Robust unfolding of MeV x-ray spectra from filter stack spectrometer data.

We present an inversion method capable of robustly unfolding MeV x-ray spectra from filter stack spectrometer (FSS) data without requiring an a priori specification of a spectral shape or arbitrary termination of the algorithm. Our inversion method is based upon the perturbative minimization (PM) algorithm, which has previously been shown to be capable of unfolding x-ray transmission data, albeit for a limited regime in which the x-ray mass attenuation coefficient of the filter material increases monotonically with x-ray energy. Our inversion method improves upon the PM algorithm through regular smoothing of the candidate spectrum and by adding stochasticity to the search. With these additions, the inversion method does not require a physics model for an initial guess, fitting, or user-selected termination of the search. Instead, the only assumption made by the inversion method is that the x-ray spectrum should be near a smooth curve. Testing with synthetic data shows that the inversion method can successfully recover the primary large-scale features of MeV x-ray spectra, including the number of x-rays in energy bins of several-MeV widths to within 10%. Fine-scale features, however, are more difficult to recover accurately. Examples of unfolding experimental FSS data obtained at the Texas Petawatt Laser Facility and the OMEGA EP laser facility are also presented.

High Fat Diet Mediated Alterations in Serum Sphingolipid Profiles in An Experimental Mouse Model Measured by Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry.

Non-alcoholic fatty liver disease (NAFLD) is associated with hepatic steatosis, a benign condition caused by accumulation of lipids in hepatocytes, which may progress to steatohepatitis and cirrhosis. Recent studies suggest that sphingolipids are involved in the development and severity of NAFLD. The goal of this study is to identify the circulating sphingolipid species that are altered by chronic high fat diet (HFD) feeding and correlate these abnormalities with hepatic sphingolipids. We utilized a previously established experimental model of NAFLD generated by HFD feeding of 8-week-old male mice for 16 weeks. Lipids were extracted from serum samples by Folch method and analyzed with matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) in the positive and negative ion modes. MALDI-TOF detected a total of 47 serum sphingolipids including sphingomyelins, sulfatides, ceramides, phosphosphingolipids, and glycosphingolipids within the mass range of 600-2000 Da. Principle component analysis demonstrated clear separation of hepatic sphingolipids from low fat diet (LFD) and HFD groups and partial overlap of serum sphingolipids with a variance of 53.5% and 15.1%, and 11.7% in PC1, PC2, and PC3, respectively. Chronic HFD feeding significantly increased expression of SM (40:0), SM(42:2), ST(42:2), Hex(6)-Cer (40:1), and Hex(4)-HexNAc (2)-Cer (34:1) in both serum and liver. In addition, HFD mediated percent changes in hepatic sphingolipids correlate linearly with the percent changes in serum sphingolipids as determined by Pearson correlation (P = 0.0002). Elevated levels of serum and hepatic sphingomyelins and glycoceramides are key factors mediating NAFLD development and may serve as peripheral markers of hepatic steatosis.

Vacuum laser acceleration of super-ponderomotive electrons using relativistic transparency injection.

Intense lasers can accelerate electrons to very high energy over a short distance. Such compact accelerators have several potential applications including fast ignition, high energy physics, and radiography. Among the various schemes of laser-based electron acceleration, vacuum laser acceleration has the merits of super-high acceleration gradient and great simplicity. Yet its realization has been difficult because injecting free electrons into the fast-oscillating laser field is not trivial. Here we demonstrate free-electron injection and subsequent vacuum laser acceleration of electrons up to 20 MeV using the relativistic transparency effect. When a high-contrast intense laser drives a thin solid foil, electrons from the dense opaque plasma are first accelerated to near-light speed by the standing laser wave in front of the solid foil and subsequently injected into the transmitted laser field as the opaque plasma becomes relativistically transparent. It is possible to further optimize the electron injection/acceleration by manipulating the laser polarization, incident angle, and temporal pulse shaping. Our result also sheds light on the fundamental relativistic transparency process, crucial for producing secondary particle and light sources.

Clinical outcomes associated with anti-coagulant therapy in patients with renal infarction.

