Black Ultra-Thin Crystalline Silicon Wafers Reach the 4n2 Absorption Limit-Application to IBC Solar Cells.

Cutting costs by progressively decreasing substrate thickness is a common theme in the crystalline silicon photovoltaic  industry for the last decades, since drastically thinner wafers would significantly reduce the substrate-related costs. In addition to the technological challenges concerning wafering and handling of razor-thin flexible wafers, a major bottleneck is to maintain high absorption in those thin wafers. For the latter, advanced light-trapping techniques become of paramount importance. Here we demonstrate that by applying state-of-the-art black-Si nanotexture produced by DRIE on thin uncommitted wafers, the maximum theoretical absorption (Yablonovitch's 4n2 absorption limit), that is, ideal light trapping, is reached with wafer thicknesses as low as 40, 20, and 10 µm when paired with a back reflector. Due to the achieved promising optical properties the results are implemented into an actual thin interdigitated back contacted solar cell. The proof-of-concept cell, encapsulated in glass, achieved a 16.4% efficiency with an JSC  = 35 mA cm- 2 , representing a 43% improvement in output power with respect to the reference polished cell. These results demonstrate the vast potential of black silicon nanotexture in future extremely-thin silicon photovoltaics.

Black-Silicon Ultraviolet Photodiodes Achieve External Quantum Efficiency above 130.

At present, ultraviolet sensors are utilized in numerous fields ranging from various spectroscopy applications via biotechnical innovations to industrial process control. Despite this, the performance of current UV sensors is surprisingly poor. Here, we break the theoretical one-photon-one-electron barrier and demonstrate a device with a certified external quantum efficiency above 130% in UV range without external amplification. The record high performance is obtained using a nanostructured silicon photodiode with self-induced junction. We show that the high efficiency is based on effective utilization of multiple carrier generation by impact ionization taking place in the nanostructures. While the results can readily have a significant impact on the UV-sensor industry, the underlying technological concept can be applied to other semiconductor materials, thereby extending above unity response to longer wavelengths and offering new perspectives for improving efficiencies beyond the Shockley-Queisser limit.

Immunoresponse against the transgene limits hematopoietic engraftment of mice transplanted in utero with virally transduced fetal liver.

In utero cell and gene therapies constitute alternative strategies to the postnatal treatment of inherited diseases. Fetal hematopoietic progenitors could be a potential source of donor cells for these strategies. In this study, hematopoietic lineage-negative fetal liver cells from 14.5-day-old fetuses were transduced under different cytokine and culture combinations using a lentiviral vector expressing the enhanced green fluorescent protein (EGFP). When cells were transduced for 6 h in the presence of mSCF, hTPO and FLT3-L in retronectin-coated dishes at a multiplicity of infection of 10 transduction units/cell, up to 70% of granulo-macrophage colony-forming cells expressed the EGFP reporter gene. In utero transplantation experiments revealed that conditions leading to high transduction efficiencies were associated with poor engraftments of syngeneic recipients. Significantly, this effect was associated with the detection of a humoral and cellular immunoresponse against the transgenic protein. Moreover, the humoral response against EGFP was detected not only in in utero transplanted recipients but also in the operated mothers, suggesting the maternal origin of the anti-EGFP immunoresponse. These observations reinforce the necessity of carefully studying the potential immunoresponses in future prenatal gene therapy protocols.

Direct etching at the nanoscale through nanoparticle-directed capillary condensation.

We report a method to locally deliver a chemical etchant at the nanoscale in the vapor phase by capillary condensation forming a meniscus at the nanoparticle/substrate interface. The process is simple, scalable and does not require functionalization of the nanoparticles. Furthermore, it does not rely on any specific chemical properties of the materials other than the solution being aqueous and the wettability properties of the surfaces involved, which should enable its application to other material and chemical combinations. In particular, in this work we demonstrate the proposed process by periodically pattering a SiO2 layer using a self-assembled monolayer of polystyrene particles exposed to HF vapors. The patterned SiO2 layer is then used as a mask to etch a pattern of inverted nanopyramids on Si. The silicon nanopatterning has been demonstrated for particles sizes ranging from 800 nm down to 100 nm, providing pyramids with a size down to 50 nm for 100 nm nanoparticles.

Increased frequencies of CD4(+)CD25(high) T(regs) correlate with disease relapse after allogeneic stem cell transplantation for chronic myeloid leukemia.

