Miracle-dz/UniFAR-FTUs huggingface dataset:
CD80 and CD86 Are Not Equivalent in Their Ability to Induce the Tyrosine Phosphorylation of CD28*

Ligation of either CD80 (B7-1) or CD86 (B7-2), two principal ligands for CD28, is thought to skew the immune response toward Th1 or Th2 differentiation. We have examined early signal transduction pathways recruited following T cell stimulation with either CD80 or CD86. Purified human peripheral T cells or Jurkat T cells were stimulated with Chinese hamster ovary (CHO) cells expressing either human CD80 (CHO-CD80) or human CD86 (CHO-CD86) or with anti-CD28 monoclonal antibody (mAb). In the presence of phorbol 12-myristate 13-acetate, both CHO-CD80 and CHO-CD86, like anti-CD28 mAb, were capable of stimulating cytokine production from both human peripheral T cells and Jurkat T cells. Both CHO-CD80 and CHO-CD86, in the presence of anti-CD3 mAb, costimulated NFAT-dependent transcriptional activation. Several intracellular signaling proteins, such as CBL and VAV, were phosphorylated on tyrosine in response to CD80, CD86, and anti-CD28 mAb. Surprisingly, although stimulation of Jurkat T cells with either CHO-CD80 or anti-CD28 mAb resulted in robust tyrosine phosphorylation of CD28 itself, ligation with CHO-CD86 was unable to induce detectable CD28 tyrosyl phosphorylation over a range of stimulation conditions. In addition, the association of phosphoinositide 3-kinase with CD28 and enhanced tyrosine phosphorylation of phospholipase Cγ were seen after anti-CD28 mAb and CHO-CD80 stimulation but to a much lesser extent after CHO-CD86 stimulation. Thus, ligation of CD28 with either CD80 or CD86 leads to shared early signal transduction events such as the tyrosine phosphorylation of CBL and VAV, to NFAT-mediated transcriptional activation, and to the costimulation of interleukin-2 and granulocyte-macrophage colony-stimulating factor production. However, CD80 and CD86 also induce distinct signal transduction pathways including the tyrosine phosphorylation of CD28 and phospholipase Cγ1 and the SH2-dependent association of phosphoinositide 3-kinase with CD28. These quantitative, if not qualitative, differences between signaling initiated by these two ligands for CD28 may contribute to functional differences (e.g. Th1 or Th2 differentiation) in T cell responses.
Reliability of the SWAG—The Standardized Way to Assess Grafts Method for Alveolar Bone Grafting in Patients with Cleft Lip and Palate

Objective The objective of this study was to test a new method, a Standardized Way to Assess Grafts (SWAG), to rate alveolar bone graft (ABG) outcomes for patients with cleft lip and palate. Design This was a retrospective comparison using the SWAG scale. Setting This study took place in four cleft palate centers with different treatment protocols. Methods A total of 160 maxillary occlusal radiographs taken 3 to 18 months post-ABG for sequentially treated patients with cleft lip and palate were assessed using the SWAG scale. Radiographs were scanned, standardized, blinded, and rated by 6 calibrated orthodontists to assess vertical thirds, bony root coverage, and complete bony fill. All radiographs were rated twice, 24 hours apart, by the same raters. Main Outcomes Intra- and interrater reliabilities were assessed. Results Intrarater reliability was good to very good (.760; .652–.834), and interrater reliability was moderate to good (.606; .569–.681), comparable to previously published methods. Conclusions Rater reliabilities were shown to be comparable to or better than existing methods. The SWAG method was validated for ABG assessments in the mixed and permanent dentitions based on reliabilities in an intercenter outcome comparison.
Nucleus accumbens mediates the pronociceptive effect of sleep deprivation: the role of adenosine A2A and dopamine D2 receptors

