Miracle-dz/UniFAR-FTUs huggingface dataset:
Signal transduction by cell adhesion receptors in leukocytes

Leukocytes usually pass through the blood stream as nonadherent cells, but during an immune response and inflammation, they become adherent in order to migrate through tissues. Three families of adhesion molecules, the immunoglobulin family, the selectins, and the integrins, participate in interactions between leukocytes and tissues. Near sites of inflammation, leukocytes initially interact with the endothelium via selectins, causing them to slow down and to roll along the walls of blood vessels. Next, chemoattractans induce the activation of integrins on leukocytes. Finally, activated integrins mediate leukocyte migration through the endothelium into the inflamed site. Interactions of leukocytes with other cells and various extracellular matrix (ECM) proteins lead to different functional cell responses, including changes in growth, behavior, and differentiation. Many of these interactions are mediated by integrins, which “integrate” ECM protein signals with the cytoskeleton and which also act as true receptors that generate biochemical signals within the cell. Changes in pH, cytoplasmic Ca2+ concentration, phosphorylation, and gene induction have all been observed after integrin engagement. Adhesion‐mediated gene induction in monocytes is perhaps the best example that integrins initiate signaling cascades in the cell to deliver information from the ECM all the way to the nucleus. J. Leukoc. Biol. 57: 189–198: 1995.
Studying the genetics of Hirschsprung's disease: unraveling an oligogenic disorder

Hirschsprung's disease is characterized by the absence of ganglion cells in the myenteric and submucosal plexuses of the gastrointestinal tract. Genetic dissection was successful as nine genes and four loci for Hirschsprung's disease susceptibility were identified. Different approaches were used to find these loci such as classical linkage in large families, identity by descent mapping in an inbred kindred, candidate gene approaches based on naturally occurring mutant mice models, and finally the use of model‐free linkage and association analyzes. In this study, we review the identification of genes and loci involved in the non‐syndromic common form and syndromic Mendelian forms of Hirschsprung's disease. The majority of the identified genes are related to Mendelian syndromic forms of Hirschsprung's disease. The non‐Mendelian inheritance of sporadic non‐syndromic Hirschsprung's disease proved to be complex; involvement of multiple loci was demonstrated in a multiplicative model. We discuss the practical implications of the elucidation of genes associated with Hirschsprung's disease susceptibility for genetic counseling. Finally, we speculate on possible strategies to identify new genes for Hirschsprung's disease.
Biodistribution of inhaled metal oxide nanoparticles mimicking occupational exposure: a preliminary investigation using enhanced darkfield microscopy

Inhalation exposure to engineered nanomaterials (ENMs) may result in adverse pulmonary and/or systemic health effects. In this study, enhanced darkfield microscopy (EDFM) was used as a novel approach to visualizing industrial metal oxide nanoparticles (NPs) (silica, ceria, or alumina) in multiple tissue types following inhalation in rats mimicking occupational exposures. Advantages of EDFM over electron microscopy (EM) include reduced cost, time, and ease of sample preparation and operation. Following 4–6 hour inhalation exposures at three concentrations (3.5–34.0 mg/m3), lungs and secondary organs were harvested at 24 hours or 7 days post‐exposure and prepared for brightfield (BF) microscopy and EDFM. NPs were visualized within the lung and associated lymphatic tissues and in major organs of excretion (liver, spleen, kidney). EDFM also revealed NPs within pulmonary blood vessels and localization within specific regions of toxicological relevance in liver and kidney, indicating pathways of excretion. Results demonstrate the utility of EDFM for rapid direct visualization of NPs in various tissue types and suggest the potential for metal oxide NPs to distribute to secondary tissues following inhalation exposure. Confirmation of the composition, distribution, and relative abundance of inhaled NPs will be pursued by combining EDFM with hyperspectral imaging (HSI) and mapping.
Crystal Structure of a Peptidoglycan Synthesis Regulatory Factor (PBP3) from Streptococcus pneumoniae*