Background: Patients with renal infarction are vulnerable to thromboembolic complications with poor outcomes. There is limited report concerning the effect of anti-coagulant therapy in this population. Aim: To assess the impact of anti-coagulant therapy on outcomes in patients with renal infarction. Design: A retrospective cohort study of 101 renal infarction patients was conducted. Methods: The association between anti-coagulant therapy, all-cause mortality, thromboembolic complications and renal outcome was evaluated. Demographic data and comorbidities were collected for analysis. Anti-coagulant therapy was treated as a time-dependent variable. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multi-variate Cox proportional hazards models. Results: Fifty-seven (56.4%) patients with renal infarction received anti-coagulant therapy during the study period. The all-cause mortality rate was 7.56 per 100 patient-years. Age (HR 1.05, 95% CI 1.02-1.08) was a risk factor for all-cause mortality and anti-coagulant therapy was associated with a 92% improved survival (HR 0.08, 95% CI 0.02-0.34). Twelve (11.9%) thromboembolic events occurred following renal infarction. Current smoking (HR 10.37, 95% CI 1.60-67.43) had an adverse effect and anti-coagulant therapy (HR 0.14, 95% CI 0.03-0.73) had a significant protective impact on thromboembolic complications. There was no significant association between anti-coagulant therapy and long-term renal outcome in renal infarction patients including the monthly change in the estimated glomerular filtration rate (eGFR), the incidence of eGFR reduction of more than 50% and end-stage renal disease. Conclusion: Anti-coagulant therapy in patients with renal infarction was associated with better survival and reduced thromboembolic complications.

An introductory study using impedance spectroscopy technique with polarizable microelectrode for amino acids characterization.

Portable, low power, yet ultra-sensitive life detection instrumentations are vital to future astrobiology flight programs at NASA. In this study, initial attempts to characterize amino acids in an aqueous environment by electrochemical impedance spectroscopy (EIS) using polarizable (blocking) electrodes in order to establish a means of detection via their electrical properties. Seven amino acids were chosen due to their scientific importance in demonstrating sensitivity levels in the range of part per billion concentration. Albeit more challenging in real systems of analyst mixtures, we found individual amino acids in aqueous environment do exhibit some degree of chemical and physical uniqueness to warrant characterization by EIS. The polar amino acids (Asp, Glu, and His) exhibited higher electrochemical activity than the non-polar amino acids (Ala, Gly, Val, and Leu). The non-polar amino acids (Gly and Ala) also exhibited unique electrical properties which appeared to be more dependent on physical characteristics such as molecular weight and structure. At concentrations above 1 mM where the amino acids play a more dominant transport role within the water, the conductivity was found to be more sensitive to concentrations. At lower concentrations <1 mM, however, the polar amino acid solution conductivity remained constant, suggesting poor chemical activity with water. As revealed by equivalent circuit modeling, the relaxation times showed a 1-2 order of magnitude difference between polar and non-polar amino acids. The pseudo-capacitance from EIS measurements on sample mixtures containing salt water and individual amino acids revealed the possibility for improvement in amino acid selectivity using gold nanoporous surface enhanced electrodes. This work establishes important methodologies for characterizing amino acids using EIS combined with microscale electrodes, supporting the case for instrumentation development for life detection and origin of life programs.

Progenitor-like cells derived from mouse kidney protect against renal fibrosis in a remnant kidney model via decreased endothelial mesenchymal transition.

