Miracle-dz/UniFAR-FTUs huggingface dataset:
Adhesion Molecules Involved in Stem Cell Niche Retention During Normal Haematopoiesis and in Acute Myeloid Leukaemia

In the bone marrow (BM) of adult mammals, haematopoietic stem cells (HSCs) are retained in micro-anatomical structures by adhesion molecules that regulate HSC quiescence, proliferation and commitment. During decades, researchers have used engraftment to study the function of adhesion molecules in HSC’s homeostasis regulation. Since the 90’s, progress in genetically engineered mouse models has allowed a better understanding of adhesion molecules involved in HSCs regulation by BM niches and raised questions about the role of adhesion mechanisms in conferring drug resistance to cancer cells nested in the BM. This has been especially studied in acute myeloid leukaemia (AML) which was the first disease in which the concept of cancer stem cell (CSC) or leukemic stem cells (LSCs) was demonstrated. In AML, it has been proposed that LSCs propagate the disease and are able to replenish the leukemic bulk after complete remission suggesting that LSC may be endowed with drug resistance properties. However, whether such properties are due to extrinsic or intrinsic molecular mechanisms, fully or partially supported by molecular crosstalk between LSCs and surrounding BM micro-environment is still matter of debate. In this review, we focus on adhesion molecules that have been involved in HSCs or LSCs anchoring to BM niches and discuss if inhibition of such mechanism may represent new therapeutic avenues to eradicate LSCs.
Play it Again: Partner Choice, Reputation Building and Learning from Finitely Repeated Dilemma Games

Often the fuller the reputational record people's actions generate, the greater their incentive to earn a reputation for cooperation. However, inability to “wipe clean” one's past record might trap some agents who initially underappreciate reputation's value in a cycle of bad behaviour, whereas a clean slate could have been followed by their “reforming” themselves. In a laboratory experiment, we investigate what subjects learn from playing a finitely repeated dilemma game with endogenous, symmetric partner choice. We find that with a high cooperation premium and good information, investment in cooperative reputation grows following exogenous restarts, although earlier end-game behaviours are observed.
The extracellular matrix of eggshell displays anti-inflammatory activities through NF-κB in LPS-triggered human immune cells

Avian eggshell membrane (ESM) is a natural biomaterial that has been used as an alternative natural bandage on burned and cut skin injuries for >400 years in Asian countries, and is available in large quantities from egg industries. Our aim was to characterize ESM that was separated and processed from egg waste, and to study whether this material possesses anti-inflammatory properties, making it suitable as an ingredient in industrial production of low cost wound healing products. Our results show that the processed ESM particles retain a fibrous structure similar to that observed for the native membrane, and contain collagen, and carbohydrate components such as hyaluronic acid and sulfated glycosaminoglycans, as well as N-glycans, mostly with uncharged structures. Furthermore, both processed ESM powder and the ESM-derived carbohydrate fraction had immunomodulation properties in monocytes and macrophage-like cells. Under inflammatory conditions induced by lipopolysaccharide, the ESM powder and the isolated carbohydrate fraction reduced the activity of the transcription factor nuclear factor-κB. The expression of the immune regulating receptors toll-like receptor 4 and ICAM-1, as well as the cell surface glycoprotein CD44, all important during inflammation response, were down-regulated by these fractions. Interestingly, our experiments show that the two fractions regulated cytokine secretion differently: ESM depressed inflammation by increased secretion of the anti-inflammatory cytokine IL-10 while the carbohydrate fraction reduced secretions of the pro inflammatory cytokines IL-1β and IL-6. Also, the phosphorylation of p65 and p50 subunits of nuclear factor-κB, as well as nuclear localization, differed between processed ESM powder and carbohydrate fraction, suggesting different down-stream regulation during inflammation. In conclusion, processed ESM powder and its soluble carbohydrate components possess anti-inflammatory properties, demonstrating the potential of ESM as a novel biological wound dressing for treatment of chronic inflammatory wounds.
Early cessation of activity in the labour market: impact of supply and demand factors

