Histological study on the effect of transplanted human umbilical cord blood CD34+ stem cells on albino rats subjected to myocardial infarction

Background: Heart failure is a significant burden to health care systems in the world. One of its major causes is myocardial infarction (MI). Recent developments in stem cells may offer ways to manage heart failure by replacing damaged cardiac muscle with healthy tissue. This study aimed at examining the regenerative effect of intravenously transplanted human umbilical cord blood CD34+ stem cell in a rat model of acute MI. Methods: Forty adult female rats were equally randomized into 5 groups. Groups I and II received saline alone or saline followed by isolation buffer respectively to serve as control groups. The other 3 groups were subjected to induction of acute MI using subcutaneous injection of isoprenaline hydrochloride. In groups III and IV, animals were sacrificed after one week and four weeks respectively. One week after induction of MI, animals in group V received intravenous injection of 4 x 106 CD34+ stem cells separated from the human umbilical cord blood of male fetuses, and were sacrificed after 3 weeks from cell injection. At the end of the experiment, heart tissue was processed for both light and electron microscopic histological studies, and for PCR analysis of the male-specific SRY gene. Results: Light microscopic results of group III revealed increased diameter and necrosis of cardiomyocytes, decreased cross-striations, vascular congestion and mononuclear cellular infiltration. Group IV revealed multiple extensive fibrotic areas. Group V revealed smaller fibrotic areas compared to Group IV. Ultrastructural results confirmed findings of the light microscope. PCR analysis revealed that 63% of heart samples were positive for the presence of SRY gene. Conclusion: CD34+ stem cells can transdifferentiate into cardiomyocyte and regenerate the injured heart subjected to MI.Keywords: HUCB, CD34+ stem cells, myocardial infarction, transdifferentiatio

Éléments d’aide au contrôle de gestion et au management de l’agrumiculture au Maroc