INTRODUCTION: Pathophysiological changes associated with chronic kidney disease impair angiogenic processes and increase renal fibrosis. Progenitor-like cells derived from adult kidney have been previously used to promote regeneration in acute kidney injury, even though it remained unclear whether the cells could be beneficial in chronic kidney disease (CKD). METHODS: In this study, we established a CKD model by five-sixths nephrectomy and mouse kidney progenitor-like cells (MKPCs) were intravenously administered weekly for 5 weeks after establishing CKD. We examined the impact of MKPCs on the progression of renal fibrosis and the potential of MKPCs to preserve the angiogenic process and prevent endothelial mesenchymal transition in vivo and in vitro. RESULTS: Our results demonstrate that the MKPCs delayed interstitial fibrosis and the progression of glomerular sclerosis and ameliorated the decline of kidney function. At 17 weeks, the treated mice exhibited lower blood pressures, higher hematocrit levels, and larger kidney sizes than the control mice. In addition, the MKPC treatment prolonged the survival of the mice with chronic kidney injuries. We observed a decreased recruitment of macrophages and myofibroblasts in the interstitium and the increased tubular proliferation. Notably, MKPC both decreased the level of vascular rarefaction and prevented endothelial mesenchymal transition (EndoMT) in the remnant kidneys. Moreover, the conditioned medium from the MKPCs ameliorated endothelial cell death under hypoxic culture conditions and prevented TGF-ß-induced EndoMT through downregulation of phosphorylated Smad 3 in vitro. CONCLUSIONS: MKPCs may be a beneficial treatment for kidney diseases characterized by progressive renal fibrosis. The enhanced preservation of angiogenic processes following MKPC injections may be associated with decreased fibrosis in the remnant kidney. These findings provide further understanding of the mechanisms involved in these processes and will help develop new cell-based therapeutic strategies for regenerative medicine in renal fibrosis.

Self-Similar Structure and Experimental Signatures of Suprathermal Ion Distribution in Inertial Confinement Fusion Implosions.

The distribution function of suprathermal ions is found to be self-similar under conditions relevant to inertial confinement fusion hot spots. By utilizing this feature, interference between the hydrodynamic instabilities and kinetic effects is for the first time assessed quantitatively to find that the instabilities substantially aggravate the fusion reactivity reduction. The ion tail depletion is also shown to lower the experimentally inferred ion temperature, a novel kinetic effect that may explain the discrepancy between the exploding pusher experiments and rad-hydro simulations and contribute to the observation that temperature inferred from DD reaction products is lower than from DT at the National Ignition Facility.

Infiltrating bone marrow mesenchymal stem cells increase prostate cancer stem cell population and metastatic ability via secreting cytokines to suppress androgen receptor signaling.

Although the contribution of the bone marrow mesenchymal stem cells (BM-MSCs) in cancer progression is emerging, their potential roles in prostate cancer (PCa) remain unclear. Here, we showed that PCa cells could recruit BM-MSCs and consequently the metastatic ability of PCa cells was increased. We also found that the increased metastatic ability of PCa cells could be due to the increased PCa stem cell population. Mechanism dissection studies found that the upregulation of Chemokine ligand 5 (CCL5) expression in BM-MSCs and PCa cells, after MSCs infiltrated into the PCa cells, subsequently downregulated androgen receptor (AR) signaling, which was due to inhibition of AR nuclear translocation. Interruption of such signaling led to suppression of the BM-MSCs-induced PCa stem cell population increase and thereby inhibited the metastatic ability of PCa cells. The PCa stem cell increase then led to the upregulation of matrix metalloproteinase 9, ZEB-1, CD133 and CXCR4 molecules, and enhanced the metastatic ability of PCa cells. Therefore, we conclude that the BM-MSCs-mediated increased metastatic ability of PCa cells can be due to the PCa stem cell increase via alteration of the CCL5-AR signaling pathway. Together, these results uncover the important roles of BM-MSCs as key components in the prostate tumor microenvironment to promote PCa metastasis and may provide a new potential target to suppress PCa metastasis by blocking BM-MSCs infiltration into PCa.

Autocrine/paracrine mechanism of interleukin-17B receptor promotes breast tumorigenesis through NF-κB-mediated antiapoptotic pathway.

