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Energy upconversion via optical processes in semiconductor nanowires (NWs) is attractive for a variety of applications in nano-optoelectronics and nanophotonics. One of the main challenges is to achieve a high upconversion efficiency and, thus, a wide dynamic range of device performance, allowing efficient upconversion even under low excitation power. Here, we demonstrate that the efficiency of energy upconversion via two-photon absorption (TPA) can be drastically enhanced in core/shell NW heterostructures designed to provide a real intermediate TPA step via the band states of the narrow-bandgap region with a long carrier lifetime, fulfilling all the necessary requirements for high-efficiency two-step TPA. We show that, in radial GaAs(P)/GaNAs(P) core/shell NW heterostructures, the upconversion efficiency increases by 500 times as compared with that of the constituent materials, even under an excitation power as low as 100 mW/cm2 that is comparable to the 1 sun illumination. The upconversion efficiency can be further improved by 8 times through engineering the electric-field distribution of the excitation light inside the NWs so that light absorption is maximized within the desired region of the heterostructure. This work demonstrates the effectiveness of our approach in providing efficient photon upconversion by exploring core/shell NW heterostructures, yielding an upconversion efficiency being among the highest reported in semiconductor nanostructures. Furthermore, our work provides design guidelines for enhancing efficiency of energy in NW heterostructures. Funding Agencies|Swedish Research Council [2019-04312]; Swedish Foundation for International Cooperation in Research and Higher Education (STINT) [JA2014-5698]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009 00971]; KAKENHI from the Japan Society for the Promotion of Science [16H05970, 19H00855, 21KK0068]; Japan Society for the Promotion of Science

Diese Studie beleuchtet die Ansteckungsgefahr mit Sars-CoV-2 im Öffentlichen Personennahverkehr (ÖPNV). Methodisch werden hierbei drei Ansätze zur Klärung dieser Aufgabenstellung verfolgt: 1) Eine Literaturstudie wurde durchgeführt, um dokumentierte Ansteckungsfälle im ÖPNV zu finden sowie typische Betriebsparameter der Fahrzeuge zu identifizieren. 2) Im Rahmen von in-situ Messungen im ÖPNV wurden Luft- und Wischproben auf Sars-CoV-2 sowie auf die ubiquitär vorkommenden Humanen Adenoviren (HAdV) als Kontrollviren untersucht. Zusätzlich wurden die Verläufe der CO2-Konzentration im Innenraum gemessen, die in Kombination mit der festgestellten Belegung der Verkehrsmittel Rückschlüsse auf die Frischluftrate zulassen. In einigen Fahrzeugen wurde die Partikelkonzentration als Marker für die mögliche Aerosolbelastung gemessen. 3) Mit einem zonal unterteilten Simulationsmodell wurde eine Parameterstudie für die verschiedenen Verkehrsmittel durchgeführt, die die Ist-Situation beleuchtet sowie technische Nachrüstlösungen und Verhaltensanpassungen der Fahrgäste bewertet. Aus dem ÖPNV wurden hierbei exemplarisch die S-Bahn, U-Bahn, Stadtbus und Straßenbahn sowie der U-Bahnsteig untersucht. Bei den in-situ Messungen wurde in keiner Probe das SARS-CoV-2 Virus nachgewiesen und die Verläufe der CO2-Konzentrationsmessungen zeigen überwiegend einen Betrieb bei hygienisch unbedenklicher Luftqualität nach den in definierten Kriterien. Simulationen zeigen, dass das persönliche Verhalten wie das Tragen einer Maske und technische Lösungen wie die Umluftfilterung zu einer geringeren Exposition führen.

Lignin, a byproduct from the pulp industry, is one of the redox active biopolymers being investigated as a component in the electrodes for sustainable energy storage applications. Due to its insulating nature, it needs to be combined with a conductor such as carbon or conducting polymer for efficient charge storage. Here, the lignin/carbon composite electrodes manufactured via mechanical milling (ball milling) are reported. The composite formation, correlation between performance and morphology is studied by comparison with manual mixing and jet milling. Superior charge storage capacity with approximate to 70% of the total contribution from the Faradaic process involving the redox functionality of lignin is observed in a mechanically milled composite. In comparison, manual mix shows only approximate to 30% from the lignin storage participation while the rest is due to the electric double layer at the carbon-electrolyte interface. The significant participation of lignin in the ball milled composite is attributed to the homogeneous, intimate mixing of the carbon and the lignin leading the electronic carrier transported in the carbon phase to reach most of the redox group of lignin. A maximum capacity of 49 mAh g(-1) is obtained at charge/discharge rate of 0.25 A g(-1) for the sample milled for 60 min. Funding Agencies|Knut and Alice Wallenberg Foundation [KAW 2019-0344, KAW 2020-0174]; Wallenberg Wood Science Center; Vetenskapradet [2016-05990]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoeping University [2009-00971]; Wallenberg Scholar grants

Semiconductor quantum dots (QDs) acting as single-photon-emitters are potential building blocks for various applications in future quantum information technology. For such applications, a thorough understanding and precise control of charge states and capture/recombination dynamics of the QDs are vital. In this work, we study the dynamics of QDs spontaneously formed in GaNAsP nanowires, belonging to the dilute nitride material system. By using a random population model modified for these highly mismatched materials, we analyze the results from photoluminescence and photon correlation experiments and show a general trend of disparity in positive and negative trion populations and also a strong dependence of the capture/recombination dynamics and QD charge states on its surroundings. Specifically, we show that the presence of hole-trap defects in the proximity to some QDs facilitates formation of negative trions, which also causes a dramatic reduction of the neutral exciton lifetime. These findings underline the importance of proper understanding of the QD capture and recombination processes and demonstrate the possibility to use highly mismatched materials and defects for charge engineering of QDs. Funding Agencies|Swedish Research CouncilSwedish Research CouncilEuropean Commission [2019-04312]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University (Faculty Grant SFO-Mat-LiU) [2009 00971]

