Miracle-dz/UniFAR-FTUs huggingface dataset:
AAV-mediated gene transfer for retinal diseases

Vectors based on the adeno-associated virus (rAAV) are able to transduce the retina of animal models, including non-human primates, for a long-term period, safely and at sustained levels. The ability of the various rAAV serotypes to transduce retinal target cells has been exploited to successfully transfer genes to photoreceptors, retinal pigment epithelium and the inner retina, which are affected in many inherited and non-inherited blinding diseases. rAAV-mediated, constitutive and regulated gene expression at therapeutic levels has been achieved in the retina of animal models, thus providing proof-of-principle of gene therapy efficacy and safety in models of dominant and recessive retinal disorders. In addition, gene transfer of molecules with either neurotrophic or antiangiogenic properties provides useful alternatives to the classic gene replacement for treatment of both mendelian and complex traits affecting the retina. Years of successful rAAV-mediated gene transfer to the retina have resulted in restoration of vision in dogs affected with congenital blindness. This has paved the way to the first attempts at treating inherited retinal diseases in humans with rAAV. Although the results of rAAV clinical trials for non-retinal diseases give a warning that the outcome of viral-mediated gene transfer in humans may be different from that predicted based on results in other species, the immune privilege of the retina combined with the versatility of rAAV serotypes may ultimately provide the first successful treatment of human inherited diseases using rAAV.
Family Firm Configurations for High Performance: The Role of Entrepreneurship and Ambidexterity

The performance drivers of family firms have spawned considerable research interest. Almost exclusively this research has relied on independent sets of explanatory variables in linear analyses. These analyses mask the complex interdependencies that are likely to exist among key success factors, leading to faulty theory and misspecified implications for practice. As treatment, the authors propose a configuration approach to family firm performance that accounts for complex interdependencies among entrepreneurial, innovation and family influence conditions. Using a fuzzy set qualitative comparative analysis of a sample of 129 Finnish family firms, the authors identify sufficient conditions with regard to the existence or absence of antecedent conditions to family firm performance. These conditions include entrepreneurial orientation, exploration and exploitation activities that form causal paths towards family firm performance. To enrich the analysis, the authors theorize and empirically analyse how these conditions might differ in family firms with high and low levels of family influence. They deepen the current understanding of configurations that promote the performance of family firms, offer important implications for theory and practice, and set new directions for future research on the strategic management of family firms. The results are also virtually identical and insensitive to change across subjective and objective performance measures.
Do Donors Reduce Bilateral Aid to Countries With Restrictive NGO Laws? A Panel Study, 1993-2012

Foreign aid contributes to about 10% of gross domestic product (GDP) of developing countries. To distribute aid in recipient countries, Western donors increasingly rely on nongovernmental organizations (NGOs). Yet, since the mid-1990s, 39 developing countries have adopted laws restricting the inflow of foreign aid to NGOs operating in their jurisdictions. In response to these restrictions, have bilateral donors reduced aid, either as a punishment or because they cannot find appropriate NGOs for aid delivery? We explore this question by examining a panel of 134 aid-receiving countries for the years 1993-2012. We find that all else equal, the adoption of a restrictive NGO finance law is associated with a 32% decline in bilateral aid inflows in subsequent years. These findings hold even after controlling for levels of democracy and civil liberties, which suggests that aid reduction responds to the removal of NGOs from aid delivery chains, and not to democracy recession.
Composite Brains: Toward a Systems Theory of Neural Reconstruction

The results of uncontrolled, open-label clinical trials indicate that reconstructive cellular therapies have the capacity to produce meaningful functional improvements in patients with brain disorders. However, the transplantation of fetal cells has not progressed to viable best practice treatment for any brain disorder. A conceptual approach, referred to as the Repair Model, has served as a useful heuristic for initiating research in the field and guiding the development of new practices. Analysis of evidence for the treatment of Parkinson's disease indicates that recovery following neural grafting is a complex process influenced by factors beyond the replacement of neurons. An alternative approach, the Composite Brain Model, is outlined to address limitations of the Repair Model. A hierarchical, open-system model is proposed, which aims to track the interactions between the grafted cells, the host brain, and the environment. The Composite Brain Model emphasizes the importance of the interactions between the patient, their physical and social environment, and the provision of rehabilitation during recovery. It is proposed that the Composite Brain Model is useful in providing an alternative perspective for research, theory building, and practice.
Temporal Trends and Molecular Epidemiology of Recently Described Serotype 6C of Streptococcus pneumoniae

ABSTRACT We studied the epidemiology of the recently described serotype 6C of Streptococcus pneumoniae among a collection of carriage isolates recovered between 1996 and 2007 in Portugal. Of 4,064 isolates, 106 (2.6%) were of serotype 6C, 17.9% of which were multidrug resistant. The strains were genetically diverse.
Flash memory-based storage device for mobile embedded applications

