Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Roles of Arrestin-2 Interaction with Clathrin and Adaptor Protein 2 in G Protein-coupled Receptor Trafficking*

The non-visual arrestins, arrestin-2 and arrestin-3, play a critical role in regulating the signaling and trafficking of many G protein-coupled receptors (GPCRs). Molecular insight into the role of arrestins in GPCR trafficking has suggested that arrestin interaction with clathrin, β2-adaptin (the β-subunit of the adaptor protein AP2), and phosphoinositides contributes to this process. In the present study, we have attempted to better define the molecular basis and functional role of arrestin-2 interaction with clathrin and β2-adaptin. Site-directed mutagenesis revealed that the C-terminal region of arrestin-2 mediated β2-adaptin and clathrin interaction with Phe-391 and Arg-395 having an essential role in β2-adaptin binding and LIELD (residues 376–380) having an essential role in clathrin binding. Interestingly, arrestin-2-R169E, an activated form of arrestin that binds to GPCRs in a phosphorylation-independent manner, has significantly enhanced binding to β2-adaptin and clathrin. This suggests that receptor-induced conformational changes in the C-terminal tail of arrestin-2 will likely play a major role in mediating arrestin interaction with clathrin-coated pits. In an effort to clarify the role of these interactions in GPCR trafficking we generated arrestin mutants that were completely and selectively defective in either clathrin (arrestin-2-ΔLIELD) or β2-adaptin (arrestin-2-F391A) interaction. Analysis of these mutants in COS-1 cells revealed that arrestin/clathrin interaction was essential for agonist-promoted internalization of the β2-adrenergic receptor, while arrestin/β2-adaptin interaction appeared less critical. Arrestin-2 mutants defective in both clathrin and β2-adaptin binding functioned as effective dominant negatives in HEK293 cells and significantly attenuated β2-adrenergic receptor internalization. These mutants should prove useful in better defining the role of arrestins in mediating receptor trafficking.
Adaptive Rational Interpolation: Arnoldi and Lanczos-like Equations

The Arnoldi and Lanczos algorithms, which belong to the class of Krylov subspace methods, are increasingly used for model reduction of large-scale systems. The standard versions of the algorithms tend to create reduced order models that poorly approximate low frequency dynamics. Rational Arnoldi and Lanczos algorithms produce reduced models that approximate dynamics at various frequencies. This paper tackles the issue of developing simple Arnoldi and Lanczos equations for the rational case. This allows a simple error analysis to be carried out for both algorithms and permits the development of computationally efficient model reduction algorithms, where the frequencies at which the dynamics are to be matched can be updated adaptively.
Iron metabolism in the lower respiratory tract

Iron metabolism is of crucial importance in the biology and pathophysiology of the lower respiratory tract. As with many other factors involved in inflammation, it is very important that an appropriate iron balance is maintained. Local deficiency could impair growth and proliferation of cells responsible for the inflammatory response and tissue repair (lymphocytes and fibroblasts) and the synthesis of mediators (for example, arachidonic acid derivatives). 1 In contrast, excessive accumulation of iron, especially in free form—that is, not bound to one of the specific iron-binding proteins—facilitates the generation of potentially toxic hydroxyl radicals2 and increases the ability of intracellular bacteria such as mycobacteria to grow.3-5 Research into iron metabolism in the lower respiratory tract has taken advantage of bronchoalveolar lavage, a technique by which it is possible to obtain the cells and fluid lining the alveoli. Determination of iron content in the alveolo-interstitial region shows that 80% is present in the cells and 20% in the epithelial lining fluid of the lung.6 Since alveolar macrophages constitute the major cell population in this region, and because the iron content of lymphocytes, neutrophils, and monocytes is very low in comparison with alveolar macrophages,6 7 these cells are of special interest. In this paper we review current knowledge of iron and iron-binding proteins in bronchoalveolar lavage fluid, and the special features of iron metabolism in alveolar macrophages. Iron is principally required for haemoglobin synthesis, and its uptake, utilisation and storage are carefully regulated to ensure an adequate supply without excessive accumulation which could lead to toxicity. Intestinal iron absorption is related to erythropoietic requirements, although the regulatory mechanism(s) remain unknown. The usual source of iron in the lung is serum iron which is derived from catabolised erythrocytes and absorbed iron. However, in pathological states, iron can enter the lung …
Clostridium difficile: A healthcare-associated infection of unknown significance in adults in sub-Saharan Africa.

