bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative proteomics analysis of leaves from two Sedum alfredii (Crassulaceae) populations that differ in cadmium accumulation
Authors: Zhang Zhongchun , Zhou Huina , Yu Qi , Li Yunxia , Mendoza‐Cózatl David G. , Qiu Baosheng , Liu Pingping , Chen Qiansi
Published: April 2017

Due to their extraordinary capacity to hypertolerate and hyperaccumulate heavy metals in above‐ground tissues, hyperaccumulator plant species have gained wide attention from researchers seeking biotechnologies to manage environmental heavy metal pollution. However, the molecular basis of hyperaccumulation is still far from being fully understood. Here, we used iTRAQ to perform a quantitative proteomics study of the leaves of Sedum alfredii (Crassulaceae) from hyperaccumulating population (HP) and non‐hyperaccumulating population (NHP). A total of 248 proteins had constitutively higher levels in HP leaves than in NHP leaves. Cadmium (Cd) treatment led to the induction of 13 proteins in HP leaves and 33 proteins in NHP leaves. Two proteins were induced by Cd in both HP leaves and NHP leaves. The annotations for many of the proteins that were higher in HP leaves and proteins that were induced by Cd treatments were associated with vacuolar sequestration, cell wall/membrane modification, and plant defense. In addition to establishing a global empirical foundation for the study of proteins in S. alfredii, our findings relating to the differential constitutive and inducible expression of proteins open potential new research avenues and bolster previously reported suppositions about Cd hyperaccumulation in hyperaccumulator plants.
Class‐paired Fuzzy SubNETs: A paired variant of the rank‐based network analysis family for feature selection based on protein complexes
Authors: Goh Wilson Wen Bin , Wong Limsoon
Published: April 2017

Identifying reproducible yet relevant protein features in proteomics data is a major challenge. Analysis at the level of protein complexes can resolve this issue and we have developed a suite of feature‐selection methods collectively referred to as Rank‐Based Network Analysis (RBNA). RBNAs differ in their individual statistical test setup but are similar in the sense that they deploy rank‐defined weights among proteins per sample. This procedure is known as gene fuzzy scoring. Currently, no RBNA exists for paired‐sample scenarios where both control and test tissues originate from the same source (e.g. same patient). It is expected that paired tests, when used appropriately, are more powerful than approaches intended for unpaired samples. We report that the class‐paired RBNA, PPFSNET, dominates in both simulated and real data scenarios. Moreover, for the first time, we explicitly incorporate batch‐effect resistance as an additional evaluation criterion for feature‐selection approaches. Batch effects are class irrelevant variations arising from different handlers or processing times, and can obfuscate analysis. We demonstrate that PPFSNET and an earlier RBNA, PFSNET, are particularly resistant against batch effects, and only select features strongly correlated with class but not batch.
A “Mitsubishi emblem” tetrauclear aluminum complex containing two unsymmetric N2O2‐ligands and a symmetric NO3‐ligand as initiator for polymerization of rac‐lactide
Authors: Hu Minggang , Wang Fugui , Han Fuzhong , Deng Qigang , Ma Wenhui , Yan Hailong , Dong Guohua , Song Weiming
Published: April 2017

A novel hydroxy‐, methoxy‐, and phenoxy‐bridge “Mitsubishi emblem” tetranuclear aluminum complex (1) is synthesized from an unsymmetric amine‐pyridine‐bis(phenol) N2O2‐ligand (H2L1) and a symmetric amine‐tris(phenol) NO3‐ligand (H2L2). Two same configuration chiral nitrogen atoms are formed in the tetranuclear Al complex upon coordination of the unsymmetric tertiary amine ligand to central Al. Complex 1 initiates controlled ring‐opening polymerization (ROP) of rac‐lactide and afford polylactide (PLA) with narrow molecular weight distributions (Mw/Mn = 1.05–1.19). The analysis of 1H NMR spectra of the oligomer indicates that the methoxy group is the initiating group and the ring‐opening polymerization of lactide follows a coordination‐insertion mechanism. The Homonuclear decoupled 1H NMR spectroscopy suggests the isotactic‐rich chains is preferentially formed in PLA. The study on kinetics of the ROP of lactide reveals the homopropagation rate is higher than the cross‐propagation rate, which is in agreement with the observed isotactic selectivity in the ROP of rac‐lactide. The stereochemistry of the polymerization was also supported by activation parameters. The introduction of unsymmetric ligand H2L1 has an effect on stereoslectivity of polymerization. This result may be of interest for the design of multinuclear metal complex catalysts containing functionalized ligands. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 2084–2091
Spontaneous evolution of nanostructures by light‐driven growth of micelles obtained from in situ nanoparticlization of conjugated polymers
Authors: Kang Eun‐Hye , Yang Sanghee , Yu So Young , Kim Jeongeun , Choi Tae‐Lim
Published: April 2017

