Enhancing the Efficiency of Organic Photovoltaics by a Photoactive Molecular Mediator

High boiling-point solvent additives, such as 1,8-diiodooctane, have been widely used to tune nanoscale phase morphology for increased efficiency in bulk heterojunction organic solar cells. However, liquid-state solvent additives remain in the active films for extended times and later migrate or evaporate from the films, leading to unstable device performance. Here, a solid-state photoactive molecular mediator, namely N(BAI)3, is reported that could be employed to replace the commonly used solvent additives to tune the morphology of bulk heterojunction films for improved device performance. The N(BAI)3 mediator not only resides in the active films locally to fine tune the phase morphology, but also contributes to the additional absorption of the active films, leading to ∼11% enhancement of power conversion efficiency of P3HT:PC60BM devices. Comparative studies are carried out to probe the nanoscale morphologies using grazing incidence wide-angle X-ray scattering and complementary neutron reflectometry. The use of 1 wt% N(BAI)3 is found to effectively tune the packing of P3HT, presumably through balanced π-interactions endowed by its large conjugated π surface, and to promote the formation of a PC60BM-rich top interfacial layer. These findings open up a new way to effectively tailor the phase morphology by photoactive molecular mediators in organic photovoltaics

Identification of five novel WASP mutations in Chinese families with Wiskott-Aldrich syndrome.

The Wiskott-Aldrich Syndrome (WAS) is an X-linked recessive immunodeficiency caused by mutation in the gene encoding WAS protein (WASP). The disease is characterized by eczema, thrombocytopenia and severe immunodeificency and is associated with extensive clinical heterogeneity. Mutation studies indicated that the mutated genotypes are also highly variable. In this study, we performed PCR-direct sequencing analysis of the WAS gene in six unrelated Chinese families. Five novel mutations identified, included two nonsense mutations (506C-->T, 1388-->T), a small insertion (685-686insCGCA) and two single-base deletions (384delT, 984delC). All of the mutations are predicted to lead to premature translational termination of WASP. Copyright 2002 Wiley-Liss, Inc.postprin

Supervised learning based multimodal MRI brain tumour segmentation using texture features from supervoxels

BACKGROUND: Accurate segmentation of brain tumour in magnetic resonance images (MRI) is a difficult task due to various tumour types. Using information and features from multimodal MRI including structural MRI and isotropic (p) and anisotropic (q) components derived from the diffusion tensor imaging (DTI) may result in a more accurate analysis of brain images. METHODS: We propose a novel 3D supervoxel based learning method for segmentation of tumour in multimodal MRI brain images (conventional MRI and DTI). Supervoxels are generated using the information across the multimodal MRI dataset. For each supervoxel, a variety of features including histograms of texton descriptor, calculated using a set of Gabor filters with different sizes and orientations, and first order intensity statistical features are extracted. Those features are fed into a random forests (RF) classifier to classify each supervoxel into tumour core, oedema or healthy brain tissue. RESULTS: The method is evaluated on two datasets: 1) Our clinical dataset: 11 multimodal images of patients and 2) BRATS 2013 clinical dataset: 30 multimodal images. For our clinical dataset, the average detection sensitivity of tumour (including tumour core and oedema) using multimodal MRI is 86% with balanced error rate (BER) 7%; while the Dice score for automatic tumour segmentation against ground truth is 0.84. The corresponding results of the BRATS 2013 dataset are 96%, 2% and 0.89, respectively. CONCLUSION: The method demonstrates promising results in the segmentation of brain tumour. Adding features from multimodal MRI images can largely increase the segmentation accuracy. The method provides a close match to expert delineation across all tumour grades, leading to a faster and more reproducible method of brain tumour detection and delineation to aid patient management

Brain tumor classification using the diffusion tensor image segmentation (D-SEG) technique.

