Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypoxia down‐regulates MCP‐1 expression: implications for macrophage distribution in tumors

Monocyte chemoattractant protein 1 (MCP‐1) is likely to contribute to the macrophage infiltrate in human ovarian carcinomas. Although MCP‐1 is predominantly expressed by the tumor parenchyma, macrophages accumulate at highest density in necrotic regions, which are associated with low oxygen tensions. Tumor necrosis factor α (TNF‐α) can stimulate MCP‐1 production and is also present within ovarian carcinomas. We have investigated the effect of hypoxia both on MCP‐1 expression in ovarian cancer cell lines and monocyte migration. Hypoxia down‐regulated TNF‐α‐induced MCP‐1 mRNA and protein production by ovarian cancer cells. The effect was mimicked by cobalt chloride and desferrioxamine, consistent with a specific oxygen‐sensing mechanism. Unlike antioxidants, hypoxia did not inhibit nuclear factor κB mobilization. Monocyte migration in response to MCP‐1 was also diminished under hypoxic conditions. Down‐regulation of MCP‐1 expression and the inhibition of monocyte migration are independent effects of hypoxia that may contribute to the distribution of macrophages within ovarian tumors. J. Leukoc. Biol. 63: 758–765; 1998.
Covariates of alcohol consumption among career firefighters.

BACKGROUND Little is known about rates of alcohol consumption in career firefighters. AIMS To assess the quantity and frequency of alcohol consumption among career firefighters and the covariates that influence consumption levels. METHODS A convenience sample of career firefighters completed an online, self-administered, health assessment survey. Hierarchical binary logistic regression assessed the ability of several covariates to predict binge drinking status. RESULTS The majority of the sample (n = 160) consumed alcohol (89%), with approximately one-third (34%) having a drinking binge in the past 30 days. The regression model explained 13-18% of the variance in binge drinking status and correctly classified 71% of cases. Race (P < 0.05) and time of service (P < 0.01) were the only covariates that made a statistically significant contribution to the model. After controlling for other factors in the model, white respondents were ~4.5 times more likely to binge drink than non-white respondents (95% CI: 1.15-17.4). For each additional year of service, firefighters were 1.08 times less likely to binge drink (95% CI: 0.87-0.97). CONCLUSIONS Drinking levels observed in this study exceed those of the general adult population, including college students. Thus, it appears that firefighters represent an at-risk drinking group. Further investigations addressing reasons for alcohol use and abuse among firefighters are warranted. This study and subsequent research will provide information necessary for the development and testing of tailored interventions aimed at reducing firefighter alcohol consumption.
Within farm variation in nutrient composition of feeds.

Estimates of the amount of variation (i.e., standard deviations and ranges) in nutrient composition of common feeds are readily available from some national feed testing labs; however, estimates of variation on feeds within a farm are needed to determine appropriate feed sampling and ration re-formulation schedules. We conducted a large national survey to determine within farm variation for some common feeds. On average, within farm variation for crude protein (CP) and neutral detergent fiber (NDF) was 2 or 3 times less than variation in the national population. Within a farm, substantial day-to-day variation in dry matter (DM), NDF, CP, and starch was observed for corn silage and haycrop silage, indicating that samples should be taken over several days and those results averaged for diet formulation purposes. In some cases, day-to-day variation was as great as monthto-month variation. The concentrations of NDF, but not CP, in high moisture corn, distillers grains, and brewers grains varied almost as much as NDF concentrations in some forages, indicating that these feeds should be sampled on a regular basis.
Generating Abstractive Summaries from Meeting Transcripts

