bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Pharmacology Tools and Evaluations to Facilitate Comprehensive Dose Finding in Oncology: A Continuous Risk‐Benefit Approach
Authors: Bullock Julie M. , Lin Tiffany , Bilic Sanela
Published: September 2017

Targeted therapies are now considered an integral component in the treatment armamentarium for many malignancies, and the approach to developing these drugs needs to be refined from the previous cytotoxic paradigm of toxicity‐guided dose finding and identification of maximum tolerated dose to a paradigm driven by target activity. Moving away from the toxicity‐driven dose finding and justification model requires an integrated approach in order to adequately characterize the risk‐benefit of a drug. This approach starts with understanding the importance of collecting samples for pharmacokinetic and pharmacodynamic assessments in all phases of clinical development to fully characterize the pharmacokinetics and identify covariates and then correlating exposure to key markers of safety and efficacy in pharmacometric analyses to perform a robust risk‐benefit assessment and establish the right dose. In addition, for oral agents, decisions on administering the drug with respect to food can impact dose among other clinical trial outcomes such as tolerability and patient compliance. Understanding the importance of model‐based drug development as a decision‐making tool to support drug development through incorporation of all relevant data allows for a robust risk‐benefit assessment at key decision points. Utilization of clinical pharmacology tools and assessments throughout development will provide the key components of a successful oncology development program.
Pharmacokinetic‐Guided Dosing of New Oral Cancer Agents
Authors: Lucas Catherine J. , Martin Jennifer H.
Published: September 2017

Generally, licensed drug‐dosing recommendations for chemotherapy are based on results from clinical trials in which subjects are usually of relatively normal body size, middle‐aged, and are relatively racially homogeneous, with minimal comorbidity and specific tumor characteristics. Very few nontrial patients meet these characteristics, resulting in clinical practice having to extrapolate dosing recommendations to the specific patient. There is insufficient research on the impact of obesity‐associated physiological changes prevalent in patients with common cancers on standard pharmacokinetic and pharmacodynamic parameters. Yet quantifying the influence of obesity on the pharmacology of chemotherapy is vital, as dosing inappropriate for body composition (ie, flat dosing or mg/kg based on total body weight) may increase the risk of adverse events and reduce clinical effectiveness. Unfortunately, there are few cancer guidelines to aid clinicians in selecting the optimal dose in the obese—even recent guidelines are based predominantly on clinical opinion/current practice in treating obese patients, rather than evidence. Data in many other vulnerable groups, for example, those with significant comorbidity and older patients, are also scarce. Because of the known limitations of body surface area–guided dosing, therapeutic drug monitoring or pharmacokinetic‐guided dosing, which predicts an individual's exposure, has increasingly been shown to be a powerful tool in cancer therapy. Used appropriately, it can adjust for differences in pharmacokinetic parameters not considered when body size–based dosing or “one dose fits all” is used. This review will focus predominantly on the rationale for pharmacokinetic‐guided dosing of the newer oral molecularly targeted antineoplastics in people whose drug exposure is not predicted by their physiology or body composition.
How Often Are Drugs Made Available Under the Food and Drug Administration's Expanded Access Process Approved?
Authors: McKee Amy E. , Markon André O. , Chan‐Tack Kirk M. , Lurie Peter
Published: September 2017

In this review of individual patient expanded‐access requests to the Center for Drug Evaluation and Research for the period Fiscal Year 2010 to Fiscal Year 2014, we evaluated the number of applications received and the number allowed to proceed. We also evaluated whether drugs and certain biologics obtained under expanded access went on to be approved by the Food and Drug Administration. Finally, we considered concerns that adverse events occurring during expanded access might place sponsors at risk for legal liability. Overall, 98% of individual patient expanded‐access requests were allowed to proceed. During the study period, among drugs without a previous approval for any indication or dosage form, 24% of unique drugs (ie, multiple applications for access to the same drug were considered to relate to 1 unique drug), and 20% of expanded‐access applications received marketing approval by 1 year after initial submission; 43% and 33%, respectively, were approved by 5 years after initial submission. A search of 3 legal databases and a database of news articles did not appear to identify any product liability cases arising from the use of a product in expanded access. Our analyses seek to give physicians and patients a realistic perspective on the likelihood of a drug's approval as well as certain information regarding the product liability risks for commercial sponsors when providing expanded access to investigational drugs. The US Food and Drug Administration (FDA)’s expanded‐access program maintains a careful balance between authorizing patient access to potentially beneficial drugs and protecting them from drugs that may have unknown risks. At the same time, the agency wishes to maintain the integrity of the clinical trials process, ultimately the best way to get safe and effective drugs to patients.
Antibody–Drug Conjugates as Cancer Therapeutics: Past, Present, and Future
Authors: Vezina Heather E. , Cotreau Monette , Han Tae H. , Gupta Manish
Published: September 2017