BACKGROUND Clostridium difficile infection (CDI) causes a high burden of disease in high-resource healthcare systems, with significant morbidity, mortality, and financial implications. CDI is a healthcare-associated infection for which the primary risk factor is antibiotic usage, and it is the leading cause of bacterial diarrhoea in HIV-infected patients in the United States. Little is known about the disease burden of CDI in sub-Saharan Africa, where HIV and healthcare-associated infections are more prevalent and antibiotic usage is less restricted. This article reviews published literature on CDI in sub-Saharan Africa, highlighting areas for future research. METHODS English language publications since 1995 were identified from online databases (PubMed, Medline, Google Scholar, and SCOPUS), using combinations of keywords "C. difficile", "Africa", and "HIV". RESULTS Ten relevant studies were identified. There was considerable variation in the methodologies used to assess for carriage of toxigenic C. difficile and its associations. Eight studies reported carriage of toxigenic C. difficile. Three (of three) studies found an association with antibiotic usage. One (of four) studies showed an association with HIV infection. One study showed no association with degree of immunosuppression in HIV. Two (of three) studies showed an association between carriage of toxigenic C. difficile and diarrhoeal illness. CONCLUSIONS While the carriage of toxigenic C. difficile is well described in sub-Saharan Africa, the impact of CDI in the region remains poorly understood and warrants further research.
Fulfilled preferences, perceived control, life satisfaction, and loneliness in elderly long-term care residents

ABSTRACT Objectives: Person-centered care constructs such as fulfilled preferences, sense of control, and life satisfaction might contribute to loneliness among nursing home residents, but these relationships have not been thoroughly explored. The aim of this study was to examine the relationship between fulfilled preferences and loneliness in nursing home residents with perceived control and life satisfaction as potential mediators. Methods: The study utilized a cross-sectional design, examining the targeted variables with a questionnaire administered by trained research staff. A convenience sample of 65 residents (median age = 71) of eight nursing homes were interviewed. Linear regression analysis was utilized to examine the mediation hypotheses. Results: The relationships between fulfilled preferences and loneliness (β = −.377, p = .002), fulfilled preferences and perceived control (β = −.577, p < .001), and perceived control and loneliness (β = .606, p < .001) were significant, and the relationship between fulfilled preferences and loneliness (β = −.040, p = .744) became non-significant when perceived control was included in the model. The relationships between fulfilled preferences and life satisfaction (β = .420, p < .001) and life satisfaction and loneliness (β = −.598, p < .001) were significant, and the relationship between fulfilled preferences and loneliness (β = −.152, p = .174) became non-significant when life satisfaction was included in the model. Conclusion: The findings suggest an important association between person-centered care, particularly fulfilling personal care and recreation preferences, and social-affective needs of long-term care residents. Fulfilling preferences may be an appropriate intervention target for loneliness.
Evaluation of antioxidant activity, phenolic, mineral contents and some physicochemical properties of several pine honeys collected from Western Anatolia

In this study, the qualities of 15 red pine honey samples from different parts of the Muğla province in Turkey were evaluated. Important chemical parameters such as °Brix, pH, moisture, ash, electrical conductivity, free acidity, proteins, diastase activity, hydroxymethylfurfurale, total reducing sugar, reducing sugar, sucrose, the five common physical parameters refractive index, density, water activity, dynamic viscosity and color index (L*,a* and b*), and mineral compositions, including potassium, sodium, magnesium, phosphorus, calcium, iron, copper, zinc, manganese, nickel, aluminum, boron, molybdenum, and chromium, were determined. Pine honey samples also were analyzed for total phenolic contents and antioxidant activity. The antioxidant activities were evaluated based on the ability of the pine honey extracts to scavenge 1,1-diphenyl-2-picrylhydrazyl. Significant correlations were obtained between the antioxidant activity and phenolic content (r = 0.887). All samples indicated proper maturity, considering the high soluble solids. The values for ash and electrical conductivity were high (0.24–0.60% and 878–1463 μS/cm, respectively). The concentration of 14 minerals of red pine honeys were determined by inductively coupled plasma-atomic emission spectrometry. All samples contained high amounts of potassium, calcium, phosphorus, sodium, iron, magnesium, aluminum, nickel, and zinc. Within the mineral contents, potassium was quantitatively the most important mineral, having an average content of 3,802 ppm, and accounted for 45% the minerals.
Sharp Uniform Martingale Concentration Bounds

