bluuebunny/crossref_metadata_2025_split huggingface dataset:
High throughput cytotoxicity screening of anti-HER2 immunotoxins conjugated with antibody fragments from phage-displayed synthetic antibody libraries
Authors: Hou Shin-Chen , Chen Hong-Sen , Lin Hung-Wei , Chao Wei-Ting , Chen Yao-Sheng , Fu Chi-Yu , Yu Chung-Ming , Huang Kai-Fa , Wang Andrew H.-J. , Yang An-Suei 
Published: August 2016

AbstractImmunotoxins are an important class of antibody-based therapeutics. The potency of the immunotoxins depends on the antibody fragments as the guiding modules targeting designated molecules on cell surfaces. Phage-displayed synthetic antibody scFv libraries provide abundant antibody fragment candidates as targeting modules for the immunoconjugates, but the discovery of optimally functional immunoconjugates is limited by the scFv-payload conjugation procedure. In this work, cytotoxicity screening of non-covalently assembled immunotoxins was developed in high throughput format to discover highly functional synthetic antibody fragments for delivering toxin payloads. The principles governing the efficiency of the antibodies as targeting modules have been elucidated from large volume of cytotoxicity data: (a) epitope and paratope of the antibody-based targeting module are major determinants for the potency of the immunotoxins; (b) immunotoxins with bivalent antibody-based targeting modules are generally superior in cytotoxic potency to those with corresponding monovalent targeting module; and (c) the potency of the immunotoxins is positively correlated with the densities of the cell surface antigen. These findings suggest that screening against the target cells with a large pool of antibodies from synthetic antibody libraries without the limitations of natural antibody responses can lead to optimal potency and minimal off-target toxicity of the immunoconjugates.
Drone exposure to the systemic insecticide Fipronil indirectly impairs queen reproductive potential
Authors: Kairo Guillaume , Provost Bertille , Tchamitchian Sylvie , Ben Abdelkader Faten , Bonnet Marc , Cousin Marianne , Sénéchal Jacques , Benet Pauline , Kretzschmar André , Belzunces Luc P. , Brunet Jean-Luc 
Published: August 2016

AbstractA species that requires sexual reproduction but cannot reproduce is doomed to extinction. The important increasing loss of species emphasizes the ecological significance of elucidating the effects of environmental stressors, such as pesticides, on reproduction. Despite its special reproductive behavior, the honey bee was selected as a relevant and integrative environmental model because of its constant and diverse exposure to many stressors due to foraging activity. The widely used insecticide Fipronil, the use of which is controversial because of its adverse effects on honey bees, was chosen to expose captive drones in hives via syrup contaminated at 0.1 μg/L and gathered by foragers. Such environmental exposure led to decreased spermatozoa concentration and sperm viability coupled with an increased sperm metabolic rate, resulting in drone fertility impairment. Subsequently, unexposed queens inseminated with such sperm exhibited fewer spermatozoa with lower viability in their spermatheca, leaving no doubt about the detrimental consequences for the reproductive potential of queens, which are key for colony sustainability. These findings suggest that pesticides could contribute to declining honey bee populations through fertility impairment, as exemplified by Fipronil. More broadly, reproductive disorders should be taken into consideration when investigating the decline of other species.
Cinnamomi Cortex (Cinnamomum verum) Suppresses Testosterone-induced Benign Prostatic Hyperplasia by Regulating 5α-reductase
Authors: Choi Hyun-Myung , Jung Yunu , Park Jinbong , Kim Hye-Lin , Youn Dong-Hyun , Kang JongWook , Jeong Mi-Young , Lee Jong-Hyun , Yang Woong Mo , Lee Seok-Geun , Ahn Kwang Seok , Um Jae-Young 
Published: August 2016

AbstractCinnamomi cortex (dried bark of Cinnamomum verum) is an important drug in Traditional Korean Medicine used to improve blood circulation and Yang Qi. Benign prostatic hyperplasia (BPH) is a common chronic disease in aging men. This study was conducted to determine the effect of Cinnamomi cortex water extract (CC) on BPH. BPH was induced by a pre-4-week daily injection of testosterone propionate (TP). Six weeks of further injection with (a) vehicle, (b) TP, (c) TP + CC, (d) TP + finasteride (Fi) was carried on. As a result, the prostate weight and prostatic index of the CC treatment group were reduced. Histological changes including epithelial thickness and lumen area were recovered as normal by CC treatment. The protein expressions of prostate specific antigen, estrogen receptor α (ERα), androgen receptor (AR), 5α-reductase (5AR), and steroid receptor coactivator 1 were suppressed by treatment of CC. Immunohistochemical assays supported the western blot results, as the expressions of AR and ERα were down-regulated by CC treatment as well. Further in vitro experiments showed CC was able to inhibit proliferation of RWPE-1 cells by suppressing 5AR and AR. These results all together suggest CC as a potential treatment for BPH.
TGF-β/BAMBI pathway dysfunction contributes to peripheral Th17/Treg imbalance in chronic obstructive pulmonary disease
Authors: Zhang Jian-Chu , Chen Gang , Chen Long , Meng Zhao-Ji , Xiong Xian-Zhi , Liu Hong-Ju , Jin Yang , Tao Xiao-Nan , Wu Jiang-Hua , Sun Sheng-Wen 
Published: August 2016

