bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermal Cyclization of Copper Carbenoid of α‐Dizao α‐Phosphorylacetate: Unexpected and Novel Access to Oxaphosphirane
Authors: Shie Jr‐Yun , Zhu Jia‐Liang , Wu Yung‐Peng
Published: June 2015

Under the catalysis of Cu(OTf)2 in refluxing CH2Cl2, ethyl α‐dizao α‐(diethylphosphoryl)acetate was shown to undergo a new cyclization reaction to afford a pentacovalent oxaphosphirane product. The reaction is proposed to occur through the addition of the P=O double bond to the copper carbenoid, followed by the hydrolysis of the ylide intermediate. Our finding represents the first example on producing oxaphosphiranes from dizao phosphoryl compounds. On the other hand, the corresponding rhodium carbenoid displayed the different reactivity under the same thermal conditions, to produce the β‐propiolactone through the well‐recognized C‐H insertion pathway.
Prevalence and genotype distribution of cervical human papillomavirus (HPV) among women in urban Tianjin, China
Authors: Chen Xiujie , Wallin Keng‐Ling , Duan Meng , Gharizadeh Baback , Zheng Biying , Qu Pengpeng
Published: June 2015

To investigate the prevalence and genotype distribution of human papillomavirus (HPV) infection among women in urban Tianjin, China. A cervical cancer screening program for 2,000 women aged 21–65 years old was performed in urban Tianjin from April to October in 2013. The program included ThinPrep cytologic tests (TCT), HPV DNA detection and genotyping using nested polymerase chain reaction (PCR) combined with Pyrosequencing technology. Colposcopy examination and biopsy were needed if TCT reported greater or equal atypical cells of undetermined significance (ASCUS). One thousand nine hundred seventy‐eight women were enrolled in the final study, 14.71% (291/1,978) of women were tested HPV positive. Of HPV‐positive specimens, 248 (85.22%) and 43 (14.78%) were infected with high‐ and low‐risk HPV genotypes, respectively. Twenty‐eight types of HPV were detected in all, the most frequently detected types were HPV16, 58, 18, and 66 orderly. The single infection rate was 92.28% among HPV‐positive samples while the multiple infection rate was 7.72%. Among multiple infection models, HPV16 was the most common type co‐infection with other types. This study is, to our knowledge, the first population‐based survey to provide data on HPV infection and genotype distribution among women in urban Tianjin, China. There was a high prevalence of HPV infection in this area, and HPV16, 58, 18, 66 were the most frequently detected genotypes. Our study provide important information regarding the necessity of early cervical cancer screenings and prophylactic HPV vaccinations, and the knowledge of HPV distribution can also inform us about the HPV ecological change after the vaccination. J. Med. Virol. 87:1966–1972, 2015. © 2015 Wiley Periodicals, Inc.
Studies on the Interaction of Some Biologically Significant Radical Scavengers on Metal‐Ion Catalyzed Phloroglucinol‐Based Chemical Oscillator
Authors: Gull Usma , Peerzada G. M. , Ganaie Nadeem B. , Rashid Sna
Published: June 2015

The response of the Ce(III)‐catalyzed phloroglucinol (1,3,5‐trihydroxybenzene)‐based Belousov Zhabotinsky system to the addition of various antioxidants (ascorbic acid, glutathione, inosine, N‐acetylcysteine) is monitored at 30°C under stirred batch conditions. This method is convenient and has good sensitivity for the determination of these antioxidants. The addition of these antioxidants to the BZ mixture influences the oscillatory parameter (number of oscillations) to an extent that depends on the concentration of the antioxidant. The experimental results have shown that the number of oscillations decrease on increasing the concentration of antioxidant. The calibration plots show a linear relationship (R2 = 0.98 for ascorbic acid and glutathione and R2 = 0.99 for inosine and N‐acetylcysteine) between the number of oscillations and the [antioxidant] over the concentration range of 0.0125‐0.5, 0.05‐0.2, 0.025‐0.1, and 0.1‐0.5 mol L−1 with detection limits 6.9 × 10−5, 2.762 × 10−4, 1.381 × 10−4, and 5.524 × 10−4 mol L−1 for ascorbic acid, glutathione, inosine, and N‐acetylcysteine, respectively. Some aspects of the mechanism of these antioxidants on the BZ system have been discussed.
Fractional carbon dioxide laser ablation for the treatment of microcystic lymphatic malformations (lymphangioma circumscriptum) in an adult patient with Klippel–Trenaunay syndrome
Authors: Saluja Sandeep , Petersen Marta , Summers Erika
Published: June 2015

Background

Lymphangioma circumscriptum (LC) is a rare, benign, vascular malformation of dilated superficial lymphatic channels. Treatment is typically undertaken for cosmetic reasons or complications such as fluid drainage, pain, and infection risk that can negatively impact quality of life. Management of LC remains challenging because of high recurrence rates, regardless of the treatment modality chosen.

Objective

Treatment of LC with the fully‐ablative carbon dioxide (CO2) laser has been reported widely, however, treatment with the fractionated CO2 laser has been limited to one case in the pediatric population. Our objective was to test the usefulness of the fractionated 10,600‐nm CO2 laser in the management of symptomatic LC in an adult.

Results

We report a case of a 27‐year‐old female with Klippel‐Trenaunay Syndrome (KTS) who presented with a 5‐year history of well‐circumscribed lesions on the right lateral and anterior thigh that drained clear lymphatic and serosanguineous fluid, respectively. These lesions caused her significant emotional distress because of extensive drainage. After only one treatment utilizing the fractionated 10,600‐nm CO2 laser, the patient had improvement with cessation of fluid drainage, and the lesions are still asymptomatic 6 months since initial treatment.