We give upper concentration bounds for martingales that are uniform over finite times and extend classical Hoeffding and Bernstein bounds. They shed light on the relationship between the central limit theorem and the law of the iterated logarithm in finite time. We also prove our upper bounds to be optimal in a strong sense with a lower bound.
Experiments with large enclosed ecosystems.

Three of the major advantages of enclosure experiments are that they ensure (1) that the same populations are sampled over a long period; (2) that populations of at least three trophic levels are initially enclosed in naturally occurring proportions and that they are self sustaining over a long experimental period; and (3) that replicate enclosed populations can be experimentally manipulated. There are two disadvantages which must be mentioned. These are (1) that vertical mixing, which may be reduced by as much as an order of magnitude compared to the open sea, will undoubtedly affect the sinking rates of phytoplankton and may influence the structure of the population; and (2) that as a general rule the larger and therefore more expensive the enclosures become, the more difficult it is to run sufficient replicates. An experiment is described in which 1 microgram Hg/l was added to two 95 m3 bags (3 mdiameter by 17 m deep) and the response of the pelagic population monitored over the following 20 days. A further 10 micrograms Hg/l was then added to each enclosure and the response measured for a further 20 days. The results indicated that: (i) inorganic mercury added to the water column is very rapidly transformed into 'bound' or 'non-reactive' mercury and that about 25% of the mercury added was recovered associated with the organic material settling to the bottom of the bags; (ii) the response of the biological population to 1 microgram Hg/l was very limited and in fact a transient reduction in photosynthetic carbon uptake per unit chlorophyll was the only noticeable effect and there were no changes in population size or structure that could be attributed to mercury; (iii) at 10 micrograms Hg/l the zooplankton population was reduced markedly and this did produce changes in the structure of both the zooplankton and phytoplankton populations. These results are similar to the results of a comparable experiment carried out in Vancouver Island (Cepex) and point to the conclusion that the levels of mercury found in surface waters around the coast of the U.K. (0.001--0.022 microgram Hg/l) are one or two orders of magnitude below the levels at which a response of the biological population can be demonstrated. The usefulness of large scale enclosed ecosystems for further pollution research is discussed and it is concluded that those facilities that provided a link between the water column and the sediments would be most useful since they would (1) enable estimates to be made of the flux rates of pollutants from the water column to the sediments; and (2) allow experiments to be carried out with the pollutant in contact with sediment in its natural form.
Tax Protein-induced Expression of Antiapoptotic Bfl-1 Protein Contributes to Survival of Human T-cell Leukemia Virus Type 1 (HTLV-1)-infected T-cells*♦

