Miracle-dz/UniFAR-FTUs huggingface dataset:
Temperature‐dependent downhill unfolding of ubiquitin. I. Nanosecond‐to‐millisecond resolved nonlinear infrared spectroscopy

Transient thermal unfolding of ubiquitin is investigated using nonlinear infrared spectroscopy after a nanosecond laser temperature jump (T‐jump). The abrupt change in the unfolding free energy surface and the ns time resolution allow us to observe a fast response on ns to μs time‐scales, which we attribute to downhill unfolding, before a cross‐over to ms kinetics. The downhill unfolding by a sub‐population of folded proteins is induced through a shift of the barrier toward the native state. By adjusting the T‐jump width, the effect of the initial (Ti) and final (Tf) temperature on the unfolding dynamics can be separated. From the amplitude of the fast downhill unfolding, the fractional population prepared at the unfolding transition state is obtained. This population increases with both Ti and with Tf. A two‐state kinetic analysis of the ms refolding provides thermodynamic information about the barrier height. By a combination of the fast and slow unfolding and folding parameters, a quasi‐two‐state kinetic analysis is performed to calculate the time‐dependent population changes of the folded state. This calculation coincides with the experimentally obtained population changes at low temperature but deviations are found in the T‐jump from 67 to 78°C. Using temperature‐dependent barrier height changes, a temperature Φ value analysis is performed. The result shows a decreasing trend of ΦT with temperature, which indicates an increase of the heterogeneity of the transition state. We conclude that ubiquitin unfolds along a well‐defined pathway at low temperature which expands with increasing temperature to include multiple routes. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Atmospheric Chemistry and Physics Changes in Aerosol Properties during Spring-summer Period in the Arctic Troposphere

The change in aerosol properties during the transition from the more polluted spring to the clean summer in the Arctic troposphere was studied. A six-year data set of observations from Ny-˚ Alesund on Svalbard, covering the months April through June, serve as the basis for the char-acterisation of this time period. In addition four-day-back trajectories were used to describe air mass histories. The observed transition in aerosol properties from an accumulation-mode dominated distribution to an Aitken-mode dominated distribution is discussed with respect to long-range transport and influences from natural and anthropogenic sources of aerosols and pertinent trace gases. Our study shows that the air-mass transport is an important factor modulating the physical and chemical properties observed. However, the air-mass transport cannot alone explain the annually repeated systematic and rather rapid change in aerosol properties, occurring within a limited time window of approximately 10 days. With a simplified phenomenological model, which delivers the nucleation potential for new-particle formation, we suggest that the rapid shift in aerosol microphysical properties between the Arctic spring and summer is mainly driven by the incoming solar radiation in concert with transport of precursor gases and changes in condensational sink.
GRK5-Mediated Exacerbation of Pathological Cardiac Hypertrophy Involves Facilitation of Nuclear NFAT Activity

Rationale: G protein–coupled receptor kinases (GRKs) acting in the cardiomyocyte regulate important signaling events that control cardiac function. Both GRK2 and GRK5, the predominant GRKs expressed in the heart, have been shown to be upregulated in failing human myocardium. Although the canonical role of GRKs is to desensitize G protein–coupled receptors via phosphorylation, it has been demonstrated that GRK5, unlike GRK2, can reside in the nucleus of myocytes and exert G protein–coupled receptor–independent effects that promote maladaptive cardiac hypertrophy and heart failure. Objective: To explore novel mechanisms by which GRK5 acting in the nucleus of cardiomyocytes participates in pathological cardiac hypertrophy. Methods and Results: In this study, we have found that GRK5-mediated pathological cardiac hypertrophy involves the activation of the nuclear factor of activated T cells (NFAT) because GRK5 causes enhancement of NFAT-mediated hypertrophic gene transcription. Transgenic mice with cardiomyocyte-specific GRK5 overexpression activate an NFAT-reporter in mice basally and after hypertrophic stimulation, including transverse aortic constriction and phenylephrine treatment. Complimentary to this, GRK5 null mice exhibit less NFAT transcriptional activity after transverse aortic constriction. Furthermore, the loss of NFATc3 expression in the heart protected GRK5 overexpressing transgenic mice from the exaggerated hypertrophy and early progression to heart failure seen after transverse aortic constriction. Molecular studies suggest that GRK5 acts in concert with NFAT to increase hypertrophic gene transcription in the nucleus via GRK5’s ability to bind DNA directly without a phosphorylation event. Conclusions: GRK5, acting in a kinase independent manner, is a facilitator of NFAT activity and part of a DNA-binding complex responsible for pathological hypertrophic gene transcription.
Ination Di¤erentials in a Currency Union: A DSGE Perspective

