bluuebunny/crossref_metadata_2025 huggingface dataset:
Localized Multi‐Component Delivery Platform Generates Local and Systemic Anti‐Tumor Immunity
Authors: Acharya Abhinav P. , Sinha Mantosh , Ratay Michelle L. , Ding Xiaochu , Balmert Stephen C. , Workman Creg J. , Wang Yadong , Vignali Dario A. A. , Little Steven R.
Published: December 2016

As tumors employ complementary overlapping and/or independent mechanisms to evade immune surveillance, many emerging cancer immunotherapies attempt to target multiple pathways to eradicate malignant cells. Although modulation of independent pathways by simultaneous administration of multiple immune modulators (e.g., checkpoint inhibitors, cytokines, and growth factors) has shown great promise, the clinical impact remains limited due to severe toxicity associated with high systemic levels of many of these drugs. Therefore, novel platforms for efficient delivery of multi‐component therapies at lower effective doses would be enabling. Here, a drug delivery platform called immunomodulatory molecule delivery system (iMods), which provides sustained extracellular delivery of a checkpoint inhibitor (anti‐PD‐L1) and simultaneously, targeted intracellular delivery of a tumor antigen (OVA) along with adjuvant (poly(I:C)), and the indoleamine deoxygenase inhibitor 1‐MT is described. In melanoma tumor‐bearing mice, combinatorial delivery of these factors with iMods leads to regression of both treated and untreated (contralateral) melanoma tumors and 100% survival. These promising therapeutic outcomes are attributed to significantly enhanced ratios of anti‐tumor CD8 T‐cell/tumor‐protective regulatory T‐cell (Treg) in tumors and tumor draining lymph nodes. Overall, the iMods delivery platform described here represents a promising advance in multi‐factor cancer immunotherapy.
Field‐Switchable Broadband Polarizer Based on Reconfigurable Nanowire Assemblies
Authors: Boehm Sarah J. , Kang Lei , Werner Douglas H. , Keating Christine D.
Published: December 2016

Reconfigurability is one of the most critical properties of nanophotonic systems and, consequently, methods for enabling a significant degree of functionality are highly sought after. However, dynamically responsive control in top‐down fabricated photonic structures often requires extreme conditions and yields moderate modulation capability. In sharp contrast to top‐down methods, directed self‐assembly of micro‐ and nanoparticles offers a distinct avenue for reconfigurable photonics. In the present work, gold nanowire lattices are formed via electric field directed assembly in order to take advantage of their collective optical properties. The lattices are reconfigured on‐demand between two different functional states, in the form of broadband polarizers. By selectively switching the electric field between two orthogonal electrode pairs, a maximum transmission contrast of ≈50% is observed in the near‐infrared regime. Moreover, the reconfigurable transmission spectra, which are highly dependent on the nanowire size and electric field conditions, are reversible. The demonstrated proof‐of‐concept nanowire lattice polarizer provides potential for electrically reconfigurable photonic devices such as ultra‐compact polarization components, electro‐optic switches, and on‐chip modulators.
Synthesis of Hydroxy‐Substituted p‐Terphenyls and some Larger Oligophenylenes via Palladium on Charcoal Catalyzed Suzuki‐Miyaura Reaction
Authors: Jansa Josef , Řezníček Tomáš , Jambor Roman , Bureš Filip , Lyčka Antonín
Published: December 2016

A ligand‐free heterogeneous palladium on charcoal (Pd/C)‐catalyzed Suzuki‐Miyaura cross‐coupling has been performed. The series of substituted p‐terphenyls were prepared in very good yields without exclusion of air and with low catalyst loadings. Moreover, the developed environmentally benign and scalable protocol enables to use electron poor and sterically hindered boronic acids.

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Cobalt‐Catalyzed Mild Ring‐Opening Addition of Arenes C−H Bond to 7‐Oxabicyclic Alkenes
Authors: Muralirajan Krishnamoorthy , Prakash Sekar , Cheng Chien‐Hong
Published: December 2016

A mild approach for a Cp*Co(III)‐catalyzed C−H naphthylation of arenes by 7‐oxabicyclic alkenes has been developed. In some cases, intermediate products with a 1,2‐dihydronaphthalen‐1‐ol group have been isolated at room temperature in good yield. The catalytic reaction proceeds via C−H activation, insertion, β‐oxygen elimination, protonation, and dehydration, respectively. These simple protocols, featuring mild conditions and tolerance of functional groups, exhibit great potential for a variety of synthetic applications.

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Acetic Acid Accelerated Visible‐Light Photoredox Catalyzed N‐Demethylation of N,N‐Dimethylaminophenyl Derivatives
Authors: Wu Guolin , Li Yazhen , Yu Xuemei , Gao Yu , Chen Haijun
Published: December 2016

N,N‐Dimethylaminophenyl moiety is a common fragment in medicinal chemistry as several pharmaceuticals bearing this privileged motif are on the market and under clinical evaluation. Oxidative N‐demethylation is generally regarded as the major metabolic pathway. However, pharmacokinetics, metabolites studies as well as the further structural modification are precluded by the impracticality of chemical synthesis. Here we report that acetic acid can significantly accelerate visible‐light photoredox catalyzed N‐demethylation of N,N‐dimethylaminophenyl derivatives. This approach is easy for large scale reaction and even for potential industrial manufacture.

