Klein

The role of Ras signaling during tooth development is poorly understood. Ras proteins-which are activated by many upstream pathways, including receptor tyrosine kinase cascades-signal through multiple effectors, such as the mitogen-activated protein kinase (MAPK) and PI3K pathways. Here, we utilized the mouse incisor as a model to study how the MAPK and PI3K pathways regulate dental epithelial stem cells and amelogenesis. The rodent incisor-which grows continuously throughout the life of the animal due to the presence of epithelial and mesenchymal stem cells-provides a model for the study of ectodermal organ renewal and regeneration...

OBJECTIVES: The RASopathies are a group of syndromes that have in common germline mutations in genes that encode components of the Ras/mitogen-activated protein kinase (MAPK) pathway and have been a focus of study to understand the role of this pathway in development and disease. These syndromes include Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML or LEOPARD syndrome), neurofibromatosis type 1 (NF1), Costello syndrome (CS), cardio-facio-cutaneous (CFC) syndrome, neurofibromatosis type 1-like syndrome (NFLS or Legius syndrome) and capillary malformation-arteriovenous malformation syndrome (CM-AVM)...

High voltage atmospheric cold plasma (HVACP) is a novel non-thermal decontamination technology that has potential for use in the food industry. In this study, HVACP was applied to treat pure aflatoxin B1 (AFB1) powder on a glass slide. AFB1 was degraded by 76% using a 5 min HVACP treatment in air having 40% relative humidity. The degradation products of AFB1 were separated and their molecular formulas were elucidated using liquid chromatography time of flight mass spectrometry (HPLC-TOF MS). Six main degradation products were observed...

Brain-Computer Interface (BCI) research is an interdisciplinary area of study within Neural Engineering. Recent interest in end-user perspectives has led to an intersection with user-centered design (UCD). The goal of user-centered design is to reduce the translational gap between researchers and potential end users. However, while qualitative studies have been conducted with end users of BCI technology, little is known about individual BCI researchers' experience with and attitudes towards UCD. Given the scientific, financial, and ethical imperatives of UCD, we sought to gain a better understanding of practical and principled considerations for researchers who engage with end users...

Resin-based composites are used for bone repair applications and comprise resin matrix and different sized filler particles. Nanometer-sized filler particles improve composite's mechanical properties compared to micrometer-sized filler particles, but whether differences exist in the biological response to these composites is unknown. Natural bone comprises a nanocomposite structure, and nanoscale interactions with extracellular matrix components influence stem cell differentiation. Therefore we hypothesized that nanometer-sized filler particles in resin-based composites enhance osteogenic differentiation of stem cells showing a more bone cell-like response to mechanical loading compared to micrometer-sized filler particles...

To contribute to the aspirations of recent international biodiversity conventions, protected areas (PAs) must be strategically located, and not simply established on economically marginal lands as they have in the past. With refined international commitments under the Convention of Biodiversity to target protected areas in places of 'importance to biodiversity', this may now be the case. Here we analyze location biases in PAs globally over both historic (pre-2004) and recent time periods. Discouragingly, we find that both old and new protected areas are not targeting places with high concentration of threatened vertebrate species...

A case of a 16-year-old female with polyarticular juvenile idiopathic arthritis (JIA) since the age of 4 years is reported here. This patient also suffered from multiple congenital anomalies. On long-term treatment with oral methotrexate (MTX) and etanercept, multiple subcutaneous nodules were detected, which were accompanied by increased lactate dehydrogenase and uric acid levels. A biopsy of the largest nodule revealed Epstein-Barr (EB) virus-positive diffuse large B-cell lymphoma (DLBCL). The patient was classified as clinical stage IIIA due to a mediastinal lesion...

Working to establish analytic contact (Waska, 2007) with a patient involves the verbal act of interpretation. But, how one interprets and what we try to hold in words is not the same with each patient. Each patient requires, invites, provokes and responds to a unique mixture of interpretive elements or approaches. The projective identification process that is so often the bedrock of the transference, and therefore the catalyst of the counter-transference, forms the psychological climate between patient and analyst...

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Many cancers share specific genetic risk factors including both rare high-penetrance mutations and common single nucleotide polymorphisms (SNPs) identified through genome-wide association studies (GWAS). However, little is known about the overall shared heritability across cancers. Quantifying the extent to which two distinct cancers share genetic origin will give insights to shared biological mechanisms underlying cancer and inform design for future genetic association studies. In this study, we estimated the pair-wise genetic correlation between six cancer types (breast, colorectal, lung, ovarian, pancreatic and prostate) using cancer-specific GWAS summary statistics data based on 66,958 case and 70,665 control subjects of European ancestry...

There are a vast number of complementary and alternative medicines (CAM) in oncology. Also patients' needs for information on these methods are growing. Helping patients to classify and evaluate CAM methods is a challenge. The Cancer Information Service at the German Cancer Research Center has developed a benefit-risk-assessment based on evidence-based medicine and individual patient traits: To rate a CAM's benefit, the scientific evidence and the patient's therapeutic goals have to be taken into account. To estimate its risks, both, the method itself and the patient's status of health must be considered...