BACKGROUNDSkeletal dysplasia (SD) conditions are rare genetic diseases of the skeleton, encompassing a heterogeneous group of over 400 disorders, and represent approximately 5% of all congenital anomalies. Developments in genetic and treatment technologies are leading to unparalleled therapeutic advances; thus, it is more important than ever to molecularly confirm SD conditions. Data on ‘rates-of-molecular yields’ in SD conditions, through exome sequencing approaches, is limited. Figures of 39% and 52.5% have been reported in the USA (n=54) and South Korea (n=185) respectively.We discuss a single-centre UK experience of whole-exome sequencing (WES) in a cohort of 15 paediatric patients (aged 5 months to 12 years) with SD disorders previously molecularly unconfirmed. Our cohort included patients with known clinical diagnoses and undiagnosed skeletal syndromes. Extensive phenotyping and expert radiological review by a panel of international SD radiology experts, coupled with a complex bioinformatics pipeline, allowed for both gene-targeted and gene-agnostic approaches. RESULTSSignificant variants leading to a likely or confirmed diagnosis were identified in 53.3% (n = 8/15) of patients; 46.7% (n= 7/15) having a definite molecular diagnosis and 6.7% (n= 1/15) having a likely molecular diagnosis. We discuss this in the context of a rare disease in general and specifically SD presentations. Of patients with known diagnoses pre-WES (n=10), molecular confirmation occurred in 7/10 cases, as opposed to 1/5 where a diagnosis was unknown pre-test. Thus, diagnostic return is greatest where the diagnosis is known pre-test. For WGS (whole genome sequencing, the next iteration of WES), careful case selection (ideally of known diagnoses pre-test) will yield highest returns.CONCLUSIONSOur results highlight the cost-effective use of WES-targeted bioinformatic analysis as a diagnostic tool for SD, particularly patients with presumed SD, where detailed phenotyping is essential. Thorough co-ordinated clinical evaluation between clinical, radiological, and molecular teams is essential for improved yield and clinical care. WES (and WGS) yields will increase with time, allowing faster diagnoses, avoiding needless investigations, ensuring individualised patient care and patient reassurance. Further diagnoses will lead to increased information on natural history/mechanistic details, and likely increased therapies and clinical trials.

III-V semiconductor nanowires (NWs), such as those based on GaAs, are attractive for advanced optoelectronic and nanophotonic applications. The addition of Bi into GaAs offers a new avenue to enhance the near-infrared device performance and to add new functionalities, by utilizing the remarkable valence band structure and the giant bowing in the bandgap energy. Here, we report that alloying with Bi also induces the formation of optically-active self-assembled nanodisks caused by Bi segregation. They are located in the vicinity to the (112) corners of the GaAsBi shell and are restricted to twin planes. Furthermore, the Bi composition in the disks is found to correlate with their lateral thickness. The higher Bi composition in the disks with respect to the surrounding matrix provides a strong confinement for excitons along the NW axis, giving rise to narrow emission lines (Funding Agencies|Swedish Research CouncilSwedish Research Council [2019-04312]; Swedish Foundation for International Cooperation in Research and Higher Education (STINT) [JA2014-5698]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University (Faculty Grant SFO-Mat-LiU) [2009 00971]; KAKENHI from Japan Society of Promotion of Science [19H00855, 16H05970]

Nanostructured III-V semiconductors have emerged as one of the most promising materials systems for future optoelectronic applications. While planar III-V compounds are already at the center of the ...

Core/shell nanowire (NW) heterostructures based on III-V semiconductors and related alloys are attractive for optoelectronic and photonic applications owing to the ability to modify their electronic structure via bandgap and strain engineering. Post-growth thermal annealing of such NWs is often involved during device fabrication and can also be used to improve their optical and transport properties. However, effects of such annealing on alloy disorder and strain in core/shell NWs are not fully understood. In this work we investigate these effects in novel core/shell/shell GaAs/GaNAs/GaAs NWs grown by molecular beam epitaxy on (111) Si substrates. By employing polarization-resolved photoluminescence measurements, we show that annealing (i) improves overall alloy uniformity due to suppressed long-range fluctuations in the N composition; (ii) reduces local strain within N clusters acting as quantum dot emitters; and (iii) leads to partial relaxation of the global strain caused by the lattice mismatch between GaNAs and GaAs. Our results, therefore, underline applicability of such treatment for improving optical quality of NWs from highly-mismatched alloys. They also call for caution when using ex-situ annealing in strain-engineered NW heterostructures. Funding Agencies|Swedish Energy AgencySwedish Energy Agency [P40119-1]; Swedish Research CouncilSwedish Research Council [2015-05532]; Swedish Foundation for International Cooperation in Research and Higher Education (STINT) [JA2014-5698]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009 00971]; KAKENHI from the Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceGrants-in-Aid for Scientific Research (KAKENHI) [16H05970, 23686004]; Kato Foundation for Promotion of Science; Kurata Memorial Hitachi Science and Technology Foundation; Murata Science Foundation; Linkoping University

Quantum dots (QDs) formed in semiconductor nanowires (NWs) form a basis for studying interesting quantum phenomena and provide an exciting platform for various device applications, where in-depth understanding of the formation and electronic properties of such QDs is a requirement. In this work we present detailed investigations of structural, electronic, and optical properties of nitrogen-induced self-assembled QDs in novel Ga(N,As,P) NWs. We show that the three-dimensional quantum confinement of the excitons caused by short-range fluctuations in the N content leads to single-photon emission. We demonstrate that valence band character varies between the QD emitters and attribute it to a varying degree of hole localization within the QDs induced by fluctuations in the As/P ratio. These fluctuations in the chemical compositions are also believed to be at least partly responsible for the observed large variation in exciton lifetimes of the QDs, ranging between 0.5 and 10 ns. The rather long lifetimes demonstrate the resilience of the QDs to nonradiative recombination-a merit for efficient single-photon emitters. Furthermore, we show that the principal axes of the formed QDs are oriented radially, normal to the NW side facets, in contrast to the N-induced QDs in GaNAs NWs which are primarily aligned along the NW axis. Our results, therefore, underline the impacts of the host alloy on the QD formation, which could provide an additional degree of freedom for band structure engineering in nanowires. Funding Agencies|Linkoping University; Swedish Research CouncilSwedish Research Council [2016-05091]; Swedish Energy AgencySwedish Energy Agency [P40119-1]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University (Faculty Grant SFO-Mat-LiU) [2009 00971]; Swiss National Foundation through the NCCR QSIT

