Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting hypoxia-inducible factor 1 to stimulate tissue vascularization

When tissue perfusion is impaired, the resulting reduction in O2 availability activates hypoxia-inducible factor 1 (HIF-1), which mediates increased transcription of genes encoding multiple angiogenic factors including vascular endothelial growth factor, stromal-derived factor 1, placental growth factor, and angiopoietins, leading to the mobilization of bone marrow-derived angiogenic cells, increased angiogenesis, and arterial remodeling. These HIF- 1-dependent responses are impaired by aging or loss of function mutations at the locus encoding the HIF-1α subunit. in mouse models of limb ischemia and lung transplant rejection, the augmentation of HIF-1 activity by gene therapy or chemical inducers was associated with maintenance of tissue perfusion that prevented limb amputation and allograft rejection, respectively. Thus, targeting HIF-1 may be of therapeutic benefit in these clinical contexts and others in which impaired tissue perfusion plays a role in disease pathogenesis.
Sex differences in ischaemic stroke: potential cellular mechanisms.

Stroke remains a leading cause of mortality and disability worldwide. More women than men have strokes each year, in part because women live longer. Women have poorer functional outcomes, are more likely to need nursing home care and have higher rates of recurrent stroke compared with men. Despite continued advancements in primary prevention, innovative acute therapies and ongoing developments in neurorehabilitation, stroke incidence and mortality continue to increase due to the aging of the U.S. POPULATION Sex chromosomes (XX compared with XY), sex hormones (oestrogen and androgen), epigenetic regulation and environmental factors all contribute to sex differences. Ischaemic sensitivity varies over the lifespan, with females having an "ischaemia resistant" phenotype that wanes after menopause, which has recently been modelled in the laboratory. Pharmacological therapies for acute ischaemic stroke are limited. The only pharmacological treatment for stroke approved by the Food and Drug Administration (FDA) is tissue plasminogen activator (tPA), which must be used within hours of stroke onset and has a number of contraindications. Pre-clinical studies have identified a number of potentially efficacious neuroprotective agents; however, nothing has been effectively translated into therapy in clinical practice. This may be due, in part, to the overwhelming use of young male rodents in pre-clinical research, as well as lack of sex-specific design and analysis in clinical trials. The review will summarize the current clinical evidence for sex differences in ischaemic stroke, and will discuss sex differences in the cellular mechanisms of acute ischaemic injury, highlighting cell death and immune/inflammatory pathways that may contribute to these clinical differences.
Changing relationship between socioeconomic status and prostate cancer incidence.

BACKGROUND Understanding the relationship between socioeconomic status (SES) and prostate cancer incidence could identify populations that should be targeted for intervention and prevention programs. We examined this relationship within the major racial/ethnic groups during the period 1972 through 1997, which spans the introduction of prostate-specific antigen (PSA) testing. METHODS We used data from the population-based Los Angeles Cancer Surveillance Program to examine age-adjusted prostate cancer incidence rates in five SES groups over three specific calendar periods by racial/ethnic subpopulation (white, black, Asian, and Hispanic) and by stage of disease at diagnosis. Linear regression analysis was used to test for trends in the age-adjusted incidence rates that were associated with increasing levels of SES. All P values were two-sided. RESULTS For men diagnosed with prostate cancer before 1987, when the test for PSA was not widely available, we found no association between SES and the incidence of prostate cancer in any of four racial/ethnic subpopulations or between SES and the stage of disease at diagnosis. In contrast, among men who were diagnosed with prostate cancer after 1987, SES was statistically significantly and positively associated with prostate cancer incidence in men from all racial/ethnic subpopulations except Asians (P =.01 for white men, P =.001 for black men, P =.02 for Hispanic men, P =.06 for Asian men, and P =.01 for all men combined). Higher SES was statistically significantly associated with cancers of earlier stage (P =.01 for localized cancer and P =.00 for regional cancer) for men who were diagnosed with prostate cancer after 1987. CONCLUSIONS The association between SES and prostate cancer incidence after 1987 may reflect more prevalent PSA screening in populations with higher SES due to their greater access to health care. SES should, therefore, be considered an important factor in interpreting variations and time trends in prostate cancer incidence.
Self-reported memory impairment and brain PET of amyloid and tau in middle-aged and older adults without dementia