BACKGROUND: There is an increasing demand for noninvasive brain tumor biomarkers to guide surgery and subsequent oncotherapy. We present a novel whole-brain diffusion tensor imaging (DTI) segmentation (D-SEG) to delineate tumor volumes of interest (VOIs) for subsequent classification of tumor type. D-SEG uses isotropic (p) and anisotropic (q) components of the diffusion tensor to segment regions with similar diffusion characteristics. METHODS: DTI scans were acquired from 95 patients with low- and high-grade glioma, metastases, and meningioma and from 29 healthy subjects. D-SEG uses k-means clustering of the 2D (p,q) space to generate segments with different isotropic and anisotropic diffusion characteristics. RESULTS: Our results are visualized using a novel RGB color scheme incorporating p, q and T2-weighted information within each segment. The volumetric contribution of each segment to gray matter, white matter, and cerebrospinal fluid spaces was used to generate healthy tissue D-SEG spectra. Tumor VOIs were extracted using a semiautomated flood-filling technique and D-SEG spectra were computed within the VOI. Classification of tumor type using D-SEG spectra was performed using support vector machines. D-SEG was computationally fast and stable and delineated regions of healthy tissue from tumor and edema. D-SEG spectra were consistent for each tumor type, with constituent diffusion characteristics potentially reflecting regional differences in tissue microstructure. Support vector machines classified tumor type with an overall accuracy of 94.7%, providing better classification than previously reported. CONCLUSIONS: D-SEG presents a user-friendly, semiautomated biomarker that may provide a valuable adjunct in noninvasive brain tumor diagnosis and treatment planning

Autosomal Dominant Gain-of-function STAT1 Mutation is a Novel Genetic Etiology of Penicillium Marneffei Infection

Symposium / Free Paper 4: ImmunologyConference Theme: Inflammatory Basis of Perinatal and Childhood DiseasesBackground: Penicillium marneffei infection is indigenous to Southeast Asia. Majority of cases occur in patients with AIDS and secondary immunodeficiencies. We previously reported 4 HIV-negative children with chronic mucocutaneous candidiasis (CMC) and severe penicilliosis. Hyper-IgE syndrome was diagnosed in one of them, but extensive genetic studies on IL12-IFNγ axis, CARD9 and AIRE were unrevealing for the rest. Recently, STAT1 hyperphosphorylation causing defective Th1 and Th17 immunity is recognized as a cause of CMC. Objective: To investigate the genetic and functional defects of STAT1 signaling in children affected by penicilliosis. Methods: Targeted sequencing of STAT1 gene or total exome sequencing was performed in 3 patients with CMC and penicilliosis. PBMCs were isolated from patients and normal controls. Intracellular STAT1 phosphorylation (pSTAT1) towards interferon-α and interferon-γ stimulation was evaluated by flow cytometry. Cytokine production in PBMCs towards PMA and ionomycin stimulation was assessed. PBMCs were co-cultured with live Candida albicans and P. marneffei to evaluate interferon-γ response. Results: Heterozygous STAT1 missense mutations were identified in all 3 patients. Two mutations were located in the coiled-coil domain (P1 and P2) and one in the DNA-binding domain (P3). All 3 patients recovered from penicilliosis, but P1 eventually died of fulminant aspergillosis. The percentage of pSTAT1-positive PBMCs induced by interferon-α and interferon-γ was significantly higher in all 3 patients than normal controls, indicating that they had gain-of-function mutations. PBMCs from all patients displayed defective interferon-γ and interleukin-17 production towards PMA and PMA plus ionomycin, respectively. Interferon-γ production induced by C. albicans and P. marneffei in P2 was significantly lower than normal controls. Conclusions: For the first time, we demonstrated STAT1 gain-of-function mutation as an important and novel genetic etiology of invasive mycosis including penicilliosis and aspergillosis. Penicilliosis should be regarded as an indicator disease for primary immunodeficiencies in children without HIV infection unless proven otherwise.published_or_final_versio

Molecular Diagnosis for Paediatric Genetic Disorders Using Whole Exome Sequencing of the Next Generation Sequencing Technology

