Miracle-dz/UniFAR-FTUs huggingface dataset:
Intracellular accumulation dynamics and fate of zinc ions in alveolar epithelial cells exposed to airborne ZnO nanoparticles at the air–liquid interface

Abstract Airborne nanoparticles (NPs) that enter the respiratory tract are likely to reach the alveolar region. Accumulating observations support a role for zinc oxide (ZnO) NP dissolution in toxicity, but the majority of in-vitro studies were conducted in cells exposed to NPs in growth media, where large doses of dissolved ions are shed into the exposure solution. To determine the precise intracellular accumulation dynamics and fate of zinc ions (Zn2+) shed by airborne NPs in the cellular environment, we exposed alveolar epithelial cells to aerosolized NPs at the air–liquid interface (ALI). Using a fluorescent indicator for Zn2+, together with organelle-specific fluorescent proteins, we quantified Zn2+ in single cells and organelles over time. We found that at the ALI, intracellular Zn2+ values peaked 3 h post exposure and decayed to normal values by 12 h, while in submerged cultures, intracellular Zn2+ values continued to increase over time. The lowest toxic NP dose at the ALI generated peak intracellular Zn2+ values that were nearly three-folds lower than the peak values generated by the lowest toxic dose of NPs in submerged cultures, and eight-folds lower than the peak values generated by the lowest toxic dose of ZnSO4 or Zn2+. At the ALI, the majority of intracellular Zn2+ was found in endosomes and lysosomes as early as 1 h post exposure. In contrast, the majority of intracellular Zn2+ following exposures to ZnSO4 was found in other larger vesicles, with less than 10% in endosomes and lysosomes. Together, our observations indicate that low but critical levels of intracellular Zn2+ have to be reached, concentrated specifically in endosomes and lysosomes, for toxicity to occur, and point to the focal dissolution of the NPs in the cellular environment and the accumulation of the ions specifically in endosomes and lysosomes as the processes underlying the potent toxicity of airborne ZnO NPs.
Scenario Building for Operator Training Simulators Using a Transient Stability Program

The operation of a modern power system has become more complicated and as a result the need for advanced and extensive operator training is becoming more critically important. An Operator Training Simulator (OTS) can significantly enhance the efficiency of power system operator training. An OTS can provide a realistic environment for operators to practice operating procedures, and understand and learn how to cope with emergency and restorative situations. To achieve efficient training through an operator training simulator, suitable training scenarios have to be developed to familiarize the trainee with the characteristics of the system under different (and stressed) conditions. Each training scenario consists of a base (starting) operating case, a system load profile to drive the simulation and a sequence of events including generator tripping, network switching, etc. The scenario building is usually a very complicated and very difficult task, imposing a heavy burden on the OTS scenario builder. One of the drawbacks of the existing power system operator training simulators is the lack of the efficient scenario building aids. As recommended in an EPRI final report, various scenario building aids should be provided for the scenario builder to efficiently develop training scenarios. One such scenario building aid is a suitable transient stability program. Due to the OTS modeling limitations, it is not possible to simulate in real time the power system transient response, such as protective relaying operations, to system faults.
Wearable Internet of Things: Concept, architectural components and promises for person-centered healthcare

The proliferation of mobile devices, ubiquitous internet, and cloud computing has sparked a new era of Internet of Things (IoT), thus allowing researchers to create application-specific solutions based on the interconnection between physical objects and the internet. Recently, wearable devices are rapidly emerging and forming a new segment-“Wearable IoT (WIoT)” due to their capability of sensing, computing and communication. Future generations of WIoT promise to transform the healthcare sector, wherein individuals are seamlessly tracked by wearable sensors for personalized health and wellness information-body vital parameters, physical activity, behaviors, and other critical parameters impacting quality of daily life. This paper presents an effort to conceptualize WIoT in terms of their design, function, and applications. We discuss the building blocks of WIoT-including wearable sensors, internet-connected gateways and cloud and big data support-that are key to its future success in healthcare domain applications. We also present a new system science for WIoT that suggests future directions, encompassing operational and clinical aspects.
AAV delivery of GRP78/BiP promotes adaptation of human RPE cell to ER stress

