Miracle-dz/UniFAR-FTUs huggingface dataset:
Elevated Nε-(Carboxymethyl)lysine Is Associated with Apoptosis of Retinal Pericytes in Streptozotocin-Induced Diabetic Rats

Advanced glycation end products including NΕ-(carboxymethyl)lysine (CML) are believed to contribute to retinal pericyte loss in diabetic retinopathy. Nuclear factor-ĸB (NF-ĸB) activation has been considered as a potential cytotoxic modulator of retinal pericytes. Herein, we investigated whether CML accumulation can trigger NF-ĸB activation and apoptosis of retinal pericytes in streptozotocin (STZ)-induced diabetic rats. Seven-week-old Sprague-Dawley rats were made diabetic (STZ, 60 mg/kg). After 5 months, CML level and NF-ĸB activation were measured in trypsin-digested retinal vessels. In diabetic rats, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling)-positive and caspase 3-positive retinal pericytes were significantly increased. CML and NF-ĸB activation was also markedly increased in diabetic retinal vessels. Moreover, the immunoreactivity of NF-ĸB was localized within the region where CML were accumulated. Apoptosis occurred in CML-accumulating retinal pericytes. These results suggest that NF-ĸB could be activated in CML-accumulating pericytes from diabetic retina. CML accumulation is responsible, at least in part, for the apoptosis of retinal pericytes.
Preponderance of clonality triggers loss of sex in Bulbophyllum bicolor, an obligately outcrossing epiphytic orchid

Vegetative propagation (clonal growth) conveys several evolutionary advantages that positively affect life history fitness and is a widespread phenomenon among angiosperms that also reproduce sexually. However, a bias towards clonality can interfere with sexual reproduction and lead to sexual extinction, although a dearth of effective genetic tools and mathematical models for clonal plants has hampered assessment of these impacts. Using the endangered tropical epiphytic or lithophytic orchid Bulbophyllum bicolor as a model, we integrated an examination of breeding system with 12 microsatellite loci and models valid for clonal species to test for the “loss of sex” and infer likely consequences for long‐term reproductive dynamics. Bagging experiments and field observations revealed B. bicolor to be self‐incompatible and pollinator‐dependent, with an absence of fruit‐set over 4 years. Challenging the assumptions that clonal populations can be as genotypically diverse as sexually reproducing ones and that clonality does not greatly influence genetic structure, just 22 multilocus genotypes were confirmed among all 15 extant natural populations, 12 of the populations were found to be monoclonal, and all three multiclonal ones exhibited a distinct phalanx clonal architecture. Our results suggest that all B. bicolor populations depend overwhelmingly on clonal growth for persistence, with a concomitant loss of sex due to an absence of pollinators and a lack of mating opportunities at virtually all sites, both of which are further entrenched by habitat fragmentation. Such cryptic life history impacts, potentially contributing to extinction debt, could be widespread among similarly fragmented, outcrossing tropical epiphytes, demanding urgent conservation attention.
Complement activation in severe Plasmodium falciparum malaria.

We determined indices of plasma complement activation (C3, C4, Bb, C4d, iC3b, and SC5b-9), levels of tumor necrosis factor (TNF) and interleukin-6, and the APACHE II score in 23 patients with complicated Plasmodium falciparum malaria. On admission, plasma concentrations of Bb, SC5b-9, and C4d were markedly increased compared to healthy control subjects (n = 24) (4.5 +/- 1.9 vs 1.5 +/- 0.6 mg/L; 1125.7 +/- 496.9 vs 183.2 +/- 76.5 microg/L; and 15.7 +/- 5.7 vs 7.2 +/- 1.4 mg/L, P < 0.01 for all). In contrast C3 and iC3b concentrations were decreased (631.4 +/- 247 vs 947.3 +/- 243.2 and 105 +/- 17.9 vs 151.3 +/- 14.5 mg/L; P < 0.01 for both). Plasma C4 concentrations in malaria were not different from normal controls. Plasma Bb, C3, and iC3b levels normalized on day 7 of treatment, whereas SC5b-9 and C4d levels remained elevated. A significant correlation between elevated TNF levels and Bb (r = 0.507) and SC5b-9 (r = 0.448, P < 0.01 for both) and a negative correlation between iC3b and SC5b-9 and TNF levels existed (r = -0.537 and r = -0.466, P < 0.01 for both). In addition, a significant correlation between C3 and iC3b (r = 0.689) and C4 and C4d (r = 0.737) existed. However, no relation between clinical disease severity and complement fragments existed. The results demonstrate that both the classical and the alternative pathways of the complement system are profoundly activated in complicated malaria.
De novo synthesis of Legionella pneumophila antigens during intracellular growth in phagocytic cells

