Miracle-dz/UniFAR-FTUs huggingface dataset:
Involvement of EGF receptor activation in the induction of cyclooxygenase‐2 in HaCaT keratinocytes after UVB

Abstract: Because selective inhibition of cyclooxygenase‐2 (COX‐2) suppressed the induction of skin tumors in mice by UV and as UV has been shown to induce expression of COX‐2 in skin and cells, COX‐2 may be crucial for photocarcinogenesis of the skin. We studied the mechanism of UVB‐induced expression of COX‐2 focusing on the signal transduction pathway involved. Hydrogen peroxide (H2O2) treatment of HaCaT cells induced expression of COX‐2 and pretreatment with the antioxidant N‐acetylcysteine (NAC) partly inhibited the UVB‐induced expression of COX‐2 protein in HaCaT cells, suggesting that oxidative stress contributes to COX‐2 induction. To examine the signaling pathways involved in the UVB‐induced expression of COX‐2 in HaCaT cells, we analysed the expression of COX‐2 protein after treatment with various inhibitors of signaling molecules. Inhibition of EGFR by a specific inhibitor and by a neutralizing antibody suppressed the induction of COX‐2 expression by UV. Although a neutralizing antibody to transforming growth factor‐α (TGF‐α) suppressed COX‐2 expression induced by TGF‐α, it did not suppress COX‐2 expression by UV, indicating that a direct activation of EGFR is involved. Treatment of cells at low temperature (4°C) inhibited UVB‐induced JNK activation, but it did not inhibit COX‐2 expression by UV. Inhibitors of MEK, p38 MAP kinase and PI3‐kinase, suppressed the induction of COX‐2 expression by UV. In contrast, an erbB‐2 inhibitor augmented the UVB‐induced increase of COX‐2 protein. These data indicate that oxidative stress in association with activation of EGFR, ERK, p38 MAP kinase, and PI3‐kinase plays crucial roles in the UVB induction of expression of COX‐2.
Differences between measurements of bone mineral densities by quantitative ultrasound and dual-energy X-ray absorptiometry in type 2 diabetic postmenopausal women.

CONTEXT Quantitative ultrasound (QUS) may be more helpful than dual-energy X-ray absorptiometry (DXA) in detecting bone deficits in patients with type 2 diabetes mellitus (T2DM). OBJECTIVE The objective of the study was to compare differences in bone mass measurement by DXA and QUS in T2DM and nondiabetic postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS This clinical investigation was a cross-sectional study in 76 patients with T2DM and 86 nondiabetic postmenopausal women. MAIN OUTCOME MEASURES The primary outcomes were speed of sound (SOS) at the radius, phalanx, and tibia measured by QUS and bone mineral density (BMD) at the lumbar spine (LS), femoral neck (FN), and total hip (TH) measured by DXA. RESULTS BMDs in T2DM patients were higher (LS, 1.06 +/- 0.12 vs. 0.90 +/- 0.23 g/cm(2); FN, 0.80 +/- 0.13 vs. 0.74 +/- 0.12 g/cm(2); TH, 0.87 +/- 0.14 vs. 0.80 +/- 0.13 g/cm(2), respectively, P < 0.001), whereas SOSs were lower than those in nondiabetics (radius, 4044 +/- 178 vs. 4129 +/- 182 m/sec; phalanx, 3902 +/- 207 vs. 3999 +/- 214 m/sec, respectively, P < 0.001). The positive relationships between SOS and BMD (r = 0.26-0.75, P < 0.05) in nondiabetics were not observed in women with T2DM. T2DM impacted negatively on SOSs (radius, beta= -0.223, P <0.01; phalanx, beta= -0.219, P <0.01) but positively on BMDs (LS, beta = 0.314, P < 0.001; FN, beta = 0.173, P < 0.05; TH, beta = 0.203, P <0.01). CONCLUSIONS Differences in bone mass as measured by DXA and QUS in postmenopausal T2DM and nondiabetic women do not change in parallel. QUS can provide useful information in the skeletal assessment of patients with T2DM.
Immunomodulation and T Helper TH1/TH2 Response Polarization by CeO2 and TiO2 Nanoparticles