Cross country studies of ination di¤erentials, and in particular in the EMU, have focused on three main explanations: (i) the role of tradable and nontradable sector productivity growth di¤erentials and the BalassaSamuelson e¤ect, (ii) the role of the demand-side e¤ects, and (iii) heterogeneity of inationary processes inside the EMU. To understand the role played by each feature in shaping ination di¤erentials, this paper estimates a two country, two sector Dynamic Stochastic General Equilibrium (DSGE) model with nominal rigidities in a currency union using data for Spain and the euro area. The paper nds that productivity shocks in both sectors are the most important source of ination di¤erentials, explaining about 75 percent of its variability. Demand shocks explain a large fraction of output growth variability, but not variability in ination di¤erentials. In addition, the estimated model nds evidence that ination dynamics are di¤erent in Spain and in the rest of the euro area. Finally, the Balassa-Samuelson e¤ect does not appear to be important during the EMU period. JEL Classi cation: F41, F42, C51.
Spam Filtering Using Statistical Data Compression Models

Spam filtering poses a special problem in text categorization, of which the defining characteristic is that filters face an active adversary, which constantly attempts to evade filtering. Since spam evolves continuously and most practical applications are based on online user feedback, the task calls for fast, incremental and robust learning algorithms. In this paper, we investigate a novel approach to spam filtering based on adaptive statistical data compression models. The nature of these models allows them to be employed as probabilistic text classifiers based on character-level or binary sequences. By modeling messages as sequences, tokenization and other error-prone preprocessing steps are omitted altogether, resulting in a method that is very robust. The models are also fast to construct and incrementally updateable. We evaluate the filtering performance of two different compression algorithms; dynamic Markov compression and prediction by partial matching. The results of our empirical evaluation indicate that compression models outperform currently established spam filters, as well as a number of methods proposed in previous studies.
Quantitative 3D Video Microscopy of HIV Transfer Across T Cell Virological Synapses

The spread of HIV between immune cells is greatly enhanced by cell-cell adhesions called virological synapses, although the underlying mechanisms have been unclear. With use of an infectious, fluorescent clone of HIV, we tracked the movement of Gag in live CD4 T cells and captured the direct translocation of HIV across the virological synapse. Quantitative, high-speed three-dimensional (3D) video microscopy revealed the rapid formation of micrometer-sized “buttons” containing oligomerized viral Gag protein. Electron microscopy showed that these buttons were packed with budding viral crescents. Viral transfer events were observed to form virus-laden internal compartments within target cells. Continuous time-lapse monitoring showed preferential infection through synapses. Thus, HIV dissemination may be enhanced by virological synapse-mediated cell adhesion coupled to viral endocytosis.
Error‐related brain activation during a Go/NoGo response inhibition task