Nanowire (NW) lasers operating in the near infrared spectral range are of significant technological importance for applications in telecommunications, sensing, and medical diagnostics. So far, lasing within this spectral range has been achieved using GaAs/AlGaAs, GaAs/GaAsP, and InGaAs/GaAs core/shell NWs. Another promising III-V material, not yet explored in its lasing capacity, is the dilute nitride GaNAs. In this work, we demonstrate, for the first time, optically pumped lasing from the GaNAs shell of a single GaAs/GaNAs core/shell NW. The characteristic "S"-shaped pump power dependence of the lasing intensity, with the concomitant line width narrowing, is observed, which yields a threshold gain, g(th), of 3300 cm(-1) and a spontaneous emission coupling factor beta, of 0.045. The dominant lasing peak is identified to arise from the HE21b, cavity mode, as determined from its pronounced emission polarization along the NW axis combined with theoretical calculations of lasing threshold for guided modes inside the nanowire. Even without intentional pas sivation of the NW surface, the lasing emission can be sustained up to 150 K. This is facilitated by the improved surface quality due to nitrogen incorporation, which partly suppresses the surface-related nonradiative recombination centers via nitridation. Our work therefore represents the first step toward development of room-temperature infrared NW lasers based on dilute nitrides with extended tunability in the lasing wavelength. Funding Agencies|Swedish Energy Agency [P40119-1]; Swedish Research Council [2015-05532]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009 00971]; KAKENHI from the Japan Society for the Promotion of Science [16H05970, 23686004]; Kato Foundation for Promotion of Science; Kurata Memorial Hitachi Science and Technology Foundation; Murata Science Foundation

Cathodoluminescence (CL) and micro-photoluminescence spectroscopies are employed to investigate effects of structural defects on carrier recombination in GaNAsP nanowires (NWs) grown by molecular beam epitaxy on Si substrates. In the NWs with a low N content of 0.08%, these defects are found to promote non-radiative (NR) recombination, which causes spatial variation of the CL peak position and its intensity. Unexpectedly, these detrimental effects can be suppressed even by a small increase in the nitrogen composition from 0.08% to 0.12%. This is attributed to more efficient trapping of excited carriers/excitons to the localized states promoted by N-induced localization and also the presence of other NR channels. At room temperature, the structural defects no longer dominate in carrier recombination even in the NWs with the lower nitrogen content, likely due to increasing importance of other recombination channels. Our work underlines the need in eliminating important thermally activated NR defects, other than the structural defects, for future optoelectronic applications of these NWs.

In this work we present a significant advancement in cubic silicon carbide (3C-SiC) growth in terms of crystal quality and domain size, and indicate its potential use in photovoltaics. To date, the use of 3C-SiC for photovoltaics has not been considered due to the band gap of 2.3 eV being too large for conventional solar cells. Doping of 3C-SiC with boron introduces an energy level of 0.7 eV above the valence band. Such energy level may form an intermediate band (IB) in the band gap. This IB concept has been presented in the literature to act as an energy ladder that allows absorption of sub-bandgap photons to generate extra electron-hole pairs and increase the efficiency of a solar cell. The main challenge with this concept is to find a materials system that could realize such efficient photovoltaic behavior. The 3C-SiC bandgap and boron energy level fits nicely into the concept, but has not been explored for an IB behavior. For a long time crystalline 3C-SiC has been challenging to grow due to its metastable nature. The material mainly consists of a large number of small domains if the 3C polytype is maintained. In our work a crystal growth process was realized by a new approach that is a combination of initial nucleation and step-flow growth. In the process, the domains that form initially extend laterally to make larger 3C-SiC domains, thus leading to a pronounced improvement in crystalline quality of 3C-SiC. In order to explore the feasibility of IB in 3C-SiC using boron, we have explored two routes of introducing boron impurities; ion implantation on un-doped samples and epitaxial growth on un-doped samples using pre-doped source material. The results show that 3C-SiC doped with boron is an optically active material, and thus is interesting to be further studied for IB behavior. For the ion implanted samples the crystal quality was maintained even after high implantation doses and subsequent annealing. The same was true for the samples grown with pre-doped source material, even with a high concentration of boron impurities. We present optical emission and absorption properties of as-grown and boron implanted 3C-SiC. The low-temperature photoluminescence spectra indicate the formation of optically active deep boron centers, which may be utilized for achieving an IB behavior at sufficiently high dopant concentrations. We also discuss the potential of boron doped 3C-SiC base material in a broader range of applications, such as in photovoltaics, biomarkers and hydrogen generation by splitting water. (C) 2015 Elsevier B.V. All rights reserved. Funding Agencies|Angpanneforeningen Research Foundation (AForsk); NFR SunSic project; Swedish Energy Agency; Swedish Governmental Agency for Innovation Systems (Vinnova); STAEDTLER Foundation

Nanowires (NWs) with embedded zero-dimensional (0D) quantum dots (QDs) have interesting fundamental properties attractive for a variety of applications. The properties of such embedded QDs can be c ...

Cytoplasmic Actin Gamma 1 (ACTG1) gene variant are autosomal dominant and can cause CNS anomalies (Baraitser Winter Malformation Syndrome; BWMS). ACTG1 anomalies in offspring include agenesis of the corpus callosum (ACC) and neuronal heterotopia which are ectopic nodules of nerve cells that failed to migrate appropriately. Subcortical and periventricular neuronal heterotopia have been described previously in association with ACC. In this case report, we investigated a neonatal brain with an ACTG1 gene variant and a phenotype of ACC, and neuronal heterotopia (ACC-H) which was diagnosed on antenatal MR imaging and was consistent with band heterotopia seen on post-mortem brain images. Histologically clusters of neurons were seen in both the subcortical and periventricular white matter (PVWM) brain region that coincided with impaired abnormalities in glial formation. Immunohistochemistry was performed on paraffin-embedded brain tissue blocks from this case with ACTG1 variant and an age-matched control. Using tissue sections from the frontal lobe, we examined the distribution of neuronal cells (HuC/HuD, calretinin, and parvalbumin), growth cone (drebrin), and synaptic proteins (synaptophysin and SNAP-25). Additionally, we investigated how the ACTG1 variant altered astroglia (nestin, GFAP, vimentin); oligodendroglia (OLIG2) and microglia (Iba-1) in the corpus callosum, cortex, caudal ganglionic eminence, and PVWM. As predicted in the ACTG1 variant case, we found a lack of midline radial glia and glutamatergic fibers. We also found disturbances in the cortical region, in glial cells and a lack of extracellular matrix components in the ACTG1 variant. The caudal ganglionic eminence and the PVWM regions in the ACTG1 variant lacked several cellular components that were identified in a control case. Within the neuronal heterotopia, we found evidence of glutamatergic and GABAergic neurons with apparent synaptic connections. The data presented from this case study with BWMS with variants in the ACTG1 gene provides insight as to the composition of neuronal heterotopia, and how disturbances of important migratory signals may dramatically affect ongoing brain development.