Immunomodulation by nanoparticles, especially as related to the biochemical properties of these unique materials, has scarcely been explored. In an in vitro model of human immunity, we demonstrate two catalytic nanoparticles, TiO2 (oxidant) and CeO2 (antioxidant), have nearly opposite effects on human dendritic cells and T helper (TH) cells. For example, whereas TiO2 nanoparticles potentiated DC maturation that led towards TH1-biased responses, treatment with antioxidant CeO2 nanoparticles induced APCs to secrete the anti-inflammatory cytokine, IL-10, and induce a TH2-dominated T cell profile. In subsequent studies, we demonstrate these results are likely explained by the disparate capacities of the nanoparticles to modulate ROS, since TiO2, but not CeO2 NPs, induced inflammatory responses through an ROS/inflammasome/IL-1β pathway. This novel capacity of metallic NPs to regulate innate and adaptive immunity in profoundly different directions via their ability to modulate dendritic cell function has strong implications for human health since unintentional exposure to these materials is common in modern societies.
Cost-Effective Enforcement of Access and Usage Control Policies Under Uncertainties

In usage control, access decisions rely on mutable attributes. A reference monitor should reevaluate security policies each time attributes change their values. Identifying all attribute changes in a timely manner is a challenging issue, especially if the attribute provider and the reference monitor reside in different security domains. Some attribute changes might be missed, corrupted, and delayed. As a result, the reference monitor may erroneously grant access to malicious users and forbid it for eligible ones. This paper proposes a set of policy enforcement models that help mitigate the uncertainties associated with mutable attributes. In our model, the reference monitor, as usual, evaluates logical predicates over attributes and, additionally, makes some estimates on how much observed attribute values differ from reality. The final access decision takes into account both factors. We assign costs for granting and revoking access to legitimate and malicious users and compare the proposed policy enforcement models in terms of cost efficiency.
Conjunctival melanoma: bladder and upper urinary tract metastases.

Introduction Malignant melanoma of the conjunctiva is a rare form of melanoma involving the mucosa of the eye and eyelids and represents only 1.6% of all noncutaneous melanomas. It can arise de novo (12%), from an existing nevus (20% to 30%), or, more frequently, from an area of primary acquired melanosis (75%). It is identified most frequently in the perilimbal interpalpebral bulbar conjunctiva. Tumors located in the palpebral, forniceal, and caruncular conjunctival regions are infrequent and are associated with poor prognosis. Because the conjunctival stroma (the substantia propria) contains blood vessels and lymphatics, local and systemic metastases can occur. In most patients, conjunctival melanoma results in metastases first to the draining regional lymph nodes. The preauricular lymph nodes are most commonly involved.We describe a unique case of conjunctival melanoma; the initial presentation of metastasis was hematuria. To our knowledge, this is the first case report of bladder and upper urinary tract metastases from conjunctival melanoma.
Validation of Five Minimally Obstructive Methods to Estimate Physical Activity Energy Expenditure in Young Adults in Semi-Standardized Settings

We compared the accuracy of five objective methods, including two newly developed methods combining accelerometry and activity type recognition (Acti4), against indirect calorimetry, to estimate total energy expenditure (EE) of different activities in semi-standardized settings. Fourteen participants performed a standardized and semi-standardized protocol including seven daily life activity types, while having their EE measured by indirect calorimetry. Simultaneously, physical activity was quantified by an ActivPAL3, two ActiGraph GT3X+’s and an Actiheart. EE was estimated by the standard ActivPAL3 software (ActivPAL), ActiGraph GT3X+ (ActiGraph) and Actiheart (Actiheart), and by a combination of activity type recognition via Acti4 software and activity counts per minute (CPM) of either a hip- or thigh-worn ActiGraph GT3X+ (AGhip + Acti4 and AGthigh + Acti4). At group level, estimated physical activities EE by Actiheart (MSE = 2.05) and AGthigh + Acti4 (MSE = 0.25) were not significantly different from measured EE by indirect calorimetry, while significantly underestimated by ActiGraph, ActivPAL and AGhip + Acti4. AGthigh + Acti4 and Actiheart explained 77% and 45%, of the individual variations in measured physical activity EE by indirect calorimetry, respectively. This study concludes that combining accelerometer data from a thigh-worn ActiGraph GT3X+ with activity type recognition improved the accuracy of activity specific EE estimation against indirect calorimetry in semi-standardized settings compared to previously validated methods using CPM only.
The Correlation of Coronary Angiography and the Electrocardiographic Response to Maximal Treadmill Testing in 76 Asymptomatic Men

