bluuebunny/crossref_metadata_2025 huggingface dataset:
High mechanical advantage design of six-bar Stephenson mechanism for servo mechanical presses
Authors: Hu Jianguo , Sun Yousong , Cheng Yongqi
Published: July 2016

This article proposed a two-phase design scheme of Stephenson six-bar working mechanisms for servo mechanical presses with high mechanical advantage. In the qualitative design phase, first, a Stephenson six-bar mechanism with a slide was derived from Stephenson six-bar kinematic chains. Second, based on the instant center analysis method, the relationship between mechanical advantage and some special instant centers was founded, and accordingly a primary mechanism configuration with high mechanical advantage was designed qualitatively. Then, a parameterized prototype model was established, and the influences of design parameters toward slide kinematical characteristics were analyzed. In the quantitative design phase, a multi-objective optimization model, aiming at high mechanical advantage and dwelling characteristics, was built, and a case design was done to find optimal dimensions. Finally, simulations based on the software ADAMS were conducted to compare the transmission characteristics of the optimized working mechanism with that of slide-crank mechanism and symmetrical toggle mechanism, and an experimental press was made to validate the design scheme. The simulation and experiment results show that, compared with general working mechanisms, the Stephenson six-bar working mechanism has higher mechanical advantage and better dwelling characteristics, reducing capacities and costs of servo motors effectively.
Design analysis of machine tool structure with artificial granite material
Authors: Chen Tsung-Chia , Chen Yong-Jun , Hung Ming-Hung , Hung Jui-Pin
Published: July 2016

Artificial granite material has been used for construction of the high-precision machine due to superior damping ability. However, its lower material stiffness also lessens the application in fabrication of the machine tool. The purpose of this study was therefore aimed to verify the structure performance of the machine tool reformed with artificial granite material, instead of the casting iron. To gain insight into the optimized configuration of the vertical columns and spindle head stock, the static and dynamic characteristics of the machine models with cast iron and granite composites were predicted for comparison. With this, evaluations of the machine with different design were made to examine the experimental measurements on the prototype machine. According to the simulation results and experimental measurements, the static stiffness of the machine tool reformed with granite material is comparable to the original casting machine, differed by 8% approximately. However, granite machine shows superior dynamic stiffness, about 0.5–1.3 times of the conventional casting machine. This study verifies the feasibility and effectiveness in fabrication of the machine tool with the artificial composite material and provides the improvements for further fabrications.
Monte Carlo simulation for relationship between magnetic Barkhausen noise and elastic stress of steel
Authors: Li Liang , Luo Xiaoyu
Published: July 2016

Monte Carlo simulations were performed for three-dimensional Ising model to study the relationships between magnetic Barkhausen noise and elastic stress of steel. The magnetization process was simulated and the dimensionless magnetic Barkhausen noise was calculated by the differentiation of magnetization. Coupling constant of energy exchange in Ising model is considered to be inversely proportional to applied tensile stress. The simulation results show that as coupling constant decreases, the magnetic Barkhausen noise increases, as proved by the experimental results.
Effects of rail materials and axle loads on the wear behavior of wheel/rail steels
Authors: Liu Jihua , Jiang Wenjuan , Chen Shuiyou , Liu Qiyue
Published: July 2016

Four kinds of rail steels were tested to investigate the wear behaviors of wheel–rail materials under three kinds of axle loads. Results indicate that the increase in axle load not only significantly enlarges the wear loss but also enlarges the depth and the length of the fatigue cracks. However, with the decreases in the hardness ratios, some ripples are exhibited on the surface, and the wear surfaces become much rougher; the subsurface analyses deliver the presence of extremely rough surface, and the deformation depths are irregular. The relationship between the total wear loss of the wheel/rail system and the hardness ratio indicates that the hardness ratio of wheel/rail steels has slight impact on the total wear loss at a low axle load; however, the decrease in the hardness ratio enlarges the total wear loss significantly at a high axle load. In summary, a quenched rail should be chosen for the heavy-haul railway, and the hardness of the wheel steel should be raised to a degree close to the rail. However, a hot rolled rail is much suitable for the high-speed railway, and the wheel hardness should be smaller than the rail.
Surface quality analysis of die steels in powder-mixed electrical discharge machining using titan powder in fine machining
Authors: Long Banh Tien , Phan Nguyen Huu , Cuong Ngo , Toan Nguyen Duc
Published: July 2016

