Search

Background: β-Glucosylceramide, a naturally occurring glycolipid, exerts modulatory effects on natural killer T (NKT) lymphocytes. Aim: To determine whether β-glucosylceramide can alter NKT function in opposite directions, colitis was induced by intracolonic installation of trinitrobenzenesulphonic acid, and hepatocellular carcinoma (HCC) was induced by transplantation of Hep3B cells. Methods: The immunological effect of β-glucosylceramide was assessed by analysis of intrahepatic and intrasplenic lymphocyte populations, serum cytokines and STAT protein expression. Results: Administration of β-glucosylceramide led to alleviation of colitis and to suppression of HCC, manifested by improved survival and decreased tumour volume. The beneficial effects were associated with an opposite immunological effect in the two models: the peripheral:intrahepatic CD4:CD8 lymphocyte ratio increased in the colitis model and decreased in the HCC group. The peripheral:intrahepatic NKT lymphocyte ratio decreased in β-glucosylceramide-treated mice solely in the HCC model. The effect of β-glucosylceramide was associated with decreased STAT1 and 4 expression, and with overexpression of STAT6, along with decreased interferon γ levels in the colitis model, whereas an opposite effect was noted in the HCC model. Conclusions: β-glucosylceramide alleviates immunologically incongruous disorders and may be associated with “fine tuning” of immune responses, by changes in plasticity of NKT lymphocytes.

The aim of this study was to determine the effect of adoptive transfer of regulatory natural killer T (NKT) lymphocytes on the metabolic disorder in leptin-deficient ob/ob mice, which feature depletion and defective function of NKT and CD4 lymphocytes. Leptin-deficient ob/ob mice were subjected to transplantation of 1 x 10(6) of either ob/ob or wild-type-derived NKT lymphocytes, or to transplantation of either ob/ob or wild-type-derived splenocytes. The effect on hepatic fat content was measured by magnetic resonance imaging (signal intensity index) and histology, using the steatohepatitis grading scale. The degree of glucose intolerance was measured by an oral glucose tolerance test (GTT). Adoptive transfer of wild-type or ob/ob-derived regulatory NKT cells led to a 12% decrease in hepatic fat content. A significant histological shift from macrosteatosis to microsteatosis was observed. Marked improvement in the GTT was noted in wild-type or ob/ob-derived NKT recipients. Metabolic effects were associated with a significant decrease in peripheral and intrahepatic CD4/CD8 lymphocyte ratios. Intrahepatic CD8 trapping was observed in all responders. Serum interleukin 10 levels decreased significantly. In conclusion, adoptive transfer of a relatively small number of regulatory NKT lymphocytes into ob/ob mice results in a significant reduction in hepatic fat content, a shift from macro to microsteatosis, and significant improvement in glucose intolerance. These effects were associated with decreased peripheral and intrahepatic CD4/CD8 ratios and decreased interleukin 10 levels. The results further support a role for regulatory NKT lymphocytes in the pathogenesis of non-alcoholic steatohepatitis in the leptin-deficient murine model.

Summary: Natural killer T (NKT) lymphocyte cells are a subset of regulatory lymphocytes with important immunemodulatory effects. Our aim was to evaluate the effect of transplantation of NKT lymphocytes on graft versus host disease (GVHD) in a murine model of semiallogeneic BMT. GVHD was generated by infusion of 2 × 107 splenocytes from C57BL/6 donor mice into irradiated (C57BL/6 × Balb/c)F1 recipient mice. Adoptive transfer of increasing numbers of DX5+ cells was performed. Recipient mice were followed for histological parameters of GVHD-associated liver, bowel, and cutaneous injury. Intrahepatic and intrasplenic lymphocytes were isolated and analyzed by FACS for CD4+ and CD8+ subpopulations. It was seen that adoptive transfer of 4.5 × 106 DX5+ cells significantly alleviated GVHD-related hepatic, bowel, and cutaneous injury, and improved survival (85% survival on day 28). In contrast, depletion of DX5+ cells led to severe GVHD-associated multiorgan injury and 100% mortality. A direct correlation with the number of transplanted DX5+ cells was noted (maximal effect with transplantation of 4.5 × 106 DX5+ cells). Tolerance induction was associated with an increased peripheral CD4/CD8 ratio, intrahepatic trapping of CD8 lymphocytes and a shift towards a Th2-type cytokine profile, manifested by decreased IL-12/IL10, IL-12/IL-4, IFNγ/IL-10, and IFNγ/IL-4 ratios. Transplantation of DX5+ cells holds promise as a novel therapeutic measure for GVHD.