The therapeutic efficacy of allogeneic hemopoietic stem cell transplantation (SCT) for chronic myeloid leukemia (CML) largely relies on the graft-versus-leukemia (GvL) effect exerted by donor T cells. CD4(+)CD25(high) regulatory T cells (T(regs)) have been shown to downregulate antitumor responses but their role on GvL has not been evaluated. We performed a cross-sectional study in which we enumerated and characterized CD4(+)CD25(high) T(regs) in the peripheral blood of CML patients undergoing allogeneic SCT. We documented higher frequencies of T(regs) in patients after transplant as compared to normal controls and newly diagnosed patients. The increment was particularly evident in patients who had received their SCT 18 months before. In vitro functional studies demonstrated that the T(regs) purified from SCT patients exhibited a more potent suppressive activity than T(regs) isolated from healthy volunteers. Patients in whom T(regs) numbers were higher than controls more than 18 months after SCT showed evidence of disease relapse. Although the increment in T(regs) might have an advantageous effect on graft rejection in the early phase post-transplant, our data suggest that T(regs) exert an inhibitory effect on GvL.

Enabling silicon-on-silicon photonics with pedestalled Mie resonators.

High-refractive-index Mie resonators are regarded as promising building blocks for low-loss all-dielectric nanophotonic applications. To avoid the otherwise excessive damping and loss of symmetry such devices typically need to be implemented over a low-index substrate, which hampers their integration in many practical applications. In this paper we propose a new photonic structure consisting of silicon-on-silicon spheroidal-like resonators, each one supported by a slim silicon pedestal that makes the micro-cavities stand optically separated from the substrate while providing both mechanical stability and electrical contact with the substrate. These structures are produced in high-quality monocrystalline Si and their size and arrangement can be precisely controlled through standard lithography. We demonstrate that such structures present an optical performance similar to the one achieved with low-index substrates, opening new avenues for developing novel hybrid photonic/electronic devices.

Efficacy, Safety, and Potential Biomarkers of Sunitinib and Transarterial Chemoembolization (TACE) Combination in Advanced Hepatocellular Carcinoma (HCC): Phase II Trial.

OBJECTIVES: To evaluate the safety/efficacy and explore biomarkers for a rationally designed combination of sunitinib and transarterial chemoembolization (TACE) in a prospective phase 2 study of advanced hepatocellular carcinoma (HCC). METHODS: Inoperable HCC patients with Child-Pugh A disease received 37.5 mg sunitinib from days 1 to 7 followed by TACE on day 8. Sunitinib was resumed from days 15 to 36 followed by 2 weeks off. Patients received subsequent sunitinib cycles of 4 weeks on and 2 weeks off. Dynamic contrast-enhanced magnetic resonance imaging and circulating soluble biomarkers were assessed at baseline, day 8, day 10, and day 36. RESULTS: Sixteen patients with liver only (n=10) and extrahepatic disease (n=6) were enrolled. After a median follow-up of 12.8 months, 2 partial responses, 11 stable disease, and 3 clinical deteriorations were seen for a clinical benefit rate of 81%. Median progression-free survival (PFS) was 8 months (95% CI, 4.3-9.3) and overall survival was 14.9 months (95% CI, 6.3-27.1). Eleven of 16 patients (69%) had grade 3/4 toxicities attributable to sunitinib, the most frequent being thrombocytopenia, amylase/lipase elevations, lymphopenia, and fatigue. Mean K (volume transfer constant) and viable tumor percent in consented patients decreased by 27% and 14.8%, respectively, with combination therapy. Soluble vascular endothelial growth factor receptor-2 (sVEGFR2) levels, cytokines (interleukin-8, interleukin-21), and monocytes decreased with combination therapy. Estimated sunitinib IC50 values of 15 and 10 ng/mL modulated K and AUC90. sVEGFR2 levels decreased with K and AUC90. CONCLUSIONS: Encouraging progression-free survival and overall survival were seen with acceptable toxicity in our study of sunitinib and TACE combination in advanced HCC. Potential imaging and serum biomarkers showed increased benefit with combination therapy.

Molecular Evidence of Genome Editing in a Mouse Model of Immunodeficiency.

