Miracle-dz/UniFAR-FTUs huggingface dataset:
Changes in Oestrogen Receptor α Expression in the Nucleus of the Solitary Tract of the Rat Over the Oestrous Cycle and Following Ovariectomy

Oestrogen is capable of modulating autonomic outflow and baroreflex function via actions on groups of neurones in the brainstem. We investigated the presence of oestrogen receptor (ER) α in a part of the nucleus of the solitary tract (NTS) associated with central cardiovascular control, aiming to determine whether ERα mRNA and protein expression is correlated with levels of circulating oestrogen during the oestrous cycle. Polymerase chain reaction (PCR) detected ERα mRNA in the NTS at each stage of the oestrous cycle, from ovariectomised, sham‐operated and male rats. Real‐time PCR showed variations in ERα mRNA expression during the oestrous cycle, with the highest levels seen in oestrus, and lowest levels in metoestrus (P < 0.05 versus oestrus) and proestrus (P < 0.05 versus oestrus). Expression in males was lower than in dioestrus and oestrus females (P < 0.05). After ovariectomy, ERα mRNA levels were decreased compared to sham‐operated animals (P < 0.01). Confocal fluorescence immunohistochemistry with stereological analysis showed that numbers of ERα immunoreactive cell nuclei per mm3 of tissue in the caudal NTS were significantly greater in proestrus than in other groups of rats (P < 0.05). There were also differences among the groups in the extent of colocalisation of ERα in neurones immunoreactive for tyrosine hydroxylase and nitric oxide synthase. These results imply a complex pattern of region‐specific oestrogen signalling in the NTS and suggest that ERα expression in this important autonomic nucleus may be related to circulating oestrogen levels. This may have consequences for the regulation of autonomic tone and baroreflex sensitivity when oestrogen levels decline, for example following menopause.
Disulfide-bonded outer membrane proteins in the genus Legionella

Legionella pneumophila and related species were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis for outer membrane proteins. Of the 10 species examined, 9 contained a 24-kilodalton (kDa) major outer membrane protein (MOMP) that was resolvable only when outer membrane material was heated in the presence of 2-mercaptoethanol. Labeling studies with [35S]cysteine indicated that the protein contained cysteine, and disulfide cross-linking of the unreduced complex was demonstrated by labeling with iodoacetamide. The unreduced outer membrane preparation contained peptidoglycan, and after treatment with lysozyme to remove peptidoglycan, a protein complex of 95 kDa was observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis in the absence of 2-mercaptoethanol. Reduction of the 95-kDa complex yielded 24-kDa monomers, suggesting that the 95-kDa complex was composed of four subunits. The 24-kDa MOMP from L. pneumophila was purified, and antibody produced to this protein cross-reacted with all species of Legionella as determined from an immunoblot of a sodium dodecyl sulfate gel. Only serogroup 1 strains of L. bozemanii lacked the 24-kDa MOMP and showed no cross-reactivity. These results suggest that the 24-kDa MOMP common to most species of Legionella contains a genus-specific epitope.
Cytolytic and Toxic Effects of Ostreolysin , a Protein from the Oyster Mushroom ( Pleurotus Ostreatus )

Ostreolysin is a 15 kDa cytolytic protein found in considerable amounts in oyster mushrooms (Pleurotus ostreatus). Ingestion of large quantities of these edible mushrooms can result in adverse reactions, and at least some of these effects can be attributed to ostreolysin. This protein is able to permeabilize erythrocytes and other cells at sub-micromolar concentrations, acting by a colloid-osmotic mechanism and inducing the formation of a membrane pore with a hydrodynamic radius of 2 nm. Its binding to and subsequent permeabilization of the membrane depend on interaction with cholesterolenriched raft-like membrane domains. When injected intravenously into rodents, ostreolysin induces cardiorespiratory arrest and is lethal for mice with an LD50 of 1170 μg/kg. In rats, it induces a transient increase in arterial blood pressure, followed by a progressive drop of blood pressure, associated with noticeable bradicardia and myocardial ischemia. Continued drop of blood pressure is accompanied with ventricular extrasystoles, related to marked hyperkalemia. Moreover, sub-micromolar concentrations of ostreolysin induce a concentration-dependent increase in aortic ring tension.
Uncertainty Analysis in Seismic Event Location