Conclusion

The favorable results observed in our patient suggest that fractionated CO2 laser may be an additional well‐tolerated, low downtime option for palliation of symptoms in patients with LC. We recognize that short‐term follow‐up cannot conclusively demonstrate effectiveness and durability of this treatment and that, given the high risk of recurrence, a longer‐term observation is needed before making definite conclusions. Lasers Surg. Med. 47:539–541, 2015. © 2015 Wiley Periodicals, Inc.
Identification of activating enzymes of a novel FBPase inhibitor prodrug, CS‐917
Authors: Kubota Kazuishi , Inaba Shin‐ichi , Nakano Rika , Watanabe Mihoko , Sakurai Hidetaka , Fukushima Yumiko , Ichikawa Kimihisa , Takahashi Tohru , Izumi Takashi , Shinagawa Akira
Published: June 2015

CS‐917 (MB06322) is a selective small compound inhibitor of fructose 1,6‐bisphosphatase (FBPase), which is expected to be a novel drug for the treatment of type 2 diabetes by inhibiting gluconeogenesis. CS‐917 is a bisamidate prodrug and activation of CS‐917 requires a two‐step enzyme catalyzed reaction. The first‐step enzyme, esterase, catalyzes the conversion of CS‐917 into the intermediate form (R‐134450) and the second‐step enzyme, phosphoramidase, catalyzes the conversion of R‐134450 into the active form (R‐125338). In this study, we biochemically purified the CS‐917 esterase activity in monkey small intestine and liver. We identified cathepsin A (CTSA) and elastase 3B (ELA3B) as CS‐917 esterases in the small intestine by mass spectrometry, whereas we found CTSA and carboxylesterase 1 (CES1) in monkey liver. We also purified R‐134450 phosphoramidase activity in monkey liver and identified sphingomyelin phosphodiesterase, acid‐like 3A (SMPADL3A), as an R‐134450 phosphoramidase, which has not been reported to have any enzyme activity. Recombinant human CTSA, ELA3B, and CES1 showed CS‐917 esterase activity and recombinant human SMPDL3A showed R‐134450 phosphoramidase activity, which confirmed the identification of those enzymes. Identification of metabolic enzymes responsible for the activation process is the requisite first step to understanding the activation process, pharmacodynamics and pharmacokinetics of CS‐917 at the molecular level. This is the first identification of a phosphoramidase other than histidine triad nucleotide‐binding protein (HINT) family enzymes and SMPDL3A might generally contribute to activation of the other bisamidate prodrugs.
Recurrence of suicide attempt in adolescents lost to contact early by clinicians: The 10‐year REPEATERS cohort of French adolescents
Authors: Ligier Fabienne , Guillemin Francis , Angot Catherine , Bourion Stéphanie , Kabuth Bernard
Published: June 2015

Losing contact with adult suicide attempters in the year after the suicide attempt (SA) increases the risk of recurrence. The situation with adolescents is unknown. We aimed to determine whether being lost to contact early (LCE) by clinicians is a risk factor of long‐term SA recurrence among adolescents and the associated factors. Data were collected 10 years after an index SA and a Cox model was used for analysis. Among the 249 SA patients included, 59 (24%) were LCE, the most important risk factor of SA recurrence up to 10 years (hazard ratio [HR] = 2.8 [95% confidence interval (95% CI) 1.4–5.5]; p = .016). Risk factors of being LCE were female sex (odds ratio [OR] = 2.9 [95% CI 1.1–8.2]; p = .009), a psychiatric comorbidity (OR = 2.2 [1.1–4.3]; p = .023) and no family history of suicide (OR = 2.1 [1.1–4.3]; p = .047). These results support the development of preventive actions early after an SA in an adolescent to maintain contact and care.
Effect of itraconazole on mouse mesencephalic neurons
Authors: Giorgi Chiara , Fausto Catia , Pardini Carla , Simili Marcella , Del Carratore Renata , Vaglini Francesca
Published: June 2015

Neuronal cells have complex geometrical shapes, long processes such as axons and dendrites, and as a response to specific stimuli, they go through polarized neuronal migration that influences connectivity and information processing. Recently, it has been discovered that itraconazole, a widely used systemic antifungal drug, has an effect on cell morphology, acting as an inhibitor of the morphogen Sonic Hedgehog (Shh) and of the mammalian target of rapamycin mTOR pathways. In this paper we evaluated the effect of itraconazole on mouse mesencephalic dopaminergic neurons following their neurite outgrowth and functional activity by [3H] DA uptake. Furthermore the expression of several neural markers, the activation of the mTOR and of the morphogenic Shh pathways in the neuronal population was examined. Our results show for the first time a strong alteration of neurons morphology and an inhibitory effect of differentiation by itraconazole, probably due to cholesterol trafficking reduction, mTOR and Shh pathways inhibition. The inhibition of mTOR and Shh pathways by this drug has also been found in other cellular systems such as endothelial cells and lung cancer cells, suggesting a conserved mechanism of intercellular communication. As itraconazole is currently involved in multiple human clinical trials as a prospective anticancer agent, the effect on neuronal differentiation should be taken into account.
Ability of magnetocardiography to detect regional dominant frequencies of atrial fibrillation
Authors: Yoshida Kentaro , Ogata Kuniomi , Inaba Takeshi , Nakazawa Yoko , Ito Yoko , Yamaguchi Iwao , Kandori Akihiko , Aonuma Kazutaka
Published: June 2015

Background

Lead V1 on electrocardiography (ECG) can detect the dominant frequency (DF) of atrial fibrillation (AF) in the right atrium (RA). Paroxysmal AF is characterized by a frequency gradient from the left atrium (LA) to the right atrium (RA). We examined the ability of magnetocardiography (MCG) to detect regional DFs in both the atria.