Penicillin-binding proteins (PBPs) are membrane-associated enzymes which perform critical functions in the bacterial cell division process. The single d-Ala,d-Ala (d,d)-carboxypeptidase in Streptococcus pneumoniae, PBP3, has been shown to play a key role in control of availability of the peptidoglycal substrate during cell growth. Here, we have biochemically characterized and solved the crystal structure of a soluble form of PBP3 to 2.8 Å resolution. PBP3 folds into an NH2-terminal, d,d-carboxypeptidase-like domain, and a COOH-terminal, elongated β-rich region. The carboxypeptidase domain harbors the classic signature of the penicilloyl serine transferase superfamily, in that it contains a central, five-stranded antiparallel β-sheet surrounded by α-helices. As in other carboxypeptidases, which are present in species whose peptidoglycan stem peptide has a lysine residue at the third position, PBP3 has a 14-residue insertion at the level of its omega loop, a feature that distinguishes it from carboxypeptidases from bacteria whose peptidoglycan harbors a diaminopimelate moiety at this position. PBP3 performs substrate acylation in a highly efficient manner (kcat/Km = 50,500 m–1·s–1), an event that may be linked to role in control of pneumococcal peptidoglycan reticulation. A model that places PBP3 poised vertically on the bacterial membrane suggests that its COOH-terminal region could act as a pedestal, placing the active site in proximity to the peptidoglycan and allowing the protein to “skid” on the surface of the membrane, trimming pentapeptides during the cell growth and division processes.
Natural Versus Cultural Salmonid Remains : Origin of The Danes Roadcut Bones , Columbia River , Oregon ,

The most secure evidence for early Holocene fishing in Pacific North-western North America resides in the huge deposit of95007600-year-old salmonid remains from The Dalles Roadcut site (Columbia River, Oregon). Recently the cultural origin for the fish remains has been challenged. Here, criteria for distinguishing natural (fluvial) from cultural salmonid deposits are developed in order to determine the agents responsible for the Roadcut faunal materials. Comparative analysis of one natural and three cultural assemblages from riverine settings indicates that body-part representation and skeletal completeness vary between natural and cultural settings. Analysis of the Roadcut assemblage suggests the salmonid deposit results largely from cultural processes, although the strength of this conclusion is weakened by significant curatorial biases with the collection.
[Ocular surface in glaucoma patients with topical treatment].

PURPOSE Our study is trying to establish the prevalence of Dry Eye Syndrome in glaucoma patients treated with topical medication. MATERIAL AND METHOD We investigated 40 patients (21 females and 19 males), age over 50, treated with topical antiglaucoma medication for at least one year. The control group was consisted of 40 healthy adults, 20 female and 20 males, age over 50, who didn't took any ocular treatment in the last three months. Each patient completed an Ocular Surface Disease Index questionnaire (OSDI) and underwent evaluation by Schirmer test and tear break-up time (TBUT). RESULTS In the control group we diagnose 9 patients (23%) with Dry Eye Syndrome. In glaucoma group 25 patients (63%) had Dry Eye Syndrome. Tear break-up time showed abnormal tear quality in all of those 25 patients. Schirmer testing showed 23 patients with decrease in tear production. Using Ocular Surface Disease Index 22 patients reported ocular symptoms. Unlike the control group, at the glaucoma patients we didn't notice any difference between the two genders. Regarding the age, we found at the control group the Dry Eye Syndrome at patients over 70 years old, and at the glaucoma group the average age was 55 years old. CONCLUSIONS In general population the prevalence of Dry Eye Syndrome is about 20%, mainly affecting females over 60 years old. In our study 63% of glaucoma patients had Dry Eye Syndrome--as a result of long term topical therapy that affects the integrity of the tear film and the ocular surface.
VICARIANCE AND DISPERSAL EFFECTS ON PHYLOGEOGRAPHIC STRUCTURE AND SPECIATION IN A WIDESPREAD ESTUARINE INVERTEBRATE