Inhibitory control and performance monitoring are critical executive functions of the human brain. Lesion and imaging studies have shown that the inferior frontal cortex plays an important role in inhibition of inappropriate response. In contrast, specific brain areas involved in error processing and their relation to those implicated in inhibitory control processes are unknown. In this study, we used a random effects model to investigate error‐related brain activity associated with failure to inhibit response during a Go/NoGo task. Error‐related brain activation was observed in the rostral aspect of the right anterior cingulate (BA 24/32) and adjoining medial prefrontal cortex, the left and right insular cortex and adjoining frontal operculum (BA 47) and left precuneus/posterior cingulate (BA 7/31/29). Brain activation related to response inhibition and competition was observed bilaterally in the dorsolateral prefrontal cortex (BA 9/46), pars triangularis region of the inferior frontal cortex (BA 45/47), premotor cortex (BA 6), inferior parietal lobule (BA 39), lingual gyrus and the caudate, as well as in the right dorsal anterior cingulate cortex (BA 24). These findings provide evidence for a distributed error processing system in the human brain that overlaps partially, but not completely, with brain regions involved in response inhibition and competition. In particular, the rostal anterior cingulate and posterior cingulate/precuneus as well as the left and right anterior insular cortex were activated only during error processing, but not during response competition, inhibition, selection, or execution. Our results also suggest that the brain regions involved in the error processing system overlap with brain areas implicated in the formulation and execution of articulatory plans. Hum. Brain Mapping 12:131–143, 2001. © 2001 Wiley‐Liss, Inc.
Characterization of human colon cancer antigens recognized by autologous antibodies

The screening of cDNA expression libraries derived from human tumors with autologous antibody (SEREX) has proven to be a powerful method for defining the structure of tumor antigens recognized by the humoral immune system. In the present study, 48 distinct antigens (NY‐CO‐1–NY‐CO‐48) reactive with autologous IgG were identified by SEREX analysis in 4 patients with colon cancer. Sequencing analysis showed that 17 of the cDNA clones were previously uncharacterized molecules and 31 represented known gene products. The individual cDNA clones were analyzed in the following manner: a search for mutations or other structural changes; an analysis of mRNA expression in a panel of normal tissues; and a frequency analysis of the antibody response to the expressed product in the sera of colon cancer patients and normal individuals. The initial analysis showed NY‐CO‐13 to be a mutated version of the p53 tumor suppressor gene. Three of the 48 antigens showed a differential pattern of mRNA expression, with NY‐CO‐27 (galectin‐4) expressed primarily in gastrointestinal tract, and NY‐CO‐37 and ‐38 showing a pattern of tissue‐specific isoforms. With regard to immunogenicity, 20 of the 48 antigens were detected by allogeneic sera; 14 of these were reactive with sera from both normal donors and cancer patients, and 6 other clones (NY‐CO‐8, ‐9, ‐13, ‐16, ‐20 and ‐38) reacted exclusively with sera from colon cancer patients (ranging from 14% to 27%). Our results on colon cancer illustrate both the complexity and the potential of the SEREX approach for analysis of the humoral immune response against human cancer. Int. J. Cancer76:652–658, 1998. © 1998 Wiley‐Liss, Inc.
Encoding of Elements and Relations of Object Arrangements by Young Children

Two experiments investigate the ability of four-year-old children to spontaneously process relations as well as elements in an immediate recognition task. The experiments also test predictions of a model proposed to account for differential processing of elements and relations. Both experiments used a two-item forcedchoice task. In each experiment, children accurately recognized the target, regardless of whether distracter items included different elements or different relations. The results of these experiments suggest that young children do spontaneously process relations as well as elements. These findings in conjunction with earlier results also suggest that more pronounced privileged processing for elements may not arise from initial encoding, but rather from events which occur later in processing such as recoding to a long-term memory representation, or retrieval from long-term memory.
Effects of Chinese Propolis in Protecting Bovine Mammary Epithelial Cells against Mastitis Pathogens-Induced Cell Damage

Chinese propolis (CP), an important hive product, can alleviate inflammatory responses. However, little is known regarding the potential of propolis treatment for mastitis control. To investigate the anti-inflammatory effects of CP on bovine mammary epithelial cells (MAC-T), we used a range of pathogens to induce cellular inflammatory damage. Cell viability was determined and expressions of inflammatory/antioxidant genes were measured. Using a cell-based reporter assay system, we evaluated CP and its primary constituents on the NF-κB and Nrf2-ARE transcription activation. MAC-T cells treated with bacterial endotoxin (lipopolysaccharide, LPS), heat-inactivated Escherichia coli, and Staphylococcus aureus exhibited significant decreases in cell viability while TNF-α and lipoteichoic acid (LTA) did not. Pretreatment with CP prevented losses in cell viability associated with the addition of killed bacteria or bacterial endotoxins. There were also corresponding decreases in expressions of proinflammatory IL-6 and TNF-α mRNA. Compared with the mastitis challenged cells, enhanced expressions of antioxidant genes HO-1, Txnrd-1, and GCLM were observed in CP-treated cells. CP and its polyphenolic active components (primarily caffeic acid phenethyl ester and quercetin) had strong inhibitive effects against NF-κB activation and increased the transcriptional activity of Nrf2-ARE. These findings suggest that propolis may be valuable in the control of bovine mastitis.
Security and Fraud Issues of E-banking

