Miracle-dz/UniFAR-FTUs huggingface dataset:
The inhibition of JNK and p38 MAPKs downregulates IL-10 and differentially affects c-Jun gene expression in human monocytes

Interleukin-10 is the most important anti-inflammatory cytokine that controls the progress of the immune response. The molecular mechanisms driving the IL10 gene regulation are not well understood. To gain insight into this process we studied the IL-10 expression on mRNA and protein levels, together with c-Jun, FOXP3 and RelA transcription factors gene expression in human monocytes. We investigated also, the involvement of JNK and p38 transduction pathways in IL-10, c-Jun, FOXP3 and RelA gene expression. The quantity determination of IL-10 was performed by ELISA. qRT-PCR was performed for the detection of mRNA transcripts. The pharmacological inhibitors SP600125 and SB202190 were used to explore JNK and p38 MAPKs involvement in IL10, c-Jun, FOXP3 and RelA gene expression. The measurement of IL-10 mRNA synthesis, triggered by lipopolysaccharide (LPS) or C3 binding glycoprotein (C3bgp) showed that stimulation with both inducers led to similar high level of IL-10 mRNA synthesis, whereas C3bgp was the stronger inducer of IL-10 production than LPS. JNK and p38 inhibition significantly decreased IL-10 expression in stimulated cells. C3bgp and LPS induced comparatively low expression of FOXP3, RelA and c-Jun mRNA in monocytes. The inhibition of p38 MAPK in stimulated monocytes resulted in significant enhancement of c-Jun mRNA synthesis suggesting the functional relation between p38 MAPK and c-Jun gene expression. We concluded that the IL10 gene transcription did not associate with enhancement of c-Jun, RelA and FOXP3 gene expression and strictly depended on the JNK and p38 MAPKs activation in stimulated human monocytes.
Antileukemic effects of piperlongumine and alpha lipoic acid combination on Jurkat, MEC1 and NB4 cells in vitro.

AIM OF STUDY This research indicated to evaluate the effects of piperlongumine (PL), a biologically active alkaloid, and alpha lipoic acid (ALA), a naturally occurring cofactor existed in multienzyme complexes regulating metabolism on leukemia cells. Excessive production of reactive oxygen species (ROS) can lead to oxidative stress, a state that has been observed in several hematopoietic malignancies, including acute and chronic myeloid leukemias. The importance of the association between oxidative stress and malignancy is not currently clear; however, there is evidence that tumor.derived ROS may promote cell survival, migration and metastasis, proliferation and even drug.resistance depending on the origin of the cancer. Increased oxidative stress in leukemic cells may represent a potential therapeutic target, although there are differing opinions on whether therapeutic strategies should aim to antagonize or further promote oxidative stress in leukemic cells. MATERIALS AND METHODS The effects of PL alone (5, 15, 30 μM) and in combination (30 μ M) with ALA (200 μ M) on Jurkat, NB4 and MEC1 leukemia cell lines were investigated through MTT, caspase-3 and cyclooxygenase-2 (COX-2) activities. RESULTS Inhibition of COX-2 and the induction of caspase.3 cleavage in Nb4 (acute promyelocytic leukemia) cells were found to be significant following PL application and synergistic effects with combination of ALA (inhibition of COX-2 as 23.74% and 3.55-fold increase of caspase-3). CONCLUSION PL and ALA may have a potential value as a therapeutic agent for patients with acute promyelocytic leukemia.
Emergency medicine residents' shiftwork tolerance and preference.

