Miracle-dz/UniFAR-FTUs huggingface dataset:
Congenital Melanocytic Nevus: Two Clinicopathological Forms

Abstract:Congenital melanocytic nevus (CMN) is a hamartomatous disease for which many attempts at classification have been proposed. This disease is relevant not only because of its functional and esthetic implications but also because it is a well-documented precursor to malignant melanoma. We performed a clinical and pathological prospective study of 200 cases of CMN and were able to identify 2 different forms of CMN, each one with biological, clinical, and histopathological features and criteria that are consistent and repeatable. We propose to name them types I and II. Type I CMN is the most common, usually, if not always, a single lesion, it consists of a plaque that involves only 1 anatomic region and does not go beyond it; type I CNM grows in proportion to the growth of the child, melanoma rarely develops from it, and when it does it usually arises at the dermoepidermal junction. Its histopathology shows cords, strands, nests, and single units of melanocytes spreading between collagen bundles only in the dermis and frequently the epidermis too, but without trespassing to the hypodermis, that is, it is superficial. Type II CMN is always made up of many lesions, one of them being very large and surrounded by many lesions; histopathologically, it involves not only the skin but also deeper structures, sometimes bone and central nervous system; therefore, it is deep; when melanoma develops, it does in the dermal component and usually from the largest plaque. This type of CMN is the one that develops neurocutaneous melanocytosis. This system is not only easy and logical but it also has biologic advantages and the clinical–pathological correlation and criteria are repeatable by clinicians and pathologists.
p 160 ROCK mediates RhoA activation of Na – H exchange

The ubiquitously expressed Na–H exchanger, NHE1, acts downstream of RhoA in a pathway regulating focal adhesion and actin stress fiber formation. p160ROCK, a serine/threonine protein kinase, is a direct RhoA target mediating RhoA-induced assembly of focal adhesions and stress fibers. Here, stress fiber formation induced by p160ROCK was inhibited by the addition of a specific NHE1 inhibitor, ethylisopropylamiloride, in CCL39 fibroblasts, and was absent in PS120 mutant fibroblasts lacking NHE1. In CCL39 cells, NHE1 activity was stimulated by expression of mutationally active p160ROCK, but not by mutationally active protein kinase N, another RhoA target kinase. Expression of a dominant interfering p160ROCK inhibited RhoA-, but not Cdc42or Rac-activation of NEH1. In addition, the p160ROCK-specific inhibitor Y-27632 inhibited increases in NHE1 activity in response to RhoA, and to lysophosphatidic acid (LPA), which stimulates RhoA, and it also inhibited LPA-increased phosphorylation of NHE1. A C-terminal truncation of NHE1 abolished both LPA-induced phosphorylation and activation of the exchanger. Furthermore, mutationally active p160ROCK phosphorylated an NHE1 C-terminal fusion protein in vitro, and this was inhibited in the presence of Y-27632. Phosphopeptide maps indicated that identical residues in NHE1 were phosphorylated by p160ROCK in vivo and in vitro. These findings identify p160ROCK as an upstream, possibly direct, activator of NHE1, and suggest that NHE1 activity and phosphorylation are necessary for actin stress fiber asssembly induced by p160ROCK.
Biomechanical Comparison of Anatomic Trajectory Pedicle Screw versus Injectable Calcium Sulfate Graft-Augmented Pedicle Screw for Salvage in Cadaveric Thoracic Bone

Many salvage options for failed thoracic pedicle screws exist including the use of a different trajectory or the augmentation of the screw with polymethylmethacrylate cement. Although polymethylmethacrylate immediately increases the construct stiffness and the pull-out strength, it may cause bone necrosis, toxin relaxation, and/or neural injury. On the other hand, calcium sulfate bone grafts have a high potential for biologic incorporation and no thermal damage effect. In the current study, polyaxial pedicle screws were first inserted with a straightforward approach on both sides in 17 fresh human cadaveric thoracic vertebrae. The maximal insertion torque for each screw was measured and then the pull-out strengths were recorded. Afterward, these pedicle screws were randomly assigned to be replaced either by graft augmentation or by anatomic trajectory technique for salvage. The graft-augmented screws were placed using the previous holes. The maximum insertional torque for each anatomic trajectory screw was measured. Finally, the pull-out strengths of the revision screws were recorded. The mean maximum insertional torque decreased with the anatomic trajectory salvage technique when compared with the straightforward approach, 0.23 versus 0.38 Nm, respectively (P=0.003). The anatomic trajectory revision resulted in decreased pull-out strength when compared with the pull-out strength of the straightforward technique, 297 versus 469 N, respectively (P=0.003). The calcium sulfate graft augmentation increased the pull-out strength when compared with the pull-out strength of the straightforward technique, 680 versus 477 N, respectively (P=0.017). The mean pull-out strength ratio of revised screw to original was 0.71 for anatomic trajectory and 1.8 for graft-augmented screws, a statistically significant difference (P=0.002).
Maslach Burnout Inventory: Factor Structures and Norms for USA Pharmacists

