Miracle-dz/UniFAR-FTUs huggingface dataset:
Transduction potential of human retroviruses in highly proliferating small‐cell lung cancer cells as well as non‐proliferating hematopoietic stem cells

Direct gene transfer to solid tissues or metastatic cancer cells requires vectors capable of in vivo transduction to specific cells. The predominant retroviral vectors of murine origin are inactivated by human complement, which precludes their use in vivo. Such inactivation does not take place with vectors based on human retroviruses. Murine retroviral vectors are also limited to proliferating cells, which human retroviruses are not. In this study we examined whether or not a vector using components from the human retroviruses HIV‐1 and HTLV‐1 could infect small‐cell lung cancer cells and resting CD34+ hematopoietic stem cells. While HIV‐1 itself was unable to infect cells lacking the CD4‐membrane molecule, chimeric viral particles (pseudotype virus) with HIV‐1 genome and HTLV‐1 envelope components were able to infect both CD4‐containing lymphocytic cells, CD4‐negative tumour cells and hematopoietic stem cells. After infection with the pseudotype vector, the RNA genome was reverse transcribed and integrated. Transduction efficiency and gene expression under the HIV‐1 LTR promoter in both tumour and stem cells were found to be of a similar or greater magnitude than in lymphocytic cells. These results suggest that gene transfer targeting proliferating as well as resting cells in vivo may be realized using components from human retroviruses.
Characterization of the novel E3 ubiquitin ligase encoded in exon 3 of herpes simplex virus-1-infected cell protein 0

Infected cell protein 0 (ICP0) of herpes simplex virus-1 is a 775-aa residue multifunctional protein that acts as a promiscuous transactivator linked to the degradation of several proteins. ICP0 is the only protein known which encodes two physically separated E3 ubiquitin (Ub) ligase domains, one, designated herpes virus Ub ligase 1 (HUL-1) located in a domain encoded in exon 3 and one designated herpes virus Ub ligase 2 (HUL-2) associated with the really interesting new gene (RING) finger domain encoded by exon 2. We report the following: (i) ICP0 residues 543–680 are sufficient for HUL-1 E3 activity and necessary determinants are encoded between residues 616 and 680. (ii) In substrate independent in vitro ubiquitylation reactions, a chimeric protein containing the HUL-1 domain promotes the ubiquitylation of itself and the ubiquitin conjugating enzyme (E2) cdc34 and interacts with cdc34. (iii) The mechanism of HUL-1 E3 function does not involve formation of a thioester between the HUL-1 domain and Ub. (iv) Residues 621–625 are essential for in vitro HUL-1 E3 activity and interaction between the HUL-1 domain and cdc34, suggesting that this interaction is required for HUL-1 E3 function.
The RPB2 Flap Loop of Human RNA Polymerase II Is Dispensable for Transcription Initiation and Elongation

ABSTRACT The flap domain of multisubunit RNA polymerases (RNAPs), also called the wall, forms one side of the RNA exit channel. In bacterial RNAP, the mobile part of the flap is called the flap tip and makes essential contacts with initiation and elongation factors. Cocrystal structures suggest that the orthologous part of eukaryotic RNAPII, called the flap loop, contacts transcription factor IIB (TFIIB), but the function of the flap loop has not been assessed. We constructed and tested a deletion of the flap loop in human RNAPII (subunit RPB2 Δ873-884) that removes the flap loop interaction interface with TFIIB. Genome-wide analysis of the distribution of the RNAPII with the flap loop deletion expressed in a human embryonic kidney cell line (HEK 293) revealed no effect of the flap loop on global transcription initiation, RNAPII occupancy within genes, or the efficiency of promoter escape and productive elongation. In vitro, the flap loop deletion had no effect on promoter binding, abortive initiation or promoter escape, TFIIS-stimulated transcript cleavage, or inhibition of transcript elongation by the complex of negative elongation factor (NELF) and 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB) sensitivity-inducing factor (DSIF). A modest effect on transcript elongation and pausing was suppressed by TFIIF. Although similar to the flap tip of bacterial RNAP, the RNAPII flap loop is not equivalently essential.
A Multilevel Study of Socioeconomic Predictors of Regular Mammography Use Among African-American Women