In this work, we carry out a comprehensive investigation of structural and optical effects in GaNAsP nanowires (NWs), which are novel materials promising for advanced photovoltaic applications. Despite a significant mismatch in electronegativity between N and As/P atoms, we show that incorporation of nitrogen does not degrade structural quality of the nanowires and the fabricated NW arrays have excellent compositional uniformity among individual wires. From temperature-dependent photoluminescence (PL) measurements, statistical fluctuations of the alloy composition are shown to lead to localization of photoexcited carriers at low temperatures but do not affect material properties at room temperature. According to time-resolved PL measurements, the room-temperature carrier lifetime increases in the GaNAsP NWs as compared with the GaAsP NWs, which indicates reduced nonradiative recombination. Moreover, in spite of the very low N content in the studied NWs (up to 0.16%), their bandgap energy can be tuned by more than 100 meV. This is accompanied by about 30% reduction in the temperature dependence of the bandgap energy. The presented results demonstrate that alloying of GaAsP with nitrogen provides an additional means of design optimization, beneficial for, e.g., NW-based intermediate band solar cells that are highly dependent on the optimum bandgap structure. Funding Agencies|Swedish Energy Agency [P40119-1]; Swedish Research Council [2015-0.5532]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University (Faculty Grant SFO-Mat-LiU) [2009 00971]; National Science Foundation [DMR-1106369]

We report the growth of dilute nitride GaNAs and GaInNAs core-multishell nanowires (NWs) using molecular beam epitaxy assisted by a plasma source. Using the self-catalyst vapor-liquid-solid growth mode, these NWs were grown on Si(111) and silicon on insulator substrates. The GaNAs and GaInNAs shells contain nitrogen up to 3%. Axial cross-sectional scanning transmission electron microscopy measurements and energy-dispersive x-ray spectrometry confirm the formation of the core-multishell NW structure. We obtained high-quality GaNAs NWs with nitrogen compositions up to 2%. On the other hand, GaNAs containing 3% nitrogen, and GaInNAs NWs, show distorted structures; moreover, the optical emissions seem to be related to defects. Further optimisations of the growth conditions will improve these properties, promising future applications in nanoscale optoelectronics. Funding Agencies|KAKENHI by the Japan Society for the Promotion of Science [16H05970]; Swedish Energy Agency [P40119-1]

Recent developments in fabrication techniques and extensive investigations of the physical properties of III-V semiconductor nanowires (NWs), such as GaAs NWs, have demonstrated their potential for a multitude of advanced electronic and photonics applications. Alloying of GaAs with nitrogen can further enhance the performance and extend the device functionality via intentional defects and heterostructure engineering in GaNAs and GaAs/GaNAs coaxial NWs. In this work, it is shown that incorporation of nitrogen in GaAs NWs leads to formation of three-dimensional confining potentials caused by short-range fluctuations in the nitrogen composition, which are superimposed on long-range alloy disorder. The resulting localized states exhibit a quantum-dot like electronic structure, forming optically active states in the GaNAs shell. By directly correlating the structural and optical properties of individual NWs, it is also shown that formation of the localized states is efficient in pure zinc-blende wires and is further facilitated by structural polymorphism. The light emission from these localized states is found to be spectrally narrow (similar to 50-130 mu eV) and is highly polarized (up to 100%) with the preferable polarization direction orthogonal to the NW axis, suggesting a preferential orientation of the localization potential. These properties of self-assembled nano-emitters embedded in the GaNAs-based nanowire structures may be attractive for potential optoelectronic applications. Funding agencies: Financial support by the Swedish Energy Agency (grant # P40119-1) and the Swedish Research Council (grants # 2015-05532 and 2008-405) is greatly appreciated. The Knut and Alice Wallenberg Foundation is gratefully acknowledged for support of the Electron Microscopy laboratory in Linkoping.

There is a strong and growing worldwide research on exploring renewable energy resources. Solar energy is the most abundant, inexhaustible and clean energy source, but there are profound material challenges to capture, convert and store solar energy. In this work, we explore 3C-SiC as an attractive material towards solar-driven energy conversion applications: (i) Boron doped 3C-SiC as candidate for an intermediate band photovoltaic material, and (ii) 3C-SiC as a photoelectrode for solar-driven water splitting. Absorption spectrum of boron doped 3C-SiC shows a deep energy level at ~0.7 eV above the valence band edge. This indicates that boron doped 3C-SiC may be a good candidate as an intermediate band photovoltaic material, and that bulk like 3C-SiC can have sufficient quality to be a promising electrode for photoelectrochemical water splitting. © 2016 Trans Tech Publications, Switzerland.

The IGHV3-21 gene has been shown to be overrepresented in Scandinavian patients with chronic lymphocytic leukemia (CLL). By investigating a population-based cohort of 337 Swedish patients with CLL, a lower (6.5%) IGHV3-21 frequency was determined relative to our previous hospital-based studies (10.1%-12.7%), yet this frequency remained higher compared to other Western CLL cohorts (2.6%-4.1%). Furthermore, we confirmed the poor outcome for patients with IGHV3-21 to be independent of mutational and stereotypy status. Background: Scandinavian patients with CLL have shown an overrepresentation of the poor-prognostic IGHV3-21 gene. Furthermore, approximately 50% of patients with IGHV3-21 carry stereotyped B-cell receptors, which implicate antigen selection in leukemogenesis. These patients have also been reported to have shorter time to progression than patients with nonstereotyped IGHV3-21. Materials and Methods: To investigate the IGHV3-21 frequency and the clinical impact of IGHV3-21 stereotypy, 337 newly diagnosed Swedish CLL patients from a population-based cohort were analyzed. Results: Interestingly, the IGHV3-21 frequency was indeed lower (6.5%) in this indolent patient cohort than in our previous hospital-based cohort studies (10.1%-12.7%). Hence, a selection bias of more-aggressive cases rendered a higher proportion of IGHV3-21 cases in our original studies. Nevertheless, the Swedish IGHV3-21 frequency still remained higher when compared with other larger European or American studies (2.6%-4.1%). Finally, we confirmed the poor outcome for IGHV3-21 patients to be independent of mutational status and found stereotypy to have no impact on survival or time to treatment. Conclusion: The Swedish geographic bias in IGHV3-21 gene frequency was validated albeit at a lower frequency than previously reported. Moreover, no prognostic value could be attributed to IGHV3-21 stereotype status.

