bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurovascular Unit: Basic and Clinical Imaging with Emphasis on Advantages of Ferumoxytol
Authors: Netto Joao Prola , Iliff Jeffrey , Stanimirovic Danica , Krohn Kenneth A , Hamilton Bronwyn , Varallyay Csanad , Gahramanov Seymur , Daldrup-Link Heike , d’Esterre Christopher , Zlokovic Berislav , Sair Haris , Lee Yueh , Taheri Saeid , Jain Rajan , Panigrahy Ashok , Reich Daniel S , Drewes Lester R , Castillo Mauricio , Neuwelt Edward A
Published: June 2017

Physiological and pathological processes that increase or decrease the central nervous system's need for nutrients and oxygen via changes in local blood supply act primarily at the level of the neurovascular unit (NVU). The NVU consists of endothelial cells, associated blood–brain barrier tight junctions, basal lamina, pericytes, and parenchymal cells, including astrocytes, neurons, and interneurons. Knowledge of the NVU is essential for interpretation of central nervous system physiology and pathology as revealed by conventional and advanced imaging techniques. This article reviews current strategies for interrogating the NVU, focusing on vascular permeability, blood volume, and functional imaging, as assessed by ferumoxytol an iron oxide nanoparticle.
Strategies for improving the lithium-storage performance of 2D nanomaterials
Authors: Mei Jun , Zhang Yuanwen , Liao Ting , Sun Ziqi , Dou Shi Xue
Published: June 2017

2D nanomaterials, including graphene, transition metal oxide (TMO) nanosheets, transition metal dichalcogenide (TMD) nanosheets, etc., have offered an appealing and unprecedented opportunity for the development of high-performance electrode materials for lithium-ion batteries (LIBs). Although significant progress has been made on 2D nanomaterials for LIB applications in the recent years, some major challenges still exist for the direct use of these sheet-like nanomaterials, such as their serious self-agglomerating tendency during electrode fabrication and low conductivity as well as the large volume changes over repeated charging–discharging cycles for most TMOs/TMDs, which have resulted in large irreversible capacity, low initial Coulombic efficiency and fast capacity fading. To address these issues, considerable progress has been made in the exploitation of 2D nanosheets for enhanced lithium storage. In this review, we intend to summarize the recent progress on the strategies for enhancing the lithium-storage performance of 2D nanomaterials, including hybridization with conductive materials, surface/edge functionalization and structural optimization. These strategies for manipulating the structures and properties of 2D nanomaterials are expected to meet the grand challenges for advanced nanomaterials in clean energy applications and thus provide access to exciting materials for achieving high-performance next-generation energy-storage devices.
Information transmission within federal fiscal architectures: theory and evidence
Authors: Dreher Axel , Gehring Kai , Kotsogiannis Christos , Marchesi Silvia
Published: June 2017

This paper explores the role of information transmission and misaligned interests across levels of governments in explaining variation in the degree of decentralization across countries. We analyse two alternative policy-decision schemes—‘decentralization’ and ‘centralization’— within a two-sided incomplete information principal–agent framework. The quality of communication depends on the conflict of interests between the government levels and on which government level controls the degree of decentralization. We show that the extent of misaligned interests and the relative importance of local and central government knowledge affect the optimal choice of policy-decision schemes. Our empirical analysis confirms that countries’ choices depend on the relative importance of private information. In line with our theory the results differ significantly between unitary and federal countries.
Integrated taxonomy reveals multiple species in the Dendrobaena byblica (Rosa, 1893) complex (Oligochaeta: Lumbricidae)
Authors: Szederjesi Tímea , Pop Victor V , Pavlíček Tomáš , Márton Orsolya , Krízsik Virág , Csuzdi Csaba
Published: June 2017

Dendrobaena byblica (Rosa, 1893) is a Circum-Mediterranean species complex composed of at least 17 nominal taxa. Regarding the most important species characters (clitellum and tubercles) the worms belonging to the genus Fitzingeria Zicsi, 1978 seem to be very close to the D. byblica species group. Here we provide the first molecular phylogenetic analysis of the byblica species group and the Fitzingeria species, and show that the genus Fitzingeria is polyphyletic and groups together with the Carpathian and Balkanic deeply pigmented byblica forms. The other main clade consists of the ‘classical’ byblica species. The morphological characteristics also support these results. On the basis of the molecular and morphological characters the species of the former Fitzingeria were relegated to Dendrobaena and four new species were described together with a new replacement name Dendrobaena carpathomontana nom. nov. for F. platyura montana (Černosvitov, 1932).
Team Investment and Longitudinal Relationships: An Innovative Global Health Education Model
Authors: Myers Kimberly R. , Fredrick N. Benjamin
Published: June 2017

Problem

Increasing student interest in global health has resulted in medical schools offering more global health opportunities. However, concerns have been raised, particularly about one-time, short-term experiences, including lack of follow-through for students and perpetuation of unintentional messages of global health heroism, neocolonialism, and disregard for existing systems and communities of care. Medical schools must develop global health programs that address these issues.

Approach

The Global Health Scholars Program (GHSP) was created in 2008–2009 at Penn State College of Medicine. This four-year program is based on values of team investment and longitudinal relationships and uses the service–learning framework of preparation, service, and reflection. Teams of approximately five students, with faculty oversight, participate in two separate monthlong trips abroad to the same host community in years 1 and 4, and in campus- and Web-based activities in years 2 and 3.