Abstract : Uncertainty in event locations derived from seismic data is caused by errors in the arrival times of picked phases, misidentification of seismic phases, and errors in the travel-time model used in the location process. The event mislocation induced by these error sources is affected by the number and spatial distribution of stations that record an event. This project is developing a statistical framework and computational techniques for accurately analyzing event location uncertainty. Our statistical approach is based on a maximum-likelihood framework, which defines an optimal location estimate to be that maximizing a likelihood function, and derives confidence regions in terms of hypothesis tests applied to likelihood ratios. An appropriate likelihood function is prescribed in terms of a probabilistic model of the various types of errors in seismic data. With appropriate computational tools, it is possible to implement a general class of error models that allow for non-Gaussian distributions, spatially correlated errors in travel-time tables, and other complexities that conventional location algorithms do not handle. Additionally, the assumption of local linearity of the forward problem (travel-time vs. location) can be avoided. We are developing such computational tools based on grid-search and Monte- Carlo simulation techniques. We have implemented our statistical formulation in a general event location algorithm that finds optimal location estimates from arrival time, slowness and azimuth measurements for regional and teleseismic phases, and computes the non-elliptical confidence regions which follow from a general error model and nonlinear analysis.
Guggulsterone Inhibits Osteoclastogenesis Induced by Receptor Activator of Nuclear Factor-κB Ligand and by Tumor Cells by Suppressing Nuclear Factor-κB Activation

Bone resorption is commonly associated with aging and with certain types of cancer, including multiple myeloma and breast cancer. What induces bone resorption is not fully understood, but the role of osteoclasts is well established. Recently, receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL), a member of the tumor necrosis factor superfamily, was implicated as a major mediator of bone resorption, suggesting that agents that can suppress RANKL signaling have the potential to inhibit bone resorption or osteoclastogenesis. Guggulsterone [4,17(20)-pregnadiene-3,16-dione], isolated from the guggul tree Commiphora mukul and used to treat osteoarthritis and bone fractures, was recently shown to antagonize the farnesoid X receptor, decrease the expression of bile acid–activated genes, and suppress the NF-κB activation induced by various carcinogens. We investigated whether guggulsterone could modulate RANKL signaling and osteoclastogenesis induced by RANKL or tumor cells. We found that treatment of monocytes with guggulsterone suppressed RANKL-activated NF-κB activation (as indicated by gel-shift assay) and that this suppression correlated with inhibition of IκBα kinase and phosphorylation and degradation of IκBα, an inhibitor of NF-κB. Guggulsterone also suppressed the differentiation of monocytes to osteoclasts in a dose-dependent and time-dependent manner. Suppression of osteoclastogenesis by the NF-κB-specific inhibitory peptide implies a link between NF-κB and osteoclastogenesis. Finally, differentiation to osteoclasts induced by coincubating human breast tumor cells (MDA-MB-468) or human multiple myeloma (U266) cells with monocytes was also completely suppressed by guggulsterone. Collectively, our results indicate that guggulsterone suppresses RANKL and tumor cell–induced osteoclastogenesis by suppressing the activation of NF-κB.
Psychogeriatric inpatient unit design: a literature review