Background: Little is known about the predictors of adherence to mammography guidelines by African-American women. We assessed individual-level and group-level socioeconomic predictors of regular mammography use in a large cohort of African-American women. Methods: We included 14,706 participants in the Black Women's Health Study who were 40 to 69 years of age at baseline in 1995. Data were obtained through mail questionnaires at entry and biennially during three 2-year follow-up periods until 2001. We linked the women's addresses to census block (neighborhood) socioeconomic data. With multilevel multivariable regression analysis, we assessed the relation of individual-level and neighborhood socioeconomic factors to “regular” mammography use (use in all three follow-up periods) relative to nonregular use, with control for other predictors. Results: Most participants had health insurance and almost half had graduated college. Having health insurance was the socioeconomic variable most strongly associated with regular mammography use (odds ratio, 3.59; 95% confidence interval 3.02-4.28); the association was present at all levels of educational attainment, household income, and neighborhood socioeconomic status. Regular mammography use increased with individual household income: odds ratio, 2.00 (95% confidence interval, 1.58-2.53) for household income >$100,000 relative to <$15,001. Regular mammography use did not vary across level of education. Higher neighborhood socioeconomic status was significantly associated with regular mammography use before, but not after, control for household income. Conclusions: Access to health insurance is strongly associated with regular mammography use among African-American women, even at higher levels of educational attainment and socioeconomic status. Neighborhood socioeconomic characteristics do not materially influence regular use.
Tc1 effector diversity shows dissociated expression of granzyme B and interferon-γ in HIV infection

Objective: To examine antigen specific cytotoxic effector T cell diversity in HIV infected individuals. Design: We used a panel of previously defined HLA class I-restricted HIV peptides to stimulate CD8 cells in freshly isolated peripheral blood mononuclear cells of HIV infected patients, to determine cognate killing via the perforin–granzyme pathway and inflammation induced by secretion of interferon (IFN)-γ. Methods: ELISPOT assays were used to measure the secretion of granzyme B (GzB) and IFN-γ at single cell resolution. Results: In all nine patients only approximately 20% of the peptides triggered a canonical Tc1 response with simultaneous release of GzB and IFN-γ. The majority of these peptides (approximately 80%) that elicited recall responses fell into the ‘single positive’ category with induction of either GzB or IFN-γ alone. The GzB positive cells did not produce interleukin (IL)-4 or IL-5. Conclusion: The GzB positive but IFN-γ negative CD8 cells are programmed to induce apoptosis mediated killing without inflammation while the GzB negative and IFN-γ positive CD8 cells could mediate inflammation without killing. This Tc1 CD8 effector cell diversity and the understanding of these differentiation mechanisms may enable the precise implementation and fine-tuning of fundamentally different defense strategies against HIV and other infections.
The C‐terminal acidic tail is responsible for the inhibitory effects of HMGB1 on efferocytosis

HMGB1 was described originally as a nuclear protein involved in DNA binding and transcriptional regulation. However, HMGB1 also has an extracellular role as a potent mediator of inflammation and can diminish the uptake of apoptotic cells by phagocytes, a process called efferocytosis. To explore the mechanism responsible for the ability of HMGB1 to inhibit efferocytosis, we examined the role of the C‐terminal acidic tail, a region of HMGB1 that has been shown to participate in specific intramolecular interactions. Deletion of the C‐terminal tail abrogated the ability of HMGB1 to decrease murine macrophage ingestion of apoptotic neutrophils and to diminish phagocytosis‐induced activation of Erk and Rac‐1 in macrophages. We found that RAGE plays a major role in efferocytosis, and deletion of the C‐terminal tail of HMGB1 prevented binding of HMGB1 to RAGE but not to other macrophage receptors involved in efferocytosis, such as the αVβ3 integrin. Whereas HMGB1 decreased ingestion of apoptotic neutrophils significantly by alveolar macrophages under in vivo conditions in the lungs of mice, this effect was lost when the C‐terminal acidic tail was absent from HMGB1. These results demonstrate that the HMGB1 C‐terminal tail is responsible for the inhibitory effects of HMGB1 on phagocytosis of apoptotic neutrophils under in vitro and in vivo conditions.
Increased vascular permeability and nitric oxide production in response to hypoxia in the pineal gland