Outcomes

As of December 2016, 191 students have been accepted into the GHSP. Since inception, applications have grown by 475% and program sites have expanded from one to seven sites on four continents. The response from students has been positive, but logistical challenges persist in sustaining team investment and maintaining longitudinal relationships between student teams and host communities.

Next Steps

Formal methods of assessment should be used to compare the GHSP model with more traditional approaches to global health education. Other medical schools with similar aims can adapt the GHSP model to expand their global health programming.
Varicella-related Primary Health-care Visits, Hospitalizations and Mortality in Norway, 2008–2014
Authors: Mirinaviciute Grazina , Kristensen Erle , Nakstad Britt , Flem Elmira
Published: June 2017

Background:

Norway does not currently implement universal varicella vaccination in childhood. We aimed to characterize health care burden of varicella in Norway in the prevaccine era.

Methods:

We linked individual patient data from different national registries to examine varicella vaccinations and varicella-coded primary care consultations, hospitalizations, outpatient hospital visits, deaths and viral infections of central nervous system in the whole population of Norway during 2008–2014. We estimated health care contact rates and described the epidemiology of medically attended varicella infection.

Results:

Each year approximately 14,600 varicella-related contacts occurred within primary health care and hospital sector in Norway. The annual contact rate was 221 cases per 100,000 population in primary health care and 7.3 cases per 100,000 in hospital care. Both in primary and hospital care, the highest incidences were observed among children 1 year of age: 2,654 and 78.1 cases per 100,000, respectively. The annual varicella mortality was estimated at 0.06 deaths per 100,000 and in-hospital case-fatality rate at 0.3%. Very few (0.2−0.5%) patients were vaccinated against varicella. Among hospitalized varicella patients, 22% had predisposing conditions, 9% had severe-to-very severe comorbidities and 5.5% were immunocompromised. Varicella-related complications were reported in 29.3% of hospitalized patients. Varicella zoster virus was the third most frequent virus found among 16% of patients with confirmed viral infections of central nervous system.

Conclusions:

Varicella causes a considerable health care burden in Norway, especially among children. To inform the policy decision on the use of varicella vaccination, a health economic assessment of vaccination and mathematical modeling of vaccination impact are needed.
Efficacy of Whole-Body Vibration Board Training on Strength in Athletes After Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Study
Authors: Costantino Cosimo , Bertuletti Silvia , Romiti Davide
Published: June 2017

Objective:

To evaluate whether an 8-week whole-body vibration training program may improve recovery of knee flexion/extension muscular strength in athletes after arthroscopic anterior cruciate ligament (ACL) reconstruction.

Design:

Randomized controlled trial.

Setting:

Single outpatient rehabilitation center.

Participants:

Thirty-eight female volleyball/basketball players (aged between 20 and 30), randomized into 2 treatment groups.

Interventions:

During a standardized six-month rehabilitation program, from week 13 to week 20 after surgery, the whole-body vibration group (n = 19) and the control group (n = 19) performed additional static knee flexor/extensor exercises on a vibration platform. For the whole-body vibration group, the vibration platform was set to 2.5 mm of amplitude and 26 Hz of frequency. The control group followed the same whole-body vibration board training with no vibrations.

Main Outcome Measures:

All patients were evaluated using an isokinetic strength test with a Biodex dynamometer at the beginning and at the end of the additional treatment protocol. The parameters tested were the peak torque and the maximum power of knee flexor and extensor muscles performing strength and endurance tests.

Results:

No vibration-related side effects were observed. Improvements were noticed in both groups, but increase in knee muscle isokinetic strength values was statistically significant in the whole-body vibration group when compared with the control group (differences in extension: peak torque 11.316/10.263 N·m and maximum power 13.684/11.211 W; flexion: peak torque 9.632/11.105 N·m and maximum power 10.158/9.474 W;P< 0.001).

Conclusions:

When combined with a standardized rehabilitation program, whole-body vibration may increase muscular strength and be an effective additional treatment option in the rehabilitation of athletes after ACL arthroscopic reconstruction.
Endocrine dysfunction following immune checkpoint inhibitor therapy
Authors: Konda Bhavana , Nabhan Fadi , Shah Manisha H.
Published: June 2017

Purpose of review

Immune checkpoint inhibitors (ICI) represent an important milestone in the modern era of antineoplastic therapy and have ushered optimism amongst oncologists and patients alike. These agents, however, are associated with significant potential toxicities, the importance of which cannot be overstated. The clinical presentation, diagnosis, and management strategies of immune-related endocrinopathies associated with ICI use are described in this case-based review.

Recent findings

An increasing number of ICI have shown promise in the management of various malignancies in the recent years. These include cytotoxic T lymphocyte antigen-4 inhibitors, programmed cell death 1 (PD-1) antibodies, and PD-ligand 1 (PD-L1) antibodies. Several endocrinopathies, including hypophysitis, thyroid dysfunction, hyperglycemia, and primary adrenal insufficiency, have been associated with the use of these agents. Toxicities may range from mild transient laboratory abnormalities to potentially life-threatening ones, warranting immediate therapeutic intervention. Combination ICI therapies may be associated with a greater risk of endocrine dysfunction when compared with monotherapy. The clinical presentation and laboratory assessment of these patients often pose a diagnostic challenge as they may be confused by the symptoms related to their underlying malignancy or potential associated acute illnesses.