OBJECTIVES To determine the shift lengths currently worked by emergency medicine (EM) residents and their shift length preferences, and to determine factors associated with EM residents' subjective tolerance of shiftwork. METHODS A survey was sent to EM-2 through EM-4 allopathic EM residents in May 1996. This questionnaire assessed the residents' shift length worked, shift length preferences, night shift schedules, and self-reported ability to overcome drowsiness, sleep flexibility, and morningness-eveningness tendencies. When providing shift length preferences, the residents were asked to assume a constant total number of hours scheduled per month. RESULTS Seventy-eight programs participated, and 62% of 1,554 eligible residents returned usable surveys. Current shift lengths worked were 8 hours (12%), 10 hours (13%), 12 hours (37%), combinations of 8-hour, 10-hour, or 12-hour (34%) shifts, and other combinations (4%). Seventy-three percent of the respondents indicated that they preferred to work 8-hour or 10-hour shifts, and only 21% preferred a 12-hour shift. Shiftwork tolerance was recorded as: not well at all (2%), not very well (14%), fairly well (70%), and very well (14%). The EM residents' eveningness preference, ability to overcome drowsiness, sleep flexibility, younger age, and having no children at home were all associated with greater shiftwork tolerance. CONCLUSIONS Emergency medicine residents generally tolerate shiftwork well and prefer 8-hour or 10-hour shift lengths compared with 12-hour shift lengths. Emergency medicine residencies with 12-hour shifts should consider changing residents' shifts to shorter shifts.
How Do Established Firms Produce Breakthrough Innovations? Managerial Identity‐Dissemination Discourse and the Creation of Novel Product‐Market Solutions

Despite the legacy of experience, some established firms are able to avoid a mindset, behaviors, and routines that can be expected to lead them down paths of local search and incremental product innovations of ever-declining value. Indeed, established firms are often adept at introducing successful path-breaking innovations. To explain this apparent paradox, this article draws on the organizational identity literature to present a model that ascribes breakthrough innovations by established firms to managerial identity-dissemination discourse (MIDD). MIDD is argued to provide a sense-giving framework, which fosters an understanding of the firm as a nexus of values around which the firm can be continuously rediscovered and reconstituted in new ways. By exposing the firm as an idea that can assume fresh forms in terms of product-market combinations, MIDD stimulates and coordinates creative endeavor, thus increasing the disposition to produce breakthrough innovations. The model also suggests that the impact of MIDD is likely to depend on transformational leadership and the level of centralization and formalization in the company. The results of a cross-sectional empirical study provide support for the model. In contrast to the focus of earlier research on behavioral and structural explanations for breakthroughs by established firms, this article advances understanding by offering a cognitive explanation. In doing so, the article highlights that creativity and innovation in firms are mentally located in an interpretive schema of the firm's identity, which has important implications in relation to organizing for breakthroughs. The article discusses these implications with particular reference to the use of multifunctional teams and advanced information and communication technologies for facilitating breakthroughs.
The hprK gene of Enterococcus faecalis encodes a novel bifunctional enzyme: the HPr kinase/phosphatase

The HPr kinase of Gram‐positive bacteria is an ATP‐dependent serine protein kinase, which phosphorylates the HPr protein of the bacterial phosphotransferase system (PTS) and is involved in the regulation of carbohydrate metabolism. The hprK gene from Enterococcus faecalis was cloned via polymerase chain reaction (PCR) and sequenced. The deduced amino acid sequence was confirmed by microscale Edman degradation and mass spectrometry combined with collision‐induced dissociation of tryptic peptides derived from the HPr kinase of E. faecalis. The gene was overexpressed in Escherichia coli, which does not contain any ATP‐dependent HPr kinase or phosphatase activity. The homogeneous recombinant protein exhibits the expected HPr kinase activity as well as a P‐Ser‐HPr phosphatase activity, which was assumed to be a separate enzyme activity. The bifunctional HPr kinase/phosphatase acts preferentially as a kinase at high ATP levels of 2 mM occurring in glucose‐metabolizing Streptococci. At low ATP levels, the enzyme hydrolyses P‐Ser‐HPr. In addition, high concentrations of phosphate present under starvation conditions inhibit the HPr kinase activity. Thus, a putative function of the enzyme may be to adjust the ratio of HPr and P‐Ser‐HPr according to the metabolic state of the cell; P‐Ser‐HPr is involved in carbon catabolite repression and regulates sugar uptake via the phosphotransferase system (PTS). Reinvestigation of the previously described Bacillus subtilis HPr kinase revealed that it also possesses P‐Ser‐HPr phosphatase activity. However, contrary to the E. faecalis enzyme, ATP alone was not sufficient to switch the phosphatase activity of the B. subtilis enzyme to the kinase activity. A change in activity of the B. subtilis HPr kinase was only observed when fructose‐1,6‐bisphosphate was also present.
DNA Interactions Probed by Hydrogen-Deuterium Exchange (HDX) Fourier Transform Ion Cyclotron Resonance Mass Spectrometry Confirm External Binding Sites on the Minichromosomal Maintenance (MCM) Helicase*