Background: Antiapoptotic Bcl-2 proteins are up-regulated in HTLV-1-infected T-cells. Results: Antiapoptotic Bfl-1 protein is regulated by viral Tax and HBZ proteins and is involved in survival of HTLV-1-transformed T-cells. Conclusion: Bfl-1, as well as Bcl-xL, induces resistance to apoptosis in HTLV-1-transformed T-cells. Significance: We provide evidence for Bfl-1 and Bcl-xL as potential therapeutic targets in the treatment of leukemia/lymphoma associated with HTLV-1. Human T lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL). ATLL is a severe malignancy with no effective treatment. HTLV-1 regulatory proteins Tax and HTLV-1 basic leucine zipper factor (HBZ) play a major role in ATLL development, by interfering with cellular functions such as CD4+ T-cell survival. In this study, we observed that the expression of Bfl-1, an antiapoptotic protein of the Bcl-2 family, is restricted to HTLV-1-infected T-cell lines and to T-cells expressing both Tax and HBZ proteins. We showed that Tax-induced bfl-1 transcription through the canonical NF-κB pathway. Moreover, we demonstrated that Tax cooperated with c-Jun or JunD, but not JunB, transcription factors of the AP-1 family to stimulate bfl-1 gene activation. By contrast, HBZ inhibited c-Jun-induced bfl-1 gene activation, whereas it increased JunD-induced bfl-1 gene activation. We identified one NF-κB, targeted by RelA, c-Rel, RelB, p105/p50, and p100/p52, and two AP-1, targeted by both c-Jun and JunD, binding sites in the bfl-1 promoter of T-cells expressing both Tax and HBZ. Analyzing the potential role of antiapoptotic Bcl-2 proteins in HTLV-1-infected T-cell survival, we demonstrated that these cells are differentially sensitive to silencing of Bfl-1, Bcl-xL, and Bcl-2. Indeed, both Bfl-1 and Bcl-xL knockdowns decreased the survival of HTLV-1-infected T-cell lines, although no cell death was observed after Bcl-2 knockdown. Furthermore, we demonstrated that Bfl-1 knockdown sensitizes HTLV-1-infected T-cells to ABT-737 or etoposide treatment. Our results directly implicate Bfl-1 and Bcl-xL in HTLV-1-infected T-cell survival and suggest that both Bfl-1 and Bcl-xL represent potential therapeutic targets for ATLL treatment.
Analyzing the Success Drivers of e-Business Companies

Although there is a growing amount of theoretical literature, only limited attention has been allocated to empirically determine the relative influence of a broad set of strategic success factors of e-business companies across several industries. We concentrate on the impact of marketing strategies and chosen business models and differentiate between direct and indirect drivers on revenue and profitability in order to estimate the total effect of a certain strategy or business model. Based on a survey of 147 e-businesses from different industries we empirically test, with the help of seemingly unrelated regression models, the relative importance of the various strategy elements. Our estimation results show that business models where the firm profits from transactions (e.g., via fixed access or usage fees) and is able to sell pricy products and services are well suited to reach profitability. The by far most important element of the marketing strategy is the achieved customer satisfaction, which has a significant and strong effect on revenue, but only a moderate direct effect on profitability. Due to our modeling approach we find that the total elasticity of this element of the marketing strategy is driven by the indirect effect from revenue on profitability
The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies

Background. This study examined the persistence of attention deficit hyperactivity disorder (ADHD) into adulthood. Method. We analyzed data from published follow-up studies of ADHD. To be included in the analysis, these additional studies had to meet the following criteria: the study included a control group and it was clear from the methods if the diagnosis of ADHD included subjects who did not meet full criteria but showed residual and impairing signs of the disorder. We used a meta-analysis regression model to separately assess the syndromatic and symptomatic persistence of ADHD. Results. When we define only those meeting full criteria for ADHD as having ‘persistent ADHD’, the rate of persistence is low, ~15% at age 25 years. But when we include cases consistent with DSM-IV's definition of ADHD in partial remission, the rate of persistence is much higher, ~65%. Conclusions. Our results show that estimates of ADHD's persistence rely heavily on how one defines persistence. Yet, regardless of definition, our analyses show that evidence for ADHD lessens with age. More work is needed to determine if this reflects true remission of ADHD symptoms or is due to the developmental insensitivity of diagnostic criteria for the disorder.
Functional Outcomes After Heel Pad Reconstruction: A Review of 7 Cases

