Tripled yield in direct-drive laser fusion through statistical modelling.

Focusing laser light onto a very small target can produce the conditions for laboratory-scale nuclear fusion of hydrogen isotopes. The lack of accurate predictive models, which are essential for the design of high-performance laser-fusion experiments, is a major obstacle to achieving thermonuclear ignition. Here we report a statistical approach that was used to design and quantitatively predict the results of implosions of solid deuterium-tritium targets carried out with the 30-kilojoule OMEGA laser system, leading to tripling of the fusion yield to its highest value so far for direct-drive laser fusion. When scaled to the laser energies of the National Ignition Facility (1.9 megajoules), these targets are predicted to produce a fusion energy output of about 500 kilojoules-several times larger than the fusion yields currently achieved at that facility. This approach could guide the exploration of the vast parameter space of thermonuclear ignition conditions and enhance our understanding of laser-fusion physics.

Betaine alleviates doxorubicin-induced nephrotoxicity by preventing oxidative insults, inflammation, and fibrosis through the modulation of Nrf2/HO-1/NLRP3 and TGF-ß expression.

Doxorubicin (Dox) is an anthracycline antibiotic used to treat various cancers and shows severe toxicity in multiple organ systems, including kidneys. Evidence shows that betaine's antioxidant and anti-inflammatory properties could prevent the onset of several disorders. Hence, the present study aims to investigate the therapeutic potential of betaine on Dox-induced nephrotoxicity (DIN). Nephrotoxicity was induced in male Sprague Dawley rats using Dox at a dose of 4 mg/kg (cumulative dose: 20 mg/kg) by the intraperitoneal route and cotreated with betaine through oral gavage (200 and 400 mg/kg) for 28 days. At the end of the experiment, biochemical, oxidative stress parameters, histopathology, and qRT-PCR were performed. DIN was indicated by elevated serum creatinine, urea, and decreased albumin levels representing kidney damage; the histopathological lesions (increased capsular space, renal tubule damage, and fibrosis) in renal tissues supported these biochemical findings. Interestingly, betaine treatment improves these alterations in Dox-treated rats. Further, betaine treatment decreases the lipid peroxidation and nitrite concentration and increases the superoxide dismutases and catalase enzyme concentration in Dox-treated rats. Fascinatingly, at the molecular level, DIN in rats shows upregulation of the Nrf2/HO-1 gene, while betaine treatment attenuated its expression along with the downregulation of inflammatory genes (NLRP3, TLR-4, TNF-α, and IL-6) and fibrosis-related genes (TGF-ß and Acta2) expression in Dox-treated rats. These results showed that betaine has reno-protective properties by reducing inflammatory and fibrotic mediators and enhancing antioxidant capacity in the renal tissue of rats treated with Dox. We believe betaine can be exploited as a dietary supplement to attenuate DIN.

Design and optimization of a high-energy optical parametric amplifier for broadband, spectrally incoherent pulses.

Spectrally incoherent laser pulses with sufficiently large fractional bandwidth are in demand for the mitigation of laser-plasma instabilities occurring in high-energy laser-target interactions. Here, we modeled, implemented, and optimized a dual-stage high-energy optical parametric amplifier for broadband, spectrally incoherent pulses in the near-infrared. The amplifier delivers close to 400 mJ of signal energy through noncollinear parametric interaction of 100-nJ-scale broadband, spectrally incoherent seed pulses near 1053 nm with a narrowband high-energy pump operating at 526.5 nm. Mitigation strategies for high-frequency spatial modulations in the amplified signal caused by index inhomogeneities in the Nd:YLF rods of the pump laser are explored and discussed in detail.

Effects of Laser Bandwidth in Direct-Drive High-Performance DT-Layered Implosions on the OMEGA Laser.