Methods

Study subjects comprised 18 consecutive patients referred for catheter ablation of persistent AF. An MCG system with 64 magnetic sensors was used to perform MCG in the frontal, lateral, and back planes prior to the ablation procedure in each patient. DFMCG and organization index (OIMCG) were calculated using fast Fourier transformation. Intracardiac electrograms (ICEs) in both the atria and the coronary sinus (CS) were mapped at 17 sites. Regional DFsICE were also determined.

Results

Mean LA DFICE was higher than mean RA DFICE (6.40±0.66 versus 6.16±0.80 Hz, P=0.03). DFMCG in the channel having the highest OIMCG was 6.61±0.88 Hz in the frontal plane, 6.52±0.64 Hz in the lateral plane, and 6.42±0.62 Hz in the back plane (P=0.3). In each plane, DFMCG correlated with DFICE at the RA appendage (R=0.95, P<0.0001), the LA appendage (R=0.91, P<0.0001), and the CS (R=0.93, P<0.0001). DFECG in V5 modestly correlated with DFICE at the LA appendage (R=0.82, P<0.0001).

Conclusions

MCG could more precisely detect the DFs in the LA and the CS than ECG. However, the usefulness of pre‐procedural detection of the AF frequency gradient for ablation therapy needs to be evaluated in future prospective studies.
Frequent expression of PD‐L1 on circulating breast cancer cells
Authors: Mazel Martine , Jacot William , Pantel Klaus , Bartkowiak Kai , Topart Delphine , Cayrefourcq Laure , Rossille Delphine , Maudelonde Thierry , Fest Thierry , Alix-Panabières Catherine
Published: June 2015

Immune checkpoint regulators such as PD‐L1 have become exciting new therapeutic targets leading to long lasting remissions in patients with advanced malignancies. However, in view of the remarkable costs and the toxicity profiles of these therapies, predictive biomarkers able to discriminate responders from non‐responders are urgently needed. In the present paper, we provide evidence that PD‐L1 is frequently expressed on metastatic cells circulating in the blood of hormone receptor‐positive, HER2‐negative breast cancer patients. We performed western blot, flow cytometry and immunocytochemical analyses to demonstrate the specificity of the PDL1 antibody used in our study and established immunoscores for PDL1 expression on single tumor cells. We then selected sixteen patients with circulating tumor cells (CTCs) using the CellSearch® system and found PD‐L1(+) CTCs in 11 patients (68.8%). The fraction of PD‐L1(+) CTCs varied from 0.2 to 100% in individual patients. This is the first report demonstrating the expression of PD‐L1 on CTCs. The established CTC/PD‐L1 assay can be used for liquid biopsy in future clinical trials for stratification and monitoring of cancer patients undergoing immune checkpoint blockade.
Observation of Age‐Related Decline in the Performance of the Transverse Abdominis Muscle
Authors: Davies Paul , Grace Fergal M. , Lewis Mark P. , Sculthorpe Nicholas
Published: June 2015

Background

Previous research has shown that the performance of skeletal muscle declines with advancing age. Coordination of the transverse abdominis (TrA), a deep postural muscle, has been shown to be reduced in persons with low back pain. No previous research has studied the effect of age on the activation on this muscle.

Objective

To assess the effect of age on TrA activation in response to rapid arm abduction.

Design

Cross‐sectional cohort study.

Setting

University exercise physiology laboratory.

Participants

A total of 18 adult men (aged 27 ± 7.0 years) for the younger group and 11 older adults (5 men and 6 women, aged 59.6 ± 4.0 years) were recruited for this study.

Method

Participants were positioned on a treatment table and performed a series of rapid arm abduction movements with their right arm while the activation of the TrA muscle was recorded using ultrasound imaging. Onset of arm abduction was measured using surface electromyography and synchronized with the ultrasound through the ultrasound unit's electrocardiogram channel. The mean time difference between the 2 events was calculated during post‐hoc analysis.

Main Outcome Measurements

A Mann‐Whitney test was performed to test for differences in the onset performance of the TrA muscle between the 2 groups.

Results

Results showed that the older group was significantly slower than the younger group in engaging their TrA in response to the rapid arm abduction (P = .036). A separate analysis of the older group data showed that no significant differences existed between the male and female participants that could potentially have acted as a confounding factor for the main finding (P = .126).

Conclusions

This study shows that older adults were slower than younger adults in activating their TrA muscle in response to rapid arm abduction. This delay has the potential to lead to increased occasions when the low back is unprotected, increasing the likelihood of injury or low back pain.
Paleoecological and climatic implications of stable isotope results from late Pleistocene bone collagen, Ziegeleigrube Coenen, Germany
Authors: Wißing Christoph , Matzerath Simon , Turner Elaine , Bocherens Hervé
Published: June 2015