L’étude est dédiée aux grandes entreprises agrumicoles structurées et décentralisées. Elle fournit les éléments agronomiques et financiers pour un modèle de contrôle de gestion de type bottom-up concevable à partir de l’expérience sur la nouvelle agrumiculture née du plan Maroc Vert. Le modèle suppose la transparence, un travail en partenariat fermes-contrôle de gestion, un système d’information fiable et une fluidité de circulation de l’information. En agriculture, il n’y a pas d’analogie parfaite avec l’industrie concernant l’évaluation des écarts de performance par rapport aux objectifs de gestion affichés par le budget. Dans l’industrie, les mêmes inputs et le même process produisent en général le même résultat, ce qui facilite amplement l’analyse des écarts constatés et aide beaucoup à proposer des mesures correctives. En agriculture, avec une même quantité d’inputs (eau, engrais, pesticides), et un même process de production (porte greffe, variété, densité, taille), le résultat peut être très différent selon l’année climatique, la région ou le type de sol. Par conséquent, le plus important dans cette activité, n’est pas l’écart de performance lui-même, mais de pouvoir expliquer la part de cet écart qui revient à la gestion et celle due aux facteurs externes non maitrisables du milieu. Une contre-performance sur la productivité ou la qualité peut être la conséquence d’effets pervers d’un Chergui (chute des fruits, marbrures, coup de soleil) alors qu’aucune modification n’a été apportée au process usuel de production. De même qu’une excellente performance est parfois en partie le fait d’une année climatique favorable et d’un bon prix sur le marché et non d’un effort particulier de gestion. Cette énorme difficulté à prévoir avec une certaine confiance, ce que sera le comportement du verger d’une année à l’autre, rend donc malaisé l’usage de « normes » figées pour le contrôle de gestion. C’est pourquoi dans la présente étude, l’effort a plus porté sur l’exploration des causes des écarts autour des chiffres moyens que sur les chiffres eux-mêmes. Au Maroc, on est en présence d’un système économique libéral certes, mais la surproduction avec l’idée d’ensuite vendre les agrumes « a dime a dozen » ou de laisser la main invisible d’Adam Smith réguler le marché n’a jamais été un objectif du plan Maroc Vert. Le but recherché, est plutôt de produire pour ensuite exporter davantage afin d’améliorer la balance commerciale du pays. Aujourd’hui, on est en situation d’offre excessive en petits fruits aggravée par un Export qui peine à monter en charge, il est donc légitime que chacun cherche à tirer son épingle du jeu. Faute de pouvoir agir sur les prix, la mission basique du contrôle de gestion est donc de maîtriser au moins les charges. Même si la vraie solution pour le Maroc, aurait été plutôt d’instaurer un super-contrôle de gestion innovant de type filière avec notamment des prérogatives de gel provisoire des plantations, le temps de conquérir de nouveaux marchés. Ce que nous craignions est maintenant arrivé en 2018, c'est-à-dire finir après autant d’investissements par vendre la clémentine de qualité sur le marché local à 10cts/kg. L’étude suggère entre autres, comment sortir de cette période trouble et surmonter la crise avec un minimum de dégâts pour le producteur. Mots clés : Contrôle de gestion, agrumes, MarocThe study concerns the large structured and decentralized citrus fruit companies. It provides the agronomic and financial tools for management control. The present management model is based on a bottom-up design. It is inspired from the new citrus cropping experience born from the Green Morocco plan. The model assumes transparency, farm and management control partnership, reliable information system and fluidity of information. In agriculture, there is no perfect analogy with the industry sector concerning the assessment of performance gaps compared to the management objectives reported by the budget. In industry, the same inputs combined to the same process generally produce the same result. Thus, the analysis of the observed performance gaps become easier and corrective measures can be suggested. In agriculture, the result can’t be similar even the same amount of inputs (water, fertilizer, pesticides), and the same production process (rootstock, cultivar, density, pruning) have been used. This situation is related to climatic year, location and soil type. Therefore, the most important in agricultural activity, is to explain the causes of the performance gap. Then, to classify these causes into manageable factors and not manageable factors of the environment. A low performance on productivity or quality can be related to the negative effect of “Chergui” wind (fall, physical damage, sunburn, ...) even we keep the same usual production process. Also, an excellent performance is sometimes related to a very good climate year and not to a specific management effort. The enormous difficulty of predicting confidently the orchard behavior, for each year, constrains the establishment of fixed "standards" useful for management control. Thus, in the present study, we try to explore causes of deviations around average numbers. In Morocco, a liberal economy is established. However, the overproduction with the idea of selling the citrus fruit as dime a dozen or leaving the Adam Smith invisible hand regulates the market has never been the goal of the Green Morocco Plan. Such plan aims to produce and to export more in order to improve the country's trade balance. Today, we are in a situation of excessive clementine supply aggravated by the difficulty to increase export quantity. This situation pushes each producer to perform well. Regarding the difficulty to regulate prices, the basic mission of the management control is to master at least the production costs. The true solution would to introduce an innovative super-control management of citrus sector. This management would include a provisional plantation freezing waiting for finding new markets. In fact, the feared problem is occurred in 2018. Indeed, high quality clementine has been sold at 10 cts kg-1. on the local market after many investments of the producer. The study aims to give suggestions to producers on how to manage this troubled period and overcome the crisis with minimal damage. Key words: Management control, citrus fruits, Morocc

Éléments d’aide au contrôle de gestion et au management de l’agrumiculture au Maroc