Abstract Vicariance and dispersal can strongly influence population genetic structure and allopatric speciation, but their importance in the origin of marine biodiversity is unresolved. In transitional estuarine environments, habitat discreteness and dispersal barriers could enhance divergence and provide insight to evolutionary mechanisms underlying marine and freshwater biodiversity. We examined this by assessing phylogeographic structure in the widespread amphipod Gammarus tigrinus across 13 estuaries spanning its northwest Atlantic range from Quebec to Florida. Mitochondrial cytochrome c oxidase I and nuclear internal transcribed spacer 1 phylogenies supported deep genetic structure consistent with Pliocene separation and cryptic northern and southern species. This break occurred across the Virginian–Carolinian coastal biogeographic zone, where an oceanographic discontinuity may restrict gene flow. Ten estuarine populations of the northern species occurred in four distinct clades, supportive of Pleistocene separation. Glaciation effects on genetic structure of estuarine populations are largely unknown, but analysis of molecular variance (AMOVA) supported a phylogeographic break among clades in formerly glaciated versus nonglaciated areas across Cape Cod, Massachusetts. This finding was concordant with patterns in other coastal species, though there was no significant relationship between latitude and genetic diversity. This supports Pleistocene vicariance events and divergence of clades in different northern glacial refugia. AMOVA results and private haplotypes in most populations support an allopatric distribution across estuaries. Clade mixture zones are consistent with historical colonization and human-mediated transfer. An isolation-by-distance model of divergence was detected after we excluded a suspected invasive haplotype in the St. Lawrence estuary. The occurrence of cryptic species and divergent population structure support limited dispersal, dispersed habitat distribution, and historical factors as important determinants of estuarine speciation and diversification.
Hedgehog signaling inhibition by the small molecule smoothened inhibitor GDC‐0449 in the bone forming prostate cancer xenograft MDA PCa 118b

Hedgehog signaling is a stromal‐mesenchymal pathway central to the development and homeostasis of both the prostate and the bone. Aberrant Hedgehog signaling activation has been associated with prostate cancer aggressiveness. We hypothesize that Hedgehog pathway is a candidate therapeutic target in advanced prostate cancer. We confirm increased Hedgehog signaling in advanced and bone metastatic castrate resistant prostate cancer and examine the pharmacodynamic effect of Smoothened inhibition by the novel reagent GDC‐0449 in an experimental prostate cancer model.
Effect of Phencyclidine in Chronic Schizophrenics *

Behavioural and the E E G response to various centrally active drugs has been suggested frequently as a way to distin­ guish schizophrenic populations (6,9). In following this model, intravenous thio­ pental 'has found increased use both in diagnosis and in prognosis (4,14). In a series of detailed studies, schizophrenic patients presenting an organic mental syndrome have exhibited a special sensi­ tivity to thiopental. Clinically they de­ veloped a deep narcosis and their EEGs showed enhanced delta activity (7). The aim of this study was to assess the value of a psychotomimetic com­ pound such as phencyclidinet for use in the diagnosis and prognosis of schizo­ phrenic patients. Because phencyclidine displays a dual effect in the central ner­ vous system, which is demonstrated by blocking sensory perception and pro­ ducing hallucinogenic activity (5, 11), it was selected for these investigations. Psychotomimetic activity is apparent following the administration of low dosages. In high dosages the anesthetic effect with changes in consciousness pre­ dominates. •
CONTINUITY OF MULTILINEAR OPERATORS ON TRIEBEL-LIZORKIN

Let T be the Calderón-Zygmund singular integral operator, a well-known result of Coifman et al. (see [6]) states that the commutator [b,T]( f ) = T(b f )− bT( f ) (where b ∈ BMO) is bounded on Lp(Rn) (1 < p <∞); Chanillo (see [1]) proves a similar result when T is replaced by the fractional integral operator; in [8, 9], these results on the TriebelLizorkin spaces and the case b ∈ Lipβ (where Lipβ is the homogeneous Lipschitz space) are obtained. The main purpose of this paper is to study the continuity of some multilinear operators related to certain convolution operators on the Triebel-Lizorkin spaces. In fact, we will obtain the continuity on the Triebel-Lizorkin spaces for the multilinear operators only under certain conditions on the size of the operators. As the applications, the continuity of the multilinear operators related to the Littlewood-Paley operator and Marcinkiewicz operator on the Triebel-Lizorkin spaces are obtained.
Enhanced Conference Organization Based On Correlation of Web Information and Ontology Based Expertise Search