Legionella pneumophilia is a gram-negative rod which is able to multiply within phagocytic cells. The process of phagocytosis leads to a rapid environmental change that might require a coordinate regulation of gene expression to ensure intracellular survival. Since there is little information on up- and downregulation of genes during the early phases of phagocytosis, we radiolabeled intracellular L. pneumophila at different times after phagocytosis by macrophages of the Mono Mac 6 cell line and immunoprecipitated antigens with antilegionella sera or monoclonal antibodies. We could identify two antigens which were upregulated, one of which was the Mip protein, three antigens which were downregulated, and three antigens which were not detectable in extracellularly grown L. pneumophila. The Mip protein was stained most intensively 4 to 8 h after intracellular infection, suggesting that it is needed during intracellular multiplication rather than initiation of infection. A 44-kDa antigen which was not detectable during extracellular growth was most prominent from 2 to 4 h postinfection when Mono Mac 6 cells were used as phagocytic cells. The 44-kDa antigen was also expressed during growth with Acanthamoeba castelanii, MRC-5, and U937 cells but with different kinetics. Synthesis of this antigen was not dependent on protein synthesis of the host cell. Since the 44-kDa antigen could be precipitated by an antiserum produced against a recombinant Escherichia coli harboring a plasmid with an L. pneumophila insert which also codes for the mip gene, we believe that the corresponding gene is within the vicinity of the mip gene. We named this protein legionella intracellular growth antigen (LIGA), since it could be found exclusively in intracellularly grown L. pneumophila.
Myofibroblasts from Scleroderma Skin Synthesize Elevated Levels of Collagen and Tissue Inhibitor of Metalloproteinase (TIMP-1) with Two Forms of TIMP-1 (*)

Cultured fibroblasts derived from skin biopsies from scleroderma patients and normal individuals were examined for the presence of smooth muscle α-actin, a marker for myofibroblasts. Six of eight scleroderma cell lines were found to be 50% or more positive for α-actin while three of four normal lines and one cell line derived from unaffected skin of a scleroderma patient were less than 10% positive. The cultured fibroblasts from affected scleroderma skin were largely myofibroblasts, a phenotype found in biopsies of scleroderma tissue, as well as other fibrotic lesions, wound healing, and tumor desmoplasia. The data support the hypothesis that a certain activated fibroblast phenotype predominates in scleroderma. The activated fibroblast is the myofibroblast. Both collagen and TIMP (tissue inhibitor of metalloproteinases) were elevated in the α-actin positive (myofibroblast enriched) cultures. In addition, the myofibroblast-enriched cultures displayed a more prominent TIMP doublet band pattern on SDS-polyacrylamide gel electrophoresis.
Dosimetry and toxicity of samarium-153-EDTMP administered for bone pain due to skeletal metastases.

UNLABELLED Palliation of bone pain in patients with cancer metastatic to bone is being evaluated in several cancer centers by the administration of the bone-seeking phosphonate ethylenediaminetetramethylenephosphonic acid (EDTMP) chelated with the beta particle-emitting radionuclide 153Sm. METHODS In this study, 153Sm-EDTMP was intravenously injected into 19 patients over a 1-min period. Patients received up to four injections of 18.5 MBq (0.5 mCi) or 37 MBq (1.0 mCi) per kilogram of body weight. Skeletal retention was calculated from urinary excretion. RESULTS No uptake of 153Sm-EDTMP in nonskeletal tissues was observed in whole-body gamma camera images. The mean skeletal uptake for all patients was 54% +/- 16% of the injected dose (%ID). This resulted in the bone marrow receiving 89 cGy/GBq +/- 27 cGy/GBq (3.28 cGy/mCi +/- 0.99 cGy/mCi), with calculated marrow doses ranging from 27 cGy to 338 cGy. For each patient, the estimated radiation absorbed dose to the marrow was correlated to the percent decrease in platelet number, ranging from 7.4% to 78.9%. CONCLUSION Since the deviation of uptake between the four injections for a given patient (7.6% ID) was less than the deviation for all patients (16% ID), the initial dose may be used to estimate the skeletal uptake for the remaining doses. These radiation dose estimates permit patients at risk to be identified prior to reaching myelotoxicity and develop dose-response models. Thirteen patients (68%) reported significant pain relief from this radionuclide therapy. Bone pain appears to be alleviated by 153Sm-EDTMP with limited red marrow doses and no toxic effects in other organs.
Effect of Corporate Social Responsibility on Profitability of Banks Working in Palestine (Case Study 2013-2014)

