Miracle-dz/UniFAR-FTUs huggingface dataset:
C1orf109L promote R-loop accumulation induced DNA damage to inhibit cell growth

As a function unknown gene, C1orf109 is lower expression in various cells. Here, we reported that C1orf109L, the longest variant of C1orf109, which interacted with R-loop-regulating proteins to trigger R-loop, a three-stranded nucleic acid structure frequently mediated genome instability, accumulation. C1orf109L induce chronic DNA damage to promote P21 upregulation and strongly inhibits cell growth in vitro and in vivo by arresting the cell cycle in the G2 phase. With camptothecin (CPT), an R-loop activator, treatment, C1orf109L further triggers R-loop accumulation-induced DNA damage and promotes cell death by activating cell-death pathway. Furthermore, CPT treatment increases C1orf109L ubiquitination and turnover, which inhibits cell death and promotes the G0/G1 phase of the cell cycle. Therefore, our data illustrated the mechanisms underlying C1orf109L-related cell growth inhibition and provide feasibility and limitations for C1orf109L as a potential target for cancer therapy.
The efficacy and cost of alternative strategies for systematic screening for type 2 diabetes in the U.S. population 45-74 years of age.

OBJECTIVE To simulate the outcomes of alternative strategies for screening the U.S. population 45-74 years of age for type 2 diabetes. RESEARCH DESIGN AND METHODS We simulated screening with random plasma glucose (RPG) and cut points of 100, 130, and 160 mg/dl and a multivariate equation including RPG and other variables. Over 15 years, we simulated screening at intervals of 1, 3, and 5 years. All positive screening tests were followed by a diagnostic fasting plasma glucose or an oral glucose tolerance test. Outcomes include the numbers of false-negative, true-positive, and false-positive screening tests and the direct and indirect costs. RESULTS At year 15, screening every 3 years with an RPG cut point of 100 mg/dl left 0.2 million false negatives, an RPG of 130 mg/dl or the equation left 1.3 million false negatives, and an RPG of 160 mg/dl left 2.8 million false negatives. Over 15 years, the absolute difference between the most sensitive and most specific screening strategy was 4.5 million true positives and 476 million false-positives. Strategies using RPG cut points of 130 mg/dl or the multivariate equation every 3 years identified 17.3 million true positives; however, the equation identified fewer false-positives. The total cost of the most sensitive screening strategy was $42.7 billion and that of the most specific strategy was $6.9 billion. CONCLUSIONS Screening for type 2 diabetes every 3 years with an RPG cut point of 130 mg/dl or the multivariate equation provides good yield and minimizes false-positive screening tests and costs.
The concentration of adiponectin in breast milk is related to maternal hormonal and inflammatory status during 6 months of lactation

Abstract Background: Varying concentrations of adiponectin are present in human breast milk. This study aimed to determine the relationship between milk adiponectin concentration and the hormonal and inflammatory status of breast-feeding women. Methods: Blood and breast milk samples were collected from 157 breast-feeding women enrolled at 1–180 post-partum lactation days. The milk and serum adiponectin concentrations were measured by radioimmunoassays. The serum oestradiol, prolactin, thyroxine, triiodothyronine, cortisol and insulin concentrations were measured by the chemiluminescent immunometric method. The leptin, resistin and ghrelin concentrations were measured by the immunometric methods. Results: The milk, but not serum, adiponectin concentration increased during the 180-day lactation period and displayed a positive correlation (r=0.748; p<0.001) to the lactation day. The milk adiponectin concentration was positively correlated to the maternal serum ghrelin concentration (r=0.299; p<0.001) and inversely to the maternal serum oestradiol (r=–0.366; p<0.001), prolactin (r=–0.444; p<0.001), thyroxine (r=–0.355; p<0.001), triiodothyronine (r=–0.291; p<0.001), cortisol (r=–0.537; p<0.001), and C-reactive protein (r=–0.483; p<0.001) concentrations. The milk adiponectin concentration was positively correlated to the milk leptin (r=0.344; p<0.001) and ghrelin (r=0.458; p<0.001) concentrations, and inversely to milk resistin concentration (r=–0.518; p<0.001). The serum adiponectin concentration in breastfed infants was positively correlated (r=0.711; p<0.001) to the adiponectin concentration in the consumed breast milk. Conclusions: The adiponectin concentration in breast milk increases over time during lactation and is affected by the maternal hormonal and inflammatory status.
Essentials of Public Sector Reform: A Case Study of Croatia