Abstract: This study examined the factors that may be involved in altering the function of pineal gland in hypoxic conditions. Adult Wistar rats were subjected to hypoxia and the pineal gland was examined for the mRNA and protein expression of hypoxia‐inducible factor‐1α (HIF‐1α), vascular endothelial growth factor (VEGF), endothelial, neuronal and inducible nitric oxide synthase (eNOS, nNOS, iNOS) at 3 hr–14 days after hypoxic exposure by real time reverse transcription‐polymerase chain reaction, Western blotting and immunohistochemistry. Upregulated mRNA and protein expression of HIF‐1α, VEGF, eNOS, nNOS and iNOS was observed in response to hypoxia. VEGF concentrations as determined by enzyme immunoassay and nitric oxide (NO) production measured by colorimetric assay were significantly higher after hypoxic exposure when compared with the controls. Melatonin content of the pineal gland, as determined by ELISA, was significantly reduced after the hypoxic exposure. Dilated blood vessels expressing eNOS were observed in hypoxic rats. Cells immunoreactive for VEGF were identified as the astrocytes whereas those immunoreactive for iNOS were pinealocytes and macrophages. Our findings indicate that excess production of VEGF and NO in pineal gland in response to hypoxia may be involved in increased vascular permeability as evidenced by an enhanced leakage of rhodamine isothiocyanate (RhIC). The increased vascular permeability may allow free access of serum‐derived substances in the pineal gland that may affect the secretory function of the pinealocytes. Administration of exogenous melatonin may be beneficial as it reduced VEGF concentration and NO production significantly in hypoxic rats, and leakage of RhIC was concomitantly reduced.
Crystal structure of (perchlorato-κO)(1,4,7,10-tetraazacyclododecane-κ4 N)copper(II) perchlorate

The crystal structure of (perchlorato-κO)(1,4,7,10-tetraazacyclododecane-κ4 N)copper(II) perchlorate is reported. The crystal was grown from a solution of methanol at ambient temperature which resulted in no co-crystallization of solvent.
Industry-specific CSR: analysis of 20 years of research

Purpose The purpose of this study is to analyze the literature on industry-specific corporate social responsibility (CSR) practices. Design/methodology/approach Using a multiple-keyword search, the authors identified 302 articles reporting on such practices, published in 99 different academic journals between 1995 and 2014. These articles were analyzed to map the CSR literature, identify which industries have been under greater scrutiny and distinguish trends in the most researched industries. Findings The authors’ findings indicate that the CSR studies are very unevenly distributed and that the issues studied and the methods used vary widely across industries. The authors also map this field of study and propose suggestions on where research on industry-specific CSR should go in the future. Originality/value The first extensive, systematic analysis of the industry-specific CSR literature is provided. The current research adds value to the literature by highlighting the key issues investigated, as well as those that require further inquiry.
The extracellular loop between TM5 and TM6 of P-glycoprotein is required for reactivity with monoclonal antibody UIC2.

P-glycoprotein (P-gp), encoded by the MDR1 gene, is a plasma membrane transporter which confers resistance to many chemotherapeutic drugs. Monoclonal antibodies raised against P-gp have been used as tools to study P-gp topology and activity. Monoclonal antibody UIC2 recognizes a functional conformation of P-gp on the cell surface and blocks P-gp-mediated drug transport. Knowledge about the UIC2 epitope and the mechanism of its inhibitory effects may be helpful for understanding P-gp structure and developing P-gp inhibitors. In the present work, using several chimeras of MDR1 and MDR2, we found that the native sequence of the predicted extracellular loop between transmembrane domains (TM) 5 and 6 of P-gp is necessary, but not sufficient, for UIC2 reactivity. In addition, UIC2 reactivity is also affected by mutations in TM6, a region known to be involved in interactions of P-gp with substrates. These observations suggest that residues in the extracellular loop between TM5 and TM6 are directly involved in the display of the UIC2 epitope. Since TM6 has been shown to be actively involved in drug transport process, the proximity of this region to TM6 may help to explain why UIC2 binding is sensitive to the functional state of P-gp and why binding of UIC2 inhibits P-gp-mediated drug transport.
Concussions Among University Football and Soccer Players: A Pilot Study