— From the importance of the conference and its constructive role in the studies discussion, there must be a strong organization that allows the exploitation of the discussions in opening new horizons. The vast amount of information scattered across the web, make it difficult to find experts, who can play a prominent role in organizing conferences. In this paper we proposed a new approach of extracting researchers’ information from various Web resources and correlating them in order to confirm their correctness. As a validator of this approach, we propose a service that will be useful to set up a conference. Its main objective is to find appropriate experts, as well as the social events for a conference. For this application we us Semantic Web technologies like RDF and ontology to represent the confirmed information, which are linked to another ontology (skills ontology) that are used to present and compute the expertise.
Formulation and in vitro–in vivo evaluation of ketoprofen-loaded albumin microspheres for intramuscular administration

Abstract The objective of this work was to prepare and evaluate ketoprofen-loaded albumin microspheres for intramuscular administration. Microspheres were prepared by emulsion cross-linking method using a 23 factorial design and the effect of different factors on entrapment efficiency was determined. Microspheres were evaluated for entrapment efficiency, percentage yield, particle size and release behaviour. Selected formulations were then tested by differential scanning calorimetry, X-ray diffraction and scanning electron microscopy. Further they were analysed for residual solvents, syringeability and stability. Microspheres were then sterilized and bioavailability studies were carried out in New Zealand white rabbits. The physical characteristics of microspheres showed that they were suitable for IM administration. The sterilization technique adopted was adequate to maintain sterility. In vivo studies showed increase in Cmax, AUC, t1/2 and MRT (p < 0.05) administered in the form of microspheres. MRT of ketoprofen was almost 3.2-times in the form of microspheres. From these results it was concluded that the developed albumin microspheres of ketoprofen is a potential delivery system for once-a-day intramuscular administration.
SUMOylation of the Human Cytomegalovirus 72-Kilodalton IE1 Protein Facilitates Expression of the 86-Kilodalton IE2 Protein and Promotes Viral Replication

ABSTRACT The 72-kDa immediate-early 1 protein (IE1-72kDa) of human cytomegalovirus has been previously shown to be posttranslationally modified by covalent conjugation to the ubiquitin-related protein SUMO-1. Using an infectious bacterial artificial chromosome clone of human cytomegalovirus, we constructed a mutant virus (BADpmIE1-K450R) that is deficient for SUMOylation of IE1-72kDa due to a single amino acid exchange in the SUMO-1 attachment site. Compared to wild-type virus, this mutant grew more slowly and generated a reduced yield in infected human fibroblasts, indicating that SUMO modification is required for the full activity of IE1-72kDa. The lack of SUMOylation did not affect the intranuclear localization of IE1-72kDa, including its ability to target to and disrupt PML bodies and to bind to mitotic chromatin. Likewise, SUMOylation-deficient IE1-72kDa activated several viral promoters as efficiently as the wild-type protein. However, the failure to modify IE1-72kDa resulted in substantially reduced levels of the IE2 transcript and its 86-kDa protein (IE2-86kDa). These observations suggest that SUMO modification of IE1-72kDa contributes to efficient HCMV replication by promoting the accumulation of IE2-86kDa.
Polymorphism of the mast cell chymase gene (CMA1) promoter region: lack of association with asthma but association with serum total immunoglobulin E levels in adult atopic dermatitis

Background Mast cell chymase has the potential to be an important mediator of inflammation and remodelling in the asthmatic lung. Previous studies have examined association between promoter polymorphism of the chymase gene (CMA1) and allergic phenotypes but the significance of this polymorphism is unclear. We have examined association of a CMA1 variant in relation to asthma in a large UK Caucasian family cohort.
Neurological disability correlates with spinal cord axonal loss and reduced N‐acetyl aspartate in chronic multiple sclerosis patients

Axonal degeneration has been proposed as a cause of irreversible neurological disability in multiple sclerosis (MS) patients. The purpose of this study was to quantify axonal loss in spinal cord lesions from 5 paralyzed (Expanded Disability Status Scale score ≥7.5) MS patients and to determine if axonal number or volume correlated with levels of the neuronal marker N‐acetyl aspartate (NAA). Axonal loss in MS lesions ranged from 45 to 84% and averaged 68%. NAA levels were significantly reduced (>50%) in cross sections of spinal cords containing MS lesions. Reduced NAA correlated with reduced axonal numbers within lesion areas. In addition, NAA levels per axonal volume were significantly reduced in demyelinated axons (42%) and in myelinated axons in normal‐appearing white matter (30%). The data support axonal loss as a major cause of irreversible neurological disability in paralyzed MS patients and indicate that reduced NAA as measured by magnetic resonance spectroscopy can reflect axonal loss and reduced NAA levels in demyelinated and myelinated axons. Ann Neurol 2000;48:893–901
The extension of Pisarenko's method to multiple dimensions

