bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristic Chromatogram: A Method of Discriminate and Quantitative Analysis for Quality Evaluation of Uncaria Stem with Hooks
Authors: Hou Jinjun , Feng Ruihong , Zhang Yibei , Pan Huiqin , Yao Shuai , Han Sumei , Feng Zijin , Cai Luying , Wu Wanying , Guo De-an 
Published: December 2017

AbstractIt remains a challenge to establish new monographs for herbal drugs derived from multiple botanical sources. Specifically, the difficulty involves discriminating and quantifying these herbs with components whose levels vary markedly among different samples. Using Uncaria stem with hooks as an example, a characteristic chromatogram was proposed to discriminate its five botanical origins and to quantify its characteristic components in the chromatogram. The characteristic chromatogram with respect to the components of Uncaria stem with hooks with the five botanical origins was established using 0.02% diethylamine and acetonitrile as the mobile phase. The total analysis time was 50 min and the detection wavelength was 245 nm. Using the same chromatogram parameters, the single standard to determine multicomponents method was validated to simultaneously quantify nine indole alkaloids, including vincosamide, 3α-dihydrocadambine, isocorynoxeine, corynoxeine, isorhynchophylline, rhynchophylline, hirsuteine, hirsutine, and geissoschizine methyl ether. The results showed that only the Uncaria stem with hooks from Uncaria rhynchophylla, the most widely used in the herbal market, showed the presence of these nine alkaloids. The conversion factors were 1.27, 2.32, 0.98, 1.04, 1.00, 1.02, 1.26, 1.33, and 1.25, respectively. The limits of quantitation were lower than 700 ng/mL. The total contents of 31 batches of Uncaria stem with hooks were in the range of 0.1 – 0.6%, except for Uncaria hirsuta Havil and Uncaria sinensis (Oliv.) Havil. The results also showed that the total content of indole alkaloids tended to decrease with an increase in the hook diameter. This showed that the characteristic chromatogram is practical for controlling the quality of traditional Chinese medicines with multiple botanical origins.
Lipid bilayer mediates ion-channel cooperativity in a model of hair-cell mechanotransduction
Authors: Gianoli Francesco , Risler Thomas , Kozlov Andrei S. 
Published: December 2017

Significance
Hearing relies on molecular machinery that consists of springs stretched by mechanical stimuli and mechanosensitive ion channels responding to the generated tension. Reproducing the experimental data theoretically without requiring unrealistically large conformational changes of the channels has been a longstanding hurdle. Here, we propose and develop a model with two mobile channels per spring, coupled by elastic forces within the membrane. The relative motion of the channels following their cooperative opening and closing produces the required change in spring extension. This study lies at the interface between the fields of membrane mechanics and mechanotransduction in the inner ear. It describes a physiological function for the bilayer-mediated cooperativity between mechanosensitive ion channels in a vertebrate sensory system.
Why conceptual competence won’t help the non-naturalist epistemologist
Authors: Werner Preston J. 
Published: December 2017

AbstractNon-naturalist normative realists face an epistemological objection: They must explain how their preferred route of justification ensures a non-accidental connection between justified moral beliefs and the normative truths. One strategy for meeting this challenge begins by pointing out that we are semantically or conceptually competent in our use of the normative terms, and then argues that this competence guarantees the non-accidental truth of some of our first-order normative beliefs. In this paper, I argue against this strategy by illustrating that this competence based strategy undermines the non-naturalist's ability to capture the robustly normative content of our moral beliefs.
Introduction: revolution and counter-revolution in Egypt
Authors: Tansel Cemal Burak , De Smet Brecht 
Published: December 2017

SUMMARY
This introduction to the ROAPE debate reasserts the centrality of revolutionary theory to understand the dynamics of social and political struggles in contemporary Middle East and North Africa. Framed around the conceptual and political interventions brought about by Brecht De Smet’s Gramsci on Tahrir (2016), we discuss the utility of Gramscian concepts in explaining the trajectories of social mobilisations in the peripheries of global capitalism.
DNCON2: improved protein contact prediction using two-level deep convolutional neural networks
Authors: Adhikari Badri , Hou Jie , Cheng Jianlin 
Published: December 2017