Genome editing is the introduction of directed modifications in the genome, a process boosted to therapeutic levels by designer nucleases. Building on the experience of ex vivo gene therapy for severe combined immunodeficiencies, it is likely that genome editing of haematopoietic stem/progenitor cells (HSPC) for correction of inherited blood diseases will be an early clinical application. We show molecular evidence of gene correction in a mouse model of primary immunodeficiency. In vitro experiments in DNA-dependent protein kinase catalytic subunit severe combined immunodeficiency (Prkdc scid) fibroblasts using designed zinc finger nucleases (ZFN) and a repair template demonstrated molecular and functional correction of the defect. Following transplantation of ex vivo gene-edited Prkdc scid HSPC, some of the recipient animals carried the expected genomic signature of ZFN-driven gene correction. In some primary and secondary transplant recipients we detected double-positive CD4/CD8 T-cells in thymus and single-positive T-cells in blood, but no other evidence of immune reconstitution. However, the leakiness of this model is a confounding factor for the interpretation of the possible T-cell reconstitution. Our results provide support for the feasibility of rescuing inherited blood disease by ex vivo genome editing followed by transplantation, and highlight some of the challenges.

Paraoxonase polymorphism Met-Leu54 is associated with modified serum concentrations of the enzyme. A possible link between the paraoxonase gene and increased risk of cardiovascular disease in diabetes.

Paraoxonase was identified as a genetic risk factor for cardiovascular disease (CVD) in recent studies focusing on a polymorphism affecting position 191. A second polymorphism of the paraoxonase gene affects position 54 and involves a methionine (M allele) to leucine (L allele) change. It was investigated in diabetic patients (n = 408) with and without vascular disease. There were highly significant differences in plasma concentrations and activities of paraoxonase between genotypes defined by the 54 polymorphism: MMAA, MLAA, LLAA; protein, 65.3+/-18.0, 77.9+/-18.0, 93.5+/-26.0 microg/ml; P < 0.0001: activity (phenylacetate), 48.6+/-13.5, 64.1+/-14.5, 68.1+/-13.0 U/ml; P < 0.0001. The 191 variant had little impact on paraoxonase concentrations. Homozygosity for the L allele was an independent risk factor for CVD (odds ratio 1.98 (1.07-3.83); P = 0.031). A linkage disequilibrium (P < 0.0001) was apparent between the mutations giving rise to leucine and arginine at positions 54 and 191, respectively. The study underlines that susceptibility to CVD correlates with high activity paraoxonase alleles. The 54 polymorphism would appear to be of central importance to paraoxonase function by virtue of its association with modulated concentrations. The latter could explain the association between both the 54 and 191 polymorphisms and CVD.

Controlling Plateau-Rayleigh instabilities during the reorganization of silicon macropores in the Silicon Millefeuille process.

The reorganization through high-temperature annealing of closely-packed pore arrays can be exploited to create ultra-thin (<20 µm) monocrystalline silicon layers that can work as cheap and flexible substrates for both the electronic and the photovoltaic industries. By introducing a periodic diameter modulation along deep etched pores, many thin layers can be produced from a single substrate and in a single technological process. Besides the periodicity, the exact shape of the modulation also has a profound impact on the process and subtle profile changes can lead to important differences on the process outcome. In this paper we study both theoretically and experimentally the effect of the initial profile on the pore reorganization dynamics and the morphology of the thin layers obtained through annealing. We show that process reliability, annealing time and final layer characteristics, all can be engineered and optimized by precisely controlling the initial pore profile.

[Performing saccadic eye movements modifies postural control organisation]. / La réalisation de mouvements de saccades oculaires affecte les stratégies de maintien de l'équilibre.

AIMS OF THE STUDY: To assess to which extent performing saccadic eye movements modifies the postural strategies aimed at maintaining balance. MATERIALS AND METHODS: Twelve healthy adults were tested on a force platform in several conditions including one in which they were required to stare a visual target and four in which small and larger saccadic eyes movements were performed vertically and horizontally. The displacements of the centre of pressure (CP) were then processed through frequency analysis and modelled as fractional Brownian motion (fBm). Through the latter, one may objectively assess from which distance and after which delay corrective process are initiated. In addition, the degree with which the CP movement is successively controlled is determined. RESULTS: A decrease of the magnitudes of the CP trajectories is observed during saccades, especially along the anteroposterior axis. The fBm modelling emphasises the setting of a particular postural strategy whose main effect consists in more delayed corrective processes associated with a better capacity to control the corrective CP displacements. CONCLUSION: This particular strategy could be linked to the difficulty for the subjects to detect pertinent visual information in this very axis and/or an increased cognitive constraint due to the saccades. On the whole, these data underline the necessity, when performing postural protocols, to ask the patients to stare a visual target in order to limit their eye movements.

In situ size sorting in CVD synthesis of Si microspheres.