To simplify processes to produce self‐assembled nanostructures from polymeric materials, there have been several attempts for in situ self‐assembly of block copolymers. As one of these strategies, we developed the in situ nanoparticlization of conjugated polymers (INCP) process to construct various stable nanostructures without postsynthetic treatments. To get spontaneous mesoscopic evolution of the nanostructures obtained by INCP, a new strategy utilizing a unique conformational change of the conjugated polymer is reported herein. The combination of living ring‐opening olefin metathesis polymerization (ROMP) and cyclopolymerization produced block and gradient copolymers through one‐pot or one‐shot polymerization, which initially formed spherical micelles via INCP. Then, the core block of the micelle stiffened through a coil‐to‐rod conformational change by simple aging in organic solvents because of cis‐to‐trans isomerization of the conjugated polymer under light. Subsequently, this enhanced the π‐π interaction among the cores, and eventually promoted the growth of stable nanostructures from spheres to 1D‐nanocaterpillars or 2D‐sheet‐like architectures. This time‐dependent macroscopic evolution provides deeper insight into the production of a variety of kinetically fixed nano‐ and mesoscale structures through INCP. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 3058–3066
Theoretical studies for forecasting the power conversion efficiencies of polymer‐based organic photovoltaic cells
Authors: Zanlorenzi Cristiano , Akcelrud Leni
Published: April 2017

Modifying the electron‐withdrawing capability in donor–acceptor conjugated copolymers allows designing new polymers with better optical properties. These materials have been successfully applied in bulk heterojunction solar cell devices, and recently a great progress in the enhancement of power conversion efficiencies (PCE) has been achieved. In 2006 Scharber proposed a design rule to obtain PCE values over 10%, optimizing the orbital energy levels of the donor material. The present work proposes a methodology capable to predict theoretically the best efficiencies imparted by a group of 65 conjugated monomeric units selected from the literature, generating 2080 possible DA combinations. The geometries, frontier levels and optical properties were estimated by DFT methods. Based on the results, it was possible to predict the PCE of the most promising 22 copolymers. The results of the calculations indicated that several polymers investigated showed the predicted PCE between 9% and 10%. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 919–927
Crystallization and melting of isotactic polypropylene crystallized from quiescent melt and stress‐induced localized melt
Authors: Lu Ying , Wang Yaotao , Chen Ran , Men Yongfeng
Published: April 2017

Temperature dependency of crystalline lamellar thickness during crystallization and subsequent melting in isotactic polypropylene crystallized from both quiescent molten state and stress‐induced localized melt was investigated using small angle X‐ray scattering technique. Both cases yield well‐defined crystallization lines where inverse lamellar thickness is linearly dependent on crystallization temperature with the stretching‐induced crystallization line shifted slightly to smaller thickness direction than the isothermal crystallization one indicating both crystallization processes being mediated a mesomorphic phase. However, crystallites obtained via different routes (quiescent melt or stress‐induced localized melt) show different melting behaviors. The one from isothermal crystallization melted directly without significant changing in lamellar thickness yielding well‐defined melting line whereas stress‐induced crystallites followed a recrystallization line. Such results can be associated with the different extent of stabilization of crystallites obtained through different crystallization routes. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 957–963
In situ grazing incidence small‐angle X‐ray scattering study of solvent vapor annealing in lamellae‐forming block copolymer thin films: Trade‐off of defects in deswelling
Authors: Sun Zhiwei , Russell Thomas P.
Published: April 2017

Solvent vapor annealing (SVA) is one route to prepare block copolymer (BCP) thin films with long‐range lateral ordering. The lattice defects in the spin‐coated BCP thin film can be effectively and rapidly reduced using SVA. The solvent evaporation after annealing was shown to have a significant impact on the in‐plane ordering of BCP microdomains. However, the effect of solvent evaporation on the out‐of‐plane defects in BCPs has not been considered. Using grazing‐incidence x‐ray scattering, the morphology evolution of lamellae‐forming poly(2‐vinlypyridine)‐b‐polystyrene‐b‐poly(2vinylpyridine) triblock copolymers, having lamellar microdomains oriented normal to substrate surface during SVA, was studied in this work. A micelle to lamellae transformation was observed during solvent uptake. The influence of solvent swelling ratio and solvent removal rate on both the in‐plane and out‐of‐plane defect density was studied. It shows that there is a trade‐off between the in‐plane and out‐of‐plane defect densities during solvent evaporation. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 980–989
A new polymer acceptor containing naphthalene diimide and 1,3,4‐thiadiazole for all‐polymer solar cells
Authors: Weng Chao , Gao Liang , Zhang Zhiguo , Liu Zhaoxia , Tan Songting , Li Yongfang
Published: April 2017

An‐type conjugated polymer containing naphthalene diimide (NDI) and 1,3,4‐thiadiazole (TZ) moieties, named PNTZ, has been synthesized and applied for all‐polymer solar cells (all‐PSCs). By the incorporation of TZ unit into the polymer main chains, the lowest unoccupied molecular orbital level of this polymer has been adjusted effectively. In addition, the electron‐acceptor PNTZ shows a broad absorption spectrum in the range of 300–700 nm, and possesses complementary absorption spectrum with the electron‐donor PTB7‐Th. On the basis of PNTZ as the acceptor and PTB7‐Th as the donor, the all‐PSCs are fabricated. After optimization, the well blend morphologies with a continuous D/A interpenetrating network are observed and the best all‐PSC device exhibits a power conversion efficiency of 4.35% with a high short‐circuit current density of 13.26 mA cm−2. This research demonstrates that the TZ‐containing polymer PNTZ is a promising non‐fullerene acceptor for high efficiency all‐PSCs. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys.2017,55, 990–996
Highly enhanced thermoelectric performance of WS2 nanosheets upon embedding PEDOT:PSS
Authors: Wang Tongzhou , Liu Congcong , Wang Xiaodong , Li Xia , Jiang Fengxing , Li Changcun , Hou Jian , Xu Jingkun
Published: April 2017