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Modulating the Surface via Polymer Brush for High‐Performance Inkjet‐Printed Organic Thin‐Film Transistors
Authors: Ge Feng , Wang Xiaohong , Zhang Yunfeng , Song Eunjoo , Zhang Guobing , Lu Hongbo , Cho Kilwon , Qiu Longzhen
Published: December 2016

A strategy is reported to control the morphologies of inkjet‐printed small organic molecule semiconductor by modifying printed surfaces with polymer brushes. Polystyrene (PS) brushes with different chain lengths from 1.66 to 7.35 nm are grafted onto a dielectric surface via surface‐initiated atom transfer radical polymerization to form uniform, hydrophobic surfaces. Single droplets of 6,13‐bis(triisopropylsilylethynyl) pentacene (TIPS‐pentacene) are then inkjet‐printed onto these PS brush‐modified substrates. TIPS‐pentacene crystals are obtained with different morphologies depending on the chain length of the PS brushes. Short PS chains behave like self‐assembled monolayers on the dielectric surface such that small crystals are formed with random orientations. Longer PS chains become partially extended in the solvent altering ink spreading, contact‐line pinning, solute migration, and ultimately crystallization. Large self‐assembled crystals are generated with highly oriented structures. Organic thin film transistors are fabricated by printing single dots of TIPS‐pentacene. The device based on PS brushes of 5.14 nm exhibits the optimal device performances with an average mobility of 0.35 ± 0.23 cm2 V−1 s−1. These results demonstrate that these polymer brushes provide a route toward further understanding inkjet‐printing techniques for high‐performance organic electronics.
Construction of Chiral Tetraorganosilicons by Tandem Desymmetrization of Silacyclobutanes/Intermolecular Dehydrogenative Silylation
Authors: Zhang Qing‐Wei , An Kun , Liu Li‐Chuan , Zhang Qi , Guo Huifang , He Wei
Published: December 2016

We report a method to construct chiral tetraorganosilicons by tandem silacyclobutane (SCB) desymmetrization–dehydrogenative silylations. A wide array of dibenzosiloles with stereogenic quaternary silicon centers were obtained in good yields and enantioselectivities up to 93 % ee. Chiral TMS‐segphos was found to be a superior ligand in terms of reactivity and enantioselectivity.
Total Synthesis of (−)‐Histrionicotoxin through a Stereoselective Radical Translocation–Cyclization Reaction
Authors: Sato Manabu , Azuma Hiroki , Daigaku Akihiro , Sato Sota , Takasu Kiyosei , Okano Kentaro , Tokuyama Hidetoshi
Published: December 2016

Stereoselective total syntheses of (−)‐histrionicotoxin and (−)‐histrionicotoxin 235A are described. The 1‐azaspiro[5.5]undecane skeleton was constructed diastereoselectively by a radical translocation–cyclization reaction involving a chiral cyclic acetal; the use of tris(trimethylsilyl)silane was crucial for the high diastereoselectivity. The cyclization product was converted into (−)‐histrionicotoxin 235A through a one‐pot partial‐reduction–allylation reaction of a derivative containing an unprotected lactam. Finally, two terminal alkenes were transformed into enynes with the 1,3‐amino alcohol protected as an oxathiazolidine oxide to complete the total synthesis of (−)‐histrionicotoxin.
Structural Basis of Sirtuin 6 Activation by Synthetic Small Molecules
Authors: You Weijie , Rotili Dante , Li Tie‐Mei , Kambach Christian , Meleshin Marat , Schutkowski Mike , Chua Katrin F. , Mai Antonello , Steegborn Clemens
Published: December 2016

Sirtuins are protein deacylases regulating metabolism and stress responses, and are implicated in aging‐related diseases. Small molecule activators for the human sirtuins Sirt1‐7 are sought as chemical tools and potential therapeutics, such as for cancer. Activators are available for Sirt1 and exploit its unique N‐terminus, whereas drug‐like activators for Sirt2–7 are lacking. We synthesized and screened pyrrolo[1,2‐a]quinoxaline derivatives, yielding the first synthetic Sirt6 activators. Biochemical assays show direct, substrate‐independent compound binding to the Sirt6 catalytic core and potent activation of Sirt6‐dependent deacetylation of peptide substrates and complete nucleosomes. Crystal structures of Sirt6/activator complexes reveal that the compounds bind to a Sirt6‐specific acyl channel pocket and identify key interactions. Our results establish potent Sirt6 activation with small molecules and provide a structural basis for further development of Sirt6 activators as tools and therapeutics.
Buttressing Salicylaldehydes: A Multipurpose Directing Group for C(sp3)−H Bond Activation
Authors: Yada Akira , Liao Wenqing , Sato Yuta , Murakami Masahiro
Published: December 2016

A palladium‐catalyzed reaction of primary amines with iodoarenes produces γ‐arylated primary amines. A bulky salicylaldehyde, which is marked as easily available, installable, removable, and recoverable, plays a key role in directing palladium to site‐selectively activate the C−H bond located γ to the amino group.
Effects of Hydroxychloroquine in Patients With Cutaneous Lupus Erythematosus: A Multicenter, Double‐Blind, Randomized, Parallel‐Group Trial
Authors: Yokogawa N. , Eto H. , Tanikawa A. , Ikeda T. , Yamamoto K. , Takahashi T. , Mizukami H. , Sato T. , Yokota N. , Furukawa F.
Published: December 2016

Objective

To assess the efficacy and tolerability of hydroxychloroquine (HCQ) in patients with cutaneous lupus erythematosus (CLE), in a phase III clinical trial conducted in Japan.

