Miracle-dz/UniFAR-FTUs huggingface dataset:
Retinal pigment epithelium protection from oxidant-mediated loss of MMP-2 activation requires both MMP-14 and TIMP-2.

PURPOSE Eyes with age-related macular degeneration (AMD) demonstrate accumulation of specific deposits and extracellular matrix (ECM) molecules under the retinal pigment epithelium (RPE). Metalloproteinases (MMP) are crucial regulators of basement membrane and ECM turnover. Accordingly, loss of RPE MMP activity most likely leads to excessive accumulation of collagen and other ECM, a potential mechanism for formation of deposits. A prior study showed that MMP-2 activity, but not pro-MMP-2 protein, decreases after RPE oxidative injury, indicating that oxidant injury disrupts the enzymatic cleavage of pro-MMP-2. Activation of MMP-2 requires the formation of a tri-molecular complex of pro-MMP-2, MMP-14, and tissue inhibitor of metalloproteinases (TIMP)-2. Therefore, a study was conducted to investigate the impact of oxidant injury on the interaction between these three molecules. METHODS Human GFP-RPE cells were oxidant injured by transient exposure to H2O2 and myeloperoxidase, and the time course of recovery determined. Supernatants and cell lysates were collected for analysis of MMP-2, MMP-14, and TIMP-2 activity, mRNA and protein expression. In some studies, overexpression with either MMP-14 or TIMP-2 was performed to revert the cells to a preinjury phenotype. RESULTS Transient injury resulted in a decrease of both MMP-14 and TIMP-2 activity and protein. Overexpression of each single molecule failed to prevent the injury-induced decrease of MMP-2 activity. In contrast, overexpression of MMP-14 together with the addition of exogenous TIMP-2 prevented the reduction of MMP-2 activation. CONCLUSIONS Loss of MMP-2 activity after oxidant injury is caused by the downregulation of MMP-14 and TIMP-2. Overexpression of either MMP-14 or TIMP-2 alone before oxidant injury is not enough to prevent loss of MMP-2 activity. All three components of the tri-molecular complex must be present to preserve normal MMP-2 activity after oxidant injury.
Bronchiectasis: Phenotyping a Complex Disease

ABSTRACT Bronchiectasis is a long-neglected disease currently experiencing a surge in interest. It is a highly complex condition with numerous aetiologies, co-morbidities and a heterogeneous disease presentation and clinical course. The past few years have seen major advances in our understanding of the disease, primarily through large real-life cohort studies. The main outcomes of interest in bronchiectasis are symptoms, exacerbations, treatment response, disease progression and death. We are now more able to identify clearly the radiological, clinical, microbiological and inflammatory contributors to these outcomes. Over the past couple of years, multidimensional scoring systems such as the Bronchiectasis Severity Index have been introduced to predict disease severity and mortality. Although there are currently no licensed therapies for bronchiectasis, an increasing number of clinical trials are planned or ongoing. While this emerging evidence is awaited, bronchiectasis guidelines will continue to be informed largely by real-life evidence from observational studies and patient registries. Key developments in the bronchiectasis field include the establishment of international disease registries and characterisation of disease phenotypes using cluster analysis and biological data.
High variation between hospitals in vena cava filter use for venous thromboembolism.