Two‐dimensional (2D) WS2 nanosheets (NSs) as a promising thermoelectric (TE) material have gained great concern recently. The low electrical conductivity significantly limits its further development. Herein, we reported an effective method to enhance the TE performance of WS2 NSs by combining poly(3,4‐ethylenedioxythiophene):poly(4‐styrenesulfonate) (PEDOT:PSS). The restacked WS2 NSs thin film with 1T phase structure obtained by a common chemical lithium intercalation show a high Seebeck coefficient of 98 μV K−1 and a poor electrical conductivity of 12.5 S cm−1. The introduction of PEDOT:PSS with different contents obviously improve the electrical conductivity of WS2 NSs thin films. Although a declining Seebeck coefficient was observed, an optimized TE power factor of 45.2 μW m−1 k−1 was achieved for WS2/PEDOT:PSS composite thin film. Moreover, the as‐prepared WS2/PEDOT:PSS thin film can be easily peeled off and transferred to other substrate leading to a more promising application. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 997–1004
Crystallization of polylactic acid under in situ deformation during nonsolvent‐induced phase separation
Authors: Rezabeigi Ehsan , Wood‐Adams Paula M. , Drew Robin A. L.
Published: April 2017

In this study, we investigate polylactic acid (PLA) crystallization under in situ biaxial extension in a nonsolvent‐induced phase separation foaming process. Our ternary system consists of PLA, dichloromethane (DCM) as solvent and hexane as nonsolvent. For the first time, the formation of a shish‐kebab crystalline morphology is observed in such a solution‐based foaming process in certain solid–liquid phase separated systems. The formation of shish‐kebabs is described based on the coil‐stretch transition concept. The rapid biaxial deformation caused by macropore growth uniaxially stretches the long chains that are tied with at least two single crystals which eventually leads to the formation of shish structures throughout the polymer‐rich phase. The kebab lamellae then form perpendicularly on the shish cores. The scanning electron microscopy (SEM) observations and our interpretation of the crystallization phenomena are confirmed by differential scanning calorimetry (DSC) analysis. The observation of various crystalline morphologies, particularly shish‐kebabs, and the elucidation of their formation mechanisms contribute to the understanding of phase separation and pore growth as well as crystallization in such polymer–solvent–nonsolvent systems. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 1055–1062
A new insight into the accident investigation: A case study of Tianjin Port fire and explosion in China
Authors: Aitao Zhou , Lingpeng Fan
Published: April 2017

By figuring out the cause and learning the lessons, accident investigation serves to avoid the like accidents effectively. Incident Management is one of the twelve key factors among China's process safety management system (PSMS), while accident investigation is central to Incident Management. This paper selected “Tianjin Port 8.12 fire and explosion accident” (“Tianjin 8.12 Accident”) as an investigation case. Three core components: cause analysis, affixing the responsibility and corrective suggestions, were unfolded. Problems were analyzed from process safety and accident development point of view. A process analysis approach, which is based on event sequence‐barrier failed, was employed for accident investigation. Affixing responsibility process based on failed analysis was used for accident investigating and affixing. In order to give corrective suggestions, safety information‐based corrective suggestions are proposed by starting from systematic and interconnected perspective and combining with finding failed behaviors and an in‐depth analysis of the causes behind the behaviors. Subsequently, an integral accident investigation approach, which consists of cause analysis based on event sequence‐barrier failed, affixing responsibility process based on failed analysis and systematic corrective measures based on safety information, can effectively render scientific theoretical guidance to investigation and analysis of an accident. © 2017 American Institute of Chemical Engineers Process Saf Prog 36: 362–367, 2017
An Investigation of the Role of Sequencing in Children's Reading Comprehension
Authors: Gouldthorp Bethanie , Katsipis Lia , Mueller Cara
Published: April 2017

To date, little is known about the high‐level language skills and cognitive processes underlying reading comprehension in children. The present study aimed to investigate whether children with high, compared with low, reading comprehension differ in their sequencing skill, which was defined as the ability to identify and recall the temporal order of events in narratives. A novel age‐appropriate reading and recall measure was developed to assess sequencing in typically developing primary school students. Sixty‐four students between the ages of 8 and 11 years read short narratives containing either a forward or backward temporal shift and then placed a set of cards depicting the scenario in either picture or text format in the correct chronological order that the events occurred. Participants also completed measures of verbal and visuospatial working memory to investigate potential relations between working memory and sequencing ability. High comprehenders were found to produce more accurate sequences than low comprehenders in all conditions of the sequencing task, suggesting that sequencing ability may be important for facilitating comprehension. Additionally, participants produced more accurate sequences in the forward condition than the backward condition, indicating that sequencing is facilitated by chronological presentation of events in text. Measures of working memory were unrelated to sequencing ability or comprehension. The results of this study provide preliminary evidence that sequencing is an important skill for children's comprehension of narrative texts and have implications for reading education and intervention programs.
Concise Review: Stem Cells in Osteoimmunology
Authors: Fierro Fernando A. , Nolta Jan A. , Adamopoulos Iannis E.
Published: April 2017