ICI use is associated with serious endocrinopathies that may have a nonspecific initial presentation. A constant eye for these symptoms and a systematic approach to diagnosis are essential for prompt initiation of therapy and prevention of significant complications.
Interactions of β-amyloid peptide with fibrinogen and coagulation factor XII may contribute to Alzheimer's disease
Authors: Ahn Hyung J. , Chen Zu-Lin , Zamolodchikov Daria , Norris Erin H. , Strickland Sidney
Published: June 2017

Purpose of review

To review the evidence that the Alzheimer peptide β-amyloid interacts with the blood coagulation system and influences the pathophysiology of the disease.

Recent findings

β-amyloid can interact with fibrinogen and blood coagulation factor XII and trigger ischemia and inflammation.

β-amyloid interacts with fibrinogen and factor XII. These interactions can lead to increased clotting, abnormal clot formation, persistent fibrin deposition, and generation of proinflammatory molecules. These events can damage neurons and could contribute to the cognitive decline in Alzheimer's disease patients.
Long‐term Outcomes of Infliximab Use for Pediatric Crohn Disease
Authors: deBruyn Jennifer C. , Jacobson Kevan , El‐Matary Wael , Carroll Matthew , Wine Eytan , Wrobel Iwona , Van Woudenberg Mariel , Huynh Hien Q.
Published: June 2017

Background:

Data on long‐term real‐world outcomes of infliximab in pediatric Crohn disease are limited.

Aim:

The aim of the study was to evaluate infliximab optimization and durability in children with Crohn disease.

Methods:

We performed a retrospective review of children with Crohn disease who started infliximab from January 2008 to December 2012 in 4 Canadian tertiary care centers. A priori factors associated with optimization and discontinuation from loss of response were evaluated using logistic regression and Cox proportional hazards model, respectively.

Results:

One hundred eighty children (54.4% boys) started infliximab; all completed induction. Median age at infliximab start was 14.3 years (Q1, Q3: 12.8, 15.9 years) and median time from diagnosis to infliximab start was 1.5 years (Q1, Q3: 0.6, 3.5 years). At last follow‐up, 87.1% were maintained on infliximab (median duration follow‐up 85.9 weeks [Q1, Q3: 43.8, 138.8 weeks]). Infliximab optimization occurred in 57.3% (dose escalation 15.2%, interval shortening 3.9%, both 38.2%), primarily due to loss of response. Younger age at diagnosis (<10 years old) and nonstricturing, nonpenetrating behavior were associated with optimization (odds ratio 6.5, 95% confidence interval [CI] 2.0–21.1 and odds ratio 2.1, 95% CI 1.0–4.2, respectively). The 1‐ and 2‐year durability of infliximab (percentage in follow‐up who were continuing on infliximab) were 95.5% (95% CI 90.4–98.3) and 91.0% (95% CI 82.4–96.3), respectively. Annual discontinuation due to loss of response occurred at 3.2% per year (95% CI 1.1–5.2).

Conclusions:

Children with Crohn disease maintain a durable response to infliximab. Optimization occurs frequently and allows for continued use. Younger age at diagnosis and nonstricturing, nonpenetrating behavior are associated with increased need for infliximab optimization.
A Morphometric Study of the Newborn Ear and an Analysis of Factors Related to Congenital Auricular Deformities
Authors: Zhao Hui , Ma Limin , Qi Xiangdong , Qin Jianzeng , Yin Baoming , Zhong Mei , He Yanjun , Wang Chenghong
Published: June 2017

Background:

The incidence of neonatal ear deformities varies widely in the literature, and the incidence of those that correct spontaneously is largely unknown. To address these questions, the authors analyzed the auricles of 1500 newborns from the Pearl River Delta within the first 7 days of life and again at 30 days of age.

Methods:

Using a combination of direct measurement and digital image measurement, the authors measured physiognomic ear length, physiognomic ear breadth, morphologic ear length, vertical distance between head and ear, and auriculocephalic angle of the newborns. The first measurement was within 1 week of birth, whereas the second measurement was performed for the same newborns 1 month after birth.

Results:

Among 1500 newborns, 862 had various forms of auricular deformities. The incidence of neonatal auricular deformity in the Pearl River Delta area was 57.46 percent, and the self-healing rate was 31.55 percent by the 30-day follow-up. Seven factors were found to be statistically significant: mother’s delivery situation, mother’s hepatitis history, abnormal pregnancy, abnormal labor, cephalopelvic disproportion, premature rupture of membranes, and neonatal weight. Birth by cesarean delivery and mother with no abnormal pregnancy or no history of hepatitis were protective factors against the newborn’s auricular deformity.

Conclusions:

Newborns have a high incidence of auricular deformities, and different types of auricular deformities have distinct incidences. Auricular deformities are caused by the interactions of a number of factors. There were large differences in the self-healing rates of different types of auricular deformities.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
Evidence-Based Medicine: Mandible Fractures
Authors: Pickrell Brent B. , Hollier Larry H.
Published: June 2017

Learning Objectives:

After reading this article, the participant should be able to: 1. Explain the epidemiology of mandible fractures. 2. Discuss preoperative evaluation of the patient with a mandible fracture. 3. Compare the various modalities of fracture fixation. 4. Identify common complications after fracture repair.