The main objective of this paper is to analyze the problem of population ageing in terms of the cessation of professional activity (and especially premature labour market withdrawals) in order to provide the various public and private administrations active in these fields with some food for thought. Results show that employer-driven obligation to stop working (owing to business closure, redundancy, dismissal, early retirement, etc.), marital status (married/widowed) and health status are the main reasons for the premature cessation of activity common to all four countries studied (Belgium, Finland, the Netherlands and the United Kingdom), while the desire to retire from the labour market or live off private wealth (voluntary cessation) has a significant effect only for Belgium and the Netherlands. However, the impact of this reason on the retirement age is much lower than that of departure enforced by the employer (2 to 3 times lower in these two countries).
Performance of a Pyrethroid-Resistant Strain of the Predator Mite Typhlodromus pyri (Acari: Phytoseiidae) Under Different Insecticide Regimes

Abstract An organophosphate pyrethroid-resistant strain of Typhlodromus pyri Scheuten imported from New Zealand was reared on potted apple trees in an outdoor insectary. From 1988 to 1995, the population was selected one to three times per year with a dilute solution (1.7 ppm) of the pyrethroid cypermethrin. Petri dish bioassays with cypermethrin in 1995 indicated that the insectary-reared T. pyri had an LC50 of 81 ppm versus 0.006 ppm for native T. pyri taken from a research orchard. The bioassays suggested that recommended orchard rates of cypermethrin would cause heavy mortality in native populations of T. pyri but only moderate losses in the imported New Zealand strain. Bioassays in 1996 with the organophosphate insecticide dimethoate indicated both New Zealand and native T. pyri were susceptible and that recommended orchard rates of dimethoate likely would cause high mortality of T. pyri in apple orchards. These findings from bioassays were supported by data from orchard trials. In June and July 1993, insectary-reared New Zealand T. pyri were placed on five apple trees in each of eight 38-tree plots in the research orchard. In late August 1994, New Zealand T. pyri from orchard trees that had been sprayed twice by airblast sprayer with the full recommended rate of 50 g (AI)/ha (83 ppm) cypermethrin were placed on the other 33 trees in each of six plots. In the summers of 1994–1996, plots were treated with one of the following insecticide regimes: (1) conventional integrated pest management (IPM) (registered neurotoxic insecticides considered harmless or slightly toxic to T. pyri); (2) advanced IPM (use of newer, more selective insecticides); (3) pyrethroid (at least one full-rate application of cypermethrin); (4) dimethoate; and (5) dimethoate plus pyrethroid. Densities of European red mite, Panonychus ulmi (Koch), were highest in all plots treated with dimethoate and in pyrethroid plots not yet inoculated with New Zealand T. pyri. Densities of apple rust mite, Aculus schlechtendali (Nalepa), and of the stigmaeid predator Zetzellia mali (Ewing) were highest in plots treated with dimethoate and were nearly absent in the IPM plots. Densities of T. pyri were high enough for effective biocontrol in the IPM plots and in the pyrethroid plots 1–2 yr after release of the New Zealand strain, provided pyrethroid was applied just before the resistant strain was released in the orchard. A recurring theme of this study was the generally negative association between densities of phytophagous mites and those of T. pyri, suggesting the ability of this predator to suppress their prey. In contrast, the positive association between phytophagous mites and Z. mali suggests the inability of this predator to regulate their prey at least under the conditions of this study.
Body Integrity Identity Disorder: The Persistent Desire to Acquire a Physical Disability