This paper reports the removal of in-band amplified spontaneous emission (ASE) noise in a 10 Gb/s noise-loaded return-to-zero (RZ) signal using a dispersion-imbalanced loop mirror. The resulting receiver sensitivity is improved from -37.0 dBm to -37.7 dBm. The dependence of receiver sensitivity on the loop mirror bias is also investigated, and the optimal bias point is found to be where the loop transmissivity decreases with increasing input power.

A multidimensional extension of the injection locking of CW lasers has been recently presented and experimentally verified when both a passively and an actively mode-locked laser were locked to injected coherent pulse trains. Harmonic injection locking of a passively mode-locked laser, where a subset of the laser cavity modes were locked to the injected signal, was also recently realized in a fiber laser to yield trains of 6-ps pulses at rates of up to 40 GHz. In this paper, the multimode injection-locking process is addressed with an emphasis on the long-term dynamics of the laser, pulse buildup under injection locking, memory effects, noise mechanism as well as potential applications, e.g., optical signal regeneration. Using a recently introduced formalism for describing passively mode-locked lasers, the experimental results are compared to numerical simulations.

The recently introduced harmonic injection locking is a method for generating pulse trains at high repetition rates from passively mode locked lasers. The buildup and dephasing mechanism which are instrumental for the fundamental understanding of the multimode locking process as well as its possible applications, were explored experimentally and by a novel model simulation which was adapted to include the pulsed injection locking. The measured locked pulse buildup time wa.5 μs, which corresponds to several tens of cavity roundtrips. When the injection was interrupted, the laser continued to emit synchronized pulses, indicating a persistence of the injection induced phase relationship of the cavity modes.

We present a method for simulating a passively mode locked laser. By selecting the simulation time step as the cavity round trip time, we achieved a proper tracking of the temporal evolution of the individual cavity modes of the laser. Employing the split step Fourier algorithm using this natural modes base, an efficient simulation method was obtained, while retaining at each propagation step the direct physical relations between the calculated phase terms in the time and frequency domains to the actual optical field and individual cavity modes, respectively. Using this method, we tracked the formation of multiple pulses in a passively mode locked fiber laser cavity, and explored the effect of delayed optical feedback as a means for pulse ordering in fiber lasers.

Voeller and Heilman (1988a) have produced evidence suggesting a right‐hemisphere dysfunction associated with attention‐deficit hyperactivity disorder (ADHD): ADHD‐related hemineglect. The present study is a constructive replication, using carefully screened children with ADHD for a number of compromising factors (e.g., no lateralized brain damage, handedness, eyedness). Each child received two tests: Line Bisection and Visual Target Cancellation Test. In addition, their performance was assessed in both binocular and monocular viewing conditions. While the ADHD children performed generally worse than the controls on target cancellation (i.e., exhibiting higher inattention), there was no evidence for hemineglect. To complicate matters, a reversed right‐left imbalance was tapped using a structured task array for this test, for left‐eye dominant ADHD children not on medication. Besides drawing attention to the role of the dominant eye in the scanning of children with ADHD, we suggest that no firm conclusions ...

We present and analyze a model of a passively mode-locked laser, which is subjected to injection of a coherent pulse train. The model, based on soliton perturbation theory, predicts the possibility of coherent injection locking, and gives analytical estimates for the locking ranges. The ability to simultaneously lock the timing and the phase of the output pulses of a mode-locked laser to an injected, coherent pulse train is shown. The interesting limiting case of phase locking the mode-locked laser to a constant amplitude external injection, is addressed with implications for future coherent soliton communication systems.