Antibody–drug conjugates (ADCs) represent an innovative therapeutic approach that provides novel treatment options and hope for patients with cancer. By coupling monoclonal antibodies (mAbs) to cytotoxic small‐molecule payloads with a plasma‐stable linker, ADCs offer the potential for increased drug specificity and fewer off‐target effects than systemic chemotherapy. As evidence for the potential of these therapies, many new ADCs are in various stages of clinical development. Because their structure poses unique challenges to pharmacokinetic and pharmacodynamic characterization, it is critical to recognize the differences between ADCs and conventional chemotherapy in the design of ADC clinical development strategies. Although some properties may be determined mainly by either the mAb or the small‐molecule portion, the behavior of these agents is not always predictable. Furthermore, because the absorption, distribution, metabolism, and excretion (ADME) of ADCs are influenced by all 3 of its components (mAb, linker, and payload), it is important to characterize the intact molecule, any target‐mediated catabolic clearance of the mAb, and the ADME properties of the small‐molecule payload. Here we describe key issues in the clinical development of ADCs, including considerations for designing first‐in‐human studies for ADCs. We discuss some difficulties of ADC pharmacokinetic characterization and current approaches to overcoming these challenges. Finally, we consider all aspects of clinical pharmacology assessment required during drug development, using examples from the literature to illustrate the discussion.
Pharmacogenomics Implementation at the National Institutes of Health Clinical Center
Authors: Sissung Tristan M. , McKeeby Jon W. , Patel Jharana , Lertora Juan J. , Kumar Parag , Flegel Willy A. , Adams Sharon D. , Eckes Ellen J. , Mickey Frank , Plona Teri M. , Mellott Stephanie D. , Baugher Ryan N. , Wu Xiaolin , Soppet Daniel R. , Barcus Mary E. , Datta Vivekananda , Pike Kristen M. , DiPatrizio Gary , Figg William D. , Goldspiel Barry R.
Published: September 2017

The National Institutes of Health Clinical Center (NIH CC) is the largest hospital in the United States devoted entirely to clinical research, with a highly diverse spectrum of patients. Patient safety and clinical quality are major goals of the hospital, and therapy is often complicated by multiple cotherapies and comorbidities. To this end, we implemented a pharmacogenomics program in 2 phases. In the first phase, we implemented genotyping for HLA‐A and HLA‐B gene variations with clinical decision support (CDS) for abacavir, carbamazepine, and allopurinol. In the second phase, we implemented genotyping for drug‐metabolizing enzymes and transporters: SLCO1B1 for CDS of simvastatin and TPMT for CDS of mercaptopurine, azathioprine, and thioguanine. The purpose of this review is to describe the implementation process, which involves clinical, laboratory, informatics, and policy decisions pertinent to the NIH CC.
Biomarkers for equine joint injury and osteoarthritis
Authors: McIlwraith C. Wayne , Kawcak Christopher E. , Frisbie David D. , Little Christopher B. , Clegg Peter D. , Peffers Mandy J. , Karsdal Morten A. , Ekman Stina , Laverty Sheila , Slayden Richard A. , Sandell Linda J. , Lohmander L. S. , Kraus Virginia B.
Published: September 2017

We report the results of a symposium aimed at identifying validated biomarkers that can be used to complement clinical observations for diagnosis and prognosis of joint injury leading to equine osteoarthritis (OA). Biomarkers might also predict pre‐fracture change that could lead to catastrophic bone failure in equine athletes. The workshop was attended by leading scientists in the fields of equine and human musculoskeletal biomarkers to enable cross‐disciplinary exchange and improve knowledge in both. Detailed proceedings with strategic planning was written, added to, edited and referenced to develop this manuscript. The most recent information from work in equine and human osteoarthritic biomarkers was accumulated, including the use of personalized healthcare to stratify OA phenotypes, transcriptome analysis of anterior cruciate ligament (ACL) and meniscal injuries in the human knee. The spectrum of “wet” biomarker assays that are antibody based that have achieved usefulness in both humans and horses, imaging biomarkers and the role they can play in equine and human OA was discussed. Prediction of musculoskeletal injury in the horse remains a challenge, and the potential usefulness of spectroscopy, metabolomics, proteomics, and development of biobanks to classify biomarkers in different stages of equine and human OA were reviewed. The participants concluded that new information and studies in equine musculoskeletal biomarkers have potential translational value for humans and vice versa. OA is equally important in humans and horses, and the welfare issues associated with catastrophic musculoskeletal injury in horses add further emphasis to the need for good validated biomarkers in the horse. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:823–831, 2018.
Next Generation of Jigless Robot Welding
Authors: Högel Ralf
Published: September 2017

Technicians around the globe are preoccupied with the concept of fully automatic, just‐in‐time welding of different components down to a batch size of 1 in unattended operation without time‐consuming set‐up. For an Austrian global market leader in formwork solutions this vision has already become lived reality.
Bright Future for the Key Technology Photonics
Authors: Löffler Annika , Tober Ursula
Published: September 2017

Light technologies provide tremendous potential for growth and innovation, as shown by two new studies. Strong core areas, impressive growth rates far above the gross domestic product and high expenditures on research and development indicate successful outlooks up to the year 2020.
Effects of sediment disturbance regimes onSpartinaseedling establishment: Implications for salt marsh creation and restoration
Authors: Cao Haobing , Zhu Zhenchang , Balke Thorsten , Zhang Liquan , Bouma Tjeerd J.
Published: September 2017