This study was conducted to establish normative data as well as evaluate the construct validity and reliability of the three subscales of the Maslach Burnout Inventory when given to a national sample of USA licensed practicing pharmacists. Data were subjected to principal factors analysis with iteration and a varimax rotation to obtain a three-factor solution. Visual analysis and statistical comparison provided empirical support for the presence of the hypothesized (a priori) constructs of Emotional Exhaustion, Depersonalization, and Lack of Personal Accomplishment. Internal consistency of the derived subscales, as measured by Cronbach's alpha coefficient, were comparable with previous data. Pharmacists' subscale scores were significantly lower than those obtained in studies of the helping professions.
Ionic dysregulatory phenotyping of pathologic retinal thinning with manganese-enhanced MRI.

PURPOSE To test the hypothesis that manganese-enhanced MRI (MEMRI) provides a sensitive and robust measure of an important retinal ionic dysregulatory phenotype in pathologic retinal thinning. METHODS Four hours after intraperitoneal MnCl(2) injection, high-resolution MEMRI data were collected from overnight dark-adapted male control Sprague-Dawley and albino Royal College of Surgeons rats before (at development stage postnatal day [P] 17) and during photoreceptor degeneration (P36 and P57). In separate experiments, control rats, with and without repetitive hypoxic preconditioning, were subjected to high IOP (100 mm Hg) for 60 minutes followed by 24 hours or 7 days of reperfusion (e.g., ischemia/reperfusion). Central retinal thickness and intraretinal ion activity were measured from the MEMRI data. Histology examination was also performed to confirm retinal damage. RESULTS In two different neurodegenerative models, MEMRI revealed first-time evidence for changes (P < 0.05) in intraretinal ion regulation before and during pathologic, but not (P > 0.05) developmental, retinal thinning. This phenotype was significantly altered by a neuroprotective repetitive hypoxic preconditioning protocol. CONCLUSIONS MEMRI and a nontoxic systemic dose of MnCl(2) provided an objective, noninvasive measure of an ionic deregulatory phenotype that appears useful for improved early diagnosis and treatment prognosis in a range of neurodegenerative diseases and their treatment.
Constructing optimal experience for the hospitalized newborn through neuro-based music therapy

Music-based intervention for hospitalized newborn infants has traditionally been based in a biomedical model, with physiological stability as the prime objective. More recent applications are grounded in other theories, including attachment, trauma and neurological models in which infant, parent and the dyadic interaction may be viewed as a dynamic system bound by the common context of the neonatal intensive care unit (NICU). The immature state of the preterm infant’s auditory processing system requires a careful and individualized approach for the introduction of purposeful auditory experience intended to support development. The infant’s experience of an unpredictable auditory environment is further compromised by a potential lack of meaningful auditory stimulation. Parents often feel disconnected from their own capacities to nurture their infant with potentially life-long implications for the infant’s neurobehavioral and psychological well-being. This perspectives paper will outline some neurological considerations for auditory processing in the premature infant to frame a premise for music-based interventions. A hypothetical clinical case will illustrate the application of music by a music therapist with an infant and family in NICU.
Multiple Bypass : Interposition Agents for Distributed Computing ( Preprint Version )

Interposition agents are a well-known device for attaching legacy applications to distributed systems. However, agents are difficult to build and are often large, monolithic pieces of software which are suited only to limited applications or systems. We solve this problem with Bypass, a language and a tool for quickly building multiple small agents that can be combined together to create powerful yet manageable software.
EARLY PREWEANING METHAMPHETAMINE AND POSTWEANING REARING CONDITIONS INTERFERE WITH THE DEVELOPMENT OF PERIPHERAL STRESS PARAMETERS AND NEURAL GROWTH FACTORS IN GERBILS

Adrenal steroid hormones and neuronal growth factors are two interacting systemic factors that mediate the environment's influence on the brain's structure and function. In order to further elucidate their role and relationship in the effects of early stressful experience and isolated rearing (IR), this study measured blood corticosterone titres and relative adrenal weights and assessed nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) concentrations in brain regions of both hemispheres of young adult Mongolian gerbils injected on postnatal day 14 with a single high dose of methamphetamine (MA) or saline and raised after weaning either in an enriched or an impoverished environment. Irrespective of MA challenge, IR decreased corticosterone titres to about half, but increased relative adrenal weights. BDNF concentrations were decreased by IR in saline-injected animals in the left prefrontal and parietal cortices and right entorhinal and hippocampal cortices, and in the subcortical regions of both hemispheres. NGF concentrations were unaltered by IR in saline-injected animals, but increased in MA challenged animals in the entorhinal/hippocampal cortices and subcortical areas of both hemispheres. MA application induced shifts of the lateral asymmetry in NGF contents in prefrontal and entorhinal cortices. The results suggest that an early pharmacological traumatization can set a switch for further brain development, and that growth factor concentrations might possibly be influenced by peripheral stress hormones.
Non-Invasive Imaging of Vascular Inflammation

