Miracle-dz/UniFAR-FTUs huggingface dataset:
Netrin and Frazzled Regulate Presynaptic Gap Junctions at a Drosophila Giant Synapse

Netrin and its receptor, Frazzled, dictate the strength of synaptic connections in the giant fiber system (GFS) of Drosophila melanogaster by regulating gap junction localization in the presynaptic terminal. In Netrin mutant animals, the synaptic coupling between a giant interneuron and the “jump” motor neuron was weakened and dye coupling between these two neurons was severely compromised or absent. In cases in which Netrin mutants displayed apparently normal synaptic anatomy, half of the specimens exhibited physiologically defective synapses and dye coupling between the giant fiber (GF) and the motor neuron was reduced or eliminated, suggesting that gap junctions were disrupted in the Netrin mutants. When we examined the gap junctions with antibodies to Shaking-B (ShakB) Innexin, they were significantly decreased or absent in the presynaptic terminal of the mutant GF. Frazzled loss of function mutants exhibited similar defects in synaptic transmission, dye coupling, and gap junction localization. These data are the first to show that Netrin and Frazzled regulate the placement of gap junctions presynaptically at a synapse.
Antifungal Therapy in a Murine Model of Disseminated Infection by Cryptococcus gattii

ABSTRACT We have evaluated the efficacy of posaconazole (PSC), voriconazole (VRC), and amphotericin B (AMB) in a murine model of systemic infection by Cryptococcus gattii using immunocompromised animals and three clinical strains of the fungus. AMB was the most effective drug in prolonging the survival of mice and also in reducing tissue burden in all organs tested. To a lesser degree, VRC at 60 mg/kg of body weight in lung tissue and PSC at 40 mg/kg also in spleen demonstrated good efficacy in reducing the fungal load. The PSC and VRC levels in serum and brain tissue, determined by an agar diffusion bioassay method at 4 h after the last dose of the therapy, were above the corresponding MIC values. However, these drugs were not able to reduce the fungal load in brain tissue. Our results demonstrated that PSC and, to a lesser degree, VRC, have fungistatic activity and potential for the treatment of human pulmonary cryptococcosis.
Network Reconnaissance in IPv6 Networks

IPv6 offers a much larger address space than that of its IPv4 counterpart. An IPv6 subnet of size /64 can (in theory) accommodate approximately 1.844 * 10^19 hosts, thus resulting in a much lower host density (#hosts/#addresses) than is typical in IPv4 networks, where a site typically has 65,000 or fewer unique addresses. As a result, it is widely assumed that it would take a tremendous effort to perform address-scanning attacks against IPv6 networks; therefore, Pv6 address-scanning attacks have been considered unfeasible. This document formally obsoletes RFC 5157, which first discussed this assumption, by providing further analysis on how traditional address-scanning techniques apply to IPv6 networks and exploring some additional techniques that can be employed for IPv6 network reconnaissance.
Pseudoporphyria following self‐medication with chlorophyll

Two cases of pseudoporphyria are described in which the clinical features of porphyria cutanea tarda occurred in the absence of abnormalities in porphyrin metabolism. Both patients presented with skin fragility and bullae on the dorsal aspect of the hands. The patients consumed a commercial liquid chlorophyll drink in which we detected fluorescent compounds with characteristics typical of previously described chlorophyll derived photosensitisers.
Central auditory dysfunction associated with exposure to a mixture of solvents