ObjectiveA pilot study to examine the incidence and characteristics of concussions for one season of university football and soccer. DesignRetrospective survey. Participants60 football and 70 soccer players reporting to 1998 fall training camp. Of these, 44 football and 52 soccer players returned a completed questionnaire. Main Outcome MeasuresBased on self-reported symptoms, calculations were made to determine the number of concussions experienced during the previous season, the duration of symptoms, the time for return to play and any associated risk factors for concussions. ResultsOf all the athletes who returned completed questionnaires, 34.1% of the football players and 46.2% of the soccer players had experienced symptoms of a concussion during the previous season. Only 16.7% of the concussed football players and 29.2% of the concussed soccer players realized they had suffered a concussion. All of the concussed football players and 75.0% of the concussed soccer players experienced more than one concussion during the season. The symptoms from the concussion lasted for at least 1 day in 28.6% of the football players and 18.1% of the soccer players. Variables that increased the odds of suffering a concussion during the previous season for football and soccer players included a past history of a recognized concussion. ConclusionMore university soccer players than football players may be experiencing sport related concussions. Variables that seem to increase the odds of suffering a concussion during the previous season for football and soccer players include a history of a recognized concussion. Despite being relatively common, many players may not recognize the symptoms of a concussion.
Electrostatic bending actuators with a liquid filled nanometer scale gap

We report a considerable improvement in the electrostatic actuation of silicon-based nano electrostatic drive (NED) structures [1] via the insertion of a liquid into the nanosystem. The dielectric liquid provides an insulating, high dielectric constant deformable medium in the electrode gaps that enhances the generated force per unit-applied volt performance. The study demonstrates that small volumes of liquids (microfluidics/nanofluidics) can be inserted into micro and nanoelectromechanical systems (MEMS/NEMS) to enhance systems' performances up to 2.75.
The Impact of Fiscal Policy on Foreign Direct Investment Inflows: A Study of India and Select Asian Economies

While the role of taxation in influencing FDI has received considerable attention in literature, there has been very less work on examining the role of fiscal policy as a whole on FDI inflows. The dimension of fiscal policy that relates to the expenditure of the government has not received much attention in terms of its impact on FDI. This study would attempt to bridge the gap in literature by examining the impact of both the revenue and expenditure side of fiscal policy on FDI inflows in India and other select economies of the Asian region. The paper identifies the determinants of FDI flows with special reference to fiscal policy variables, namely tax treaties and developmental expenditure of the government. With the help of principle component regression, we have estimated a panel equation with the Least Squared Dummy Variables (fixed effects model) approach. The determinants which have emerged as significant are FDI openness and infrastructure. Our variables of interest, that is, the fiscal policy variables turn out to be insignificant. Thus while a competitive fiscal policy may facilitate operations of business, it is still not a prime consideration in investment decisions.
Postdrinking sexual perceptions and behaviors toward another person: Alcohol expectancy set and gender differences

Based on research showing that alcohol expectancy and gender both play a role in sexual perceptions, we factorially crossed the apparent drinking status of yoked pairs consisting of a participant and a target person (a confederate posing as co‐participant). Alcohol expectancy interacted with gender in complex ways to influence sexual perceptions. We also found behavioral effects: men showed more erotic material to both male and female targets than women did. Men perceived the target as more sexually aroused by erotic material than women did. Men also showed more erotic material to drinking targets than to non‐drinking targets. Sexual perceptions and erotica‐showing behavior were correlated significantly and positively. We discuss these findings in terms of implications for postdrinking heterosexual encounters.
Flexible and sensitive foot pad for sole distributed force detection

