Evidence for the Band-Edge Exciton of CuInS2 Nanocrystals Enables Record Efficient Large-Area Luminescent Solar Concentrators

AbstractTernary I‐III‐VI2 nanocrystals (NCs), such as CuInS2, are receiving attention as heavy‐metals‐free materials for solar cells, luminescent solar concentrators (LSCs), LEDs, and bio‐imaging. The origin of the optical properties of CuInS2 NCs are however not fully understood. A recent theoretical model suggests that their characteristic Stokes‐shifted and long‐lived luminescence arises from the structure of the valence band (VB) and predicts distinctive optical behaviours in defect‐free NCs: the quadratic dependence of the radiative decay rate and the Stokes shift on the NC radius. If confirmed, this would have crucial implications for LSCs as the solar spectral coverage ensured by low‐bandgap NCs would be accompanied by increased re‐absorption losses. Here, by studying stoichiometric CuInS2 NCs, it is revealed for the first time the spectroscopic signatures predicted for the free band‐edge exciton, thus supporting the VB‐structure model. At very low temperatures, the NCs also show dark‐state emission likely originating from enhanced electron‐hole spin interaction. The impact of the observed optical behaviours on LSCs is evaluated by Monte Carlo ray‐tracing simulations. Based on the emerging device design guidelines, optical‐grade large‐area (30×30 cm2) LSCs with optical power efficiency (OPE) as high as 6.8% are fabricated, corresponding to the highest value reported to date for large‐area devices

Half versus full vacuum suction drainage after modified radical mastectomy for breast cancer- a prospective randomized clinical trial[ISRCTN24484328]

BACKGROUND: Suction drains are routinely used after modified radical mastectomy and are an important factor contributing to increased hospital stay as the patients are often discharged only after their removal. Amongst various factors that influence the amount of postoperative drainage, the negative suction pressure applied to the drain has been reported to be of great significance. While a high negative suction pressure is expected to drain the collection and reduce the dead space promptly, it may also prevent the leaking lymphatics from closing and lead to increased drainage from the wound. Against this background a prospective randomized clinical study was conducted to compare the amount and duration of drainage between a half negative suction and full vacuum suction drainage in patients following modified radical mastectomy. The associated postoperative morbidity was also compared between the two groups. METHODS: 85 FNAC (fine needle aspiration cytology) proven cases of locally advanced breast cancer were randomized. (Using randomly ordered sealed envelops, which were opened immediately before the closure of the wound) in to 50 patients with full vacuum suction (pressure = 700 g/m2) and 35 cases in to half vacuum suction drainage (pressure = 350 g/m2) groups. The two groups were comparable in respect of age, weight, and technique of operation and extent of axillary dissection. Surgery was performed by the same surgical team comprising of five surgeons (two senior and three resident surgeons) using a standardized technique with electrocautery. External compression dressing was provided over the axilla for first 48 hrs and following that patients were encouraged to do active and passive shoulder exercises. The outcomes measured were postoperative morbidity and the length of hospital stay. Statistical methods used: Descriptive studies were performed with SPSS version 10 and group characteristics were compared using student t-test. RESULTS: Half vacuum suction drains were removed earlier than the full suction vacuum suction drains. There was no significant difference in the incidence of seroma formation in the two groups and there was a significant reduction in the total hospital stay in patients with half vacuum suction drainage systems as compared to the full suction drainage group (p < 0.001) without any added morbidity. CONCLUSIONS: Half negative suction drains provide an effective compromise between no suction and full or high suction drainage after modified radical mastectomy by reducing the hospital stay and the post operative morbidity including post operative seromas

Neuroregeneration versus neurodegeneration: Toward a paradigm shift in Alzheimer's disease drug discovery

Alzheimer's disease represents an enormous global burden in terms of human suffering and economic cost. To tackle the current lack of effective drugs and the continuous clinical trial failures might require a shift from the prevailing paradigm targeting pathogenesis to the one targeting neural stem cells (NSCs) regeneration. In this context, small molecules have come to the forefront for their potential to manipulate NSCs, provide therapeutic tools and unveil NSCs biology. Classically, these molecules have been generated either by target-based or phenotypic approaches. To circumvent specific liabilities, nanomedicines emerge as a feasible alternative. However, this review is not intended to be comprehensive. Its purpose is to focus on recent examples that could accelerate development of neuroregenerative drugs against Alzheimer's disease

Structural and biochemical characterization of the Cutibacterium acnes exo-β-1,4-mannosidase that targets the N-glycan core of host glycoproteins.