Abstract Objective: The aim of the present research was to investigate central auditory functioning in normal-hearing, solvent-exposed subjects compared to normal-hearing subjects without solvent exposure, with a comprehensive test battery of behavioural central auditory functioning procedures. Study sample: Forty-six normal-hearing, solvent-exposed subjects and 46 normal-hearing, control subjects were selected to participate in the study. Design: All subjects must present with normal hearing thresholds and absence of history of variables related to the onset of auditory dysfunction. Subjects were evaluated with a test battery comprising pure-tone audiometry (PTA), dichotic digits (DD), pitch pattern sequence (PPS), filtered speech (FS), random gap detection (RGD), masking level difference (MLD), and hearing-in-noise (HINT) tests. Results: Analyses of covariance (ANCOVA) were performed to compare the mean values of the dependent variables (results for DD, PPS, FS, RGD, MLD, and HINT) between solvent-exposed and control subjects. Age and average hearing thresholds (500–8000 Hz) were included in the analyses as covariates. Significant differences for DD, PPS, FS, and RGD results were found between groups. Conclusion: This study provides further evidence of the central auditory dysfunction associated with solvent exposure. Sumario Objetivo: El objetivo de este trabajo fue investigar el funcionamiento auditivo central en personas con audición normal expuestas a solventes, comparados con sujetos normales sin exposición a solventes, por medio de una batería integral de procesos de funcionamiento comportamental auditivo central. Muestra de estudio: Se seleccionaron cuarenta y seis sujetos normo-oyentes expuestos a solventes y 46 sujetos normales como grupo control, para participar en este estudio. Diseño: Todos los sujetos deb an presentar umbrales auditivos normales y ausencia de datos de variables relacionadas con el inicio de disfunción auditiva. Los sujetos fueron evaluados con una batería de pruebas que comprendió la audiometr a por tonos puros (PTA), Digitos dicóticos (DD), Secuencia de patrones de frecuencia (PPS), Lenguaje filtrado (FS), Detección de intervalos al azar (RGD), diferencia de niveles de enmascaramiento (MLD) y Audición en ruido (HINT). Resultados: se realizó el análisis de covarianza (ANCOVA) para comparar los valores de las variables dependientes (resultados de DD, PPS, FS, RGD, MLD y HINT) entre los sujetos expuestos a solventes y los del grupo control. La edad y los umbrales auditivos promedio (500–8000 Hz) se incluyeron en el análisis como covariables. Se encontraron diferencias significativas con los resultados para DD, PPS, FS y RGD entre ambos grupos. Conclusión: Este estudio proporciona evidencias adicionales de disfunción audtiva central asociada a la exposición a solventes.
Coronary arteriovenous fistulas: Collective review and management of six new cases—changing etiology, presentation, and treatment strategy

We considered it worthwhile to review the literature of the last decade (1985–1995) to answer the question whether the etiology and the clinical picture of coronary arteriovenous fistulas (CAVFs) have changed. Furthermore, new therapeutic modalities such as percutaneous transcatheter embolization have been developed. We tried to define the place of these techniques in the therapeutic arena. Clinical presentation and management of six patients with eight congenital CAVFs and 76 subjects with 96 congenital and acquired CAVFs taken from a review of the recent literature are presented. Sixty‐three review subjects (78%) were treated medically, with one fatal case. Ligation of the fistula was achieved by surgical techniques in 10% of review subjects, while percutaneous transcatheter embolization (PTE) was performed in nine patients (12%). Percutaneous transcatheter embolization techniques are being increasingly used in the treatment of CAVFs. The etiology of CAVFs has a tendency to show alterations toward the acquired pathogenesis. In 64% of the review subjects the fistula was congenital in origin, and in 36% it had an acquired cause. Among the patients of the current review, the clinical presentations were 55% asymptomatic, 34% chest pain (anginal or atypical), and 13% congestive heart failure. The CAVFs of our six patients are all congenital in origin. In the current review, the clinical presentation showed a trend toward increasing chest complaints (34%) compared with the review (10%) published in the mid 1970s. This may be due to a higher mean age, and hence increased concurrent coronary artery disease due to aging compared with the review population of two decades ago.
The Answer Machine

Abstract The Answer Machine is a practical, non-technical guide to the technologies behind information seeking and analysis. It introduces search and content analytics to software buyers, knowledge managers, and searchers who want to understand and design effective online environments. The book describes how search evolved from an expert-only to an end user tool. It provides an overview of search engines, categorization and clustering, natural language processing, content analytics, and visualization technologies. Detailed profiles for Web search, eCommerce search, eDiscovery, and enterprise search contrast the types of users, uses, tasks, technologies, and interaction designs for each. These variables shape each application, although the underlying technologies are the same. Types of information tasks and the trade-offs between precision and recall, time, volume and precision, and privacy vs. personalization are discussed within this context. The book examines trends toward convenient, context-aware comp.
Lactulose and neomycin attenuate leukocyte‐endothelial cell adhesion in an animal model of inflammatory bowel disease