This paper describes wide-band electrooptic modulation of a short-cavity distributed Bragg reflector laser. Efficient amplitude modulation, in both small and large signal regimes, is obtained by modulation of the center Bragg reflector wavelength via electrooptic tuning. The role of the refractive index dynamics in determining the characteristics of a diode laser employing wavelength dependent feedback is also addressed. >

Harmonic injection locking can generate pulse trains at high repetition rates from passively mode-locked lasers. We have examined experimentally the mutual interaction of noise with the locking process. For injected signals with large timing and amplitude noise, the mode-locked fiber laser generated a pulse train with reduced noise. Injected signals with low timing and amplitude noise were employed for the reduction of the internal noise of the passively mode-locked laser. The achieved output pulse-to-pulse timing jitter in the range of 20-2500 Hz was ~0.6 ps, comparable with that of actively stabilized fiber lasers.

Background and aim Limited data suggests that pseudomembranes are uncommon in patients with inflammatory bowel disease (IBD) and C. difficile associated disease (CDAD), but the reason for this is unknown. We aimed to evaluate the rate of pseudomembranes in this population, identify predictive factors for pseudomembranes' presence and assess its clinical impact. Methods This was a sub-study of a retrospective European Crohn's & Colitis Organization (ECCO) multi-center study on the outcome of hospitalized IBD patients with C. difficile. The present study included only patients who underwent lower endoscopy during hospitalization, and compared demographic and clinical parameters in the group of patients with discernable pseudomembranes versus those without. Results Out of 155 patients in the original cohort, 93 patients underwent lower endoscopy and constituted the study population. Endoscopic pseudomembranes were found in 12 (13%) of these patients. Patients with pseudomembranes presented more commonly with fever (p = 0.02) compared to patients without pseudomembranes. No difference between the two groups was found with respect to the use of immunosuppressant drugs, background demographics or disease characteristics. Neither was there a difference between the group with or without pseudomembranes in the frequency of severe adverse clinical outcome or in the duration of hospitalization. On multi-variate analysis the presence of fever remained independently associated with the finding of pseudomembranes (OR 6, 95% CI 1.2–32, p = 0.03). Conclusions This study documents that hospitalized IBD patients with CDAD have low rate of endoscopic pseudomembranes, which is not accounted for by the use of immunosuppressant drugs. IBD patients with CDAD and discernable pseudomembranes more commonly present with fever, but their clinical outcome is similar to patients without pseudomembranes.

While the presence of Epstein-Barr virus (EBV) in colonic specimens from patients with inflammatory bowel disease (IBD) has been documented, diarrhea secondary to gastrointestinal involvement by EBV in the context of primary EBV infection in patients with IBD has not been reported. We describe a patient with IBD who presented with diarrhea and primary EBV infection and propose a role for colonic involvement by EBV in the pathogenesis of his symptoms.

We directly measure the time-independent nonlinear self-phase shift of a pulse after fiber propagation by spectral interferometry. Both the soliton and the nonsoliton case were studied. We verify numerically that the measured phase shift approximates this time-independent phase well.

In this letter, we report stable operation of a 1-GHz passively modelocked fiber laser synchronized by regenerative phase modulation. The minimum pulsewidth obtained was 600 fs and the laser amplitude noise was typical of low-noise passively mode-locked fiber lasers.

We describe an energy-resolved and spatially selective time domain technique for optically excited measurements of diode laser modulation responses. We report application of the technique to a study of an InGaAs-GaAs quantum well laser. We emphasize the significance of the spatial characteristics of the excitation in resolving effects related either solely to the active region or to the entirety of the laser structure. >

Primary sclerosing cholangitis (PSC), a condition usually associated with inflammatory bowel disease, is a chronic inflammatory state of the biliary tract characterized by fibrotic strictures of intrahepatic and extrahepatic bile ducts. Between 5-15% of patients with PSC will develop cholangiocarcinoma. The diagnosis of cholangiocarcinoma in patients with PSC is difficult, as it is often impossible to distinguish benign PSC-related strictures from lesions associated with cholangiocarcinoma. Consequently, most patients are diagnosed with advanced disease and have a dismal prognosis at the time of diagnosis. The importance of characterizing patients with PSC who have an increased risk of developing cholangiocarcinoma and of developing means for early detection of this disease cannot be over-emphasized. Detection of cholangiocarcinoma in asymptomatic patients is additionally important, as this condition is considered a contraindication for liver transplantation. We describe a patient with longstanding Crohn's disease and PSC who developed cholangiocarcinoma, and review the literature regarding risk factors for cholangiocarcinoma, early detection of cholangiocarcinoma and the significance of existing cholangiocarcinoma in the context of liver transplantation.