ABSTRACT Background: In many parts of the world the provision of psychogeriatric inpatient units (PGUs) remains limited. More units will be required over coming decades given rapid population aging. Methods: Medline (1950–2010), psycINFO (1806–2009), EMBASE (1980–2009) and CINAHL (1982–2009) were searched for papers about PGU design. Selected non-peer reviewed literature such as government reports and unpublished academic dissertations were also reviewed. Data were also obtained from the literature related to general adult psychiatry inpatient units where there was limited information from studies of units designed for older people. Over 200 papers were reviewed and 130 were included. Results: There are few good quality studies to guide the design of acute PGUs and much of the existing literature is based on opinion and anecdote or, at best, based on observational studies. Randomized controlled studies comparing different designs and assessing outcomes are virtually non-existent. Several studies have identified violence and trauma resulting from hospitalization as significant problems with current acute PGU care. Despite its limitations the available literature provides useful guidance on how PGU design can optimize patient and staff safety and improve clinical outcomes. Conclusions: There are significant problems with current acute PGUs, and patient mix on existing units is an important issue. Future research should examine patient and staff perceptions of different PGU ward environments, the relationship between ward design and clinical outcomes, the effects of segregating patients with challenging behaviors in dementia and the benefits or otherwise of gender segregation.
αv‐Integrin isoform expression in primary human tumors and brain metastases

To determine whether metastasis to brain is associated with altered expression patterns of integrins, we investigated the expression of αvβ3, αvβ5, αvβ6 and αvβ8 integrins in primary malignancies and metastases to brain of breast, lung and renal carcinomas and in malignant melanoma. Inhibitors of αv integrins are currently in clinical trials for glioblastoma. The role of integrins in the process of brain metastasis from other human tumors is unknown. Immunohistochemistry with novel integrin subtype specific rabbit monoclonal antibodies was performed on tissue microarrays of archival material of surgical biopsies taken from primary tumors and brain metastases. Integrin αvβ3 expression was increased in brain metastases compared to primary tumors of breast adenocarcinoma, non‐small cell lung cancer, renal clear cell cancer and malignant cutaneous melanoma (all p < 0.01). Similarly, integrin αvβ8 expression was increased in brain metastases compared to primary tumors of breast cancer (p < 0.0001), lung cancer (p < 0.01) and renal cancer (p < 0.0001), with a similar trend in metastatic melanoma. Integrin αvβ5 was expressed in most primary tumors (98% breast cancer; 67% lung cancer; 90% renal cancer; 89% melanoma) and showed a stronger expression in brain metastases compared to primary tumors from lung cancer and melanoma (p < 0.05). Also integrin αvβ6 expression was increased in brain metastases compared to primary breast cancer (p < 0.001). Conclusions: The stronger αv‐integrin expression in brain metastases, especially of αvβ3 and αvβ8 integrins, suggests that certain αv integrin are involved in the process of brain metastasis. αv Integrins may be therapeutic targets for patients with metastatic cancer in brain.
In silico studies of potential phosphoresidues in the human nucleophosmin/B23: Its kinases and related biological processes

Human nucleophosmin/B23 is a phosphoprotein involved in ribosome biogenesis, centrosome duplication, cancer, and apoptosis. Its function, localization, and mobility within cells, are highly regulated by phosphorylation events. Up to 21 phosphosites of B23 have been experimentally verified even though the corresponding kinase is known only for seven of them. In this work, we predict the phosphorylation sites in human B23 using six kinase‐specific servers (KinasePhos 2.0, PredPhospho, NetPhosK 1.0, PKC Scan, pkaPS, and MetaPredPS) plus DISPHOS 1.3, which is not kinase specific. The results were integrated with information regarding 3D structure and residue conservation of B23, as well as cellular localizations, cellular processes, signaling pathways and protein–protein interaction networks involving both B23 and each predicted kinase. Thus, all 40 potential phosphosites of B23 were predicted with significant score (>0.50) as substrates of at least one of 38 kinases. Thirteen of these residues are newly proposed showing high susceptibility of phosphorylation considering their solvent accessibility. Our results also suggest that the enzymes CDKs, PKC, CK2, PLK1, and PKA could phosphorylate B23 at higher number of sites than those previously reported. Furthermore, PDK, GSK3, ATM, MAPK, PKB, and CHK1 could mediate multisite phosphorylation of B23, although they have not been verified as kinases for this protein. Finally, we suggest that B23 phosphorylation is related to cellular processes such as apoptosis, cell survival, cell proliferation, and response to DNA damage stimulus, in which these kinases are involved. These predictions could contribute to a better understanding, as well as addressing further experimental studies, of B23 phosphorylation. J. Cell. Biochem. 113: 2364–2374, 2012. © 2012 Wiley Periodicals, Inc.
Epidermal stem cells: properties, markers, and location.