Abstract Sleep disorders increase pain sensitivity and the risk of developing painful conditions; however, the underlying mechanisms are poorly understood. It has been suggested that nucleus accumbens (NAc) influences sleep-wake cycle by means of a balance between adenosine activity at A2A receptors and dopamine activity at D2 receptors. Because the NAc also plays an important role in pain modulation, we hypothesized that the NAc and its A2A and D2 receptors mediate the pronociceptive effect of rapid eye movement (REM) sleep deprivation (SD). We found that 24 hours of REM-SD induced an intense pronociceptive effect in Wistar rats, which decreases progressively over a sleep rebound period. Although the level of fecal glucocorticoid metabolites increased with SD within group, it did not differ between sleep-deprived group and control group, indicating a stress response with similar magnitude between groups. The pronociceptive effect of REM-SD was prevented by excitotoxic lesion (N-Methyl-D-aspartate, 5.5 &mgr;g) of NAc and reverted by its acute blockade (Qx-314, 2%). The administration of an A2A receptor antagonist (SCH-58261, 7 ng) or a D2 receptor agonist (piribedil, 6 &mgr;g) into the NAc increased home cage activity and blocked the pronociceptive effect of REM-SD. Complementarily, an A2A receptor agonist (CGS-21680, 24 ng) impaired the reversal of the pronociceptive effect and decreased home cage activity, as it did a D2 receptor antagonist (raclopride, 5 &mgr;g). Rapid eye movement SD did not affect the expression of c-Fos protein in NAc. These data suggest that SD increases pain by increasing NAc adenosinergic A2A activity and by decreasing NAc dopaminergic D2 activity.
Physiological alterations consequent to circuit weight training.

The efficacy of a 10-week program of circuit weight training to elicit specific physiological alterations was evaluated in a group of men (n = 16) and a group of women (n = 12), with an additional group of men (n = 10) and a group of women (n = 11) serving as controls. The circuit consisted of 10 stations performed on a Universal Gym, 3 circuits per day (approximately 22.5 min/day), 3 days/week. The subjects exercised at 40-55% of 1-RM, executing as many repetitions as possible in 30 sec on each of the lifts, followed by a 15 sec rest as the subject moved to the next station. Following the training program, the experimental groups demonstrated significant increases in lean body weight, flexed biceps girth, treadmill endurance time, VEmax (women only), Vo2max in ml/kg-min (women only), flexibility and strength. Significant decreases were found in selected skinfold measurements, and in resting heart rate (control group showed similar decreases). No change was found in body weight or in relative or absolute body fat. Generally, the women exhibited equal or greater changes when compared to the men for all variables assessed, which could be a function of their lower initial starting levels, or a more intense training program. It was concluded that circuit weight training is a good general conditioning activity, i.e., attends to more than one component of fitness.
Protein Kinase R (PKR) Interacts with and Activates Mitogen-activated Protein Kinase Kinase 6 (MKK6) in Response to Double-stranded RNA Stimulation*

The double-stranded RNA (dsRNA)-activated protein kinase R (PKR) has been invoked in different signaling pathways. In cells pre-exposed to the PKR inhibitor 2-aminopurine or in PKR-null cells, the activation of p38 mitogen-activated protein kinase (MAPK) following dsRNA stimulation is attenuated. We found that the p38 MAPK activator MKK6, but not its close relatives MKK3 or MKK4, exhibited an increased affinity for PKR following the exposure of cells to poly(rI:rC), a dsRNA analog. In vitro kinase assays revealed that MKK6 was efficiently phosphorylated by PKR, and this could be inhibited by 2-aminopurine. Expression of kinase-inactive PKR (K296R) in cells inhibited the poly(IC)-induced phosphorylation of MKK3/6 detected by phosphospecific antiserum but did not affect the poly(IC)-induced gel migration retardation of MKK3. This suggests that poly(IC)-mediated in vivo activation of MKK6, but not MKK3, is through PKR. Consistent with this observation, PKR was capable of activating MKK6 as assessed in a coupled kinase assay containing the components of the p38 MAPK pathway. Our results indicate that the interaction of MKK6 and PKR provides a mechanism for regulating p38 MAPK activation in response to dsRNA stimulation.
Experiences of nurses working in a stroke rehabilitation unit.

AIM This paper is a report of a study to explore the perceptions, beliefs and feelings of a group of nurses who provided care to individuals admitted to a stroke rehabilitation unit. BACKGROUND Following a stroke, survivors should ideally be referred to multidisciplinary inpatient rehabilitation programmes, which attain better outcomes compared to the care provided on general medical wards. However, to achieve these outcomes, team members must work closely together. Communication problems have been reported in these teams, and other members may consider that nurses do not practise functional activities with patients. METHODS An interpretive phenomenological approach was adopted. Eight nurses in one Canadian stroke rehabilitation unit were interviewed during 2004-2005 about their experiences of providing care to stroke survivors. FINDINGS The nurses enjoyed giving this type of care, feeling that their role was pivotal to the rehabilitation process. At times, they found it difficult to let patients struggle to complete their activities of daily living. The nurses felt that lack of resources, including time, contributed to stroke survivors being short-changed in their rehabilitation nursing care. Despite holding strong views that others devalued their role within the stroke team, the nurses retained positive attitudes. CONCLUSION Stroke teams need to recognize the constraints nurses experience in fulfilling their stroke rehabilitation role in order to foster the collegial support that could contribute to a more interactive and respectful work environment. They also need to consider ways to increase the job satisfaction of nurses working in stroke rehabilitation settings.
Women's susceptibility to tobacco carcinogens and survival after diagnosis of lung cancer.