Improving the quality of surface molds after electrical discharge machining is still being considered by many researchers. Powder-mixed dielectric in electrical discharge machining showed that it is one of the processing methods with high efficiency. This article reports on the results of surface quality of mold steels after powder-mixed electrical discharge machining using titanium powder in fine machining. The process parameters such as electrode material, workpiece material, electrode polarity, pulse on-time, pulse off-time, current, and titanium powder concentration were considered in the research. These materials are most commonly used with die-sinking electrical discharge machining in the manufacture of molds and has been selected as the subject of research: workpiece materials were SKD61, SKT4, and SKD11 mold steels, and electrode materials were copper and graphite. Taguchi’s method is used to design experiments. The influence of the parameters on surface roughness was evaluated through the average value and ratio ( S/ N). Results showed that the parameters such as electrical current, electrode material, pulse on-time, electrode polarity, and interaction between the electrode materials with concentration powder mostly influence surface roughness and surface roughness at optimal parameters SRopt = 1.73 ± 0.39 µm. Analysis of the surface layer after powder-mixed electrical discharge machining using titanium powder in optimal conditions has shown that the white layer with more uniform thickness and increased hardness (≈861.0 HV), and amount and size of microscopic cracks, is reduced. This significantly leads to the increase in the quality of the surface layer.
Pragmatic clinical trials: Emerging challenges and new roles for statisticians
Authors: Califf Robert M
Published: July 2016

Patients, clinicians, and policymakers alike need access to high-quality scientific evidence in order to make informed choices about health and healthcare, but the current national clinical trials enterprise is not yet optimally configured for the efficient creation and dissemination of such evidence. However, new technologies and methods hold significant potential for accelerating the rate at which we are able to translate raw findings gathered from both patient care and clinical research into actionable knowledge. We are now entering a period in which the quantitative sciences are emerging as the critical disciplines for advancing knowledge about health and healthcare, and statisticians will increasingly serve as critical mediators in transforming data into evidence. In this new, data-centric era, biostatisticians not only need to be expert at analyzing data but should also be involved directly in diverse efforts, including the review and analysis of research portfolios in order to optimize the relevance of research questions, the use of “quality by design” principles to improve reliability and validity of each individual trial, and the mining of aggregate knowledge derived from the clinical research enterprise as a whole. In order to meet these challenges, it is imperative that we (1) nurture and build the biostatistical workforce, (2) develop a deeper understanding of the biological and clinical context among statisticians, (3) facilitate collaboration among biostatisticians and other members of the clinical trials enterprise, (4) focus on communication skills in training and education programs, and (5) enhance the quantitative capacity of the research and clinical practice worlds.
Notch signaling in lung diseases: focus on Notch1 and Notch3
Authors: Zong Dandan , Ouyang Ruoyun , Li Jinhua , Chen Yan , Chen Ping
Published: July 2016

Notch signaling is an evolutionarily conserved cell–cell communication mechanism that plays a key role in lung homeostasis, injury and repair. The loss of regulation of Notch signaling, especially Notch1 and Notch3, has recently been linked to the pathogenesis of important lung diseases, in particular, chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis, pulmonary arterial hypertension (PAH), lung cancer and lung lesions in some congenital diseases. This review focuses on recent advances related to the mechanisms and the consequences of aberrant or absent Notch1/3 activity in the initiation and progression of lung diseases. Our increasing understanding of this signaling pathway offers great hope that manipulating Notch signaling may represent a promising alternative complementary therapeutic strategy in the future.
Surrogate and clinical endpoints in interventional cardiology: are statistics the brakes?
Authors: Waliszewski Matthias , Rittger Harald
Published: July 2016

Background:

Randomized controlled trials are the gold standard for demonstrating safety and efficacy of coronary devices with or without accompanying drug treatments in interventional cardiology. With the advent of last-generation drug-eluting stents having enhanced technical attributes and long-term clinical benefits, the proof of incremental angiographic or long-term clinical efficacy becomes more challenging. The purpose of this review is to provide an overview of the most common and alternative study endpoints in interventional cardiology and their potential reimbursement value. Moreover, we intend to describe the statistical limitations in order to demonstrate differences between potential treatment groups. Furthermore, careful endpoint recommendations for a given patient number are offered for future study designs.

Methods:

The number of patients per treatment group was estimated for various study designs such as noninferiority test hypotheses with hard clinical endpoints and various surrogate endpoints. To test for differences in various surrogate endpoint scenarios, the corresponding patient group sizes were explored. To evaluate these endpoints in terms of their reimbursement impact, preferred endpoints for technical appraisals in interventional cardiology at the National Institute of Health and Care Excellence (NICE) were used.

Results:

Even with the most stringent experimental control to reduce bias-introducing factors, studies with hard primary clinical endpoints such as the occurrence of major adverse cardiac events (MACE) or target-lesion revascularization (TLR) rates remain the gold standard, with numbers reaching into the 300–700 patient range per group. Study designs using loss in fractional-flow reserve (FFR) or stent-strut-coverage rates can be statistically formulated; however, the clinical ramifications for the patient remain to be discussed. Nonrandomized study designs with intrapatient angiographic controls in nontarget vessels may merit further thoughts and explorations.