In this Maintenance of Certification/Continuing Medical Education article, the reader is provided with a review of the epidemiology, preoperative evaluation, perioperative management, and surgical outcomes of mandible fractures. The objective of this series is to present a review of the literature so that the practicing physician can remain up-to-date on key evidence-based guidelines to enhance management and improve outcomes. The physician can also seek further in-depth study of the topic through the references provided.
Palliative care and interstitial lung disease
Authors: Bajwah Sabrina , Yorke Janelle
Published: June 2017

Purpose of review

The palliative care needs of people with interstitial lung disease (ILD) have recently been highlighted by the National Institute for Health and Care Excellence. All people with progressive ILD should receive best supportive care to improve symptom control and quality of life and where possible this should be evidence based.

Recent findings

Deaths from ILD are increasing and deaths in hospital are more common compared to home. People with ILD experience a wide range of symptoms including breathlessness and cough. People living with ILD often suffer unmet physical and psychological needs throughout the disease journey. Few appropriately validated outcome measures exist for ILD which has hampered research on the longitudinal experience of symptoms and quality of life and the evaluation of interventions. Recent recommendations from the National Institute of Clinical Excellence promote the use of a new palliative care needs assessment tool. Use of a tool in busy respiratory clinics may help to highlight those requiring specialist input.

Further research into the role of opioids, oxygen and neuromodulatory agents in symptom management are needed. In addition, exploration of breathlessness and case conference interventions in transitioning patients from the hospital to community settings is a priority. Further work is needed to identify a core set of validated ILD-specific patient-reported outcome measures for the robust evaluation of interventions.
Urinary Incontinence in Pregnant Young Women and Adolescents: An Unrecognized At-Risk Group
Authors: Jean-Michel Marjorie , Kroes Jessica , Marroquin Guillermo A. , Chau Emily Man-Shan , Salafia Carolyn M. , Mikhail Magdy
Published: June 2017

Objectives

The aims of this study were to determine the prevalence of urinary incontinence (UI) in pregnant young women and adolescents, characterize UI subtype, and identify characteristics associated with UI.

Methods

This was a cross-sectional study of pregnant females aged 25 years or below, presenting for routine obstetrical care at a New York City community hospital. Subjects were stratified into 2 groups: adolescents (age, ≤19 years) and young adults (age, >19 years). Demographic and obstetric data were collected. The 3 Incontinence Questions questionnaire was used to screen and evaluate UI symptoms.

Results

A total of 98 young females with a mean age of 20.3 ± 2.6 years were enrolled. Most participants were nulliparous (64%). Of parous women, route of previous obstetric delivery was primarily vaginal (83%). Mean gestational age at recruitment was 34.5 ± 7.5 weeks. The prevalence of UI was 52%. Urinary incontinence was associated with the following conditions: strenuous activity, 73%; urinary urgency, 67%; and absence of either, 20%. However, the most predominant UI subtype was with strenuous activity (63%). There was no statistical difference detected in demographic characteristics (such as age, parity, mode of delivery, race, education, and trimester of pregnancy) between continent and incontinent pregnant females (P > 0.18). No differences were appreciated between pregnant adolescents and young adult females with UI (P > 0.18).

Conclusions

Urinary incontinence was present in 52% of pregnant females aged 25 years or below. By age group, approximately 50% of both adolescents and young adults reported UI during pregnancy. Continent and incontinent patients did not seem to differ demographically. Our study highlights the extent of UI in this segment of the population. This data may support the need for services targeting UI prevention and early intervention in this newly identified at-risk group.
Penetrating injuries to the duodenum: An analysis of 879 patients from the National Trauma Data Bank, 2010 to 2014
Authors: Phillips Bradley , Turco Lauren , McDonald Dan , Mause Alison , Walters Ryan W.
Published: June 2017

BACKGROUND

Despite wide belief that the duodenal Organ Injury Scale has been validated, this has not been reported in the published literature. Based on clinical experience, we hypothesize that the American Association for Surgery of Trauma Organ Injury Scale (AAST-OIS) for duodenal injuries can independently predict mortality. Our objectives were threefold: (1) describe the national profile of penetrating duodenal injuries, (2) identify predictors of morbidity and mortality, and (3) validate the duodenum AAST-OIS as a statistically significant predictor of mortality.

METHODS

Using the Abbreviated Injury Scale 2005 and International Classification of Diseases—9th Rev.—Clinical Modification (ICD-9-CM) E-codes, we identified 879 penetrating duodenal trauma patients from the National Trauma Data Bank between 2010 and 2014. We controlled patient-level covariates of age, biological sex, systolic blood pressure (SBP), Glasgow Coma Scale (GCS) score, pulse, Injury Severity Score (ISS), and Organ Injury Scale (OIS) grade. We estimated multivariable generalized linear mixed models to account for the nesting of patients within trauma centers.