Objective The role of intestinal flora in the pathogenesis of inflammatory bowel disease is under discussion. The objective of this study was to assess the effect of lactulose (Lac) and neomycin (Neo), both of which are used clinically for changing or reducing intestinal flora, on leukocyte-endothelial cell interaction in an indomethacin (Indo)-induced long-lasting ileitis in Sprague-Dawley rats. Methods Two doses of Indo (7.5 mg/kg, s.c.) were given 24 h apart. Animals were fed with standard rat chow for 10 days until 12 h prior to the experiment. Solutions of Lac (1.0 mg/kg b.w.) or Neo (0.1 g/kg) were gavaged daily for 10 days between Indo administration and the experiment. Ten mesenteric venules (30 μm diameter) per animal (n = 5 per group) were observed using intravital microscopy, and the following parameters were monitored: number of adherent and emigrated leukocytes, leukocyte rolling velocity, erythrocyte velocity, venular blood flow, and shear rate. Macroscopically visible injury was scored 0 to 5, and faecal pH was measured in the distal 20 cm of ileum. Results Ten days after Indo treatment leukocyte adherence and emigration were increased (2.2-fold and 3.3-fold vs. control, respectively) while leukocyte rolling velocity and venular wall shear rate were reduced (both parameters to 81 % of control). Lac and Neo attenuated microcir-culatory parameters to a similar extent while macroscopic damage was prevented only by Neo but not by Lac. The effects of both substances were accompanied by a normalization of faecal pH to control level which had been lowered by Indo. Conclusion The Indo-induced increase in leukocyte-endothelial cell interaction is blunted by Lac and Neo. At the same time the Indo-induced lowering of faecal pH is normalized by both substances. The reduction of macroscopic injury by Neo but not by Lac in the chronic phase of Indo inflammation might be due to additional effects on other inflammatory cells such as macrophages.
Case of coexisting psoriatic arthritis and bullous pemphigoid improved by etanercept

lide acetate is a synthetic analog of GnRH and indicated in the treatment of premenopausal breast cancer. Injectable depot formulations deliver the drug over a period of 3 months. Larmore and Klein showed that estrogen, progesterone, and luteinizing and follicle-stimulating hormone levels are significantly suppressed as at menopause by 3 weeks after the initial dose and start to recover in 6 weeks after stopping depot injections. In this case, the timeline of precipitation and exacerbation of psoriatic lesions are coincident with sex hormone level changes in the patient. Movad et al. have reported psoriatic worsening at menopause. Also, it was suggested that elevated levels of progesterone and estrogen have a role in improvement of T-helper 1-mediated autoimmune diseases. In the present case, suppressed levels of hormones or ratio differences between progesterone and estrogen during leuprolide acetate treatment might have been responsible for psoriatic lesions. To conclude, the case presented is the first report of precipitation and/or exacerbation of psoriasis due to leuprolide acetate and supports the view that sex hormone level changes influence the precipitation and exacerbation of psoriasis. The chronological association between application of leuprolide acetate and severity of psoriatic lesions is documented in this case. The possible psoriasiform side-effects of drugs should be considered in hormonal therapy.
Utility of p16INK4a, CEA, Ki67, P53 and ER/PR in the Differential Diagnosis of Benign, Premalignant, and Malignant Glandular Lesions of the Uterine Cervix and Their Relationship with Silverberg Scoring System for Endocervical Glandular Lesions