Gain of function of membrane receptor was a good strategy exploited by cancer cells to benefit own growth and survival. Overexpression of HER2 has been found to serve as a target for developing trastuzumab to treat 20-25% of breast cancer. However, little or none of the other membrane receptor was found to be useful as a potential target for breast cancer treatment since then. Here, we showed that amplified signaling of interleukin-17 receptor B (IL-17RB) and its ligand IL-17B promoted tumorigenicity in breast cancer cells and impeded acinus formation in immortalized normal mammary epithelial cells. External signal transmitted through IL-17RB activated nuclear factor-κB to upregulate antiapoptotic factor Bcl-2 and induced etoposide resistance. Elevated expression of IL-17RB had a stronger correlation with poor prognosis than HER2 in breast cancer patients. Interestingly, breast cancer patients with high expression of IL-17RB and HER2 had the shortest survival rate. Depletion of IL-17RB in trastuzumab-resistant breast cancer cells significantly reduced their tumorigenic activity, suggesting that IL-17RB and HER2 have an independent role in breast carcinogenesis. Furthermore, treatment with antibodies specifically against IL-17RB or IL-17B effectively attenuated tumorigenicity of breast cancer cells. These results suggest that the amplified IL-17RB/IL-17B signaling pathways may serve as a therapeutic target for developing treatment to manage IL-17RB-associated breast cancer.

Mitochondrial genome instability resulting from SUV3 haploinsufficiency leads to tumorigenesis and shortened lifespan.

Mitochondrial dysfunction has been a hallmark of cancer. However, whether it has a causative role awaits to be elucidated. Here, using an animal model derived from inactivation of SUV3, a mitochondrial helicase, we demonstrated that mSuv3+/- mice harbored increased mitochondrial DNA (mtDNA) mutations and decreased mtDNA copy numbers, leading to tumor development in various sites and shortened lifespan. These phenotypes were transmitted maternally, indicating the etiological role of the mitochondria. Importantly, reduced SUV3 expression was observed in human breast tumor specimens compared with corresponding normal tissues in two independent cohorts. These results demonstrated for the first time that maintaining mtDNA integrity by SUV3 helicase is critical for cancer suppression.

Effects of ultraviolet germicidal irradiation and swirling motion on airborne Staphylococcus aureus, Pseudomonas aeruginosa and Legionella pneumophila under various relative humidities.

UNLABELLED: Staphylococcus aureus, Pseudomonas aeruginosa, and Legionella pneumophila have been detected in indoor air and linked to human infection. It is essential to adopt control methods to inactivate airborne pathogens. By passing bioaerosols horizontally into a UV device at two flow rates (Qs) and moving cells around a central UVC lamp at relative humidity (RH) of 12.7-16.7%, 58.7-59.6%, and 87.3-90%, the effects of swirling motion and 254-nm ultraviolet germicidal irradiation (UVGI) against bioaerosols were assessed under UV-off and UV-on settings, respectively. An inverse relationship between RH and UVGI effectiveness was observed for every test bioaerosol (r = -0.74 ∼ -0.81, P < 0.0001). Increased UV resistance with RH is likely associated with the hygroscopicity of bioaerosols, evident by increased aerodynamic diameters at high RH (P < 0.05). UVGI effectiveness was significantly increased with decreasing Q (P < 0.0001). Moreover, P. aeruginosa was the most susceptible to UVGI, while the greatest UV resistance occurred in L. pneumophila at low RH and S. aureus at medium and high RH (P < 0.05). Results of UV off show P. aeruginosa and L. pneumophila were more sensitive to air-swirling motion than S. aureus (P < 0.05). Overall, test bioaerosols were reduced by 1.7-4.9 and 0.2-1.7 log units because of the UVGI and swirling movement, respectively. PRACTICAL IMPLICATIONS: The studied UV device, with a combination of swirling motion and UVGI, is effective to inactivate airborne S. aureus, P. aeruginosa, and L. pneumophila. This study also explores the factors governing the UVGI and swirling motion against infectious bioaerosols. With understanding the environmental and operational parameters, the studied UV device has the potential to be installed indoors where people are simultaneously present, for example, hospital wards and nursing homes, to prevent the humans from acquiring infectious diseases.

Efficiency enhancement of silicon solar cells using a nano-scale honeycomb broadband anti-reflection structure.