The problem of efficient smoothing and compression of large sets of two-dimensional data is addressed. Global surface fitting methods using radial basis functions are shown to have inherent characteristics which enable a simplification of the general nonlinear problem. An efficient placement of basis functions reduces their number considerably. The separate calculation of basis function locations leaves only the problem of evaluating their linear coefficients. A least-square method can be used, but for large sets of data, a further relaxation using information gained during the placement process, enables the application of linear programming techniques. A few examples of fitting topographical data are given. >

The dynamical characteristics of distributed Bragg reflection lasers with a Bragg reflection bandwidth narrower than the cavity mode spacing are reported. The operation of this Bragg reflector as an amplitude modulator (unlike the usual frequency modulator) is demonstrated in the small and large signal modulation regimes. In the conventional mode of gain modulation, this narrow Bragg reflector exhibits detuned loading effects. The laser is capable of efficient digital modulation as well as Q‐switching, both with a very small drive current.

Dual harmonic injection locking of a passively mode-locked diode laser yielded a simultaneous emission of two /spl sim/100 GHz pulse trains at two different wavelengths. High pulse rates exceeding /spl sim/900 GHz were obtained using a single locking source. The passively mode-locked diode laser was a Fabry-Perot laser based on a InGaAs/InGaAsP multiple quantum well layer structure operating near 1540 nm.

Summary form only given. We describe small and large signal modulation characteristics of distributed Bragg reflection lasers with a Bragg reflection bandwidth narrower than the cavity mode spacing.

Summary form only given. We report the first observation of synchronous injection locking of a mode locked semiconductor laser. Locking ranges, both in the time and in the frequency domains, were measured, as well as noise parameters. Experimental results were compared to a model, with an emphasis on possible instabilities.

The determination of receiver sensitivity and bit-error rate (BER) is important in the design of high bit rate optical digital communication systems at the 1.5 /spl mu/m wavelength, where the most sensitive receivers use optical preamplification. There exists two classes of models for the analysis of optically amplified signals. The first class uses the semiclassical square-law model for detection, resulting in a Gaussian distribution for the photocurrent. The second class uses quantum mechanics to treat spontaneous and stimulated processes in the optical amplifier. The advantages of the semiclassical models are simplicity and the fact that it yields an analytical expression for the BER, while the advantage of the quantum mechanical model is its correctness in describing the physical processes. In this paper, we show that the photon distribution of the zeros obtained experimentally is indeed Bose-Einstein distributed. We then demonstrate that we can predict the sensitivity of the receiver based on the quantum mechanical model.

Recently, a novel way of generating an amplitude-squeezed state using the Kerr nonlinearity has been demonstrated. In this scheme, a pulse with an energy greater than that of the fundamental soliton is launched into an optical fiber with a length of several soliton periods. At the fiber output, the pulse is filtered and detected. The resulting photocurrent has a noise level lower then the shot noise, indicating an amplitude-squeezed state. Here, we demonstrate that soliton amplitude squeezing can be obtained without postfiltering.

We examined the noise properties and the temporal dynamics of the multimode injection locking process in an Er-doped fiber laser. The actively mode locked extended cavity diode laser, operating at 1.53 /spl mu/m produced pulse trains with a repetition of 1GHz and pulse widths of 25 ps.

The application of ozone is widely practised as a form of alternative medicine, particularly in Germany and Eastern Europe. Ozone major autohemotherapy (the return of a small amount of a patient's blood to the circulation after ex vivo exposure to ozone) has been reported to have a therapeutic effect in various pathological conditions, including ischemic, infectious, autoimmune and neoplastic disorders. Ozone has an effect on the expression of cytokines, adhesion molecules and acute phase reactants, which are responsible in part for the respiratory inflammatory response observed after exposure to this gas. The purpose of the present study was to investigate the effect of ozone administration ex vivo, at a concentration commonly used in major autohemotherapy, on peripheral blood neutrophil function in vitro. Blood drawn from healthy volunteers was studied for neutrophil adhesion, chemotaxis and O-2 production before and after exposure to 30 microg/ml ozone. There was no significant difference in adhesion and chemotaxis of neutrophils exposed to ozone versus unexposed cells. O-2 production was minimally decreased (20.3 +/- 5.0 vs. 22.1 +/- 5.5 nmol/106 cells/10 min, respectively; P=0.01), a reduction of no clinical significance. This study confirms that major autohemotherapy with ozone is safe as far as neutrophil function is concerned. Combined with previous data, it seems that well-designed clinical trials to assess the efficacy of major autohemotherapy would pose no danger to blood cell populations, and should be encouraged.