AbstractBMP and activin membrane-bound inhibitor (BAMBI) is postulated to inhibit or modulate transforming growth factor β (TGF-β) signaling. Furthermore, strong upregulation of BAMBI expression following in vitro infection of chronic obstructive pulmonary disease (COPD) lung tissue has been demonstrated. In this study, we investigated whether TGF-β/BAMBI pathway is associated with COPD. Blood samples were obtained from 27 healthy controls (HC), 24 healthy smokers (HS) and 29 COPD patients. Elevated Th17/Treg ratios and increased levels of BAMBI protein and mRNA (in plasma and CD4+ T cells respectively), were observed in COPD compared with HC and HS. BAMBI expression was first observed on human CD4+ T cells, with a typical membrane-bound pattern. The enhanced plasma BAMBI levels in COPD positively correlated with the increased plasma TGF-β1 levels and Th17/Treg ratio. Together, an impaired TGF-β/BAMBI pathway may promote the inflammation leading to Th17/Treg imbalance, which is a new mechanism in smokers who develop COPD.
The Hippo-Salvador signaling pathway regulates renal tubulointerstitial fibrosis
Authors: Seo Eunjeong , Kim Wan-Young , Hur Jeongmi , Kim Hanbyul , Nam Sun Ah , Choi Arum , Kim Yu-Mi , Park Sang Hee , Chung Chaeuk , Kim Jin , Min Soohong , Myung Seung-Jae , Lim Dae-Sik , Kim Yong Kyun 
Published: August 2016

AbstractRenal tubulointerstitial fibrosis (TIF) is the final pathway of various renal injuries that result in chronic kidney disease. The mammalian Hippo-Salvador signaling pathway has been implicated in the regulation of cell proliferation, cell death, tissue regeneration, and tumorigenesis. Here, we report that the Hippo-Salvador pathway plays a role in disease development in patients with TIF and in a mouse model of TIF. Mice with tubular epithelial cell (TEC)-specific deletions of Sav1 (Salvador homolog 1) exhibited aggravated renal TIF, enhanced epithelial-mesenchymal transition-like phenotypic changes, apoptosis, and proliferation after unilateral ureteral obstruction (UUO). Moreover, Sav1 depletion in TECs increased transforming growth factor (TGF)-β and activated β-catenin expression after UUO, which likely accounts for the abovementioned enhanced TEC fibrotic phenotype. In addition, TAZ (transcriptional coactivator with PDZ-binding motif), a major downstream effector of the Hippo pathway, was significantly activated in Sav1-knockout mice in vivo. An in vitro study showed that TAZ directly regulates TGF-β and TGF-β receptor II expression. Collectively, our data indicate that the Hippo-Salvador pathway plays a role in the pathogenesis of TIF and that regulating this pathway may be a therapeutic strategy for reducing TIF.
Disease-Homologous Mutation in the Cation Diffusion Facilitator Protein MamM Causes Single-Domain Structural Loss and Signifies Its Importance
Authors: Barber-Zucker Shiran , Uebe René , Davidov Geula , Navon Yotam , Sherf Dror , Chill Jordan H. , Kass Itamar , Bitton Ronit , Schüler Dirk , Zarivach Raz 
Published: August 2016

AbstractCation diffusion facilitators (CDF) are highly conserved, metal ion efflux transporters that maintain divalent transition metal cation homeostasis. Most CDF proteins contain two domains, the cation transporting transmembrane domain and the regulatory cytoplasmic C-terminal domain (CTD). MamM is a magnetosome-associated CDF protein essential for the biomineralization of magnetic iron-oxide particles in magnetotactic bacteria. To investigate the structure-function relationship of CDF cytoplasmic domains, we characterized a MamM M250P mutation that is synonymous with the disease-related mutation L349P of the human CDF protein ZnT-10. Our results show that the M250P exchange in MamM causes severe structural changes in its CTD resulting in abnormal reduced function. Our in vivo, in vitro and in silico studies indicate that the CTD fold is critical for CDF proteins’ proper function and support the previously suggested role of the CDF cytoplasmic domain as a CDF regulatory element. Based on our results, we also suggest a mechanism for the effects of the ZnT-10 L349P mutation in human.
Onco-lncRNA HOTAIR and its functional genetic variants in papillary thyroid carcinoma
Authors: Zhu Hui , Lv Zheng , An Changming , Shi Meng , Pan Wenting , Zhou Liqing , Yang Wenjun , Yang Ming 
Published: August 2016