In direct-drive inertial confinement fusion, the laser bandwidth reduces the laser imprinting seed of hydrodynamic instabilities. The impact of varying bandwidth on the performance of direct-drive DT-layered implosions was studied in targets with different hydrodynamic stability properties. The stability was controlled by changing the shell adiabat from (α_{F}≃5) (more stable) to (α_{F}≃3.5) (less stable). These experiments show that the performance of lower adiabat implosions improves considerably as the bandwidth is raised indicating that further bandwidth increases, beyond the current capabilities of OMEGA, would be greatly beneficial. These results suggest that the future generation of ultra-broadband lasers could enable achieving high convergence and possibly high gains in direct drive ICF.

Proof-of-Principle Experiment on the Dynamic Shell Formation for Inertial Confinement Fusion.

In the dynamic-shell (DS) concept [V. N. Goncharov et al., Novel Hot-Spot Ignition Designs for Inertial Confinement Fusion with Liquid-Deuterium-Tritium Spheres, Phys. Rev. Lett. 125, 065001 (2020).PRLTAO0031-900710.1103/PhysRevLett.125.065001] for laser-driven inertial confinement fusion the deuterium-tritium fuel is initially in the form of a homogeneous liquid inside a wetted-foam spherical shell. This fuel is ignited using a conventional implosion, which is preceded by a initial compression of the fuel followed by its expansion and dynamic formation of a high-density fuel shell with a low-density interior. This Letter reports on a scaled-down, proof-of-principle experiment on the OMEGA laser demonstrating, for the first time, the feasibility of DS formation. A shell is formed by convergent shocks launched by laser pulses at the edge of a plasma sphere, with the plasma itself formed as a result of laser-driven compression and relaxation of a surrogate plastic-foam ball target. Three x-ray diagnostics, namely, 1D spatially resolved self-emission streaked imaging, 2D self-emission framed imaging, and backlighting radiography, have shown good agreement with the predicted evolution of the DS and its stability to low Legendre mode perturbations introduced by laser irradiation and target asymmetries.

Optical characterization of the on-target OMEGA focal spot at high energy using the full-beam in-tank diagnostic.

The full-beam in-tank (FBIT) diagnostic has been deployed to directly measure the target-plane beam fluence profile, when operated at high energy, of the OMEGA Laser System at the University of Rochester's Laboratory for Laser Energetics. This paper presents the results of early measurements taken with this diagnostic and discusses an improvement that has overcome performance limitations discovered during the initial testing. The diagnostic gives new insight into the ability of the OMEGA Laser System to provide uniform fluence profiles that are consistent across all 60 beams in the laser. The ultimate goal of the FBIT diagnostic is to allow accurate assessment of the fluence uniformity on a spherical target in 60-beam implosion experiments.

Power balancing the multibeam OMEGA laser.

Multibeam lasers often require an output beam balance that specifies the degree of simultaneity of the laser output energy, instantaneous power, or instantaneous irradiance (power per unit area). This work describes the general problem of balancing a multibeam laser. Specific techniques used to balance the output power of the 60-beam pulsed OMEGA Laser System are discussed along with a measured reduction of beam-to-beam imbalance. In particular, the square-pulse distortion induced by a simple saturating amplifier operating with its output at some fraction of its saturation fluence is derived, and a method to exchange gain between saturated amplifiers in a single beam that have different saturation fluences to adjust balance is described.

Sulfur ion concentration dependent morphological evolution of CdS thin films and its subsequent effect on photo-electrochemical performance.

The sulfur ion concentration dependent morphological evolution and its subsequent effect on photo-electrochemical properties of chemically synthesized CdS thin films have been systematically investigated. The plausible growth mechanism for the morphological evolution of CdS thin films due to a change in sulfur ion concentration has been proposed. Scanning electron micrographs (SEMs) reveal that the morphology of CdS thin films has been changed from spherical grains to vertically aligned nanoflakes by systematic control of sulfur ion concentration. This article elucidates the astute relationships between precursor concentrations, reaction rate and morphological evolution. The X-ray diffraction (XRD) patterns reveal the formation of hexagonal wurtzite CdS thin films with the preferred (002) orientation for CdS nanoflakes, which is further supported by the analysis of the high resolution transmission electron micrographs (HRTEMs). Optical absorption studies show a red shift in the absorption edge with an increase in sulfur concentration. The beneficial role of nanoflake formation is easily reflected in the photo-electrochemical performance. Improved solar cell performances are observed for CdS nanoflakes grown with a sulfur to cadmium ion concentration ratio of 4 (S : Cd = 4).