This study aims to identify the relationship between thecorporatesocial responsibility of banks and profitability measured by return on assets and property rights. To fulfill this purpose, the simple regression analysis was utilized. This study covers the period between 2013- 2014 and includes all the banks operating in Palestine. The findings of the study showed donations have a positive impact, which is statistically significant on the returns on assets and equity. The study recommended that banks should not only focus on economic and legal issues but also on social ones.
Metabolic signatures of GS‐CHO cell clones associated with butyrate treatment and culture phase transition

Chinese hamster ovary (CHO) cells are preferred hosts for the production of recombinant biopharmaceuticals. Efforts to optimize these bioprocesses have largely relied on empirical experience and our knowledge of cellular behavior in culture is incomplete. More recently, comprehensive investigations of metabolic network operation have started to be used to uncover traits associated with optimal growth and recombinant protein production. In this work, we used 1H‐nuclear magnetic resonance (1H‐NMR) to analyze the supernatants of glutamine‐synthetase (GS)‐CHO cell clones expressing variable amounts of an IgG4 under control and butyrate‐treated conditions. Exometabolomic data revealed accumulation of several metabolic by‐products, indicating inefficiencies at different metabolic nodes. These data were contextualized in a detailed network and the cellular fluxomes estimated through metabolic flux analysis. This approach allowed comparing metabolic activity across different clones, growth phases and culture conditions, in particular the efficiency pertaining to carbon lost to glycerol and lactate accumulation and the characteristic nitrogen metabolism involving high asparagine and serine uptake rates. Importantly, this study shows that early butyrate treatment has a marked effect on sustaining high nutrient consumption along culture time, being more pronounced during the stationary phase when extra energy generation and biosynthetic activity is fueled to increase IgG formation. Collectively, the information generated contributes to deepening our understanding of CHO cells metabolism in culture, facilitating future design of improved bioprocesses. Biotechnol. Bioeng. 2013;110: 3244–3257. © 2013 Wiley Periodicals, Inc.
Neuroticism, depressive symptoms and white-matter integrity in the Lothian Birth Cohort 1936

Background Clinical depression is associated with reductions in white-matter integrity in several long tracts of the brain. The extent to which these findings are localized or related to depressive symptoms or personality traits linked to disease risk remains unclear. Method Members of the Lothian Birth Cohort 1936 (LBC936) were assessed in two waves at mean ages of 70 and 73 years. At wave 1, they underwent assessments of depressive symptoms and the personality traits of neuroticism and extraversion. Brain diffusion magnetic resonance imaging (MRI) data were obtained at the second wave and mood assessments were repeated. We tested whether depressive symptoms were related to reduced white-matter tract fractional anisotropy (FA), a measure of integrity, and then examined whether high neuroticism or low extraversion mediated this relationship. Results Six hundred and sixty-eight participants provided useable data. Bilateral uncinate fasciculus FA was significantly negatively associated with depressive symptoms at both waves (standardized β=0.12–0.16). Higher neuroticism and lower extraversion were also significantly associated with lower uncinate FA bilaterally (standardized β=0.09–0.15) and significantly mediated the relationship between FA and depressive symptoms. Conclusions Trait liability to depression and depressive symptoms are associated with reduced structural connectivity in tracts connecting the prefrontal cortex with the amygdala and anterior temporal cortex. These effects suggest that frontotemporal disconnection is linked to the etiology of depression, in part through personality trait differences.
Terrorism and the Response of Investors at Capital Market: A Case of Pakistan

The impact of terrorism on capital market of Pakistan has been examined in this research by using the ten biggest attacks of the last decade (with different targets and venue) out of a total of 941 attacks of this period. Event study methodology has been applied using one way ANOVA post-hoc and multivariate Regression techniques to investigate the impact of terrorist attacks on Karachi Stock Exchange. The results indicated that KSE is becoming insensitive to terrorist attacks. The assaults which target some important political figure and create countrywide violence can only disturb the functioning of KSE. The findings suggest that investors, unlike the stock exchanges of developed countries, should confidently invest at KSE because of numb behavior of market against terrorist attacks. However, the study has picked by only the biggest attack of every year, so future research can be made on all important attacks.
Cryogen spray cooling and higher fluence pulsed dye laser treatment improve port-wine stain clearance while minimizing epidermal damage.