Adeno associated virus (AAV)‐mediated gene delivery of GRP78 (78 kDa glucose‐regulated protein) attenuates the condition of endoplasmic reticulum (ER) stress and prevents apoptotic loss of photoreceptors in Retinitis pigmentosa (RP) rats. In the current study we overexpressed Grp78 with the help of AAV‐2 in primary human retinal pigmented epithelium (hRPE) cell cultures and examined its effect on cell response to ER stress. The purpose of this work was studying potential stimulating effect of GRP78 on adaptation/pro‐survival of hRPE cells under ER stress, as an in vitro model for RPE degeneration. To investigate the effect of Grp78 overexpression on unfolded protein response (UPR) markers under ER stress, hRPE primary cultures were transduced by recombinant virus rAAV/Grp78, and treated with ER stressor drug, tunicamycin. Expression changes of four UPR markers including GRP78, PERK, ATF6α, and GADD153/CHOP, were assessed by real‐time PCR and western blotting. We found that GRP78 has a great contribution in modulation of UPR markers to favor adaptive response in ER‐stressed hRPE cells. In fact, GRP78 overexpression affected adaptation and apoptotic phases of early UPR, through enhancement of two master regulators/ER stress sensors (PERK and ATF6α) and down‐regulation of a key pro‐apoptotic cascade activator (GADD153/CHOP). Together these findings demonstrate the promoting effect of GRP78 on adaptation/pro‐survival of hRPE cells under ER stress. This protein with anti‐apoptotic actions in the early UPR and important role in cell fate regulation, can be recruited as a useful candidate for future investigations of RPE degenerative diseases.
IL-33 Activates Unprimed Murine Basophils Directly In Vitro and Induces Their In Vivo Expansion Indirectly by Promoting Hematopoietic Growth Factor Production1

IL-33, a new member of the IL-1 family, has been described as an important inducer of Th2 cytokines and mediator of inflammatory responses. In this study, we demonstrate that murine basophils sorted directly from the bone marrow, without prior exposure to IL-3 or FcεR cross-linking, respond to IL-33 alone by producing substantial amounts of histamine, IL-4, and IL-6. These cells express ST2 constitutively and generate a cytokine profile that differs from their IL-3-induced counterpart by a preferential production of IL-6. In vivo, IL-33 promotes basophil expansion in the bone marrow (BM) through an indirect mechanism of action depending on signaling through the βc chain shared by receptors for IL-3, GM-CSF, and IL-5. IL-3 can still signal through its specific βIL-3 chain in these mutant mice, which implies that it is not the unique growth-promoting mediator in this setup, but requires IL-5 and/or GMCSF. Our results support a major role of the latter growth factor, which is readily generated by total BM cells as well as sorted basophils in response to IL-33 along with low amounts of IL-3. Furthermore, GM-CSF amplifies IL-3-induced differentiation of basophils from BM cells, whereas IL-5 that is also generated in vivo, affects neither their functions nor their growth in vitro or in vivo. In conclusion, our data provide the first evidence that IL-33 not only activates unprimed basophils directly, but also promotes their expansion in vivo through induction of GM-CSF and IL-3.
Smoking as a modifiable risk factor for type 2 diabetes in middle-aged men.