AbstractThe role of long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) and its functional single nucleotide polymorphisms (SNPs) in papillary thyroid carcinoma (PTC) is still largely unclear. Therefore, we investigated the involvement of lncRNA HOTAIR and its three haplotype-tagging SNPs (htSNPs) in PTC. There was higher expression of HOTAIR in PTC tissues compared to normal tissues. A series of gain-loss assays demonstrated that HOTAIR acts as a PTC oncogene via promoting tumorigenic properties of PTC cells. Additionally, the functional HOTAIR rs920778 genetic variant was a PTC susceptibility SNP. Subjects with the HOTAIR rs920778 TT genotype had an odds ratio (OR) of 1.88, 1.25 and 1.61 (P = 6.0 × 10−6, P = 0.028 and P = 3.2 × 10−5) for developing PTC in Shandong, Jiangsu and Jilin case-control sets compared with subjects with the CC genotype. This statistically significant associations were only found between the rs920778 genetic polymorphism and PTC risk in females but not in males. The allele-specific regulation on HOTAIR expression by the rs920778 SNP was confirmed both in vitro and in vivo. Our results demonstrate that functional SNPs influencing lncRNA regulation may explain a part of PTC genetic basis.
Synthesis of Vertically Standing MoS2 Triangles on SiC
Authors: Lan Feifei , Lai Zhanping , Xu Yongkuan , Cheng Hongjuan , Wang Zaien , Qi Chengjun , Chen Jianli , Zhang Song 
Published: August 2016

AbstractLayered material MoS2 has been attracting much attention due to its excellent electronical properties and catalytic property. Here we report the synthesis of vertically standing MoS2 triangles on silicon carbon(SiC), through a rapid sulfidation process. Such edge-terminated films are metastable structures of MoS2, which may find applications in FinFETs and catalytic reactions. We have confirmed the catalytic property in a hydrogen evolution reaction(HER). The Tafel slope is about 54mV/decade.
Concentric Circular Grating Generated by the Patterning Trapping of Nanoparticles in an Optofluidic Chip
Authors: Dai Hailang , Cao Zhuangqi , Wang Yuxing , Li Honggen , Sang Minghuang , Yuan Wen , Chen Fan , Chen Xianfeng 
Published: August 2016

AbstractDue to the field enhancement effect of the hollow-core metal-cladded optical waveguide chip, massive nanoparticles in a solvent are effectively trapped via exciting ultrahigh order modes. A concentric ring structure of the trapped nanoparticles is obtained since the excited modes are omnidirectional at small incident angle. During the process of solvent evaporation, the nanoparticles remain well trapped since the excitation condition of the optical modes is still valid and a concentric circular grating consisting of deposited nanoparticles can be produced by this approach. Experiments via scanning electron microscopy, atomic force microscopy and diffraction of a probe laser confirmed the above hypothesis. This technique provides an alternative strategy to enable effective trapping of dielectric particles with low-intensity nonfocused illumination and a better understanding of the correlation between the guided modes in an optical waveguide and the nanoparticles in a solvent.
Bilateral ECT induces bilateral increases in regional cortical thickness
Authors: van Eijndhoven P , Mulders P , Kwekkeboom L , van Oostrom I , van Beek M , Janzing J , Schene A , Tendolkar I 
Published: August 2016

AbstractElectroconvulsive therapy (ECT) is the most effective treatment for patients suffering from severe or treatment-resistant major depressive disorder (MDD). Unfortunately its underlying neurobiological mechanisms are still unclear. One line of evidence indicates that the seizures produced by ECT induce or stimulate neuroplasticity effects. Although these seizures also affect the cortex, the effect of ECT on cortical thickness is not investigated until now. We acquired structural magnetic resonance imaging data in 19 treatment-resistant MDD patients before and after a bilateral ECT course, and 16 healthy controls at 2 time points, and compared changes in cortical thickness between the groups. Our results reveal that ECT induces significant, bilateral increases in cortical thickness, including the temporal pole, inferior and middle temporal cortex and the insula. The pattern of increased cortical thickness was predominant in regions that are associated with seizure onset in ECT. Post hoc analyses showed that the increase in thickness of the insular cortex was larger in responders than in non-responders, which may point to a specific relationship of this region with treatment effects of ECT.
Language Sampling for Preschoolers With Severe Speech Impairments
Authors: Binger Cathy , Ragsdale Jamie , Bustos Aimee 
Published: August 2016

Purpose
The purposes of this investigation were to determine if measures such as mean length of utterance (MLU) and percentage of comprehensible words can be derived reliably from language samples of children with severe speech impairments and if such measures correlate with tools that measure constructs assumed to be related.