Bone remodeling is a lifelong process in which mature bone tissue is removed from the skeleton by bone resorption and is replenished by new during ossification or bone formation. The remodeling cycle requires both the differentiation and activation of two cell types with opposing functions; the osteoclast, which orchestrates bone resorption, and the osteoblast, which orchestrates bone formation. The differentiation of these cells from their respective precursors is a process which has been overshadowed by enigma, particularly because the precise osteoclast precursor has not been identified and because the identification of skeletal stem cells, which give rise to osteoblasts, is very recent. Latest advances in the area of stem cell biology have enabled us to gain a better understanding of how these differentiation processes occur in physiological and pathological conditions. In this review we postulate that modulation of stem cells during inflammatory conditions is a necessary prerequisite of bone remodeling and therefore an essential new component to the field of osteoimmunology. In this context, we highlight the role of transcription factor nuclear factor of activated T cells cytoplasmic 1 (NFATc1), because it directly links inflammation with differentiation of osteoclasts and osteoblasts.
An association study between CHEK2 gene mutations and susceptibility to breast cancer
Authors: Jalilvand Manizheh , Oloomi Mana , Najafipour Reza , Alizadeh Safar Ali , Saki Najmaldin , Rad Fatemeh Samiee , Shekari Mohammad
Published: April 2017

CHEK2 gene is known as a tumor suppressor gene in breast cancer (BC), which plays a role in DNA repair. The germ line mutations in CEHK2 have been associated with different types of cancer. The present study was aimed at studying the association between CHEK2 mutations and BC. Peripheral blood was collected from patients into a test tube containing EDTA, and DNA was extracted from blood samples. Then, we analyzed mutations including 1100delc, IVS2+1>A, del5395bp, and I157T within CHEK2 gene in patients with BC and 100 normal healthy controls according to PCR-RFLP, allelic specific PCR, and multiplex-PCR. Although IVS2+1G>A mutation within CHEK2 gene was found in two BC patients, other defined mutants were not detected. For the first time, we identified CHEK2 IVS2+1G>A mutation, one out of four different CHEK2 alterations in two Iranian BC patients (2%). Also, our results showed that CHEK2 1100elC, del5395bp, and I157T mutations are not associated with genetic susceptibility for BC among Iranian population.
Phase I trial and pharmacokinetic study of tanibirumab, a fully human monoclonal antibody to vascular endothelial growth factor receptor 2, in patients with refractory solid tumors
Authors: Lee Su Jin , Lee Seon Young , Lee Weon Sup , Yoo Jin San , Sun Jong-Mu , Lee Jeeyun , Park Se Hoon , Park Joon Oh , Ahn Myung-Ju , Lim Ho Yeong , Kang Won Ki , Park Young Suk
Published: April 2017

Background Tanibirumab is a fully human monoclonal antibody to vascular endothelial growth factor receptor 2 (VEGFR-2). We conducted a first-in-human phase I study of tanibirumab in patients with solid tumors refractory to standard chemotherapy. Primary endpoints were evaluating safety, pharmacokinetics (PKs), estimating maximum-tolerated dose (MTD) and recommended phase II dose (RP2D). Methods We designed our study to escalate tanibirumab at 9 different dose levels with a 3 + 3 method and tanibirumab (1–28 mg/kg) was administered intravenously on D1, 8, 15 in 28-day courses. Dose limiting toxicities (DLTs) were only assessed during the first cycle of treatment and response evaluation was performed every 2 cycles. The effects of tanibirumab on several angiogenic factors were analyzed. Results From October 2011 to September 2013, a total of 26 patients with refractory solid tumors were enrolled. The median age was 58 years (range, 27–75) and 20 patients were male. The most common tumor type was colorectal cancer (N = 19) and seven patients had a history of previous bevacizumab treatment. As hemangioma continued to occur, the final dose level, 28 mg/kg, was not performed. DLTs were not found, and the MTD was confirmed to be 24 mg/kg. Hemangioma was observed in 16 patients (61.5%), but all were grade 1–2 and disappeared after discontinuation of the study drug. Among the 18 patients in the efficacy set, no objective response was observed, but 11 patients showed stable disease. PKs were characterized by dose-dependent linear exposure and the mean trough concentrations exceeded biologically relevant target levels at 12 mg/kg and above. Serum VEGF, soluble VEGFR-2, and PlGF increased at the 4 mg/kg dose level and above. Conclusions Treatment with tanibirumab showed a tolerable toxicity profile and modest clinical efficacy in patients with refractory solid tumors. A phase II trial of tanibirumab is ongoing now.
Long-Term Oral Toxicity and Anti-osteoporotic Effect of Sintered Dicalcium Pyrophosphate in Rat Model of Postmenopausal Osteoporosis
Authors: Tsai Yuh-Feng , Hsu Li-Ho , Wu Chang-Chin , Cai Wei-Hua , Yang Kai-Chiang , Fan Fang-Yu
Published: April 2017