In large-vessel vasculitides, inflammatory infiltrates may cause thickening of the involved arterial vessel wall leading to progressive stenosis and occlusion. Dilatation, aneurysm formation, and thrombosis may also ensue. Activated macrophages and T lymphocytes are fundamental elements in vascular inflammation. The amount and density of the inflammatory infiltrate is directly linked to local disease activity. Additionally, patients with autoimmune disorders have an increased cardiovascular (CV) risk compared with age-matched healthy individuals as a consequence of accelerated atherosclerosis. Molecular imaging techniques targeting activated macrophages, neovascularization, or increased cellular metabolic activity can represent effective means of non-invasive detection of vascular inflammation. In the present review, novel non-invasive imaging tools that have been successfully tested in humans will be presented. These include contrast-enhanced ultrasonography, which allows detection of neovessels within the wall of inflamed arteries; contrast-enhanced CV magnetic resonance that can detect increased thickness of the arterial wall, usually associated with edema, or mural enhancement using T2 and post-contrast T1-weighted sequences, respectively; and positron emission tomography associated with radio-tracers such as [18F]-fluorodeoxyglucose and the new [11C]-PK11195 in combination with computed tomography angiography to detect activated macrophages within the vessel wall. Imaging techniques are useful in the diagnostic work-up of large- and medium-vessel vasculitides, to monitor disease activity and the response to treatments. Finally, molecular imaging targets can provide new clues about the pathogenesis and evolution of immune-mediated disorders involving arterial vessels.
Epigenetic dynamics of the Kcnq1 imprinted domain in the early embryo

The mouse Kcnq1 imprinted domain is located on distal chromosome 7 and contains several imprinted genes that are paternally repressed. Repression of these genes is regulated by a non-coding antisense transcript, Kcnq1ot1, which is paternally expressed. Maternal repression of Kcnq1ot1 is controlled by DNA methylation originating in the oocyte. Some genes in the region are imprinted only in the placenta, whereas others are imprinted in both extra-embryonic and embryonic lineages. Here, we show that Kcnq1ot1 is paternally expressed in preimplantation embryos from the two-cell stage, and that ubiquitously imprinted genes proximal to Kcnq1ot1 are already repressed in blastocysts, ES cells and TS cells. Repressive histone marks such as H3K27me3 are present on the paternal allele of these genes in both ES and TS cells. Placentally imprinted genes that are distal to Kcnq1ot1, by contrast, are not imprinted in blastocysts, ES or TS cells. In these genes, paternal silencing and differential histone marks arise during differentiation of the trophoblast lineage between E4.5 and E7.5. Our findings show that the dynamics during preimplantation development of gene inactivation and acquisition of repressive histone marks in ubiquitously imprinted genes of the Kcnq1 domain are very similar to those of imprinted X inactivation. By contrast, genes that are only imprinted in the placenta, while regulated by the same non-coding RNA transcript Kcnq1ot1, undergo epigenetic inactivation during differentiation of the trophoblast lineage. Our findings establish a model for how epigenetic gene silencing by non-coding RNA may depend on distance from the non-coding RNA and on lineage and differentiation specific factors.
Secure and practical identity-based encryption

A variant of Waters' identity-based encryption scheme with a much smaller system parameters size (only a few kilobytes) is presented. It is shown that this variant is semantically secure against passive adversaries in the standard model. In essence, the new variant divides Waters' system parameters size by a factor l at the cost of (negligibly) reducing security by l bits. The construction yields a fully secure practical identity-based encryption scheme.
High performance IP lookup circuit using DDR SDRAM

DDR-SDRAM based data lookup techniques are evolving into a core technology for packet lookup applications for data network, benefitting from the features of high density, high bandwidth and low price of DDR memory products in the market. Our proposed DDR-SDRAM based lookup circuit is capable of achieving IP header lookup for network line-rates of up to 10 Gbps, providing a solution on high-performance and economic packet header inspections.
Problematic Internet Use in High School Students in Guangdong Province, China