Method
Language samples of 15 preschoolers with severe speech impairments (but receptive language within normal limits) were transcribed independently by 2 transcribers. Nonparametric statistics were used to determine which measures, if any, could be transcribed reliably and to determine if correlations existed between language sample measures and standardized measures of speech, language, and cognition.

Results
Reliable measures were extracted from the majority of the language samples, including MLU in words, mean number of syllables per utterance, and percentage of comprehensible words. Language sample comprehensibility measures were correlated with a single word comprehensibility task. Also, language sample MLUs and mean length of the participants' 3 longest sentences from the MacArthur–Bates Communicative Development Inventory (Fenson et al., 2006) were correlated.

Conclusion
Language sampling, given certain modifications, may be used for some 3-to 5-year-old children with normal receptive language who have severe speech impairments to provide reliable expressive language and comprehensibility information.
Extending design space of continuous inverse class‐FJ mode PAs
Authors: Gao Yong , Li En , Guo Gaofeng 
Published: August 2016

The impedance space of inverse class‐FJ mode power amplifiers (PAs) is extended by introducing a resistive part into the voltage waveform. Unlike traditional inverse class‐FJ mode, the new continuous inverse class‐FJ possesses a complex fundamental and third‐harmonic terminals. For validating the theory, a broadband PA working across 1.6–2.7 GHz is designed. The experimental results show a drain efficiency of 69–84.9% in the whole working band. The measured output power of the fabricated PA is 40.1–42.5 dBm with a gain of 10.6–12.5 dB across 1.6–2.7 GHz.
Single‐core soft‐switching high step‐up three‐level boost converter with active clamp
Authors: Poorali Behzad , Moradmand Jazi Hamed , Adib Ehsan 
Published: August 2016

In this study, a new three‐level boost converter is introduced which has high voltage gains suitable for photovoltaic applications. Three‐level structure has the advantage of low voltage stresses of the switches and diodes. In the proposed converter, semiconductor devices operate under soft‐switching conditions which results in low switching losses. It utilises an active clamp circuit with one auxiliary switch to absorb the leakage energy. Therefore, elimination of the voltage spikes across the switches as well as efficiency improvement is achieved. On the other hand, the proposed converter has one magnetic core, and consequently, reduced size. Operating principles of the proposed converter along with its theoretical analysis are presented. Experimental results of a 200 W laboratory prototype for voltage conversion of 40 V/400 V are provided in order to verify the proposed converter performance.
OCTSF for torque ripple minimisation in SRMs
Authors: Sun Qingguo , Wu Jianhua , Gan Chun , Hu Yihua , Si Jikai 
Published: August 2016

In this study, a new online compensation of torque sharing function (OCTSF) method is proposed to minimise the torque ripple in switched reluctance motors (SRMs). For SRMs, the torque ripple is a serious issue which is mainly produced by the overlapped conduction phases in the commutation region. In conventional TSF‐based direct instantaneous torque control system, the incoming phase torque cannot achieve its reference torque perfectly and the outgoing phase torque also cannot drop down to its torque reference quickly in the commutation region. Hence, in order to minimise the torque ripple, the TSF of the outgoing phase is proposed to realise the positive compensation at the start of the commutation and the TSF of the incoming phase is used to achieve the negative compensation at the end of the commutation. Moreover, compared with the hard‐chopping mode in conventional TSF strategies, the hard‐chopping and soft‐chopping modes are both employed in the proposed scheme to reduce the switching actions and switching loss. The simulation and experiments based on a 750 W three‐phase 12/8 SRM are carried out to verify the effectiveness of the proposed OCTSF method.
Angestellte Ärzte in der ambulanten Versorgung – Trends, Status quo und Auswirkungen
Authors: Hahn Ursula , Müller T. , Awe B. , Koch J. 
Published: August 2016