BACKGROUND The extent to which vena cava filter (VCF) use varies between hospitals in the management of acute venous thromboembolism (VTE) is not clear. METHODS We conducted a retrospective observational study that compared the frequency of VCF use among California hospitals from January 1, 2006, through December 31, 2010. Using administrative hospital discharge data, we followed explicit criteria to identify nontrauma patients with acute VTE, and determined the frequency of VCF placement in each of the hospitals that admitted more than 55 VTE patients. Multivariable hierarchical regression models to predict VCF use included important clinical and demographic variables as fixed effects and hospital as a random effect. RESULTS Among the 263 hospitals included, 130 643 acute VTE hospitalizations occurred with the placement of 19 537 VCFs (14.95%). Variation in the percentage of acute VTE hospitalizations that included VCF placement was very high, from 0% to 38.96% (interquartile range, 6.23%-18.14%), with 18.49% of the observed variation due to differences among the hospitals that provided care. Significant clinical predictors of VCF use included acute bleeding at the time of admission (odds ratio, 3.4 [95% CI, 3.2-3.6]), a major operation after admission for VTE (3.4 [3.3-3.5]), presence of metastatic cancer (1.7 [1.6-1.8]), and extreme severity of illness (2.5 [2.3-2.7] vs mild). Insertion of VCFs occurred more frequently than expected in 109 hospitals and less frequently in 59. Hospital characteristics associated with VCF use included a small number of beds (odds ratio, 0.2 [95% CI, 0.2-0.4], <100 vs >400 beds), a rural location (0.4 [0.2-0.5]), and other private vs Kaiser hospitals (1.5 [1.1-2.0]). Use of VCFs varied widely even in geographically proximate areas. CONCLUSIONS The frequency of VCF use in patients with acute VTE varied widely and depended on which hospital provided the care, even after adjusting for clinical and socioeconomic factors. Further research is needed to determine whether this variation is associated with local cultural differences between hospitals or with differences in the availability of interventional radiologists or specialists, or whether it reflects the absence of high-quality evidence that VCFs are effective.
Single Arginine Mutation in Two Yeast Isocitrate Dehydrogenases: Biochemical Characterization and Functional Implication

Isocitrate dehydrogenase (IDH), a housekeeping gene, has drawn the attention of cancer experts. Mutation of the catalytic Arg132 residue of human IDH1 (HcIDH) eliminates the enzyme's wild-type isocitrate oxidation activity, but confer the mutant an ability of reducing α-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG). To examine whether an analogous mutation in IDHs of other eukaryotes could cause similar effects, two yeast mitochondrial IDHs, Saccharomyces cerevisiae NADP+-IDH1 (ScIDH1) and Yarrowia lipolytica NADP+-IDH (YlIDH), were studied. The analogous Arg residues (Arg148 of ScIDH1 and Arg141 of YlIDH) were mutated to His. The K m values of ScIDH1 R148H and YlIDH R141H for isocitrate were determined to be 2.4-fold and 2.2-fold higher, respectively, than those of the corresponding wild-type enzymes. The catalytic efficiencies (k cat/K m) of ScIDH1 R148H and YlIDH R141H for isocitrate oxidation were drastically reduced by 227-fold and 460-fold, respectively, of those of the wild-type enzymes. As expected, both ScIDH1 R148H and YlIDH R141H acquired the neomorphic activity of catalyzing α-KG to 2-HG, and the generation of 2-HG was confirmed using gas chromatography/time of flight-mass spectrometry (GC/TOF-MS). Kinetic analysis showed that ScIDH1 R148H and YlIDH R141H displayed 5.2-fold and 3.3-fold higher affinities, respectively, for α-KG than the HcIDH R132H mutant. The catalytic efficiencies of ScIDH1 R148H and YlIDH R141H for α-KG were 5.5-fold and 4.5-fold, respectively, of that of the HcIDH R132H mutant. Since the HcIDH Arg132 mutation is associated with the tumorigenesis, this study provides fundamental information for further research on the physiological role of this IDH mutation in vivo using yeast.
Piloting the use of personal digital assistants for tuberculosis and human immunodeficiency virus surveillance, Kenya, 2007.

SETTING Improved documentation of human immunodeficiency virus (HIV) testing and care among tuberculosis (TB) patients is needed to strengthen TB-HIV programs. In 2007, Kenya piloted the use of personal digital assistants (PDAs) instead of paper registers to collect TB-HIV surveillance data from TB clinics. OBJECTIVE To evaluate the acceptability, data quality and usefulness of PDAs. DESIGN We interviewed four of 31 district coordinators who collected data in PDAs for patients initiating TB treatment from April to June 2007. In 10 of 93 clinics, we randomly selected patient records for comparison with corresponding records in paper registers or PDAs. Using Cochran-Mantel-Haenszel tests, we compared missing data proportions in paper registers with PDAs. We evaluated PDA usefulness by analyzing PDA data from all 93 clinics. RESULTS PDAs were well accepted. Patient records were more frequently missing (28/97 vs. 1/112, P < 0.001) and data fields more frequently incomplete (148/1449 vs. 167/2331, P = 0.03) in PDAs compared with paper registers. PDAs, however, facilitated clinic-level analyses: 48/93 (52%) clinics were not reaching the targets of testing >or=80% of TB patients for HIV, and 8 (9%) clinics were providing <80% of TB-HIV co-infected patients with cotrimoxazole (CTX). CONCLUSION PDAs had high rates of missing data but helped identify clinics that were undertesting for HIV or underprescribing CTX.
Ontological Modelling of Situational Awareness in Surgical Interventions