This paper reviews Flash memory technology and flash translation layer (FTL) that provides a block device interface out of flash memory. It also describes two implementations of FTL that represent two extreme points in the spectrum of cost-performance trade-offs in FTL implementation. After presenting results on the performance and energy- efficiency of the two FTLs, this paper argues for a configurable FTL to address the diversity of mobile embedded systems in terms of cost and performance requirements.
Specificity of activation by phosphoinositides determines lipid regulation of Kir channels

Phosphoinositides are critical regulators of ion channel and transporter activity. Defects in interactions of inwardly rectifying potassium (Kir) channels with phosphoinositides lead to disease. ATP-sensitive K+ channels (KATP) are unique among Kir channels in that they serve as metabolic sensors, inhibited by ATP while stimulated by long-chain (LC) acyl-CoA. Here we show that KATP are the least specific Kir channels in their activation by phosphoinositides and we demonstrate that LC acyl-CoA activation of these channels depends on their low phosphoinositide specificity. We provide a systematic characterization of phosphoinositide specificity of the entire Kir channel family expressed in Xenopus oocytes and identify molecular determinants of such specificity. We show that mutations in the Kir2.1 channel decreasing phosphoinositide specificity allow activation by LC acyl-CoA. Our data demonstrate that differences in phosphoinositide specificity determine the modulation of Kir channel activity by distinct regulatory lipids.
Anti‐tumor efficacy of an anti‐epidermal‐growth‐factor‐ receptor monoclonal antibody and its F(ab′)2 fragment against high‐ and low‐egfr‐expressing carcinomas in nude mice

Monoclonal antibody (MAb) MINTS specifically detects the epidermal‐growth‐factor receptor (EGFR). In vitro analyses of intact MINTS (IgG,) and its F(ab′)2 fragment indicated that both forms of the MAb inhibited binding of ′25l‐mEGF to EGFR, induced receptor internalization and blocked EGF‐induced EGFR tyrosine‐kinase activation in A431 cells. Both forms of the MAb also inhibited to the same extent the proliferation of the carcinoma cell lines A431 and IGROVI, despite the difference in EGFR levels on the cells. The detection of TGFα mRNA and the inhibition of cell growth in EGF‐free conditions by anti‐EGFR MAb indicated the involvement of an EGFR/TGFα autocrine/ paracrine pathway in the in vitro growth of both cell lines. Analysis of mice xenotransplanted s.c. with A43I cells and treated with MINTS revealed a block in A431 tumor take in 6 of 10 animals when intact MAb was administered from day 0 to day 11. On a molar basis, F(ab)2 at the same dose was ineffective, although at a 7‐fold higher dose F(ab′)2 reduced s.c. tumor growth by 80%. At the same dose, intact MINTS MAb reduced s.c. growth of the EGFR‐negative MeWo cell line by 5%. Survival of mice bearing IGROV I i.p. xenotransplants and treated locally with either form of MAb was significantly prolonged even when treatment was initiated on day 3. Corrected doses of intact and F(ab′)2 fragment, which accounted for the difference in serum half‐lives of the MAb forms, resulted in similar survival rates in the tumor‐bearing mice. These pre‐clinical results suggest that MINTS MAb might be safely used for systemic therapy of EGFR‐over‐expressing tumors. Loco‐regional therapy might be contemplated in the case of tumors with moderate/low EGFR expression. © 1995 Wiley‐Liss, Inc.
Lack of cool, not warm, extremes distinguishes late 20th Century climate in 979-year Tasmanian summer temperature reconstruction

Very few annually resolved millennial-length temperature reconstructions exist for the Southern Hemisphere. Here we present four 979-year reconstructions for southeastern Australia for the austral summer months of December–February. Two of the reconstructions are based on the Australian Water Availability Project dataset and two on the Berkeley Earth Surface Temperature dataset. For each climate data set, one reconstruction is based solely on Lagarostrobos franklinii (restricted reconstructions) while the other is based on multiple Tasmanian conifer species (unrestricted reconstructions). Each reconstruction calibrates ~50−60% of the variance in the temperature datasets depending on the number of tree-ring records available for the reconstruction. We found little difference in the temporal variability of the reconstructions, although extremes are amplified in the restricted reconstructions relative to the unrestricted reconstructions. The reconstructions highlight the occurrence of numerous individual years, especially in the 15th−17th Centuries, for which temperatures were comparable with those of the late 20th Century. The 1950−1999 period, however, stands out as the warmest 50-year period on average for the past 979 years, with a sustained shift away from relatively low mean temperatures, the length of which is unique in the 979-year record. The reconstructions are strongly and positively related to temperatures across the southeast of the Australian continent, negatively related to temperatures in the north and northeast of the continent, and uncorrelated with temperatures in the west. The lack of a strong relationship with temperatures across the continent highlights the necessity of a sub-regional focus for Australasian temperature reconstructions.
A Parallel Hybrid Excitation Flux-Switching Generator DC Power System Based on Direct Torque Linear Control