This paper explores the challenges faced by developing countries and countries in transition in their attempt at reforming the inherited bureaucratic public service. The paper explores how the public sector in Croatia has managed to come this far after the turbulent years of political and technocratic dislocation. Croatia is determined to reform its public sector to become eligible for joining the European Union (EU) in near future. This has posed a major challenge for top senior officials and consultants alike. Adopting 'action research' as both a methodology and a strategy, a programme of intervention for change was designed and implemented in the Ministry of Finance. The overall results suggest that for the successful implementation of public sector reforms in the 21st century, attention should focus on strategic issues including systems thinking, HRMD, behavioural and attitudinal change, skills and competencies development and, above all, honest and responsible transformational leadership.
The Primarily Political Functions of the Left-Right Continuum

The concepts of left and right-or liberal and conservative in their American versions-are common terms in politics, in political discourse, and in political analysis. Their meaning, however, is multifaceted at best, elusive at worst, and-over time and across polities-quite divergent. The left-right continuum in politics has been used for 200 years as a means to order a cognitive map of political and ideological relationships. Right and left make sense only if you happen to be the king of France chairing the first joint meeting of the States General on May 5, 1789, or the second meeting on June 23. There the nobility took the place of honor to the king's right, and the representatives of the Third Estate were to the king's left. In August 1789 when the Aristocrats and the Patriots met at the Tuilleries to form the Constituent Assembly in order to write a constitution, it was the Patriots who sat to the left and the Aristocrats to the right of the speaker's tribune. It was on August 26 that this group voted the Declaration of the Rights of Man, a landmark of political thought and practice. Most often in political discourse the left-right continuum has been given economic meaning, referring to equality as opposed to inequality, government intervention as opposed to free enterprise, tolerance of change as opposed to adherence to the status quo. Political activists, commentators, and scientists have widened the scope of the terms to include the major issues of the day. Thus hawks and doves were labeled conservative and liberal in the United States, and similarly in Israel the hawks are right, the doves left. Issues such as divorce laws, abortion, foreign aid, and integration have also been subsumed under these headings. The concept of left-right or liberal-conservative has come to be regarded as an overall ideological dimension, as a kind of "superissue," as ideology. For political savants the continuum denotes ideological content; political scientists and elites use these terms more or less consistently to reflect the political and ideological realities of the time.
Tumor necrosis factor-associated protein 1 (TRAP-1) protects cells from oxidative stress and apoptosis

TRAP-1 is a mitochondrial heat shock protein (HSP), recently identified in Saos-2 osteosarcoma cells adapted to mild oxidative stress induced by diethylmaleate (DEM). TRAP-1 mRNA expression is increased in DEM-adapted cells as well as in tumor cells resistant to 5-fluorouracil and to platin derivatives. Since a strong decrease of TRAP-1 protein levels, upon cisplatin treatment, is observed only in controls but not in the DEM-adapted counterpart, a possible role for this protein in the development of resistant phenotypes could be hypothesized. To characterize the protective role of TRAP-1 against oxidative stress and apoptosis, stable transfectants were generated and characterized for their response to different stress types. These stable clones expressing constitutively high TRAP-1 levels: (i) are more resistant to H2O2-induced DNA damage and to apoptosis by cisplatin; (ii) contain higher reduced glutathione (GSH) levels than control cells; and (iii) do not release the apoptosis-inducing factor into the nucleus upon cisplatin treatment. Furthermore, high TRAP-1 levels interfere with caspase 3 activation. These results confirm the anti-apoptotic role of TRAP-1, and suggest that increased expression of this mitochondrial HSP in DEM-adapted and chemoresistant cells could be part of a pro-survival signaling pathway aimed to evade toxic effects of oxidants and anticancer drugs.
Aldose Reductase-catalyzed Reduction of Aldehyde Phospholipids*