Seedling establishment is an important process relevant for the restoration of salt marsh within the framework of sustainable coastal defense schemes. Recent studies have increasingly highlighted how the short‐term (i.e., the day‐to‐day) sediment dynamics can form major bottlenecks for seedling establishment. Until recently, studies on quantifying the threshold values of such short‐term sediment dynamics for marsh seedlings remain rare. As accretion/erosion trends and dynamics may differ greatly under global change, we study the effects of short‐term sediment disturbance‐regimes on seedling establishment of two globally distributed foundation species:Spartina alternifloraandSpartina anglica. Seedlings with different disturbance‐free periods were exposed to a set of different accretion/erosion‐regimes in the laboratory. Seedling survival appeared to be much more sensitive to erosion than accretion, seedlings with short disturbance‐free periods were more sensitive than seedlings with longer ones, andS. alterniflorawas more sensitive thanS. anglica. Seedlings were less sensitive to gradual changes in sediment height (accretion/erosion) than to abrupt changes where time for morphological adjustment is lacking. Critical erosion depth (the maximum erosion that seedlings are able to withstand) was shown to mainly depend on sedimentation history. Our results confirm that the establishment ofSpartinaseedlings requires a flooding disturbance‐free “window of opportunity” and that sediment disturbances affect their survival both directly and via morphological adjustment. These results provide fundamental insights into seedling establishment that can be used for designing engineering measures to create suitable conditions and enable marsh creation/restoration for nature goals or as part of coastal defense schemes under global change.
HOW TO BE HAPPY AT WORK
Authors: McKee Annie
Published: September 2017

Are you happy at work? For too many people, the answer is no. McKee discusses why people are unhappy in these settings and what can be done about it. She explains certain myths (such as that you are not necessarily supposed to be happy on the job) and traps (such as the overwork trap). To counter these, she notes the power of purpose, hope, and friendships, and emotional intelligence, an area in which she has co‐authored books with Daniel Goleman and Richard Boyatzis. Within this construct, she cites the components of self‐awareness, empathy, self‐management, and emotional self‐control. Happiness at work is within your own power and your own reach—a comforting thought.
Green Tea Makes Polyphenol Nanoparticles with Radical‐Scavenging Activities
Authors: Xiang Siying , Yang Peng , Guo Hao , Zhang Shu , Zhang Xiaokang , Zhu Fang , Li Yiwen
Published: September 2017

The constant demand for functional nanomaterials from natural biomass polymers usually requires new “green” synthetic strategies without using any foreign additives. Here, the green fabrication of a series of polyphenol nanoparticles (PNs) only from green tea extraction compounds is reported (i.e., tea polyphenols and theophylline). It is found that the nanoparticle formation process involves covalent copolymerization of monomers, as well as noncovalent self‐assembly pathways. Additionally, the resulting PNs exhibit better free‐radical scavenging activities compared with similar‐sized, polydopamine‐based synthetic melanin nanoparticles. This class of biomass‐based functional nanoparticles is promising as green and effective antioxidant agents in general.
Automatic labeling of MR brain images through extensible learning and atlas forests
Authors: Xu Lijun , Liu Hong , Song Enmin , Yan Meng , Jin Renchao , Hung Chih‐Cheng
Published: September 2017

Purpose

Multiatlas‐based method is extensively used in MR brain images segmentation because of its simplicity and robustness. This method provides excellent accuracy although it is time consuming and limited in terms of obtaining information about new atlases. In this study, an automatic labeling of MR brain images through extensible learning and atlas forest is presented to address these limitations.

Methods

We propose an extensible learning model which allows the multiatlas‐based framework capable of managing the datasets with numerous atlases or dynamic atlas datasets and simultaneously ensure the accuracy of automatic labeling. Two new strategies are used to reduce the time and space complexity and improve the efficiency of the automatic labeling of brain MR images. First, atlases are encoded to atlas forests through random forest technology to reduce the time consumed for cross‐registration between atlases and target image, and a scatter spatial vector is designed to eliminate errors caused by inaccurate registration. Second, an atlas selection method based on the extensible learning model is used to select atlases for target image without traversing the entire dataset and then obtain the accurate labeling.

Results

The labeling results of the proposed method were evaluated in three public datasets, namely, IBSR, LONI LPBA40, and ADNI. With the proposed method, the dice coefficient metric values on the three datasets were 84.17 ± 4.61%, 83.25 ± 4.29%, and 81.88 ± 4.53% which were 5% higher than those of the conventional method, respectively. The efficiency of the extensible learning model was evaluated by state‐of‐the‐art methods for labeling of MR brain images. Experimental results showed that the proposed method could achieve accurate labeling for MR brain images without traversing the entire datasets.

Conclusion

In the proposed multiatlas‐based method, extensible learning and atlas forests were applied to control the automatic labeling of brain anatomies on large atlas datasets or dynamic atlas datasets and obtain accurate results.
The role of whole‐brain diffusion MRI as a tool for studying human in vivo cortical segregation based on a measure of neurite density
Authors: Calamante Fernando , Jeurissen Ben , Smith Robert E. , Tournier Jacques‐Donald , Connelly Alan
Published: September 2017

Purpose

To investigate whether diffusion MRI can be used to study cortical segregation based on a contrast related to neurite density, thus providing a complementary tool to myelin‐based MRI techniques used for myeloarchitecture.

Methods

Several myelin‐sensitive MRI methods (e.g., based on T1, T2, and
) have been proposed to parcellate cortical areas based on their myeloarchitecture. Recent improvements in hardware, acquisition, and analysis methods have opened the possibility of achieving a more robust characterization of cortical microstructure using diffusion MRI. High‐quality diffusion MRI data from the Human Connectome Project was combined with recent advances in fiber orientation modeling. The orientational average of the fiber orientation distribution was used as a summary parameter, which was displayed as inflated brain surface views.