Silicon microspheres produced in gas-phase by hot-wall CVD offer unique quality in terms of sphericity, surface smoothness, and size. However, the spheres produced are polydisperse in size, which typically range from 0.5 µm to 5 µm. In this work we show through experiments and calculations that thermophoretic forces arising from strong temperature gradients inside the reactor volume effectively sort the particles in size along the reactor. These temperature gradients are shown to be produced by a convective gas flow. The results prove that it is possible to select the particle size by collecting them in a particular reactor region, opening new possibilities towards the production by CVD of size-controlled high-quality silicon microspheres.

Ki67 score as a potential predictor in the selection of liver-directed therapies for metastatic neuroendocrine tumors: a single institutional experience.

BACKGROUND: Neuroendocrine tumors (NETs) metastatic to the liver are treated with transarterial radioembolization (TARE) using yttrium-90 (Y-90) microspheres or transarterial chemoembolization (TACE). However the criteria for patient selection are not well defined. We sought to determine if Ki67 score could help select patients for one therapy over the other in the management of hepatic neuroendocrine metastases. METHODS: Single institution analysis of patients treated with Y-90 or TACE between 2001 and 2014. Pathologists blinded to clinical information performed Ki67 staining. Data were analyzed using multivariate association for survival outcomes. RESULTS: Amongst 72 patients (male: 39, female: 33, median age: 57 years) with metastatic NET, the most common site of origin was small bowel (n=35, 49%), while pancreas constituted 32% (n=23). Forty-four patients were treated with Y-90 (61%) and 28 patients received TACE (39%). Ki67 score was available in 28 patients (64%) treated with Y-90 and 16 patients (57%) with TACE. Within Y-90 group, there was greater use of Sandostatin (95% vs. 75%, P=0.02) and less number of total treatments completed (89% vs. 46%, P<0.001). There was no significant difference in overall survival (OS) between Y-90 and TACE when used without selection (median, 69 vs. 82 months, P=0.47). When adjusted for Ki67, patients with Ki67 score ≥3% had better OS with Y-90 compared to TACE (HR, 0.1; CI, 0.01-0.9), however for Ki67 <3%, OS was better when treated with TACE compared to Y-90 (HR, 13.5; CI, 1.22-148.87). CONCLUSIONS: There is significant interaction between Ki-67 score and liver-directed treatment benefit in patients with hepatic neuroendocrine metastases. Ki-67 score ≥3% predicts greater benefit with Y-90 and a Ki-67 score <3% predicts greater benefit with TACE.

Promoter polymorphism T(-107)C of the paraoxonase PON1 gene is a risk factor for coronary heart disease in type 2 diabetic patients.

The serum enzyme paraoxonase (PON) protects LDLs from oxidative stress. We recently identified promoter polymorphisms of the PON gene that strongly affect gene expression and serum levels of the enzyme. The present study tested the hypothesis that promoter polymorphism T(-107)C could be a risk factor for vascular disease in type 2 diabetic patients by virtue of its ability to modulate serum concentrations of the antioxidant enzyme. The low-expressor genotype (TT) was associated with significantly lower serum PON concentrations, and it was over-represented in type 2 diabetic patients with coronary heart disease (CHD) (TT vs. TC+CC: odds ratio [OR] 1.64 [95% CI 1.03-2.61], P < 0.05). The association of the low-expressor genotype with an increased risk of disease was independent of other risk factors, including the coding region Q191R polymorphism (OR 2.12 [95% CI 1.19-3.70], P = 0.01). However, an interaction of the promoter polymorphism with the Q191R polymorphism, which was previously identified as an independent risk factor, was observed. The low-expressor promoter allele (-107T) associated with the high-risk 191R allele showed a lower-than-expected level of risk (OR 2.21 vs. the expected 4.76). The data are consistent with the hypothesis that low expression of the antioxidant enzyme PON increases the risk of CHD. Moreover, the promoter polymorphism appears to have a modulating effect on risk that is associated with the coding region polymorphism Q191R. This study indicates a strong genetic component to the antioxidant capacity of HDLs.

Modulated serum activities and concentrations of paraoxonase in high density lipoprotein deficiency states.