E-banking has a lot of benefits that add value to customer’s satisfaction in term of better service quality, and at the same time enable banks to gain a competitive advantage over other competitors. However, more attention towards e-banking security is required and needed against fraudulent behavior because the lack of control over security makes e-banking still un-trusted for many till today. This paper presents security issues related to e-banking along with the characteristics and challenges of e-banking fraud. Different types of attacks, some fraud detection strategies, and some prevention methods used by electronic banks, are also presented in this paper. An expert opinion method was used to rank different model and techniques in security. Results indicated that the most effective model is “Transaction Monitoring” and the worst models based on respondent’s opinions are “Virtual Keyboards”, “Browser Protection”, and “Device Identification”. The organization of this paper go in the following manner: section 1 will introduce the topic, followed by a literature review in section 2. Section 3 depicts the research methodology adopted and the data analysis process. Finally, conclusions and future work are stated at the
Inactivation of Prions and Amyloid Seeds with Hypochlorous Acid

Hypochlorous acid (HOCl) is produced naturally by neutrophils and other cells to kill conventional microbes in vivo. Synthetic preparations containing HOCl can also be effective as microbial disinfectants. Here we have tested whether HOCl can also inactivate prions and other self-propagating protein amyloid seeds. Prions are deadly pathogens that are notoriously difficult to inactivate, and standard microbial disinfection protocols are often inadequate. Recommended treatments for prion decontamination include strongly basic (pH ≥~12) sodium hypochlorite bleach, ≥1 N sodium hydroxide, and/or prolonged autoclaving. These treatments are damaging and/or unsuitable for many clinical, agricultural and environmental applications. We have tested the anti-prion activity of a weakly acidic aqueous formulation of HOCl (BrioHOCl) that poses no apparent hazard to either users or many surfaces. For example, BrioHOCl can be applied directly to skin and mucous membranes and has been aerosolized to treat entire rooms without apparent deleterious effects. Here, we demonstrate that immersion in BrioHOCl can inactivate not only a range of target microbes, including spores of Bacillus subtilis, but also prions in tissue suspensions and on stainless steel. Real-time quaking-induced conversion (RT-QuIC) assays showed that BrioHOCl treatments eliminated all detectable prion seeding activity of human Creutzfeldt-Jakob disease, bovine spongiform encephalopathy, cervine chronic wasting disease, sheep scrapie and hamster scrapie; these findings indicated reductions of ≥103- to 106-fold. Transgenic mouse bioassays showed that all detectable hamster-adapted scrapie infectivity in brain homogenates or on steel wires was eliminated, representing reductions of ≥~105.75-fold and >104-fold, respectively. Inactivation of RT-QuIC seeding activity correlated with free chlorine concentration and higher order aggregation or destruction of proteins generally, including prion protein. BrioHOCl treatments had similar effects on amyloids composed of human α-synuclein and a fragment of human tau. These results indicate that HOCl can block the self-propagating activity of prions and other amyloids.
Patient-specific dosimetry calculations using mathematic models of different anatomic sizes during therapy with 111In-DTPA-D-Phe1-octreotide infusions after catheterization of the hepatic artery.