Sintered dicalcium pyrophosphate (SDCP), a synthetic pyrophosphate analog, has shown potential for the management of osteoporosis. The long-term oral toxicity and anti-osteoporotic effect of SDCP in a postmenopausal osteoporosis rat model were evaluated in this study. SDCP was orally administered to bilateral ovariectomized (OVX) Wistar rats at a dose of 0.75 mg/kg daily for 24 weeks following by 2 weeks of observation. There were no abnormal findings in clinical signs of toxicity, food consumption, body weight, blood examination, necropsy, and histological inspection attributable to the ingestion of SDCP. The serum level of type I collagen fragments, a bone resorption marker, decreased in SDCP-treated rats, and the bone formation markers alkaline phosphatase, osteocalcin, and osteopontin significantly decreased. These findings indicate that the bone turnover rate decreased in SDCP-treated animals. Relative to OVX rats, the increase in serum tartrate-resistant acid phosphatase 5b level represents an increase in bony tissues in the SDCP-treated rats. Histological examinations of distal femoral metaphyses further revealed that the ingestion of SDCP improved the trabecular bone architecture and decreased bone porosity. Analysis of limb bone ashes showed a significant increase in bone mineral content. Our results show that SDCP inhibits bone resorption to restore bone mass in OVX rats without deleterious effects, and therefore that SDCP has potential in the management of osteoporosis.
Level of functioning, perceived work ability, and work status among psychiatric patients with major mental disorders
Authors: Karpov B. , Joffe G. , Aaltonen K. , Suvisaari J. , Baryshnikov I. , Näätänen P. , Koivisto M. , Melartin T. , Oksanen J. , Suominen K. , Heikkinen M. , Isometsä E.
Published: April 2017

Background:

Major mental disorders are highly disabling conditions that result in substantial socioeconomic burden. Subjective and objective measures of functioning or ability to work, their concordance, or risk factors for them may differ between disorders.

Methods:

Self-reported level of functioning, perceived work ability, and current work status were evaluated among psychiatric care patients with schizophrenia or schizoaffective disorder (SSA, n = 113), bipolar disorder (BD, n = 99), or depressive disorder (DD, n = 188) within the Helsinki University Psychiatric Consortium Study. Correlates of functional impairment, subjective work disability, and occupational status were investigated using regression analysis.

Results:

DD patients reported the highest and SSA patients the lowest perceived functional impairment. Depressive symptoms in all diagnostic groups and anxiety in SSA and BD groups were significantly associated with disability. Only 5.3% of SSA patients versus 29.3% or 33.0% of BD or DD patients, respectively, were currently working. About half of all patients reported subjective work disability. Objective work status and perceived disability correlated strongly among BD and DD patients, but not among SSA patients. Work status was associated with number of hospitalizations, and perceived work disability with current depressive symptoms.

Conclusions:

Psychiatric care patients commonly end up outside the labour force. However, while among patients with mood disorders objective and subjective indicators of ability to work are largely concordant, among those with schizophrenia or schizoaffective disorder they are commonly contradictory. Among all groups, perceived functional impairment and work disability are coloured by current depressive symptoms, but objective work status reflects illness course, particularly preceding psychiatric hospitalizations.
Mediating role of borderline personality disorder traits in the effects of childhood maltreatment on suicidal behaviour among mood disorder patients
Authors: Aaltonen K.I. , Rosenström T. , Baryshnikov I. , Karpov B. , Melartin T. , Suominen K. , Heikkinen M. , Näätänen P. , Koivisto M. , Joffe G. , Isometsä E.
Published: April 2017

Background:

Substantial evidence supports an association between childhood maltreatment and suicidal behaviour. However, few studies have examined factors mediating this relationship among patients with unipolar or bipolar mood disorders.

Methods:

Depressive disorder and bipolar disorder (ICD-10-DCR) patients (n = 287) from the Helsinki University Psychiatric Consortium (HUPC) Study were surveyed on self-reported childhood experiences, current depressive symptoms, borderline personality disorder traits, and lifetime suicidal behaviour. Psychiatric records served to complement the information on suicide attempts. We examined by formal mediation analyses whether (1) the effect of childhood maltreatment on suicidal behaviour is mediated through borderline personality disorder traits and (2) the mediation effect differs between lifetime suicidal ideation and lifetime suicide attempts.

Results:

The impact of childhood maltreatment in multivariate models on either lifetime suicidal ideation or lifetime suicide attempts showed comparable total effects. In formal mediation analyses, borderline personality disorder traits mediated all of the total effect of childhood maltreatment on lifetime suicide attempts, but only one fifth of the total effect on lifetime suicidal ideation. The mediation effect was stronger for lifetime suicide attempts than for lifetime suicidal ideation (P = 0.002) and independent of current depressive symptoms.

Conclusions:

The mechanisms of the effect of childhood maltreatment on suicidal ideation versus suicide attempts may diverge among psychiatric patients with mood disorders. Borderline personality disorder traits may contribute to these mechanisms, although the influence appears considerably stronger for suicide attempts than for suicidal ideation.
Informing the homeopathic practice for Turkish pharmacists: reviewing the example of Portuguese community pharmacies
Authors: Cavaco Afonso Miguel , Arslan Miray , Sar Sevgi
Published: April 2017

Introduction:
Alternative and complementary therapy systems, such as homeopathy, have long been used around the world. Since 1995 homeopathy has been officially recognized in Europe as a system of medicine or a medical specialty. Portuguese community pharmacists have long-standing experience with homeopathic products. By contrast, healthcare professionals in Turkey are less experienced with homeopathic practice although there is a new regulatory setting in place. There are a limited number of studies addressing pharmacists' role within the homeopathic system.