Conclusions:

From a reimbursement impact, the primary endpoints MACE and TLR are the best choices for a moderately sized study population of 500 patients per group. Angiographic endpoints, in particular minimal lumen diameter (MLD), are not useful in this context. The emerging endpoints such as loss in FFR or stent coverage require smaller patient populations. However, their impact on reimbursement-related decisions is limited.
Pharmacokinetic and Pharmacodynamic Properties of a Novel Inhaled Insulin
Authors: Heinemann Lutz , Baughman Robert , Boss Anders , Hompesch Marcus
Published: July 2016

Advances in insulin treatment options over recent decades have markedly improved the management of diabetes. Despite this, glycemic control remains suboptimal in many people with diabetes. Although postprandial glucose control has been improved with the development of subcutaneously injected rapid-acting insulin analogs, currently available insulins are not able to fully mimic the physiological time–action profile of endogenously secreted insulin after a meal. The delayed onset of metabolic action and prolonged period of effect induce the risk of postprandial hyperglycemia and late postprandial hypoglycemia. A number of alternative routes of insulin administration have been investigated over time in an attempt to overcome the limitations associated with subcutaneous administration and to provide an improved time–action insulin profile more closely simulating physiological prandial insulin release. Among these, pulmonary insulin delivery has shown the most promise. Technosphere® Inhaled Insulin (TI) is a rapid-acting inhaled human insulin recently approved by the FDA for prandial insulin therapy. In this article we discuss the pharmacokinetic and pharmacodynamic properties of TI, and, based on key studies performed during its clinical development, the implications for improved postprandial glucose control.
Intraoperative Ultrasound Guidance for the Removal of Nonmetallic Foreign Body from the Foot
Authors: Holmes George B. , Bitterman Adam , Hsu Andrew R. , Sclamberg Joy S. , Gitelis Steven
Published: July 2016

Ultrasound has become an increasingly valuable diagnostic tool throughout all areas of medicine. The role of diagnostic ultrasonography has an evolving role in orthopaedic surgery and particularly in the field of foot and ankle. Whether in the clinic or hospital setting, ultrasound has proven to be pivotal in the identification and localization of foreign bodies. The inherent limitations of plain films in identifying nonmetallic penetrating foreign bodies of the foot can be overcome or enhanced with the assistance of diagnostic ultrasound.

Levels of Evidence: Therapeutic, Level IV: Case report
The association between prolongation in QRS duration and presence of coronary collateral circulation in patients with acute myocardial infarction
Authors: Karahan Zülküf , Altıntaş Bernas , Uğurlu Murat , Kaya İlyas , Uçaman Berzal , Uluğ Ali Veysel , Altındağ Rojhat , Altaş Yakup , Adıyaman Mehmet Şahin , Öztürk Önder
Published: July 2016

Background

It is known that QRS duration is related to prognosis in acute myocardial infarction. The relation between QRS duration and coronary collateral circulation is uncertain. In the present study, we aimed to determine the relation between QRS duration and coronary collateral circulation in patients admitted with acute myocardial infarction.

Methods

The present study was composed of 109 consecutive patients with acute myocardial infarction. All patients had total occlusion in the left anterior descending coronary artery. Electrocardiographic recordings on admission were obtained for the assessment of QRS duration. The Rentrop classification was used to define coronary collateral circulation on coronary angiography. Patients were divided into two groups as follows: Group 1 with poor coronary collateral circulation (Rentrop 0–1) and Group 2 with good coronary collateral circulation (Rentrop 2–3).

Results

Of all patients, 62 patients were included in group 1 and 47 patients in group 2, respectively. In the present study, patients in the group 1 had longer QRS duration than patients in the group 2 (p < 0.005). Additionally, we found that Rentrop grading had negative correlation with both QRS duration and white blood cell count (r: −0.28; p < 0.005 and r: −0.35; p < 0.001).

Conclusion

Our study showed that there was an inverse relationship between QRS duration on admission and presence of coronary collateral circulation in patients with acute myocardial infarction.
Creating a better picture of chronic pain: improving pain pictogram designs through systematic evaluation of user responses
Authors: Stones Catherine , Knapp Peter , Closs S Jose
Published: July 2016

This article discusses the challenges of visually representing pain qualities in pictogram design. An existing set of 12 pictograms designed for people with literacy problems was evaluated to understand more about misunderstandings of pictogram interpretation. Two sets of university students from different disciplines were asked to interpret the pictograms, and a novel classification system was developed to categorise answer types, as ‘location’, ‘affective’, temporal’ or ‘literal’. Several design recommendations are made as a result that will help improve the design of pain pictograms as a whole as well as guide designers of related pictogram work. We demonstrate how, through the robust classification of incorrect responses, it is possible to extract useful comprehension error patterns to inform future design.
The current status of community-acquired pneumonia management and prevention in children under 5 years of age in India: a review
Authors: Yadav Krishna Kumar , Awasthi Shally
Published: July 2016