Abstract

Motivation
Significant improvements in the prediction of protein residue–residue contacts are observed in the recent years. These contacts, predicted using a variety of coevolution-based and machine learning methods, are the key contributors to the recent progress in ab initio protein structure prediction, as demonstrated in the recent CASP experiments. Continuing the development of new methods to reliably predict contact maps is essential to further improve ab initio structure prediction.

Results
In this paper we discuss DNCON2, an improved protein contact map predictor based on two-level deep convolutional neural networks. It consists of six convolutional neural networks—the first five predict contacts at 6, 7.5, 8, 8.5 and 10 Å distance thresholds, and the last one uses these five predictions as additional features to predict final contact maps. On the free-modeling datasets in CASP10, 11 and 12 experiments, DNCON2 achieves mean precisions of 35, 50 and 53.4%, respectively, higher than 30.6% by MetaPSICOV on CASP10 dataset, 34% by MetaPSICOV on CASP11 dataset and 46.3% by Raptor-X on CASP12 dataset, when top L/5 long-range contacts are evaluated. We attribute the improved performance of DNCON2 to the inclusion of short- and medium-range contacts into training, two-level approach to prediction, use of the state-of-the-art optimization and activation functions, and a novel deep learning architecture that allows each filter in a convolutional layer to access all the input features of a protein of arbitrary length.

Availability and implementation
The web server of DNCON2 is at http://sysbio.rnet.missouri.edu/dncon2/ where training and testing datasets as well as the predictions for CASP10, 11 and 12 free-modeling datasets can also be downloaded. Its source code is available at https://github.com/multicom-toolbox/DNCON2/.

Supplementary information
Supplementary data are available at Bioinformatics online.
Genetic Methodologies and Applications
Authors: Purcell Shaun M. 
Published: December 2017

Abstract
Mental illness is highly heritable, yet it has been difficult historically to identify the specific genes that comprise that risk. This difficulty resides in the fact that the genetic risk for all common mental disorders is polygenic, with perhaps hundreds of genetic variations, each of small effect, contributing to the overall risk. Despite these challenges, the field has made dramatic advances over the past decade in beginning to understand the genetic basis of mental illness. This chapter provides an overview of the experimental approaches used, beginning with epidemiology and population genetics to define the heritability of an illness, to classic studies of large families and linkage disequilibrium analysis, to genome-wide investigations including genome-wide association studies (GWAS), exome sequencing, and whole genome sequencing. Increasingly, these genetic advances are being understood within the biological context of disease pathophysiology.
Network Methods for Elucidating the Complexity of Common Human Diseases
Authors: Schadt Eric E. 
Published: December 2017

Abstract
The life sciences are now a significant contributor to the ever expanding digital universe of data, and stand poised to lead in both the generation of big data and the realization of dramatic benefit from it. We can now score variations in DNA across whole genomes; RNA levels and alternative isoforms, metabolite levels, protein levels, and protein state information across the transcriptome, metabolome and proteome; methylation status across the methylome; and construct extensive protein–protein and protein–DNA interaction maps, all in a comprehensive fashion and at the scale of populations of individuals. This chapter describes a number of analytical approaches aimed at inferring causal relationships among variables in very large-scale datasets by leveraging DNA variation as a systematic perturbation source. The causal inference procedures are also demonstrated to enhance the ability to reconstruct truly predictive, probabilistic causal gene networks that reflect the biological processes underlying complex phenotypes like disease.
Methods for In Vivo Gene Manipulation
Authors: Monteggia Lisa M. , Xu Wei 
Published: December 2017