Inferred UV fluence focal-spot profiles from soft x-ray pinhole-camera measurements on OMEGA.

A method was developed with laser-irradiated Au planar foils to characterize the focal spot of UV laser beams on a target at full energy from soft x-ray emission. A pinhole camera with a back-thinned charge-coupled device detector and filtration with thin Be and Al foil filters provides images of the x-ray emission at photon energies <2 keV. This method requires a careful measurement of the relationship between the applied UV fluence and the x-ray signal, which can be described by a power-law dependence. The measured exponent γ ∼ 2 provides a dynamic range of ∼25 for the inferred UV fluence. UV fluence profiles of selected beams were measured for 100-ps and 1-ns laser pulses and were compared to directly measured profiles from an UV equivalent-target-plane diagnostic. The inferred spot size and super-Gaussian order from the x-ray technique agree within several percent with the values measured with the direct UV measurements.

Reverse distal femoral locking compression plate a salvage option in nonunion of proximal femoral fractures.

BACKGROUND: When primary fixation of proximal femoral fractures with implants fails, revision osteosynthesis may be challenging. Tracts of previous implants and remaining insufficient bone stock in the proximal femur pose unique problems for the treatment. Intramedullary implants like proximal femoral nail (PFN) or surface implants like Dynamic Condylar Screw (DCS) are few of the described implants for revision surgery. There is no evidence in the literature to choose one implant over the other. We used the reverse distal femur locking compression plate (LCP) of the contralateral side in such cases undergoing revision surgery. This implant has multiple options of fixation in proximal femur and its curvature along the length matches the anterior bow of the femur. We aimed to evaluate the efficacy of this implant in salvage situations. MATERIALS AND METHODS: Twenty patients of failed primary proximal femoral fractures who underwent revision surgery with reverse distal femoral locking plate from February 2009 to November 2012 were included in this retrospective study. There were 18 subtrochanteric fractures and two ipsilateral femoral neck and shaft fractures, which exhibited delayed union or nonunion. The study included 14 males and six females. The mean patient age was 43.6 years (range 22-65 years) and mean followup period was 52.1 months (range 27-72 months). Delayed union was considered when clinical and radiological signs of union failed to progress at the end of four months from initial surgery. RESULTS: All fractures exhibited union without any complications. Union was assessed clinically and radiologically. One case of ipsilateral femoral neck and shaft fracture required bone grafting at the second stage for delayed union of the femoral shaft fracture. CONCLUSIONS: Reverse distal femoral LCP of the contralateral side can be used as a salvage option for failed fixation of proximal femoral fractures exhibiting nonunion.

Chemokine IP-10 expression in cultured human keratinocytes.

IP-10, a member of the CXC family of chemokines, is considered to play an important role in inflammation via its T-cell chemotactic and adhesion-promoting properties. Elevated IP-10 levels in the epidermis of psoriasis, delayed-type hypersensitivity reactions, cutaneous T-cell lymphoma and fixed drug eruptions prompted us to study its expression in keratinocytes. IP-10 mRNA could be detected using the sensitive RT-PCR method, but not by Northern blotting in RNA preparations from unstimulated normal cultured keratinocytes, indicating a low steady-state level of IP-10 mRNA. Upon stimulation with IFN-gamma, IP-10 mRNA was found to accumulate in high amounts in a time- and dose-dependent manner. Superexpression was found with the combination of IFN-gamma and TNF-alpha or IL-1, although these latter cytokines by themselves did not induce accumulation of IP-10 mRNA. Nuclear run-on experiments performed to investigate the regulation of IP-10 mRNA expression, showed a very high constitutive transcriptional activity of the IP-10 gene in unstimulated keratinocytes, which was not affected by stimulation with IFN-gamma, TNF-alpha, or a combination of IFN-gamma and TNF-alpha. Protein kinase C (PKC) was shown to be involved in IP-10 mRNA expression since the PKC inhibitor H7 decreased IP-10 mRNA accumulation. A protein was isolated from culture supernatants of stimulated keratinocytes using HPLC techniques and, by sequence analysis, was found to be identical to IP-10. The dynamics of secretion of IP-10 protein as monitored by ELISA was shown to parallel the mRNA expression.