Climatic and ecological conditions during Marine Oxygen Isotope Stage (MIS) 3 are complex and the impact of cold spells on the ecosystems in Central Europe still needs to be investigated thoroughly. Ziegeleigrube Coenen (ZC) is a late Pleistocene MIS 3 locality in the Lower Rhine Embayment of Germany, radiocarbon-dated to > 34 14C ka BP. The site yielded a broad spectrum of mammal species. We investigated the carbon (δ13C), nitrogen (δ15N) and sulfur (δ34S) isotope signatures of bone collagen, since these are valuable tools in characterizing ecological niches, environmental conditions and aspects of climate and mobility. By comparison with pre- and post-Last Glacial Maximum (LGM) sites in Central Europe we show that ZC belongs in a cold event of MIS 3 and was climatically more similar to post-LGM sites than to pre-LGM sites. However, the trophic structure resembled that of typical pre-LGM sites in Belgium. This cold event in MIS 3 changed the bottom of the foodweb, but do not seem to have had a direct impact on the occurrence of the mammalian species and their ecological distribution. Apparently the (mega-) faunal community could adapt also to harsher environmental conditions during MIS 3.
WIELDING THE EPOKOLO: CORPORAL PUNISHMENT AND TRADITIONAL AUTHORITY IN COLONIAL OVAMBOLAND
Authors: JONES DAVID CRAWFORD
Published: June 2015

Based on both archival research and oral interviews conducted in northern Namibia, this article traces the history of public flogging in Ovamboland throughout the twentieth century. In contrast to recent scholarship that views corporal punishment in modern Africa mainly through the lens of colonial governance, the article argues that because the South African colonial state never withdrew the power to punish from the region's traditional authorities, these indigenous leaders were able to maintain a degree of legitimacy among their subjects, who looked to the kings and headmen to punish wrongdoers and maintain communal norms. Finally, the article explores why nostalgia for corporal punishment remains a salient feature in Namibian society today, 25 years after the end of colonial rule.
FROM ‘MIGRANTS’ TO ‘REFUGEES’: IDENTITY, AID, AND DECOLONIZATION IN NGARA DISTRICT, TANZANIA
Authors: ROSENTHAL JILL
Published: June 2015

This article argues that international aid to Rwandan refugees in Ngara district during decolonization unfolded as part of a broader project of nation-state formation and regulation – one that deeply affected local narratives of community and belonging. While there is an extensive scholarship on decolonization and nationalism, we know less about the history of the nation-state as a refugee-generating project, and the role of international aid agencies therein. The history of Rwandan refugees in Ngara district, Tanzania, reveals the constitutive relationship between nation-building and refugee experiences, illustrating that during decolonization local political imaginations congealed around internationally-reified categorizations of the ‘refugee’ and the ‘citizen’.
Innocents Abroad? Liberal Educators in Illiberal Societies
Authors: Sleeper Jim
Published: June 2015

It might seem an American Dream come true: About 100 Massachusetts Institute of Technology professors, ten at a time, are managing five laboratories stocked with “totally state-of-the-art equipment” in a gleaming new tower on the National University of Singapore campus. As the New York Times reports, the campus houses the Singapore-MIT Alliance for Research and Technology and other projects, involving “world-class universities from Britain, China, France, Germany, Israel and Switzerland.” The MIT professors and their forty PhD and postdoctoral researchers are designing “myriad innovations”: driverless cars that would respond to “killer app” sensors throughout Singapore; stingray-like robots that will collect ocean-bottom data to fight noxious algae; and technologies that will track infectious diseases, energy consumption, and other movements in this tightly run, wealthy city-state of 5.4 million people.
Just War Theory and the Last of Last Resort
Authors: Aloyo Eamon
Published: June 2015

The last resort criterion has a hallowed place in the just war theory tradition. Many leading just war theory scholars accept it as ajus ad bellumrequirement and some powerful politicians reference it. While there are several versions of last resort, many take it to mean that peaceful options that have a reasonable chance of achieving a just cause must be exhausted before the use of force is permissible. Its justification is straightforward and commonsensical: war is terrible, inevitably results in the deaths of numerous innocents and destruction of their property, and thus should be avoided whenever possible. I argue that last resort should be dropped from the just war tradition because its inclusion in the just war tradition can result in a greater number of harms to innocents than if the precept did not exist. What should matter morally is the severity and numbers of harms inflicted on innocents, not whether those harms are inflicted violently or nonviolently. I suggest that in the context of achieving a just cause, the only actions that are permissible are those that are likely to inflict the fewest morally weighted harms and that meet the other just war theory precepts (excluding last resort). Three accounts of last resort do not permit this, whereas while a fourth does, it is redundant with an important account of thejus ad bellumproportionality precept. Thus violent policies may be preferable in some rare circumstances to nonviolent alternatives such as non-targeted sanctions and negotiations because nonviolent policies sometimes are more likely to foreseeably and avoidably result in far greater harms to innocents than violent options.
Occlusion rate, venous symptoms and patient satisfaction after radiofrequency-induced thermotherapy (RFITT®): are there differences between the great and the small saphenous veins?
Authors: Doerler Martin , Blenkers Thomas , Reich-Schupke Stefanie , Altmeyer Peter , Stücker Markus
Published: June 2015