Early detection of premalignant and malignant glandular lesions of the uterine cervix and their distinction from benign mimics is crucial but sometimes difficult. In this study, we investigated utility of expression of p16INK4a, CEA, Ki67, p53 and ER/PR in evaluating the benign, premalignant, and malignant glandular lesions of the uterine cervix. A total of 35 cervical cone or LEEP cases were collected including 14 adenocarcinoma in situ (AIS), 7 endocervical glandular dysplasia (EGD), and 14 benign mimics (BM). A histological score for each case according to the criteria proposed by Silverberg group was assigned independently by 4 pathologists. Formalin-fixed, paraffin-embedded sections were immunostained with p16, CEA, p53, Ki67, and ER/PR. Immunoreactivity was scored based on intensity (0 = none, 1 = mild, 2 = moderate, 3 = marked) and percentage of cells staining (0 = <1%,1 = 2-10%, 2 = 11-40%, 3 = >40%). A comparison of histological scores and immunoscores in 3 diagnostic categories was analysed. The histological scores assigned independently by 4 pathologists were all equal or above 6 for AIS, between 3 and 5 for EGD, and equal or below 3 for BM. There was increased expression of p16 and CEA in EGD compared with BM (P < 0.05), with further increase in expression of these markers in AIS compared with EGD (P < 0.05). Ki67 expression was significantly increased in AIS compared to EGD (P < 0.05) as well as compared to BM (P < 0.05). Ki67 expression was only slightly increased in EGD as compared to BM. There was a loss of ER/PR in cervical AIS, but not in EGD. Our results indicate that the Silverberg scoring system is a useful tool in differential diagnosis of cervical glandular lesions for increased diagnostic accuracy and interobserver agreement. Most cervical glandular lesions can be differentiated by using a combination of histological scores with a panel of immunomarkers.
Surgery for Intractable Infantile Spasms: Neuroimaging Perspectives

Summary: Twenty‐three infants and children underwent cortical resection (n= 15) or hemispherectomy (n =8) for intractable infantile spasms. Infantile spasms were present at the time of surgery in 17 of the 23 patients; in six, spasms had evolved to other seizure types during surgical evaluation. Children with a remote history of infantile spasms were excluded from this study. Focal or hemispheric lesions were identified by magnetic resonance imaging in seven children; an additional two showed focal atrophy without a discrete lesion. Positron emission tomography (PET) showed lateralized or localized abnormalities of cerebral glucose utilization in all patients; in 14, PET was the only neuroimaging modality to identify the epileptogenic cortex. When this occurred, neuropathological examination of resected brain tissue typically showed malformative and dysplastic cortical lesions. Focal interictal and/or ictal electrographic abnormalities were present in all patients, and corresponded well with localization from neuroimaging. None of the patients were subjected to chronic invasive electrographic monitoring with intracranial electrodes. At follow‐up (range 4–67 months; mean 28.3 months), 15 children were seizure‐free, three had 90% seizure control, one had 75% seizure control, and four failed to benefit from surgery with respect to seizure frequency.
Initiating the inflammatory phase of incisional healing prior to tissue injury.

BACKGROUND The time required for incisional healing accounts for the majority of postoperative pain and convalescence. Impaired healing prolongs the process further. If a method for accelerating acute incisional wound healing could be developed, patients would benefit from decreased wound failure and an earlier return to their premorbid condition. MATERIALS AND METHODS In a rat dermal model, cytokine or vehicle infiltration prior to incision was performed using a single dose or four daily doses preincision. Planned incision sites were primed with the proinflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) or platelet-derived growth factor BB (PDGF-BB) in an effort to activate the inflammatory phase of healing prior to wounding. At the time of incision closure, one half of the incisions were treated with transforming growth factor beta(2) (TGF-beta(2)). Incisional sites were biopsied and stained with hematoxylin and eosin and immunohistochemistry for inflammatory cells and fibroblast populations and breaking strength was measured. RESULTS Priming skin with GM-CSF or PDGF-BB mimicked the early inflammatory phase of wound healing. Macrophage staining (EB1) and fibroblast staining (vimentin) were significantly increased prior to incision. Inflammatory priming as well as priming coupled with TGF-beta(2) at the time of the incision closure synergistically improved breaking strength. CONCLUSION This study demonstrates that sequential therapy consisting of priming of tissue with an inflammatory cytokine followed by application of a proliferative cytokine at the time of incision closure nearly doubles the breaking strength of an acute wound. By manipulating the inflammatory and early proliferative phases of wound healing with tissue growth factors, it may be possible to accelerate acute wound repair and shift the wound healing trajectory to the left.
Notch1 mediates uterine stromal differentiation and is critical for complete decidualization in the mouse