Effect of calcitriol on growth, differentiation, chemokine mRNA expression of cultured keratinocytes and on keratinocyte-T cell binding.

Calcitriol has recently been shown to be effective against psoriasis. However, its mode of action is not exactly known. The present study focused on the influence of calcitriol on growth, differentiation, chemokine mRNA and ICAM-1 mRNA expression of keratinocytes (KC) and on the binding of T-cells to keratinocytes. In vitro studies showed that calcitriol has a strong anti-proliferative effect and induces terminal differentiation. gamma-IP-10 and ICAM-1 mRNA were induced by gamma-IFN, an induction not influenced by calcitriol. Moreover, the functional expression of ICAM-1 on the KC cell surface as measured by a cell adhesion assay, was not influenced either. IL-8 and huGRO mRNAs were constitutively produced in KC, as was demonstrated after incubation with cycloheximide. Up-regulation of both IL-8 and huGRO mRNA by IL-1 alpha was also not affected by calcitriol. It is concluded that calcitriol has a strong antiproliferative activity and does not interfere with KC responsiveness to gamma-IFN and IL-alpha induced chemokine expression or with the adhesion of T-cells to keratinocytes.

Of insects and eggs: a case report.

A middle aged woman presented with delusions of infestation and multimodal hallucinations due to an underlying glioma of the corpus callosum. After surgery, the phenomena in question changed and finally disappeared. A recurrence of the tumour caused dementia.

The significance of Leu 8 negative T cells in lymphoid skin infiltrates: malignant transformation, selective homing or T-cell activation?

The expression of Leu 8 was studied on skin biopsies from a large group of patients with benign and malignant skin disorders and correlated with the expression of T-cell differentiation antigens and activation markers. The effect of in vitro stimulation of peripheral blood T cells and T-cell subsets on the expression of Leu 8 antigen was also determined. In all the skin diseases studied an inverse relationship was found between the proportions of cells expressing Leu 8 and HLA-DR. A deficiency of Leu 8 positive cells was not specific for mycosis fungoides, but was also found in several reactive dermatoses. Stimulation of peripheral blood cells with phytohaemagglutinin (PHA), concanavalin A (Con A), and anti-CD3-PMA resulted in a considerable decrease of Leu 8 antigen expression on day 3 in both CD4+ and CD8+ T cells. These data suggest that the low proportion of Leu 8+ T cells in mycosis fungoides and several reactive skin disorders is not related to malignant transformation or selective homing of Leu 8- T cells, but probably results from local T-cell activation.

The antipsoriatic drug dimethylfumarate strongly suppresses chemokine production in human keratinocytes and peripheral blood mononuclear cells.