ABSTRACT Background: Whether perceived changes in memory parallel changes in brain pathology is uncertain. Positron emission tomography (PET) scans using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP) can measure levels of amyloid plaques and tau neurofibrillary tangles in vivo. Here we investigate whether degree of self-reported memory impairment is associated with FDDNP-PET binding levels in persons without dementia. Methods: Fifty-seven middle-aged and older adults without dementia (mean age ±standard deviation = 66.3 ± 10.6 years), including 25 with normal aging and 32 with mild cognitive impairment (MCI), were assessed. The outcome measures were the four factor scores of the Memory Functioning Questionnaire (MFQ) (frequency of forgetting, seriousness of forgetting, retrospective functioning, and mnemonics use) and FDDNP-PET binding levels in medial temporal, lateral temporal, posterior cingulate, parietal, frontal, and global (overall average) regions of interest. Results: After controlling for age, higher reported frequency of forgetting was associated with greater medial temporal (r = −0.29, p = 0.05), parietal (r = −0.30, p = 0.03), frontal (r = −0.35, p = 0.01), and global FDDNP-PET binding levels (r = −0.33, p = 0.02). The remaining MFQ factor scores were not significantly associated with FDDNP-PET binding levels, and no significant differences were found between normal aging and MCI subjects. Item analysis of the frequency of forgetting factor revealed five questions that yielded similar results as the full 32-question scale (r = −0.52, p = 0.0002). Conclusions: These findings suggest that some forms of memory self-awareness, in particular the reported frequency of forgetting, may reflect the extent of cerebral amyloid and tau brain pathology.
Effect of Sulfur Source on the Performance and Metal Retention of Methanol‐Fed UASB Reactors

The effect of a sulfur source on the performance and metal retention of methanol‐fed upflow anaerobic sludge bed (UASB) reactors was investigated. For this purpose, two UASB reactors were operated with cobalt preloaded granular sludge (1 mM CoCl2; 30 °C; 24 h) at an organic loading rate (OLR) of 5 g COD·L reactor−1·d−1. One UASB reactor (R1) was operated without a sulfur source in the influent during the first 37 days. In this period the methanol conversion to methane remained very poor, apparently due to the absence of a sulfur source, because once cysteine, a sulfur‐containing amino acid, was added to the influent of R1 (day 37) a full conversion of methanol to methane occurred within 6 days. The second reactor (R2) was operated with sulfate (0.41 mM) in the influent during the first 86 days of operation, during which no limitation in the methanol conversion to methane manifested. Cobalt washed out from the sludge at similar rates in both reactors. The leaching of cobalt occurred at two distinct rates, first at a high rate of 22 μg·g TSS−1·d−1, which proceeded mainly from the exchangeable and carbonate fraction and later at a relatively slow rate of 9 μg·g TSS−1·d−1 from the organic/sulfide fraction. This study showed that the supply of the sulfur source l‐cysteine has a pronounced positive effect on the methanogenic activity and the retention of metals such as iron, zinc and molybdenum.
Symptom panorama in upper secondary school students and symptoms related to iron deficiency Screening with laboratory tests, questionnaire and interventional treatment with iron