India has the highest number of global deaths of children under 5 years of age. In the year 2015, it was reported that there were 5.9 million deaths of children under 5 years of age globally, of which 1.2 million (20%) occurred in India alone. Currently, India has an under 5 mortality rate of 48 per 1000 live births. Community-acquired pneumonia contributes to about one sixth of this mortality. Fast breathing is the key symptom of community-acquired pneumonia. The World Health Organization recently categorized community-acquired pneumonia in children under 5 years of age into two, pneumonia, and severe pneumonia. Fast breathing with or without chest in-drawing is categorized as pneumonia and fast breathing with any of danger signs as severe pneumonia. Because effective vaccines against two of the common organisms causing community-acquired pneumonia, namely Streptococcus pneumoniae and Haemophilus influenzae type b, are available, there should be urgent and phased introduction into the Indian Universal Immunization Programme. Several preventable risk factors of community-acquired pneumonia such as lack of exclusive breast feeding for first 6 months of life, inappropriate complimentary feeding, iron deficiency anemia, malnutrition, and indoor air pollution should be adequately addressed. The community should be aware about the signs and symptoms of community-acquired pneumonia and its danger signs so that delay in qualified care seeking can be avoided. To achieve the sustainable development goal of ⩽25 under five deaths per 1000 live births by 2030, a multipronged approach is the need of the hour.
Challenges in the diagnosis and treatment of CNS demyelinating disorders in Zambia
Authors: Miskin Dhanashri P , Saadi Altaf , Chikoya Laston , Sloane Jacob A , Koralnik Igor J , Siddiqi Omar K
Published: July 2016

Demyelinating disease occurs in a population of black adult Zambians whose genetic and environmental risk factors for multiple sclerosis are thought to be rare. The diagnosis of demyelinating disease was based predominantly on compatible clinical history and neurologic exam findings, and in some cases, more definitely established by cerebrospinal fluid exam and imaging findings. When available, laboratory studies excluded other known causes of CNS demyelination. Timely evaluation and treatment with disease-modifying therapies was related to the patient’s employment status. Lack of financial means to go abroad was a major hurdle in a patient’s ability to receive treatment. Significant barriers often prohibit timely diagnosis and prevent proper management of these patients.
The Engulfing Mother in Indian Mythology: Masculinity and Conflicting Desires
Authors: Kakar Sudhir
Published: July 2016

The article describes a key complex of male Hindu development in India that is often met with in clinical work and in products of Hindu cultural imagination. This complex, which the author calls ‘maternal enthrallment’, has deep influence on adult male attitudes towards women in India. The article explores the three elements of maternal enthrallment through an analysis of well-known and popular myths and legends of Hindu India.
Mothers and Daughters in Ismat Chugtai’s Writings
Authors: Farooqi Baran , Tiwari Kusha
Published: July 2016

This article delves into the discourse of motherhood and the girl-child as deconstructed by Ismat Chughtai in A Life in Words (2012) and The Crooked Line (2003). These two works due to their intertextual connections and thematic similarities become appropriate tools for analyzing Ismat’s concern with femininity as a complex web of tangible relations. Ismat’s women, even though living cloistered lives exert their individuality and authority in discursive ways. The girl-child narrator in both these works is a spectator to the wiles that women employ to empower themselves in the male dominated society. In these two works, Ismat unscrupulously deconstructs the images of the sacrificing mother and the dutiful daughter that are ingrained within the patriarchal system. In the process she liberates the experience of motherhood from age-old categories and gives voice to hidden anger, angst and discontent in the mothering self. At the same time Ismat also destabilizes the stereotypical image of the girl-child who not only acquires a certain subject position but also challenges motherly domination and familial authority. Thus both Shaman and young Ismat devalue and delegitimize the figure of the ideal daughter as exhibited in the polished conduct of Bari Apa and Manjhu (Shaman’s elder sisters). In deconstructing these established discourses, Ismat is also creating new ones that recognize alternative subject positions for women.
Protesting Rape in India
Authors: Gomes Chandan
Published: July 2016

This photo essay is an account from the perspective of an unknown citizen of the protest movement that happened in Delhi after the rape of a young girl on a bus in the city in December 2012. Chandan Gomes documents the movement not as a documentary photographer or a photo journalist, but as a protestor.
Ambedkar and the Struggle for Women’s Equality
Authors: Vajpeyi Ananya
Published: July 2016

The article highlights Dr B. R. Ambedkar’s battle for equality and sketches out his political campaigns which were designed to boycott caste rules and allow ‘untouchables’ access to temples, wells and other civic resources—all with the intention to raise public consciousness against the practice of untouchability. And, importantly, the article talks about how women were included in these campaigns. It throws light on how Ambedkar addressed women as mothers and social change initiators; and how, as a lawyer and legislator, he engaged with the issues of not only the ‘untouchable’ women but also of women as a part of the labour force.
A checklist for health research priority setting: nine common themes of good practice
Authors: Viergever Roderik F , Olifson Sylvie , Ghaffar Abdul , Terry Robert F
Published: July 2016