RESULTS

Our results indicated an overall mortality rate of 14.4%. Approximately 10% of patients died within 24 hours of admission, of whom 76% died in the first 6 hours. Patients averaged approximately five associated injuries, 45% of which involved the liver and colon. Statistically significant independent predictors of mortality were firearm mechanism, SBP, GCS, pulse, ISS, and AAST-OIS grade. Specifically, odds of death were decreased with 10 mm Hg higher admission SBP (13% decreased odds), one point higher GCS (14.4%), 10-beat lower pulse (8.2%), and 10-point lower ISS (51.0%).

CONCLUSION

This study is the first to report the national profile of penetrating duodenal injuries. Using the National Trauma Data Bank, we identified patterns of injury, predictors of outcome, and validated the AAST-OIS for duodenal injuries as a statistically significant predictor of morbidity and mortality.

LEVEL OF EVIDENCE

Epidemiologic/Prognostic, level IV.
Uncovering the underlying mechanism of cancer tumorigenesis and development under an immune microenvironment from global quantification of the landscape
Authors: Wenbo Li , Wang Jin
Published: June 2017

The study of the cancer–immune system is important for understanding tumorigenesis and the development of cancer and immunotherapy. In this work, we build a comprehensive cancer–immune model including both cells and cytokines to uncover the underlying mechanism of cancer immunity based on landscape topography. We quantify three steady-state attractors, normal state, low cancer state and high cancer state, for the innate immunity and adaptive immunity of cancer. We also illustrate the cardinal inhibiting cancer immunity interactions and promoting cancer immunity interactions through global sensitivity analysis. We simulate tumorigenesis and the development of cancer and classify these into six stages. The characteristics of the six stages can be classified further into three groups. These correspond to the escape, elimination and equilibrium phases in immunoediting, respectively. Under specific cell–cell interactions strength oscillations emerge. We found that tumorigenesis and cancer recovery processes may need to go through cancer–immune oscillation, which consumes more energy. Based on the cancer–immune landscape, we predict three types of cells and two types of cytokines for cancer immunotherapy as well as combination immunotherapy. This landscape framework provides a quantitative way to understand the underlying mechanisms of the interplay between cancer and the immune system for cancer tumorigenesis and development.
Addressing current challenges in cancer immunotherapy with mathematical and computational modelling
Authors: Konstorum Anna , Vella Anthony T. , Adler Adam J. , Laubenbacher Reinhard C.
Published: June 2017

The goal of cancer immunotherapy is to boost a patient's immune response to a tumour. Yet, the design of an effective immunotherapy is complicated by various factors, including a potentially immunosuppressive tumour microenvironment, immune-modulating effects of conventional treatments and therapy-related toxicities. These complexities can be incorporated into mathematical and computational models of cancer immunotherapy that can then be used to aid in rational therapy design. In this review, we survey modelling approaches under the umbrella of the major challenges facing immunotherapy development, which encompass tumour classification, optimal treatment scheduling and combination therapy design. Although overlapping, each challenge has presented unique opportunities for modellers to make contributions using analytical and numerical analysis of model outcomes, as well as optimization algorithms. We discuss several examples of models that have grown in complexity as more biological information has become available, showcasing how model development is a dynamic process interlinked with the rapid advances in tumour–immune biology. We conclude the review with recommendations for modellers both with respect to methodology and biological direction that might help keep modellers at the forefront of cancer immunotherapy development.
The Victoria West: earliest prepared core technology in the Acheulean at Canteen Kopje and implications for the cognitive evolution of early hominids
Authors: Li Hao , Kuman Kathleen , Lotter Matt G. , Leader George M. , Gibbon Ryan J.
Published: June 2017

Prepared core technology illustrates in-depth planning and the presence of a mental template during the core reduction process. This technology is, therefore, a significant indicator in studying the evolution of abstract thought and the cognitive abilities of hominids. Here, we report on Victoria West cores excavated from the Canteen Kopje site in central South Africa, with a preliminary age estimate of approximately 1 Ma (million years ago) for these cores. Technological analysis shows that the Victoria West cores bear similarities to the ‘Volumetric Concept’ as defined for the Levallois, a popular and widely distributed prepared core technology from at least 200 ka (thousand years ago). Although these similarities are present, several notable differences also occur that make the Victoria West a unique and distinctive prepared core technology; these are: elongated and convergent core shapes, consistent blow directions for flake removal, a predominance of large side-struck flakes, and the use of these flakes to make Acheulean large cutting tools. This innovative core reduction strategy at Canteen Kopje extends the roots of prepared core technology to the latter part of the Early Acheulean and clearly demonstrates an increase in the cognitive abilities and complexities of hominids in this time period.
An indirect watermark hiding in discrete cosine transform–singular value decomposition domain for copyright protection
Authors: Roy Soumitra , Pal Arup Kumar
Published: June 2017