Optical navigation systems are the means of choice to overcome spatial association problems of the endoscopic imaging in minimally invasive surgery. Using optical markers, the patient's real position, his medical imaging data and surgical tool locations are mapped into the same workspace. Such visual-based assistance systems however, suffer from their technical requirements. The BIOPASS project aims to develop a navigation system based on a novel marker less localization method that uses only the current surgical situation and the procedure’s history to identify the present anatomy. The ontology, presented in this paper, plays an integral part in this system as it translates the situational information of a surgical procedure into an internal machine-readable representation. This representation combines multimodal sensor data, e.g. endoscopic images, endoscope movement or surgical work steps, to allow a classification of the apparent situation and provide navigation support based on identified anatomical landmarks and work steps. Furthermore, it is a foundation of situational awareness based on spatiotemporal reasoning.
Proposal and Fabrication of an Electrooptically Controlled Multimode Microresonator for Continuous Fast-to-Slow Light Tuning

We propose a scheme to utilize a multimode microdisk resonator in silicon controlled through free-carrier injection for continuous fast-to-slow light tuning. Two nearby resonant modes are employed, i.e., undercoupling and overcoupling. The optical properties of a device are analytically investigated considering the resonance spacing, bandwidth, and density change of free carriers. Pulse propagation simulations are implemented, and the pulse delay/advance is studied for wavelengths between the two resonances. As the density of injected free carriers increases, a continuous transition from fast to slow light occurs for a range of wavelengths. Consequently, a microdisk resonator in silicon is experimentally realized with the desired two resonances, exhibiting electrooptical tuning with a fast response. The experimental results agree well with the simulation in power transmission, and the tunable time delay and advance are also predicted.
Malware Obfuscation Techniques: A Brief Survey

As the obfuscation is widely used by malware writers to evade antivirus scanners, so it becomes important to analyze how this technique is applied to malwares. This paper explores the malware obfuscation techniques while reviewing the encrypted, oligomorphic, polymorphic and metamorphic malwares which are able to avoid detection. Moreover, we discuss the future trends on the malware obfuscation techniques.
Linking individual phenotype to density- dependent population growth: the influence of body size on the population dynamics of malaria vectors

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Rhythmic Changes in Synapse Numbers in Drosophila melanogaster Motor Terminals

Previous studies have shown that the morphology of the neuromuscular junction of the flight motor neuron MN5 in Drosophila melanogaster undergoes daily rhythmical changes, with smaller synaptic boutons during the night, when the fly is resting, than during the day, when the fly is active. With electron microscopy and laser confocal microscopy, we searched for a rhythmic change in synapse numbers in this neuron, both under light:darkness (LD) cycles and constant darkness (DD). We expected the number of synapses to increase during the morning, when the fly has an intense phase of locomotion activity under LD and DD. Surprisingly, only our DD data were consistent with this hypothesis. In LD, we found more synapses at midnight than at midday. We propose that under LD conditions, there is a daily rhythm of formation of new synapses in the dark phase, when the fly is resting, and disassembly over the light phase, when the fly is active. Several parameters appeared to be light dependent, since they were affected differently under LD or DD. The great majority of boutons containing synapses had only one and very few had either two or more, with a 70∶25∶5 ratio (one, two and three or more synapses) in LD and 75∶20∶5 in DD. Given the maintenance of this proportion even when both bouton and synapse numbers changed with time, we suggest that there is a homeostatic mechanism regulating synapse distribution among MN5 boutons.
DAuth: Fine-Grained Authorization Delegation for Distributed Web Application Consumers

