Miracle-dz/UniFAR-FTUs huggingface dataset:
Lymphomagenic CARD11/BCL10/MALT1 signaling drives malignant B-cell proliferation via cooperative NF-κB and JNK activation

Significance The activated B cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) has a poor clinical outcome and is characterized by constitutive caspase recruitment domain-containing protein 11 (CARD11)/B-cell CLL/lymphoma 10 (BCL10)/mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) signaling and nuclear factor kappa-B (NF-κB) activation, which is essential for tumor cell survival. However, NF-κB inhibitors have not reached the clinic due to high toxicity, and alternative strategies for targeted therapies are needed. Using mouse genetics, we demonstrate that forced CARD11/BCL10/MALT1 signaling drives lethal lymphoproliferation through simultaneous NF-κB and c-Jun N-terminal kinase (JNK) activation. Pharmacological inhibition of JNK was similar to NF-κB blockage and toxic to autonomously proliferating murine B cells, and constitutive JNK activity was observed in human ABC-DLBCL cells, which are also sensitive to JNK inhibitors. Our results identify the JNK pathway as a therapeutic target for DLBCL. The aggressive activated B cell-like subtype of diffuse large B-cell lymphoma is characterized by aberrant B-cell receptor (BCR) signaling and constitutive nuclear factor kappa-B (NF-κB) activation, which is required for tumor cell survival. BCR-induced NF-κB activation requires caspase recruitment domain-containing protein 11 (CARD11), and CARD11 gain-of-function mutations are recurrently detected in human diffuse large B-cell lymphoma (DLBCL). To investigate the consequences of dysregulated CARD11 signaling in vivo, we generated mice that conditionally express the human DLBCL-derived CARD11(L225LI) mutant. Surprisingly, CARD11(L225LI) was sufficient to trigger aggressive B-cell lymphoproliferation, leading to early postnatal lethality. CARD11(L225LI) constitutively associated with B-cell CLL/lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) to simultaneously activate the NF-κB and c-Jun N-terminal kinase (JNK) signaling cascades. Genetic deficiencies of either BCL10 or MALT1 completely rescued the phenotype, and pharmacological inhibition of JNK was, similar to NF-κB blockage, toxic to autonomously proliferating CARD11(L225LI)-expressing B cells. Moreover, constitutive JNK activity was observed in primary human activated B cell-like (ABC)-DLBCL specimens, and human ABC-DLBCL cells were also sensitive to JNK inhibitors. Thus, our results demonstrate that enforced activation of CARD11/BCL10/MALT1 signaling is sufficient to drive transformed B-cell expansion in vivo and identify the JNK pathway as a therapeutic target for ABC-DLBCL.
Functionally diverse reef-fish communities ameliorate coral disease

Coral reefs, the most diverse of marine ecosystems, currently experience unprecedented levels of degradation. Diseases are now recognized as a major cause of mortality in reef-forming corals and are complicit in phase shifts of reef ecosystems to algal-dominated states worldwide. Even so, factors contributing to disease occurrence, spread, and impact remain poorly understood. Ecosystem resilience has been linked to the conservation of functional diversity, whereas overfishing reduces functional diversity through cascading, top-down effects. Hence, we tested the hypothesis that reefs with trophically diverse reef fish communities have less coral disease than overfished reefs. We surveyed reefs across the central Philippines, including well-managed marine protected areas (MPAs), and found that disease prevalence was significantly negatively correlated with fish taxonomic diversity. Further, MPAs had significantly higher fish diversity and less disease than unprotected areas. We subsequently investigated potential links between coral disease and the trophic components of fish diversity, finding that only the density of coral-feeding chaetodontid butterflyfishes, seldom targeted by fishers, was positively associated with disease prevalence. These previously uncharacterized results are supported by a second large-scale dataset from the Great Barrier Reef. We hypothesize that members of the charismatic reef-fish family Chaetodontidae are major vectors of coral disease by virtue of their trophic specialization on hard corals and their ecological release in overfished areas, particularly outside MPAs.
The sensitivity of three commonly used outcome measures to detect change amongst patients receiving inpatient rehabilitation following stroke