Results

Diffusion MRI identifies cortical patterns consistent with those previously seen by MRI methods used for studying myeloarchitecture, which have shown patterns of high myelination in the sensorimotor strip, visual cortex, and auditory areas and low myelination in frontal and anterior temporal areas.

Conclusion

In vivo human diffusion MRI provides a useful complementary noninvasive approach to myelin‐based methods used to study whole‐brain cortical parcellation, by exploiting a contrast based on tissue microstructure related to neurite density, rather than myelin itself. Magn Reson Med 79:2738–2744, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Spontaneous mechanical and electrical activities of human calf musculature at rest assessed by repetitive single‐shot diffusion‐weighted MRI and simultaneous surface electromyography
Authors: Schwartz Martin , Steidle Günter , Martirosian Petros , Ramos‐Murguialday Ander , Preißl Hubert , Stemmer Alto , Yang Bin , Schick Fritz
Published: September 2017

Purpose

Assessment of temporal and spatial relations between spontaneous mechanical activities in musculature (SMAM) at rest as revealed by diffusion‐weighted imaging (DWI) and electrical muscular activities in surface EMG (sEMG). Potential influences of static and radiofrequency magnetic fields on muscular activity on sEMG measurements at rest were examined systematically.

Methods

Series of diffusion‐weighted stimulated echo planar imaging were recorded with concurrent sEMG measurements. Electrical activities in sEMG were analyzed by non‐parametric Friedman and two‐sample Kolmogorov–Smirnov test. Direct correlation of both modalities was investigated by temporal mapping of electrical activity in sEMG to DWI repetition interval.

Results

Electrical activities in sEMG and number of visible SMAMs in DWI showed a strong correlation (ρ = 0.9718). High accordance between sEMG activities and visible SMAMs in DWI in a near‐surface region around sEMG electrodes was achieved. Characteristics of sEMG activities were almost similar under varying magnetic field conditions.

Conclusion

Visible SMAMs in DWI have shown a close and direct relation to concurrent signals recorded by sEMG. MR‐related magnetic fields had no significant effects on findings in sEMG. Hence, appearance of SMAMs in DWI should not be considered as imaging artifact or as effects originating from the special conditions of MR examinations. Spatial and temporal distributions of SMAMs indicate characteristics of spontaneous (microscopic) mechanical muscular action at rest. Therefore, DWI techniques should be considered as non‐invasive tools for studying physiology and pathophysiology of spontaneous activities in resting muscle. Magn Reson Med 79:2784–2794, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Macrophage Area Content and Phenotype in Hepatic and Adipose Tissue in Patients with Obesity Undergoing Roux‐en‐Y Gastric Bypass
Authors: Kristensen Marianne D. , Lund Michael T. , Hansen Merethe , Poulsen Steen S. , Ploug Thorkil , Dela Flemming , Helge Jørn W. , Prats Clara
Published: September 2017

Objective

To investigate hepatic and adipose tissue macrophage content in subjects with obesity and the role of adipose tissue macrophages in weight loss‐induced improved insulin sensitivity (IS).

Methods

A cross‐sectional and a longitudinal study were combined to investigate the role of macrophages in subcutaneous (SAT) and visceral (VAT) adipose tissue and the liver in obesity‐induced impaired IS and improvements with weight loss. Macrophage markers (CD68, CD163, and CD206) in SAT, VAT, and the liver from patients with obesity were investigated. The same macrophage markers were investigated in SAT from 18 patients with obesity before and ∼18 months after a diet‐ and Roux‐en‐Y gastric bypass‐induced weight loss.

Results

SAT macrophage markers did not decrease with weight loss, but macrophage concentration may have increased, concomitant with improved IS. Hepatic macrophage markers did not correlate to VAT mass or macrophage markers, but they were higher in patients with obesity compared with patients without obesity. Hepatic anti‐inflammatory macrophage markers correlated positively with hepatic IS. VAT and SAT macrophage markers did not correlate.

Conclusions

The results indicate that decreased SAT macrophage content is not a primary driver for weight loss‐induced IS improvements, but a better hepatic CD163 and CD206 macrophage profile may contribute to improved glycemic control. SAT macrophage markers were not predictive for VAT macrophage markers.
Obesity Alters B Cell and Macrophage Populations in Brown Adipose Tissue
Authors: Peterson Kristin R. , Flaherty David K. , Hasty Alyssa H.
Published: September 2017

Objective

The prevalence of obesity continues to rise, and it is understood that regulation of white adipose tissue (WAT) function is important to systemic metabolic homeostasis. Immune cells play a central role in the maintenance of WAT, and their compositions change in number and inflammatory phenotype with the progression of obesity. Because of its energy‐burning capabilities, brown adipose tissue (BAT) has become a focus of obesity research. Although novel studies have focused on the function of brown adipocytes in thermogenesis, the tissue as a whole has not been immunologically characterized.

Methods

BAT immune cell populations were analyzed by flow cytometry and immunohistochemistry in mice with diet‐induced obesity (3, 8, or 16 weeks of diet) and in aged mice (1, 6‐7, and 10‐15 months).

Results

The data confirmed the presence of macrophages and eosinophils, as previously reported, and showed that 20% to 30% of the immune cells in BAT were B cells. The number of B cells and eosinophils increased with diet‐induced obesity, whereas macrophages decreased. There was no change in number of any immune cell quantified with age.