Methods

We conducted a double‐blind, randomized, parallel‐group clinical trial. This was a baseline‐controlled study, and the group differences were evaluated in an exploratory analysis. A total of 103 patients with active CLE (according to a Cutaneous Lupus Erythematosus Disease Area and Severity Index [CLASI] activity score of ≥4) were included. Patients were randomized 3:1 to receive HCQ or placebo during the 16‐week double‐blind period, and all patients were given HCQ during the following 36‐week single‐blind period. The primary efficacy end point was a reduction in the CLASI activity score at week 16. The secondary end points included the central photo evaluation (5‐point scale), patient's global assessment (7‐point scale), the Skindex‐29 score, and investigator's global assessment (7‐point scale, based on the other 3 secondary end points). In patients with systemic lupus erythematosus, fatigue and musculoskeletal pain were assessed. Safety was assessed up to week 55.

Results

The mean CLASI score at week 16 was significantly improved from baseline in both the HCQ group and the placebo group: mean change −4.6 (95% confidence interval [95% CI] −6.1, −3.1) (P < 0.0001), and mean change −3.2 (95% CI −5.1, −1.3) (P = 0.002), respectively, without between‐group difference (P = 0.197). The investigator's global assessment demonstrated a greater proportion of “improved” and “remarkably improved” patients in the HCQ group (51.4% versus 8.7% in the placebo group [P = 0.0002 between groups]). The other secondary end points supported the efficacy of HCQ. Cellulitis, drug eruption, hepatic dysfunction, and Stevens‐Johnson syndrome were shown to be serious adverse events related to HCQ use.

Conclusion

The results of this randomized clinical trial support the efficacy and tolerability of HCQ in patients with CLE.
Build personal relationships with students for a safe campus
Authors: Hope Joan
Published: December 2016

Time to pick up your mail? Need to finish a paper and the computer lab is full? Would a peanut butter and jelly sandwich keep your blood sugar level on track?
Assuring me that it is as ‘Good as New’ just makes me think about how someone else used it. Examining consumer reaction toward marketer‐provided information about secondhand goods
Authors: Ackerman David S. , Hu Jing
Published: December 2016

The current study explores consumer reaction to marketer‐provided information regarding secondhand products. Contamination fears and repugnance have not been addressed at length in consumer research. This study seeks to understand why consumers react negatively to used goods from a perspective of the Accessibility and Diagnosticity of information, addressing the issue of consumer reaction elicited by information about contamination of those goods by others. Specifically, it looks at the process of information processing in consumer reaction to marketer‐provided information, assuring them that secondhand goods are as good as new. Two studies were done to determine the difference in consumer reaction to information about a pair of pants between three conditions: used pants, used pants with assurance that they are as good as new and new pants.

Results find that consumers may react negatively to positive marketer‐provided information, even if they believe it. Even though marketer‐provided information can persuade consumers to believe that a secondhand product is as good as new, consumer reaction is more negative than if consumers saw no such information. Negative emotions revolving around perceived contamination are elicited by this information that influences consumer reaction seemingly independent of beliefs about used goods. These results have implications for understanding the impact of information processing on consumer reaction to secondhand goods and to marketing communications in general. Copyright © 2016 John Wiley & Sons, Ltd.
Platinum Electrodes for Oxygen Reduction Catalysis Designed by Ultrashort Pulse Laser Structuring
Authors: Lange Karsten , Schulz‐Ruhtenberg Malte , Caro Jürgen
Published: December 2016

Compact platinum plates have been micro‐ and nanostructured by using a one‐step process with ultrashort laser pulses. Depending on the parameters of the laser treatment (power, line distance, and scan speed), distinct surface structures can be produced by different spot energy densities. The platinum plates structured this way were tested for their electrochemical activity in the oxygen reduction reaction in aqueous HClO4 by using cyclic voltammetry and rotating disk electrode approaches. The laser‐induced surface structuring yields a substantial enhancement in the electrochemical activity of platinum surfaces. The observed rise of the electrochemical activity by a factor of 1500 is attributed to the considerable increase of the surface area.
Elongated Dihydrogen versus Compressed Dihydride in Osmium Complexes
Authors: Eguillor Beatriz , Esteruelas Miguel A. , Lezáun Virginia , Oliván Montserrat , Oñate Enrique
Published: December 2016

Small modifications on the co‐ligands of complexes containing two coordinated hydrogen atoms can determine the elongated dihydrogen versus compressed dihydride nature of these species and therefore their chemical behavior. 2,6‐diphenylpyridine favors the formation of the osmium(IV) cation [OsH2(C6H4pyPh)(PiPr3)2]+, whereas 2‐phenoxy‐6‐phenylpyridine, which contains an oxygen atom between the heterocycle and one of the phenyl groups, stabilizes the osmium(II) elongated dihydrogen species [Os(C6H4pyOPh)(η2‐H2)(PiPr3)2]+. In contrast to the latter, the former shows a marked tendency to undergo reductive elimination of the heterocycle.
Developments in the design and construction of continuous full‐scale ultrasonic devices for the EVOO industry
Authors: Amirante Riccardo , Clodoveo Maria Lisa
Published: December 2016

The road of scientific research from the pilot scale plant to the industrial applications is often long and winding. The introduction of an ultrasound device able to replace the malaxers into the virgin olive oil extraction plants is a matter deeply discussed. However, a full‐scale industrial plant able to work in an effectively continuous mode is still lack in the market of olive oil extraction industrial plants. In order to overcome one of the main weaknesses of olive oil extraction plants, the discontinuity of the process due to the presence of the malaxer, a batch machine placed between the crusher and the decanter, effectively continuous ultrasonic full‐scale solutions for the extra virgin olive oil industry have been developed.