Summaries of meetings are very important as they convey the essential content of discussions in a concise form. Both participants and non-participants are interested in the summaries of meetings to plan for their future work. Generally, it is time consuming to read and understand the whole documents. Therefore, summaries play an important role as the readers are interested in only the important context of discussions. In this work, we address the task of meeting document summarization. Automatic summarization systems on meeting conversations developed so far have been primarily extractive, resulting in unacceptable summaries that are hard to read. The extracted utterances contain disfluencies that affect the quality of the extractive summaries. To make summaries much more readable, we propose an approach to generating abstractive summaries by fusing important content from several utterances. We first separate meeting transcripts into various topic segments, and then identify the important utterances in each segment using a supervised learning approach. The important utterances are then combined together to generate a one-sentence summary. In the text generation step, the dependency parses of the utterances in each segment are combined together to create a directed graph. The most informative and well-formed sub-graph obtained by integer linear programming (ILP) is selected to generate a one-sentence summary for each topic segment. The ILP formulation reduces disfluencies by leveraging grammatical relations that are more prominent in non-conversational style of text, and therefore generates summaries that is comparable to human-written abstractive summaries. Experimental results show that our method can generate more informative summaries than the baselines. In addition, readability assessments by human judges as well as log-likelihood estimates obtained from the dependency parser show that our generated summaries are significantly readable and well-formed.
Mechanical Behaviour of Cold-formed Hollow Structural Section Material

In this thesis, the static and dynamic properties of cold-formed Rectangular Hollow Sections (RHS) produced by different manufacturing techniques (direct-forming versus continuousforming; heat-treated versus non-heat-treated) were studied comparatively for the first time. The aim of this research was to quantify the effects of different manufacturing processes on the mechanical behaviour of RHS such that the implications of using RHS with different production histories can be better appreciated during the design of structures made of RHS and their welded joints. The static properties of seven cold-formed RHS specimens were investigated by performing tensile coupon tests, stub column tests, and residual stress measurements. Analytical column curves were generated to reflect their compression behaviour, based on the experimental results. It was found that, in general, the static properties of a direct-formed RHS are midway between those of its continuous-formed and continuous-formed plus heat-treated counterparts. The Charpy V-notch (CVN) impact toughness properties of six RHS specimens were studied via 378 CVN coupons. For RHS with different cross-sectional geometries and produced by different methods, complete CVN toughness-temperature curves of the flat face and the corner were compared to quantify the decrease of notch toughness from the flat face to the
Double-Blind, Randomised, Controlled Trial Assessing Controller Medications in Asthma

Background: The motive behind conducting this study was to determine if better control of asthma can be achieved by adding a second controller medication and to assess its use to reduce the dose of inhaled steroids. Objectives: The study aimed to determine whether either oral sustained-release theophylline or montelukast added to inhaled steroids improved clinical symptoms and pulmonary function test parameters when compared to high-dose steroids alone. Methods: Ninety patients with incompletely controlled asthma were allocated, in a randomised, double-blind fashion, to one of three treatment groups: group A: double dose of inhaled budesonide (400 µg b.i.d.), group B: 400 mg oral sustained-release theophylline plus budesonide (200 µg b.i.d.) and group C: 10 mg montelukast plus budesonide (200 µg b.i.d.). The primary endpoints were forced expiratory volume in 1 s (FEV1) and mean morning peak expiratory flow rate (PEFR). Results: All three groups had improved FEV1 and PEFR at 8 weeks (p < 0.001). Group C increased their PEFR by 18.7 l/min (95% confidence interval, CI, 12.4–25.1) more than group A and by 19.8 l/min (95% CI 13.4–26.1) more than group B (both p = 0.001). Similarly, group C had a 114 ml (95% CI 45–183 ml) greater improvement in FEV1 than group A and a 95 ml (95% CI 26–164 ml) greater improvement than group B (both p = 0.01). Conclusions: Addition of montelukast to budesonide is safe and results in greater improvement in pulmonary function test parameters than high-dose budesonide treatment or addition of theophylline.
The initial development and assessment of an automatic alert warning of acute kidney injury.