When propagating through an optical fiber, a pulse accumulates a nonlinear phase shift. If the pulse is a soliton this nonlinear phase is time-independent across the pulse profile. However even for a nonsoliton pulse a time-independent DC component of this phase shift exists and can be computed via a Taylor expansion. We use spectral interferometry (SI) to directly measure this DC phase by measuring the shift of the reference-signal interference fringes. However, if the fiber forms one arm of the Mach-Zehnder interferometer the fluctuations of the length and the refractive index of the fiber shifts the signal phase randomly. To surmount this obstacle we propagate both reference and signal through the fiber and attenuate the reference so that it only experiences linear effects in the fiber.

A splenectomised patient with Gaucher’s disease who developed multiple foci of osteomyelitis and soft tissue abcesses, after a severe episode of group C salmonella sepsis, is described. Aggressive antibiotic treatment and surgical drainage had little effect and the patient’s condition continued to deteriorate. With initiation of enzyme replacement therapy (ERT) in addition to specific antibiotic treatment, defervescence and gradual healing occurred. Complete resolution of the infection was seen after 15 months. The possible role of ERT in healing bacterial infections in Gaucher’s disease is discussed.

Relations among self-reported social skills, teacher ratings of classroom behavior, and direct observations of social interactions among 87 adolescents with mild mental retardation were investigated and variables predicting the students' task orientation identified. Three information sources were employed. Results demonstrated that the four domains of social skills were related to the students' task orientation. The regression analysis revealed that students who were characterized by better social skills and fewer occurrences of hyperactivity and behavioral difficulties were viewed by teachers as evidencing more compliant and task-oriented behavior, implying their better ability to benefit from the special curriculum. The three sources of information validated one another and added information to the conceptualization and appraisal of social and academic competence among students with mental retardation.

Backgrounds and Aims: The rate of HCV seroconversion after needle stick injury with an HCV-contaminated needle is frequently described in textbooks to be between 1-3%. However, these data are based on studies that were performed in the early nineties and few large follow-up studies on health care workers (HCW) exposed to HCV are available from Europe. Methods: We here analysed data obtained in our institution on 166 needle stick injuries with HCV-contaminated needles between 2000 and 2005. In addition, a systematic review on the literature on HCV-seroconversions was performed. We could identify 21 studies including a total of 6,692 HCW with occupational exposure to HCV Results: Between 2000 and 2005 a total of 1,431 occupational injuries were reported at our institution with about two thirds being needle stick injuries. From 2003 on more detailed information on professions of HCW were available with 38% being nurses, 29% doctors, 15% interns, 11% medical students, 6% technicians and 1% cleaning personal. In 166 of the 1,431 injuries the index patients had proven HCV infection and, importantly, none of the exposed HCWs seroconverted to anti-HCV antibodies with a follow-up of at least six month after the injury. Published studies reported seroconversion rates between 0% and 10.3% with a mean of 0.76% (51/6, 692). Studies including at least 100 HCW (n=7) reported seroconversion rates between 0.3% and 2.8%. Mean seroconversion rates for studies from East Asia (n = 9) and Europe (n = 8) were 1.7% (24 out of 1,425) and 0.42% (22 out of 5,128; p