Practical applications: High power ultrasound for the treatment of olive paste represents a system to replace the malaxing phase, the weakest link of the chain in the VOO extraction process. The malaxer is a batch machine, which works between two continuous devices, the fruit crusher and the decanter. It is also a bad heat exchanger due to a not favorable ratio between the big volume of olive paste that should be warmed and the small surface for the heat exchange. New devices need to be developed in order to optimize the extraction plant, reducing the time of process, the resource consumption without compromise the oil quality, in order to guarantee a right profit for the olive millers.

Shock waves and micro jets are produced when cavitation bubbles are collapsed. Cell layers of the fruit pericarp are destroyed by the cavitation effects.
Two ovine mitochondrial DNAs harboring a fifth 75/76 bp repeat motif without altered gene expression in Northern Spain
Authors: Lopez‐Oceja A. , Gamarra D. , Cardoso S. , Palencia‐Madrid L. , Juste R. A. , De Pancorbo M. M.
Published: December 2016

The Basque Country is home to the Latxa sheep breed, which is divided in several varieties such as Latxa Black Face (LBKF) and Latxa Blonde Face (LBLF). Mitochondrial DNA control region analysis of 174 male sheep (97 LBKF and 77 LBLF) was performed with the objective of characterizing the maternal lineages of these two varieties that are the basis to produce the cheese with Idiazabal quality label. The percentage of unique haplotypes was 77.32% in LBKF and 67.53% in LBLF. Most of the individuals were classified into B haplogroup (98.85%), while A haplogroup was much less frequent. Two Latxa individuals (one LBKF and one LBLF), both belonging to B haplogroup, displayed an additional 75/76 bp tandem repeat motif. Only 33 other sequences with this repeat motif were found among 11 061 sheep sequences included in the GenBank database. Gene expression was analyzed in peripheral blood leukocytes since the additional 75/76 bp repeat motif falls within ETAS1, a domain with a possible function in regulation of replication and transcription. The mRNA expression from four mitochondrial genes (COI, cyt b, ND1, and ND2) was analyzed in the two individuals of this study with a fifth repeat motif and in four without it. Although lower transcription was observed when the additional 75/76 bp repeat motif was present, no statistically significant differences were observed. Therefore, the variation in the number of the 75/76 repeat motif does not seem to modify the gene expression rate in mitochondrial genes.
Measurement of electroosmotic and electrophoretic velocities using pulsed and sinusoidal electric fields
Authors: Sadek Samir H. , Pimenta Francisco , Pinho Fernando T. , Alves Manuel A.
Published: December 2016

In this work, we explore two methods to simultaneously measure the electroosmotic mobility in microchannels and the electrophoretic mobility of micron‐sized tracer particles. The first method is based on imposing a pulsed electric field, which allows to isolate electrophoresis and electroosmosis at the startup and shutdown of the pulse, respectively. In the second method, a sinusoidal electric field is generated and the mobilities are found by minimizing the difference between the measured velocity of tracer particles and the velocity computed from an analytical expression. Both methods produced consistent results using polydimethylsiloxane microchannels and polystyrene micro‐particles, provided that the temporal resolution of the particle tracking velocimetry technique used to compute the velocity of the tracer particles is fast enough to resolve the diffusion time‐scale based on the characteristic channel length scale. Additionally, we present results with the pulse method for viscoelastic fluids, which show a more complex transient response with significant velocity overshoots and undershoots after the start and the end of the applied electric pulse, respectively.
New Hybrid Materials for Improved Hydrogen Production by the Sorption‐Enhanced Steam Reforming of Butanol
Authors: Dewoolkar Karan D. , Vaidya Prakash D.
Published: December 2016

Catalytically assisted steam reforming coupled with the selective separation of the produced CO2 is a promising approach for improved H2 production. In this work, we synthesized a new mixture (K‐Ni‐CaO/HTlc) of two potential sorbents CaO and hydrotalcite (HTlc), the promoter K, and the reforming catalyst Ni. This hybrid material was tested for the sorption‐enhanced steam reforming of butanol (SESRB) and its performance was compared to that of two unpromoted hybrid materials Ni‐CaO/HTlc and Ni‐CaO/Al2O3. All these hybrid materials were able to produce high‐purity H2. In particular, K‐Ni‐CaO/HTlc exhibited the highest H2 concentration (98.7 mol %) and adsorption capacity (12.8 mol CO2 kgsorbent−1) at 823 K. The cyclic durability was tested for 25 cycles, and K‐Ni‐CaO/HTlc was stable for up to 21 cycles. Conversely, Ni‐CaO/HTlc and Ni‐CaO/Al2O3 remained stable for 15 and 11 cycles only. The addition of K as a promoter was justified by the improved H2 production and multicycle resilience. Finally, a plausible reaction mechanism for SESRB that predominates over the investigated hybrid materials was suggested.
Energy‐Efficient Heat Storage using Gypsum Board with Fatty Acid Ester as Layered Phase Change Material
Authors: Wi Seunghwan , Jeong Su‐Gwang , Chang Seong Jin , Lee Jongki , Kim Sumin
Published: December 2016

The thermal performance of phase change materials (PCMs) for energy savings is important in various fields. Fatty acid waxes are types of organic fatty acid ester PCMs made from under‐used and renewable feedstocks. However, they possess one major drawback, namely their phase instability in the liquid state. Therefore, to improve stability during phase transitions, a new method of leakage prevention was developed to form the layer. The thermal properties of the layered PCM gypsum boards were analyzed by differential scanning calorimetry (DSC), phase change, enthalpy, and leakage tests. Finally, a dynamic heat transfer analysis of the layered PCM gypsum board was performed for the evaluation of the peak temperature reduction time lag effects of the prepared specimen. The latent heats of palm wax (PW) and beeswax (BW) were 178.1 and 173.6 J g−1 during heating, 159.7 and 140.9 J g−1, during freezing, respectively. Furthermore, the peak temperatures of the three wax‐infused layered PCM gypsum board samples were reduced by 4.6, 6.6 and 0.9 °C, respectively, compared with reference gypsum board.
Natural Gas: Bridge or Wall in Transition to Low‐Carbon Economy?
Authors: Littell David
Published: December 2016