Oxidation of unsaturated phospholipids results in the generation of aldehyde side chains that remain esterified to the phospholipid backbone. Such “core” aldehydes elicit immune responses and promote inflammation. However, the biochemical mechanisms by which phospholipid aldehydes are metabolized or detoxified are not well understood. In the studies reported here, we examined whether aldose reductase (AR), which reduces hydrophobic aldehydes, metabolizes phospholipid aldehydes. Incubation with AR led to the reduction of 5-oxovaleroyl, 7-oxo-5-heptenoyl, 5-hydroxy-6-oxo-caproyl, and 5-hydroxy-8-oxo-6-octenoyl phospholipids generated upon oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC). The enzyme also catalyzed the reduction of phospholipid aldehydes generated from the oxidation of 1-alkyl, and 1-alkenyl analogs of PAPC, and 1-palmitoyl-2-arachidonoyl phosphatidic acid or phosphoglycerol. Aldose reductase catalyzed the reduction of chemically synthesized 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphatidylcholine (POVPC) with a Km of 10 μm. Addition of POVPC to the culture medium led to incorporation and reduction of the aldehyde in COS-7 and THP-1 cells. Reduction of POVPC in these cells was prevented by the AR inhibitors sorbinil and tolrestat and was increased in COS-7 cells overexpressing AR. Together, these observations suggest that AR may be a significant participant in the metabolism of several structurally diverse phospholipid aldehydes. This metabolism may be a critical regulator of the pro-inflammatory and immunogenic effects of oxidized phospholipids.
Adenosine receptor subtype expression and activation influence the differentiation of mesenchymal stem cells to osteoblasts and adipocytes

Osteoblasts and adipocytes differentiate from a common precursor cell, the mesenchymal stem cell (MSC). Adenosine is known to signal via four adenosine receptor subtypes, and significantly, recent findings indicate that these may play a role in MSC differentiation. We therefore investigated adenosine receptor expression and activation during the differentiation of MSCs to osteoblasts and adipocytes. The A2BR was dominant in MSCs, and its expression and activity were transiently upregulated at early stages of osteoblastic differentiation. Both activation and overexpression of A2BR induced the expression of osteoblast‐related genes [Runx2 and alkaline phosphatase (ALP)], as well as ALP activity, and stimulation increased osteoblast mineralization. The expression of A2AR was upregulated during later stages of osteoblastic differentiation, when its activation stimulated ALP activity. Differentiation of MSCs to adipocytes was accompanied by significant increases in A1R and A2AR expression, and their activation was associated with increased adipogenesis. Enhanced A2AR expression was sufficient to promote expression of adipocyte‐related genes (PPARγ and C/EBPα), and its activation resulted in increased adipocytic differentiation and lipid accumulation. In contrast, the A1R was involved mainly in lipogenic activity of adipocytes rather than in their differentiation. These results show that adenosine receptors are differentially expressed and involved in lineage‐specific differentiation of MSCs. We conclude, therefore, that fruitful strategies for treating diseases associated with an imbalance in the differentiation and function of these lineages should include targeting adenosine receptor signal pathways. Specifically, these research avenues will be useful in preventing or treating conditions with insufficient bone or excessive adipocyte formation. © 2011 American Society for Bone and Mineral Research
Balassa-Samuelson and Wage, Price and Unemployment Dynamics in the Spanish Transition to EMU Membership

Abstract This paper provides an empirical investigation of the wage, price and unemployment dynamics that have taken place in Spain during the last two decades. The aim of this paper is to shed light on the impact of the European economic integration on Spanish labour market and the convergence to a European level of prosperity. We found that the Balassa-Samuelson effect, product market competition, and capital liberalization have been the main driving forces in this period. The adjustment dynamics show that Spanish inflation has adjusted in the long run to the European purchasing power parity level (as measured by the German price level) corrected for the Balassa-Samuelson effect. In the medium run this long-run convergence was achieved by two types of Phillips curve mechanisms; one where the inflation/unemployment trade-off was triggered off for different levels of the interest rate and real wage costs, another one where the trade-off was a function of the real exchange rate and the interest rate. Excess wages and/or increasing cost levels in the tradable sector led to higher unemployment rather than higher prices. Thus, much of the burden of adjustment was carried by unemployment in this period.
Blood pressure response during long-term treatment with magnesium is dependent on magnesium status. A double-blind, placebo-controlled study in essential hypertension and in subjects with high-normal blood pressure.