Commensal and pathogenic bacteria have evolved efficient enzymatic pathways to feed on host carbohydrates, including protein-linked glycans. Most proteins of the human innate and adaptive immune system are glycoproteins where the glycan is critical for structural and functional integrity. Besides enabling nutrition, the degradation of host N-glycans serves as a means for bacteria to modulate the host's immune system by for instance removing N-glycans on immunoglobulin G. The commensal bacterium Cutibacterium acnes is a gram-positive natural bacterial species of the human skin microbiota. Under certain circumstances, C. acnes can cause pathogenic conditions, acne vulgaris, which typically affects 80% of adolescents, and can become critical for immunosuppressed transplant patients. Others have shown that C. acnes can degrade certain host O-glycans, however, no degradation pathway for host N-glycans has been proposed. To investigate this, we scanned the C. acnes genome and were able to identify a set of gene candidates consistent with a cytoplasmic N-glycan-degradation pathway of the canonical eukaryotic N-glycan core. We also found additional gene sequences containing secretion signals that are possible candidates for initial trimming on the extracellular side. Furthermore, one of the identified gene products of the cytoplasmic pathway, AEE72695, was produced and characterized, and found to be a functional, dimeric exo-β-1,4-mannosidase with activity on the β-1,4 glycosidic bond between the second N-acetylglucosamine and the first mannose residue in the canonical eukaryotic N-glycan core. These findings corroborate our model of the cytoplasmic part of a C. acnes N-glycan degradation pathway

High-resolution crystal structure of a polyextreme GH43 glycosidase from Halothermothrix orenii with a-l-arabinofuranosidase activity

A gene from the heterotrophic, halothermophilic marine bacterium Halothermothrix orenii has been cloned and overexpressed in Escherichia coli. This gene encodes the only glycoside hydrolase of family 43 (GH43) produced by H. orenii. The crystal structure of the H. orenii glycosidase was determined by molecular replacement and refined at 1.10 Å resolution. As for other GH43 members, the enzyme folds as a five-bladed β-propeller. The structure features a metal-binding site on the propeller axis, near the active site. Based on thermal denaturation data, the H. orenii glycosidase depends on divalent cations in combination with high salt for optimal thermal stability against unfolding. A maximum melting temperature of 76°C was observed in the presence of 4 M NaCl and Mn2+ at pH 6.5. The gene encoding the H. orenii GH43 enzyme has previously been annotated as a putative α-L-arabinofuranosidase. Activity was detected with p-nitrophenyl-α-L-arabinofuranoside as a substrate, and therefore the name HoAraf43 was suggested for the enzyme. In agreement with the conditions for optimal thermal stability against unfolding, the highest arabinofuranosidase activity was obtained in the presence of 4 M NaCl and Mn2+ at pH 6.5, giving a specific activity of 20-36 µmol min-1 mg-1. The active site is structurally distinct from those of other GH43 members, including arabinanases, arabinofuranosidases and xylanases. This probably reflects the special requirements for degrading the unique biomass available in highly saline aqueous ecosystems, such as halophilic algae and halophytes. The amino-acid distribution of HoAraf43 has similarities to those of mesophiles, thermophiles and halophiles, but also has unique features, for example more hydrophobic amino acids on the surface and fewer buried charged residues

Is DD3 a new prostate-specific gene?

The search for new and more specific molecular markers of prostatic cancers has led, in recent years, to the identification of the DD3 gene. Using reverse transcription (RT)-PCR, we investigated DD3 gene expression in human cell lines, in blood samples from healthy men and women donors and in various neoplastic and non-neoplastic tissues from the prostate and other organs. Whereas RT-PCR analysis using primers that amplified the region spanning exons 1 and 3 yielded DD3 gene expression in all samples examined, a primer downstream to exon 4 detected the expected size DD3 band only in benign and malignant prostatic tissues. These findings indicate that the only prostate specific region of DD3 is exon 4

Structural Basis for Binding of Fluorinated Glucose and Galactose to <i>Trametes multicolor</i> Pyranose 2-Oxidase Variants with Improved Galactose Conversion