BACKGROUND Acute kidney injury (AKI) recognition by clinicians has been shown to be suboptimal. Little work has focused on the use of an automated warning of a rise in a patient's creatinine, indicating AKI. METHODS Over 3 months in 2008 we ran a prospective observational study of 'alerts' sent by our Integrated Clinical Environment pathology system, identifying all patients with a ≥ 75% rise in their creatinine from its previous value. Information was collected on subsequent renal function, comorbidities and other potential predictors of survival. RESULTS In the 3-month period 463 adults with a first episode of AKI were identified by an alert; 87% were hospital inpatients. Median follow-up was 404 days. In-hospital mortality was 36% for those who were admitted. After performing Weibull survival analysis, significant predictors of poorer survival were the presence of metastatic, haematological or lower risk malignancy, a residential or nursing home address and higher age, number of non-malignant comorbidities or C-reactive protein level. Predictors of better survival were higher serum albumin level or nadir GFR during the episode and Indian subcontinent ethnicity. A receiver-operator curve for a prognostic score developed from the analysis showed an area under the curve of 0.84. CONCLUSIONS The alerts identified a group of AKI patients who are at moderately high risk of death. The prognostic score using a combination of covariates shows early promise. Both the alerts and the score warrant further development as tools for earlier intervention in AKI.
Histone deacetylase inhibitor FK228 is a potent inducer of human fetal hemoglobin

We investigated the induction of the human fetal globin gene using five potent histone deacetylase (HDAC) inhibitors: FK‐228, HC‐Toxin, Trichostatin, MS‐275, and Apicidin, using in vitro assays and cultures of primary human erythroblasts. The results showed that FK228 is the most potent inducer of fetal hemoglobin and exhibits its effects in picomolar concentrations. FK228 should be considered as a potential therapeutic for induction of fetal hemoglobin in patients with β chain hemoglobinopathies. Am. J. Hematol. , 2006. © 2006 Wiley‐Liss, Inc.
Testosterone and Vascular Function in Aging

Androgen receptors are widely distributed in several tissues, including vascular endothelial and smooth muscle cells. Through classic cytosolic androgen receptors or membrane receptors, testosterone induces genomic and non-genomic effects, respectively. Testosterone interferes with the vascular function by increasing the production of pro-inflammatory cytokines and arterial thickness. Experimental evidence indicates that sex steroid hormones, such as testosterone modulate the synthesis and bioavailability of NO and, consequently, endothelial function, which is key for a healthy vasculature. Of interest, aging itself is accompanied by endothelial and vascular smooth muscle dysfunction. Aging-associated decline of testosterone levels is accompanied by age-related diseases, such as metabolic and cardiovascular diseases, indicating that very low levels of androgens may contribute to cardiovascular dysfunction observed in these age-related disorders or, in other words, that testosterone may have beneficial effects in the cardiovascular system. However, testosterone seems to play a negative role in the severity of renal disease. In this mini-review, we briefly comment on the interplay between aging and testosterone levels, the vascular actions of testosterone and its implications for vascular aging. Renal effects of testosterone and the use of testosterone to prevent vascular dysfunction in elderly are also addressed.
BIOTECHNOLOGICALLY RELEVANT ENZYMES AND PROTEINS Identification and characterization of DGA2, an acyltransferase of the DGAT1 acyl-CoA:diacylglycerol acyltransferase family in the oleaginous yeast Yarrowia lipolytica. New insights into the storage lipid metabolism of oleaginous yeasts

Triacylglycerols (TAG) and steryl esters (SE) are the principal storage lipids in all eukaryotic cells. In yeasts, these storage lipids accumulate within special organelles known as lipid bodies (LB). In the lipid accumulationoriented metabolism of the oleaginous yeast Yarrowia lipolytica, storage lipids are mostly found in the form of TAG, and only small amounts of SE accumulate. We report here the identification of a new DAG acyltransferase gene, DGA2, homologous to the ARE genes of Saccharomyces cerevisiae. This gene encodes a member of the type 1 acylCoA:diacylglycerol acyltransferase family (DGAT1), which has not previously been identified in yeasts, but is commonly found in mammals and plants. Unlike the Are proteins in S. cerevisiae, Dga2p makes a major contribution to TAG synthesis via an acyl-CoA-dependent mechanism and is not involved in SE synthesis. This enzyme appears to affect the size and morphology of LB, suggesting a direct role of storage lipid proteins in LB formation. We report that the Are1p of Y. lipolytica was essential for sterol esterification, as deletion of the encoding gene (ARE1) completely abolished SE synthesis. Unlike its homologs in yeasts, YlARE1 has no DAG acyltransferase activity. We also reconsider the role and function of all four acyltransferase enzymes involved in the final step of neutral lipid synthesis in this oleaginous yeast.
Novel Oligomeric Proanthocyanidin Derivatives Interact with Membrane Androgen Sites and Induce Regression of Hormone-Independent Prostate Cancer