Chronic lymphocytic leukemia (CLL) cells express the receptor for Epstein-Barr virus (EBV) and can be infected in vitro. Infected cells do not express the growth-promoting set of EBV-encoded genes and therefore they do not yield LCLs, in most experiments. With exceptional clones, lines were obtained however. We describe a new line, HG3, established by in vitro EBV-infection from an IGHV1–2 unmutated CLL patient clone. All cells expressed EBNA-2 and LMP-1, the EBV-encoded genes pivotal for transformation. The karyotype, FISH cytogenetics and SNP-array profile of the line and the patient's ex vivo clone showed biallelic 13q14 deletions with genomic loss of DLEU7, miR15a/miR16–1, the two micro-RNAs that are deleted in 50% of CLL cases. Further features of CLL cells were: expression of CD5/CD20/CD27/CD43 and release of IgM natural antibodies reacting with oxLDL-like epitopes on apoptotic cells (cf. stereotyped subset-1). Comparison with two LCLs established from normal B cells showed 32 genes expressed at higher levels (> 2-fold). Among these were LHX2 and LILRA. These genes may play a role in the development of the disease. LHX2 expression was shown in self-renewing multipotent hematopoietic stem cells, and LILRA4 codes for a receptor for bone marrow stromal cell antigen-2 that contributes to B cell development. Twenty-four genes were expressed at lower levels, among these PARD3 that is essential for asymmetric cell division. These genes may contribute to establish precursors of CLL clones by regulation of cellular phenotype in the hematopoietic compartment. Expression of CD5/CD20/CD27/CD43 and spontaneous production of natural antibodies may identify the CLL cell as a self-renewing B1 lymphocyte.

The expression levels of LPL, ZAP70, TCL1A, CLLU1 and MCL1 have recently been proposed as prognostic factors in chronic lymphocytic leukemia. However, few studies have systematically compared these different RNA-based markers.Using real-time quantitative PCR, we measured the mRNA expression levels of these genes in unsorted samples from 252 newly diagnosed chronic lymphocytic leukemia patients and correlated our data with established prognostic markers (for example Binet stage, CD38, IGHV gene mutational status and genomic aberrations) and clinical outcome.High expression levels of all RNA-based markers, except MCL1, predicted shorter overall survival and time to treatment, with LPL being the most significant. In multivariate analysis including the RNA-based markers, LPL expression was the only independent prognostic marker for overall survival and time to treatment. When studying LPL expression and the established markers, LPL expression retained its independent prognostic strength for overall survival. All of the RNA-based markers, albeit with varying ability, added prognostic information to established markers, with LPL expression giving the most significant results. Notably, high LPL expression predicted a worse outcome in good-prognosis subgroups, such as patients with mutated IGHV genes, Binet stage A, CD38 negativity or favorable cytogenetics. In particular, the combination of LPL expression and CD38 could further stratify Binet stage A patients.LPL expression is the strongest RNA-based prognostic marker in chronic lymphocytic leukemia that could potentially be applied to predict outcome in the clinical setting, particularly in the large group of patients with favorable prognosis.

We report the growth of GaAs/GaNAs/GaAs core-multishell nanowires having N compositions exceeding 2%. The structures were grown by plasma-assisted molecular beam epitaxy using constituent Ga-induced vapor-liquid-solid growth on Si(111) substrates. The GaNAs shell nominally contains 0%, 2%, and 3% nitrogen. The axial cross-sectional scanning transmission electron microscopy measurements confirm the existence of core-multishell structure. The room temperature micro-photoluminescence measurements reveal a red-shift of the detected emission with increasing N content in the nanowires, consistent with the expected changes in the GaNAs bandgap energy due to the bowing effect.

Background The existence of multiple subsets of chronic lymphocytic leukemia expressing ‘stereotyped’ Bcell receptors implies the involvement of antigen(s) in leukemogenesis. Studies also indicate that ‘stereotypy’ may influence the clinical course of patients with chronic lymphocytic leukemia, for example, in subsets with stereotyped IGHV3-21 and IGHV4-34 B-cell receptors; however, little is known regarding the genomic profile of patients in these subsets. Design and Methods We applied 250K single nucleotide polymorphism-arrays to study copy-number aberrations and copy-number neutral loss-of-heterozygosity in patients with stereotyped IGHV3-21 (subset #2, n=29), stereotyped IGHV4-34 (subset #4, n=17; subset #16, n=8) and non-subset #2 IGHV3-21 (n=13) and non-subset #4/16 IGHV4-34 (n=34) patients. Results Over 90% of patients in subset #2 and non-subset #2 carried copy-number aberrations, whereas 75-76% of patients in subset #4 and subset #16 showed copy-number aberrations. Subset #2 and non-subset #2 patients also displayed a higher average number of aberrations compared to patients in subset #4. Deletion of 13q was the only known recurrent aberration detected in subset #4 (35%); this aberration was even more frequent in subset #2 (79%). del(11q) was more frequent in subset #2 and non-subset #2 (31% and 23%) patients than in subset #4 and nonsubset #4/16 patients. Recurrent copy-number neutral loss-of-heterozygosity was mainly detected on chromosome 13q, independently of B-cell receptor stereotypy. Conclusions Genomic aberrations were more common in subset #2 and non-subset #2 than in subset #4. The particularly high frequency of del(11q) in subset #2 may be linked to the adverse outcome reported for patients in this subset. Conversely, the lower prevalence of copy-number aberrations and the absence of poor-prognostic aberrations in subset #4 may reflect an inherently low-proliferative disease, which would prevent accumulation of genomic alterations.

Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease with no known single predisposing genetic factor shown in all cases. Recently, a single nucleotide polymorphism (SNP) T393C in the GNAS1 gene has been reported to have a clinical impact on CLL progression and overall survival. In order to further investigate the T393C SNP in CLL, we have genotyped 279 CLL cases and correlated the genotypes to clinical outcome and other known prognostic factors such as the immunoglobulin heavy chain variable (IGHV) gene mutation status and CD38 expression. In the present study, no difference in overall survival or time to treatment was observed in the CLL patients with the different genotypes in contrast to the previous report. Furthermore, no correlation was observed with the T393C genotypes and IGHV mutational status, Binet stage or CD38 in this cohort. In summary, our data does not support the use of the T393C GNAS SNP as a clinical prognostic factor in CLL.

The Glutathione S-transferase M1 (GSTM1) gene is reported to be involved in glaucoma, an eye disease with a largely unknown mechanism. The gene is polymorphic and three alleles have been characterized. These are one complete deletion of the gene, GSTM1*0, and two alleles differing only in a single amino acid substitution, GSTM1*A and *B. The two latter alleles seem to have equivalent function. Approximately 45% of the European populations are GSTM1 positive. An Estonian study has found that 60% of the glaucoma patients are GSTM1 positive as compared to 45% of controls (P=0.002). We genotyped 200 primary open angle glaucoma patients (POAG), 188 exfoliative glaucoma patients and 200 matched controls using multiplex PCR and pyrosequencing. Forty four per cent of the POAG patients and exfoliative glaucoma patients, and 44.5% of the matched controls were GSTM1 positive. Using pyrosequencing we were able to determine if the patients were homo- or hemizygous for the GSTM1 gene. Five per cent of the POAG patients, 7.4% of the exfoliative glaucoma patients and 4.6% of the controls were homozygous for the presence of the GSTM1 gene. There is no evidence of association between GSTM1 and glaucoma in the Swedish population.

We report structural studies on the epitaxial growth of GaAs/GaNAs core-shell nanowires (NWs) on patterned Si (111) substrates by self-catalyzed selective area growth using Gas-Source Molecular Beam Epitaxy. Epitaxial growth conditions were obtained using a combination of dry and time-sensitive wet etching of the SiO2 growth mask and native SiO2 layer, respectively. We found that higher growth temperatures resulted in a higher yield for the epitaxial growth of patterned self-catalyzed GaAs NWs on Si with an optimal temperature of 690 °C. The GaNAs shell growth at 500 °C was found to be conformal and maintained an epitaxial and dislocation-free interface with both the Si substrate and the GaAs nanowire. The micro-photoluminescence (μ-PL) measurement at 6 K revealed two bands peaking at 1.45 and 1.17 eV, which could be emission from the GaAs core and GaNAs shell. Transmission electron microscopy showed the zincblende crystal structure of GaAs and GaAs/GaNAs core-shell NWs with minimal twinning near the base...

Chronic lymphocytic leukemia (CLL) B-cells resemble self-renewing CD5 + B-cells carrying auto/xeno-antigen-reactive B-cell receptors (BCRs) and multiple innate pattern-recognition receptors, such as Toll-like receptors and scavenger receptors. Integration of signals from BCRs with multiple surface membrane receptors determines whether the cells will be proliferating, anergic or apoptotic. To better understand the role of antigen in leukemogenesis, CLL cell lines producing monoclonal antibodies (mAbs) will facilitate structural analysis of antigens and supply DNA for genetic studies. We present here a comprehensive genotypic and phenotypic characterization of available CLL and normal B-cell-derived lymphoblastoid cell lines (LCLs) from the same individuals (n = 17). Authenticity and verification studies of CLL-patient origin were done by IGHV sequencing, fluorescence in situ hybridization (FISH) and DNA/short tandem repeat (STR) fingerprinting. Innate B-cell features, i.e. natural Ab production and CD5 receptors, were present in most CLL cell lines, but in none of the normal LCLs. This panel of immortalized CLL-derived cell lines is a valuable reference representing a renewable source of authentic Abs and DNA.

Photoluminescence and optically detected magnetic resonance (ODMR) spectroscopies are used to investigate the formation and role of defects in GaAs/GaNxAs1-x core/shell nanowires (NWs) grown by molecular beam epitaxy on Si substrates. Gallium vacancies, which act as non-radiative recombination (NRR) centers, are identified by ODMR. It is shown that the defects are formed in bulk regions, i.e., not on the surface, of the GaNAs shell and that their concentration increases with increasing nitrogen content. Temperature dependent photoluminescence experiments reveal, on the other hand, suppressed thermal quenching of the near-band-edge emission with increasing [N]. This leads to the conclusion that the dominant NRR processes in the studied NWs are governed by surface defects, whereas the role of gallium vacancies in the observed thermally activated NRR is minor.

Comprehensive studies of GaAs/GaNAs coaxial nanowires grown on Si substrates are carried out by temperature-dependent photoluminescence (PL) and PL excitation, to evaluate effects of the shell formation on carrier recombination. The PL emission from the GaAs core is found to transform into a series of sharp PL lines upon radial growth of the GaNAs shell, pointing toward the formation of localization potentials in the core. This hampers carrier transfer at low temperatures from the core in spite of its wider bandgap. Carrier injection from the core to the optically active shell is found to become thermally activated at T > 60 K, which implies that the localization potentials are rather shallow.