CONTEXT It has been hypothesized that women are more susceptible to tobacco carcinogens than men, but after diagnosis of lung cancer, they have better survival rates than men. OBJECTIVE To add to the evidence on the lung cancer risk of women who smoke and their survival after diagnosis of lung cancer, conditional on other prognostic indicators and compared with men of the same age who smoke. DESIGN, SETTING, AND PARTICIPANTS Nonexperimental, etiologic study with prospective collection of data based on baseline computed tomographic screening for lung cancer and follow-up of diagnosed cases of lung cancer in North America in 1993-2005. A total of 7498 women and 9427 men were screened, all of whom were asymptomatic, aged at least 40 years, and had a history of cigarette smoking. MAIN OUTCOME MEASURES Comparing women with men, the prevalence odds ratio (OR) for screen-detectable lung cancer (conditional on age and smoking history) and the hazard ratio of fatal outcome of lung cancer (conditional on smoking history, disease stage, tumor cell type, and resection). RESULTS Lung cancer was diagnosed in 156 women and 113 men (rates of 2.1% and 1.2%, respectively). The prevalence OR comparing women with men was 1.9 (95% confidence interval [CI], 1.5-2.5). The hazard ratio of fatal outcome of lung cancer comparing women with men was 0.48 (95% CI, 0.25-0.89). CONCLUSION Women appear to have increased susceptibility to tobacco carcinogens but have a lower rate of fatal outcome of lung cancer compared with men.
Apparent fractality emerging from models of random distributions.

The fractal properties of models of randomly placed $n$-dimensional spheres ($n=1, 2, 3$) are studied using standard techniques for calculating fractal dimensions in empirical data (the box counting and Minkowski-sausage techniques). Using analytical and numerical calculations it is shown that in the regime of low volume fraction occupied by the spheres, apparent fractal behavior is observed for a range of scales between physically relevant cutoffs. The width of this range, typically spanning between one and two orders of magnitude, is in very good agreement with the typical range observed in experimental measurements of fractals. The dimensions are not universal and depend on density. These observations are applicable to spatial, temporal, and spectral random structures. Polydispersivity in sphere radii and impenetrability of the spheres (resulting in short range correlations) are also introduced and are found to have little effect on the scaling properties. We thus propose that apparent fractal behavior observed experimentally over a limited range may often have its origin in underlying randomness.
Intensity-Modulated Radiotherapy ( IMRT ) : Central Nervous System Tumors Policy

When Policy Topic is covered Intensity-modulated radiotherapy (IMRT) may be considered medically necessary for the treatment of tumors of the central nervous system when the tumor is in close proximity to organs at risk (brain stem, spinal cord, cochlea and eye structures including optic nerve and chiasm, lens and retina) and 3-D CRT planning is not able to meet dose volume constraints for normal tissue tolerance. (see Considerations)
Autocrine amplification loop in statin‐induced apoptosis of human melanoma cells

Background and purpose: Beside their cholesterol lowering effect, statins exert pleiotropic effects, which include anti‐inflammatory, immunosuppressive and anti‐proliferative actions. In higher concentrations, statins trigger apoptosis in primary cells and tumour cells. In particular, melanoma cells have been found to be susceptible to statin‐induced apoptosis, although only after longer incubation times. The molecular mechanisms behind this delayed drug‐induced apoptosis are still unclear.
Molecular Characterization and Differential Gene Induction of the Neuroendocrine‐Specific Genes Neurotensin, Neurotensin Receptor, PC1, PC2, and 7B2 in the Human Ocular Ciliary Epithelium