Health research priority setting processes assist researchers and policymakers in effectively targeting research that has the greatest potential public health benefit. Many different approaches to health research prioritization exist, but there is no agreement on what might constitute best practice. Moreover, because of the many different contexts for which priorities can be set, attempting to produce one best practice is in fact not appropriate, as the optimal approach varies per exercise. Therefore, following a literature review and an analysis of health research priority setting exercises that were organized or coordinated by the World Health Organization since 2005, we propose a checklist for health research priority setting that allows for informed choices on different approaches and outlines nine common themes of good practice. It is intended to provide generic assistance for planning health research prioritization processes. The checklist explains what needs to be clarified in order to establish the context for which priorities are set; it reviews available approaches to health research priority setting; it offers discussions on stakeholder participation and information gathering; it sets out options for use of criteria and different methods for deciding upon priorities; and it emphasizes the importance of well-planned implementation, evaluation and transparency.
Evaluation of off-target and on-target scoring algorithms and integration into the guide RNA selection tool CRISPOR
Authors: Haeussler Maximilian , Schönig Kai , Eckert Hélène , Eschstruth Alexis , Mianné Joffrey , Renaud Jean-Baptiste , Schneider-Maunoury Sylvie , Shkumatava Alena , Teboul Lydia , Kent Jim , Joly Jean-Stephane , Concordet Jean-Paul
Published: July 2016

Background

The success of the CRISPR/Cas9 genome editing technique depends on the choice of the guide RNA sequence, which is facilitated by various websites. Despite the importance and popularity of these algorithms, it is unclear to which extent their predictions are in agreement with actual measurements.

Results

We conduct the first independent evaluation of CRISPR/Cas9 predictions. To this end, we collect data from eight SpCas9 off-target studies and compare them with the sites predicted by popular algorithms. We identify problems in one implementation but found that sequence-based off-target predictions are very reliable, identifying most off-targets with mutation rates superior to 0.1 %, while the number of false positives can be largely reduced with a cutoff on the off-target score. We also evaluate on-target efficiency prediction algorithms against available datasets. The correlation between the predictions and the guide activity varied considerably, especially for zebrafish. Together with novel data from our labs, we find that the optimal on-target efficiency prediction model strongly depends on whether the guide RNA is expressed from a U6 promoter or transcribed in vitro. We further demonstrate that the best predictions can significantly reduce the time spent on guide screening.

Conclusions

To make these guidelines easily accessible to anyone planning a CRISPR genome editing experiment, we built a new website (http://crispor.org) that predicts off-targets and helps select and clone efficient guide sequences for more than 120 genomes using different Cas9 proteins and the eight efficiency scoring systems evaluated here.
A survey of studies in systemic functional language description and typology
Authors: Mwinlaaru Isaac N. , Xuan Winfred Wenhui
Published: July 2016

Systemic functional theory embodies a multilingual perspective to language from its earliest formulation. However, it was not until the last two decades that descriptions of languages other than English, particularly in the light of language typology, garnered much interest among scholars working with systemic theory. The objective of the present study is to survey the growing literature in this field. The survey consists of two main parts. The first part discusses theoretical developments in relation to language description and typology. The second part presents a meta-analysis of empirical studies in the field. The meta-analysis examines the historical progress in systemic typology and description of non-Anglo languages, the coverage of descriptions in terms of areal and genetic language families, mode of publication and, finally, methodological procedures employed by the studies. Challenges arising from these analytical decisions are also examined. The motivation for the study is to provide a state of the art review of the field in order to guide new descriptions and draw implications for further research in functional language typology, in general, and systemic typology, in particular.
DISCUSSION*Received by the Editor October 31, 1958.
Authors: JOHNSON CURTIS H.
Published: July 2016

I am in complete accord with this paper. I feel, however, that some additional suggestions are desirable concerning the mechanics of delivery of an orally presented paper.
DIFFICULTIES IN SCANNING CURRENT GEOPHYSICAL LITERATURE
Authors: DE GERY JEROME CHASTENET , NAUDY HENRI
Published: July 2016

We have read with great interest Mr. Hutchison's paper entitled “Magnetic Analysis by Logarithmic Curves” (GEOPHYSICS, v. 23, p. 749-769) concerning a problem treated by ourselves at the 12th Congress of the European Association of Exploration Geophysicists at Brussels in June, 1957.
Autocrine Positive Feedback Regulation of Prolactin Release From Tilapia Prolactin Cells and Its Modulation by Extracellular Osmolality
Authors: Yamaguchi Yoko , Moriyama Shunsuke , Lerner Darren T. , Grau E. Gordon , Seale Andre P.
Published: July 2016