Natural gas as a power plant fuel has already played an important role in a transition to a low‐carbon economy. Electricity‐sector carbon dioxide emissions in many US states are at some of the lowest levels in the past two decades thanks to a variety of factors, including increased efficiency, deployment of renewables, and structural changes in the electricity sector, such as a transition from coal to natural gas–fueled power generation.
Wind Power Works as Low‐Cost CPP Compliance
Authors: Mahan Simon
Published: December 2016

The United States currently does not have a nationwide policy to reduce carbon dioxide (CO2) missions. However, in June 2014, the United States Environmental Protection Agency (EPA) proposed a new regulatory action to do just that.
Toward amino acid typing for proteins in FFLUX
Authors: Fletcher Timothy L. , Popelier Paul L. A.
Published: December 2016

Continuing the development of the FFLUX, a multipolar polarizable force field driven by machine learning, we present a modern approach to atom‐typing and building transferable models for predicting atomic properties in proteins. Amino acid atomic charges in a peptide chain respond to the substitution of a neighboring residue and this response can be categorized in a manner similar to atom‐typing. Using a machine learning method called kriging, we are able to build predictive models for an atom that is defined, not only by its local environment, but also by its neighboring residues, for a minimal additional computational cost. We found that prediction errors were up to 11 times lower when using a model specific to the correct group of neighboring residues, with a mean prediction of ∼0.0015 au. This finding suggests that atoms in a force field should be defined by more than just their immediate atomic neighbors. When comparing an atom in a single alanine to an analogous atom in a deca‐alanine helix, the mean difference in charge is 0.026 au. Meanwhile, the same difference between a trialanine and a deca‐alanine helix is only 0.012 au. When compared to deca‐alanine models, the transferable models are up to 20 times faster to train, and require significantly lessab initiocalculation, providing a practical route to modeling large biological systems. © 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.
Calretinin Immunoreactivity in the Human Testis Throughout Fetal Life
Authors: Altobelli Giovanna G. , Pentimalli Francesca , D'Armiento Mariarosaria , Van Noorden Susan , Cimini Vincenzo
Published: December 2016

The main functions of the testis are sex hormone and sperm cell production. Steroidogenesis occurs in the Leydig interstitial cells and spermatogenesis in the seminiferous tubules. Male gonad morphogenesis is a finely orchestrated process, mainly coordinated by hormones, whose actions can significantly affect post‐pubertal testicular function. Calcium is a key intracellular messenger, which regulates many signal transduction pathways, and is also implicated in steroidogenesis. Calcium homeostasis and signaling rely on many calcium‐binding proteins including calretinin, of the “EF‐hand” protein family. Calretinin is a highly conserved protein mainly expressed in the nervous system but also detected in rat and human adult and fetal testis as well as in pathological conditions. Calretinin expression in the fetal testis, however, has not been thoroughly analyzed probably owing to limited availability and paucity of tissues. Here, we examined by immunocytochemistry the expression of calretinin in human fetal testis specimens, obtained from natural and therapeutic abortions, at various developmental ages. We found that calretinin‐immunoreactive Leydig cells were visible throughout the timeframe studied (14th–27th week). Immunoreactivity was also observed in Sertoli cells and in the germ cells of the immature seminiferous tubules. Overall our data indicate that calretinin expression parallels the decline in Leydig cell number, suggesting that its presence is indeed correlated to their steroidogenic activity. They also suggest that the intratubular positivity of calretinin could be linked to the ability of Sertoli cells to produce locally acting hormones contributing to the histodifferentiation of the male genital tract. J. Cell. Physiol. 232: 1872–1878, 2017. © 2016 Wiley Periodicals, Inc.
Lavandula multifida response to salinity: Growth, nutrient uptake, and physiological changes
Authors: García‐Caparrós Pedro , Llanderal Alfonso , Pestana Maribela , Correia Pedro José , Lao María Teresa
Published: December 2016

Fern leaf lavender (Lavandula multifida L.) is a perennial shrub native to Almería with known medicinal properties, which grows in saline soils that are increasingly present in the Mediterranean region. However, the effects of salinity on the mineral nutrition and physiology of L. multifida are unknown. In the present study, we evaluated the salt resistance of this species and compared it with other members of the Lamiaceae. Plants of L. multifida were grown in pots in a mixture of sphagnum peat‐moss and Perlite, and treated with five different NaCl concentrations [10 (control), 30, 60, 100, and 200 mM NaCl] over a period of 60 d. The effects of different levels of salinity on mineral nutrient and osmolyte concentrations and on biomass were evaluated. Our results show that L. multifida plants were able to grow with 60 mM NaCl without significant biomass reduction. Na+ and Cl− were the main contributors to the osmotic potential in both roots and leaves, whereas total soluble sugars (TSS) and proline made only a small contribution. The concentrations of TSS and proline showed different trends in the different organs: in roots, both showed the highest concentrations at 60 mM NaCl, whereas in leaves TSS increased and proline decreased with increasing salt stress. To survive salinity, L. multifida plants increased salt excretion (Na+ and Cl−) by leaves at 100 and 200 mM NaCl and leaf succulence at 60, 100, and 200 mM NaCl. Excessive accumulation of Na+ and Cl− was avoided by shedding leaves. Our results indicate that L. multifida is better adapted to salinity compared to other members of the Lamiaceae¸ a consideration that is particularly relevant for their growth in arid saline areas.
An optimised version of the secretome protein enrichment with click sugars (SPECS) method leads to enhanced coverage of the secretome
Authors: Serdaroglu Alperen , Müller Stephan A. , Schepers Ute , Bräse Stefan , Weichert Wilko , Lichtenthaler Stefan F. , Kuhn Peer‐Hendrik
Published: December 2016