Background: Chronic graft-versus-host-disease (cGVHD) is a major obstacle to successful bone marrow transplantation. NKT lymphocytes may have a role in regulation of the immune attack in cGVHD. Glucocerebroside (GC) is a naturally occurring glycolipid that plays a role in the immune modulation of NKT lymphocytes. Objectives: To determine the immune modulatory effect of GC in a murine model of cGVHD. Methods: cGVHD was generated by infusion of 2x107 splenocytes from B10.D2 donor mice into Balb/c recipient mice, which received 7Gy 60Co total body irradiation (TBI) prior to transplantation. Recipient mice were followed for 55 days. Histological parameters of cGVHD-associated cutaneous, liver and bowel injury were assessed. To determine the mechanism of GC-mediated immune modulation, intrahepatic and intrasplenic lymphocytes were isolated and analyzed by FACS for CD4+, CD8+,CD56+ and NKT subpopulations. Serum cytokine levels were determined. Results: Treatment with GC significantly alleviated cGVHD. GC-treated mice gained weight and manifested a significant decrease in skin cGVHD clinical score (0.91 vs. 1.66 in GC treated vs. control mice, respectively). The beneficial effect of GC was associated with a 58% and a 31% reduction of the intrasplenic and the intrahepatic NKT cell number, respectively, accompanied by a 27% decrease of intrasplenic CD3+CD4+ T cells. Intrasplenic (but not intrahepatic) decrease in NK cell number was also observed in GC treated animals (48% vs. 7%). Administration of GC led to increased serum IFNγ and TNFa levels in GC treated compared to untreated controls (46 vs. 27, and 92 vs. 52 pg/ml, respectively), while IL10 levels decreased (61 vs. 83 pg/ml, respectively). Conclusions: Administration of GC led to significant amelioration of chronic GVHD. This effect was associated with an altered NKT lymphocyte distribution, decreased numbers of effector T lymphocytes and a shift towards a Th1-type cytokine profile. Glucocerebroside may serve as a new therapeutic measure for amelioration of cGVHD.

The master equation of mode locking written in operator notation is supplemented with noise-source terms that conserve commutator brackets. The noise sources are associated with the reservoirs responsible for loss and gain. The output of a mode-locked laser with the least possible quantum noise is determined.

We verify experimentally, over a dynamic range of 55 dB in the probability distribution, that the amplified spontaneous emission noise of the 0's from an optically preamplified receiver is degenerate Bose-Einstein distributed. Using the noise parameters extracted from the experiment, we are able to predict the sensitivity of a 10-Gbit/s direct-detection receiver.

Squeezing with solitons has been analyzed thoroughly both numerically and analytically. Here we extend the analysis of soliton squeezing to account for the continuum and address the issue of squeezing detection when using nonoptimal pulses.

We report a novel nonlinear filter that transmits and shortens incident pulses while rejecting cw background as well as resonant continuum. A relative extinction of 22 dB is reported for the cw background.

Large two-dimensional arrays of vertical cavity semiconductor lasers, unlike similar one-dimensional arrays, exhibit a single lasing mode because of their immunity to defects and inhomogeneities. Both experiments and theoretical study of the coherence of the arrays verified this improved performance and attributed it to possible bypass routes for the propagation of phase information in the two-dimensional structure, which ensured the locking of remote array elements even in the presence of defects.

Summary form only given. The simultaneous operation of a passively mode-locked laser at two different wavelengths is important as a source for high-pulse-rate, wavelength-division multiplexing (WDM) schemes, for wideband pump probe and four-wave mixing experiments. Using the recently introduced harmonic injection-locking scheme, we achieved synchronized locking of a passively mode-locked fiber laser, at two wavelengths (1.53 /spl mu/m and 1.55 /spl mu/m) simultaneously, producing pulses of several picoseconds with 7.5-GHz pulse repetition rates. Because the same scheme can also serve as a storage ring, this work demonstrates the feasibility of a two-color memory ring.

We report what is to our knowledge the first observation of synchronous coherent injection locking of an actively mode-locked extended cavity semiconductor laser to an external light pulse train. In the temporal domain, we observed experimentally and verified theoretically a significant narrowing of the output pulse of the mode-locked laser. In the spectral domain, we demonstrated experimentally the narrowing of the output optical spectrum that was due to rejection of spectral components outside the spectral band of the locking pulses. Locking ranges, in the time and the frequency domains, were measured to be ~200 ps and ~5 nm, respectively.

We demonstrate bistable operation and optical control of a specially designed distributed-Bragg-reflector laser. Optically controlled turn-on and turn-off with 1-pJ pulses at 1.5 μm and 2-pJ pulses at 1.3 μm, respectively, is demonstrated as well as all-optical flip-flop operation.