Aim:
To investigate the attitudes (knowledge, feelings and behaviour) of experienced Portuguese pharmacy practitioners who deal with homeopathy, and thus to inform Turkish pharmacy practice and policy on homeopathy-related success factors.

Methods:
A qualitative cross-sectional design was followed, using semi-structured and face-to-face individual interviews with purposively selected Portuguese pharmacists experienced with homeopathic medicines. Audio-recordings were transcribed verbatim and the transcriptions imported into QSR NVivo v10 software for qualitative coding and analysis. Using a thematic content approach, the extracted codes were grouped and indexed by recurrent themes through a reflective procedure and constant comparison.

Results & discussion:
Six general themes emerged, the most relevant being participants' feelings of gratitude for the ability to work in homeopathy; other themes were a helpful regulatory body, clear practice boundaries, scientific support and product quality assurance. Specialized homeopathic education was considered the most important factor for success. This was related to patients' positive perceptions and acceptance, suggesting an increase in public awareness through the pharmacy network.

Conclusions:
Portuguese pharmacists' attitudes towards their homeopathic practices highlighted the key elements for success in a field that is usually distant from traditional pharmaceutical education and practice. The present findings provide guidance for Turkish pharmacists willing to expand their professional scope and to embrace complementary medicines.
Differential effects of Zincum metallicum on cell models
Authors: Gonçalves Jenifer Pendiuk , dos Santos Maria Luiza Ferreira , Rossi Gustavo Rodrigues , Costa Gagosian Viviana Stephanie , de Oliveira Carolina Camargo
Published: April 2017

Introduction: Zinc is an essential trace element necessary for life. Traditional and complementary medicines use zinc-based formulations to treat different classes of diseases. Basic research on homeopathic preparations of zinc are rare and there are a few published clinical cases describing its effects on patients. The use of cell-based models in drug screening is a reliable source of evidence.

Methods: We sought to investigate experimental end-points using cell-based models to determine the effects of dilutions of Zincum metallicum prepared according to the Brazilian Homeopathic Pharmacopoeia. Murine RAW 264.7 macrophages and melanoma B16-F10 cell lines were cultured according to standard procedures. Cells were treated with either 5c, 6c or 30c Zincum metallicum and control cells with its respective vehicle (5c, 6c, or 30c Lactose). Macrophage activation by CD54 immunolabeling and intracellular reactive oxygen species (ROS) using DCFH-DA (2,7-dichlorodihydrofluorescein diacetate) were detected by flow cytometry. Phagocytic capacity (endocytic index) was quantified by light microscopy. Features of melanoma cells were analyzed by colorimetric assays to determine melanin content and cell proliferation rate. All obtained data were submitted to normality test followed by statistical analysis.

Results: Zincum metallicum 6c shifted high ROS-producing macrophages to a low ROS-producing phenotype. Macrophage CD54 expression was increased by Zincum metallicum 5c. No changes in endocytic index were observed. Melanoma cells were not affected by any treatment we tested.

Conclusions: Differing responses and non-linearity were found on macrophages challenged with Zincum metallicum at high dilutions. No changes in melanoma cells were observed. Customised assays using target cells can be useful to investigate high-dilution effects. Other cell types and conditions should be explored.
In vitro effects of Zinc in soluble and homeopathic formulations on macrophages and astrocytes
Authors: Bonafini Clara , Marzotto Marta , Bellavite Paolo
Published: April 2017

Zinc is an important metal in body homeostasis. Zinc in soluble form (Zn2+) and homeopathic Zincum metallicum were tested in macrophages and astrocytes in order to investigate its potential toxic or therapeutic effects. We evaluated cell viability (WST assay), cytokine production such as tumour necrosis factor alpha (TNF-α) and interleukin 10 (IL-10) by enzyme-linked immunosorbent assay (ELISA) and nitric oxide release by Griess reaction. The effect of zinc-depletion and high zinc pre-treatments on the cell adaptation capability was also investigated. In THP-1 macrophage cell line and in human primary macrophages, Zn2+ at sub-toxic doses (30 μM) caused stimulation of TNF-α and IL-10 with different dynamics reaching the maximum peak at the zinc concentration 100 μM, before the cell death. Highest doses (300 μM) impaired dramatically cell vitality. Similar effects on cell viability were obtained also in C6 astrocytes, where Zn2+ slightly increased the nitric oxide release only in cells activated by one of the pro-inflammatory stimuli used in our cellular model (interferon gamma plus TNF-α). Zinc depletion markedly reduced IL-10 production and cell viability. Zincum metallicum did not cause toxicity in any cell type and showed some small stimulation in WST assay that was statistically significant in a few experimental conditions.
Neuroanatomical demonstration of calbindin 2a‐ and calbindin 2b‐like calcium binding proteins in the early embryonic development of zebrafish: mRNA study
Authors: Bhoyar Rahul C. , Jadhao Arun G. , Sivasubbu Sridhar , Singh A.R. , Sabharwal Ankit , Palande Nikhil V. , Biswas Saikat
Published: April 2017