Prolactin (PRL) is a vertebrate hormone with diverse actions in osmoregulation, metabolism, reproduction, and in growth and development. Osmoregulation is fundamental to maintaining the functional structure of the macromolecules that conduct the business of life. In teleost fish, PRL plays a critical role in osmoregulation in fresh water. Appropriately, PRL cells of the tilapia are directly osmosensitive, with PRL secretion increasing as extracellular osmolality falls. Using a model system that employs dispersed PRL cells from the euryhaline teleost fish, Oreochromis mossambicus, we investigated the autocrine regulation of PRL cell function. Unknown was whether these PRL cells might also be sensitive to autocrine feedback and whether possible autocrine regulation might interact with the well-established regulation by physiologically relevant changes in extracellular osmolality. In the cell-perfusion system, ovine PRL and two isoforms of tilapia PRL (tPRL), tPRL177 and tPRL188, stimulated the release of tPRLs from the dispersed PRL cells. These effects were significant within 5–10 minutes and lasted the entire course of exposure, ceasing within 5–10 minutes of removal of tested PRLs from the perifusion medium. The magnitude of response varied between tPRL177 and tPRL188 and was modulated by extracellular osmolality. On the other hand, the gene expression of tPRLs was mainly unchanged or suppressed by static incubations of PRL cells with added PRLs. By demonstrating the regulatory complexity driven by positive autocrine feedback and its interaction with osmotic stimuli, these findings expand upon the knowledge that pituitary PRL cells are regulated complexly through multiple factors and interactions.
Generation of intestinal surface: an absorbing tale
Authors: Walton Katherine D. , Freddo Andrew M. , Wang Sha , Gumucio Deborah L.
Published: July 2016

The vertebrate small intestine requires an enormous surface area to effectively absorb nutrients from food. Morphological adaptations required to establish this extensive surface include generation of an extremely long tube and convolution of the absorptive surface of the tube into villi and microvilli. In this Review, we discuss recent findings regarding the morphogenetic and molecular processes required for intestinal tube elongation and surface convolution, examine shared and unique aspects of these processes in different species, relate these processes to known human maladies that compromise absorptive function and highlight important questions for future research.
Asymmetric Total Synthesis of Crotophorbolone: Construction of the 5/7/6-Fused Ring System via an α-Alkoxy Bridgehead Radical Reaction
Authors: Urabe Daisuke , Asaba Taro , Inoue Masayuki
Published: July 2016

This account describes the development of a synthetic route to crotophorbolone (1). Compound 1 is classified as a derivative of the tigliane diterpenoids, and possesses a highly oxygenated 5/7/6-fused ABC-ring system. First, the six-membered C-ring fragment with five contiguous stereocenters was stereoselectively constructed from (R)-carvone. Nucleophilic addition of the three-carbon unit to the C-ring and stereoselective attachment of the five-membered A-ring through a π-allyl Stille coupling reaction provided the substrate for the key radical cyclization. Next, treatment of the O,Se-acetal with V-40 and (TMS)3SiH in refluxing toluene generated the α-alkoxy bridgehead radical, which participated in the endo-cyclization of the seven-membered B-ring with formation of the sterically congested bond in C9-stereospecific and C10-stereoselective manners. The C11-methyl group controlled the C10-stereochemical outcome via a long-range steric interaction, which was supported by the calculated transition state of the abbreviated α-alkoxy bridgehead radical structure. Finally, the functional groups on the 5/7/6-membered ring system were manipulated by Rh-catalyzed C2-olefin isomerization, C13-decarboxylative oxidation and C4-hydroxylation, completing the first total synthesis of 1 in 33 steps from (R)-carvone.
Automated analysis of retinal imaging using machine learning techniques for computer vision
Authors: De Fauw Jeffrey , Keane Pearse , Tomasev Nenad , Visentin Daniel , van den Driessche George , Johnson Mike , Hughes Cian O , Chu Carlton , Ledsam Joseph , Back Trevor , Peto Tunde , Rees Geraint , Montgomery Hugh , Raine Rosalind , Ronneberger Olaf , Cornebise Julien
Published: July 2016

There are almost two million people in the United Kingdom living with sight loss, including around 360,000 people who are registered as blind or partially sighted. Sight threatening diseases, such as diabetic retinopathy and age related macular degeneration have contributed to the 40% increase in outpatient attendances in the last decade but are amenable to early detection and monitoring. With early and appropriate intervention, blindness may be prevented in many cases.

Ophthalmic imaging provides a way to diagnose and objectively assess the progression of a number of pathologies including neovascular (“wet”) age-related macular degeneration (wet AMD) and diabetic retinopathy. Two methods of imaging are commonly used: digital photographs of the fundus (the ‘back’ of the eye) and Optical Coherence Tomography (OCT, a modality that uses light waves in a similar way to how ultrasound uses sound waves). Changes in population demographics and expectations and the changing pattern of chronic diseases creates a rising demand for such imaging. Meanwhile, interrogation of such images is time consuming, costly, and prone to human error. The application of novel analysis methods may provide a solution to these challenges.

This research will focus on applying novel machine learning algorithms to automatic analysis of both digital fundus photographs and OCT in Moorfields Eye Hospital NHS Foundation Trust patients.