The secretome, the entirety of all soluble proteins either being secreted or proteolytically released by a cell, plays a key role in inter‐cellular communication of multi‐cellular organisms. Pathological alterations contribute to diseases such as hypertension, cancer, autoimmune disorders or neurodegenerative diseases. Hence, studying disease‐related perturbations of the secretome and the secretome itself covers an important aspect of cellular physiology. We recently developed the secretome protein enrichment with click sugars (SPECS) method that enables the analysis of secretomes of in vitro cell cultures even in the presence of FCS with MS. So far, SPECS facilitated the identification of protease substrates of BACE1, SPPL3 and ADAM10. Though, the SPECS method has already enabled deep insights into secretome biology, we aimed to improve the SPECS protocol to obtain even more information from MS‐based secretome analysis and reduce the amount of input material. Here, we optimised the reaction buffer, the pH and replaced Dibenzocyclooctyne (DBCO) PEG12‐biotin with the more water‐soluble variant DBCO‐sulpho‐biotin to finally provide an optimised protocol of the recently published SPECS protocol. Overall, the number of quantified glycoproteins and their average sequence coverage was increased by 1.6‐ and 2.4‐fold, respectively. Thus, the opzimised SPECS protocol allows reducing the input material by half without losing information. These improvements make the SPECS method more sensitive and more universal applicable to cell types with limited availability.
Polydopamine Nanoparticle as a Multifunctional Nanocarrier for Combined Radiophotodynamic Therapy of Cancer
Authors: Yu Xiaojun , Tang Xing , He Jingkang , Yi Xuan , Xu Guiying , Tian Longlong , Zhou Rui , Zhang Chen , Yang Kai
Published: December 2016

Combination of different therapeutic strategies to treat cancer has attracted tremendous attention in recent years. Herein, the authors develop polydopamine (PDA) nanoparticles with polyethylene glycol (PEG) modification as a multifunctional nanocarrier for coloading photosensitizer chlorine6 (Ce6) and curcumin (Cur) for combined photodynamic therapy (PDT) and radiotherapy (RT) of cancer. PEGylated PDA nanoparticles (PDA‐PEG) exhibit well water soluble and biocompatible in different physiological solutions and cause no obvious toxicity to cancer cells. In this nanoparticle, the loaded Ce6 can trigger the generation of single oxygen under near‐infrared laser irradiation for PDT, while the loaded Cur can act as an excellent radiosensitizer under X‐ray irradiation for enhanced external RT. As demonstrated by in vitro and in vivo therapeutic efficiency, combined PDT and RT based on PDA‐PEG/Cur/Ce6 nanoparticles exhibits significant inhibition the growth of cancer cells, revealing perfect performance in cancer treatment. Therefore, the study not only presents a polymer‐based theranostic platform for cancer treatment but also demonstrates the potential applications of combined RT and PDT for the future clinic cancer therapy.
Comparative proteomics analyses for 139A and ME7 scrapie infected mice brains in the middle and terminal stages
Authors: Shi Qi , Chen Li‐Na , Lv Yan , Zhang Bao‐Yun , Xiao Kang , Zhou Wei , Chen Cao , Sun Jing , Yang Xiao‐Dong , Dong Xiao‐Ping
Published: December 2016

Purpose

To analyze the proteomics patterns in the cortex regions of scrapie strains 139A‐ and ME7‐infected mice collected in the middle and terminal stages.

Experimental design

Western Blot and immunohistochemistry methods are used to analyze the pathological changes in mice collected in the middle and terminal stages. The technique of iTRAQ and multidimensional LC and MS are used to analyze the proteomics patterns of mice in different stages.

Results

In total, 2891 with 95% confidence interval are identified. The study here also demonstrates a similar protein expressions in the CNS tissues of two scrapie strains infected mice at the terminal stages, but markedly different one between the middle and terminal samples, not only in the numbers of differentially expressed proteins and involved gene ontologies and pathways but also in the relevant functional constitutions.

Conclusions

It may provide useful clue in exploring the abnormalities of biological functions at different time points of prion infections and in searching for potential therapeutic and diagnostic biomarkers for prion diseases.
Ames Test Prediction on High Energy Molecules by On‐The‐Fly QSAR (OTF‐QSAR)
Authors: Alliod Charlotte , Chemelle Julie‐Anne , Jacob Guy , Terreux Raphaël
Published: December 2016