&NA; Sensate, durable heel pad reconstruction is challenging. The present study assessed the functional outcomes after heel pad reconstruction using various flap techniques at our institution. From June 2011 to June 2016 (5‐year period), 7 consecutive patients underwent heel pad reconstruction for various etiologies, with 3 microvascular free flaps (42.9%; 2 musculocutaneous flaps [66.7%] and 1 contralateral medial plantar flap [33.3%]) and 4 local pedicle flaps (57.1%; 3 instep medial plantar artery flaps [75.0%] and 1 distally based reverse sural flap [25.0%]). The patient records and demographic data were reviewed, and surgically related information was obtained and analyzed. The subjective components of the American Orthopaedic Foot and Ankle Society hindfoot clinical ratings scale were used to evaluate the pain and functional outcomes. Sensation was assessed using Semmes‐Weinstein monofilaments, and ulcer recurrence was recorded. The mean age of the patients was 41.7 (range 11 to 70) years, the mean defect size was 59 (range 12 to 270) cm2, and the mean follow‐up duration was 22 (range 15 to 43) months. Complete flap survival was achieved without significant complications in all 7 patients. Patients treated with the sensate medial plantar artery flap recorded the highest mean American Orthopaedic Foot and Ankle Society score of 57.3 (maximum score of 60) and experienced a return of deep sensation at 6 (range 6 to 24) months and protective sensation at 1 year. This was followed by the reverse sural flap and the musculocutaneous flap. No recurrent heel ulceration was observed in our series of patients. In conclusion, the sensate medial plantar flap is a satisfactory method for coverage of small‐ to moderate‐size heel defects. &NA; Level of Clinical Evidence: 4
Predictive Ability of Emotional Intelligence Scores on Employee Self-Reported Perception of Comprehensive Organizational Credibility Inventory

Predictive Ability of Emotional Intelligence Scores on Employee Self-Reported Perception of Comprehensive Organizational Credibility Inventory by Leif A. Ford B.S., Northwest Christian University, 1994 M.B.A., Northwest Christian University, 2008 Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Organizational Psychology
Phases I–III Clinical Trials Using Adult Stem Cells

First randomized clinical trials have demonstrated that stem cell therapy can improve cardiac recovery after the acute phase of myocardial ischemia and in patients with chronic ischemic heart disease. Nevertheless, some trials have shown that conflicting results and uncertainties remain in the case of mechanisms of action and possible ways to improve clinical impact of stem cells in cardiac repair. In this paper we will examine the evidence available, analyze the main phase I and II randomized clinical trials and their limitations, discuss the key points in the design of future trials, and depict new directions of research in this fascinating field.
Uncle Tom and Mr. Charlie: Metaphysical Pathos in the Study of Racism and Personal Disorganization

The commonly held hypothesis the Negro Americans are very likely to experience "crisis of identity" and exhibit low self-esteem is questioned. After a brief description of the prevailing view, several major theoretical statements explaining the assumed state of affairs are presented. The third section reviews a variety of empirical evidence revealing considerable ambiguity over, if not directly challenging, currently held assumptions. The concluding section presents a series of alternative perspectives which suggest hypotheses which conflict those derived from the traditional position.
Quantitative Analysis of Asbestos Burden in a Series of Individuals with Lung Cancer and a History of Exposure to Asbestos

Asbestos is recognized as a lung carcinogen. In the present study, tissue from 20 individuals who died from lung cancer and who had a history of exposure to asbestos was evaluated for the presence of asbestos bodies and uncoated asbestos fibers. A digestion procedure was used to isolate the particulates from the tissue. The samples were evaluated by light microcopy to quantify the numbers of ferruginous bodies in the tissue. The uncoated fibers (which included all fibers equal to or greater than 0.5 μm) were analyzed by analytical transmission electron microscopy. Seventeen of the 20 cases were positive for ferruginous bodies (which were morphologically consistent with asbestos bodies). Five of these were found to have concentrations within the range used in our laboratory for the general population (<20 ferruginous bodies/g wet tissue). Nineteen of the 20 cases were found to have asbestos fibers in the higher magnification scan (either 16 K or 20 K). Some of the asbestos fibers identified were specific for the types of exposures that were reported. Most individuals in this study were found to have mixed populations of asbestos fibers in the lung tissue. This suggests that when there are exposures to products containing commercial asbestos there are likely exposures to dust containing noncommercial asbestos. A contrast exists in the dust burden within the lung of these individuals as compared to samples from the general population in that occupational or “occupational-like” exposures such as in these cases are often reflected by the presence of longer fibers of asbestos in the tissue.