This experiment demonstrates the process for manufacturing a ZnO honeycomb sub-wavelength structure using nanosphere lithography technology exhibiting excellent anti-reflection properties from the UV to NIR wavelength regions. This honeycomb nanostructure, combined with commercially available crystalline Si solar cells, show substantially improved conversion efficiency from 15.6% to 16.6% using optimized honeycomb sizes and precursor concentrations of ZnO. The present work develops an unsophisticated and economical technique suitable for industrial applications in producing a uniform and low-reflective texture.

Biomimetic nanostructured antireflection coating and its application on crystalline silicon solar cells.

In this report, we demonstrate the implementation of biomimetic nanostructured antireflection coatings with polymethyl methacrylate (PMMA) layer on the micro-textured surface of silicon crystalline solar cells. To reduce cost, the process combines colloidal lithography, cast molding method, and reversal nanoimprint lithography. The technique is simple, low cost, and does not cause damage to the thin and brittle conventional crystalline solar cells. The antireflection properties of this biomimetic nanostructure coating are considered as effective as those of a conventional single-layer SiNx thin film. The resultant structures alone could reduce the average reflectance of solar cell from 13.2% to 7.8% and enhance power conversion efficiency from 12.85% to 14.2%.

Effective dose evaluation for BNCT treatment in the epithermal neutron beam at THOR.

This paper aims to evaluate the effective dose as well as equivalent doses of several organs of an adult hermaphrodite mathematical phantom according to the definition of ICRP Publication 60 for BNCT treatments of brain tumors in the epithermal neutron beam at THOR. The MCNP5 Monte Carlo code was used for the calculation of the average absorbed dose of each organ. The effective doses for a typical brain tumor treatment with a tumor treatment dose of 20 Gy-eq were evaluated to be 0.59 and 0.35 Sv for the LLAT and TOP irradiation geometries, respectively. In addition to the stochastic effect, it was found that it is also likely to produce deterministic effects, such as cataracts and depression of haematopoiesis.

miR-495 is upregulated by E12/E47 in breast cancer stem cells, and promotes oncogenesis and hypoxia resistance via downregulation of E-cadherin and REDD1.

MicroRNAs (miRNAs) are involved in tumorigenecity by regulating specific oncogenes and tumor suppressor genes, and their roles in breast cancer stem cells (BCSCs) are becoming apparent. Distinct from the CD44(+)/CD24(-/low) sub-population, we have isolated a novel PROCR(+)/ESA(+) BCSC sub-population. To explore miRNA-regulatory mechanisms in this sub-population, we performed miRNA expression profiling and found miR-495 as the most highly upegulated miRNA in PROCR(+)/ESA(+) cells. Coincidently, high upregulation of miR-495 was also found in CD44(+)/CD24(-/low) BCSCs, reflecting its potential importance in maintaining common BCSC properties. Ectopic expression of miR-495 in breast cancer cells promoted their colony formation in vitro and tumorigenesis in mice. miR-495 directly suppressed E-cadherin expression to promote cell invasion and inhibited REDD1 expression to enhance cell proliferation in hypoxia through post-transcriptional mechanism. miR-495 expression was directly modulated by transcription factor E12/E47, which itself is highly expressed in BCSCs. These findings reveal a novel regulatory pathway centered on miR-495 that contributes to BCSC properties and hypoxia resistance.

Association of primary cutaneous amyloidosis with atopic dermatitis: a nationwide population-based study in Taiwan.

BACKGROUND: Primary cutaneous amyloidosis (PCA) is a pruritic skin disorder most commonly seen in Southeast Asia and South America. Association of PCA with atopic dermatitis (AD) has been reported in the literature. However, no large-scale epidemiological study of PCA and its associations with other diseases has been conducted so far. OBJECTIVES: We aimed to provide overall demographic data and comorbidities of patients with PCA based on a nationwide database in Taiwan. METHODS: Cases of PCA were collected from records of National Health Insurance claims from 2000 to 2007. We analysed patients' gender, age when the diagnosis was first made, and the overall 8-year prevalence. We also investigated comorbidities. RESULTS: The overall 8-year prevalence of PCA was 7·87 per 10,000 persons. Although there was no significant gender difference in the prevalence of PCA, men and women showed a different peak age (men, 71-80 years; women, 41-50 years) and a different age distribution at diagnosis. The mean age at diagnosis of PCA was significantly younger for women than for men. Men sought medical assistance for PCA more frequently than women. There was a higher disease activity from May to September than during other months. PCA was strongly associated with AD (odds ratio 7·18). Patients with PCA had a higher comorbidity of hyperlipidaemia and diabetes mellitus. CONCLUSIONS: This is the first nationwide population-based epidemiological study of PCA. We demonstrate that PCA can be associated with other disorders, especially AD.