Digital image watermarking has emerged as a promising solution for copyright protection. In this paper, a discrete cosine transform (DCT) and singular value decomposition (SVD) based hybrid robust image watermarking method using Arnold scrambling is proposed and simulated to protect the copyright of natural images. In this proposed scheme, before embedding, watermark is scrambled with Arnold scrambling. Then, the greyscale cover image and encrypted watermark logo are decomposed into non-overlapping blocks and subsequently some selected image blocks are transformed into the DCT domain for inserting the watermark blocks permanently. For better imperceptibility and effectiveness, in this proposed algorithm, watermark image blocks are embedded into singular values of selected blocks by multiplying with a feasible scaling factor. Simulation result demonstrates that robustness is achieved by recovering satisfactory watermark data from the reconstructed cover image after applying common geometric transformation attacks (such as rotation, flip operation, cropping, scaling, shearing and deletion of lines or columns operation), common enhancement technique attacks (such as low-pass filtering, histogram equalization, sharpening, gamma correction, noise addition) and jpeg compression attacks.
Rensching cats and dogs: feeding ecology and fecundity trends explain variation in the allometry of sexual size dimorphism
Authors: Johnson P. J. , Noonan M. J. , Kitchener A. C. , Harrington L. A. , Newman C. , Macdonald D. W.
Published: June 2017

The tendency for sexual size dimorphism (SSD) to increase with body mass in taxa where males are larger, and to decrease when females are larger, is known as Rensch's rule. In mammals, where the trend occurs, it is believed to be the result of a competitive advantage for larger males, while female mass is constrained by the energetics of reproduction. Here, we examine the allometry of SSD within the Felidae and Canidae, demonstrating distinctly different patterns: in felids, there is positive allometric scaling, while there is no trend in canids. We hypothesize that feeding ecology, via its effect on female spacing patterns, is responsible for the difference; larger male mass may be advantageous only where females are dispersed such that males can defend access to them. This is supported by the observation that felids are predominately solitary, and all are obligate carnivores. Similarly, carnivorous canids are more sexually dimorphic than insectivores and omnivores, but carnivory does not contribute to a Rensch effect as dietary variation occurs across the mass spectrum. The observed inter-familial differences are also consistent with reduced constraints on female mass in the canids, where litter size increases with body mass, versus no observable allometry in the felids.
Some aspects of an induced electric dipole moment in rotating and non-rotating frames
Authors: Oliveira Abinael B. , Bakke Knut
Published: June 2017

Quantum effects on a neutral particle (atom or molecule) with an induced electric dipole moment are investigated when it is subject to the Kratzer potential and a scalar potential proportional to the radial distance. In addition, this neutral is placed in a region with electric and magnetic fields. This system is analysed in both non-rotating and rotating reference frames. Then, it is shown that bound state solutions to the Schrödinger equation can be achieved and, in the search for polynomial solutions to the radial wave function, a restriction on the values of the cyclotron frequency is analysed in both reference frames.
Widespread Negative Frequency-Dependent Selection Maintains Diversity in the Legume-Rhizobia Symbiosis: Balancing nodulation may explain the paradox of rhizobium diversity
Authors: Siler Eleanor , Friesen Maren L.
Published: June 2017

The evolutionary origin and ecological maintenance of biodiversity is a central problem in biology. For diversity to be stable through time, each genotype or species must have an advantage when rare. This negative frequency-dependence prevents deterministic extinction and mitigates the stochastic loss of diversity (1–4). However, models of mutualism typically generate positive frequency-dependence that reduces diversity (5–8). Here, we report empirical evidence for negative frequency-dependence in the legume-rhizobium mutualism within a single host generation, a phenomenon that we term balancing nodulation. Balancing nodulation increases rare rhizobia across all 13 legume genera investigated to date, at high and low inoculum densities, and with minimal genetic differentiation between rhizobia strains. While the mechanism generating this phenomenon is currently unknown, balancing nodulation could actively maintain variation in the rhizobia-legume symbiosis.
Melanism patches up the defective cuticular morphological traits through promoting the up-regulation of cuticular protein-coding genes in Bombyx mori
Authors: Qiao Liang , Wang Ri-xin , Hao You-jin , Hu Hai , Xiong Gao , He Song-zhen , Song Jiang-bo , Lu Kun-peng , Xin Ya-qun , Mallet James , Chen Bin , Dai Fang-yin
Published: June 2017

Melanin and cuticular proteins are important cuticle components in insect. Cuticle defects caused by mutations in cuticular protein-encoding genes can hinder melanin deposition. However, the effects of melanin variation on cuticular protein-encoding genes and the corresponding morphological traits associated with these genes are remain largely unknown. Using Bombyx mori as a model, we showed that the melanism levels during larval cuticle pigmentation correlated positively with the expression of cuticular protein-encoding genes. This correlation stemmed from the simultaneous induction of these genes by the melanin precursors. More importantly, the effect of the melanism background on the cuticles induced the up-regulation of other functionally redundant cuticular protein-encoding genes to rescue the morphological and adaptive defects caused by the dysfunction of some mutated cuticular proteins, and the restorative ability increased with increasing melanism levels, which gives a novel evidence that melanism enhances insect adaptability. These findings deepen our understanding of the interactions among cuticle components, as well as their importance in the stabilizing of the normal morphology and function of the cuticle.
CD55 regulates self-renewal and cisplatin resistance in endometrioid tumors
Authors: Saygin Caner , Wiechert Andrew , Rao Vinay S. , Alluri Ravi , Connor Elizabeth , Thiagarajan Praveena S. , Hale James S. , Li Yan , Chumakova Anastasia , Jarrar Awad , Parker Yvonne , Lindner Daniel J , Nagaraj Anil Belur , Kim J Julie , DiFeo Analisa , Abdul-Karim Fadi W. , Michener Chad , Rose Peter G. , DeBernardo Robert , Mahdi Haider , McCrae Keith R. , Lin Feng , Lathia Justin D. , Reizes Ofer
Published: June 2017