Background High-resolution genomic microarrays enable simultaneous detection of copy-number aberrations such as the known recurrent aberrations in chronic lymphocytic leukemia [del(11q), del(13q), del(17p) and trisomy 12], and copy-number neutral loss of heterozygosity. Moreover, comparison of genomic profiles from sequential patients' samples allows detection of clonal evolution. Design and Methods We screened samples from 369 patients with newly diagnosed chronic lymphocytic leukemia from a population-based cohort using 250K single nucleotide polymorphism-arrays. Clonal evolution was evaluated in 59 follow-up samples obtained after 5-9 years. Results At diagnosis, copy-number aberrations were identified in 90% of patients; 70% carried known recurrent alterations, including del(13q) (55%), trisomy 12 (10.5%), del(11q) (10%), and del(17p) (4%). Additional recurrent aberrations were detected on chromosomes 2 (1.9%), 4 (1.4%), 8 (1.6%) and 14 (1.6%). Thirteen patients (3.5%) displayed recurrent copy-number neutral loss of heterozygosity on 13q, of whom 11 had concurrent homozygous del(13q). Genomic complexity and large 13q deletions correlated with inferior outcome, while the former was linked to poor-prognostic aberrations. In the follow-up study, clonal evolution developed in 8/24 (33%) patients with unmutated IGHV, and in 4/25 (16%) IGHV-mutated and treated patients. In contrast, untreated patients with mutated IGHV (n=10) did not acquire additional aberrations. The most common secondary event, del(13q), was detected in 6/12 (50%) of all patients with acquired alterations. Interestingly, aberrations on, for example, chromosome 6q, 8p, 9p and 10q developed exclusively in patients with unmutated IGHV. Conclusions Whole-genome screening revealed a high frequency of genomic aberrations in newly diagnosed chronic lymphocytic leukemia. Clonal evolution was associated with other markers of aggressive disease and commonly included the known recurrent aberrations.

The 309T>G polymorphism in the promoter region of the MDM2gene, known as SNP309, has recently been suggested as an unfavorable prognostic marker in chronic lymphocytic leukemia (CLL) although this has been questioned. To investigate this further, we analyzed the MDM2 SNP309 genotypes in 418 CLL patients and correlated the results with established CLL prognostic factors, time to treatment and overall survival. In this Swedish cohort, no association existed between any particular MDM2 SNP309 genotype, overall survival and time to treatment. Furthermore, no correlation was shown between the MDM2 SNP309 genotypes and Binet stage, IGHV mutational status and recurrent genomic aberrations. In summary, this study argues against the use of the MDM2 SNP309 as a prognostic marker in CLL.

Screening for gene copy-number alterations (CNAs) has improved by applying genome-wide microarrays, where SNP arrays also allow analysis of loss of heterozygozity (LOH). We here analyzed 10 chronic lymphocytic leukemia (CLL) samples using four different high-resolution platforms: BAC arrays (32K), oligonucleotide arrays (185K, Agilent), and two SNP arrays (250K, Affymetrix and 317K, Illumina). Cross-platform comparison revealed 29 concordantly detected CNAs, including known recurrent alterations, which confirmed that all platforms are powerful tools when screening for large aberrations. However, detection of 32 additional regions present in 2-3 platforms illustrated a discrepancy in detection of small CNAs, which often involved reported copy-number variations. LOH analysis using dChip revealed concordance of mainly large regions, but showed numerous, small nonoverlapping regions and LOH escaping detection. Evaluation of baseline variation and copy-number ratio response showed the best performance for the Agilent platform and confirmed the robustness of BAC arrays. Accordingly, these platforms demonstrated a higher degree of platform-specific CNAs. The SNP arrays displayed higher technical variation, although this was compensated by high density of elements. Affymetrix detected a higher degree of CNAs compared to Illumina, while the latter showed a lower noise level and higher detection rate in the LOH analysis. Large-scale studies of genomic aberrations are now feasible, but new tools for LOH analysis are requested.

Nitric oxide has many beneficial functions in the human body at the right amounts, but it can also be hazardous if it is produced in amounts more than needed and has therefore been studied in relation to several neurological and non-neurological disorders. In vitro and in vivo studies demonstrate a connection between the inducible form of Nitric Oxide Synthase, iNOS, and the neuropathological disorder glaucoma, one of the major causes of blindness in the world. In this study, we sought to establish the genetic association between iNOS and primary open angle glaucoma, POAG, and to find the functional element(s) connected with the pathogenesis of the disease.Two microsatellites, 1 insertion/deletion, and 8 single nucleotide polymorphisms (SNPs) in the regulatory region of iNOS were genotyped in 200 POAG patients and 200 age-matched controls. Also, the CCTTT-microsatellite was examined for its protein-binding capability in an electrophoretic mobility shift assay, EMSA.There was a significant difference in allele distribution of the CCTTT-microsatellite, between patients and controls. (CCTTT)14, which has been reported to have a higher activity in a reporter-construct, was significantly more abundant in POAG patients, while (CCTTT)10 and (CCTTT)13 were less common. In EMSA, the (CCTTT)14 allele exhibited specific binding of nuclear proteins.These results, together with other studies on this gene and the CCTTT-microsatellite, establish, for the first time, a genetic association of iNOS with POAG and suggest a regulatory function for the microsatellite.

Glaucoma, a leading cause of blindness in the world, is characterized by neuropathy of the retinal ganglion cells and the optic nerve. Recently, sequence alterations in the optineurin gene were shown to be associated with the disease in families with primarily normal tension glaucoma.In the present study, 200 patients with primary open-angle glaucoma, 200 patients with exfoliative glaucoma, and 200 matched controls were tested for alterations in the coding sequences using denaturing high-performance liquid chromatography and sequencing. In addition, single nucleotide polymorphisms distributed throughout the gene were typed and haplotypes were constructed.No disease-causing alterations were found in either of the patient cohorts. The risk-associated allele M98K was found in equal amounts in both patients and controls. Analysis of haplotype frequencies and distribution revealed high haplotype diversity but no differences between patients and controls.These experiments show no association between optineurin and our Swedish cohorts of high-pressure glaucoma cases, either in coding sequence or in haplotype frequency and distribution.

One of the leading causes of blindness in the world is glaucoma. The most common form is primary open-angle glaucoma (POAG). The only gene identified so far as being associated with POAG is the MYOC gene; 2-4% of the patients have been reported to carry mutations in this gene. Exfoliative glaucoma is a secondary glaucoma, in which one of the symptoms is exfoliations on the lens capsule and anterior segment of the eye. No gene has been identified as being associated with this variant. The aim of the present study was to analyze Swedish patient material for allelic variants and mutations in the coding region of the MYOC gene. Two hundred patients with POAG and 200 with exfoliative glaucoma were analyzed using enzymatic cleavage assay and denaturing high-performance liquid chromatography (dHPLC). An age-matched control group (n = 200), in whom glaucoma had been excluded, was also analyzed using dHPLC. Eight allele variants were identified, two of which were determined to be disease-causing mutations. These two disease-causing mutations were only found in POAG patients, indicating a prevalence of 1% in this patient group. This frequency is lower than that reported in other studies of other populations. No disease-causing mutations were found in the exfoliative glaucoma patients, indicating a fundamentally different genetic basis for that glaucoma variant.