Background: Body integrity identity disorder (BIID) is a rare and unusual psychiatric condition characterized by a persistent desire to acquire a physical disability (e.g., amputation, paraplegia) since childhood that to date has not been formally described in the psychiatric nosology. Most BIID sufferers experience a chronic and dysphoric sense of inappropriateness regarding their being able-bodied, and many have been driven to actualize their desired disability through surreptitious surgical or other more dangerous methods. This review aims to characterize the history and phenomenology of this condition, to present its differential diagnosis, and to consider possible etiologies, treatment options, and ethical considerations. Sampling and Method: Review of the psychiatric and neurological literature. Results: A growing body of data suggests the existence of a discrete entity with onset by early adolescence and a negative impact on functioning. Parallel neurological conditions and preliminary experimental investigations suggest a possible neurobiological component in at least a portion of cases. While attempts at treatment have been described, no systematic evidence for efficacy has emerged. Discussion: BIID is a unique nosological entity with significant consequences for its sufferers and as such may warrant inclusion in some form in the forthcoming DSM-5 and ICD-11.
Regulation of Embryonic Stem Cell Self-renewal by Phosphoinositide 3-Kinase-dependent Signaling*

The maintenance of murine embryonic stem (ES) cell self-renewal is regulated by leukemia inhibitory factor (LIF)-dependent activation of signal transducer and activator of transcription 3 (STAT3) and LIF-independent mechanisms including Nanog, BMP2/4, and Wnt signaling. Here we demonstrate a previously undescribed role for phosphoinositide 3-kinases (PI3Ks) in regulation of murine ES cell self-renewal. Treatment with the reversible PI3K inhibitor, LY294002, or more specific inhibition of class IA PI3K via regulated expression of dominant negative Δp85, led to a reduction in the ability of LIF to maintain self-renewal, with cells concomitantly adopting a differentiated morphology. Inhibition of PI3Ks reduced basal and LIF-stimulated phosphorylation of PKB/Akt, GSK3α/β, and S6 proteins. Importantly, LY294002 and Δp85 expression had no effect on LIF-induced phosphorylation of STAT3 at Tyr705, but did augment LIF-induced phosphorylation of ERKs in both short and long term incubations. Subsequently, we demonstrate that inhibition of MAP-Erk kinases (MEKs) reverses the effects of PI3K inhibition on self-renewal in a time- and dose-dependent manner, suggesting that the elevated ERK activity observed upon PI3K inhibition contributes to the functional response we observe. Surprisingly, upon long term inhibition of PI3Ks we observed a reduction in phosphorylation of β-catenin, the target of GSK-3 action in the canonical Wnt pathway, although no consistent alterations in cytosolic levels of β-catenin were observed, indicating this pathway is not playing a major role downstream of PI3Ks. Our studies support a role for PI3Ks in regulation of self-renewal and increase our understanding of the molecular signaling components involved in regulation of stem cell fate.
QE and the Gilt Market: A Disaggregated Analysis

We examine the impact of the first phase of the Bank of England’s quantitative easing (QE) programme during March 2009 to January 2010 on the UK government bond (gilt) market, using high-frequency disaggregated data on individual gilts. We find that: QE announcements took varying amounts of time to get incorporated into market prices and had significant effects on the shape of the term structure; the Bank’s reverse auctions were initially associated with additional yield reductions on gilts both eligible and ineligible for purchase; and, allowing for fiscal news and the changing macroeconomic outlook, QE appears to have had persistent effects on gilt yields. In general, our results provide evidence of local supply and duration risk effects consistent with imperfect asset substitution, which has implications beyond the financial crisis for how we think about price determination in the gilt market.
Population pharmacokinetics of naloxegol in a population of 1247 healthy subjects and patients.

