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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

[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.

Molecular characterization of the mouse Tem1/endosialin gene regulated by cell density in vitro and expressed in normal tissues in vivo.

Human tumor endothelial marker 1/endosialin (TEM1/endosialin) was recently identified as a novel tumor endothelial cell surface marker potentially involved in angiogenesis, although no specific function for this novel gene has been assigned so far. It was reported to be expressed in tumor endothelium but not in normal endothelium with the exception of perhaps the corpus luteum. Here we describe the cDNA and genomic sequences for the mouse Tem1/endosialin homolog, the identification and characterization of its promoter region, and an extensive characterization of its expression pattern in murine and human tissues and murine cell lines in vitro. The single copy gene that was mapped to chromosome 19 is intronless and encodes a 92-kDa protein that has 77.5% overall homology to the human protein. The remarkable findings are 1) this gene is ubiquitously expressed in normal human and mouse somatic tissues and during development, and 2) its expression at the mRNA level is density-dependent and up-regulated in serum-starved cells. In vitro, its expression is limited to cells of embryonic, endothelial, and preadipocyte origin, suggesting that the wide distribution of its expression in vivo is due to the presence of vascular endothelial cells in all the tissues. The ubiquitous expression in vivo is in contrast to previously reported expression limited to corpus luteum and highly angiogenic tissues such as tumors and wound tissue.

Elimination of the truncated message from the herpes simplex virus thymidine kinase suicide gene.

Introduction of the Herpes simplex virus thymidine kinase (HSV-tk) gene into target cells renders them susceptible to killing by ganciclovir (GCV). We are studying the use of HSV-tk-transduced T lymphocytes in the context of hematopoietic stem cell transplantation. We have previously shown, in vitro and in vivo, the occurrence of transduced cells resistant to GCV due to a deletion within HSV-tk. This deletion, a consequence of the presence of cryptic splice donor and acceptor sites, originates in the retroviral producer cell. Here we adopt two different methods that introduce third-base degenerate changes at the cryptic splice sites and so prevent splicing. Consequently, the HSV-tk protein is unaltered and the sensitivity of the target cells to GCV is preserved. The use of this mutated HSV-tk should reduce the likelihood of the development of resistant genetically modified cells during clinical trials.

The apolipoprotein epsilon2 allele and the severity of coronary artery disease in Type 2 diabetic patients.

AIMS: To examine the hypothesis that apolipoprotein E2 is associated with more severe coronary disease in Type 2 diabetic patients. RESEARCH DESIGN AND METHODS: In this retrospective cohort study, 491 patients with angiographically assessed coronary disease were recruited from those attending a university hospital cardiology department. Participants completed detailed questionnaires, from which the presence or absence of diabetes was determined. Fasting blood samples were obtained for apolipoprotein E genotype and measurement of blood lipid parameters. RESULTS: The prevalence of triple vessel disease was significantly lower in non-diabetic, epsilon2 allele carriers (39.3% vs. 16.2%; odds ratio (OR) 0.30 (0.12-0.71), P < 0.03) compared with E3/3 carriers. In Type 2 diabetic patients, epsilon2 allele carriers had an excess of triple vessel disease compared with E3/3 genotypes (43.3 vs. 68.8%; OR 2.8 (1.07-7.30), P < 0.05). The differences were independent of other variables. The apo E4 subgroup showed no significant differences in the frequency of triple vessel disease. CONCLUSIONS: Diabetic epsilon2 allele carriers had more severe coronary artery disease than diabetic patients with other apo E isoforms. In non-diabetic patients the epsilon2 allele appeared to protect against severe coronary disease. We hypothesize that interaction between the diabetic milieu and the epsilon2 allele accelerates plaque progression. It suggests that diabetic patients who are carriers of the epsilon2 allele, even in the heterozygous form, should be the focus of particular therapeutic attention. Diabet. Med. 18, 445-450 (2001)

Molecular mechanism for ganciclovir resistance in human T lymphocytes transduced with retroviral vectors carrying the herpes simplex virus thymidine kinase gene.

The herpes simplex virus thymidine kinase gene type 1 (HSV-Tk) ganciclovir (GCV) system is a novel therapeutic strategy for the modulation of graft-versus-host disease (GVHD), a major complication of allogeneic stem cell transplantation (allo-SCT). Retroviral-mediated gene transfer of the HSV-Tk gene into donor T lymphocytes before allo-SCT may allow their in vivo selective depletion after treatment with GCV. The expression of the HSV-Tk gene was analyzed in vitro in CEM cells, a human lymphoblastoid cell line, transduced with 2 different vectors, each containing the HSV-Tk gene and a selectable marker gene. GCV-resistant clones were identified within the clones expressing the marker gene. Characterization of the molecular events leading to this resistance revealed a 227-bp deletion in the HSV-Tk gene due to the presence of cryptic splice donor and acceptor sites within the HSV-Tk gene sequence. Furthermore, it was confirmed that this deletion was present in human primary T cells transduced with either vector and in 12 patients who received transduced donor T cells, together with a T-cell-depleted allo-SCT. In vivo circulating transduced T cells containing the truncated HSV-Tk gene were identified in all patients immediately after infusion and up to 800 days after transplantation. In patients who received GCV as treatment for GVHD, a progressive increase in the proportion of transduced donor T cells carrying the deleted HSV-Tk gene was observed. These results suggest that the limitations within the HSV-Tk/GCV system can be improved by developing optimized retroviral vectors to ensure maximal killing of HSV-Tk-transduced cells.

Ex vivo expansion and characterisation of CD34+ cells derived from chronic myeloid leukaemia bone marrow and peripheral blood, and from normal bone marrow and mobilised peripheral blood.

Ex vivo culture of CD34+ has the potential to provide large numbers of cells for clinical use in autologous and allogeneic transplantation and for experimental research involving genetic manipulation. We evaluated the ex vivo expansion of CD34+ cells obtained from bone marrow (BM) and peripheral blood (PB) of untreated patients with chronic myeloid leukaemia (CML) in the chronic phase and compared these results with those obtained from BM from normal volunteers (NBM) and peripheral blood after mobilising chemotherapy from patients with non-haematological disorders (MPB). Selected CD34+ cells were stimulated with interleukin 1(beta), interleukin IL-3, interleukin IL-6 and stem cell factor. The proliferation observed in patients with CML was similar to that seen in normal donors. CD34+ cells derived from patients with CML are more differentiated than their normal counterparts, as shown by the coexpression of CD34 and CD33 antigens on day 0 (85.6% for CML-BM and 76.8% for CML-PB). The culture conditions allowed a significant expansion of granulocyte-macrophage colony-forming units (CFU-GM) from NBM (33-fold increase) and MPB (22-fold increase), in contrast with CML-derived BM and PB CD34+ cells (2.3-fold increase). These results indicate that the optimal time to harvest ex vivo expanded cells is dependent on a critical compromise between cell numbers and successful retention of their repopulating potential.