Objective: To investigate the sensitivity of three commonly used functional outcome measures to detect change over time in subjects receiving inpatient rehabilitation post stroke. Design: Subjects were assessed within one week of admission and one week of discharge from an inpatient rehabilitation facility. Several parameters of sensitivity were calculated, including floor and ceiling effects, the percentage of subjects showing no change and the effect size of the change between admission and discharge. Setting: The medical rehabilitation ward of an inpatient rehabilitation facility. Subjects: Seventy-eight subjects receiving inpatient rehabilitation following a first or recurrent stroke. Measures: Five-metre walk, comfortable pace (gait speed), the Berg Balance Scale and the Motor Assessment Scale. Results: Sixty-one subjects had complete admission and discharge data. Gait speed and the Berg Balance Scale were both sensitive to change and demonstrated large effect sizes. The Motor Assessment Scale item five also showed a large effect size and was able to detect change amongst lower functioning subjects. The other items of the Motor Assessment Scale were less useful, in particular, the effect sizes for upper extremity change scores were small (d=0.36–0.5) and the majority of subjects (44.3–63.9%) showed no change over time on these measures. Conclusion: Gait speed, the Berg Balance Scale and the Motor Assessment Scale item five were sensitive to change over time in this sample.
Optimization of power flow with energy storage using genetic algorithms

This paper applies genetic algorithms to optimize the operation of a transmission network with energy storage capabilities, to optimize its costs, which include both generation and storage costs, for cases when the data inherent to the system is assumed to be perfectly known. The problem is formulated through the DC optimal power flow equations, including losses across the transmission lines, therefore allowing solutions regarding the network generation costs to be obtained, with and without storage. In this way, the financial impact inherent to the usage of energy storage can be derived. Since we are dealing with a large combinatorial problem, the search throughout the solution space was done by means of the Genetic Algorithms. The solutions consist of the storage device's charging or discharging rate at which it must be operating during each sub-interval considered for the simulations. The results delivered by the GA have proven the profitability of including energy storage capabilities in the transmission network of São Miguel (Portugal) and the usefulness of such algorithm in a real world application.
The design of an asynchronous microprocessor

Abstract : Prejudices are as tenacious in science and engineering as in any other human activity. One of the most firmly held prejudices in digital VLSI design is that asynchronous circuits-a.k. a. self-timed or delay-insensitive circuits-are necessarily slow and wasteful in area and logic. Whereas asynchronous techniques would be appropriate for control, they would be inadequate for data paths because of the cost of dual-rail encoding of data, the cost of generating completion signals for write operations on registers, and the difficulty of designing self-timed buses. Because a general-purpose microprocessor contains a complex data path, a corollary of the previous opinion is that it is impossible to design an efficient asynchronous microprocessor. Since we have been developing a design method for asynchronous circuits that gives excellent results, and since the above objections to large-scale data path designs are genuine but untested, we decided to "pick up the gauntlet" and design a complete processor. The design of an asynchronous microprocessor poses new challenges and opens new avenues to the computer architect. Hence, the experiment unavoidably developed a dual purpose: We are refining an already well-tested design method and we are starting a new series of experiments in asynchronous architectures. (As far as we know, this is the first entirely asynchronous microprocessor ever built.) The results we are reporting have a different implication depending on whether they are related to the first or second goal of the experiment. Whereas we are convinced that our design methods have reached maturity, we are quite aware that asynchronous techniques may influence the computer architects in completely new ways that this first design is just starting to explore.
Engaging public servants: Public service motivation, work engagement and work-related stress

Purpose – Considering the ongoing international debate on the role of public administrations in economic systems, the interest around public service motivation (PSM) has significantly grown among practitioners and scholars in the past two decades. Following the research streams that have investigated topics of organizational behavior within the public context, the purpose of this paper is to examine the influence of PSM on public employees’ feelings of job satisfaction. The novelty of the study lies in linking some characteristics of the work context presumed to be more prevalent in public organizations with specific job characteristics, regarded as relevant antecedents of job satisfaction. Design/methodology/approach – The study is based on two complementary studies conducted in an Italian public administration. The paper shows how PSM influences job satisfaction, job engagement, and life satisfaction. Findings – This paper shows how PSM influences job satisfaction, job engagement, and life satisfaction.
Real-time dispatch based on effective steady-state security regions of power systems