Oral PresentationMolecular diagnosis for paediatric genetic diseases is important for targeted or tailored treatment, more informative genetic counselling and guiding the families for prenatal or pre-implantation diagnosis. Traditionally, linkage analysis using large multiplex families or multiple families with the same molecular cause is essential and the process could take years before a diagnosis can be reached. Candidate gene screening is usually the only method available for clinical laboratories for genetic diseases in Hong Kong. Next generation sequencing technology has virtually revolutionised the way genetic studies are conducted and provides opportunities for molecular diagnosis for genetic disorders that were never available before. With the possibility of sequencing the whole genome or almost all the coding exons of the genome, the method does not require the availability of large, multiple affected families and prior knowledge of candidate causal genes. It can be applied to a single patient or, as a usual practice, whole genome or whole exome sequencing for the patient plus parents. For whole exome sequencing (WES), it usually produces up to 100 million short sequencing reads of usually 100bp long. These short reads were firstly compared with sequences of a reference human genome and mapped to genomic regions from which they were generated. Each position (base pair) of a coding exon is usually covered with dozens to hundreds of sequencing reads. Analysing the sequences of these reads allows for identification of mutations that are different from the reference sequences. For WES for a single individual, up to 100,000 variants can be identified, with some of which are common variants in a population and some of which rare or private. The population frequencies of these variants are looked up in public databases such as those from the 1000 Genome Project or ESP6500, a project that sequenced 6500 individuals in the US. An internal database is also established with WES data from 200 samples from the local population. For rare, severe genetic disorders that are likely to be caused by mutations from a single gene, we can safely rule out the common (>1% in a population) variants and only focus on the rare or private variants. The nature of the mutations, such as with or without amino acid changes, changes in the open reading frame of the protein, the nature of the amino acid changes (similarity of the amino acid changed to), the conservation of this amino acid in different species, and the function of the gene in relationship to the disease phenotype, are considered to help pinpoint the causal mutations. We will present examples on using WES for molecular diagnosis for paediatric genetic disorders in our Department. These include detection of de novo mutations (mutations that are not detected in parents), somatic mutations and compound heterozygous mutations, and mutations missed by traditional laboratory testing, which demonstrated the power of this new technology in providing accurate molecular diagnosis.published_or_final_versio

Superfluid vs Ferromagnetic Behaviour in a Bose Gas of Spin-1/2 Atoms

We study the thermodynamic phases of a gas of spin-1/2 atoms in the Hartree-Fock approximation. Our main result is that, for repulsive or weakly-attractive inter-component interaction strength, the superfluid and ferromagnetic phase transitions occur at the same temperature. For strongly-attractive inter-component interaction strength, however, the ferromagnetic phase transition occurs at a higher temperature than the superfluid phase transition. We also find that the presence of a condensate acts as an effective magnetic field that polarizes the normal cloud. We finally comment on the validity of the Hartree-Fock approximation in describing different phenomena in this system.Comment: 10 pages, 2 figure

HAM-5 functions as a MAP kinase scaffold during cell fusion in Neurospora crassa.

Cell fusion in genetically identical Neurospora crassa germlings and in hyphae is a highly regulated process involving the activation of a conserved MAP kinase cascade that includes NRC-1, MEK-2 and MAK-2. During chemotrophic growth in germlings, the MAP kinase cascade members localize to conidial anastomosis tube (CAT) tips every ∼8 minutes, perfectly out of phase with another protein that is recruited to the tip: SOFT, a recently identified scaffold for the MAK-1 MAP kinase pathway in Sordaria macrospora. How the MAK-2 oscillation process is initiated, maintained and what proteins regulate the MAP kinase cascade is currently unclear. A global phosphoproteomics approach using an allele of mak-2 (mak-2Q100G) that can be specifically inhibited by the ATP analog 1NM-PP1 was utilized to identify MAK-2 kinase targets in germlings that were potentially involved in this process. One such putative target was HAM-5, a protein of unknown biochemical function. Previously, Δham-5 mutants were shown to be deficient for hyphal fusion. Here we show that HAM-5-GFP co-localized with NRC-1, MEK-2 and MAK-2 and oscillated with identical dynamics from the cytoplasm to CAT tips during chemotropic interactions. In the Δmak-2 strain, HAM-5-GFP localized to punctate complexes that did not oscillate, but still localized to the germling tip, suggesting that MAK-2 activity influences HAM-5 function/localization. However, MAK-2-GFP showed cytoplasmic and nuclear localization in a Δham-5 strain and did not localize to puncta. Via co-immunoprecipitation experiments, HAM-5 was shown to physically interact with NRC-1, MEK-2 and MAK-2, suggesting that it functions as a scaffold/transport hub for the MAP kinase cascade members for oscillation and chemotropic interactions during germling and hyphal fusion in N. crassa. The identification of HAM-5 as a scaffold-like protein will help to link the activation of MAK-2 cascade to upstream factors and proteins involved in this intriguing process of fungal communication