Paraoxonase is a high density lipoprotein (HDL) associated enzyme with a hypothesised role in the protection of low density lipoproteins (LDL) from oxidative stress. The present study examined paraoxonase in several genetically distinct HDL deficiency states. Despite reduction or even absence of detectable HDL, enzyme activity was present in sera from A-I-Pisa, A-I-Helsinki, A-I-Milano and Tangier patients. Both enzyme activities and peptide concentrations were modulated (reduced) but specific activities were broadly similar to controls, suggesting an impact on peptide concentration rather than an inhibition of enzyme activity. Despite the absence of HDL in A-I-Pisa and Tangier subjects, there was no association of paraoxonase with very low density lipoproteins or LDL. Paraoxonase function is maintained in HDL deficient states. It implies that certain HDL-associated anti-atherogenic processes may not be entirely compromised by HDL deficiency. This has important implications for the cardiovascular risk associated with modulated HDL concentrations.

Properties of hypotonized, crosslinked and crosslinked- permeabilized rat erythrocytes as potential carrier systems.

The osmotic fragility curves of isotonic rat RBCs, studied at pH 8 to avoid the Hb insolubility, are similar to those in humans at pH 7.4. Hypotonized rat RBCs, either directly or dialysed (0-24 h), are more hemolysis-resistant than isotonic rat RBCs. The discocyte-stomatocyte-spherocyte transformation can be observed with scanning electron microscopy. Protein crosslinking with dimethyl suberimidate can stabilize RBCs. The crosslinking level (60%), the cellular yield (80%), the mechanical and hemolytic resistance and the protective effect of enzyme activities, were studied in crosslinked or crosslinked- permeabilized RBCs after digitonin treatment. The normal discocytic shape of RBCs under scanning electron microscopy becomes stomatocytic in crosslinked and crosslinked- permeabilized RBCs with an erosioned surface.

All-silicon spherical-Mie-resonator photodiode with spectral response in the infrared region.

Silicon is the material of choice for visible light photodetection and solar cell fabrication. However, due to the intrinsic band gap properties of silicon, most infrared photons are energetically useless. Here, we show the first example of a photodiode developed on a micrometre scale sphere made of polycrystalline silicon whose photocurrent shows the Mie modes of a classical spherical resonator. The long dwell time of resonating photons enhances the photocurrent response, extending it into the infrared region well beyond the absorption edge of bulk silicon. It opens the door for developing solar cells and photodetectors that may harvest infrared light more efficiently than silicon photovoltaic devices that are so far developed.

[Cholera. Epidemiologic clinical analysis of 7 cases]. / Colera. Analisis clinico epidemiologico de 7 casos.

Chile had been free from cholera in the last century. An outbreak of the disease affected Chile since april 1991, as part of the 7th pandemic of this disease. The present communication summarizes the clinical and epidemiologic characteristics of the first 7 patients seen at Dr Lucio Cordova's Hospital in Santiago. Four patients were males, 4 older than 58 years. None was a contact of persons travelling from the heavily affected Peru or had eaten raw fish or shellfish. Diarrhea was the most prominent sign with a daily volume over 8 liters in 2 patients. Vomiting and cramps occurred in 5 patients, 6 had some degree of dehydration and 3 were hypotensive. Metabolic acidosis was the main electrolyte alteration and renal insufficiency was evident in 3 cases. Treatment was based on rehydration and antibiotics. There were no deaths.

Lactate catabolism by enzyme-loaded red blood cells.

Two different enzymes that metabolize lactate in the presence of oxygen, either to acetate plus CO2 (lactate 2-mono-oxygenase; Lmox) or to pyruvate plus H2O2 (lactate oxidase; Lox) were encapsulated in human and murine red blood cells (RBCs). Lmox shows a low affinity for lactate (Km 22 mM) and thus works at a low rate at the lactate concentrations found in hyperlactataemia (5-20 mM). Encapsulation of Lox provides a constant catabolic rate under the same range of blood lactate concentrations, but generates H2O2, which is toxic to the enzyme-loaded RBCs. Co-encapsulation of both enzymes at a ratio of 20 units of Lmox/unit of Lox results in significant rates of lactate metabolism over a wide range (1-30 mM) of lactate concentrations with modest methaemoglobin formation (5-8.5%) and normal cellular ATP concentrations (1.1-1.23 mM). In vitro experiments with [1-14C]glucose and [U-14C]glucose have shown that Lmox/Lox-loaded RBCs counteract the production of H2O2 by increasing the amount of glucose metabolized in the pentose phosphate pathway. In vivo attempts to prove the efficacy of these engineered RBCs in removal of blood lactate in mice have failed because of the high aerobic capacity and high lactate metabolism of these animals. However, the results obtained in vitro suggest that the encapsulation of lactate-catabolizing enzymes may be useful in the treatment of hyperlactataemia.