The archaeal minichromosomal maintenance (MCM) helicase from Sulfolobus solfataricus (SsoMCM) is a model for understanding structural and mechanistic aspects of DNA unwinding. Although interactions of the encircled DNA strand within the central channel provide an accepted mode for translocation, interactions with the excluded strand on the exterior surface have mostly been ignored with regard to DNA unwinding. We have previously proposed an extension of the traditional steric exclusion model of unwinding to also include significant contributions with the excluded strand during unwinding, termed steric exclusion and wrapping (SEW). The SEW model hypothesizes that the displaced single strand tracks along paths on the exterior surface of hexameric helicases to protect single-stranded DNA (ssDNA) and stabilize the complex in a forward unwinding mode. Using hydrogen/deuterium exchange monitored by Fourier transform ion cyclotron resonance MS, we have probed the binding sites for ssDNA, using multiple substrates targeting both the encircled and excluded strand interactions. In each experiment, we have obtained >98.7% sequence coverage of SsoMCM from >650 peptides (5–30 residues in length) and are able to identify interacting residues on both the interior and exterior of SsoMCM. Based on identified contacts, positively charged residues within the external waist region were mutated and shown to generally lower DNA unwinding without negatively affecting the ATP hydrolysis. The combined data globally identify binding sites for ssDNA during SsoMCM unwinding as well as validating the importance of the SEW model for hexameric helicase unwinding.
The association between contact sensitization and atopic disease by linkage of a clinical database and a nationwide patient registry

Experimental studies have shown that individuals with atopic dermatitis are likely to have suppressed contact sensitivity secondary to their disease whereas some clinical and epidemiological studies have shown that individuals with atopic dermatitis might have a higher prevalence of contact sensitization than controls. The objective was to study the association between contact sensitization and, respectively, atopic dermatitis and asthma using clinical databases.
The Human Capital Valuation: A Methodological Proposal Among Intellectual Capital Elements

Intellectual Capital (IC) is an important source of value for companies and in recent years has been the focus of attention for scholars. In a knowledge-based economic scenario the role of human resources has been reallocated over time in the theory of the firm to a higher degree than in the past. The worker's labor and management have been transformed as a result of the growing attention to the intangible assets held by each business system. In knowledge economy, manufacturing industries are investing more and more in the processes of scientific and technological research in order to introduce new knowledge in production systems and ensure its survival by creating business value. The competitive firm invests in new productive ideas through scientific and technological research, the human factor and services. The knowledge worker, at every organizational level, has the knowledge that allows the organization to be competitive and deal with the complexity of the environment by creating intellectual added value. The traditional factors of "old economy" based on physical assets has been replaced, or at least reinforced with the belief that the "new economy" takes it steps mainly through CI. The aim of this paper is to examine the methods of evaluation of human capital and to provide an empirical methodology proposed by using an intersection logic concerning the increase in value of the three components of intelle ctual capital. In particular, the proposed methodology consists in the construction of an adjusted multiplier based on a simplified version of VAIC TM capable of expressing a direct relationship with the Return on Equity (ROE) from the perspective of creating value for shareholders based on the dynamics of the company‘s performance compared to that of industry.
Antiprotozoal activities of some constituents of Markhamia tomentosa (Bignoniaceae)