Recent data indicate that stem cells exist in many tissues, including skeletal muscle, liver, and the central nervous system, some of them not known classically as having stem cells. The unexpected plasticity and the tremendous disease implications of these findings have created a lot of excitement (1, 2). However, a major obstacle in these areas has been a lack of molecular markers and of the precise in vivo localization of the putative stem cells. Because epidermis is an excellent example of a self-renewing tissue containing stem cells, it is of interest to examine the current status of this field. Like stem cells of other tissues, epidermal stem cells are important because they not only play a central role in homeostasis and wound repair, but also represent a major target of tumor initiation and gene therapy.
Nucleotide sequence of an mRNA transcribed in latent growth-transforming virus infection indicates that it may encode a membrane protein

The most abundant Epstein-Barr virus mRNA in a latently infected cell line, IB4, established by in vitro growth transformation with virus, was a 2,8-kilobase RNA encoded by largely unique DNA near the right end of the genome. The RNA was transcribed from right to left, and two introns were spliced out. This region of the genome was sequenced, and the exons of the RNA were identified by S1 analysis of DNA-RNA hybrids and primer extension. The first start codon in the RNA was 40 nucleotides from its 5' end. Beginning with the start codon, there was a 1,158-nucleotide open reading frame which crossed both introns. The important characteristics of the translated protein were as follows. (i) The amino terminus was highly charged and not suggestive of a leader sequence. (ii) There were six markedly hydrophobic alpha-helical domains, each having 21 amino acids and connected by 5 to 7 amino acid segments predicted to be reverse turns. (iii) The carboxy-terminal 200 amino acids were markedly acidic, containing 6 glutamic and 37 aspartic acids. The hydrophobic region is predicted to form six membrane-spanning regions, leaving the short charged amino terminus and long acidic carboxy terminus on the inside of the membrane. This protein could be responsible for the new antigen detected in the plasma membrane of Epstein-Barr virus-transformed cells, lymphocyte-determined membrane antigen. There were two other open reading frames in the RNA.
Multifocal Motor Neuropathy: Pathologic Alterations at the Site of Conduction Block

Abstract The pathologic changes of nerves in multifocal motor neuropathy (MMN), a rare neuropathy with selective focal conduction block of motor fibers in mixed nerves, remain essentially unstudied. Fascicular nerve biopsy of 8 forearm or arm nerves in 7 patients with typical MMN was undertaken for diagnostic reasons at the site of the conduction block. Abnormalities were seen in 7 of 8 nerves, including a varying degree of multifocal fiber degeneration and loss, an altered fiber size distribution with fewer large fibers, an increased frequency of remyelinated fiber profiles, and frequent and prominent regenerating fiber clusters. Small epineurial perivascular inflammatory infiltrates were observed in 2 nerves. We did not observe overt segmental demyelination or onion bulb formation. We hypothesize that an antibody-mediated attack directed against components of axolemma at nodes of Ranvier could cause conduction block, transitory paranodal demyelination and remyelination, and axonal degeneration and regeneration. Alternatively, the antibody attack could be directed at components of paranodal myelin. We favor the first hypothesis because in nerves studied by us, axonal pathological alteration predominated over myelin pathology. Irrespective of which mechanism is involved, we conclude that the unequivocal multifocal fiber degeneration and loss and regenerative clusters at sites of conduction block explains the observed clinical muscle weakness and atrophy and alterations of motor unit potentials. The occurrence of conduction block and multifocal fiber degeneration and regeneration at the same sites suggests that the processes of conduction block and fiber degeneration and regeneration are linked. Finding discrete multifocal fiber degeneration may also provide an explanation for why the functional abnormalities remain unchanged over long periods of time at discrete proximal to distal levels of nerve and may emphasize a need for early intervention (assuming that efficacious treatment is available).
HAC-POA policy effects on hospitals, other payers, and patients.