Certain calcium binding proteins (CaBPs) are essential for metabolic processes but the role of these proteins in the development is not well known. We have investigated the mRNA expression of CaBPs, calbindin 2a (Calb2a) and calbindin 2b (Calb2b) in the zebrafish embryos 24, 36, 48 and 72 h post fertilization (hpf). We have seen very high Calb2a mRNA expression in the tegmentum (Tg), midbrain–hindbrain boundary (Mhb), hindbrain (Hb), spinal cord (Sc), retina and cranial ganglion (Crg). Also very high Calb2b mRNA expression was noted in olfactory cells, cerebellum, Tg, Mhb, Hb, optic tectum, retina, retinal ganglion cell layer, retinal inner nuclear layer, Sc, Neural crest, infraorbital neuromasts, pharyngeal arch 3‐7 skeleton and mandibular neuromasts. It is known that many factors are involved in the differentiation of Mhb. Here we are reporting for the first time the mRNA expression of CaBPs (Calb2a and Calb2b) in the Mhb indicating their role in the differentiation of Mhb and development of the brain, eyes and other tissues in the zebrafish. We suggest that Calb2a and Calb2b play an important role in the regulation of zebrafish early embryonic development.
The inferior displacement of the His bundle and fast pathway in a patient with common type atrioventricular nodal tachycardia: Three‐dimensional computed tomography analysis
Authors: Kiuchi Kunihiko , Fukuzawa Koji , Shumpei Mori , Nishii Tatsuya
Published: April 2017

A 66‐year‐old woman with palpitations was referred to our center for catheter ablation due to drug‐refractory, common type atrioventricular nodal tachycardia (AVNRT). A selective slow pathway ablation was attempted. A fast junctional rhythm with transient ventriculoatrial block followed by transient prolongation of the A–H interval occurred immediately after the radiofrequency (RF) application at the coronary sinus ostium (CSOS) level. To assess the location of the fast pathway and His bundle, we sought to visualize the anatomy of the triangle of Koch (TOK) by three‐dimensional computed tomography (CT).
Distinguishing Failure to Cure From Complication After Penile Prosthesis Implantation
Authors: Pineda Miguel , Burnett Arthur L.
Published: April 2017

Background

A successful penile prosthesis implantation (PPI) surgery can be defined by outcomes beyond the absence of complications.

Aim

To introduce the concept of failure to cure (FTC) in the context of PPI to more accurately gauge postoperative outcomes after PPI.

Methods

Consecutive patients from our sexual function registry who underwent PPI from January 2011 to December 2013 were analyzed. Demographics, previous treatment of erectile dysfunction, comorbidities, social history, postoperative problems (POPs), and surgical outcomes were tabulated. Patients completed the International Index of Erection Function (IIEF) and the Erectile Dysfunction Inventory of Treatment Satisfaction questionnaires. We defined a complication, according to the Clavien-Dindo classification, as any deviation from the ideal postoperative course that is not inherent in the procedure and does not constitute an FTC. FTC was defined as a POP that was not a complication. The χ2 tests, t-tests, or Wilcoxon rank-sum tests were used.

Outcomes

Patient-reported and objective outcomes after PPI.

Results

Our enrollment consisted of 185 patients, and we contacted 124 (67%). Of these, 16 (12.9%) had a POP requiring reoperation. Eight patients developed surgical complications (three infections, four erosions, and one chronic pain). Eight patients had FTC (four malpositions and four malfunctions). Factors that correlated with POPs were previous PPI, body mass index higher than 30 kg/m2, and previous treatment with intracorporal injections (P < .05 for all comparisons). Patients who had POPs scored significantly lower on the IIEF erectile function and intercourse satisfaction domains (P < .05 for the two comparisons), but not on the orgasmic function, sexual desire, and overall satisfaction domains (P > .05 for all comparisons).

Clinical Implications

POPs after PPI surgery can be more accurately categorized using the Clavien-Dindo classification of surgical complications to more clearly distinguish surgical complications from FTC.

Strengths and Limitations

Limitations of our study include its retrospective approach. Our series included a large proportion of patients treated for prostate cancer, which limits the generalizability of our findings. We also had a relatively short median follow-up time of 27 months.

Conclusions

Patient-reported outcome assessments can vary greatly from what physicians determine to be successful PPI. An assessment of POPs encompasses more than just complication rates; it also reflects FTC. Even when POPs occur, patients can still derive satisfaction if they are correctively managed. Factors that possibly predispose to POPs include previous PPI surgery, body mass index greater than 30 kg/m2, and history of intracorporal injections.
The commodity super price cycle and real options: Implications for the Greeks of mining firms
Authors: Guedes José
Published: April 2017

The Real Options Approach (ROA) to the management and valuation of mining firms should impart a distinctive pattern to the time path of the Greeks displayed by such firms during the recent price super cycle. This paper simulates the delta, gamma, vega and rho of a gold mining firm holding a portfolio of heterogeneous mines over the recent gold price cycle, to find out the telltale signs that the ROA should leave on the trajectories exhibited by such variables during that period. We show that the ROA and the standard NPV approach to mine management and valuation predict markedly different trajectories for the Greeks.
A dopamine receptor genetic variant enhances perceptual speed in cognitive healthy subjects
Authors: Barral Sandra , Habeck Christian G. , Gazes Elaine , De Jager Philip L. , Bennett David A. , Stern Yaakov
Published: April 2017

Introduction

Cognition is under strong genetic control, yet the specific genes are unknown.