Abstract
Recent advances in mouse genetics have opened many new avenues of research in which to explore gene function in the brain, and contributions to the pathophysiology and treatment of psychiatric disorders. The use of the mouse to explore gene function has contributed a better understanding of the role of specific genes in the nervous system including their influence on neural circuits and complex behavior.
This chapter explores current approaches to manipulate gene function in a mouse. Genetically modified mice allow for the investigation of a particular gene in vivo. The approaches discussed highlight recent advances to specifically overexpress or disrupt a specific gene of interest in the brain. We also highlight viral-mediated gene transfer approaches to allow for spatial and temporal control of gene function.
Application of Stem Cells to Understanding Psychiatric Disorders
Authors: Brennand Kristen 
Published: December 2017

Abstract
While much has been learned through clinical post-mortem and neuroimaging studies of patients and animal models of autism spectrum disorder (ASD), bipolar disorder (BD) and schizophrenia (SZ), these classical approaches have yet to fully elucidate the interaction of complex genetic risk factors on disease predisposition. The derivation of human induced pluripotent stem cells (hiPSCs) from patients with psychiatric disorders permits the study of the full complement of risk variants (known and unknown) that underlie disease predisposition, precisely in the cell types relevant to disease. The following chapter covers work to date regarding the advancements in the use of hiPSCs to model psychiatric disorders.
Immune Mechanisms of Depression
Authors: Ménard Caroline , Pfau Madeline L. , Hodes Georgia E. , Russo Scott J. 
Published: December 2017

Abstract
Mood disorders such as major depressive disorder (MDD) are diagnosed largely based upon behavioral symptoms rather than biological factors. Some have argued that a lack of rigorous biomarker-based diagnosis is the reason why 30%–50% of MDD patients are unresponsive to traditional antidepressant medications. Over the past few decades, MDD has been shown to be highly prevalent in patients suffering from chronic inflammatory conditions, such as lupus erythematosus, multiple sclerosis, etc. Moreover, subgroups of MDD patients have shown consistently higher levels of circulating pro-inflammatory cytokines. Together, these clinical findings suggest that alterations within the immune system might contribute to the behavioral symptoms of MDD. In this chapter, we review the growing literature in both humans with MDD and in rodent stress models of depression that support a role for the immune system in depression.
Synaptic and Circuit Mechanisms of Anxiety Disorders
Authors: Li Anfei , Lee Francis S. 
Published: December 2017

Abstract
A fundamental issue in treating anxiety disorders—and many other mental illnesses—is the lack of mechanistic understanding of the underlying pathophysiology. Recent studies, both in human and rodent, have taken the steps to elucidate the key brain regions and circuits that are implicated in anxiety disorders. In this chapter, we highlight how human and rodent studies can complement each other, and how an integrative approach provides bridges between the relevant but complex and imprecise phenomenology of human behavior and the solid findings of rodent neurobiology that can be difficult to extrapolate to human behavior and anxiety disorders. Recent findings in both humans and rodent models, and more importantly, how the two models have complemented each other, have enhanced our understanding of the pathophysiology of anxiety disorders.
The Neurobiology of Resilience
Authors: Feder Adriana , Horn Sarah R. , Haglund Margaret , Southwick Steven M. , Charney Dennis S. 
Published: December 2017

Abstract
Resilience is the ability to adapt successfully in the face of severe stress, trauma, or adversity. Over the past several decades, a wide range of studies in children and later in adults identified several key psychosocial characteristics associated with resilience, including emotion regulation, cognitive flexibility, positive emotions, and the availability of social support, among others. More recent studies are increasingly employing integrative approaches, incorporating genomic, neuroendocrine, and neuroimaging data to the study of resilience. This chapter reviews our current understanding of the neurobiology of resilience from genomic, developmental, psychosocial, neuroendocrine, brain circuitry, and integrative perspectives, and includes a final section focusing on implications for prevention and treatment of stress-related psychopathology.
Animal Models of Addiction
Authors: Christopher Evans J. , Kieffer Brigitte L. , Jentsch David , Maldonado Rafael J. 
Published: December 2017