BACKGROUND When a cryogen spurt is applied to the skin surface for an appropriately short period of time (on the order of tens of milliseconds), the cooling remains localized in the epidermis, while leaving the temperature of the deeper port-wine stain (PWS) blood vessels unchanged. OBJECTIVE The objective of this study was to compare the efficacy and safety of noncooled laser treatment (NC-LT), and cryogen spray cooled laser treatment (CSC-LT) of PWS birthmarks in a large series of patients. METHODS A retrospective review was conducted of 196 patients with head or neck PWS birthmarks treated with the pulsed dye laser (lambda = 585 nm; taup = 450 microseconds) over a 7-year period. Subjects' ages ranged between 2 months and 62 years; there were 109 females and 87 males, all of whom were Asian. Ninety-eight patients received NC-LT using light dosages of 5-7 J/cm2. Subsequently, 98 patients received CSC-LT using light dosages of 8-10 J/cm2. The primary efficacy measure was the quantitative assessment of the blanching response scores of NC-LT PWSs as compared, on a blinded basis, to CSC-LT PWSs. RESULTS Based on chi-squared analysis, there were clinical, and statistically significant, differences in the blanching response scores favoring PWS receiving CSC-LT as compared to the NC-LT group (P <.001). Permanent scarring was noted in 3.1% (n = 3) of the patients in the NC-LT group. Permanent scarring was not observed in the CSC-LT treatment group. Transient hyperpigmentation was noted in 57% (n = 56) and 48% (n = 47) of the patients in the NC-LT and CSC-LT groups, respectively. In both groups, the transient hyperpigmentation resolved in all patients within 1 year. Two patients in the NC-LT group developed delayed permanent hypopigmentation. Permanent hypopigmentation was not observed in the CSC-LT group. CONCLUSION CSC permitted the use of higher incident light dosages leading to improved PWS clearance without producing complications such as permanent scarring or dyspigmentation.
No evidence for disruption of normal patterns of mRNA localization in dendrites or dendritic transport of recently synthesized mRNA in FMR1 knockout mice, a model for human fragile‐X mental retardation syndrome

RECENT studies have revealed that FMRP, the gene product of the fragile-X gene FMR1, is an RNA-binding protein. These and other data have led to the idea that FMRP may play a role in targeting mRNAs for transport to synaptic sites. The present study evaluated whether a null mutation of FMR1 disrupts the patterns of localization of three mRNAs that are present constitutively in dendrites (the mRNAs for MAP2, CAMII kinase and dendrin), or disrupt the rapid dendritic transport of the mRNA for activity-regulated cytoskeletal protein (ARC), coded for by an immediate-early gene. In situ hybridization analyses revealed that the patterns of mRNA localization in dendrites and the dendritic transport of ARC mRNA are indistinguishable from normal in FMR1 knockout mice. These results indicate that FMRP does not play an obligatory role in targeting this set of mRNAs to dendrites, although it might be involved in targeting other dendritic mRNAs yet to be identified.
Multiuser detection of overloaded systems employing HARQ

We propose two schemes to perform multiuser detection (MUD) for multiuser multiple-input multiple-output (MIMO) systems under overload. Typically linear MUD algorithms fail to perform under overload and maximum likelihood detection is often prohibitively complex. In this paper, we use hybrid automatic repeat request (HARQ) retransmissions to transform an overloaded system into a critically or underloaded system based on the concept of virtual receive antennas. Hence, low complexity linear MUD algorithms can be used and achieve diversity gains. Simulation results clearly highlight the advantages obtained by the proposed schemes.
Staging, Resectability, and Outcome in 225 Patients With Hilar Cholangiocarcinoma