Methods

One hundred and fifty‐three cognitive healthy European subjects from the Reference Abilities Study (RANN) were genotyped for 1,160 variants within 446 neuropsychiatric genes. Adjusted linear regression models evaluated the association between the genetic variants and four reference abilities (Vocabulary, Episodic Memory, Perceptual Speed, and Reasoning).

Results

One hundred and fifty‐nine variants nominally were found significant in the RANN cohort and re‐evaluated in an independent cohort of 868 cognitive healthy subjects from the Religious Orders Study and Rush Memory Aging Project. Meta‐analysis yielded a Bonferroni adjusted statistically significant association between perceptual speed and a variant located in the promoter of the dopamine receptor D4 gene, rs3756450 (β = 0.23, standard error = 0.05, Pmeta = 2.3 × 10−5).

Discussion

Our data suggest that genetic variation in a dopamine pathway gene influences perceptual speed performance in cognitively healthy individuals.
Tackling Sexual Harassment in Science: A Long Road Ahead
Authors: Wendel JoAnna
Published: April 2017

At the National Academies of Sciences, Engineering, and Medicine last week, scientists discussed weaknesses in their fields' handling of sexual harassment and how to address shortcomings.
Identification of residues critical for proton-coupled glutathione translocation in the yeast glutathione transporter, Hgt1p
Authors: Zulkifli Mohammad , Bachhawat Anand Kumar
Published: April 2017

The proton gradient acts as the driving force for the transport of many metabolites across fungal and plant plasma membranes. Identifying the mechanism of proton relay is critical for understanding the mechanism of transport mediated by these transporters. We investigated two strategies for identifying residues critical for proton-dependent substrate transport in the yeast glutathione transporter, Hgt1p, a member of the poorly understood oligopeptide transporter family of transporters. In the first strategy, we tried to identify the pH-independent mutants that could grow at higher pH when dependant on glutathione transport. Screening a library of 269 alanine mutants of the transmembrane domains (TMDs) along with a random mutagenesis strategy yielded two residues (E135K on the cusp of TMD2 and N710S on TMD12) that permitted growth on glutathione at pH 8.0. Further analysis revealed that these residues were not involved in proton symport even though they conferred better transport at a higher pH. The second strategy involved a knowledge-driven approach, targeting 31 potential residues based on charge, conservation and location. Mutation of these residues followed by functional and biochemical characterization revealed E177A, Y193A, D335A, Y374A, H445A and R554A as being defective in proton transport. Further analysis enabled possible roles of these residues to be assigned in proton relay. The implications of these findings in relation to Hgt1p and the suitability of these strategic approaches for identifying such residues are discussed.
Bacteriocins: antibiotics in the age of the microbiome
Authors: Egan Kevin , Ross R. Paul , Hill Colin
Published: April 2017

Antibiotics have revolutionised the treatment of infectious disease and improved the lives of billions of people worldwide over many decades. With the rise in antimicrobial resistance (AMR) and corresponding lack of antibiotic development, we find ourselves in dire need of alternative treatments. Bacteriocins are a class of bacterially produced, ribosomally synthesised, antimicrobial peptides that may be narrow or broad in their spectra of activity. Animal models have demonstrated the safety and efficacy of bacteriocins in treating a broad range of infections; however, one of the principal drawbacks has been their relatively narrow spectra when compared with small-molecule antibiotics. In an era where we are beginning to appreciate the role of the microbiota in human and animal health, the fact that bacteriocins cause much less collateral damage to the host microbiome makes them a highly desirable therapeutic. This review makes a case for the implementation of bacteriocins as therapeutic antimicrobials, either alone or in combination with existing antibiotics to alleviate the AMR crisis and to lessen the impact of antibiotics on the host microbiome.
Drug repurposing for antivirulence therapy against opportunistic bacterial pathogens
Authors: Rampioni Giordano , Visca Paolo , Leoni Livia , Imperi Francesco
Published: April 2017

Antibiotic resistance is a serious public health concern at the global level. Available antibiotics have saved millions of lives, but are progressively losing their efficacy against many bacterial pathogens, and very few new antibiotics are being developed by the pharmaceutical industry. Over the last few decades, progress in understanding the pathogenic process of bacterial infections has led researchers to focus on bacterial virulence factors as potential targets for ‘antivirulence' drugs, i.e. compounds which inhibit the ability of bacteria to cause damage to the host, as opposed to inhibition of bacterial growth which is typical of antibiotics. Hundreds of virulence inhibitors have been examined to date in vitro and/or in animal models, but only a few were entered into clinical trials and none were approved, thus hindering the clinical validation of antivirulence therapy. To breathe new life into antivirulence research and speed-up its transfer to the clinic, antivirulence activities have also been sought in drugs already approved for different therapeutic purposes in humans. If effective, these drugs could be repositioned for antivirulence therapy and have an easier and faster transfer to the clinic. In this work we summarize the approaches which have led to the identification of repurposing candidates with antivirulence activities, and discuss the challenges and opportunities related to antivirulence therapy and drug repurposing. While this approach undoubtedly holds promise for boosting antivirulence drug research, some important issues remain to be addressed in order to make antivirulence drugs viable alternatives to traditional antibacterials.