Background: Previous studies on the therapy of insufficient saphenous veins mainly compare different treatment methods. Only a few investigate differences of a specific treatment option between the great (GSV) and the small saphenous vein (SSV). The aim of this study was to evaluate the efficacy, clinical improvement and patient satisfaction after radiofrequency-induced thermotherapy (RFITT®) with regard to the treated vein. Patients and methods: We included 65 patients (40 women, 25 men; mean age 54.75 years) who were treated with RFITT® for incompetent saphenous veins (n = 83: 62 GSV, 21 SSV). Occlusion rates were determined by duplex-sonography. Additionally, we performed a prospective analysis of venous symptoms and signs by means of a standardized questionnaire and of patient satisfaction using a semi-quantitative rating (1 = very good, 6 = insufficient). Results: The GSV group showed a significantly greater reduction of venous symptoms in comparison to the SSV group (p = 0.005) despite no significant differences in long term occlusion rates (mean time after operation: 22 months) of 90 % in the GSV group and 81.8 % in the SSV group (p = 0.598). Following the procedure, detailed analysis revealed significantly more swelling (p = 0.022), feeling of heavy legs (p = 0.002) and nightly calf cramps (p = 0.001) in the SSV group. Additionally, RFITT® led to a significant improvement in patient satisfaction in the GSV group (from 1.93 at day 1 - 3 to 1.41 after 6 - 12 months, p = 0.009) but not in the SSV group (from 2.29 to 2.07, p = 0.43). Conclusions: With regard to the improvement of venous symptoms and patient satisfaction, the benefit of RFITT® is greater for patients with incompetent GSV compared to those with incompetent SSV.
In welchem Zusammenhang stehen quälende Beinschmerzen und eine intrauterine Spirale?
Authors: Jäckel Kristian , Braschler Thomas , Jochum Wolfram , Hülder Tanja , Knechtle Beat
Published: June 2015

Wir berichten über eine typische klinische Verlaufsform einer pelvinen Aktinomykose: Nach anfänglich uncharakteristischen Beschwerden entwickelt sich eine systemische Erkrankung, die mit einer pelvinen Masse einhergeht, die so schnell wächst, dass man die weiteren Symptome auf ihre Wachstumsgeschwindigkeit und die systemische Infektion zurückführen kann – Müdigkeit, Bauchschmerzen, Miktionsstörung und Beinschmerzen. Erst intraoperativ konnte die klare Unterscheidung zwischen einem malignen Tumor und einer pelvinen Aktinomykose getroffen werden. Nach Hysterektomie und unter Antibiose erholte sich die Patientin rasch.
Imaging of built-in electric field at a p-n junction by scanning transmission electron microscopy
Authors: Shibata Naoya , Findlay Scott D. , Sasaki Hirokazu , Matsumoto Takao , Sawada Hidetaka , Kohno Yuji , Otomo Shinya , Minato Ryuichiro , Ikuhara Yuichi
Published: June 2015

Precise measurement and characterization of electrostatic potential structures and the concomitant electric fields at nanodimensions are essential to understand and control the properties of modern materials and devices. However, directly observing and measuring such local electric field information is still a major challenge in microscopy. Here, differential phase contrast imaging in scanning transmission electron microscopy with segmented type detector is used to image a p-n junction in a GaAs compound semiconductor. Differential phase contrast imaging is able to both clearly visualize and quantify the projected, built-in electric field in the p-n junction. The technique is further shown capable of sensitively detecting the electric field variations due to dopant concentration steps within both p-type and n-type regions. Through live differential phase contrast imaging, this technique can potentially be used to image the electromagnetic field structure of new materials and devices even under working conditions.
Early detection and late cognitive control of emotional distraction by the prefrontal cortex
Authors: García-Pacios Javier , Garcés Pilar , Del Río David , Maestú Fernando
Published: June 2015

Unpleasant emotional distraction can impair the retention of non-emotional information in working memory (WM). Research links the prefrontal cortex with the successful control of such biologically relevant distractors, although the temporal changes in this brain mechanism remain unexplored. We use magnetoencephalography to investigate the temporal dynamics of the cognitive control of both unpleasant and pleasant distraction, in the millisecond (ms) scale. Behavioral results demonstrate that pleasant events do not affect WM maintenance more than neutral ones. Neuroimaging results show that prefrontal cortices are recruited for the rapid detection of emotional distraction, at early latencies of the processing (70-130 ms). Later in the processing (360-450 ms), the dorsolateral, the medial and the orbital sections of the prefrontal cortex mediate the effective control of emotional distraction. In accordance with the behavioral performance, pleasant distractors do not require higher prefrontal activity than neutral ones. These findings extend our knowledge about the brain mechanisms of coping with emotional distraction in WM. In particular, they show for the first time that overriding the attentional capture triggered by emotional distractors, while maintaining task-relevant elements in mind, is based on the early detection of such linked-to-survival information and on its later cognitive control by the prefrontal cortex.
Statistical iterative reconstruction algorithm for X-ray phase-contrast CT
Authors: Hahn Dieter , Thibault Pierre , Fehringer Andreas , Bech Martin , Koehler Thomas , Pfeiffer Franz , Noël Peter B.
Published: June 2015

Grating-based phase-contrast computed tomography (PCCT) is a promising imaging tool on the horizon for pre-clinical and clinical applications. Until now PCCT has been plagued by strong artifacts when dense materials like bones are present. In this paper, we present a new statistical iterative reconstruction algorithm which overcomes this limitation. It makes use of the fact that an X-ray interferometer provides a conventional absorption as well as a dark-field signal in addition to the phase-contrast signal. The method is based on a statistical iterative reconstruction algorithm utilizing maximum-a-posteriori principles and integrating the statistical properties of the raw data as well as information of dense objects gained from the absorption signal. Reconstruction of a pre-clinical mouse scan illustrates that artifacts caused by bones are significantly reduced and image quality is improved when employing our approach. Especially small structures, which are usually lost because of streaks, are recovered in our results. In comparison with the current state-of-the-art algorithms our approach provides significantly improved image quality with respect to quantitative and qualitative results. In summary, we expect that our new statistical iterative reconstruction method to increase the general usability of PCCT imaging for medical diagnosis apart from applications focused solely on soft tissue visualization.
Biochemical properties and yields of diverse bacterial laccase-like multicopper oxidases expressed in Escherichia coli
Authors: Ihssen Julian , Reiss Renate , Luchsinger Ronny , Thöny-Meyer Linda , Richter Michael
Published: June 2015