BACKGROUND: The effectiveness of systemic treatment of psoriasis with fumaric acid esters has been proven, but their mode of action at the cellular and molecular level has not yet been fully elucidated. OBJECTIVES: To study the effect of dimethylfumarate (DMF) on the production of the chemokines CXCL1, CXCL8, CXCL9, CXCL10 and CXCL11, formerly known as GROalpha, interleukin-8, Mig, IP-10 and IP-9/I-TAC, respectively, in human keratinocytes and peripheral blood mononuclear cells (PBMC). METHODS: Cultured keratinocytes were stimulated with interferon (IFN) -gamma to produce CXCL9, CXCL10 and CXCL11 and with phorbol myristate acetate to produce CXCL1 and CXCL8 in the absence and presence of DMF (5, 15 and 45 micromol L(-1)). PBMC were stimulated with either IFN-gamma to produce CXCL9 and CXCL10 or lipopolysaccharide to produce CXCL8, in the absence and presence of DMF (5, 15 and 45 micromol L(-1)). RNA preparations from isolated keratinocytes were analysed by Northern blotting; protein production by keratinocytes and PBMC was monitored by an enzyme-linked immunosorbent assay. RESULTS: Northern blot analysis on isolated keratinocyte RNA preparations showed a dose-dependent inhibition of CXCL1, CXCL8, CXCL9, CXCL10 and CXCL11 transcription by DMF. At 45 micromol L(-1) the inhibition was almost complete. In addition, keratinocytes and PBMC showed in the presence of DMF a dose-dependent inhibition of CXCL8, CXCL9 and CXCL10 protein production. CONCLUSIONS: These results show the ability of DMF to inhibit the production of chemokines that may be critically involved in the development and perpetuation of psoriatic lesions. This might explain, at least in part, the beneficial effects of treatment with fumaric acid esters in psoriasis patients.

Comparison of toxicity tests on human skin and epidermoid (A431) cells using free fatty acids as test substances.

Several in-vivo methods can be used to determine the ability of chemical compounds to induce skin irritancy. In this study we estimated in vivo the capacity of several free fatty acids to induce skin irritancy and compared the results with those found in in vitro tests. Skin irritancy induced by free fatty acids (chain lengths: C6, C7, C9, C10, C11, C13 and C18) was evaluated in humans by means of laser-Doppler flowmetry (LDF) and visual scoring (VS). Both methods demonstrated that the toxic effect of free fatty acids determined by LDF and VS increased from C6 through C11 and decreased again for C13 and C18. The cytotoxic effect of these free fatty acids on cells was measured in vitro by incubation of human epidermoid cells (A431) with these compounds. It was determined by measuring: (a) the number of dead cells by inclusion of Trypan blue (TB); and (b) the number of living cells by mitochondrial metabolism of 3-[4,5-dimethylthiazole-2-yl]-2,5 diphenyltetrazolium bromide (MTT). The LD-50 concentrations decreased from C6 through C11 in both in-vitro assays. The results of the in-vitro assays for C13 and C18 both demonstrated a discrepancy. The cytotoxic effect of the free fatty acids expressed as LD-50 values, determined after 20 min with the TB assay, was seen at higher concentrations than after incubation for 18 h (MTT assay). From the results it was concluded that C13 in particular affected skin blood flow. We also determined correlation coefficients between the in-vivo and in-vitro methods. When C13 is excluded these coefficients ranged from -0.77 to -0.92.(ABSTRACT TRUNCATED AT 250 WORDS)

IP-10 mRNA expression in cultured keratinocytes is suppressed by inhibition of protein kinase-C and tyrosine kinase and elevation of cAMP.

IFN-gamma-inducible protein-10 (IP-10) is a chemokine, which plays an important role in mediating inflammation by attracting activated T cells, and it has been demonstrated in inflammatory skin diseases and cutaneous T cell lymphomas. Keratinocytes can abundantly produce IP-10 mRNA after IFN-gamma treatment. In this study we explored possibilities to downregulate IP-10 expression using human cultured keratinocytes as a model system. Decreased IP-10 mRNA levels were found using specific inhibitors of protein kinase (PK)-C (H-7 and Calphostin C). Moreover, depletion of PK-C by pretreatment of the cells with phorbol myristate (PMA) also down-regulated IP-10 mRNA expression. In addition, elevated cAMP levels were shown to inhibit IP-10 mRNA expression as could be concluded from experiments with forskolin and W-7, substances which, directly or indirectly, raise the intracellular cAMP level. With Genistein, an inhibitor of tyrosine kinase, the IFN-gamma-induced IP-10 mRNA expression was also found to be diminished. These data suggest that inhibitors of the IP-10 mRNA expression in cultured keratinocytes may be potentially of clinical relevance to suppress inflammatory processes in the skin.