Zusammenfassung
Zielsetzung Der aktuelle und perspektivische Versorgungsbeitrag angestellter Ärzte in der vertragsärztlichen Versorgung soll insgesamt, für einzelne Betriebsformen sowie für die Fachgruppen quantifiziert werden. Quantitative wie qualitative Konsequenzen für die Versorgung werden diskutiert.
Methode Die Analyse nutzt die „Statistischen Informationen aus dem Bundesarztregister Bundesgebiet insgesamt per 31.12.2015“ der Kassenärztlichen Bundesvereinigung und berücksichtigt Personenzahlen und Bedarfsplanungsgewichte (BPG) (als Maß der geleisteten Arbeitszeit) angestellter und selbstständiger Ärzte in den Betriebsformen Einzelpraxen (EP), Berufsausübungsgemeinschaften (BAG) und Medizinische Versorgungszentren (MVZ) sowie in den Fachgruppen.
Ergebnisse Von den per 31.12.2015 insgesamt tätigen 135 365 Ärzten entfielen auf angestellte Ärzte 19 % (nach Personen) bzw. 14 % (nach BPG). In 2015 kamen insgesamt 7537 Ärzte neu hinzu, davon 65 % (Personen) bzw. 54 % (BPG) angestellt. In EPs waren 7336 (11 %) der 69 860 dort tätigen Ärzte, in BAG 6325 (12 %) der 51 679 Ärzte, in MVZ 12 430 (90 %) der 13 826 Ärzte als Angestellte tätig. Der Anteil angestellter Ärzte in der Urologie (13 %) und in der hausärztlichen Versorgung (14 %) war am geringsten, der in der Humangenetik (69 %) und Labormedizin (81 %) am höchsten.
Diskussion und Schlussfolgerung Innerhalb weniger Jahre hat sich ein massiver Wandel in den Teilnahmeformen von Ärzten in der vertragsärztlichen Versorgung vollzogen. Angestellte Ärzte sind ubiquitär im Einsatz, sie sind auch in den traditionellen Betriebsformen EP und BAG und in der hausärztlichen Versorgung tätig. Allerdings variiert ihre Versorgungsrelevanz nach Betriebsformen und Fächern z. T. erheblich. Der Anteil wird übergreifend perspektivisch deutlich weiter steigen.Angestellte Ärzte arbeiten sehr viel häufiger in Teilzeit als selbstständige Ärzte, die Arztzahl (Personen) muss zur Aufrechterhaltung des Versorgungs-Status-quo steigen. Es fehlen Studien zu möglichen qualitativen Versorgungskonsequenzen z. B. aus der Ausdifferenzierung der ärztlichen Rollen von „Kollegen“ in „Chefs“ und „Angestellte“. Diskutiert wird, dass die Versorgung in der Fläche möglicherweise besser mit angestellten Ärzten sichergestellt werden kann.
NK cells activated by Interleukin-4 in cooperation with Interleukin-15 exhibit distinctive characteristics
Authors: Kiniwa Tsuyoshi , Enomoto Yutaka , Terazawa Natsumi , Omi Ai , Miyata Naoko , Ishiwata Kenji , Miyajima Atsushi 
Published: August 2016

SignificanceNatural killer (NK) cells are well known to serve as effecter cells in Th1-type immune responses, whereas their roles in Th2-type immune responses are largely unknown. In this study, we describe a previously unidentified pathway wherein IL-4, an initiator cytokine of Th2-type immune responses, induces development of highly activated murine NK cells in vivo. We show that IL-4 overexpression remarkably increases tissue-resident macrophages, which contributes to NK-cell proliferation via production of IL-15. The NK cells induced by IL-4 secrete a large amount of IFN-γ in response to IL-12, an initiator cytokine of Th1-type immune responses, and also exhibit high cytotoxicity against tumor cells. These results reveal the novel role of IL-4 in immune responses through the induction of unique NK cells.
Bird assemblage vulnerability depends on the diversity and biogeographic histories of islands
Authors: Weeks Brian C. , Gregory Nichar , Naeem Shahid 
Published: August 2016

SignificanceBiodiversity is broadly thought to be positively associated with a wide array of ecosystem functions and properties. Because these properties may reduce extinction risk, for example, by making functioning more stable and ecosystems less prone to invasion, biodiverse islands have the potential to accumulate species over evolutionary time that are more vulnerable to extinction. We find that bird diversity is positively related to the collective vulnerability of species in a set of assemblages. This relationship is highly contingent on biogeographic history, a factor often overlooked in biodiversity and ecosystem-functioning studies. Our findings expose a paradox: biodiverse systems, as more robust systems, may experience greater biodiversity loss over ecological time because they accumulate more vulnerable species over evolutionary time.