This report presents the results of coronary angiography in 76 asymptomatic aircrewmen with exercise testing responses suggestive of coronary artery disease. There were two subgroups: 18 men with normal resting electrocardiograms; and 58 men with a history of repolarization changes on their resting electrocardiogram after at least one normal ECG. Of the 76 men, 53% had angiographically demonstrated coronary artery disease, and many of them had high risk lesions. Forty-seven percent had no angiographic evidence of lesions and were recommended for return to flying status. Those individuals with normal angiograms will be closely followed at the USAF School of Aerospace Medicine in an effort to determine their natural history and prognosis. The findings in this study, the lack of significant complications resulting from coronary angiography, the concern for public safety, and the economics of maintaining a flying force all support the continued use of elective coronary angiography in selected asymptomatic aircrewmen.
Inherited predisposition to myeloid neoplasms

Myeloid neoplasms include myelodysplastic/ myeloproliferative neoplasms (MDS/MPN) and acute myeloid leukemia (AML). While majority of these disorders are still sporadic, it is becoming clear that a subset of them have a germline predisposition and is familial in nature. With the advancement and integration of molecular studies, it has been recognized that approximately 5-10% of hematological malignancies have germline predisposition. Timely diagnosis of these cases is not only important for treatment purposes i.e. tailor-made conditioning regime for some of the bone marrow failure syndromes but also for genetic counseling, risk assessment and follow-up of the family members. Recent updates to “WHO classification of tumours of haematopoetic and Lymphoid tissues”(1) has also identified its importance and included this as a major change to its WHO revision. Now these myeloid neoplasms (MDS, MDS/MPN and Acute leukemia) have their own WHO sub-category “Myeloid Neoplasms with Germline Predisposition. ” (Table 1) also known as familial predisposition to myeloid disorders (FPMD).
The OXL format for the exchange of integrated datasets

Abstract A prerequisite for systems biology is the integration and analysis of heterogeneous experimental data stored in hundreds of life-science databases and millions of scientific publications. Several standardised formats for the exchange of specific kinds of biological information exist. Such exchange languages facilitate the integration process; however they are not designed to transport integrated datasets. A format for exchanging integrated datasets needs to i) cover data from a broad range of application domains, ii) be flexible and extensible to combine many different complex data structures, iii) include metadata and semantic definitions, iv) include inferred information, v) identify the original data source for integrated entities and vi) transport large integrated datasets. Unfortunately, none of the exchange formats from the biological domain (e.g. BioPAX, MAGE-ML, PSI-MI, SBML) or the generic approaches (RDF, OWL) fulfil these requirements in a systematic way. We present OXL, a format for the exchange of integrated data sets, and detail how the aforementioned requirements are met within the OXL format. OXL is the native format within the data integration and text mining system ONDEX. Although OXL was developed with the ONDEX system in mind, it also has the potential to be used in several other biological and non-biological applications described in this paper. Availability: The OXL format is an integral part of the ONDEX system which is freely available under the GPL at http://ondex.sourceforge. net/. Sample files can be found at http://prdownloads.sourceforge. net/ondex/ and the XML Schema at http://ondex.svn. sf.net/viewvc/*checkout*/ondex/trunk/backend/data/xml/ondex.xsd.
Dynamic Routing and Wavelength Assignment using Adaptive Weight Function for All-Optical WDM Networks

We propose a novel WDM aware weight function for solving the Routing and Wavelength Assignment (RWA) problem in optical WDM networks taking into consideration factors like number of used wavelengths , availability of free wavelengths and route length jointly under dynamic traffic conditions. The performance of proposed routing strategy is studied in combination with first-fit, and most used wavelength heuristics using simulation with and without wavelength continuity constraint. Firstly we demonstrate that the recently proposed weighted least congested routing algorithm with first-fit wavelength assignment (WLCR-FF) if instead used with most used wavelength assignment, gives better blocking performance. We further compare the performance of new weight function with most used wavelength assignment with systems employing WLCR-FF and FAR-FF algorithms for ring and mesh networks. The results show that the routing based on proposed weight function together with most used wavelength assignment achieve better performance in terms of blocking probability.
Incremental learning of environment interactive structures from trajectories of individuals