Effective targeting of cancer stem cells (CSCs) requires neutralization of self-renewal and chemoresistance, however these phenotypes are often regulated by distinct molecular mechanisms. Here we report the ability to target both of these phenotypes via CD55, an intrinsic cell surface complement inhibitor, which was identified in a comparative analysis between CSCs and non-CSCs in endometrioid cancer models. In this context, CD55 functions in a complement-independent manner and required lipid raft localization for CSC maintenance and cisplatin resistance. CD55 regulated self-renewal and core pluripotency genes via ROR2/JNK signaling and in parallel cisplatin resistance via LCK signaling, which induced DNA repair genes. Targeting LCK signaling via saracatinib, an inhibitor currently undergoing clinical evaluation, sensitized chemoresistant cells to cisplatin. Collectively, our findings identify CD55 as a unique signaling node that drives self-renewal and therapeutic resistance via a bifurcating signaling axis and provide an opportunity to target both signaling pathways in endometrioid tumors.

CD55 is a membrane complement regulatory protein that attenuates complement-mediated cytotoxicity. Saygin et al. elucidate a new role for CD55 as a signaling hub for cancer stem cell self-renewal and cisplatin resistance pathways in endometrioid tumors and open a new line of research into chemotherapeutic-refractory cancers.

Abbreviations

GPI

glycophosphatidylinositol

LIME

LCK interacting transmembrane adaptor

PAG

protein associated with glycosphingolipid-enriched microdomains

CSC

cancer stem cell

DAF

decay accelerating protein

LCK

Endometrioid Tumor, ET

CSC

cancer stem cell

mCRP

membrane-bound complement regulatory protein

ROR2

receptor tyrosine kinase like orphan receptor 2

LCK

lymphocyte-specific protein tyrosine kinase

JNK

c-Jun N-terminal kinase
A comprehensive portrait of cilia and ciliopathies from a CRISPR-based screen for Hedgehog signaling
Authors: Breslow David K. , Hoogendoorn Sascha , Kopp Adam R. , Morgens David W. , Vu Brandon K. , Han Kyuho , Li Amy , Hess Gaelen T. , Bassik Michael C. , Chen James K. , Nachury Maxence V.
Published: June 2017

The primary cilium organizes Hedgehog signaling, shapes embryonic development and is the unifying cause of the ciliopathies. We conducted a functional genomic screen for Hedgehog signaling by engineering antibiotic-based selection of Hedgehog-responsive cells and applying genome-wide CRISPR-mediated gene disruption. The screen robustly identifies factors required for ciliary signaling with few false positives or false negatives. Characterization of hit genes uncovers novel components of several ciliary structures including a protein complex containing ε- and δ- tubulin that is required for centriole maintenance. The screen also provides an unbiased tool for classifying ciliopathies and reveals that many forms of congenital heart defects are ciliopathies. Collectively, this screen enables a systematic analysis of ciliary function and of ciliopathies and also defines a versatile platform for dissecting signaling pathways through CRISPR-based screening.
Habitat preference of an herbivore shapes the habitat distribution of its host plant
Authors: Alexandre Nicolas M. , Humphrey Parris T. , Gloss Andrew D. , Lee Jimmy , Frazier Joseph , Affeldt Henry A. , Whiteman Noah K.
Published: June 2017

Plant distributions can be limited by habitat-biased herbivory, but the proximate causes of such biases are rarely known. Distinguishing plant-centric from herbivore-centric mechanisms driving differential herbivory between habitats is difficult without experimental manipulation of both plants and herbivores. Here we tested alternative hypotheses driving habitat-biased herbivory in bittercress (Cardamine cordifolia), which is more abundant under shade of shrubs and trees (shade) than in nearby meadows (sun) where herbivory is intense from the specialist flyScaptomyza nigrita. This system has served as a textbook example of habitat-biased herbivory driving a plant’s distribution across an ecotone, but the proximate mechanisms underlying differential herbivory are still unclear. First, we found that higherS. nigritaherbivory in sun habitats contrasts sharply with their preference to attack plants from shade habitats in laboratory choice experiments. Second,S. nigritastrongly preferred leaves in simulated sun over simulated shade habitats, regardless of plant source habitat. Thus, herbivore preference for brighter, warmer habitats overrides their preference for more palatable shade plants. This promotes the sun-biased herbivore pressure that drives the distribution of bittercress into shade habitats.
Engagement of spinal- vs prefrontal-projecting locus coeruleus neurons parses analgesia from aversion & anxiety in rats
Authors: Hirschberg Stefan , Li Yong , Randall Andrew , Kremer Eric J , Pickering Anthony E
Published: June 2017