OBJECTIVE To examine the effects of cigarette smoking, giving up smoking, and primary or secondary pipe or cigar smoking on the risk of type 2 diabetes. RESEARCH DESIGN AND METHODS A prospective study followed 7,735 men aged 40-59 years from general practices in 24 British towns for an average of 16.8 years. Incident cases of physician-diagnosed diabetes were ascertained by repeated postal questionnaires and systematic reviews of primary care records. RESULTS A total of 290 incident cases of diabetes were found in 7,124 men with no history of diabetes, coronary heart disease, or stroke. Cigarette smoking was associated with a significant increase in risk of diabetes, even after adjustment for age, BMI, and other potential confounders. The benefit of giving up smoking was only apparent after 5 years of smoking cessation, and risk reverted to that of never-smokers only after 20 years. The risk of diabetes in those who switched from smoking cigarettes to pipe or cigars remained equal to the risk in continuing cigarette smokers. Men who gave up smoking during the first 5 years of follow-up showed significant weight gain and subsequently higher risk of diabetes than continuing smokers. CONCLUSIONS Cigarette smoking is an independent and modifiable risk factor for type 2 diabetes. Smoking cessation is associated with weight gain and a subsequent increase in risk of diabetes, but in the long term, the benefits of giving up smoking outweigh the adverse effects of early weight gain.
Use of RNA fingerprinting to identify fungal genes specifically expressed during ectomycorrhizal interaction

The ecosystem soil is characterized by interactions between microorganisms and plants including mycorrhiza – mutualistic interactions between fungi and plant roots. Species of the basidiomycete genus Tricholoma form ectomycorrhiza with tree roots which is characterized by morphological and metabolic changes of both partners, yet molecular mechanisms of the interaction are poorly understood. We performed differential display with arbitrarily primed RT–PCR using ectomycorrhiza between the basidiomycete Tricholoma vaccinum and its compatible host spruce (Picea abies) to isolate mycorrhiza‐specific fungal gene fragments. 76 differentially expressed PCR fragments were verified and checked for plant or fungal origin and expression pattern. Of 20 fungal fragments with mycorrhiza‐specific expression, sequence analyses were performed to identify homologs with known function of the encoded protein. Among the genes identified were orthologs to an aldehyde dehydrogenase, an alcohol dehydrogenase and a protein of the MATE transporter family, all with possible function in plant pathogen response. A phospholipase B, a β‐glucosidase and a binding protein of basic amino acids might play a role in nutrient exchange and growth in planta. A protein similar to inactive E2 compounds of ubiquitin‐conjugating enzymes like CROC‐1 and MMS2, a Ras protein and an APS kinase were placed in signal transduction and two retrotransposons of the Ty3‐gypsy and the Ty1‐copia family are expressed most likely due to stress. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Radiofrequency Ablation of Hepatocellular Cancer in 110 Patients With Cirrhosis

ObjectiveTo determine the treatment efficacy, safety, local tumor control, and complications related to radiofrequency ablation (RFA) in patients with cirrhosis and unresectable hepatocellular carcinoma (HCC). Summary Background DataMost patients with HCC are not candidates for resection because of tumor size, location, or hepatic dysfunction related to cirrhosis. RFA is a technique that permits in situ destruction of tumors by means of local tissue heating. MethodsOne hundred ten patients with cirrhosis and HCC (Child class A, 50; B, 31; C, 29) were treated during a prospective study using RFA. Patients were treated with RFA using an open laparotomy, laparoscopic, or percutaneous approach with ultrasound guidance to place the RF needle electrode into the hepatic tumors. All patients were followed up at regular intervals to detect treatment-related complications or recurrence of disease. ResultsAll 110 patients were followed up for at least 12 months after RFA (median follow-up 19 months). Percutaneous or intraoperative RFA was performed in 76 (69%) and 34 patients (31%), respectively. A total of 149 discrete HCC tumor nodules were treated with RFA. The median diameter of tumors treated percutaneously (2.8 cm) was smaller than that of lesions treated during laparotomy (4.6 cm). Local tumor recurrence at the RFA site developed in four patients (3.6%); recurrent HCC subsequently developed in other areas of the liver in all four. New liver tumors or extrahepatic metastases developed in 50 patients (45.5%), but 56 patients (50.9%) had no evidence of recurrence. There were no treatment-related deaths, but complications developed in 14 patients (12.7%) after RFA. ConclusionsIn patients with cirrhosis and HCC, RFA produces effective local control of disease in a significant proportion of patients and can be performed safely with minimal complications.
Culturally Tailored Diabetes Prevention in the Workplace