Abstract
Drug addiction, now officially diagnosed as substance use disorder (SUD), is a chronic brain syndrome characterized by the compulsive use of drugs, loss of control over drug taking in spite of its adverse consequences, and relapse even after long periods of drug abstinence. Animal models have played a critical role in our understanding of the molecules, circuits, and behaviors associated with substance use disorders. This chapter reviews animal models that have been widely used to assess all stages of the addiction cycle: from drug initiation, through drug seeking, to withdrawal and relapse. We discuss the power of genetics, especially in generating rodent models for the discovery of essential proteins and pathways regulating behaviors exhibited during the different stages of the addiction cycle. Preclinical research in animal models will undoubtedly continue to reveal therapeutic strategies for substance use disorders.
Diagnosis and Epidemiology of Dementia
Authors: Kreisl William C. , Reitz Christiane 
Published: December 2017

Abstract
Dementia is a neurodegenerative clinical syndrome encompassing a wide range of diseases characterized by progressive deterioration in cognitive ability, function and behavior. More than 24 million people worldwide are currently affected, and this prevalence is predicted to quadruple by the year 2050. The most common cause of dementia is Alzheimer’s disease, clinically characterized by a progressive impairment in cognitive function. To date, Alzheimer’s disease cannot be prevented or cured; the available treatments only slightly improve cognitive symptoms. In this chapter, we provide an overview of the most common neurodegenerative causes of dementia, beginning with Alzheimer’s disease, and summarize current information relating to the prevalence and incidence of dementia.
Neurobiology of FTD
Authors: Chung Dah-Eun Chloe , Stankowski Jeannette N. , Petrucelli Leonard 
Published: December 2017

Abstract
Frontotemporal dementia (FTD) is the third most common form of dementia, and is one that predominantly affects the frontal and temporal lobes. Pathological heterogeneity of FTD is highlighted in various types of protein inclusions in the brain, which can include tau, TDP-43, or FUS. The discovery of novel genes and mutations associated with FTD, along with the exciting advancement of molecular technologies, led to the development of numerous animal- and human-based model systems. These valuable models allow not only for the investigation of pathogenic mechanisms underlying FTD, but also for their utilization as powerful platforms for the screening of novel therapies.
Population ageing in South and Central America
Authors: Junior Carlos M. Paixao , Lourenço Roberto A. , Morales-Martínez Fernando 
Published: December 2017

Abstract
Considering questions related to South and Central America probably is best done by using the better-known term of Latin America. Although much of the history of the region has common roots, many specificities make these countries somewhat heterogeneous. However, one can say that ageing in the region has been accelerated and diverse from what was witnessed in more affluent countries elsewhere in the world, because of the persistent problem of poverty still unresolved in Latin America. The over-60 population has been growing in the region for the past 30 years, producing an increase in old-age indices and old-age dependency ratios. This raises important issues about the social protection models that should be adopted to cope with these demographic trends.
Population ageing in Oceania
Authors: Flicker Leon , Kerse Ngaire 
Published: December 2017

Abstract
The region of Oceania describes a collection of islands scattered throughout the Pacific Ocean between Asia and the Americas. The region is vast and largely covered by ocean. There are four subregions of this region including Australasia (Australia and New Zealand), Melanesia (Papua and New Guinea, Fiji, Solomon Islands, Vanuatu, and New Caledonia), Micronesia (Federated States of Micronesia and Guam), and Polynesia (includes French Polynesia, Samoa, Tonga, Tokalau, and Niue). Australasia is relatively affluent and developed with an ageing population, whereas the other nations are of a developing nature with relatively younger populations but will face dramatic population ageing over the next 40 years. Australasia has well-developed services for older people. The Indigenous populations of Australasia have worse health outcomes than the non-Indigenous populations. However, outside Australasia there is an urgent need to develop health and community services for older people in the remainder of the region.
Implications of population ageing for societies and governments
Authors: Beard John R. , Pot Anne Margriet , Peeters Geeske 
Published: December 2017