<div><p>Each year, about six million tons of lactose are generated from liquid whey as industrial byproduct, and optimally this large carbohydrate waste should be used for the production of value-added products. <i>Trametes multicolor</i> pyranose 2-oxidase (<i>Tm</i>P2O) catalyzes the oxidation of various monosaccharides to the corresponding 2-keto sugars. Thus, a potential use of <i>Tm</i>P2O is to convert the products from lactose hydrolysis, D-glucose and D-galactose, to more valuable products such as tagatose. Oxidation of glucose is however strongly favored over galactose, and oxidation of both substrates at more equal rates is desirable. Characterization of <i>Tm</i>P2O variants (H450G, V546C, H450G/V546C) with improved D-galactose conversion has been given earlier, of which H450G displayed the best relative conversion between the substrates. To rationalize the changes in conversion rates, we have analyzed high-resolution crystal structures of the aforementioned mutants with bound 2- and 3-fluorinated glucose and galactose. Binding of glucose and galactose in the productive 2-oxidation binding mode is nearly identical in all mutants, suggesting that this binding mode is essentially unaffected by the mutations. For the competing glucose binding mode, enzyme variants carrying the H450G replacement stabilize glucose as the <i>α</i>-anomer in position for 3-oxidation. The backbone relaxation at position 450 allows the substrate-binding loop to fold tightly around the ligand. V546C however stabilize glucose as the <i>β</i>-anomer using an open loop conformation. Improved binding of galactose is enabled by subtle relaxation effects at key active-site backbone positions. The competing binding mode for galactose 2-oxidation by V546C stabilizes the <i>β</i>-anomer for oxidation at C1, whereas H450G variants stabilize the 3-oxidation binding mode of the galactose <i>α</i>-anomer. The present study provides a detailed description of binding modes that rationalize changes in the relative conversion rates of D-glucose and D-galactose and can be used to refine future enzyme designs for more efficient use of lactose-hydrolysis byproducts.</p></div

Uromodulin facilitates neutrophil migration across renal epithelial monolayers

The glycosylated protein uromodulin is exclusively found in the thick ascending limb cells (TAL) of the kidney, where it is produced on mass and apically targeted, eventually being secreted into the urine. Recently, there has been a renewed interest in this protein due to its ability to interact with the immune system, implicating this protein as a renal inflammatory molecule. Here we investigated the potential role of membrane bound uromodulin on neutrophil adhesion and trans-epithelial migration. The renal tubular epithelial cell line, LLC-PK1, stably transfected with human uromodulin was used to investigate the influence of uromodulin on neutrophil adherence and migration. Uromodulin expression resulted in a significant increase of neutrophil adherence and trans-epithelial migration, in both the apical to basolateral and the basolateral to apical direction. Although uromodulin is GPI anchored and targeted to the apical membrane, we could also observe expression in the basal and lateral membranes domains, which may be responsible for basolateral to apical migration. Furthermore we show that uromodulin binds both the heavy and light chain of IgG, and that IgG enhances neutrophil migration. This study demonstrates that uromodulin can facilitate neutrophil trans-epithelial migration and that this migration can be amplified by co-factors such as IgG

Principal productive and competing binding modes for fluorinated glucose and galactose.

<p>Structural overlay of the active sites in <i>Tm</i>P2O V546C (beige) and H450G (green). The V546C mutant is used as a reference since it displays the same binding modes as the H167A mutant, and for 2- or 3-fluorinated glucose, also agrees with the binding modes observed for the wild type. (a) Binding of <i>3F</i>Glc in the productive 2-oxidation binding mode. The sugar is stabilized as the <i>β</i>-anomer with O2 coordinated by His458 and Asn593 and C2 appropriately positioned for oxidation. The substrate-binding loop is in the semi-open conformation positioning Phe454 closely packed against the pyranose as has been described for the productive binding mode earlier <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086736#pone.0086736-Tan1" target="_blank">[19]</a>. (b) <i>2F</i>Glc in the competing 3-oxidation binding mode. In H450G, the C1 hydroxyl in <i>2F</i>Glc is stabilized in axial configuration (<i>α</i>-anomer) by Asp452 and Thr169 and the substrate-binding loop assumes the semi-open conformation. V546C stabilizes the <i>β</i>-anomer and reveals the open conformation of the substrate-binding loop as observed earlier for H167A in complex with <i>2F</i>Glc <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086736#pone.0086736-Kujawa1" target="_blank">[14]</a>. (c) <i>3F</i>Gal in productive 2-oxidation binding mode with the axial C4 hydroxyl group coordinated by Asp452 and Thr169. The substrate-binding loop is in the semi-open conformation. (d) <i>2F</i>Gal in competing binding modes. The competing binding mode observed for V546C corresponds to the <i>2F</i>Gal <i>β</i>-anomer oriented for oxidation at C1. The competing binding mode for H450G shows the <i>α-</i>anomer of <i>2F</i>Gal oriented for oxidation at C3. In both cases, the substrate-binding loop assumes the semi-open conformation compatible with the productive sugar-oxidation mode. All structures that bind sugar substrate show the Thr169 Oγ1 atom pointing <i>away</i> from the flavin N(5)/O(4) locus, which constitutes an additional hallmark of the productive binding mode. For clarity, the covalent link between the flavin and His167 is not shown in the pictures. The pictures were produced using the program PyMOL <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086736#pone.0086736-DeLano1" target="_blank">[43]</a>.</p