BACKGROUND Prior to the implementation of the Hospital-Acquired Condition-Present on Admission (HAC-POA) payment policy, concerns regarding its potential impact were raised by a number of organizations and individuals. The purpose of this study was to explore direct and indirect effects of the HAC-POA payment policy on hospitals, patients, and other payers during the policy's first 3 years of implementation. METHODS The study included semi-structured telephone interviews with representatives of national organizations, hospitals, patient advocacy organizations, and other payers. Interview notes were coded using QSR NVivo qualitative analysis software using inductive and deductive qualitative analysis techniques. We conducted interviews with 106 individuals representing 56 organizations. Hospital staff included physicians, nurses, patient safety officers, coders, and finance, senior management, and information management staff. Individuals from other organizations represented leadership positions. RESULTS Key changes to hospitals included: cultural shifts involving attention, commitment, and support from hospital leadership for patient safety; hiring new staff to assure the accuracy of clinical documentation and POA oversight structures; increased time burden for physicians, nurses, and coders; need to upgrade or purchase new software; and need to collaborate with hospital departments or staff that did not interface directly in the past. The policy was adopted by a majority of other payers, although the list of conditions and payment penalties varies. The HAC-POA policy is invisible to patients; therefore, the presence or lack of unintended consequences to patients cannot be fully assessed at this time. Understanding of policy effects to all stakeholders is important for maximizing its successful implementation and desired impact.
The eliminability of the actuality operator in propositional modal logic

The modal logic S5 is determined by the class of Kripke models in which the accessibility relation is the universal relation over the set of possible worlds or is an equivalence, or by the class of "pure" Kripke models, with no epicycles or accessibility relation, Lp(Mp) being counted true at a world in a model structure just in case p is true at every (at least one) world of that structure. It has been argued (c/. [4], in which ideas related to the actuality operator are also introduced, especially page 475) that it is the correct modal logic for the notions of metaphysical or logical necessity and possibility.
Lung Abscess Revisited: A Survey of 184 Cases

One hundred eighty-four patients with lung abscess, admitted to the Hospital of the University of Mississippi between 1960 and 1982, were studied with respect to sex (149 men and 35 women), age (mainly fourth to sixth decades), location of ab-scess(es) (RLL, RUL, and LLL mainly), predisposing factors (aspiration in sensorium disorders, obstruction, gingivo-dental suppuration, immunoincompetence) and nonoperative (89%) and operative (11%) therapy, usually lobectomy. Data from the different decades were compared, but there were few major differences. Mortality rate was 22% in the 1960s, 25% in the 1970s, and 28% in 1980–1982. Major management problems involved massive pulmonary hemorrhage, impaired immune defenses, old-age debility, bronchopleural fistula with em-pyema, or very large cavity. Anaerobic bacteria predominate and penicillin is the treatment of choice. Incidence of operation is declining, but cases are more often complicated. Prognosis is good in the uncomplicated case.
The relationship between anogenital distance and age

In humans, recent studies have correlated anogenital distance (AGD) in adult men to intrinsic testicular function. Although rodent studies suggest that AGD is determined in utero and remains constant in adult life, it is not certain if AGD remains constant across a man's adult life. We sought to determine if adult male AGD varies based on age. A cross‐sectional study of men being evaluated at a men's health clinic. Anogenital distance (the distance from the posterior aspect of the scrotum to the anal verge) and penile length (PL) were measured using digital callipers. anova and linear regression were used to determine correlations between AGD, fatherhood status and age. In all, 473 men were included in the analysis with a mean age of 43 ± 13 years. The mean AGD for the group was 39 ± 13 mm. Anogenital distance did not vary between age categories for the entire group, for fathers, and for childless men. Moreover, penile length also remained constant across age categories. On adjusted analyses stratified by fatherhood status, there was no relationship between AGDp and age. The current cross‐sectional study demonstrates that anogenital distance, defined as the distance from the posterior scrotum to the anal verge, is similar for men of different ages. As such, AGD may provide a measure for genital development and function throughout adult life. However, confirmation with longitudinal studies is needed.