Prostate cancer is the most common malignancy among men in Western societies, and current therapeutic approaches are evolving to manage growth, recurrence, and mortality neoplasia. Membrane androgen receptors (mARs) have been characterized in human prostate cancer, being preferentially expressed in tumor rather than benign gland areas. Furthermore, mAR agonists (protein-conjugated testosterone) decrease in vitro prostate cancer cell growth and induce apoptosis, whereas in vivo they regress growth of tumor xenografts alone or in combination with taxane drugs. In this respect, targeting mARs might be a novel therapeutic approach in prostate cancer. In our search for new small-molecule ligands of mAR, we report that flavanol dimers B1-B4 (oligomeric procyanidins) decrease in vitro growth of the androgen-sensitive (LnCaP) and androgen-resistant (DU145) human prostate cancer cell lines in the following order: B3 = B4 > B2 ≫ B1 (LnCaP) and B2 ≫ B3 = B4 ≫ B1 (DU145). Some of these analogs were previously shown to trigger signaling cascades similar to testosterone-bovine serum albumin (BSA) conjugate. Galloylation does not confer an additional advantage; however, oleylation increases the dimers' antiproliferative potency by a factor of 100. In addition, we report that B2, oleylated or not, displaces testosterone from mARs with an IC50 value at the nanomolar range and induces DU145 tumor xenograft regression by 50% (testosterone-BSA 40%). In this respect, oleylated B2 is a potent small-molecule agonist of mAR and could be a novel therapeutic agent for advanced prostate cancer, especially when taking into account the absence of androgenic actions and (liver) toxicity.
Near-infrared fluorescence imaging of prostate cancer using heptamethine carbocyanine dyes

Near-infrared fluorescence (NIRF) imaging is an attractive novel modality for the detection of cancer. A previous study defined two organic polymethine cyanine dyes as ideal NIRF probes, IR-783 and its derivative MHI-148, which have excellent optical characteristics, superior biocompatibility and cancer targeting abilities. To investigate the feasibility of NIRF dye-mediated prostate cancer imaging, dye uptake and subcellular co-localization were investigated in PC-3, DU-145 and LNCaP human prostate cancer cells and RWPE-1 normal prostate epithelial cells. Different organic anion transporting peptide (OATP) inhibitors were utilized to explore the potential role of the OATP subtype, including the nonspecific OATP inhibitor bromosulfophthalein, the OATP1 inhibitor 17β-estradiol, the selective OATP1B1 inhibitor rifampicin and the selective OATP1B3 inhibitor cholecystokinin octapeptide. NIRF dyes were also used for the simulated detection of circulating tumor cells and the rapid detection of prostate cancer in human prostate cancer tissues and prostate cancer xenografts in mouse models. The results revealed that the cancer-specific uptake of these organic dyes in prostate cancer cells occurred primarily via OATP1B3. A strong NIRF signal was detected in prostate cancer tissues, but not in normal tissues that were stained with IR-783. Prostate cancer cells were recognized with particular NIR fluorescence in isolated mononuclear cell mixtures. The results of the present study demonstrated that NIRF dye-mediated imaging is a feasible and practicable method for prostate cancer detection, although further investigative studies are required before clinical translation.
Biomechanical Conditioning Enhanced Matrix Synthesis in Nucleus Pulposus Cells Cultured in Agarose Constructs with TGFβ

Biomechanical signals play an important role in normal disc metabolism and pathology. For instance, nucleus pulposus (NP) cells will regulate metabolic activities and maintain a balance between the anabolic and catabolic cascades. The former involves factors such as transforming growth factor-β (TGFβ) and mechanical stimuli, both of which are known to regulate matrix production through autocrine and paracrine mechanisms. The present study examined the combined effect of TGFβ and mechanical loading on anabolic activities in NP cells cultured in agarose constructs. Stimulation with TGFβ and dynamic compression reduced nitrite release and increased matrix synthesis and gene expression of aggrecan and collagen type II. The findings from this work has the potential for developing regenerative treatment strategies which could either slow down or stop the degenerative process and/or promote healing mechanisms in the intervertebral disc.
Association between Self-Rated Health and the Ethnic Composition of the Residential Environment of Six Ethnic Groups in Amsterdam