Laccases are multi-copper oxidases that oxidize a broad range of substrates at the expense of molecular oxygen, without any need for co-factor regeneration. These enzymes bear high potential for the sustainable synthesis of fine chemicals and the modification of (bio)polymers. Here we describe cloning and expression of five novel bacterial laccase-like multi copper oxidases (LMCOs) of diverse origin which were identified by homology searches in online databases. Activity yields under different expression conditions and temperature stabilities were compared to three previously described enzymes from Bacillus subtilis, Bacillus pumilus and Bacillus clausii. In almost all cases, a switch to oxygen-limited growth conditions after induction increased volumetric activity considerably. For proteins with predicted signal peptides for secretion, recombinant expression with and without signal sequence was investigated. Bacillus CotA-type LMCOs outperformed enzymes from Streptomyces and Gram-negative bacteria with respect to activity yields in Escherichia coli and application relevant biochemical properties. The novel Bacillus coagulans LMCO combined high activity yields in E. coli with unprecedented activity at strong alkaline pH and high storage stability, making it a promising candidate for further development.
VRK1 regulates Cajal body dynamics and protects coilin from proteasomal degradation in cell cycle
Authors: Cantarero Lara , Sanz-García Marta , Vinograd-Byk Hadar , Renbaum Paul , Levy-Lahad Ephrat , Lazo Pedro A.
Published: June 2015

Cajal bodies (CBs) are nuclear organelles associated with ribonucleoprotein functions and RNA maturation. CBs are assembled on coilin, its main scaffold protein, in a cell cycle dependent manner. The Ser-Thr VRK1 (vaccinia-related kinase 1) kinase, whose activity is also cell cycle regulated, interacts with and phosphorylates coilin regulating assembly of CBs. Coilin phosphorylation is not necessary for its interaction with VRK1, but it occurs in mitosis and regulates coilin stability. Knockdown of VRK1 or VRK1 inactivation by serum deprivation causes a loss of coilin phosphorylation in Ser184 and of CBs formation, which are rescued with an active VRK1, but not by kinase-dead VRK1. The phosphorylation of coilin in Ser184 occurs during mitosis before assembly of CBs. Loss of coilin phosphorylation results in disintegration of CBs and of coilin degradation that is prevented by proteasome inhibitors. After depletion of VRK1, coilin is ubiquitinated in nuclei, which is partly mediated by mdm2, but its proteasomal degradation occurs in cytosol and is prevented by blocking its nuclear export. We conclude that VRK1 is a novel regulator of CBs dynamics and stability in cell cycle by protecting coilin from ubiquitination and degradation in the proteasome and propose a model of CB dynamics.
Caveolin-1 is Associated with Tumor Progression and Confers a Multi-Modality Resistance Phenotype in Pancreatic Cancer
Authors: Chatterjee Moumita , Ben-Josef Edgar , Thomas Dafydd G. , Morgan Meredith A. , Zalupski Mark M. , Khan Gazala , Andrew Robinson Charles , Griffith Kent A. , Chen Ching-Shih , Ludwig Thomas , Bekaii-Saab Tanios , Chakravarti Arnab , Williams Terence M.
Published: June 2015

Caveolin-1 (Cav-1) is a 21 kDa protein enriched in caveolae and has been implicated in oncogenic cell transformation, tumorigenesis and metastasis. We explored roles for Cav-1 in pancreatic cancer (PC) prognostication, tumor progression, resistance to therapy and whether targeted downregulation could lead to therapeutic sensitization. Cav-1 expression was assessed in cell lines, mouse models and patient samples and knocked down in order to compare changes in proliferation, invasion, migration, response to chemotherapy and radiation and tumor growth. We found Cav-1 is overexpressed in human PC cell lines, mouse models and human pancreatic tumors and is associated with worse tumor grade and clinical outcomes. In PC cell lines, disruption/depletion of caveolae/Cav-1 reduces proliferation, colony formation and invasion. Radiation and chemotherapy up-regulate Cav-1 expression, while Cav-1 depletion induces both chemosensitization and radiosensitization through altered apoptotic and DNA repair signaling. In vivo, Cav-1 depletion significantly attenuates tumor initiation and growth. Finally, Cav-1 depletion leads to altered JAK/STAT, JNK and Src signaling in PC cells. Together, higher Cav-1 expression is correlated with worse outcomes, is essential for tumor growth and invasion (both in vitro and in vivo), is responsible for promoting resistance to therapies and may serve as a prognostic/predictive biomarker and target in PC.
Atomic-layer molybdenum sulfide optical modulator for visible coherent light
Authors: Zhang Yuxia , Wang Shuxian , Yu Haohai , Zhang Huaijin , Chen Yanxue , Mei Liangmo , Di Lieto Alberto , Tonelli Mauro , Wang Jiyang
Published: June 2015

Coherent light sources in the visible range are playing important roles in our daily life and modern technology, since about 50% of the capability of the our human brains is devoted to processing visual information. Visible lasers can be achieved by nonlinear optical process of infrared lasers and direct lasing of gain materials and the latter has advantages in the aspects of compactness, efficiency, simplicity, etc. However, due to lack of visible optical modulators, the directly generated visible lasers with only a gain material are constrained in continuous-wave operation. Here, we demonstrated the fabrication of a visible optical modulator and pulsed visible lasers based on atomic-layer molybdenum sulfide (MoS2), a ultrathin two-dimensional material with about 9–10 layers. By employing the nonlinear absorption of the modulator, the pulsed orange, red and deep red lasers were directly generated. Besides, the present atomic-layer MoS2 optical modulator has broadband modulating properties and advantages in the simple preparation process. The present results experimentally verify the theoretical prediction for the low-dimensional optoelectronic modulating devices in the visible wavelength region and may open an attractive avenue for removing a stumbling block for the further development of pulsed visible lasers.
RETRACTED ARTICLE: Obesity-induced adipokine imbalance impairs mouse pulmonary vascular endothelial function and primes the lung for injury
Authors: Shah Dilip , Romero Freddy , Duong Michelle , Wang Nadan , Paudyal Bishnuhari , Suratt Benjamin T. , Kallen Caleb B. , Sun Jianxin , Zhu Ying , Walsh Kenneth , Summer Ross
Published: June 2015

Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese mice expressed higher levels of leukocyte adhesion markers and lower levels of cell-cell junctional proteins when compared to lean mice. We tested whether systemic factors are responsible for these alterations in the pulmonary endothelium; treatment of primary lung endothelial cells with obese serum enhanced the expression of adhesion proteins and reduced the expression of endothelial junctional proteins when compared to lean serum. Alterations in pulmonary endothelial cells observed in obese mice were associated with enhanced susceptibility to LPS-induced lung injury. Restoring serum adiponectin levels reversed the effects of obesity on the lung endothelium and attenuated susceptibility to acute injury. Our work indicates that obesity impairs pulmonary vascular homeostasis and enhances susceptibility to acute injury and provides mechanistic insight into the increased prevalence of ARDS in obese humans.
Toward a Green Laboratory: One Reaction at a Time
Authors: Shuster Leanna E. , Redman Anikó M.
Published: June 2015

The choice of small scale reaction conditions in drug discovery can have significant impact, both in cumulative material use throughout the industry and by influencing methods of further scale-up processes. Design of synthetic routes and choice of solvents and reagents are discussed along with greener techniques for reaction setup and workup. Specific examples are highlighted to provide chemists with a wider range of synthetic options beyond the scope of traditional medicinal chemistry practices.
Applying Green Chemistry Principles in Biologics Drug Development
Authors: Budzinski Kristi L.
Published: June 2015

Biologics are an ever-growing sector of the pharmaceutical industry driven predominately by the approval of monoclonal antibody therapies. Biologics are a widely diverse group of compounds including peptides, proteins, antibodies, and some vaccines, which provide an equally wide range of therapeutic benefits. Manufactured by living cells (with the exception of peptides), biologics were generally considered to be environmentally friendly pharmaceuticals. However, biologics drug research, development, and production consume large quantities of water and energy, require the use of caustic acids and bases, significant volumes of single-use plastics and filters, and other raw materials that can be hazardous at the required concentrations for manufacturing. Several initial environmental analyses have been performed for biologics production and underscore the need for incorporating sustainability into the development process. The principles of green chemistry provide an excellent starting point for this endeavor but must be modified to represent the needs of biologics drug development. This chapter provides an overview of the biologics drug production process and how green biologics principles can guide development methodologies and processes to reduce the environmental impact of biologics.
The Need for a Green Electronic Lab Notebook
Authors: Clark Alex M. , Ekins Sean
Published: June 2015

Green chemistry is currently underserved by chemical informatics. One approach that software can be used to accelerate the adoption of green chemistry principles is by capturing the complete definition of a chemical reaction using an electronic lab notebook. By designing the data-structures, algorithms, and supporting databases into the software, the opportunity exists to make planning and recording of environmentally favorable reactions both easier and more accessible to a larger audience of chemists who are not experts in the field of green chemistry. These tools include always-on calculation of metrics such as process mass intensity, E-factor, and atom economy; facile structure-based lookup of appropriate solvents, sustainable feedstocks, and troublesome reagents or byproducts; use of ligand-based models for various kinds of toxicity; and partial or complete lookup of reaction transforms curated from the green chemistry literature. These benefits stand in addition to the many well-established reasons for recording chemical reactions in an electronic format. Incorporation of relevant chemistry data and calculations into the tools of everyday use by practicing chemists has the potential to lower the barrier to evaluating more sustainable chemistry options, with the goal being to make optimization of green chemistry properties as universal and straightforward as calculating yield.
Environmental Regulations and the Green Chemist
Authors: Taylor David
Published: June 2015

Although the pharmaceutical industry is known to be a highly regulated one, most people are only aware of the impact of legislation arising from the medical regulators such as FDA in the USA and EMA in the European Union. However, all scientists, including those who work in the pharmaceutical sector, are subject to environmental regulations, and in some cases these can have major impacts on many aspects of their work. This chapter explores the range of environmental legislation that impacts on the work of medicinal chemists in the pharmaceutical industry, from the direct impact of health safety and environmental regulation in the laboratory to indirect impacts on manufacturing routes and the products themselves.
Patent Protection and Green Chemistry Innovation
Authors: Cohen Andrew D. , Trask Andrew V.
Published: June 2015

A great deal of innovation is required to discover and develop a new drug, and a great deal more is needed to develop products and processes that merit the “green chemistry” label. Not all of that innovation is patentable, however. To be awarded a patent, an invention must meet the criteria set out in the patent laws. Although patent laws vary by country, they typically share many common principles. This chapter focuses on the patent laws of the United States of America. It begins with a summary of patentability criteria. It then describes some examples of patents covering inventions in the field of green pharmaceutical chemistry. The chapter next describes a few pertinent case law examples. Finally, the chapter sets out some considerations on patent strategy for inventions involving green chemistry in the pharmaceutical field.
Rhodium(iii)-catalyzed cyanation of vinylic C–H bonds: N-cyano-N-phenyl-p-toluenesulfonamide as a cyanation reagent
Authors: Su Wei , Gong Tian-Jun , Xiao Bin , Fu Yao
Published: June 2015