Web applications are becoming the predominant means by which users interact with online content. However, current authentication approaches use a single authentication credential to manage access permissions, which is too inflexible for distributed programs with unique security and privacy requirements for each component. In this paper, we introduce DAuth, an authorization mechanism that allows fine-grained and flexible control of access permissions derived from a single authentication credential for distributed consumers of web applications. We implement DAuth as a proxy for a Twitter social networking application within our distributed Elastic Application framework and find it introduces negligible overhead and requires only minor modification of existing applications. Through our evaluation, we demonstrate DAuth improves on existing web authentication mechanisms to support distributed web application consumers and can be implemented as a proxy to web applications that do not wish to develop their own implementation.
Has1 regulates consecutive maturation and processing steps for assembly of 60S ribosomal subunits

Ribosome biogenesis requires ∼200 assembly factors in Saccharomyces cerevisiae. The pre-ribosomal RNA (rRNA) processing defects associated with depletion of most of these factors have been characterized. However, how assembly factors drive the construction of ribonucleoprotein neighborhoods and how structural rearrangements are coupled to pre-rRNA processing are not understood. Here, we reveal ATP-independent and ATP-dependent roles of the Has1 DEAD-box RNA helicase in consecutive pre-rRNA processing and maturation steps for construction of 60S ribosomal subunits. Has1 associates with pre-60S ribosomes in an ATP-independent manner. Has1 binding triggers exonucleolytic trimming of 27SA3 pre-rRNA to generate the 5′ end of 5.8S rRNA and drives incorporation of ribosomal protein L17 with domain I of 5.8S/25S rRNA. ATP-dependent activity of Has1 promotes stable association of additional domain I ribosomal proteins that surround the polypeptide exit tunnel, which are required for downstream processing of 27SB pre-rRNA. Furthermore, in the absence of Has1, aberrant 27S pre-rRNAs are targeted for irreversible turnover. Thus, our data support a model in which Has1 helps to establish domain I architecture to prevent pre-rRNA turnover and couples domain I folding with consecutive pre-rRNA processing steps.
Hepatic Artery Chemotherapy in the Management of Colorectal Metastases

Each year in the USA, approximately 200,000 people are diagnosed with primary colorectal cancer; 75,000 patients with colorectal cancer do not survive, and half of those who survive develop tumor recurrence. Sixty percent of recurrences are found in the liver, ≤10% of which will be resectable. Patients at high risk of developing metastases from colorectal cancer are those with T3 lesions, node-positive disease, a rectal vs colonic primary tumor, and vascular invasion determined by pathologic examination. The National Comprehensive Cancer Network has different patient surveillance guidelines for node-positive patients and node-negative patients. For node-positive patients, the guidelines recommend a carcinoembryonic antigen (CEA) level every 3 months and a computed tomography (CT) scan initially and annually thereafter. For node-negative patients, the guidelines recommend a CEA level every 6 months and a CT scan at 1 and 2 years (1).
Expression of cell cycle–regulatory proteins Rb, p16/MTS1, p27/KIP1, p21/WAF1, cyclin D1 and cyclin E in breast cancer: Correlations with expression of activating protein‐1 family members

The activating protein‐1 (AP‐1) complex is a mitogen‐activated composite transcription factor that leads to activation of various target genes and enhanced proliferation of many cells after stimulation by TPA, EGF, serum, etc. The molecular mechanism of cell‐cycle activation by AP‐1 complexes remains unclear. Therefore, we studied protein expression of 6 cell cycle–regulatory proteins (Rb, p16, p21, p27, cyclin D1, and cyclin E) in protein extracts from 53 breast cancer samples and 4 mammary cell lines and correlated the data with expression of the 7 AP‐1 family members (c‐jun, junB, junD, c‐fos, fosB, fra‐1, and fra‐2) as determined in a previous study. After Western blot analysis, we found significant associations between members of both groups: whereas c‐jun was associated with Rb expression (p = 0.002), strong junD and c‐fos expression correlated with high cyclin E reactivity (p = 0.017 and p = 0.013, respectively). Over‐expression of fosB was found mainly in tumors with strong Rb (p = 0.013) and weak p16 (p = 0.004) expression. Fra‐1 expression was significantly associated with p16 and cyclin E over‐expression, whereas fra‐2 results correlated with both cyclin D1 and cyclin E. These results point to direct or indirect activation of some cell cycle–regulatory proteins by AP‐1 complexes. In addition, our data suggest differential regulation of cell cycle–stimulating and –inhibiting factors depending on the abundance of single AP‐1 family members. Int. J. Cancer 87:468–472, 2000. © 2000 Wiley‐Liss, Inc.
Energy Intake and Risk of Postmenopausal Breast Cancer: An Expanded Analysis in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) Cohort