Through analysis of the images used in ophthalmology, along with relevant clinical and demographic information, Google DeepMind Health will investigate the feasibility of automated grading of digital fundus photographs and OCT and provide novel quantitative measures for specific disease features and for monitoring the therapeutic success.
Hospital and patient influencing factors of treatment schemes given to type 2 diabetes mellitus inpatients in Inner Mongolia, China
Authors: Zhang Nan , McNeil Edward , Assanangkornchai Sawitri , Fan Yancun
Published: July 2016

Background:

In clinical practice, the physician’s treatment decision making is influenced by many factors besides the patient’s clinical conditions and is the fundamental cause of healthcare inequity and discrimination in healthcare settings. Type 2 diabetes mellitus (T2DM) is a chronic disease with high prevalence, long average length of stay and high hospitalization rate. Although the treatment of T2DM is well guideline driven, there is a large body of evidence showing the existence of treatment disparities. More empirical studies from the provider side are needed to determine if non-clinical factors influence physician’s treatment choices.

Objective:

To determine the hospital and patient influencing factors of treatment schemes given to T2DM inpatients in Inner Mongolia, China.

Methods:

A cross-sectional, hospital-based survey using a cluster sampling technique was conducted in three tertiary hospitals and three county hospitals in Inner Mongolia, China. Treatment schemes were categorized as lifestyle management, oral therapy or insulin therapy according to the national guideline. Socio-demographic characteristics and variables related to severity of disease at the individual level and hospital level were collected. Weighted multinomial logistic regression models were used to determine influencing factors of treatment schemes.

Results:

Regardless of patients’ clinical conditions and health insurance types, both hospital and patient level variables were associated with treatment schemes. Males were more likely to be given oral therapy (RRR=1.72, 95% CI=1.06-2.81) and insulin therapy (RRR=1.94, 95% CI=1.29-2.91) compared to females who were given lifestyle management more frequently. Compared to the western region, hospitals in the central regions of Inner Mongolia were less likely to prescribe T2DM patients oral therapy (RRR = 0.18, 95% CI=0.05-0.61) and insulin therapy (RRR = 0.20, 95% CI=0.06-0.67) than lifestyle management. Compared with non-reformed tertiary hospitals, reformed tertiary hospitals and county hospitals were less likely to give T2DM patients oral therapy (RRR = 0.07 and 0.1 respectively) and insulin therapy (RRR = 0.11 and 0.17 respectively).

Conclusion:

Gender was the only socio-demographic factors associated with treatment scheme for T2DM patients. Hospitals from different regions have different T2DM treatment patterns. Implementation of reform was shown to be associated with controlling medication use for T2DM inpatients. Further studies are needed to investigate the causes of unreasonable treatment disparities so that policies can be generated accordingly.
An open RNA-Seq data analysis pipeline tutorial with an example of reprocessing data from a recent Zika virus study
Authors: Wang Zichen , Ma'ayan Avi
Published: July 2016

RNA-seq analysis is becoming a standard method for global gene expression profiling. However, open and standard pipelines to perform RNA-seq analysis by non-experts remain challenging due to the large size of the raw data files and the hardware requirements for running the alignment step. Here we introduce a reproducible open source RNA-seq pipeline delivered as an IPython notebook and a Docker image. The pipeline uses state-of-the-art tools and can run on various platforms with minimal configuration overhead. The pipeline enables the extraction of knowledge from typical RNA-seq studies by generating interactive principal component analysis (PCA) and hierarchical clustering (HC) plots, performing enrichment analyses against over 90 gene set libraries, and obtaining lists of small molecules that are predicted to either mimic or reverse the observed changes in mRNA expression. We apply the pipeline to a recently published RNA-seq dataset collected from human neuronal progenitors infected with the Zika virus (ZIKV). In addition to confirming the presence of cell cycle genes among the genes that are downregulated by ZIKV, our analysis uncovers significant overlap with upregulated genes that when knocked out in mice induce defects in brain morphology. This result potentially points to the molecular processes associated with the microcephaly phenotype observed in newborns from pregnant mothers infected with the virus. In addition, our analysis predicts small molecules that can either mimic or reverse the expression changes induced by ZIKV. The IPython notebook and Docker image are freely available at: http://nbviewer.jupyter.org/github/maayanlab/Zika-RNAseq-Pipeline/blob/master/Zika.ipynb and https://hub.docker.com/r/maayanlab/zika/.
2016 ISCB Overton Prize awarded to Debora Marks
Authors: Fogg Christiana N. , Kovats Diane E.
Published: July 2016

The International Society for Computational Biology (ISCB) recognizes the achievements of an early- to mid-career scientist with the Overton Prize each year. The Overton Prize was established to honor the untimely loss of Dr. G. Christian Overton, a respected computational biologist and founding ISCB Board member. Winners of the Overton Prize are independent investigators in the early to middle phases of their careers who are selected because of their significant contributions to computational biology through research, teaching, and service. 2016 will mark the fifteenth bestowment of the ISCB Overton Prize.  ISCB is pleased to confer this award the to Debora Marks, Assistant Professor of Systems Biology and director of the Raymond and Beverly Sackler Laboratory for Computational Biology at Harvard Medical School.
From biorhetorics to zoorhetorics
Authors: Pain Stephen
Published: July 2016