As the regulating range is limited in the real-time dispatch, the security improvement is more prominent than the economic improvement for the real-time dispatch. Based on the preemptive goal programming and the steady-state security region estimation methods, this paper proposed a model for the real-time dispatch, in which the base-points and the participation factors of the AGC (Automatic Generation Control) units are co-optimized. The model has two goals. One is to maximize the ability of the power system to depress the load disturbances by maximizing the overlap region of the steady-state security region and the load variation region (named as the effective steady-state security region). The other one is to minimize the operating costs including the generation costs and the reserve costs. By setting the first goal as the preemptive goal, the economic dispatch results are obtained with respected to the maximized effective steady-state security region. Numerical tests demonstrate the effectiveness of the proposed approach.
Risk factors associated with severe viral croup in hospitalised Malaysian children.

OBJECTIVE To determine the risk factors associated with severe viral croup in hospitalised Malaysian children. METHODOLOGY The medical records of children aged less than five years admitted with a diagnosis of viral croup between 1994 and 1999 were reviewed. Severe viral croup was diagnosed in children who had stridor at rest with marked recession associated with central cyanosis or altered level of consciousness. Multivariate logistic regression analysis was performed to identify risk factors associated with severe viral croup. RESULTS Eighteen (14.7%) of 122 children with viral croup were severe. These children were older (mean age 16.8 +/- 7.2 vs 12.6 +/- 6.6 months, p = 0.01) and had a shorter duration of illness prior to admission (1.7 +/- 0.7 days vs 2.3 +/- 1.4 days, p = 0.03). Age between 12 and 24 months (OR 3.8 95% Cl 1.3, 12.7, p = 0.02) and fever (OR 5.7 95% Cl 2.9, 15.6, p = 0.02) were the only risk factors associated with severe viral croup after multivariate logistic regression analysis. Only three children or 2.5 per 100 children admitted with viral croup required ventilation. CONCLUSION Only a small number of children admitted particularly those between 12 to 24 months with fever developed severe viral croup. Recognition of these risk factors provides a guide in selecting children who will most likely benefit from steroid therapy. The overall outcome was nonetheless favourable.
On shape-preserving boundary conditions for diffusion smoothing

Several boundary treatments for attenuating shape deformation introduced by Gaussian smoothing are discussed. The author models Gaussian smoothing by a diffusion equation, a general mathematical framework particularly useful for scale-space analysis. An adaptive, shape-reserving boundary condition for diffusion smoothing range images is introduced. It is shown that this condition is more general than similar techniques found in the literature. <<ETX>>
Diameter of the Cochlear Nerve in Deaf Humans: Implications for Cochlear Implantation

Although the parameters that are most important for postoperative speech perception in cochlear implantation have not been identified, it is assumed that the numbers of remaining cochlear neurons and spiral ganglion cells in the implanted deaf ears are critical. In this study, we evaluated the correlation of the maximum diameter of the cochlear and vestibular nerve trunks with the number of spiral ganglion cells in horizontal sections of the temporal bone of 42 patients who were profoundly deaf during life, and in 5 patients with normal hearing. The maximum diameters of the cochlear, vestibular, and eighth cranial nerves were significantly smaller in the deaf population as compared to normal-hearing controls. In addition, the counts of the remaining spiral ganglion cells were significantly correlated with the maximum diameter of the cochlear (p = .0006), vestibular (p = .001), and eighth cranial nerves (p = .0003). The regression equation estimated that 25% of the variance of the spiral ganglion cell count was predicted by the maximum diameter of the eighth nerve. Although the results of this study suggest that preoperative radiographic imaging of the diameter of the eighth nerve may be helpful in predicting the residual spiral ganglion cell count, the wide variability of diameters of the eighth nerve in hearing and deaf subjects militates against this theoretic usefulness.
FXYD5 Protein Has a Pro-inflammatory Role in Epithelial Cells*