Rh(iii)-catalyzed direct vinylic C–H cyanation reaction has been developed as a practical method for the synthesis of alkenyl nitriles.
Nickel-catalyzed asymmetric transfer hydrogenation of conjugated olefins
Authors: Guo Siyu , Yang Peng , Zhou Jianrong (Steve)
Published: June 2015

A nickel catalyst is used for asymmetric hydrogenation of electron-deficient olefins using formic acid as hydrogen source.
Copper(ii)-catalyzed oxidative N-nitrosation of secondary and tertiary amines with nitromethane under an oxygen atmosphere
Authors: Sakai Norio , Sasaki Minoru , Ogiwara Yohei
Published: June 2015

The combination of Cu(OTf)2 and DBU under an O2 atmosphere effectively promoted the N-nitrosation of both secondary aromatic/aliphatic amines and tertiary aromatic amines with nitromethane (CH3NO2).
Mechanism of the hydroxyl radical oxidation of methacryloyl peroxynitrate (MPAN) and its pathway toward secondary organic aerosol formation in the atmosphere
Authors: Nguyen Tran B. , Bates Kelvin H. , Crounse John D. , Schwantes Rebecca H. , Zhang Xuan , Kjaergaard Henrik G. , Surratt Jason D. , Lin Peng , Laskin Alexander , Seinfeld John H. , Wennberg Paul O.
Published: June 2015

The photooxidation of MPAN forms an energetic alkyl radical that promptly cyclizes, producing an α-lactone that participates in particle-phase chemistry.
The rotational barrier of ethane and some of its hexasubstituted derivatives in terms of the forces acting on the electron distribution
Authors: Cortés-Guzmán Fernando , Cuevas Gabriel , Martín Pendás Ángel , Hernández-Trujillo Jesús
Published: June 2015

The rotational barrier of ethane and some of its hexasubstituted derivatives is mainly a consequence of the decrease of the attractive forces acting on the electron density of the central C atoms.
Mechanisms of AC losses in magnetic fluids based on substituted manganites
Authors: Kalita V. M. , Tovstolytkin A. I. , Ryabchenko S. M. , Yelenich O. V. , Solopan S. O. , Belous A. G.
Published: June 2015

Dependence of heating efficiency vs. magnetic field for magnetic fluid based on La0.78Sr0.22MnO3 nanoparticles provides information about the mechanism of AC losses.
Synthesis and characterization of novel niccolites [(CH3)2NH2][FeIIIMII(HCOO)6] (MII= Zn, Ni, Cu)
Authors: Ciupa Aneta , Mączka Mirosław , Gągor Anna , Pikul Adam , Ptak Maciej
Published: June 2015

We report the synthesis, structural, magnetic, Raman and IR studies of novel niccolite-type heterometallic [(CH3)2NH2][FeIIIMII(HCOO)6] compounds (MII= Ni, Zn and Cu). The Ni and Cu compounds order ferromagnetically at 42 and 28.5 K, respectively. The monoclinic Cu member exhibits different structural changes on cooling than the trigonal Zn and Ni compounds.
Production of methyl levulinate from cellulose: selectivity and mechanism study
Authors: Ding Daqian , Xi Jinxu , Wang Jianjian , Liu Xiaohui , Lu Guanzhong , Wang Yanqin
Published: June 2015

An efficient and environmentally friendly catalytic process for the production of methyl levulinate through cellulose alcoholysis was developed. The formation of methyl levulinate follows the sequence: cellulose → methyl glucoside → 5-MMF → methyl levulinate, and Brönsted acid played a key role in its high selectivity.
Speciation of metal-based nanomaterials in human serum characterized by capillary electrophoresis coupled to ICP-MS: a case study of gold nanoparticles
Authors: Matczuk Magdalena , Anecka Karolina , Scaletti Federica , Messori Luigi , Keppler Bernhard K. , Timerbaev Andrei R. , Jarosz Maciej
Published: June 2015

A high-resolution CE-ICP-MS method is presented for monitoring and comprehensive understanding of the protein-mediated transformations of gold nanoparticles in human serum.
Reaction of a bulky amine borane with lanthanide trialkyls. Formation of alkyl lanthanide imide complexes
Authors: Li Jianfeng , Gao Dongjing , Hu Hongfan , Cui Chunming
Published: June 2015

Lanthanide imidoborane complexes with terminal alkyl groups are synthesized from the reactions of simple lanthanide trialkyls with a bulky amine borane.
Stable iso-bacteriochlorin mimics from porpholactone: effect of a β-oxazolone moiety on the frontier π-molecular orbitals
Authors: Yu Yi , Furuyama Taniyuki , Tang Juan , Wu Zhuo-Yan , Chen Jia-Zhen , Kobayashi Nagao , Zhang Jun-Long
Published: June 2015

A β-oxazolone moiety on porpholactone plays an important role in stabilizing such hydroporphyrin structures through tuning energy gaps between the frontier π-molecular orbitals, which is verified by MCD studies combined with TD-DFT calculations.
Syntheses of sceptrins and nakamuric acid and insights into the biosyntheses of pyrrole–imidazole dimers
Authors: Wang Xiaolei , Gao Yang , Ma Zhiqiang , Rodriguez Rodrigo A. , Yu Zhi-Xiang , Chen Chuo
Published: June 2015

The SET-promoted homodimerization of pyrrole–imidazole alkaloids is a stepwise reaction favoring the [2 + 2] pathway.