The present article aims to introduce the field of “Zoorhetorics”, as a particular case of Biorhetorics, earlier introduced by the author in the academic world. A brief explanation will be provided of its aims, methods and models, while particular attention will be devoted to the concept of “sustainable good”, considered crucial in both the “Bio-” and “Zoorhetorics” formulations.
Conditioning or cognition? Understanding interspecific communication as a way of improving animal training (a case study with elephants in Nepal)
Authors: Telkänranta Helena
Published: July 2016

When animals are trained to function in a human society (for example, pet dogs, police dogs, or sports horses), different trainers and training cultures vary widely in their ability to understand how the animal perceives the communication efforts of the trainer. This variation has considerable impact on the resulting performance and welfare of the animals. There are many trainers who frequently resort to physical punishment or other pain-inflicting methods when the attempts to communicate have failed or when the trainer is unaware of the full range of the potential forms of human-animal communication. Negative consequences of this include animal suffering, imperfect performance of the animals, and sometimes risks to humans, as repeated pain increases aggression in some animals. The field of animal training is also interesting from a semiotic point of view, as it effectively illustrates the differences between the distinct forms of interaction that are included in the concept of communication in the zoosemiotic discourse. The distinctions with the largest potential in improving human-animal communication in animal training, is understanding the difference between verbal communication of the kind that requires rather high cognitive capabilities of the animal, and communication based on conditioning, which is a form of animal learning that does not require high cognitive ability. The differences and potentials of various types of human-animal communication are discussed in the form of a case study of a novel project run by a NGO called Working Elephant Programme of Asia (WEPA), which introduces humane, science-based training and handling methods as an alternative to the widespread use of pain and fear that is the basis of most existing elephant training methods.
Abstraction, cruelty and other aspects of animal play (exemplified by the playfulness of Muki and Maluca)
Authors: Tønnessen Morten
Published: July 2016

Play behaviour is notorious for constituting a much debated, yet little clarified field of research. In this article, attempts are made to reach conclusions on the relation between human play and the play of other animals (especially cat play), as well as on the very character of play. The concept of Umwelt is reviewed, as are definitions of animal play, categorization of animal play and the role of meta-communication in playful behaviour. For some, play is a symbol of everything that is good. The author of the current article does not deny that social morality may have originated from play behaviour, but stresses the existence of cruelty play, which leads to additional assumptions. Another notion that is treated in some detail is perceptual play, which proves to demonstrate complex semiotic play that is related first of all to signification. At the end of the article an alternative categorization of animal play is suggested, in which the fundamental role of mind games is emphasized. Throughout the text, examples of play behaviour are offered by the two domestic cats Muki and Maluca.
An owl and a mirror: On Bosch’s visual motif’s meaning
Authors: Melnikova-Grigorjeva Jelena , Bogdanova Olga
Published: July 2016

Our main goal in this paper is to study one Hieronymus Bosch’s iconographic motif, an owl, considering the iconography, production of meaning and connotations. Pursuant to the comparative analysis of the variants of the formal model we intend to ascertain the meaning of Bosch’s “owl” motif. We supplement its pure visual legend throughout European art history with mythological and symbolic (mainly verbal) legend. Methodologically, we base the vast range of interpretations on the school of history of ideas (Aby Warburg, Ernst Gombrich, Erwin Panofsky, Francis Yates, Carlo Ginzburg) and the Tartu-Moscow school of semiotics of culture and text analysis. The article concludes that the “owl” motif, including in the works of Bosch, conveys the semantic aura of the “blind sight” (“blind foresight”). This ideological concept is in turn included into the archaic concept of mutual communication between the worlds carried out by a mythological observer — shaman, trickster.
Re-semblance and re-evolution: Paramorphism and semiotic co-option may explain the re-evolution of similar phenotypes
Authors: Kleisner Karel
Published: July 2016

The independent emergence of similar features in phylogenetically nonallied groups of organisms has usually been explained as the result of similar selection pressures particular to specific environments. This explanation has been more or less helpful in elucidating convergent resemblances among organisms since the times of Darwin. Nevertheless, intensive research has brought new knowledge on the emergence of structural similarity among organisms, especially during the last two decades. We now have manifold evidence of the phenomena of evolutionary re-entries or re-evolution, which happens when a particularcharacter present in one organic taxon also appears in another taxon which does not share an immediate ancestry. This is not the re-appearance of the same character, but rather of a similar one. Here I propose a model of threefold origin of similar phenotypic features in unrelated organisms stemming from intrinsic, extrinsic and semiosic causation. It is suggested that neither externalist nor internalist explanations per se, nor any combination thereof, are sufficient to cover all the manifold instances of character re-evolution. There is also a special group of resemblances that consists of what is originated, shaped, and retained in evolution due to meaning attributed to them by particular organic subjects. These cases cannot be fully understood without inviting a biosemiotic approach. Integrating Uexküll’s theory of meaning with the recent evolutionary developmental perspective could complete our understanding of phenotypic re-evolution.