A parallel hybrid excitation flux-switching (PHEFS) generator dc power system is presented in this paper. The PHEFS topology is proposed to achieve good flux regulation capability of the system as well as capability of deexcitation at fault and avoid permanent magnet (PM) magnetic shortcircuit and demagnetization. In order to improve the system's steady state and dynamic performance, a direct torque linear control (DTLC) scheme is proposed then. This DTLC scheme, which contains a voltage loop only and develops the direct linear relationship between the torque and sinusoidal value of the torque angle, can regulate the instantaneous torque directly and smoothly without current loop. The flux-weakening control of the DTLC scheme is also studied; the PHEFS generator system with excellent dynamic performance and lower flux and torque ripple has been achieved experimentally.
Twin Momentum: Fundamental Trends Matter

Using time-series trends of a set of firms’ major fundamentals, we find that there is a fundamental momentum in the stock market. Buying stocks in the top quintile of fundamental trends and selling stocks in the bottom quintile earns a monthly average return of 0.88%, whose magnitude is comparable to price momentum. Combining price momentum and fundamental momentum produces a twin momentum, earning an average return that exceeds the sum of the two momentum returns. Our results show that firm fundamental trends play an economically much more important role than previously thought. Theoretically, we show that investors can learn from fundamental trends about future stock returns in an equilibrium model, providing an economic rationale for fundamental momentum.
Policy work and capacities in a developing country: evidence from the Philippines

Are policy work and the capacities required in developing countries different from those in the developed world? This article addresses this question using data from a survey of policy professionals in the Philippines. The individuals surveyed have similar characteristics as their counterparts in developed countries, but their specific policy analytical style appears to be largely coordinative rather being directed at substantive and procedural aspects of policy work – which raises questions about whether or not their capacities as various skills and resources enable them to carry out their work effectively. An important finding is that, despite their work being primarily of an analytical nature, they are more comfortable performing political and operational tasks than conducting substantive, rigorous analysis. Overall, while organisational systems and processes are in place, systemic capacities, particularly political capacity, continue to be an on-going constraint to their work.
DIGITAL TECHNOLOGY, LITERACIES, AND IDENTITY: EXPERIENCES OF HISTORICALLY MARGINALIZED ADOLESCENTS

New media and digital technologies shape the literacy practices and identity development of adolescents (Ellison, 2014, Barton & Hamilton, 2000; Perry, 2012; Lotherington & Jenson, 2011). Research into this phenomenon has largely focused on the general adolescent population. However, this narrative inquiry focuses on the experiences of four adolescents of color in New York City who live in poverty. Participants in this study visit a neighborhood library to access computers and the Internet. The researcher conducted semi-structure interviews in the library to evoke narratives about participants’ use of digital media and observed participants as they used the library computers. Analysis of data revealed several patterns in their stories. None of the participants had daily, personal access to technology outside of school. Their schools provide little time on computers and minimal access to the Internet. One student did have extended computer time for English language learning, and another had a used cell phone with no data plan. All participants exerted enormous effort to gain limited access to computer time after school on weekdays only. At the library computers, they completed school work, played games, used social media,
Determinants of accounting policy choices under international accounting standards: Evidence from South Asia

Purpose - The purpose of this paper is to examine the determinants of accounting policy choices under International Accounting Standards (IASs) of listed firms in South Asia. Design/methodology/approach - We selected three IASs-based accounting policy choices from 369 listed companies in India, Pakistan and Bangladesh for the financial year 2007-2008. Findings - Our results show that firm size, investment opportunity set, leverage and ownership by the general public are significant determinants of accounting policy choice in South Asian countries. However, we do not find a significant relationship between firms’ accounting policy choices and profitability, assets-in-place and taxes. Practical implications - Our results suggest that as some flexibility exists in IASB’s accounting standards, this may allow managers to use income-increasing/decreasing methods. There is scope for regulators and standards setters to reduce the alternative methods which are likely improve firms’ reporting quality. Originality/value - Our study contributes to the understanding as to what determines managers’ choice of a particular accounting method allowed in IAS.
Safety Standards: Implementing Fall Prevention Interventions and Sustaining Lower Fall Rates by Promoting the Culture of Safety on an Inpatient Rehabilitation Unit