Conclusions

These studies reveal a novel finding of B220 + B cells in BAT and show that BAT immune cell populations change in response to diet‐induced obesity.
Review on micromechanics of nano‐ and micro‐fiber reinforced composites
Authors: Kundalwal Shailesh I.
Published: September 2017

This article deals with the prediction of thermomechanical properties of fiber reinforced composites using several micromechanics models. These include strength of material approach, Halpin–Tsai equations, multi‐phase mechanics of materials approaches, multi‐phase Mori–Tanaka models, composite cylindrical assemblage model, Voigt–Reuss models, modified mixture rule, Cox model, effective medium approach and method of cells. Several composite systems reinforced with short and long, aligned, random and wavy reinforcements were considered. In addition, different aspects such as fiber‐matrix interphase, fiber‐matrix interfacial thermal resistance, fiber geometry, and multiple types of reinforcements were considered to model the composites systems. The current study also presents some important preliminary concepts and application of developed micromechanics models to advanced nanocomposites such as carbon nanotube reinforced composite. Main contribution of the current work is the investigation of several analytical micromechanical models, while most of the existing studies on the subject deal with only one or two approaches considering few aspects. POLYM. COMPOS., 39:4243–4274, 2018. © 2017 Society of Plastics Engineers
Finite element simulation and analysis of the dielectric properties of unidirectional aramid/epoxy composites
Authors: Xu Xiangyu , Zhang Boming , Liu Kai , Liu Dawei , Bai Ming , Li Yun
Published: September 2017

Aramid fiber reinforced composites have drawn much attention due to outstanding mechanical and dielectric properties. Dielectric properties should be predicted exactly when such composites are used as electromagnetic functional materials. A simulation method was proposed to predict the effective dielectric constants of unidirectional aramid/epoxy composites in this study. Randomly planar distributed 3D models were created to describe the microstructures of the composites. Parallel and series models were calculated by classical formulas and finite element method to verify the simulation. The distributions of aramid fibers and the dielectric anisotropy of unidirectional composites were analyzed. Dielectric measurements were carried out by the rectangular waveguide method in X‐band and excellent agreements between simulations and experiments were observed. The compression of aramid fibers and interface effect were taken into account to improve the forecasting precision. Comparative analysis was conducted between our simulation method and classical formulas, and it was found that the Maxwell‐Garnett model gives the best fit to the simulation. In addition, the effect of the fiber orientation in electric field was analyzed. POLYM. COMPOS., 39:E2226–E2233, 2018. © 2017 Society of Plastics Engineers
Influence of side chain linker length on ion‐transport properties of polymeric ionic liquids
Authors: Keith Jordan R. , Mogurampelly Santosh , Wheatle Bill K. , Ganesan Venkat
Published: September 2017

We used atomistic molecular dynamics simulations to study the properties of polymerized 1‐alkene‐3‐butylimidazolium‐hexafluorophosphate, a polymerized ionic liquid electrolyte, and characterized the influence of the linear alkene length on the mobility of the hexafluorophosphate ions. Consistent with experimental observations, our simulations indicate that as the alkene length increases, the diffusivity of hexafluorophosphate anion monotonically increases. We demonstrate that such a trend arises from the influence of linker segments on the intermolecular ion hopping rates, which is in turn modulated by intermolecular cationic separation distances. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 1718–1723
Resonant Effects in SERS Spectra of Linear Carbon Chains
Authors: Arutyunyan Natalia R. , Kononenko Vitaly V. , Gololobov Victor M. , Obraztsova Elena D.
Published: September 2017

Linear carbon chains are synthesized by laser ablation of graphite flakes suspended in ethanol. The optical absorption spectra of the material are measured, and the typical absorption lines at the positions 216, 226, 239, 252, 261, 276, 287, 306 and 325 nm are attributed to the linear carbon chains consisting of 8–16 atoms of C. The surface‐enhanced Raman scattering (SERS) spectra are registered from the material in the presence of silver nanoparticles. While the Raman spectra of linear carbon chains in ethanol demonstrate only the Raman lines of ethanol, the addition of silver nanoparticles lead to the appearance of a carbon chain signal with enormous intensity. The bands at 1850–2200 cm−1 originating from CC vibrations in polyynic chains dominated in the SERS spectra. The gain of the signal of linear carbon chains exceeded 105. SERS spectra are excited by various wavelengths in the visible range. The resonant re‐distribution of the lines attributed to chains with different length is revealed.
Contributions to Hysteresis in Magnetocaloric Materials
Authors: Cohen Lesley F.
Published: September 2017

Hysteresis is detrimental to the refrigeration cooling cycle efficiency and yet many of the magnetocaloric materials under consideration as solid state refrigerants possess this property. This article discusses some aspects related to the factors leading to hysteresis in real materials. In the absence of high quality single crystals, determining the intrinsic energy cost associated with the transformation between metastable phases is an experimental challenge. We describe a micro‐calorimetric method that provides valuable insight into intrinsic behavior with the sensitivity to measure micro‐crystallites. We show that there is no correlation between the strength of first order character and magnitude of hysteresis between material families. We review some of the extrinsic factors which contribute to the hysteresis in real materials particularly those that can be accounted for using local imaging techniques such as scanning Hall probe microscopy. We discuss a number of mechanisms by which the extrinsic hysteretic properties of a material can be modified.
Role of Defects in Tuning the Electronic Properties of Monolayer WS2 Grown by Chemical Vapor Deposition
Authors: Yang Jie , Gordiichuk Pavlo , Zheliuk Oleksandr , Lu Jianming , Herrmann Andreas , Ye Jianting
Published: September 2017