Although animal experiments have consistently shown a positive relationship between breast cancer and energy intake, evidence from human studies remains inconclusive. In the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort, 29,170 women, ages 55 to 75 years, who successfully completed a food frequency questionnaire (FFQ) at entry (1993-2001), were followed through 2007, and 1,319 incident breast cancers were ascertained (median time from FFQ completion to diagnosis, 4.4 years). Women in the highest quartile of energy intake, relative to the lowest, had modestly, but significantly, increased breast cancer risk [multivariate relative risk (RR), 1.21; 95% confidence interval (95% CI), 1.03-1.42; Ptrend = 0.03]. The inclusion of body mass index and physical activity in the model reduced risk slightly (RR, 1.18; 95% CI, 1.00-1.39; Ptrend = 0.07). However, in similar analyses using energy intake from a FFQ administered approximately five years after entry (27,428 women; 806 incident breast cancers; median time from FFQ completion to diagnosis, 2.7 years), women in the highest and lowest quartiles of energy intake had similar risk. When follow-up time after the first FFQ was divided into three 4-year periods, the multivariate RRs for high versus low energy intake increased from 1.21 to 1.37 to 1.55 with increasing time since dietary assessment. Although the divergent results for the two FFQs could be due to subtle questionnaire differences, our findings suggest a modest positive association between energy intake and postmenopausal breast cancer that strengthens with time since dietary assessment. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2842–50)
Mediterranean Conference on Information Systems ( MCIS ) 2009 Analyzing RFID Data For The Management Of Reusable Packaging

A common issue that most automotive manufacturers have to face in production logistics is the efficient handling of a considerable number of cost-intensive pallets, trays, boxes and similar reusable packaging goods. As empirical studies show, deficiencies in monitoring, controlling and optimizing packaging material are widespread within this industry. In this contribution a case study is used to investigate the potential of supporting these managerial tasks with a combined use of RFID infrastructures and Business Intelligence (BI) infrastructures. This includes a derivation of relevant RFID reader locations, the identification of further relevant data sources as well as crafting concrete analysis and reporting scenarios based on the paradigm of multidimensional data modeling. The results are used to design a concept for a BI and RFID based system architecture. They highlight the need to include data management systems that bring data integration capabilities and that are capable of tracking historical data – as a possible component of a wider BI infrastructure for manufacturing and logistics.
Ticagrelor: Pharmacokinetics, Pharmacodynamics, Clinical Efficacy, and Safety

Dual antiplatelet therapy, composed of aspirin plus a P2Y12‐receptor antagonist, is the cornerstone of treatment for patients with acute coronary syndrome (ACS). A number of U.S. Food and Drug Administration–approved P2Y12‐receptor antagonists are available for treating patients with ACS, including the thienopyridine compounds clopidogrel and prasugrel. Ticagrelor, the first of a new class of antiplatelet agents, is a noncompetitive, direct‐acting P2Y12‐receptor antagonist. Unlike the thienopyridine compounds, ticagrelor does not require metabolism for activity. Also, whereas clopidogrel and prasugrel are irreversible inhibitors of the P2Y12 receptor, ticagrelor binds reversibly to inhibit receptor signaling and subsequent platelet activation. In pharmacodynamic studies, ticagrelor demonstrated faster onset and more potent inhibition of platelet aggregation than clopidogrel. These properties of ticagrelor may contribute to reduced rates of thrombotic outcomes compared with clopidogrel, as demonstrated in a phase III clinical trial. However, in addition to bleeding, distinctive adverse effects of this new chemical entity have not been reported with the thienopyridine P2Y12‐receptor inhibitors. Although ticagrelor represents an advancement in P2Y12‐receptor inhibition therapy, a thorough understanding of this compound as an antiplatelet therapy remains to be elucidated.