In collaboration with Herakles, a research program was set up to have, in the future, optimized tools for predicting the toxicity of High Energy Molecules (HEM). Because of the number of mutagenicity tests commonly use in the society, a variety of internationally agreed testing protocols on chemicals was set up, described by REACh (Registration, Evaluation, Authorization and Restriction of Chemicals) and OECD (Organization for the Economic Cooperation and Development). The first test described for the mutagenicity is the Ames test. Several methods can be used to predict toxicity such as (Quantitative) Structure Activity Relationship [(Q)SAR] and “On‐The‐Fly” QSAR (OTF‐QSAR). The aim of this paper is to evaluate the reliability of the SAR and the OTF‐QSAR predictions in accordance with various similarities used. The goal is to obtain a good prediction tool for the Ames test. The prediction tool is compared with softwares often used in the scientific community. It was found that the OTF‐QSAR predictions were more accurate and increased the efficiency of predictions. The precision of the system increases as the degree of similarity increased. A new zone was discovered and the best similarity found and refined. At the end of the study, we validate the similarity information and the OTF‐QSAR on HEM molecules.
Association of Obesity‐Related Hemodilution of Prostate‐Specific Antigen, Dihydrotestosterone, and Testosterone
Authors: Klaassen Zachary , Howard Lauren E. , Moreira Daniel M. , Andriole Gerald L. , Terris Martha K. , Freedland Stephen J.
Published: December 2016

BACKGROUND

Prostate‐specific antigen (PSA) hemodilution is the leading theory for lower PSA values in obese men. However, testosterone and dihydrotestosterone (DHT), which are necessary for PSA production, are reduced in obese men. We assessed the relationship of body mass index (BMI) and PSA, taking into consideration the effect of testosterone and DHT.

METHODS

Among 8,122 participants in Reduction by Dutasteride of Prostate Cancer Events (REDUCE), complete data were available for 7,275. BMI was categorized as normal (<25 kg/m2), overweight (25–29.9 kg/m2), obese (30–34.9 kg/m2), or moderate + severely obese (≥35 kg/m2). Associations between BMI, testosterone, and DHT and the outcome variable of PSA were examined using linear regression.

RESULTS

There were 1,964 (27.0%) normal weight, 3,826 (52.6%) overweight, 1,200 (16.5%) obese, and 285 (3.9%) moderately + severely obese patients. With increasing BMI, there was a progressive decrease in PSA (P = 0.02), increase in prostate volume (P < 0.001), and decrease in both testosterone (P < 0.001) and DHT (P < 0.001). Using linear regression, increasing BMI was associated with decreasing serum PSA values. Furthermore, BMI remained inversely associated with PSA after individually adjusting for testosterone and DHT, as well as when adjusting for testosterone and DHT in the same model. Decreased androgen levels accounted for only 19% of the lower PSA in men with higher BMI.

CONCLUSIONS

Only a fraction of lower PSA in obese men could be attributed to testosterone and DHT levels. The remaining factors explaining lower PSA are unaccounted for, presumably secondary to hemodilution associated with increased plasma volume in obese men. Prostate 77:466–470, 2017. © 2016 Wiley Periodicals, Inc.
Clinical Correlates of Benefit From Radium‐223 Therapy in Metastatic Castration Resistant Prostate Cancer
Authors: Alva Ajjai , Nordquist Luke , Daignault Stephanie , George Saby , Ramos Jorge , Albany Costantine , Isharwal Sudhir , McDonald Matthew , Campbell Gregory , Danchaivijitr Pongwut , Yentz Sarah , Anand Aseem , Yu Evan Y.
Published: December 2016

BACKGROUND

We sought to identify potential clinical variables associated with outcomes after radium‐223 therapy in routine practice.

METHODS

Consecutive non‐trial mCRPC patients who received ≥1 dose of radium dichloride‐223 at four academic and one community urology‐specific cancer centers from May 2013 to June 2014 were retrospectively identified. Association of baseline and on‐therapy clinical variables with number of radium doses received and clinical outcomes including overall survival were analyzed using chi‐square statistics, cox proportional hazards, and Kaplan–Meier methods. Bone Scan Index (BSI) was derived from available bone scans using EXINI software.

RESULTS

One hundred and forty‐five patients were included. Radium‐223 was administered for six cycles in 74 patients (51%). One‐year survival in this heavily pre‐treated population was 64% (95%CI: 54–73%). In univariate and multivariate analysis, survival was highly associated with receiving all six doses of Radium‐223. Receipt of six doses was associated with ECOG PS of 0–1, lower baseline PSA & pain level, no prior abiraterone/enzalutamide, <5 BSI value, and normal alkaline phosphatase. In patients who reported baseline pain (n = 72), pain declined in 51% after one dose and increased in 7%. PSA declined ≥50% in 16% (18/110). Alkaline phosphatase declined ≥25% in 48% (33/69) and ≥50% in 16/69 patients. BSI declined in 17 (68%) of the 25 patients who had bone scan available at treatment follow‐up. Grade ≥3 neutropenia, anemia, and thrombocytopenia occurred in 4% (n = 114), 4% (n = 125), and 5% (n = 123), respectively.

CONCLUSIONS

Patients earlier in their disease course with <5 BSI, low pain score, and good ECOG performance status are optimal candidates for radium‐223. Radium‐223 therapy is well tolerated with most patients reporting declines in pain scores and BSI. Prostate 77:479–488, 2017. © 2016 Wiley Periodicals, Inc.
How the use of nitrogen fertiliser may switch plant suitability for aphids: the case of Miscanthus, a promising biomass crop, and the aphid pest Rhopalosiphum maidis
Authors: Bogaert Florent , Chesnais Quentin , Catterou Manuella , Rambaud Caroline , Doury Géraldine , Ameline Arnaud
Published: December 2016

BACKGROUND

The use of nitrogen fertiliser in agrosystems can alter plant nitrogen and consequently improve nutrient availability for herbivores, potentially leading to better performance for herbivores and higher pest pressure in the field. We compared, in laboratory conditions, the effects of nitrogen fertilisation on a promising biomass crop, Miscanthus × giganteus, and its parents M. sinensis and M. sacchariflorus. The plant‐mediated effects were compared on the second trophic level, the green corn leaf aphid Rhopalosiphum maidis.