This work proposes a novel method for estimating the influence that unknown static objects might have over mobile agents. Since the motion of agents can be affected by the presence of fixed objects, it is possible use the information about trajectories deviations to infer the presence of obstacles and estimate the forces involved in a scene. Artificial neural networks are used to estimate a non-parametric function related to the velocity field influencing moving agents. The proposed method is able to incrementally learn the velocity fields due to external static objects within the monitored environment. It determines whether an object has a repulsive or an attractive influence and provides an estimation of its position and size. As stationarity is assumed, i.e., time-invariance of force fields, learned observation models can be used as prior knowledge for estimating hierarchically the properties of new objects in a scene.
The androgen receptor CAG repeat polymorphism and risk of breast cancer in the Nurses' Health Study.

Shorter alleles of a polymorphic [CAG](n) repeat in exon 1 of the androgen receptor (AR) have been associated with increased risk of prostate cancer and decreased risk of breast cancer. We prospectively assessed the association between the [CAG](n) repeat polymorphism in the androgen receptor and breast cancer risk among Caucasian women in a case-control study nested within the Nurses' Health Study cohort (cases, n = 727; controls, n = 969). In addition, we assessed whether androgen receptor genotype influences endogenous steroid hormone levels in women and whether the associations between androgen receptor alleles and breast cancer risk differed according to established breast cancer risk factors. Women with one or more long AR [CAG](n) repeat alleles (>or=22 repeats) were not at increased risk of breast cancer [odds ratio (OR), 1.06; 95% confidence interval (CI), 0.83-1.35]. Significant associations were not observed between AR genotypes comprised of two short alleles ([CAG](n) <or=20 versus both alleles >or=22: OR, 0.92; 95% CI, 0.62-1.36) or two long alleles ([CAG](n) >or= 25 versus both alleles <or= 22: OR, 1.42; 95% CI, 0.81-2.50) and breast cancer risk. We also observed no strong overall association between average repeat length and breast cancer risk (OR, 1.04 per CAG repeat; 95% CI, 0.99-1.10) or between average repeat length and plasma hormone levels. We also examined the cross-classification of AR genotype and first-degree family history of breast cancer. Compared with women with both alleles <22 and no family history, we observed a significant positive association limited to women with both a first-degree family history of breast cancer and longer alleles (one or two [CAG](n) alleles >or=22; OR, 1.70; 95% CI, 1.20-2.40; P for interaction = 0.04). In summary, we observed no overall relation of AR genotype with breast cancer risk among mostly postmenopausal Caucasian women. However, these data suggest that longer AR [CAG](n) repeat alleles may increase breast cancer risk among women with a first-degree family history of breast cancer.
Chemopreventive Effects of Sarcophine-diol on Ultraviolet B-induced Skin Tumor Development in SKH-1 Hairless Mice

Sarcophine-diol (SD), one of the structural modifications of sarcophine, has shown chemopreventive effects on 12-dimethylbenz(a)anthracene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted skin tumor development in female CD-1 mice. The objective of this study was to determine the chemopreventive effects of SD on UVB-induced skin tumor development in hairless SKH-1 mice, a model more relevant to human skin cancer, and to determine the possible mechanisms of action. Carcinogenesis was initiated and promoted by UVB radiation. Female hairless SKH-1 mice were divided into two groups having 27 mice in each group: control and SD treatment. The control group was topically treated with 100 μL acetone and SD treatment group was topically treated with SD (30 μg/100 μL in acetone) 1 hour before each UVB radiation for 32 weeks. Tumor counts were recorded on a weekly basis for 30 weeks. Effects of SD on the expression of caspases were investigated to elucidate the possible mechanism of action. The proteins from epidermal homogenates of experimental mice were used for SDS-PAGE and Western blotting using specific antibodies against caspase-3, caspase-8 and caspase-9 respectively. TUNEL assay was used for determining DNA fragmented apoptotic cells in situ. Results showed that at the end of experiment, tumor multiplicity in control and SD treatment groups was 25.8 and 16.5 tumors per mouse respectively. Furthermore, Topical treatment of SD induced DNA fragmented apoptotic cells by upgrading the expressions of cleaved caspase-3 and caspase-8. This study clearly suggested that SD could be an effective chemopreventive agent for UVB-induced skin cancer by inducing caspase dependent apoptosis.
ERP Systems Development: Enhancing Organization's Strategic Control through Monitoring Agents