Unique pattern of infections in chronic granulomatous disease – The Asian experience

Conference Theme: Inflammatory Basis of Perinatal and Childhood DiseasesSymposium 40: InfectionBackground: Chronic granulomatous disease (CGD) is a phagocytic disorder caused by defective NADPH oxidase activity. Affected individuals are susceptible to bacterial infections, mycosis and hyperinflammatory complications. Variations in the epidemiology of infectious diseases across geographical regions can lead to distinct clinical phenotypes. Objective: To identify the unique clinical characteristics of a large cohort of CGD patients in China and Southeast Asia referred for genetic studies from 2003 to 2012. Methods: 53 patients with genetically-confirmed CGD were included and their clinical features were analyzed. CYBB and CYBA mutations were studied by Sanger sequencing, and NCF1 ‘GT’ deletion hotspot mutation was studied on genomic DNA by GeneScan. Results: 44 patients with X-CGD had CYBB mutations (missense[n=16]; nonsense[n=8]; deletion[n=9]; insertion[n=2]; intron mutation[n=9]). Nine patient had AR-CGD (CYBA[n=5]; NCF1 75_76delGT[n=4]). The median age at presentation and diagnosis was higher in AR-CGD (7m and 66m) compared with X-CGD (3m and 22m). The commonest presentations were pneumonia (58%), skin and perianal abscess (49%), lymphadenitis (42%) and recurrent diarrhea (30%). Aspergillosis and salmonellosis occurred at a frequency similar to published studies (13% and 19% respectively), but the commonest infection was BCG (43%) and 11% had disseminated BCG. 21% of patients had tuberculosis. Fulminant melioidosis and Chromobacterium violaceum infections occurred in 3 patients and two of their male siblings. Hyperinflammatory conditions included polyarthritis (n=3) and pulmonary granuloma (n=2). Death was recorded in 8 patients (15%). Conclusion: Melioidosis and C. violaceum indigenous to Southeast Asia can cause life-threatening infections in CGD patients. The high incidence of mycobacterial infections is associated with universal BCG vaccination and endemicity of tuberculosis. Such observations emphasize the role of respiratory burst as an immune defense mechanism against these pathogens. These infections are seldom reported in Caucasian cohorts, illustrating the importance of regional collaborative studies to facilitate pattern recognition and early diagnosis of primary immunodeficiencies.published_or_final_versio

Direct observation of delithiation as the origin of analog memristance in LixNbO2

The discovery of analog LixNbO2 memristors revealed a promising new memristive mechanism wherein the diffusion of Li+ rather than O2- ions enables precise control of the resistive states. However, directly correlating lithium concentration with changes to the electronic structure in active layers remains a challenge and is required to truly understand the underlying physics. Chemically delithiated single crystals of LiNbO2 present a model system for correlating lithium variation with spectroscopic signatures from operando soft x-ray spectroscopy studies of device active layers. Using electronic structure modeling of the x-ray spectroscopy of LixNbO2 single crystals, we demonstrate that the intrinsic memristive behavior in LixNbO2 active layers results from field-induced degenerate p-type doping. We show that electrical operation of LixNbO2-based memristors is viable even at marginal Li deficiency and that the analog memristive switching occurs well before the system is fully metallic. This study serves as a benchmark for material synthesis and characterization of future LixNbO2-based memristor devices and suggests that valence change switching is a scalable alternative that circumvents the electroforming typically required for filamentary-based memristors