Abstract
Population ageing presents both opportunities and challenges to societies and governments. While even today, the economic contribution of older people is likely to outweigh the expenditure on them by governments, this balance could be even more positive in the future. Yet, outdated stereotypes of ageing are pervasive and limit the way older people are viewed and the way policy is framed. Moving forward will require a broader understanding of the diversity of older populations, the inequities that underpin it, and of the many and varied opportunities for societal responses that can enable the abilities of older people. What population ageing ultimately implies for societies and governments will therefore depend as much on societal attitudes and response as it will on the intrinsic capacities and needs of older populations.
Policy options for responding to population ageing
Authors: Sidorenko Alexandre , Walker Alan 
Published: December 2017

Abstract
We live in the time of multifaceted societal transition: demographic, familial, and epidemiological. All three transitions are advancing globally, though not universally, and there are enduring deviations. All three transitions bring us significant and welcome opportunities: longer, healthier, and potentially more fulfilling lives. Healthier and happier citizens should benefit their societies and promote development. However, the above opportunities are accompanied by challenges. After highlighting the major challenges and opportunities of ageing societies, the chapter turns to reviewing the international policy frameworks on ageing, focusing on the Madrid International Plan of Action on Ageing and its regional implementation strategies. A brief overview of international policy players in the area of ageing is also included.
Ageing, multimorbidity, and daily functioning
Authors: Gryglewska Barbara , Piotrowicz Karolina , Grodzicki Tomasz 
Published: December 2017

Abstract
Multimorbidity is defined as any combination of a chronic disease with at least one other acute or chronic disease or biopsychosocial or somatic risk factor. Old age is a leading risk factor for multimorbidity. It has a negative impact on short- and long-term prognosis, patients’ cognitive and functional performance, self-care, independence, and quality of life. It substantially influences patients’ clinical management and increases healthcare-related costs. There is a great variety of clinical measures to assess multimorbidity; some are presented in this chapter. Despite its high prevalence in older adults, clinical guidelines for physicians managing patients with multimorbidity are underdeveloped and insufficient.
Engaging older patients in their treatment and care
Authors: Coulter Angela 
Published: December 2017

Abstract
Nowadays we use the term ‘patient-centred care’ to describe responsiveness to people’s personal, practical, emotional, and social needs alongside their biomedical ones. This chapter looks at what patient-centred care means for older people, what they want from healthcare, and how to ensure that the healthcare they receive is appropriate to their needs. Despite evidence that most patients, including those in the oldest age groups, want to be informed and involved in decisions about their care, there is a gap between these aspirations and the reality. This chapter looks at evidence on what patients want and expect. Ways in which clinicians can support them to become active partners in their care are discussed and evidence on what works is briefly reviewed. Examples include shared decision-making, personalized care planning, use of advance care plans, technologies to support independent living, and care coordination.
Limitations in the evidence for safe and effective medications for older people
Authors: Cherubini Antonio , Onder Graziano 
Published: December 2017

Abstract
In the last decades, evidence-based medicine has emerged as the approach to promote the best clinical practice for health problems. It collates the best published evidence, preferentially based on randomized clinical trials, to guide clinical practice. However, the growing older population challenges the evidence underpinning ‘best practice’. Many older patients are characterized by multimorbidity and polypharmacotherapy, present various degrees of functional and cognitive impairment, and are at risk of developing geriatric syndromes. For these reasons they have been almost systematically excluded from clinical trials. In addition, the results of clinical trials are difficult to apply to patients with these characteristics, given the high risk of drug–drug and drug–disease interactions. An effort to promote a greater involvement of older patients in clinical research is needed, using specific measures to facilitate the participation of complex older patients, who are representative of those treated in clinical practice.