Abstract Phytochemical investigation of an ethyl-acetate extract of the stem bark of Markhamia tomentosa (Bignoniaceae), which had good antimalarial activity in vitro, resulted in the isolation of eight known compounds: 2-acetylnaphtho[2,3-b]furan-4,9-dione (1), 2-acetyl-6-methoxynaphtho[2,3-b]furan-4,9-dione (2), oleanolic acid (3), pomolic acid (4), 3-acetylpomolic acid (5), tormentic acid (6), β-sitosterol (7) and β-sitosterol-3-O-β-D-glucopyranoside (8). The structures of these compounds were established by spectroscopic methods. Each of compounds 1, 2, 4 and 5 was evaluated in vitro for its antiprotozoal activities against the ring stages of two chloroquine-resistant strains of Plasmodium falciparum (K1 and W2), the amastigotes of Leishmania donovani, and the bloodstream trypomastigotes of Trypanosoma brucei rhodesiense (the species responsible for human malaria, visceral leishmaniasis and African trypanosomiasis, respectively). Although compounds 1 and 2 exhibited potent antiprotozoal activities, they also showed high toxicity against a mammalian (L-6) cell line.
Inappropriate secretion of follicle-stimulating hormone and luteinizing hormone in polycystic ovarian disease.

ABSTRACT The concentrations and the pattern of gonadotropin secretion were determined in 16 patients with documented polycystic ovarian disease (PCO). Sequential measurements of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in serum by specific radioimmunoassays were made. The data showed that the mean LH concentrations in patients with PCO were consistently and significantly higher than the mean LH concentration observed during the follicular phase of the normal cycle. There was random fluctuation. By contrast, the mean serum FSH concentrations were remarkably constant and were significantly lower than the mean FSH concentrations observed during the early follicular phase, but comparable to the levels of FSH during the late follicular phase of the normal cycle. The daily concentrations of LH in individual patients were highly variable. Likewise, the pattern of LH secretion varied markedly from patient to patient. In general, the serum LH pattern was that of an erratic fluctuation with a.
Antioxidants from Tropical Herbs

Plants that contain high amounts of polyphenolic compounds are potential candidates for natural antioxidant sources. Studies are on going in the search for new sources of antioxidants. Not much data are available on the antioxidant capacity of tropical herbs. With this in mind, 19 commonly consumed Malaysian herbs were analyzed for their polyphenolic content and antioxidant activities. A majority of these plants have never been studied before with regards to their polyphenolic content and antioxidant activities. The shoots of Anacardium occidentale, the shoots and fruits of Barringtonia racemosa, Pithecellobium jiringa and Parkia speciosa had high polyphenolic contents (> 150 μg gallic acid equivalents/mg dried plant) and antioxidant activities when measured using the ferric reducing antioxidant power (FRAP) (>1.2 mM) and Trolox equivalent antioxidant capacity (TEAC) assays (>2.4 mM). A strong correlation was observed between the two antioxidant assays (FRAP vs TEAC) implying that the plants could both scavenge free radicals and reduce oxidants. There was also a strong correlation between the antioxidant activities and polyphenolic content suggesting the observed antioxidant activities were contributed mainly by the polyphenolics in the plants.
Application of probability density forecast of demand in short term portfolio optimization

Electricity demand is a random variable. Most point forecasting methods do not give any information about stochastic nature of the demand. A probability density forecast (PDF) provides a complete description of the random variable (i.e., demand) by assigning probability to its possible values in future. Some work has been published on probability density forecast of demand in the short, medium and long term. However, application of such forecasts has not been discussed in detail. We propose an application of the PDF in short term (day-ahead) portfolio optimization (PO) for a load serving entity. PO helps in determining an optimal quantity of power to be procured from different available sources of supply. The proposed formulation not only considers the stochasticity in price but also in the demand. The PO problem also models the expected cost of errors. We have formulated a linear programming problem for portfolio optimization with conditional value-at-risk (CVaR). A case study is presented to illustrate the proposed approach.
Harmonizing textual and graphical visualizations of domain specific models

Domain-specific models, and the modeling languages that support them, have played a central role in the success of model-driven development and its ability to bridge the abstraction gap between software implementation technologies and human developers. However, the current generation of domain-specific modeling tools is firmly split into two camps --- those that support textual domain-specific languages and those that support graphical domain-specific languages. Both camps have enjoyed significant success, but at the time of writing no mainstream tool supports both at the same time. This stops developers from swapping freely between textual and graphical visualizations of a given subject of interest, even if each form has clear advantages and/or disadvantages for different stakeholders. In this paper we present an environment which offers a solution to this problem by strictly separating concerns for notation (i.e. concrete syntax) and concerns for concepts (i.e. abstract syntax) and allowing them to be connected and mixed dynamically as required.
NdhO, a Subunit of NADPH Dehydrogenase, Destabilizes Medium Size Complex of the Enzyme in Synechocystis sp. Strain PCC 6803*