Glaucoma is a disease of the retinal ganglion cells leading to reduction of peripheral vision. It is often associated with an increase in intraocular pressure, leading to mechanical stress of tissues. The oculomedin gene is activated by such stretching and is therefore a candidate for causing glaucoma.The coding sequence and part of the promoter was screened for sequence variants in Swedish cohorts of primary open angle glaucoma, exfoliative glaucoma, and matched controls.Only rare variants were detected in the patient material.There was no evidence that the oculomedin gene participates in the etiology of glaucoma.

Abstract 1254 Poster Board I-276 Introduction Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with varying clinical outcome, where many patients have an indolent course for many years, whereas others show a more aggressive disease despite treatment. This has prompted the search for biomarkers that can predict outcome in this disease. Recent studies have proposed the RNA expression levels of certain genes, i.e. LPL, CLLU1, TCL1, MCL1 and ZAP70 to be novel predictors of clinical outcome in CLL. However, a comprehensive assessment of these RNA-based markers is still lacking. The current study aimed to investigate the potential of these markers in CLL prognostication, either as single markers or in combination with established markers. Patients and Methods By applying real-time quantitative PCR, we measured the RNA expression levels of LPL, CLLU1, TCL1, MCL1 and ZAP70 in 256 newly diagnosed CLL samples from a Scandinavian population-based cohort collected from 1999 to 2002 (median follow-up, 89 months) and correlated with clinical outcome. The expression cut-offs for each RNA marker was determined by constructing ROC curves. Additionally, Binet stage, IGHV mutation status, CD38 expression (cut-off 7%) and the presence of recurrent genomic aberrations (i.e. 11q-, 17p-, 13q- and +12) were evaluated for all cases. Results High expression of all RNA-based markers except MCL1 predicted significantly shorter overall survival (OS) and time to treatment (TTT), with LPL being the most significant prognostic marker in both log-rank (Table 1) and Cox univariate regression analyses. In multivariate analysis including the RNA markers, LPL expression was the only independent prognostic factor for OS, whereas both LPL and CLLU1 could predict TTT. When including all established markers, LPL lost its significance in the model, due to its close association to the IGHV mutation status. Once the mutation status was excluded from the analysis, LPL regained its prognostic power in addition to genomic aberrations and CD38. Interestingly, all of the RNA-based markers added further prognostic information to established markers in subgroups of patients, with LPL expression status giving the most significant results. Notably, high LPL expression predicted a worse outcome in favorable prognostic subgroups such as patients with Binet stage A, CD38 negativity or favorable genomic aberrations (Table 2). Conclusions Altogether, we conclude that LPL expression appear to be the strongest among the RNA-based markers for prediction of clinical outcome in CLL and thus could potentially be applied in the clinical laboratory to predict outcome, particularly in combination with established markers. Disclosures No relevant conflicts of interest to declare.

Chronic lymphocytic leukemia (CLL) is a biologically heterogeneous disease where no common genetic aberration so far has been described. Although recurrent genomic aberrations of prognostic significance are well established (e.g. deletions of 11q, 13q, 17p and trisomy 12), less is known about the overall genetic complexity. Recent development of high-resolution single nucleotide polymorphism (SNP)-arrays will allow screening of genetic complexity, which includes detection of smaller copy-number alterations (CNAs) in addition to the known, recurrent aberrations. We here applied the Affymetrix GeneChip® Mapping 250K Nsp arrays and screened peripheral blood samples from 203 newly diagnosed CLL patients (≥70% tumor cells) from a population-based Scandinavian cohort. The male:female ratio was 2:1, the majority of patients was in stage A (70%) and the median age at diagnosis 61 years. Sixty percentage of cases displayed mutated IGHV genes whereas 35% showed unmutated IGHV genes. The Nexus copy-number software (Biodiscovery, Inc.) was applied and CNAs were identified in all CLL samples investigated, where deletions were more commonly detected than gains (in average, 3.5 vs. 2.2 per sample, respectively). The average length of deletions was 3.5 Mb while gains had an average length of 9.5 Mb (3.6 Mb when excluding trisomy 12). More than 50% of deletions and gains had a size ranging between 0.1–1 Mb, whereas 22% of CNAs were less than 0.1 Mb and 25% larger than 1 Mb. When investigating known, recurrent alterations, 105 samples (52%) carried del(13)(q14); 82 samples displayed a mono-allelic deletion, 15 samples a bi-allelic deletion and 8 samples carried 2 mono-allelic deletions of different sizes. The minimal overlapping region was 0.44 Mb and most of the 13q14 deletions covered the genomic region of miR-15, miR-16 and/or DLEU7. Twenty-one samples (10%) showed trisomy 12 and del(11q) was detected in 27 samples (13%), all covering the ATM gene. del(17p) was detected in 7 patients (3.4%) with one patient also carrying several gains and losses of 17q. Moreover, large alterations involving chromosome arms or entire chromosomes were recurrently observed among the samples, for instance, 3 large 8p losses and 4 large 8q gains. Interestingly, 5 samples, which all carried del(11q), displayed a gain covering whole or large parts of the p-arm of chromosome 2, a region which covers MYCN, REL and BCL11A. Furthermore, comparison of samples with different IGHV mutation status (M vs. UM) illustrated a significantly higher frequency of del(11q) (32% of UM vs. 4% of M), trisomy 12 (22% of UM vs. 5% of M) and gain of 2p (12% vs. 0% in M) in samples with unmutated IGHV genes. As expected, patients with mutated IGHV genes showed a higher frequency of del(13q) (61% of M vs. 31% of UM). In addition, large aberrations (>1Mb) were more common in UM samples which in average displayed 0.57 gains and 1.22 deletions compared to 0.26 gains and 0.67 deletions in M samples. In conclusion, with whole-genome screening using high resolution SNP-arrays, higher complexity was revealed in CLL, including a higher number of gains and losses and a higher frequency of larger aberrations in UM compared to M samples. A novel, recurrent combination of del(11q) and gain of 2p was demonstrated which deserves further investigation.