Background Problematic Internet Use (PIU) is a growing problem in Chinese adolescents. There are many risk factors for PIU, which are found at school and at home. This study was designed to investigate the prevalence of PIU and to investigate the potential risk factors for PIU among high school students in China. Methodology/Principal Findings A cross-sectional study was conducted. A total of 14,296 high school students were surveyed in four cities in Guangdong province. Problematic Internet Use was assessed by the 20-item Young Internet Addiction Test (YIAT). Information was also collected on demographics, family and school-related factors and Internet usage patterns. Of the 14,296 students, 12,446 were Internet users. Of those, 12.2% (1,515) were identified as problematic Internet users (PIUs). Generalized mixed-model regression revealed that there was no gender difference between PIUs and non-PIUs. High study-related stress, having social friends, poor relations with teachers and students and conflictive family relationships were risk factors for PIU. Students who spent more time on-line were more likely to develop PIU. The habits of and purposes for Internet usage were diverse, influencing the susceptibility to PIU. Conclusions/Significance PIU is common among high school students, and risk factors are found at home and at school. Teachers and parents should pay close attention to these risk factors. Effective measures are needed to prevent the spread of this problem.
Tolerant versus intolerant testing for Boolean properties

A property tester with high probability accepts inputs satisfying a given property and rejects inputs that are far from satisfying it. A tolerant property tester, as defined by Parnas, Ron and Rubinfeld, must also accept inputs that are close enough to satisfying the property. We construct two properties of binary functions for which there exists a test making a constant number of queries, but yet there exists no such tolerant test. The first construction uses Hadamard codes and long codes. Then, using probabilistically checkable proofs of proximity as constructed by Ben-Sasson et. al., we exhibit a property which has constant query intolerant testers but for which any tolerant tester requires n/sup /spl Omega/(1)/ queries.
TRPV1 mediates cellular uptake of anandamide and thus promotes endothelial cell proliferation and network-formation

ABSTRACT Anandamide (N-arachidonyl ethanolamide, AEA) is an endogenous cannabinoid that is involved in various pathological conditions, including cardiovascular diseases and tumor-angiogenesis. Herein, we tested the involvement of classical cannabinoid receptors (CBRs) and the Ca2+-channel transient receptor potential vanilloid 1 (TRPV1) on cellular AEA uptake and its effect on endothelial cell proliferation and network-formation. Uptake of the fluorescence-labeled anandamide (SKM4-45-1) was monitored in human endothelial colony-forming cells (ECFCs) and a human endothelial-vein cell line (EA.hy926). Involvement of the receptors during AEA translocation was determined by selective pharmacological inhibition (AM251, SR144528, CID16020046, SB366791) and molecular interference by TRPV1-selective siRNA-mediated knock-down and TRPV1 overexpression. We show that exclusively TRPV1 contributes essentially to AEA transport into endothelial cells in a Ca2+-independent manner. This TRPV1 function is a prerequisite for AEA-induced endothelial cell proliferation and network-formation. Our findings point to a so far unknown moonlighting function of TRPV1 as Ca2+-independent contributor/regulator of AEA uptake. We propose TRPV1 as representing a promising target for development of pharmacological therapies against AEA-triggered endothelial cell functions, including their stimulatory effect on tumor-angiogenesis.
Nearness diagram (ND) navigation: collision avoidance in troublesome scenarios

This paper addresses the reactive collision avoidance for vehicles that move in very dense, cluttered, and complex scenarios. First, we describe the design of a reactive navigation method that uses a "divide and conquer" strategy based on situations to simplify the difficulty of the navigation. Many techniques could be used to implement this design (since it is described at symbolic level), leading to new reactive methods that must be able to navigate in arduous environments (as the difficulty of the navigation is simplified). We also propose a geometry-based implementation of our design called the nearness diagram navigation. The advantage of this reactive method is to successfully move robots in troublesome scenarios, where other methods present a high degree of difficulty in navigating. We show experimental results on a real vehicle to validate this research, and a discussion about the advantages and limitations of this new approach.
Comparative Genomics of the Dormancy Regulons in Mycobacteria

ABSTRACT In response to stresses, Mycobacterium cells become dormant. This process is regulated by the DosR transcription factor. In Mycobacterium tuberculosis, the dormancy regulon is well characterized and contains the dosR gene itself and dosS and dosT genes encoding DosR kinases, nitroreductases (acg; Rv3131), diacylglycerol acyltransferase (DGAT) (Rv3130c), and many universal stress proteins (USPs). In this study, we apply comparative genomic analysis to characterize the DosR regulons in nine Mycobacterium genomes, Rhodococcus sp. RHA1, Nocardia farcinica, and Saccharopolyspora erythraea. The regulons are highly labile, containing eight core gene groups (regulators, kinases, USPs, DGATs, nitroreductases, ferredoxins, heat shock proteins, and the orthologs of the predicted kinase [Rv2004c] from M. tuberculosis) and 10 additional genes with more restricted taxonomic distribution that are mostly involved in anaerobic respiration. The largest regulon is observed in M. marinum and the smallest in M. abscessus. Analysis of large gene families encoding USPs, nitroreductases, and DGATs demonstrates a mosaic distribution of regulated and nonregulated members, suggesting frequent acquisition and loss of DosR-binding sites.