Objective To study symptom panorama in students, to identify undiagnosed iron deficiency, and to evaluate any changes in symptoms and laboratory test results after treatment with iron supplementation. Design Descriptive and prospective, interventional study. Setting Healthcare in upper secondary school. Intervention Treatment with iron supplementation for a period of 3 months. Subjects Students in the first grade of one upper secondary school. Main outcome measures Frequency of iron deficiency related to symptoms measured by a questionnaire (30 questions) on symptoms related to quality of life and 9 questions about diet and exercise. Results Iron deficiency was diagnosed in 12% of the students (two or more abnormal laboratory tests) and in 61% of the students one or more laboratory tests were abnormal. Symptoms of vertigo/dizziness were significantly more common in students with iron deficiency. After iron supplementation there was a significant increase in s-ferritin levels and a decrease in s-transferrin levels, with an accompanying significant reduction of the symptom scores of vertigo/dizziness, irritability, depressive symptoms, and indisposition. Conclusions Symptoms of vertigo/dizziness were significantly more common in students with iron deficiency. Iron supplementation reduced the symptoms of vertigo/dizziness, irritability, depressive symptoms, and indisposition.
Triamcinolone acetonide suppresses early proangiogenic response in retinal pigment epithelial cells after photodynamic therapy in vitro

Objective: To investigate the expression of proangiogenic and antiangiogenic factors, vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in retinal pigment epithelial (RPE) cells after photodynamic therapy (PDT), especially focusing on their change in the presence of triamcinolone acetonide. Methods: Firstly, the cellular uptake of verteporfin was quantified after confluent ARPE-19 (human retinal pigment epithelial) cells were exposed to 5 μg/ml verteporfin combined with or without 1 μg/ml triamcinolone acetonide for 1 h. Secondly, ARPE-19 cells exposed to various doses of verteporfin were irradiated with 120 mJ/cm2 light. After incubation with or without 1 μg/ml triamcinolone acetonide for 2 days, cell viability and expressions of VEGF and PEDF were assessed. Results: Cellular uptake of verteporfin was not significantly changed by the presence of 1 μg/ml triamcinolone acetonide. In addition, 0.01–0.1 μg/ml of verteporfin showed a dose-dependent toxicity on the ARPE-19 cells 2 days after the light exposure. The presence of verteporfin at a concentration of 0.01 μg/ml did not affect the cell viability but significantly increased VEGF (p<0.001) and reduced PEDF (p = 0.03) expression. Administration of triamcinolone acetonide significantly suppressed both this increase in VEGF (p<0.001) and decrease in PEDF (p = 0.001). Conclusions: VEGF was increased and PEDF reduced in cultured RPE cells shortly after PDT even at a sublethal dose. Triamcinolone acetonide suppressed this proangiogenic response.
Diurnal Variation in Energetic Arousal, Tense Arousal, and Hedonic Tone in Extreme Morning and Evening Types

The aim of the present study was to examine levels of energetic arousal (EA), tense arousal (TA), and hedonic tone (HT) in individuals with different circadian preferences. Subjects were males with extreme either morning (M‐type) or evening (E‐type) preferences (N=31), selected using the Morningness‐Eveningness Questionnaire cutoff points derived from the Polish population norms. They completed the UWIST Mood Adjective Check List every 1.5 h between 08:00 to 20:00 h in laboratory conditions. The obtained data showed higher levels of TA and lower levels of HT in E‐types over the whole day as compared to M‐types. As for EA, M‐types showed higher levels than E‐types between 08:00 to 17:00 h, but the two groups showed no differences during the later hours of the day. Both groups were found to exhibit similar diurnal patterns in TA and HT, and dissimilarity between M‐types and E‐types appeared in the daily course of EA. The results show the three‐dimensional model of mood is more advantageous in M‐types than in E‐types during the hours of typical human activity.
Corrigendum to “Unique solutions”

To exclude any unintended interpretation, I need to make more precise some parts of [3], especially of the (complementary) Section 4. First, the name “modulus of uniqueness” was already used in [1]; some history of this concept can also be found in [2, Section 4.1]. Next, WKL is part of the extension of PA which occurs in the premiss of the rules proved in [1, Section 4]. Moreover, the rule from [1, Theorem 4.3] corresponds to the implication from FAN to MUN, and thus to the one from FAN to UAM, which is one half of the classification of UAM given in [3, Section 3]. A further matter of concern is the very end of [3, Section 4]. When, in [2, p. 145, second paragraph], a sequence was presented as a means to approximate the solution, the existence of the latter was indeed not at issue. This, however, comes short of giving a true picture of the content of [1, Section 4]: with the two rules from [1, Theorem 4.4, Corollary 4.5], a formal classical proof of the uniqueness of the desired solution is converted into a formal constructive proof of its existence as a continuous function in the parameters. As hinted at before [3, p. 536, lines 10 – 14], the idea standing behind [3, Proposition 2.1, Corollary 2.2] can be found in the deductions of these two rules [1, Theorem 4.4, Corollary 4.5] from the aforementioned one [1, Theorem 4.3].
Assessing Knowledge Management Services through Discourse Analysis