The FXYD proteins are a family of small membrane proteins that share an invariant four amino acid signature motif F-X-Y-D and act as tissue-specific regulatory subunits of the Na,K-ATPase. FXYD5 (also termed dysadherin or RIC) is a structurally and functionally unique member of the FXYD family. As other FXYD proteins, FXYD5 specifically interacts with the Na,K-ATPase and alters its kinetics by increasing Vmax. However, unlike other family members FXYD5 appears to have additional functions, which cannot be readily explained by modulation of transport kinetics. Knockdown of FXYD5 in MDA-MB-231 breast cancer cells largely decreases expression and secretion of the chemokine CCL2 (MCP-1). A related effect has also been observed in renal cell carcinoma cells. The current study aims to further characterize the relationship between the expression of FXYD5 and CCL2 secretion. We demonstrate that transfection of M1 epithelial cell line with FXYD5 largely increases lipopolysaccharide (LPS) stimulated CCL2 mRNA and secretion of the translated protein. We have completed a detailed analysis of the molecular events leading to the above response. Our key findings indicate that FXYD5 generates a late response by increasing the surface expression of the TNFα receptor, without affecting its total protein level, or mRNA transcription. LPS administration to mice demonstrates induced secretion of CCL2 and TNFα in FXYD5-expressing lung peripheral tissue, which suggests a possible role for FXYD5 in normal epithelia during inflammation.
Effect of lung volume reduction surgery on pulmonary diffusion capacity in a rabbit model of emphysema.

BACKGROUND While there is renewed interest in lung volume reduction surgery (LVRS) for treatment of emphysema, many aspects of the operation such as patient selection and surgical end points of excision are uncertain. We studied the effects of LVRS on measured lung volumes and diffusion capacity in an animal model to investigate optimal resection volumes. METHODS Emphysema was induced in 32 New Zealand white (NZW) rabbits using aerosolized elastase. Helium dilution lung volumes and single breath DLCO were measured concurrently at baseline, following induction of emphysema (preop), and 1 week postoperatively (postop) following LVRS. Bilateral upper and middle lobe stapled lung resections were performed through midline sternotomies with excision of variable amounts of lung tissue from 1.8 to 5.8 g. RESULTS FRC increased following induction of emphysema and decreased postoperatively. DLCO improved with increasing lung tissue resection up to 3 g of tissue and then decreased as even greater amounts were removed (r = 0.54). CONCLUSIONS Measured lung volumes increase with development of emphysema and appropriately decrease in response to LVRS in this rabbit model. DLCO improves with moderate resection but then decreases with excessive excision of lung quantities and may help define one physiologic operative end point. In this rabbit model, excision of approximately 30% of lung volume was optimal and prevented further decrease in diffusion capacity.
Adenoviral vector–mediated gene transfer of IL‐13Rα2 chain followed by IL‐13 cytotoxin treatment offers potent targeted therapy for cytotoxin‐resistant cancers

Previous studies demonstrated that IL‐13Rα2 chain–overexpressing cancer cells were highly sensitive to IL‐13 cytotoxin (IL13‐PE38QQR) and could be targeted by cytotoxin treatment. However, the majority of human tumors do not express high levels of IL‐13Rα2 chain. To expand the IL‐13 cytotoxin–mediated cancer targeting therapy, we combined cytotoxin treatment with gene transfer of IL‐13Rα2 chain. We constructed a recombinant adenoviral vector carrying the human IL‐13Rα2 gene (Ad‐IL‐13Rα2), which expresses high levels of IL‐13Rα2 chain on infected cells. Human cancer cell lines A549 and HOS, which originally show no IL‐13Rα2 expression and little sensitivity to IL‐13 cytotoxin, were effectively converted to become sensitive to this cytotoxin after Ad‐IL‐13Rα2 infection. The CC50 of IL‐13 cytotoxin for Ad‐IL‐13Rα2‐infected A549 cells was <10 ng/ml, whereas the CC50 for uninfected or control vector‐infected cells was >500 ng/ml. We also examined the antitumor activity of IL‐13 cytotoxin in an established xenograft model of cytotoxin‐resistant human lung tumor. Only a single i.t. injection of Ad‐IL‐13Rα2 markedly enhanced the sensitivity of established tumors to IL‐13 cytotoxin treatment; furthermore, this antitumor effect was significantly sustained for more than 1 month after the last treatment with IL‐13 cytotoxin. Taken together, these results suggest the combination of adenoviral vector–mediated IL‐13Rα2 gene transfer and IL‐13 cytotoxin administration can be an effective targeting approach for several types of IL‐13 cytotoxin–resistant cancers which show no or little expression of IL‐13Rα2 chain. © 2005 Wiley‐Liss, Inc.
Characterization of presystemic elimination of trichloroethylene and its nonlinear kinetics in rats.