AIMS Naloxegol, a polyethylene glycol conjugated derivative of the opioid antagonist naloxone, is in clinical development for treatment of opioid-induced constipation (OIC). The aim of the study was to develop a population pharmacokinetic model describing the concentration vs. time profile of orally administered naloxegol, and determine the impact of pre-specified demographic and clinical factors and concomitant medication on population estimates of apparent clearance (CL/F) and apparent central compartment volume of distribution (Vc /F). METHODS Analysis included 12,844 naloxegol plasma concentrations obtained from 1247 healthy subjects, patients with non-OIC and patients with OIC in 14 phase 1, 2b and 3 clinical studies. Pharmacokinetic analysis used the non-linear mixed effects modelling program. Goodness of fit plots and posterior predictive checks were conducted to confirm concordance with observed data. RESULTS The final model was a two compartment disposition model with dual absorptions, comprising one first order absorption (ka1 4.56 h(-1) ) and one more complex absorption with a transit compartment (ktr 2.78 h(-1) ). Mean (SE) parameter estimates for CL/F and Vc /F, the parameters assessed for covariate effects, were 115 (3.41) l h(-1) and 160 (27.4) l, respectively. Inter-individual variability was 48% and 51%, respectively. Phase of study, gender, race, concomitant strong or moderate CYP3A4 inhibitors, strong CYP3A4 inducers, P-glycoprotein inhibitors or inducers, naloxegol formulation, baseline creatinine clearance and baseline opioid dose had a significant effect on at least one pharmacokinetic parameter. Simulations indicated concomitant strong CYP3A4 inhibitors or inducers had relevant effects on naloxegol exposure. CONCLUSIONS Administration of strong CYP3A4 inhibitors or inducers had a clinically relevant influence on naloxegol pharmacokinetics.
ω–3 Fatty Acids, Genetic Variants in COX-2 and Prostate Cancer

Dietary intake of fish and ω–3 polyunsaturated fatty acids (ω–3 PUFAs) may decrease the risk of prostate cancer development and progression to advanced stage disease. This could reflect the anti-inflammatory effects of PUFAs, possibly through mediation of cyclooxygenase (COX), a key enzyme in fatty acid metabolism and inflammation. Despite promising experimental evidence, epidemiological studies have reported somewhat conflicting results regarding the effects of fish/PUFAs on prostate cancer development and progression. The literature suggests that fish, and particularly long-chain ω–3 PUFAs, may have a more pronounced protective effect on biologically aggressive tumors or on their progression, and less on early steps of carcinogenesis. Moreover, the impact of LC ω–3 PUFAs may be modified by variation of the COX-2 gene. Overall, results to date support the hypothesis that long-chain ω–3 PUFAs may impact prostate inflammation and carcinogenesis via the COX-2 enzymatic pathway.
Stock market, capital flow and output: some analytical and policy perspectives

The article will theoretically examine how financial opening up can influence the real sector under alternative exchange rate regimes. We will show that private capital flows can produce favourable macroeconomic outcomes through an adjustment in stock market valuation and wealth effect induced by a change in asset prices. What we choose for analytical purpose is an effective demand framework, which can apply to a large class of emerging market economies.
A novel design of optical cross-connects with multi-granularity provisioning support for the next-generation Internet

This paper proposes a scalable design for next-generation optical cross-connects (OXCs), where a novel strategy for dimensioning the network switching capability as a long term planning is presented. When traffic demand grows, the proposed scheme simply expands the switching capacity of OXCs in waveband- and fiber-switching tiers. To minimize the number of extra fibers for waveband- and fiber-switching tiers required to satisfy a given traffic matrix, we formulate the problem of routing and wavelength assignment with tunnel allocation (RWAT) into two integer linear programming (ILP) processes that are performed sequentially. Experiments are conducted on two sample networks to compare the throughput and the number of switch points when the networks adopt different switching architectures with different traffic loads. We conclude that the proposed optimization scheme can dimension the networks with expandability and scalability to the growing traffic demand.
Arcuate neuropeptide Y inhibits sympathetic nerve activity via multiple neuropathways

Obesity increases sympathetic nerve activity (SNA) via activation of proopiomelanocortin neurons in the arcuate nucleus (ArcN), and this action requires simultaneous withdrawal of tonic neuropeptide Y (NPY) sympathoinhibition. However, the sites and neurocircuitry by which NPY decreases SNA are unclear. Here, using designer receptors exclusively activated by designer drugs (DREADDs) to selectively activate or inhibit ArcN NPY neurons expressing agouti-related peptide (AgRP) in mice, we have demonstrated that this neuronal population tonically suppresses splanchnic SNA (SSNA), arterial pressure, and heart rate via projections to the paraventricular nucleus (PVN) and dorsomedial hypothalamus (DMH). First, we found that ArcN NPY/AgRP fibers closely appose PVN and DMH presympathetic neurons. Second, nanoinjections of NPY or an NPY receptor Y1 (NPY1R) antagonist into PVN or DMH decreased or increased SSNA, respectively. Third, blockade of DMH NPY1R reversed the sympathoinhibition elicited by selective, DREADD-mediated activation of ArcN NPY/AgRP neurons. Finally, stimulation of ArcN NPY/AgRP terminal fields in the PVN and DMH decreased SSNA. Considering that chronic obesity decreases ArcN NPY content, we propose that the ArcN NPY neuropathway to the PVN and DMH is pivotal in obesity-induced elevations in SNA.
Incentivizing reproducibility