Both experimental and epidemiological studies support the idea of magnesium supplementation in essential hypertension. We added 15 mmol Mg to a free diet in 71 subjects with mild essential hypertension or a high-normal blood pressure in a double-blind, placebo-controlled study over 6 months. The treatment, which raised urinary magnesium excretion 30%, induced no general effects on the blood pressure. However, when the changes in blood pressure in the actively treated group were related to the pretreatment magnesium status, a correlation was found between pretreatment urinary magnesium excretion and the induced change in supine blood pressure (P less than .05) with a blood pressure reduction in subjects with a low pretreatment urinary excretion of magnesium, and a pressor effect in the subjects with the highest pretreatment levels of urinary magnesium. The induced change in blood pressure was furthermore found to be inversely correlated to the changes in serum magnesium and urinary excretion of sodium (P less than .03) induced by treatment indicating that both a direct calcium antagonist action of magnesium at the cellular level as well as a diuretic effect of the increased magnesium load might be involved in the blood pressure effects of magnesium. Pretreatment serum potassium concentration also appeared to be a predictor of the induced change in standing blood pressure (P less than .03). In conclusion, magnesium supplementation does not seem to be effective in unselected mild hypertensive subjects or in subjects with a high-normal blood pressure and can therefore not be generally recommended. (ABSTRACT TRUNCATED AT 250 WORDS)
A fault detection strategy based on intelligent particle filter for nonlinear systems

The general particle filter (GPF) provides an effective tool of fault detection for non-linear systems with non-Gaussian cases. However, due to the particle impoverishment problem of the GPF, the estimation of hidden state in process may get misleading results and thus lead to undesired conclusion for fault detection purpose. To solve this problem, a fault detection strategy, which employs a novel kind of particle filter, i.e. intelligent particle filter (IPF), is proposed in this paper. The proposed IPF strategy could improve the impoverishment problem of GPF and increase the accuracy of hidden state estimation, thus offers desired results for fault detection. Two numerical examples show superior performance of the proposed IPF for fault detection of nonlinear system with high non-Gaussian noises compared with the GPF-based strategy.
Arm movement and gap as factors influencing the reaction time of the second saccade in a double‐step task

To guide our hand for reaching, we explore our visual environment by sequences of saccades. In the present paper, we studied the eye and hand movements of human subjects looking or looking and pointing at a target that is instantaneously displaced two times (double‐step task). It was previously shown that the second saccade has a much longer reaction time than the first one [Feinstein & Williams (1972) Vision Res., 12, 33–44]. The second reaction time is even longer if the subject also has to point to the target with the hand [Lünenburger et al. (2000) Eur. J. Neurosci. , 12, 4107–4116]. The conditions and objective for these effects are further examined in the present paper. It is shown that vision of the hand reduces the first and second saccadic reaction times in parallel. The second reaction time is prolonged for shorter delays between both target steps as well as for larger amplitudes of the second saccade. However, the long second reaction time does not reflect an absolute saccadic refractory period, because a gap before the second target step reduces the second reaction time to a value similar to the first. Hand response time and average hand velocity were increased when the second target step was larger. The response time for the eyes was about 30% of the response time of the hand. We argue that the observed effects reflect the coordination of eye and hand movement to allow a precise and efficient reaching behaviour.
The Performance of the Nottingham Prognosis Index and the Adjuvant Online Decision Making Tool for Prognosis in Early-stage Breast Cancer Patients