Enterprise Resource Planning Systems (ERP) are powerful software packages that enable the integration of a variety of business activities. There are many success stories of ERP systems use and implementation, but there are also significant evidence of failures. So far, there is not enough research that investigates the technical factors that determine the success of use of an ERP system.This paper investigates the case study of a bus company that needs to enhance its ERP system to support the alignment between business processes and strategy. The specific problem of the company was the low level of managerial control over the bus maintenance process, resulting in a poor performance of the process and a consequent low quality of the final service to the customer. The solution to the problem we proposed was the integration of monitoring agents called probes into the ERP system that are able to link the process performances to the strategic goals, objectives or constraints.The introduction of the probes enhances the organization's strategic control by offering a continuous monitoring of the strategic goals achievement, hence increasing the understanding of the company behavior. That has determined the adoption of strategic changes that managed to obtain higher performances of the maintenance process and consequentially an higher quality of the offered service.
The Dublo architecture pattern for smooth migration of business information systems: an experience report

While the importance of multi-tier architectures for enterprise information systems is widely accepted and their benefits are well published, the systematic migration from monolithic legacy systems toward multi-tier architectures is known to a much lesser extent. In this paper we present a pattern on how to re-use elements of legacy systems within multi-tier architectures, which also allows for a smooth migration path. We report on experience we made with migrating existing municipal information systems towards a multitier architecture. The experience is generalized by describing the underlying pattern such that it can be re-used for similar architectural migration tasks. The emerged Dublo pattern is based on the partial duplication of business logic among legacy system and newly deployed application server. While this somehow contradicts the separation-of-concerns principle, it offers a high degree of flexibility in the migration process and allows for a smooth transition. Experience with the combination of outdated database technology with modern server-side component and Web services technologies is discussed. In this context, we also report on technology and architecture selection processes.
VIP modulates neuronal nicotinic acetylcholine receptor function by a cyclic AMP-dependent mechanism

Neuronal nicotinic ACh receptors (AChRs) mediate synaptic transmission throughout the nervous system, and are regulated by cellular processes and interactions that include second messenger signaling pathways. In the case of chick ciliary ganglion neurons, activation of the cAMP- dependent signaling pathway with cAMP analogs enhances ACh sensitivity in a manner consistent with an increase in the number of functional nicotinic receptors. We have now identified vasoactive intestinal peptide (VIP) as a neuromodulator or “first messenger” in the cAMP- mediated pathway that regulates neuronal AChRs. Using cAMP imaging and biochemical detection assays, we find that bath application of VIP elevates intracellular cAMP in freshly isolated ciliary ganglion neurons within minutes. The VIP treatment also enhances neuronal ACh sensitivity assessed with whole-cell recording. The enhanced ACh sensitivity produced by VIP appears with a short latency, similar to that associated with the increase in cAMP, and is not additive with the enhanced ACh sensitivity produced by bath application of a cAMP analog. In contrast, calcitonin gene-related peptide (CGRP), known to regulate muscle nicotinic AChRs via a cAMP-dependent pathway, has no detectable effect on levels of either cAMP or ACh sensitivity in the neurons. The results indicate that VIP enhances the ACh sensitivity of ciliary ganglion neurons via a cAMP-dependent signaling pathway, presumably by interaction with a specific receptor. Since VIP-like immunoreactivity is present in the presynaptic nerve terminals of avian ciliary ganglia, a VIP-like peptide could modulate AChRs in vivo.
A CASE STUDY OF IV&V COST EFFECTIVENESS

This paper looks at the independent verification and validation (IV&V) of NASA's Space Shuttle Day of Launch 1-Load Update (DoLILU) project. IV&V is defined. The system's development life cycle is explained. Data collection and analysis are described. DoLILU Issue Tracking Reports (DITRs) authored by IV&V personnel are analyzed to determine the effectiveness of IV&V in finding errors before the code, testing, and integration phase of the software development life cycle. The study's findings are reported along with the limitations of the study and planned future research. 1