p>Abstract</p> <p>Background</p> <p>Autoimmune diabetes (T1D) onset is preceded by a long inflammatory process directed against the insulin-secreting β cells of the pancreas. Deciphering the early autoimmune mechanisms represents a challenge due to the absence of clinical signs at early disease stages. The aim of this study was to identify genes implicated in the early steps of the autoimmune process, prior to inflammation, in T1D. We have previously established that insulin autoantibodies (E-IAA) predict early diabetes onset delineating an early phenotypic check point (window 1) in disease pathogenesis. We used this sub-phenotype and applied differential gene expression analysis in the pancreatic lymph nodes (PLN) of 5 weeks old Non Obese Diabetic (NOD) mice differing solely upon the presence or absence of E-IAA. Analysis of gene expression profiles has the potential to provide a global understanding of the disease and to generate novel hypothesis concerning the initiation of the autoimmune process.</p> <p>Methods</p> <p>Animals have been screened weekly for the presence of E-IAA between 3 and 5 weeks of age. E-IAA positive or negative NOD mice at least twice were selected and RNAs isolated from the PLN were used for microarray analysis. Comparison of transcriptional profiles between positive and negative animals and functional annotations of the resulting differentially expressed genes, using software together with manual literature data mining, have been performed.</p> <p>Results</p> <p>The expression of 165 genes was modulated between E-IAA positive and negative PLN. In particular, genes coding for insulin and for proteins known to be implicated in tissue remodelling and Th1 immunity have been found to be highly differentially expressed. Forty one genes showed over 5 fold differences between the two sets of samples and 30 code for extracellular proteins. This class of proteins represents potential diagnostic markers and drug targets for T1D.</p> <p>Conclusion</p> <p>Our data strongly suggest that the immune related mechanisms taking place at this early age in the PLN, correlate with homeostatic changes influencing tissue integrity of the adjacent pancreatic tissue. Functional analysis of the identified genes suggested that similar mechanisms might be operating during pre-inflammatory processes deployed in tissues i) hosting parasitic microorganisms and ii) experiencing unrestricted invasion by tumour cells.</p