Abstract: The ocular ciliary epithelium is a bilayer of neuroepithelial cells specialized in the secretion of aqueous humor fluid and the regulation of intraocular pressure. In this study, we report on the expression of the regulatory peptide neurotensin (NT) and a set of differentiated neuroendocrine markers including neurotensin receptors (NTrs), the prohormone convertases furin, PC1, and PC2, and the neuroendocrine polypeptide 7B2 in the ciliary epithelium. Using a human cell line, ODM‐2, derived from the nonpigmented ciliary epithelium, we demonstrate that (1) NT expression is highly activated by nerve growth factor, glucocorticoid, and activators of adenylate cyclase; (2) NTr expression is up‐regulated by selective ligand‐activated β2‐adrenergic receptor; and (3) PC1 and PC2 expression are up‐regulated via distinct signaling transduction pathways. PC1 gene expression is activated by phorbol ester, and PC2 by the same inducers as those of NT expression. A radioimmunoassay for NT detected an NT‐like immunoreactivity in human ciliary epithelium and ODM‐2 cell extracts, in aqueous humor, and in conditioned culture medium. The results support the view that the entire ciliary epithelium functions as a neuroendocrine tissue, synthesizing, processing, and releasing NT into the aqueous humor where it may exert important physiological functions through autocrine and/or paracrine mechanisms.
Activation of M1 Muscarinic Receptors Triggers Transmitter Release from Rat Sympathetic Neurons Through an Inhibition of M‐Type K+ Channels

Acetylcholine has long been known to excite sympathetic neurons via M1 muscarinic receptors through an inhibition of M‐currents. Nevertheless, it remained controversial whether activation of muscarinic receptors is also sufficient to trigger noradrenaline release from sympathetic neurons. In primary cultures of rat superior cervical ganglia, the muscarinic agonist oxotremorine M inhibited M‐currents with half‐maximal effects at 1 μm and induced the release of previously incorporated [3H]noradrenaline with half‐maximal effects at 10 μm. This latter action was not affected by the nicotinic antagonist mecamylamine which, however, abolished currents through nicotinic receptors elicited by high oxotremorine M concentrations. Ablation of the signalling cascades linked to inhibitory G proteins by pertussis toxin potentiated the release stimulating effect of oxotremorine M, and the half‐maximal concentration required to stimulate noradrenaline release was decreased to 3 μm. Pirenzepine antagonized the inhibition of M‐currents and the induction of release by oxotremorine M with identical apparent affinity, and both effects were abolished by the muscarinic toxin 7. These results indicate that one muscarinic receptor subtype, namely M1, mediates these two effects. Retigabine, which enhances M‐currents, abolished the release induced by oxotremorine M, but left electrically induced release unaltered. Moreover, retigabine shifted the voltage‐dependent activation of M‐currents by about 20 mV to more negative potentials and caused 20 mV hyperpolarisations of the membrane potential. In the absence of retigabine, oxotremorine M depolarised the neurons and elicited action potential discharges in 8 of 23 neurons; in its presence, oxotremorine M still caused equal depolarisations, but always failed to trigger action potentials. Action potential waveforms caused by current injection were not affected by retigabine. These results indicate that the inhibition of M‐currents is the basis for the stimulation of transmitter release from sympathetic neurons via M1 muscarinic receptors.
Cognitive algorithm to solve the impairment-aware virtual topology design problem in reconfigurable optical networks

A key problem in current optical telecommunication networks is that of virtual topology design, where a set of optical connections (or lightpaths) are established between network nodes in order to accommodate traffic demands. Those virtual topologies are designed with the aim of optimizing a set of network parameters while complying with quality of transmission requirements. In this paper, we show the advantages of using cognition when solving that problem. In particular, we present two multiobjective genetic algorithms (one of them enhanced with an additional cognitive technique) and evaluate their performance under realistic traffic demands. Results show that the new method enhanced with cognition obtains more and better results than the other method.
Annulatascus aquatorba sp. nov., a lignicolous freshwater ascomycete from Sirindhorn Peat Swamp Forest, Narathiwat, Thailand

As part of a long term study of fungi colonizing submerged wood in freshwater streams a new Annulatascus species, A. aquatorba, is described and illustrated from Erythrophleum teysmannii test blocks from Sirindhorn Peat Swamp Forest, southern Thailand. It differs from other species in the genus in ascospore measurements, thickness of the cell wall, 1–3-septate, fusoid to lunate shape, with central brown cells and subhyaline end cells and without a mucilaginous sheath. Asci are cylindrical, pedicellate, with a distinct, wedge-shaped and non-amyloid apical ring. Phylogenetic relationships of this species, based on the combined partial 18S and 28S rDNA, place it in the same clade as A. velatisporus (type species), A. hongkongensis and A. nilensis.
Assessment of cardiac troponin I (cTnI) and tissue velocity imaging (TVI) in 14 dogs with malignant lymphoma undergoing chemotherapy treatment with doxorubicin