Purpose The purpose was to conduct focus groups with Hispanic employees to obtain input into adaptation of previous DSME interventions for use as a workplace diabetes prevention program. Methods From a list of interested Hispanic employees who attended a local health fair (n = 68), 36 were randomly selected to participate in focus groups held during supper mealtime breaks. An experienced bilingual moderator directed the sessions, using interview guidelines developed by the research team. Results Participants’ ages ranged from 22 to 65 years (mean = 50.4, n = 36, SD = 10.7), 7 males and 29 females attended, and 53% had type 2 diabetes mellitus (T2DM). Employees expressed a keen interest in diabetes classes and recommended a focus on preparing healthier Hispanic foods. Primary barriers to promoting healthier lifestyles were work schedules; many employees worked 2 part-time or full-time jobs. Administrators and direct supervisors of the employees were highly supportive of a workplace diabetes prevention program. Conclusions The consistent message was that a workplace program would be the ideal solution for Hispanic employees to learn about diabetes and healthy behaviors, given their busy schedules, family responsibilities, and limited resources. If found to be effective, such a workplace program would be generalizable to other service employees who have disproportionate diabetes rates.
Differential genotypic effects of sexual trait size on offspring mating success and viability

Indicator models of sexual selection predict that females mating with the most ornamented males should produce offspring with enhanced expression of fitness-related traits, such as overall vigor and viability. Empirical support for this prediction, however, is limited. We quantified the effects of a heritable and condition-dependent secondary sexual trait on offspring performance traits in Drosophila bipectinata Duda (Diptera: Drosophilidae). Forty-eight genetic (isofemale) lines were extracted from a natural population, reared in a common environment, and characterized in terms of sex comb size. We measured pupal viability and adult mating success among the progeny of the 5 lines with the largest combs (high line category) and the 5 lines with the smallest combs (low line category). The high line category produced offspring that were significantly more viable than the low line category, and this advantage held across 2 developmental temperatures. In contrast, there was no effect of line category on male mating success, although at the individual-level, comb size was significantly positively correlated with mating success. Our results indicate that the relative size of the D. bipectinata sex comb taps genotypic properties that enhance offspring fitness in a trait-specific manner. Thus, distinct proximate mechanisms likely underlie relationships between secondary sexual trait expression and different performance traits in offspring, offering a possible explanation for inconsistent support for the existence of indirect benefits in sexual selection.
Anatomic and Molecular Correlates of Divergent Selection for Basal Metabolic Rate in Laboratory Mice

Proximal mechanisms describing the evolution of high levels of basal metabolic rate (BMR) in endotherms are one of the most intriguing problems of evolutionary physiology. Because BMR mostly reflects metabolic activity of internal organs, evolutionary increase in BMR could have been realized by an increase in relative organ size and/or mass‐specific cellular metabolic rate. According to the “membrane pacemaker” theory of metabolism, the latter is mediated by an increase in the average number of double bonds (unsaturation index) in cell membrane fatty acids. To test this, we investigated the effect of divergent artificial selection for body‐mass‐corrected BMR on the mass of internal organs and the fatty acid composition of cell membranes in laboratory mice (Mus musculus). Mice from the high‐BMR line had considerably larger liver, kidneys, heart, and intestines. In contrast, the unsaturation index of liver cell membranes was significantly higher in low‐BMR mice, mainly because of the significantly higher content of highly polyunsaturated 22:6 docosahexanoic fatty acid. Thus, divergent selection for BMR did not affect fatty acyl composition of liver and kidney phospholipids in the direction predicted by the membrane pacemaker theory. We conclude that an intraspecific increase in BMR may rapidly evolve mainly as a result of the changes in size of internal organs, without simultaneous increase of the unsaturation index in cell membrane lipids.
Losartan, an angiotensin type I receptor antagonist, improves conduit vessel endothelial function in Type II diabetes.