RESULTS

Results showed that the biomass and leaf C:N ratio of M. sinensis plants treated with nitrogen fertiliser were significantly greater than those of non‐treated plants. As regards M. × giganteus and M. sacchariflorus, the only reported change was a significantly smaller leaf C:N ratio for treated M. sacchariflorus compared with non‐treated plants. Surprisingly, nitrogen fertilisation had opposite effects on plant–herbivore interactions. Following nitrogen treatments, M. sinensis was less suitable in terms of intrinsic rate of increase for R. maidis, the feeding behaviour of which was negatively affected, while M. sacchariflorus and M. × giganteus exhibited greater suitability in terms of aphid weight.

CONCLUSION

Nitrogen fertilisation had contrasting effects on the three species of Miscanthus plants. These effects cascaded up to the second trophic level, R. maidis aphid pests, either through a modification of their weight or demographic parameters. The implications of these results were discussed in the context of agricultural sustainability and intensive production practices. © 2016 Society of Chemical Industry
Statistical assessment of treatment response in a cancer patient based on pre‐therapy and post‐therapy FDG‐PET scans
Authors: Wolsztynski E. , O'Sullivan F. , O'Sullivan J. , Eary J. F.
Published: December 2016

This work arises from consideration of sarcoma patients in which fluorodeoxyglucose positron emission tomography (FDG‐PET) imaging pre‐therapy and post‐chemotherapy is used to assess treatment response. Our focus is on methods for evaluation of the statistical uncertainty in the measured response for an individual patient. The gamma distribution is often used to describe data with constant coefficient of variation, but it can be adapted to describe the pseudo‐Poisson character of PET measurements. We propose co‐registering the pre‐therapy and post‐ therapy images and modeling the approximately paired voxel‐level data using the gamma statistics. Expressions for the estimation of the treatment effect and its variability are provided. Simulation studies explore the performance in the context of testing for a treatment effect. The impact of misregistration errors and how test power is affected by estimation of variability using simplified sampling assumptions, as might be produced by direct bootstrapping, is also clarified. The results illustrate a marked benefit in using a properly constructed paired approach. Remarkably, the power of the paired analysis is maintained even if the pre‐image and post‐ image data are poorly registered. A theoretical explanation for this is indicated. The methodology is further illustrated in the context of a series of fluorodeoxyglucose‐PET sarcoma patient studies. These data demonstrate the additional prognostic value of the proposed treatment effect test statistic. Copyright © 2016 John Wiley & Sons, Ltd.
Design Considerations for the Next Generation Hip Resurfacing Implant
Authors: Su Edwin P.
Published: December 2016

The current generation of hip resurfacing consists of a metal-on-metal ball and monoblock socket of minimal thickness. Although results in certain patient subgroups have been excellent at up to 15 years of follow-up, other subgroups have had poor results. The hard-on-hard bearing is susceptible to edge-loading conditions and may produce excessive metallic debris; furthermore, other patients have had allergic reactions to the metal byproducts. In both situations, there can be clinical failures from adverse local tissue reactions. As such, the role of hip resurfacing has diminished over the last decade because of these issues. Developing the next generation hip resurfacing is essential to address these problems, and there are multiple design considerations in doing so. The choice of materials will be of prime concern, with the decision to use a hard-on-soft or hard-on-hard articulation. The dimensions of the resurfacing implant also pose a challenge, because of the requirement to preserve the bone. Fixation of the implant is another area of interest, in order to maximize implant longevity.
Beyond the Liberal Democracy Paradigm: A Fresh Look at Power and Institutions
Authors: Hyden Goran
Published: December 2016

Compared to political developments in Eastern Europe and Latin America, democratization in sub-Saharan Africa has been more problematic and uneven. Looking at the performance in four subregions—central Africa, East Africa, southern Africa, and West Africa—yields no convincing evidence of a “wave” of democratization; countries next to each other differ considerably with regard to their Freedom House scores. This does not mean that democratization has necessarily stalled, but it does demonstrate that the prevailing vertical cleavages along ethnic, racial, or religious lines can make such a transition volatile, as suggested by the cases of Burundi, Mali, and even Kenya. While political competition in mature democracies, typically divided along horizontal group or class lines, tends to generate positive-sum outcomes, such competition in Africa easily turns into “prisoner’s dilemma” games. The uncertainty about the value of cooperation in such situations usually produces political “truces” that are easily abandoned if the costs of adherence exceed the benefits. Against the background of this prevailing political logic, this article calls for a new approach to conceptualizing notions of “institution” and “power” in the analysis of politics in the region.
Staging a “Revolution”: The 2011–12 Electoral Protests in Senegal
Authors: Demarest Leila
Published: December 2016

This paper advances a resource mobilization perspective on the 2011–12 electoral protests in Senegal based on social movement theory. Motivational explanations, in the form of grievance accounts, have already been used to explain successful protest mobilization in this case. Here the emphasis is placed on organizational efforts and the financial and human resources behind social movements. Using this approach to analyze the rise and fall of the social movement created to protest against President Abdoulaye Wade reveals its strategic role for opposition parties and their leaders. These findings add nuance to the perception of a democratic revolution in Senegal.
Putting the Third Wave into Practice: Democracy Promotion in Kenya
Authors: Harbeson John W.
Published: December 2016

Joel Barkan’s work as the U.S. Agency for International Development’s Regional Democracy and Governance Advisor for Eastern and Southern Africa brought both realism and conceptual strengthening to democracy promotion, most notably giving legitimacy and practical meaning to the concept of civil society as an essential dimension of democratization.