Purpose: The purpose of this article is to review a quality improvement project aimed to examine how nurse leaders in an inpatient rehabilitation (IPR) unit can reduce the number of patient falls by implementing multiple fall prevention interventions and sustain their results by promoting a strong culture of safety on the unit. Design and Methods: A retrospective review of IPR fall rates was performed. Quarterly fall rates were then compared with implementation dates of fall prevention interventions (safety huddles, signage, and hourly rounding). Culture of safety scores were also examined to assess the effect of an enhanced culture of safety on the sustainability of lowered fall rates. Findings: The largest decrease in fall rate was noted after initial revitalization efforts of the IPR unit's culture of safety concurrently with hourly rounding. Conclusions: Fall rates rise and fall despite multiple fall prevention interventions and encouraging a positive shift in the culture of safety. Clinical Relevance: Physical injuries following a fall can reduce mobility and increase morbidity. Costs associated with falls negatively impact costs and reimbursement. Employing evidence‐based fall prevention strategies are then of critical importance to nurse leaders as falls remain an ongoing serious adverse event.
Characterization of cell membrane response to ultrasound activated microbubbles

Contrast agents for ultrasound imaging, composed of tiny gas microbubbles, have become a reality in clinical routine. They are extensively used in radiology for detection and characterization of various tumors and in cardiology for left ventricular opacification. Recent experimental studies showed that ultrasound waves in combination with contrast agent microbubbles increase transiently cell membrane permeability in a process known as sonoporation. This effect is thought to allow foreign molecules to enter the cell. In that context, we explored the cell membrane's responses to microbubbles' oscillations as the mechanism is not completely understood. Breast cancer cell line in combination with contrast microbubbles were used. Ultrasound was applied using a transducer of 1 MHz center frequency transmitting a 10-cycle burst of different acoustic pressures repeated every 100 mus. Patch-clamp technique in whole cell configuration was used to explore transmembrane ion exchange through the variations in membrane potential. To characterize the activated ion channels, the variations of the intracellular calcium (Ca2+) concentration were explored using a fluorescent marker. The results revealed that ultrasound stimulation induces a rapid hyperpolarization of cell membrane potential when the microbubble is in direct contact with the cell, but the potential returned to its initial value when ultrasound stimulation stopped. The change in cell membrane potential indicates the activation of specific ion channels and depends on the quality of microbubble adhesion to the cell membrane. Microbubbles were shown to induce a mechanical stretch activating BKca channels. Simultaneous Ca2+ measurements indicate a slow and progressive Ca2+ increase that is likely a consequence of BKca channels opening not a cause. These results demonstrate that microbubbles' oscillations under ultrasound activation entail modulation of cellular function and signaling by triggering the modulation of ionic transports through the cell membrane. Cells response to the mechanical stretch caused by gentle microbubble oscillations is characterized by the opening of BKca stretch channels and a Ca2+ flux, which might potentially trigger other cellular responses responsible for membrane sonopermeabilization.
The market dynamics of socially embedded trading

Social embeddedness has provided a compelling challenge to neoclassical descriptions of markets. Nevertheless, without a corresponding description of the micro-social forces that counter embeddedness, the description of embeddedness is essentially static, and does not integrate the dual forces of embeddedness and markets. In this study, we identify a sociological force counter to embeddedness residing in third parties whose presence may interrupt socially embedded informal trading partnerships. Using data from the Helsinki Stock Exchange in 1996–1997, we confirm that stock trades are socially embedded in partnerships in which trading persists from week to week and in which prices deviate from immediate trading prices. Importantly, we find that trading partnerships are more likely to be interrupted when prices deviate from immediate trading prices and when third parties are present who trade with one or both members of the partnership. Thus, third parties are a critical sociological force in the embeddedness-market dynamic.
Molecular characterization, occurrence, and immunogenicity in infected sheep and cattle of two minor outer membrane proteins of Brucella abortus

Screening of a Brucella abortus genomic library with two sets of monoclonal antibodies allowed the isolation of the genes corresponding to two minor outer membrane proteins (OMP10 and OMP19) found in this bacterial species. Sequence analysis of the omp10 gene revealed an open reading frame capable of encoding a protein of 126 amino acids. The nucleotide sequence of the insert producing the OMP19 protein contains two overlapping open reading frames, the largest of which (177 codons) was shown to encode the protein of interest. Analysis of the N-terminal sequences of both putative proteins revealed features of a bacterial signal peptide, and homology to the bacterial lipoprotein processing sequence was also observed. Immunoblotting with monoclonal antibodies specific for OMP10 or OMP19 showed that both proteins are present in the 34 Brucella strains tested, representing all six Brucella species and all their biovars. The OMP19 detected in the five Brucella ovis strains examined migrated at an apparent molecular weight that is slightly higher than those of the other Brucella species, confirming the divergence of B. ovis from these species. OMP10 and OMP19 were produced in recombinant Escherichia coli and purified to homogeneity for serological analysis. A large fraction of sera from sheep naturally infected with Brucella melitensis were reactive with these proteins in an enzyme-linked immunosorbent assay, whereas sera from B. abortus-infected cattle were almost completely unreactive in this assay.