Background: There is no report on Ndh subunits that destabilize the NDH-1 complex and repress activity. Results: Deletion of ndhO in Synechocystis 6803 increased the activity of cyclic electron transport around photosystem I, whereas overexpression repressed the activity and destabilized NDH-1M complex. Conclusion: NdhO destabilizes NDH-1M and represses the activity. Significance: NdhO is a new type subunit that controls NDH-1M negatively. Two mutants that grew faster than the wild-type (WT) strain under high light conditions were isolated from Synechocystis sp. strain PCC 6803 transformed with a transposon-bearing library. Both mutants had a tag in ssl1690 encoding NdhO. Deletion of ndhO increased the activity of NADPH dehydrogenase (NDH-1)-dependent cyclic electron transport around photosystem I (NDH-CET), while overexpression decreased the activity. Although deletion and overexpression of ndhO did not have significant effects on the amount of other subunits such as NdhH, NdhI, NdhK, and NdhM in the cells, the amount of these subunits in the medium size NDH-1 (NDH-1M) complex was higher in the ndhO-deletion mutant and much lower in the overexpression strain than in the WT. NdhO strongly interacts with NdhI and NdhK but not with other subunits. NdhI interacts with NdhK and the interaction was blocked by NdhO. The blocking may destabilize the NDH-1M complex and repress the NDH-CET activity. When cells were transferred from growth light to high light, the amounts of NdhI and NdhK increased without significant change in the amount of NdhO, thus decreasing the relative amount of NdhO. This might have decreased the blocking, thereby stabilizing the NDH-1M complex and increasing the NDH-CET activity under high light conditions.
A Study on Forecasting Spare Parts Demand based on Data-Mining

Demand forecasting is one of the most critical tasks in defense logistics, because the failure of the task can bring about a huge waste of budget. Up to date, ROK-MND(Republic of Korea - Ministry of National Defense) has analyzed past component consumption data with time-series techniques to predict each component's demand. However, the accuracy of the prediction still needs to be improved. In our study, we attempted to find consumption pattern using data mining techniques. We gathered an 18,476 component consumption data first, and then derived diverse features to utilize them in identification of demanding patterns in the consumption data. The results show that our approach improves demand forecasting with higher accuracy
Urinary angiotensinogen excretion and ambulatory blood pressure

Objective: Previous studies have demonstrated that urinary angiotensinogen excretion, a biomarker of the intrarenal renin–angiotensin system activity, is associated with clinic blood pressure (BP). In the present study, we investigated the determinants of urinary angiotensinogen excretion and its associations with ambulatory BP. Methods: The study participants were suspected hypertensive patients being off antihypertensive medication for at least 2 weeks and referred to our hypertension clinic for 24-h ambulatory BP monitoring. Ambulatory hypertension was defined as a 24-h BP of at least 130 mmHg systolic or 80 mmHg diastolic. We collected a first morning urine sample for the measurement of angiotensinogen by ELISA kits. Results: The 446 participants (mean age 51.7 years) included 218 (48.9%) men, and 275 (61.7%) patients had ambulatory hypertension. In addition to age and sex, 24-h urinary sodium excretion was an independent determinant of urinary angiotensinogen-to-creatinine ratio (P = 0.0008). Urinary angiotensinogen-to-creatinine ratio was 34% (P = 0.04) and 82% (P ⩽ 0.0001) higher in tertiles 2 and 3 of 24-h urinary sodium excretion, respectively, than in tertile 1. In multivariate analyses, urinary angiotensinogen-to-creatinine ratio was significantly and positively associated with clinic and ambulatory BP (P ⩽ 0.02) and the prevalence of ambulatory hypertension [odds ratio (95% confidence interval) associated with two-time increase, 1.24 (1.09–1.39); P = 0.0007]. Conclusion: Urinary angiotensinogen excretion is higher with greater urinary sodium excretion, and is associated with clinic and ambulatory BP.