We have demonstrated previously that inhibition of angiotensin-converting enzyme (ACE) with enalapril and angiotensin II blockade with losartan improve acetylcholine-dependent endothelial function in resistance vessels of patients with Type II diabetes. It was therefore of interest to examine the effect of losartan on conduit vessel function in this group. The influence of losartan (50 mg daily for 4 weeks) on endothelium-dependent and -independent vasodilator function was determined in 12 subjects with Type II diabetes using a randomized, double-blind, placebo-controlled crossover protocol. Conduit vessel endothelial function was assessed using high-resolution ultrasound and the brachial artery response to reactive hyperaemia (flow-mediated dilation; FMD); glyceryl trinitrate (GTN) was used as a non-endothelium-dependent dilator. Losartan administration significantly increased the FMD response from 5.2+/-0.7% (mean+/-S.E.M.) to 7.4+/-0.6% of vessel diameter (P<0.05; paired t-test). There was no effect of losartan on the endothelium-independent responses to GTN (17.8+/-1.8% to 17.6+/-1.2%). Consistent with our previous findings in resistance vessels, administration of 50 mg of losartan daily improves NO-mediated dilation in the conduit vessels of subjects with Type II diabetes. Together with the findings that both ACE inhibition and angiotensin II blockade improve resistance vessel function in this group, it is likely that at least some of the beneficial effect is mediated through the angiotensin II/type I receptor pathway. A type I receptor antagonist seems a reasonable alternative to an ACE inhibitor to maintain conduit vessel endothelial function in Type II diabetic subjects.
Production of immunoreactive growth hormone by mononuclear leukocytes

In the present study, we evaluated whether mononuclear leukocytes could synthesize and secrete growth hormone (GH) in vitro. By using RNA slot blot analysis, we detected maximum spontaneous levels of specific GH mRNA in the cytoplasm of rat leukocytes after a 4‐h incubation. Northern gel analysis demonstrated that the specific leukocyte GH RNA was polyadenylated and had a molecular mass of 1.0 kb. Further studies using immunofluorescence, antibody affinity chromatography, and Sephacryl gel filtration indicate that leukocytes secrete a high molecular weight ( > 300,000) and a low molecular weight (~ 22,000) immunoreactive GH (irGH). A substantial amount of the high molecular weight irGH can be converted to the lower molecular weight form after reduction with mercaptoethanol. The irGH appeared to be de novo synthesized because it could be radiolabeled with tritiated amino acids and its production could be blocked by previous incubation of leukocytes with cycloheximide. The replication of Nb2 rat node lymphoma cells was stimulated by affinity‐purified human lymphocyte‐derived irGH. The growth stimulation was blocked by specific antibodies to hGH. We conclude that lymphocytes produce an irGH that is similar to if not identical to pituitary GH in terms of bioactivity, antigenicity, and molecular weight. The findings demonstrate a potential regulatory loop between the immune and neuroendocrine tissues. —Weigent, D. A. ; Baxter, J. B. ; Wear, W. E. ; Smith, L. R. ; Bost, K. L. ; Blalock, J. E. Production of immunoreactive growth hormone by mononuclear leukocytes. FASEB J. 2: 2812‐2818; 1988.
Making Heads Turn: The Effect of Familiarity and Stimulus Rotation on a Gender-Classification Task

Recent work has demonstrated that facial familiarity can moderate the influence of inversion when completing a configural processing task. Here, we examine whether familiarity interacts with intermediate angles of orientation in the same way that it interacts with inversion. Participants were asked to make a gender classification to familiar and unfamiliar faces shown at seven angles of orientation. Speed and accuracy of performance were assessed for stimuli presented (i) as whole faces and (ii) as internal features. When presented as whole faces, the task was easy, as revealed by ceiling levels of accuracy and no effect of familiarity or angle of rotation on response times. However, when stimuli were presented as internal features, an influence of facial familiarity was evident. Unfamiliar faces showed no increase in difficulty across angle of rotation, whereas familiar faces showed a marked increase in difficulty across angle, which was explained by significant linear and cubic trends in the data. Results were interpreted in terms of the benefit gained from a mental representation when face processing was impaired by stimulus rotation.