A SCIENTIFIC RESULT is not truly established until it is independently confirmed. This is one of the tenets of experimental science. Yet, we have seen a rash of recent headlines about experimental results that could not be reproduced. In the biomedical field, efforts to reproduce results of academic research by drug companies have had less than a 50% success rate, a resulting in billions of dollars in wasted effort. b In most cases the cause is not intentional fraud, but rather sloppy research protocols and faulty statistical analysis. Nevertheless, this has led to both a loss in public confidence in the scientific enterprise and some serious soul searching within certain fields. Publishers have begun to take the lead in insisting on more careful reporting and review, as well as facilitating government open science initiatives mandating sharing of research data and code. But what about experimental computer science? Fortunately, we haven't been in the headlines. But, it is rare for research studies in computing to be reproduced. On the surface this seems odd, since we have an advantage over science done in wet labs. For us, the object of study is often software, so it, along with the associated experimental scaffolding , is a collection of bits that can be easily shared for the purpose of audit and inspection, for an assisted attempt at replication, or for building upon the work to advance science further or to transfer technologies to commercial use. Certainly the situation is a bit more complex in practice, but there is no reason for us not to be leaders in practices that enable audit and reuse when technically and legally possible. Some communities within ACM have taken action. SIGMOD has been a true pioneer, establishing a reproducibility review of papers at the SIGMOD conference since 2008. The Artifact Evaluation for Software Conferences initiative has led to formal evaluations of artifacts (such as software and data) associated with papers in 11 major conferences since 2011, including OOPSLA, PLDI, and ISSTA. Here the extra evaluations are optional and are performed only after acceptance. In 2015 the ACM Transactions on Mathematical Software announced a Replicated Computational Results initiative, c also optional, in which the main results of a paper are independently replicated by a third party (who works cooperatively with the author and uses author-supplied artifacts) before acceptance. The ACM Transactions on Modeling and Computer Simulation is also now doing …
Two-layered audio-visual integration in voice activity detection and automatic speech recognition for robots

Automatic Speech Recognition (ASR) which plays an important role in human-robot interaction should be noise-robust because robots are expected to work in noisy environments. Audio-Visual (AV) integration is one of the key ideas to improve the robustness in such environments. This paper proposes two-layered AV integration for ASR which applies AV integration to Voice Activity Detection (VAD) and ASR decoding process. We implemented a prototype ASR system based on the proposed two-layered AV integration and evaluated the system in dynamically-changing situations where audio and/or visual information is noisy or missing. Preliminary results showed that the proposed method improves the robustness of ASR system even in auditory-or visually-contaminated situations.
Conceptualising Social Enterprise in Housing Organisations

Recent changes in the provision, funding and management of social housing in Europe have led to the emergence of new types of providers. While some of them can be portrayed with traditional ‘state’, ‘market’ or ‘civil society’ labels, many correspond to hybrid organisational forms, encompassing characteristics of all three in varying combinations. Nonetheless, evidence suggests that there is a ‘common thread’ linking these organisations together, namely their core missions and values, which can be classified using the term ‘social enterprise’. Despite the growing body of literature on social enterprise, this concept has been poorly defined and applied to the housing sector. This paper aims to address this gap through a critical literature review encompassing Europe and the United States. Existing models of social enterprise are reviewed and a classification system for social enterprise is developed to reflect the specific features of the social housing association sector and as framework for future research.