Pisarenko's method of spectral estimation, which models the spectrum as a sum of impulses plus a white noise component, was originally formulated for the time series case. The extension of this method to multiple dimensions and non-uniformly spaced correlation samples involves several fascinating problems. Pisarenko's estimate, which in the time series case involves the solution of an eigenvalue problem, is shown more generally to involve the solution of a linear optimization problem. The computation of Pisarenko's estimate by the application of the simplex method to the linear programming problem is considered. The possibility of a faster multiple exchange algorithm is discussed.
Update on magnetic resonance imaging, ProstaScint, and novel imaging in prostate cancer*

Purpose of review Despite marked stage migration, approximately a third of patients with clinically organ-confined prostate cancer will have extracapsular extension on pathological analysis. To improve outcomes further, alternative modalities of determining extraprostatic disease must be investigated beyond the current clinical parameters of digital rectal examination, prostate-specific antigen, and Gleason score. In addition, discerning the location of tumor in patients with biochemical recurrence directly affects treatment choice. This review highlights developments in prostate cancer imaging that may improve staging and treatment planning for prostate cancer patients. Recent findings Magnetic resonance imaging is most useful in the initial evaluation of men with prostate cancer. Its high specificity for the diagnosis of extracapsular extension is tempered by its low sensitivity. Positron emission tomography is used to assess regional and distant metastasis in many malignancies. Investigation into the most appropriate radiotracer for prostate cancer is paramount in any future applicability. The unique role of ProstaScint has been in evaluating patients with biochemical failure and in trying to discern metastasis before definitive therapy. The addition of spectroscopic imaging and nanoparticle infusion may lead to further improvements. Therefore, in differentiating local versus distant recurrence, appropriate interventions with radiotherapy or hormonal manipulation may be instituted. Summary Magnetic resonance imaging, ProstaScint, and to some extent positron emission tomography are all relevant imaging modalities for the evaluation of patients with prostate cancer. Current technological advances in each arena are improving the accuracy of diagnosis. Despite their specific limitations, use in the proper clinical setting may provide essential information to improve management decisions and disease outcomes.
Social correlates of reproductive success in the gibbon colony on Ko Klet Kaeo, Thailand.

The free-ranging colony of gibbons established on an island in the Gulf of Thailand by the SEATO Medical Research Laboratory in 1966–1967 was terminated in 1970. Out of the 20 gibbons originally introduced, four adults of each sex remained until near the end of the project. The four females each gave birth to one infant. In all cases the young were conceived five or more months after pairbonds and ranges had stabilized into a more natural-like pattern, with fairly regular morning inter-group vocal sessions and territorial boundaries between groups containing the most feral individuals. The maximum effective breeding density on the 60-acre island was found to be about four or five pairs. The chances of reproductive success appear to be maximized in a free-ranging colony containing several pairs by maintaining a one-to-one sex ratio and allowing enough space so that natural patterns of social behavior may be expressed. The amount of area required per group may vary with the individual gibbons and the environment, but we found it to be about ten acres.
Relationship between repression-sensitization and physical illness.

It was hypothesized that both sensitizers and repressers exceed those individuals falling in the middle of the distribution with respect to frequency and severity of illnesses. The 1st investigation utilized 2 independent samples of undergraduates (N= 173 and 319) who were given the Repression-Sensitization (R-S) Scale and a health survey. Though there was no support for the curvilinearity hypothesis, on 12 of the health items in both samples sensitizers indicated greater frequency and/or severity of illness than did repressers. In the 2nd investigation, a subsample of 85 extreme scorers on the R-S Scale from a pool of 319 students were compared with respect to the number of visits made to the University Health Center during 1 academic yr. Analysis of variance indicated that male sensitizers do in fact seek medical help significantly more frequently than male repressers; for females, Health Center visits were unrelated to R-S scores.