Background: Studies on the association between health and neighborhood ethnic composition yielded inconsistent results, possibly due to methodological limitations. We assessed these associations at different spatial scales and for different measures of ethnic composition. Methods: We obtained health survey data of 4673 respondents of Dutch, Surinamese, Moroccan, Turkish other non-Western and other Western origin. Neighborhood ethnic composition was measured for buffers varying from 50–1000 m. Associations with self-rated health were measured using logistic multilevel regression analysis, with control for socioeconomic position at the individual and area level. Results: Overall ethnic heterogeneity was not related to health for any ethnic group. The presence of other Surinamese was associated with poor self-rated health among Surinamese respondents. The presence of Moroccans or Turks was associated with poor health among some groups. The presence of Dutch was associated with better self-rated health among Surinamese and Turks. In most cases, these associations were stronger at lower spatial scales. We found no other associations. Conclusions: In Amsterdam, self-rated health was not associated with ethnic heterogeneity in general, but may be related to the presence of specific ethnic groups. Policies regarding social and ethnic mixing should pay special attention to the co-residence of groups with problematic interrelations.
Cysteine‑rich 61 RNA interference inhibits pathological angiogenesis via the phosphatidylinositol 3‑kinase/Akt‑vascular endothelial growth factor signaling pathway in endothelial cells.

Hypoxia is a key factor in the pathogenesis of angiogenesis, and cysteine‑rich 61 (CCN1), an angiogenic factor, is involved in the development of pathological angiogenesis. The aim of the present study was to investigate the mechanism of CCN1 RNA interference (RNAi)‑induced inhibition of hypoxia‑induced pathological angiogenesis in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were cultured under hypoxic conditions in vitro. The effects of inhibiting phosphoinositide 3‑kinase (PI3K)/Akt signaling using LY294002 were investigated in hypoxic HUVECs. The proliferation and apoptosis of HUVECs under hypoxia were assessed using CCN1 RNAi. The CCN1‑PI3K/Akt‑vascular endothelial growth factor (VEGF) pathway was analyzed under hypoxic conditions using reverse transcription‑quantitative polymerase chain reaction and western blotting. CCN1 RNAi inhibited the proliferation and induced the apoptosis of the HUVECs under hypoxia, with hypoxia significantly increasing the mRNA and protein expression levels of CCN1, Akt and VEGF. By contrast, CCN1 RNAi reduced the mRNA and protein expression levels of CCN1, Akt and VEGF in the HUVECs (P<0.05). Furthermore, LY294002 reduced the mRNA and protein expression levels of CCN1 in the hypoxic cells (P<0.05). These data indicated that CCN1 inhibits apoptosis and promotes proliferation in HUVECs. Therefore, CCN1 RNAi may offer a novel therapeutic strategy, which may aid in the treatment of pathological angiogenesis via inhibition of the PI3K/Akt‑VEGF pathway.
Chemical, Bioactive, and Antioxidant Potential of Twenty Wild Culinary Mushroom Species

The chemical, bioactive, and antioxidant potential of twenty wild culinary mushroom species being consumed by the people of northern Himalayan regions has been evaluated for the first time in the present study. Nutrients analyzed include protein, crude fat, fibres, carbohydrates, and monosaccharides. Besides, preliminary study on the detection of toxic compounds was done on these species. Bioactive compounds evaluated are fatty acids, amino acids, tocopherol content, carotenoids (β-carotene, lycopene), flavonoids, ascorbic acid, and anthocyanidins. Fruitbodies extract of all the species was tested for different types of antioxidant assays. Although differences were observed in the net values of individual species all the species were found to be rich in protein, and carbohydrates and low in fat. Glucose was found to be the major monosaccharide. Predominance of UFA (65–70%) over SFA (30–35%) was observed in all the species with considerable amounts of other bioactive compounds. All the species showed higher effectiveness for antioxidant capacities.