ObjectiveTo analyze resectability and survival in patients with hilar cholangiocarcinoma according to a proposed preoperative staging scheme that fully integrates local, tumor-related factors. Summary Background DataIn patients with hilar cholangiocarcinoma, long-term survival depends critically on complete tumor resection. The current staging systems ignore factors related to local tumor extent, preclude accurate preoperative disease assessment, and correlate poorly with resectability and survival. MethodsDemographics, results of imaging studies, surgical findings, pathology, and survival were analyzed prospectively in consecutive patients. Using data from imaging studies, all patients were placed into one of three stages based on the extent of ductal involvement by tumor, the presence or absence of portal vein compromise, and the presence or absence of hepatic lobar atrophy. ResultsFrom March 1991 through December 2000, 225 patients were evaluated, 77% of whom were seen and treated within the last 6 years. Sixty-five patients had unresectable disease; 160 patients underwent exploration with curative intent. Eighty patients underwent resection: 62 (78%) had a concomitant hepatic resection and 62 (78%) had an R0 resection (negative histologic margins). Negative histologic margins, concomitant partial hepatectomy, and well-differentiated tumor histology were associated with improved outcome after all resections. However, in patients who underwent an R0 resection, concomitant partial hepatectomy was the only independent predictor of long-term survival. Of the 9 actual 5-year survivors (of 30 at risk), all had a concomitant hepatic resection and none had tumor-involved margins; 3 of these 9 patients remained free of disease at a median follow-up of 88 months. The rates of complications and death after resection were 64% and 10%, respectively. In the 219 patients whose disease could be staged, the proposed system predicted resectability and the likelihood of an R0 resection and correlated with metastatic disease and survival. ConclusionBy taking full account of local tumor extent, the proposed staging system for hilar cholangiocarcinoma accurately predicts resectability, the likelihood of metastatic disease, and survival. Complete resection remains the only therapy that offers the possibility of long-term survival, and hepatic resection is a critical component of the surgical approach.
Stimulation of the adenovirus E2 promoter by simian virus 40 T antigen or E1A occurs by different mechanisms

We have examined the ability of simian virus 40 T antigen to stimulate transcription from the adenovirus E2 promoter. T antigen, produced from a cotransfected plasmid, stimulated chloramphenicol acetyltransferase enzyme and mRNA production from an E2 promoter-chloramphenicol acetyltransferase fusion plasmid (pEC113) in monkey kidney CV-1 cells. The level of stimulation of E2 transcription by simian virus 40 T antigen was equal to that observed in cotransfections of pEC113 and the adenovirus E1A gene product. Deletion mutations from the 5' end of the E2 promoter were examined for their ability to express basal, T-antigen, or E1A trans-activated promoter activity. In each case, deletion of upstream promoter sequences to -70 base pairs reduced chloramphenicol acetyltransferase expression to approximately 30% of the level observed with the intact E2 promoter. Deletion to -59 base pairs resulted in chloramphenicol acetyltransferase expression that was 3 to 5% of that observed with the intact E2 promoter. At saturating levels of the stimulatory proteins, the chloramphenicol acetyltransferase levels obtained in response to T antigen and adenovirus E1A were additive. COS-1 cells, which are derived from CV-1 cells and constitutively express simian virus 40 T antigen, do not support E2 promoter trans activation by T antigen. E1A trans activation of the E2 promoter is efficient in COS-1 cells. These results suggest that although promoter sequence requirements are similar, T antigen and E1A trans activate the E2 promoter by different mechanisms.
Effects of postnatal ethanol exposure on neurotrophic factors and signal transduction pathways in rat brain

Exposure to ethanol during development induces severe brain damage, resulting in a number of CNS dysfunctions including microencephaly and mental retardation. Potential targets of ethanol‐induced neurotoxicity include neurotrophic factors and their signal transduction pathways. In the present study, rat pups were given ethanol at the dose of 5 g kg−1 via gavage from postnatal day (PND) 5 to 8, and mRNA expression of nerve growth‐factor (NGF), brain‐derived neurotrophic factor (BDNF), and neurotrophic factor‐3 (NT‐3) in the cerebral cortex was examined, with attention to signal transduction, on PND 8. The mRNA level of BDNF was decreased by ethanol while those of NGF or NT‐3 were not changed. Brain weights were decreased and the levels of phospho‐MAPK, phospho‐p70S6K and phospho Akt were decreased while phosphor‐PKCζ and phospho‐CREB remained unchanged. These results suggest that BDNF and its related signal pathways involving Akt, MAPK and p70S6K are potential targets of ethanol‐induced developmental neurotoxicity. Copyright © 2007 John Wiley & Sons, Ltd.