The concept of immune privilege of the central nervous system (CNS) has dominated the study of inflammatory processes in the brain. However, clinically relevant models have highlighted that innate pathways limit pathogen invasion of the CNS and adaptive immunity mediates control of many neural infections. As protective responses can result in bystander damage, there are regulatory mechanisms that balance protective and pathological inflammation, but these mechanisms might also allow microbial persistence. The focus of this review is to consider the host-pathogen interactions that influence neurotropic infections and to highlight advances in our understanding of innate and adaptive mechanisms of resistance as key determinants of the outcome of CNS infection...

FCRL4 is an immunoregulatory receptor that belongs to the Fc receptor-like (FCRL) family. In healthy individuals, FCRL4 is specifically expressed by memory B cells (MBCs) localized in sub-epithelial regions of lymphoid tissues. Expansion of FCRL4+ B cells has been observed in blood and other tissues in various infectious and autoimmune disorders. Currently, the mechanisms involved in pathological FCRL4+ B cell generation are actively studied, but they remain elusive. As in vivo FCRL4+ cells are difficult to access and to isolate, here we developed a culture system to generate in vitro FCRL4+ B cells from purified MBCs upon stimulation with soluble CD40 ligand and/or CpG DNA to mimic T-cell dependent and/or T-cell independent activation, respectively...

Rational design of conductive carbon hosts for high energy density lithium-sulfur batteries requires an understanding of the fundamental limitations to insulating active material loading. In this work, we investigate the electrochemistry of lithium sulfide films ranging in thickness from 30 to 3500 nm. We show that films thicker than approximately 40 nm cannot be charged at local charge densities above 1 μA cm-2, and by implication, the maximum useful pore diameter is near 60 nm in a practical cathode. 'Activation' overpotentials for Li2S are identified in thicker films, resulting from polysulfide generation, but are shown not to improve the fundamental areal charge limitations...

AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, panlobular inflammation, liver fibrosis and increased cardiovascular mortality. Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are indirect glucagon like peptide 1 (GLP-1) agonists with antidiabetic and anti-inflammatory activity, used for the treatment of type 2 diabetes. Their potential and underlying mechanisms to treat metabolic liver inflammation and fibrosis as well as the associated vascular dysfunction remain to be explored...

BACKGROUND: Adherence to evidence-based antibiotic therapy guidelines for treatment of upper respiratory tract infections (URIs) varies widely among clinicians. Understanding this variability is key for reducing inappropriate prescribing. OBJECTIVE: To measure how emergency department (ED) clinicians' perceptions of antibiotic prescribing risks affect their decision-making. DESIGN: Clinician survey based on fuzzy-trace theory, a theory of medical decision-making, combined with retrospective data on prescribing outcomes for URI/pneumonia visits in two EDs...

BACKGROUND: Relaxin-2 (RLX) is a peptide hormone that exerts beneficial anti-fibrotic and anti-inflammatory effects in diverse models of cardiovascular disease. The goal of this study was to determine the effects of RLX treatment on the susceptibility to atrial fibrillation (AF) after myocardial infarction (MI). METHODS: Mice with cryoinfarction of the left anterior ventricular wall were treated for two weeks with either RLX (75 μg/kg/d) or vehicle (sodium acetate) delivered via subcutaneously implanted osmotic minipumps...

The aim of this study was to assess the biomechanical stability of six different osteosynthesis methods after sagittal split osteotomy. Sixty polyurethane hemimandibles were divided into two groups, with six subgroups in each. After 10-mm advancement of the distal segment (group 1) and 10-mm advancement combined with 20° counterclockwise rotation (group 2), the bone segments were fixed using 2.0-mm plates/screws as follows: subgroup A, one conventional straight plate; subgroup B, two conventional straight plates; subgroup C, one conventional sagittal plate; subgroup D, one locking straight plate; subgroup E, two locking straight plates; subgroup F, one locking sagittal plate...

STUDY OBJECTIVES: To determine if the application of continuous negative external pressure (cNEP) is effective and safe in individuals with obstructive sleep apnea (OSA) during an overnight in-laboratory sleep study. METHODS: A prospective, open-label pilot study in subjects with documented OSA recruited from the patient population at one sleep clinic. The intervention was application and titration of cNEP during overnight polysomnography. RESULTS: Of the 15 subjects studied (mean apnea-hypopnea index [AHI] at baseline, 43...

To decide optimally between available options, organisms need to learn the values associated with these options. Reinforcement learning models offer a powerful explanation of how these values are learnt from experience. However, human choices often violate normative principles. We suggest that seemingly counterintuitive decisions may arise as a natural consequence of the learning mechanisms deployed by humans. Here, using fMRI and a novel behavioural task, we show that, when suddenly switched to novel choice contexts, participants' choices are incongruent with values learnt by standard learning algorithms...