The prognosis for patients with osteosarcoma who have received prior manipulative therapy.

We evaluated the long-term outcome of patients with an osteosarcoma who had undergone prior manipulative therapy, a popular treatment in Asia, and investigated its effects on several prognostic factors. Of the 134 patients in this study, 70 (52%) patients had manipulative therapy and 64 (48%) did not. The age, location, and size of tumour were not significantly different between the groups. The five-year overall survival rate was 58% and 92% in the groups with and without manipulative therapy (p = 0.004). Both the primary and overall rates of lung metastasis were significantly higher in the manipulative group (primary: 32% vs 3%, p = 0.003; overall lung metastasis rate: 51.4% vs 18.8%, p < 0.001). Patients who had manipulative therapy had higher local recurrence rates in comparison to patients who did not (29% vs 6%, p = 0.011). The prognosis for patients with osteosarcoma who had manipulative therapy was significantly poorer than those who had not. Manipulative therapy was an independent factor for survival. This form of therapy may serve as a mechanism to accelerate the spread of tumour cells, and therefore must be avoided in order to improve the outcome for patients with an osteosarcoma.

Prospective study of health-related quality of life after Roux-en-Y bypass surgery for morbid obesity.

BACKGROUND: The aim of this study was to evaluate the effects of Roux-en-Y gastric bypass for morbid obesity on health-related quality of life (QOL) during the first year of follow-up. METHODS: The World Health Organization Quality of Life-Brief (WHOQOL-BREF) was administered 1 month before operation, and at 1, 3, 6 and 12 months after surgery. Body mass index, co-morbidities and operation-related complications were measured at these times. A mixed-effect model was constructed to analyse repeated measurements and determine the relationships between body mass index, WHOQOL-BREF scores and other variables. RESULTS: A total of 102 patients were enrolled. The mixed-effect model showed that the physical, psychological and social domains improved after bariatric surgery, with simultaneous reduction in weight and improvement in co-morbidities. There was a dip in scores in physical and psychological domains 3-6 months after surgery, significantly related to complications. All patients gradually improved between 6 and 12 months after surgery, reaching levels similar to those of healthy subjects. CONCLUSION: Health-related QOL improved dramatically after bariatric surgery, dipped slightly between 3 and 6 months, and improved again up to the end of the first year.

Risk factors for extra-pulmonary tuberculosis compared to pulmonary tuberculosis.

BACKGROUND: Tuberculosis (TB) continues to be a major global health problem. Extra-pulmonary TB (EPTB) manifests with protean symptoms, and establishing a diagnosis is more difficult than pulmonary TB (PTB). SETTING: A university-affiliated hospital in southern Taiwan. OBJECTIVE: To analyse the risk factors for EPTB compared with PTB. DESIGN: This retrospective study compared patients with EPTB and PTB in southern Taiwan by analysing their demographic data and clinical underlying diseases. Risk factors for EPTB were further analysed. RESULTS: A total of 766 TB patients were enrolled in this study, with 102 (13.3%) EPTB and 664 (86.7%) PTB cases. Of the 766 patients, 3% of PTB patients had EPTB, while 19.6% of EPTB patients also had PTB. The most frequently involved EPTB site was the bone and joints (24.5%). The incidence of EPTB vs. PTB decreased significantly for each decade increase in patient age. Multivariate logistic regression analysis showed that being female, not being diabetic, having end-stage renal disease and not smoking were independent risk factors for EPTB. CONCLUSION: This study defines the risk factors for EPTB compared with PTB. Awareness of these factors is essential for physicians to have a high index of suspicion for accurate and timely diagnosis.