This paper presents a case study in which discourse analysis was used to suggest process improvements in two knowledge management services (KMS). It employs linguistic analysis as the means for assessing the degree to which each KMS is aligned to the users’ needs. Areas requiring improvement are identified linguistically based on the differences between users’ experience of the services and the perspectives of the information technology professionals. The case study was carried out in a large, global corporation operating in the property services sector. We studied two user communities and the group of IT professionals who developed and managed the services. Discourse analysis using Systemic Functional Linguistics forms the basis for the assessment of the extent to which language enacts or restricts such alignment.
Vesical regeneration in the human after total cystectomy and implantation of a plastic mould.

SUMMARY 1. Regeneration of the bladder after extensive partial cystectomy or accidental necrosis has been reported in the medical literature of our time. 2. We report a case of total cystectomy with implantation of a plastic mould in the place previously occupied by the bladder. 3. When the plastic mould was removed twelve weeks later, we found that the cavity was similar to a normal bladder, with transitional epithelium of vesical type. 4. This cavity was larger than the plastic mould. 5. A descending pyelogram made after the mould was removed showed that kidney function was normal; that the ureters drained normally to the newly formed cavity; and that the mild hydronephrosis produced during the time the mould had remained in place had practically disappeared. 6. Histological study of biopsies taken in different areas of the newly formed cavity showed that it was lined by a transitional epithelium of vesical type over a membrane formed of connective tissue infiltrated with round cells. We did not find plain muscular fibres isolated or grouped in bundles. 7. We are not aware of this operation having been performed previously in human beings.
Paclitaxel versus sirolimus eluting stents in diabetic patients: Does stent type and/or stent diameter matter?: Long‐term clinical outcome of 2,429‐patient multicenter registry

Drug‐eluting stents (DES) are more effective in reducing restenosis than bare‐metal stents. Less certain is the relative performance of the two widely used DES—sirolimus‐eluting stents (SES) and paclitaxel‐eluting stents (PES)—in diabetic patients undergoing percutaneous coronary intervention (PCI).
Night-shift work and risk of colorectal cancer in the nurses' health study.

Exposure to light at night suppresses the physiologic production of melatonin, a hormone that has antiproliferative effects on intestinal cancers. Although observational studies have associated night-shift work with an increased risk of breast cancer, the effect of night-shift work on the risk of other cancers is not known. We prospectively examined the relationship between working rotating night shifts and the risk of colorectal cancers among female participants in the Nurses' Health Study. We documented 602 incident cases of colorectal cancer among 78 586 women who were followed up from 1988 through 1998. Compared with women who never worked rotating night shifts, women who worked 1-14 years or 15 years or more on rotating night shifts had multivariate relative risks of colorectal cancer of 1.00 (95% confidence interval [CI] = 0.84 to 1.19) and 1.35 (95% CI = 1.03 to 1.77), respectively (P(trend) =. 04). These data suggest that working a rotating night shift at least three nights per month for 15 or more years may increase the risk of colorectal cancer in women.
THE MANAGEMENT OF OVERHEAD COSTS IN CONSTRUCTION COMPANIES