1,1,2-Trichloroethylene (TCE) is a volatile organic chemical which contaminates drinking water and food supplies and is primarily of concern because of the risk of cancer it may pose. The objectives of the present study were to evaluate the efficiency and dose dependency of presystemic elimination of TCE in rats. Cannulas were surgically implanted into male Sprague-Dawley rats (330-380 g) 24 hr before TCE dosing. TCE (0.17, 0.33, 0.71, 2, 8, 16, and 64 mg/kg) in a 5% aqueous Alkamuls emulsion was administered over 30 sec into the carotid artery, jugular vein (JV), hepatic portal vein, or the stomach. Serial arterial blood samples of 1-500 microliters were collected for up to 12 hr from the unanesthetized animals and analyzed for TCE content by headspace gas chromatography. Pharmacokinetic analyses indicated that TCE was eliminated through dose-dependent nonlinear processes. A three-compartment model with Michaelis-Menten and first-order elimination was derived to fit simultaneously the TCE blood data following JV administration. Total presystemic elimination of TCE was inversely related to dose, ranging from approximately 60 to < 1%. A dose-dependent decrease in hepatic extraction was primarily responsible for the reduction in total first-pass elimination at high doses, whereas pulmonary extraction (i.e., 5-8%) was relatively constant over the dosage range. When metabolic saturation was minimal or absent, hepatic presystemic elimination of TCE accounted for approximately 45-55% of the administered dose. These findings indicate that a substantial proportion of trace amounts of VOCs ingested in environmental media may not enter the systemic circulation nor reach extrahepatic target organs.
Who makes European Cohesion Policy: a practitioners’ learning perspective

Abstract Through the European Social Fund (ESF), the European Union subsidizes social inclusion and occupational trainee projects. This policy instrument is formulated by European Union institutions and implemented by regions through a call for projects which requires innovative actions and a result-oriented strategy. It is a key vantage point to observe sub-national implementation of an European Union policy instrument in a sub-national practitioner’s perspective, a topic under-investigated in the literature. For a project to receive funding, sub-national practitioners must take the European Union requirements (accounting standards, evidence of innovation etc.) and their social needs into account. Against this backdrop, this research tackles an original question: how can local practitioners adapt their policy actions to fit with European Union requirements? Taking the region of Wallonia in Belgium as a case study, the ESF implementation is considered as a specific policy process in sub-national policy sectors. Adopting an in-depth qualitative perspective, this research contends that it depends on practitioners’ learning, practices and experience of past applications, their specific socio-economic context and income maximization.
Rehabilitation Myths? How Transaction Costs Reduce Farmer Welfare After Land Acquisition

In this article, we show how transaction costs lead to farmer marginalization as displaced farmers embark on the process of acquiring new land. Existing studies have focused on the links between monetary compensation and landowners’ investment decisions, but before new land is acquired. However, the post-displacement scenario and the investment decisions of land owners to restore income have not been carefully examined. We use a transaction cost framework to suggest that local specificities related to land characteristics, uncertainties in search for alternatives and information constraints may impose high non-monetary costs on displaced farmers and force them to settle for inferior new land. The article concludes with a preliminary assessment of whether the newly enacted land acquisition framework, the Right to Fair Compensation and Transparency in Land Acquisition, Rehabilitation and Resettlement (RFCTLARR) Act 2013, promises to minimize these ex-post transaction costs that farmers face.