Background: Prognostic tools are widely used in the practice of Oncology and have been developed to help stratify patients into specific risk-related grouping. We sought to apply of two such tools used for patients with early-stage breast cancer and to correlate them with actual outcomes. Methods: A retrospective study was designed to include early-stage breast cancer cases seen from 1994 to 2014 at the Seyedoshohada Hospital in Isfahan, Iran. Information was derived from the patients’ records, and indices were derived from prognostic tools. Information was analyzed using descriptive statistics and one sample t-test. Results: In 233 patients, the difference between the predicted overall survival (OS) by the Adjuvant Online (AO) prognosis tools (69.28) and the observed OS (71.2) was not statistically significant (P = 0.52), and the AO prognosis tools had predicted the patients’ OS correctly. In the Nottingham prognosis index (NPI), this difference in all groups except the very poor prognosis group was not statistically significant. Conclusions: Adjuvant Online prognosis tools were capable of predicting the 10-year OS rate although not in all of the subgroups. The NPI was capable of distinguishing good, moderate, and poor survival rates, but this ability was not visible in more specific groups with moderate and poor prognosis.
Voice recognition software: effect on radiology report turnaround time at an academic medical center.

OBJECTIVE Previous studies have documented reductions in turnaround time after implementation of voice recognition software in the generation of radiology reports. Our preliminary observations suggested that improvement in report turnaround time varies among users. The purpose of this study was to analyze the effect of work habits and caseload on such variations. SUBJECTS AND METHODS Data were collected for 9 months before and after the implementation of voice recognition after a 6-month training period. Thirty faculty members were ranked according to their report turnaround time before and after implementation of voice recognition and according to their percentage reduction in report turnaround time. The report turnaround times before and after implementation of voice recognition for faculty were compared with the number of verified reports and work habit type. RESULTS The average report turnaround time for the department before implementation of voice recognition was 28 hours. After implementation of voice recognition, the average turnaround time was 12.7 hours, and the volume of verified reports increased 5% between the two study periods. The improvement in report turnaround time for individual faculty members ranged from -33% to +93%, and the rank order did not change significantly (Spearman coefficient, 0.58; p < 0.05). Faculty members' ranks in report turnaround time did not correlate significantly with volume rank before and after implementation of voice recognition (Spearman coefficients, 0.341 and 0.346; p > 0.05). Faculty members who had type 1 work habits, that is, reviewed, revised, and finalized reports at the time of image review, benefited the most from use of voice recognition. CONCLUSION Use of voice recognition software decreased report turnaround time for the department and for 28 of 30 individual faculty members. Improvement in report turnaround time does not correlate with workload but does correlate with work habits, suggesting human behavior may play a role in determining the outcome of adopting a productivity-enhancing technology.
Periodontal wound healing following GTR therapy of dehiscence-type defects in the monkey: short-, medium- and long-term healing.

OBJECTIVE To describe periodontal wound healing in dehiscence-type defects following guided tissue re-generation (GTR) therapy. METHODS Ten adult Macaca fascicularis monkeys were used. Buccal dehiscence-type defects were created at the maxillary second pre-molars and second molars. After 3 months, GTR surgery was performed. The animals were euthanized at 6 weeks, 6 months and 2 years after surgery. Block biopsies were harvested, and prepared for histological analysis. RESULTS A new attachment apparatus was structured already after 6 weeks of healing. A 10-20 microm thin layer of acellular extrinsic fibre cementum (AEFC) had formed along the instrumented root surface. At 6 months, the thickness of the supracrestal cementum was comparable with that at 6 weeks, while the thickness of the subcrestal cementum had increased to 40-60 microm. In this zone, the cementum consisted of an inner layer of AEFC attached to the circum-pulpal dentin and an outer layer of cellular mixed fibre cementum (CMFC). The numerical extrinsic fibre density was twice that at 6 weeks. At 2 years, the periodontal tissues resembled the pristine periodontium. CONCLUSION Periodontal healing following GTR therapy of recession-type defects will result in a restitutio ad integrum, i.e. healing by re-generation. A continuous maturation process occurs over at least 2 years.