Costs not directly attributable to or recoverable from production and sales are often loosely referred to as overhead costs. In construction, some of these result from the organisation structure, size and form of the enterprise, some apply more directly to site operations and some may lie somewhere in between. Overhead costs largely represent the enterprise’s operational capacity, including aspects of both physical capacity such as plant and equipment and intellectual capacity such as data, records, expertise, experience and knowledge. The fluctuating nature of the construction market periodically compels enterprises, for competitive and survival reasons, to adopt shrinkage strategies. These may include retrenchments and downscaling of office and other facilities and often represents loss of capacity. When markets again expand, replacing lost capacity is problematic. Budgeting for overheads when bidding and recovering them from contract revenues in a dynamic market is a further challenging factor in optimally balancing overheads against capacity. By means of a review of literature and the results of preliminary surveys among large and mediumsized contractors, this paper presents progress on current research into managing overheads in South African construction enterprises. The objective of the project is to promote productivity through optimal management of overheads.
Bile acid depletion and repletion regulate cholangiocyte growth and secretion by a phosphatidylinositol 3-kinase-dependent pathway in rats.

BACKGROUND & AIMS We tested the hypothesis that during bile duct obstruction, increased biliary bile acids trigger cholangiocyte proliferation and secretion by a phosphatidylinositol 3-kinase (PI3-K)-dependent pathway. METHODS In bile duct-incannulated (BDI) rats, bile duct obstruction present for 7 days was relieved for 24 hours by external bile drainage. During the 24-hour drainage period, animals received either Krebs Ringer Henseleit (the bile-depleted group), or sodium taurocholate (the bile-depleted, taurocholate-infused group). We evaluated cholangiocyte proliferation and secretin-stimulated ductal secretion. Apical bile acid transporter (ABAT) expression and bile acid transport activity was determined. In pure preparations of cholangiocytes, we examined the effect of taurocholate (in the absence or presence of wortmannin or PI 3,4-bisphosphate the lipid product of PI3-K) on cholangiocyte proliferation and secretin-stimulated cyclic adenosine 3',5'-monophosphate (cAMP) levels. RESULTS Bile depletion reduced cholangiocyte proliferation and secretin-stimulated ductal secretion and ABAT expression and bile acid transport activity compared with 1-week BDI control rats. In bile-depleted, taurocholate-infused rats, cholangiocyte proliferation and secretion and ABAT expression and bile acid transport activity were maintained at levels similar to those seen in BDI control rats. In vitro, taurocholate stimulation of DNA replication and secretin-stimulated cAMP levels was blocked by wortmannin. The inhibitory effect of wortmannin on taurocholate stimulation of cholangiocyte proliferation and secretion was prevented by PI 3,4-bisphosphate. CONCLUSIONS Bile acid uptake by ABAT and the PI3-K pathway are important for bile acids to signal cholangiocyte proliferation. In bile duct obstruction, increased biliary bile acid concentration and ABAT expression initiate increased cholangiocyte proliferation and secretion.
The Nuclear Receptor Corepressors NCoR and SMRT Decrease Peroxisome Proliferator-activated Receptor γ Transcriptional Activity and Repress 3T3-L1 Adipogenesis*

The peroxisome proliferator-activated receptor γ (PPARγ) is a central regulator of adipogenesis and recruits coactivator proteins in response to ligand. However, the role of another class of nuclear cofactors, the nuclear receptor corepressors, in modulating PPARγ transcriptional activity is less clear. Such corepressors include the nuclear receptor corepressor (NCoR) and the silencing mediator of retinoid and thyroid hormone receptors (SMRT). Our data suggest that PPARγ recruits SMRT and NCoR in the absence of ligand and that these corepressors are capable of down-regulating PPARγ-mediated transcriptional activity. The addition of the PPARγ ligand pioglitazone results in dissociation of the PPARγ-corepressor complex. To define the role of SMRT and NCoR in PPARγ action, 3T3-L1 cells deficient in SMRT or NCoR were generated by RNA interference. When these cells are exposed to differentiation media, they exhibit increased expression of adipocyte-specific genes and increased production of lipid droplets, as compared with control cells. These data suggest that the nuclear receptor corepressors decrease PPARγ transcriptional activity and repress the adipogenic program in 3T3-L1 cells.