Doxorubicin has been shown to be cardiotoxic at high doses but is an efficacious chemotherapeutic agent in the treatment of canine lymphoma. Echocardiographic measurements and serum ultrasensitive cardiac troponin I (cTnI) levels were obtained before and after doxorubicin administration in 14 dogs diagnosed with lymphoma. The aim of this prospective study was to evaluate changes in cTnI concentrations and tissue velocity imaging (TVI) values in dogs with lymphoma undergoing chemotherapy with doxorubicin. A total of 182 cTnI and 1017 TVI measurements were performed. Standard echocardiographic parameters, tissue Doppler indices and cTnI concentrations did not differ at any time point within a 12-week cyclic combination protocol. In conclusion, the use of doxorubicin at standard doses in the treatment of canine lymphoma may not be associated with significant myocardial damage.
Prognostic significance of tumor emboli in intramammary lymphatics in patients with mammary carcinoma

Approximately 20% of patients with invasive mammary carcinoma who do not have axillary metastases develop recurrent carcinoma within 10 years of initial therapy. There is clearly a need to identify those patients most likely to develop recurrences in this group since they may benefit from adjuvant therapy. This study was undertaken to evaluate the prognostic significance of intramammary lymphatic tumor emboli in patients with invasive breast carcinoma who did not have lymph node metastases. Twenty-three such patients treated in 1974 and 15 from 1964 were compared with matched groups of control patients who did not have lymphatic emboli. About 43% of patients with lymphatic emboli and 4% of those without emboli followed for 5 or more years in the 1964 group developed distant metastases (p < 0.001). Local recurrences were found in only one study patient and one control in the entire series of 1964 and 1974 patients. The results suggest that among patients without axillary metastases, the finding of tumor cells in lymphatic spaces within the breast is associated with a substantial risk of distant metastases but not local recurrence.
Specificity Mutants of the Binding Protein of the Oligopeptide Transport System of Lactococcus lactis

ABSTRACT The kinetic properties of wild-type and mutant oligopeptide binding proteins of Lactococcus lactis were determined. To observe the properties of the mutant proteins in vivo, the oppAgene was deleted from the chromosome of L. lactis to produce a strain that was totally defective in oligopeptide transport. Amplified expression of the oppA gene resulted in an 8- to 12-fold increase in OppA protein relative to the wild-type level. The amplified expression was paralleled by increased bradykinin binding activity, but had relatively little effect on the overall transport of bradykinin via Opp. Several site-directed mutants were constructed on the basis of a comparison of the primary sequences of OppA fromSalmonella enterica serovar Typhimurium and L. lactis, taking into account the known structure of the serovar Typhimurium protein. Putative peptide binding-site residues were mutated. All the mutant OppA proteins exhibited a decreased binding affinity for the high-affinity peptide bradykinin. Except for OppA(D471R), the mutant OppA proteins displayed highly defective bradykinin uptake, whereas the transport of the low-affinity substrate KYGK was barely affected. Cells expressing OppA(D471R) had a similarKm for transport, whereas theVmax was increased more than twofold as compared to the wild-type protein. The data are discussed in the light of a kinetic model and imply that the rate of transport is determined to a large extent by the donation of the peptide from the OppA protein to the translocator complex.
Гистологическое строение трехчастных грибовидных тел жужелиц (Insecta, Coleoptera: Carabidae)

Установлено, что в противоположность жукам подотряда Polyphaga жужелицы обладают трехчастными грибовидными телами, которые слабо развиты у представителей базальных таксонов и достигают максимального развития и дифференцировки у представителей эволюционно продвинутых групп. Тем не менее они не достигают той степени развития, которая ранее была найдена в ряде других семейств жуков. Отмечено, что новообразование клеток Кеньона продолжается у жужелиц по крайней мере в течение первых месяцев имагинальной жизни, а неактивные нейробласты сохраняются даже у годовалых жуков. Предположено существование связи между числом клеток Кеньона и степенью развития центров новообразования клеток Кеньона.