Uterine receptivity implies a dialogue between the hormonally primed maternal endometrium and the free‐floating blastocyst. Endometrial stromal cells proliferate, avert apoptosis, and undergo decidualization in preparation for implantation; however, the molecular mechanisms that underlie differentiation into the decidual phenotype remain largely undefined. The Notch family of transmembrane receptors transduce extracellular signals responsible for cell survival, cell‐to‐cell communication, and differentiation, all fundamental processes for decidualization and pregnancy. Using a murine artificial decidualization model, pharmacological inhibition of Notch signaling by γ‐secretase inhibition resulted in a significantly decreased deciduoma. Furthermore, a progesterone receptor (PR)‐Cre Notch1 bigenic (Notch1d/d) confirmed a Notch1‐dependent hypomorphic decidual phenotype. Microarray and pathway analysis, following Notch1 ablation, demonstrated significantly altered signaling repertoire. Concomitantly, hierarchical clustering demonstrated Notch1‐dependent differences in gene expression. Uteri deprived of Notch1 signaling demonstrated decreased cellular proliferation; namely, reduced proliferation‐specific antigen, Ki67, altered p21, cdk6, and cyclinD activity and an increased apoptotic‐profile, cleaved caspase‐3, Bad, and attenuated Bcl2. The results demonstrate that the preimplantation uterus relies on Notch signaling to inhibit apoptosis of stromal fibroblasts and regulate cell cycle progression, which together promotes successful decidualization. In summary, Notch1 signaling modulates multiple signaling mechanisms crucial for decidualization and these studies provide additional perspectives to the coordination of multiple signaling modalities required during decidualization. —Afshar, Y. , Jeong, J.‐W. , Roqueiro, D. , DeMayo, F. , Lydon, J., Radtke, F. , Radnor, R. , Miele, L. , Fazleabas, A. Notch1 mediates uterine stromal differentiation and is critical for complete decidualization in the mouse. FASEB J. 26, 282–294 (2012). www.fasebj. org
Arcuate nucleus neurons that project to the hypothalamic paraventricular nucleus: Neuropeptidergic identity and consequences of adrenalectomy on mRNA levels in the rat

The possible role that the hypothalamic arcuate nucleus might play in mediating the increase in paraventricular nucleus corticotropin‐releasing hormone mRNA levels following adrenalectomy was investigated in two series of experiments. In the first series, in situ hybridization histochemistry was used to quantify levels of eight arcuate nucleus neuropeptide and neurotransmitter mRNAs in neurons that potentially relay adrenal steroid feedback to the paraventricular nucleus. In the second series of experiments, arcuate neuropeptidergic projections to the hypothalamic paraventricular nucleus were characterized using retrograde tracing in combination with in situ hybridization histochemistry. Despite an increase in paraventricular nucleus corticotropin‐releasing hormone (60%) and pituitary proopiomelanocortin mRNA levels (sixfold), arcuate mRNA levels for proopiomelanocortin, neuropeptide Y, somatostatin, galanin, dynorphin, tyrosine hydroxylase, glutamate decarboxylase, and the glucocorticoid receptor were unchanged 14 days following adrenalectomy. Neuropeptidergic characterization of arcuatoparaventricular projections was achieved by injection of the retrograde tracer fluorogold into the paraventricular nucleus; retrogradely labeled neurons were characterized with polyclonal antisera against fluorogold in combination with oligonucleotide probes directed against neuropeptide Y, proopiomelanocortin, or somatostatin. Out of these three arcuate neuropeptides, neuropeptide Y mRNA was contained in 18% of the fluorogold‐positive neurons in the arcuate, proopiornelanocortin mRNA was contained in 8%, and somatostatin mRNA was contained in 6%. Overall, the results from both experiments suggest that the arcuatoparaventricular neuropeptide Y, proopiomelanocortin, and somatostatin projections are not sensitive to a chronic (14 day) lack of adrenal steroids. These projections as well as the other arcuate neurotransmitter and neuropeptide systems appear not to contribute to the persistent elevations in paraventricular nucleus corticotropin‐releasing hormone mRNA levels or pituitary proopiomelanocortin mRNA levels found in 14 day adremlectomized rats. © 1995 Wiley‐Liss, Inc. This article is a US Government work and, as in the public domain in the United States of America.