We develop highly flexible and compressible 3D interconnected porous PDMS structures by using sugar cubes as templates. The porous structures can be compressed to more than 80% without any side-wall buckling comparable with bulk polymers. Force sensitive resistors were fabricated by filtration of the CNT solution inside the porous structure of PDMS. We found that sufficient acid treatment can increase the adhesion and bonding between CNTs and PDMS. Force sensitive resistors respond the applied pressure and compressive strains by high linearity (R2>0.97) and sensitivity (GFs>2) with a reliable manner. Finally, as an application of our force sensitive resistors, a flexible foot pad containing force sensitive resistors arrays is developed for the foot sole distributed force detection.
Local festivals, social capital and sustainable destination development: experiences in East London

ABSTRACT This paper explores the nature of social capital arising from engagement in local festivals and the implications of this for the social sustainability of an emerging destination. Two case studies are developed from a longitudinal research project which investigates local festivals staged in the Hackney Wick and Fish Island area adjacent to Queen Elizabeth Olympic Park in East London, UK between 2008 and 2014. This area has been directly affected by extensive development and regeneration efforts associated with the staging of the London 2012 Olympic Games. The two festivals considered here respond to the challenges and opportunities arising for local people as the area changes. One festival aims to foster a sense of community by creating shared experiences and improving communication across diverse groups. The other draws together the cultural community, links them to the opportunities arising as the area emerges as a destination, and attracts visitors. These festivals increase social capital in the area, but its distribution is very uneven. The accrual of social capital exacerbates existing inequalities within the host community, favouring the “haves” at the expense of the “have nots”. There are tensions between the development of social capital and social sustainability in this emerging destination.
YM872, a novel selective alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, reduces brain damage after permanent focal cerebral ischemia in cats.

YM872 ([2,3-dioxo-7-(1H-imidazol-1-yl)-6-nitro-1,2,3, 4-tetrahydro-1-quinoxalinyl]-acetic acid monohydrate), a selective, potent and highly water-soluble competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, was investigated for its neuroprotective effect against focal cerebral ischemia in halothane-anesthetized cats. Cats were subjected to permanent occlusion of the left middle cerebral artery for 6 h, then sacrificed and examined histologically. The electroencephalogram and cerebral blood flow were monitored. Intravenous infusion of YM872 starting 10 min after the onset of ischemia at a rate of 2 mg/kg/h for 6 h markedly reduced the volume of ischemic damage by 61% (from 2604 +/- 202 mm3 of the cerebral hemisphere in saline-treated cats to 1025 +/- 277 mm3 in YM872-treated cats; P < .01), as assessed in 12 stereotaxically determined coronal sections. No significant differences were observed between YM872- and saline-treated cats concerning physiological variables including brain temperature. No precipitation of YM872 in the kidney was seen in any YM872-treated animal. The present data further support the notion that the AMPA receptor plays an important role in the progression of focal ischemic damage in a gyrencephalic model. This evidence for the neuroprotective efficacy of YM872 suggests its therapeutic potential in the treatment of acute stroke in humans.
Investigating the moderating effect of family on the relationship between entrepreneurial orientation and success of enterprise: case of Pakistani manufacturing SMEs

Entrepreneurial orientation (EO) is one of the widely researched areas in entrepreneurship studies. Yet researchers have to come to agreement to the dimensionality of this important construct. EO is a multi-dimensional construct with varying impact on the performance and success of an enterprise in a developing context. Likewise, family ownership of the entrepreneurial business is one of the oldest phenomena in business circles. In developing countries family owned businesses makeup sizeable majority. The present study is conducted to investigate the role EO plays in the success of an enterprise with the moderating influence of family involvement. The study results indicate that proactiveness and autonomy are the most significant dimensions in the success of an enterprise. The results indicate that when family is taken as a moderator, the overall influence of EO dimensions is considerably reduced. The study concludes that cultural setting of entrepreneurial businesses and entrepreneurs themselves are subject to cultural norms and values and this cultural setting inhibit certain aspects of entrepreneurial activity, limiting the growth of entrepreneurship in a country. The study also recommends and points out future directions for further research.