Two‐dimensional transition metal dichalcogenides have already attracted enormous research interest. To understand the dependence of electronic properties on the quality and defect morphology is vital for synthesizing high quality materials and the realization of functional devices. Here, we demonstrate the mapping of the conductive variations by conducting atomic force microscopy (C‐AFM) in the monolayer tungsten disulfide (WS2) grown by chemical vapor deposition. The electronic properties are strongly affected by the formation of vacancies in monolayer WS2 during growth, which is also verified by the photoluminescence. This spatial study of defects provides opportunities for optimization of the growth process for enhancing devices performance of TMDs monolayers.
Prenatal undernutrition disrupted the sexual maturation, but not the sexual behavior, in male rats
Authors: Matsuzaki Toshiya , Munkhzaya Munkhsaikhan , Tungalagsuvd Altankhuu , Mayila Yiliyasi , Iwasa Takeshi , Yano Kiyohito , Yanagihara Rie , Tokui Takako , Kato Takeshi , Kuwahara Akira , Matsui Sumika , Irahara Minoru
Published: September 2017

Purpose

Exposure to various stressors, including psychological, metabolic, and immune, in the perinatal period induces long‐lasting effects in physiological function and increase the risk of metabolic disorders in later life. In the present study, sexual maturation and sexual behavior were assessed in prenatally undernourished mature male rats.

Methods

All the pregnant rats were divided into the maternal normal nutrition (mNN) group and the maternal undernutrition (mUN) group. The mUN mothers received 50% of the amount of the daily food intake of the mNN mothers. Preputial separation and sexual behavior were observed in randomly selected pups of the mNN and mUN groups.

Results

The body weight of the mothers was significantly lighter in the mUN group than in the mNN group. Similarly, the pups in the mUN group showed a significantly lower body weight than those in the mNN group from postnatal day (PND) 1 to PND 15. The preputial separation day was significantly delayed in the mUN group, compared to the mNN group. Sexual behavior did not show any significant difference between the two groups.

Conclusion

These findings indicated that prenatal undernutrition delayed sexual maturation, but did not suppress sexual behavior, in mature male rats.
Age‐specific serum anti‐Müllerian hormone concentration in Japanese women and its usefulness as a predictor of the ovarian response
Authors: Asada Yoshimasa , Morimoto Yoshiharu , Nakaoka Yoshiharu , Yamasaki Takahiro , Suehiro Yutaka , Sugimoto Hikaru , Yoshida Masayuki , Irahara Minoru
Published: September 2017

Purpose

To compare the ovarian response predictive ability of anti‐Müllerian hormone (AMH), follicle‐stimulating hormone (FSH), and estradiol (E2) and to determine the age‐specific distribution of serum AMH concentrations of Japanese women.

Methods

This was a multicenter (four‐site), observational, analytic, cross‐sectional Japanese study consisting of two parts: Study 1 (the prediction of the ovarian response of 236 participants who were undergoing controlled ovarian stimulation [COS]) and Study 2 (the distribution of the AMH concentration with an assay of 417 healthy women who were aged 20‐49 years and who had normal menstrual cycles).

Results

The AMH had a significantly higher predictive value for the normal and high responders than FSH and E2 as a stronger correlation between the ovarian response and AMH was observed than for FSH and E2. The serum AMH concentration decreased proportionally with age.

Conclusion

The AMH concentration correlated well with the oocyte count in the patients who were undergoing COS for in vitro fertilization and was shown to predict the risk of ovarian hyperstimulation syndrome among these patients.
Montmorillonite K‐10‐Supported Palladium Nanoparticles for Copper‐Free Acyl Sonogashira Reaction
Authors: Loganathan Roopesh K. , Ramachandra Sagar N. , Shekharappa  , Sureshbabu Vommina V.
Published: September 2017

Preparation of palladium nanoparticles supported on montmorillonite K‐10 clay is described. The utility of thus prepared catalyst was examined for copper free acyl Sonogashira reaction of acid chlorides with phenyl acetylenes to achieve various ynone scaffolds. Coumarin derived ynones were also synthesized under mild optimized reaction conditions. All the title compounds were obtained in good to excellent yield. The recycling efficiency of the catalyst was extremely good and used successfully for seven cycles without significant drop in the yield.
New Anti‐Inflammatory Hybrid N‐Acyl Hydrazone‐Linked Isoxazole Derivatives as COX‐2 Inhibitors:Rational Design, Synthesis and Biological Evaluation
Authors: Gorantla Vasubabu , Gundla Rambabu , Jadav Surender Singh , Anugu Sreenivasa Reddy , Chimakurthy Jithendra , Rao NS Kameswara , Korupolu Raghubabu
Published: September 2017