UNLABELLED The aim of the study was to provide dosimetric data on intrahepatic (111)In-diethylenetriaminepentaacetic acid (DTPA)-D-Phe(1)-octreotide therapy for neuroendocrine tumors with overexpression of somatostatin receptors. METHODS A dosimetric protocol was designed to estimate the absorbed dose to the tumor and healthy tissue in a course of 48 treatments for 12 patients, who received a mean activity of 5.4 +/- 1.7 GBq per session. The patient-specific dosimetry calculations, based on quantitative biplanar whole-body scintigrams, were performed using a Monte Carlo simulation program for 3 male and 3 female mathematic models of different anatomic sizes. Thirty minutes and 2, 6, 24, and 48 h after the radionuclide infusion, blood-sample data were collected for estimation of the red marrow radiation burden. RESULTS The mean absorbed doses per administered activity (mGy/MBq) by the critical organs liver, spleen, kidneys, bladder wall, and bone marrow were 0.14 +/- 0.04, 1.4 +/- 0.6, 0.41 +/- 0.08, 0.094 +/- 0.013, and (3.5 +/- 0.8) x 10(-3), respectively; the tumor absorbed dose ranged from 2.2 to 19.6 mGy/MBq, strongly depending on the lesion size and tissue type. CONCLUSION The results of the present study quantitatively confirm the therapeutic efficacy of transhepatic administration; the tumor-to-healthy-tissue uptake ratio was enhanced, compared with the results after antecubital infusions. Planning of treatment was also optimized by use of the patient-specific dosimetric protocol.
Estimating PMTCT's Impact on Heterosexual HIV Transmission: A Mathematical Modeling Analysis

Introduction Prevention of mother-to-child HIV transmission (PMTCT) strategies include combined short-course antiretrovirals during pregnancy (Option A), triple-drug antiretroviral treament (ART) during pregnancy and breastfeeding (Option B), or lifelong ART (Option B+). The WHO also recommends ART for HIV treatment and prevention of sexual transmission of HIV. The impact of PMTCT strategies on prevention of sexual HIV transmission of HIV is not known. We estimated the population-level impact of PMTCT interventions on heterosexual HIV transmission in southwestern Uganda and KwaZulu-Natal, South Africa, two regions with different HIV prevalence and fertility rates. Materials and Methods We constructed and validated dynamic, stochastic, network-based HIV transmission models for each region. PMTCT Options A, B, and B+ were simulated over ten years under three scenarios: 1) current ART and PMTCT coverage, 2) current ART and high PMTCT coverage, and 3) high ART and PMTCT coverage. We compared adult HIV incidence after ten years of each intervention to Option A (and current ART) at current coverage. Results At current coverage, Options B and B+ reduced heterosexual HIV incidence by about 5% and 15%, respectively, in both countries. With current ART and high PMTCT coverage, Option B+ reduced HIV incidence by 35% in Uganda and 19% in South Africa, while Option B had smaller, but meaningful, reductions. The greatest reductions in HIV incidence were achieved with high ART and PMTCT coverage. In this scenario, all PMTCT strategies yielded similar results. Discussion Implementation of Options B/B+ reduces adult HIV incidence, with greater effect (relative to Option A at current levels) in Uganda than South Africa. These results are likely driven by Uganda’s higher fertility rates.
Hsc70 is required for endocytosis and clathrin function in Drosophila

By screening for Drosophila mutants exhibiting aberrant bride of sevenless (Boss) staining patterns on eye imaginal disc epithelia, we have recovered a point mutation in Hsc70-4, the closest homologue to bovine clathrin uncoating ATPase. Although the mutant allele was lethal, analysis of mutant clones generated by FLP/FRT recombination demonstrated that the Sevenless-mediated internalization of Boss was blocked in mutant Hsc70-4 eye disc epithelial cells. Endocytosis of other probes was also greatly inhibited in larval Garland cells. Immunostaining and EM analysis of the mutant cells revealed disruptions in the organization of endosomal/lysosomal compartments, including a substantial reduction in the number of clathrin-coated structures in Garland cells. The Hsc70-4 mutation also interacted genetically with a dominant-negative mutant of dynamin, a gene required for the budding of clathrin-coated vesicles (CCVs). Consistent with these phenotypes, recombinant mutant Hsc70 proteins exhibited diminished clathrin uncoating activity in vitro. Together, these data provide genetic support for the long-suspected role of Hsc70 in clathrin-mediated endocytosis, at least in part by inhibiting the uncoating of CCVs.