The locus coeruleus (LC) projects throughout the brain and spinal cord and is the major source of central noradrenaline. It remains unclear whether the LC acts functionally as a single global effector or as discrete modules. Specifically, while spinal-projections from LC neurons can exert analgesic actions, it is not known whether they can act independently of ascending LC projections. Using viral vectors taken up at axon terminals, we expressed chemogenetic actuators selectively in LC neurons with spinal (LC:SC) or prefrontal cortex (LC:PFC) projections. Activation of theLC:SCmodule produced robust, lateralised analgesia while activation ofLC:PFCproduced aversion. In a neuropathic pain model,LC:SCactivation reduced hind-limb sensitization and induced conditioned place preference. By contrast, activation ofLC:PFCexacerbated spontaneous pain, produced aversion and increased anxiety-like behaviour. This independent, contrasting modulation of pain-related behaviours mediated by distinct noradrenergic modules provides evidence for a discrete functional organisation of the LC.
Replacing reprogramming factors with antibodies selected from autocrine antibody libraries
Authors: Blanchard Joel W. , Xie Jia , El-Mecharrafie Nadja , Gross Simon , Lee Sohyon , Lerner Richard A. , Baldwin Kristin K.
Published: June 2017

Signaling pathways initiated at the membrane establish and maintain cell fate during development and can be harnessed in the nucleus to generate induced pluripotent stem cells (iPSCs) from differentiated cells. Yet, the impact of extracellular signaling on reprogramming to pluripotency has not been systematically addressed. Here, we screen a lentiviral library encoding ˜100 million secreted and membrane-bound antibodies and identify multiple antibodies that can replaceSox2/c-MycorOct4during reprogramming. We show that one Sox2-replacing antibody initiates reprogramming by antagonizing the membrane-associated protein Basp1, thereby inducing nuclear factorsWT1andEsrrb/Lin28independent ofSox2. By successively manipulating this pathway we identify three new methods to generate iPSCs. This study expands current knowledge of reprogramming methods and mechanisms and establishes unbiased selection from autocrine antibody libraries as a powerful orthogonal platform to discover new biologics and pathways regulating pluripotency and cell fate.
Evolution with a seed bank: the population genetic consequences of microbial dormancy
Authors: Shoemaker WR , Lennon JT
Published: June 2017

Dormancy is a bet-hedging strategy that allows organisms to persist through conditions that are sub-optimal for growth and reproduction by entering a reversible state of reduced metabolic activity. Dormancy allows a population to maintain a reservoir of genetic and phenotypic diversity (i.e., a seed bank) that can contribute to the long-term survival of a population. This strategy can be potentially adaptive and has long been of interest to ecologists and evolutionary biologists. However, comparatively little is known about how dormancy influences the fundamental evolutionary forces of genetic drift, mutation, selection, recombination, and gene flow. Here, we investigate how seed banks affect the processes underpinning evolution by reviewing existing theory, implementing novel simulations, and determining how and when dormancy can influence evolution as a population genetic process. We extend our analysis to examine how seed banks can alter macroevolutionary processes, including rates of speciation and extinction. Through the lens of population genetic theory, we can understand the extent that seed banks influence microbial evolutionary dynamics.
Tension-dependent stretching and folding of ZO-1 controls the localization of its interactors
Authors: Spadaro Domenica , Le Shimin , Laroche Thierry , Mean Isabelle , Jond Lionel , Yan Jie , Citi Sandra
Published: June 2017

Tensile forces regulate epithelial homeostasis, but the molecular mechanisms behind this regulation are poorly understood. Using structured illumination microscopy and proximity ligation assays we show that the tight junction protein ZO-1 undergoes actomyosin tension-dependent stretching and folding in vivo. Magnetic tweezers experiments using purified ZO-1 indicate that pN-scale tensions (~2-4 pN) are sufficient to maintain the stretched conformation of ZO-1, while keeping its structured domains intact. Actomyosin tension and substrate stiffness regulate the localization and expression of the transcription factor DbpA and the tight junction membrane protein occludin in a ZO-1/ZO-2-dependent manner, resulting in modulation of gene expression, cell proliferation, barrier function and cyst morphogenesis. Interactions between the N-terminal (ZPSG) and C-terminal domains of ZO-1 prevent binding of DbpA to the ZPSG, and folding is antagonized by heterodimerization with ZO-2. We propose that tensile forces regulate epithelial homeostasis by activating ZO proteins through stretching, to modulate their protein interactions and downstream signaling.
Scikit-ribo: Accurate estimation and robust modeling of translation dynamics at codon resolution
Authors: Fang Han , Huang Yi-Fei , Radhakrishnan Aditya , Siepel Adam , Lyon Gholson J. , Schatz Michael C.
Published: June 2017

Ribosome profiling (Riboseq) is a powerful technique for measuring protein translation, however, sampling errors and biological biases are prevalent and poorly understand. Addressing these issues, we present Scikit-ribo (https://github.com/hanfang/scikit-ribo), the first open-source software for accurate genome-wide A-site prediction and translation efficiency (TE) estimation from Riboseq and RNAseq data. Scikit-ribo accurately identifies A-site locations and reproduces codon elongation rates using several digestion protocols (r= 0.99). Next we show commonly used RPKM-derived TE estimation is prone to biases, especially for low-abundance genes. Scikit-ribo introduces a codon-level generalized linear model with ridge penalty that correctly estimates TE while accommodating variable codon elongation rates and mRNA secondary structure. This corrects the TE errors for over 2000 genes inS. cerevisiae, which we validate using mass spectrometry of protein abundances (r= 0.81) and allows us to determine the Kozak-like sequence directly from Riboseq. We conclude with an analysis of coverage requirements needed for robust codon-level analysis, and quantify the artifacts that can occur from cycloheximide treatment.