Selectivity of a drug becomes a major problem in the treatment of a clinical disease and many nonsteroidal anti‐inflammatory drugs (NSAID's) are classic examples of this conundrum. In the present study, we designed a set of hybrid compounds (11 a‐p, 12 a‐i) that compose new N‐acyl hydrazones (NAH) linked with isoxazoles, using rational drug design approach. The binding affinities of newly designed compounds were calculated and compared with known non anti‐inflammatory NAH and cyclooxygenase‐2 (COX‐2) inhibitors (coxibs) at the active sites of cyclooxygenase‐1 (COX‐1) and COX‐2. The comparison revealed that the hybrid compounds bind with COX‐2 active site in a fashion quite similar to known non anti‐inflammatory compounds (4). Based on these findings, we further synthesized the compounds (11 a‐p, 12 a‐i) and subjected them to in vitro, in vivo anti‐inflammatory studies. Compound 11 l (IC50=5.8 μM) and 12 c (IC50 = 4.1 μM) were found to be active COX‐2 inhibitors. Compounds 12 a, 12 b and 12 e displayed COX‐2 enzyme inhibition at lower micro molar concentrations. The compounds were also evaluated for antioxidant activity and compound 11 h exhibited an effective antioxidant activity when compared with ascorbic acid. Additionally, these compounds were screened for anti‐bacterial activities and compound 11 l and 12 h were exhibited greater anti‐bacterial activity against gram +ve and ‐ve than standards Ciprofloxacin and Flucloxacillin.
Electronic Absorption, Emission and Two‐Photon Absorption Properties of Some Functional 1,3,5‐Triphenylbenzenes
Authors: Streatfield Suzy L. , Pradels Claire , Ndimba Alphonsine Ngo , Richy Nicolas , Amar Anissa , Boucekkine Abdou , Cifuentes Marie P. , Humphrey Mark G. , Mongin Olivier , Paul Frédéric
Published: September 2017

We report herein the linear optical properties of some extended 1,3,5‐triphenylbenzene derivatives 1,3,5‐[(1, 4‐C6H4)C≡C(4‐C6H4X)]3(C6H3) (3‐X; X=NO2, CN, H, OMe, NMe2, NPh2) and briefly discuss the two‐photon absorption (2PA) cross‐sections determined for the derivatives featuring the most electron‐rich substituents, contrasting their 2PA performance with the 2PA values previously gathered for their triphenylisocyanurate analogues N,N’,N”‐[(1, 4‐C6H4)C≡C(4‐C6H4X)]3(N3{C(O)}3) (1‐X). When functionalized by electron‐releasing substituents at their periphery, 3‐X derivatives are potent substitutes for 1‐X compounds in NLO applications, especially when maximal transparency is not required in the visible range. Some rationalization of this unexpected outcome is proposed based on DFT calculations.
Flexible Photodetectors Based on Novel Functional Materials
Authors: Xie Chao , Yan Feng
Published: September 2017

Flexible photodetectors have attracted a great deal of research interest in recent years due to their great possibilities for application in a variety of emerging areas such as flexible, stretchable, implantable, portable, wearable and printed electronics and optoelectronics. Novel functional materials, including materials with zero‐dimensional (0D) and one‐dimensional (1D) inorganic nanostructures, two‐dimensional (2D) layered materials, organic semiconductors and perovskite materials, exhibit appealing electrical and optoelectrical properties, as well as outstanding mechanical flexibility, and have been widely studied as building blocks in cost‐effective flexible photodetection. Here, we comprehensively review the outstanding performance of flexible photodetectors made from these novel functional materials reported in recent years. The photoresponse characteristics and flexibility of the devices will be discussed systematically. Summaries and challenges are provided to guide future directions of this vital research field.
Mesoporous Nanosheet Networked Hybrids of Cobalt Oxide and Cobalt Phosphate for Efficient Electrochemical and Photoelectrochemical Oxygen Evolution
Authors: Liu Bin , Peng Hui‐Qing , Ho Cheuk‐Nam , Xue Hongtao , Wu Shuilin , Ng Tsz‐Wai , Lee Chun‐Sing , Zhang Wenjun
Published: September 2017

A novel mesoporous nanosheet networked hybrid comprising Co3O4 and Co3(PO4)2 is successfully synthesized using a facile and scalable method through calcinating the carbon, cobalt hydroxy carbonate, and cobalt phosphate composite precursor. Electron transfer from Co3O4 to Co3(PO4)2, together with the special networked structure and the porous nature of the nanosheets enable the Co3(PO4)2‐Co3O4 hybrid to have a high oxygen evolution reaction (OER) activity and outstanding stability in alkaline electrolyte, e.g., an overpotential of 270 mV at current density of 10 mA cm−2, and a Tafel slope of 39 mV dec−1, which are superior to most non‐noble metal‐based OER electrocatalysts reported thus far and as well the commercial RuO2 electrocatalyst. Furthermore, Co3(PO4)2‐Co3O4 hybrid is demonstrated to be used as an efficient cocatalyst to enhance the photoelectrochemical OER performance of BiVO4 photoanode. A significantly increased photocurrent density of 3.0 mA cm−2 at 1.23 V (vs reversible hydrogen electrode, RHE), and a potential reduction of 530 mV with respect to that of bare BiVO4 at the photocurrent density of 0.5 mA cm−2 are achieved. The electron transfer‐induced enhancement of OER by a hybrid structure may pave the new routes for the design and synthesis of low‐cost catalysts for electrochemical and photoelectrochemical oxygen evolution.
Baum–Welch algorithm on directed acyclic graph for mixtures with latent Bayesian networks
Authors: Li Jia , Lin Lin
Published: September 2017

We consider a mixture model with latent Bayesian network (MLBN) for a set of random vectors
. Each X(t) is associated with a latent state st, given which X(t) is conditionally independent from other variables. The joint distribution of the states is governed by a Bayes net. Although specific types of MLBN have been used in diverse areas such as biomedical research and image analysis, the exact expectation–maximization (EM) algorithm for estimating the models can involve visiting all the combinations of states, yielding exponential complexity in the network size. A prominent exception is the Baum–Welch algorithm for the hidden Markov model, where the underlying graph topology is a chain. We hereby develop a new Baum–Welch algorithm on directed acyclic graph (BW‐DAG) for the general MLBN and prove that it is an exact EM algorithm. BW‐DAG provides insight on the achievable complexity of EM. For a tree graph, the complexity of BW‐DAG is much lower than that of the brute‐force EM. Copyright © 2017 John Wiley & Sons, Ltd.
The Events in 1991
Authors: Gunneriusson Håkan
Published: September 2017

This chapter deals with the final blows against Yugoslavia as the state it once was and its eventual reduction to an extension of Serbian politics. From the point of legitimacy, one can see this as the height of Milošević political career, even if his power would be strong well beyond this year. Serbian forces attack eastern Croatia and sack the city of Vukovar as the first major hostilities between the two parts of the former Yugoslavia.
Integrating isotopic, microbial, and modeling approaches to understand methane dynamics in a frequently disturbed deep reservoir in Taiwan
Authors: Itoh Masayuki , Kojima Hisaya , Ho Pei‐Chi , Chang Chun‐Wei , Chen Tzong‐Yueh , Hsiao Silver Sung‐Yun , Kobayashi Yuki , Fujibayashi Megumu , Kao Shuh‐Ji , Hsieh Chih‐hao , Fukui Manabu , Okuda Noboru , Miki Takeshi , Shiah Fuh‐Kwo
Published: September 2017

It has been estimated that more than 48% of global methane emissions from lakes and reservoirs occur at low latitudes (<24°). To improve this estimate, knowledge regarding underexplored ecosystems, particularly deep lakes and reservoirs in Asian monsoon regions, is needed because the magnitude of methane emissions is influenced by lake bathymetry and climatic conditions. We conducted long‐term studies beginning in 2004 at Feitsui Reservoir (FTR) in Taiwan, a subtropical monomictic system with a maximum depth of 120 m to monitor seasonal and interannual variations of three key characteristics and to understand the mechanisms underlying these variations. Key characteristics investigated were as follows: (1) the balance of primary production and heterotrophic respiration as a determinant of vertical oxygen distribution, (2) methane production at the bottom of the reservoir, oxidation in the water column, and emissions from the lake surface, and (3) the contribution of methane‐originated carbon to the pelagic food web through methane‐oxidizing bacteria (MOB). This review highlights major achievements from FTR studies integrating isotopic, microbial, and modeling approaches. Based on our findings, we proposed two conceptual models: (1) a model of methane dynamics, which addresses the differences in methane emission mechanisms between deep and shallow lakes, and (2) a spatially explicit model linking benthic methane production to the pelagic food web, which addresses the diversity of MOB metabolisms and their dependence on oxygen availability. Finally, we address why long‐term studies of subtropical lakes and reservoirs are important for better understanding the effects of climate on low‐ to mid‐latitude ecosystems.
SETTLEMENT SCALING IN MIDDLE-RANGE SOCIETIES
Authors: Ortman Scott G. , Coffey Grant D.
Published: September 2017

The contemporary relevance of archaeology would be greatly enhanced if archaeologists could develop theory that frames human societies of all scales in the same terms. We present evidence that an approach known as settlement scaling theory can contribute to such a framework. The theory proposes that a variety of aggregate socioeconomic properties of human networks emerge from individuals arranging themselves in space so as to balance the costs of movement with the benefits of social interactions. This balancing leads to settlements that concentrate human interactions and their products in space and time in an open-ended way. The parameters and processes embedded in settlement scaling models are very basic, and this suggests that scaling phenomena should be observable in the archaeological record of middle-range societies just as readily as they have been observed in contemporary first-world nations. In this paper, we show that quantitative scaling relationships observed for modern urban systems, and more recently for early civilizations, are also apparent in settlement data from the Central Mesa Verde and northern Middle Missouri regions of North America. These findings suggest that settlement scaling theory may help increase the practical relevance of archaeology for present-day concerns.
Non-linear model calibration for off-design performance prediction of gas turbines with experimental data
Authors: Tsoutsanis Elias , Li Yi-Guang , Pilidis Pericles , Newby Mike
Published: September 2017

One of the key challenges of the gas turbine community is to empower the condition based maintenance with simulation, diagnostic and prognostic tools which improve the reliability and availability of the engines. Within this context, the inverse adaptive modelling methods have generated much attention for their capability to tune engine models for matching experimental test data and/or simulation data. In this study, an integrated performance adaptation system for estimating the steady-state off-design performance of gas turbines is presented. In the system, a novel method for compressor map generation and a genetic algorithm-based method for engine off-design performance adaptation are introduced. The methods are integrated into PYTHIA gas turbine simulation software, developed at Cranfield University and tested with experimental data of an aero derivative gas turbine. The results demonstrate the promising capabilities of the proposed system for accurate prediction of the gas turbine performance. This is achieved by matching simultaneously a set of multiple off-design operating points. It is proven that the proposed methods and the system have the capability to progressively update and refine gas turbine performance models with improved accuracy, which is crucial for model-based gas path diagnostics and prognostics.