L’étude est dédiée aux grandes entreprises agrumicoles structurées et décentralisées. Elle fournit les éléments agronomiques et financiers pour un modèle de contrôle de gestion de type bottom-up concevable à partir de l’expérience sur la nouvelle agrumiculture née du plan Maroc Vert. Le modèle suppose la transparence, un travail en partenariat fermes-contrôle de gestion, un système d’information fiable et une fluidité de circulation de l’information. En agriculture, il n’y a pas d’analogie parfaite avec l’industrie concernant l’évaluation des écarts de performance par rapport aux objectifs de gestion affichés par le budget. Dans l’industrie, les mêmes inputs et le même process produisent en général le même résultat, ce qui facilite amplement l’analyse des écarts constatés et aide beaucoup à proposer des mesures correctives. En agriculture, avec une même quantité d’inputs (eau, engrais, pesticides), et un même process de production (porte greffe, variété, densité, taille), le résultat peut être très différent selon l’année climatique, la région ou le type de sol. Par conséquent, le plus important dans cette activité, n’est pas l’écart de performance lui-même, mais de pouvoir expliquer la part de cet écart qui revient à la gestion et celle due aux facteurs externes non maitrisables du milieu. Une contre-performance sur la productivité ou la qualité peut être la conséquence d’effets pervers d’un Chergui (chute des fruits, marbrures, coup de soleil) alors qu’aucune modification n’a été apportée au process usuel de production. De même qu’une excellente performance est parfois en partie le fait d’une année climatique favorable et d’un bon prix sur le marché et non d’un effort particulier de gestion. Cette énorme difficulté à prévoir avec une certaine confiance, ce que sera le comportement du verger d’une année à l’autre, rend donc malaisé l’usage de « normes » figées pour le contrôle de gestion. C’est pourquoi dans la présente étude, l’effort a plus porté sur l’exploration des causes des écarts autour des chiffres moyens que sur les chiffres eux-mêmes. Au Maroc, on est en présence d’un système économique libéral certes, mais la surproduction avec l’idée d’ensuite vendre les agrumes « a dime a dozen » ou de laisser la main invisible d’Adam Smith réguler le marché n’a jamais été un objectif du plan Maroc Vert. Le but recherché, est plutôt de produire pour ensuite exporter davantage afin d’améliorer la balance commerciale du pays. Aujourd’hui, on est en situation d’offre excessive en petits fruits aggravée par un Export qui peine à monter en charge, il est donc légitime que chacun cherche à tirer son épingle du jeu. Faute de pouvoir agir sur les prix, la mission basique du contrôle de gestion est donc de maîtriser au moins les charges. Même si la vraie solution pour le Maroc, aurait été plutôt d’instaurer un super-contrôle de gestion innovant de type filière avec notamment des prérogatives de gel provisoire des plantations, le temps de conquérir de nouveaux marchés. Ce que nous craignions est maintenant arrivé en 2018, c'est-à-dire finir après autant d’investissements par vendre la clémentine de qualité sur le marché local à 10cts/kg. L’étude suggère entre autres, comment sortir de cette période trouble et surmonter la crise avec un minimum de dégâts pour le producteur. Mots clés : Contrôle de gestion, agrumes, MarocThe study concerns the large structured and decentralized citrus fruit companies. It provides the agronomic and financial tools for management control. The present management model is based on a bottom-up design. It is inspired from the new citrus cropping experience born from the Green Morocco plan. The model assumes transparency, farm and management control partnership, reliable information system and fluidity of information. In agriculture, there is no perfect analogy with the industry sector concerning the assessment of performance gaps compared to the management objectives reported by the budget. In industry, the same inputs combined to the same process generally produce the same result. Thus, the analysis of the observed performance gaps become easier and corrective measures can be suggested. In agriculture, the result can’t be similar even the same amount of inputs (water, fertilizer, pesticides), and the same production process (rootstock, cultivar, density, pruning) have been used. This situation is related to climatic year, location and soil type. Therefore, the most important in agricultural activity, is to explain the causes of the performance gap. Then, to classify these causes into manageable factors and not manageable factors of the environment. A low performance on productivity or quality can be related to the negative effect of “Chergui” wind (fall, physical damage, sunburn, ...) even we keep the same usual production process. Also, an excellent performance is sometimes related to a very good climate year and not to a specific management effort. The enormous difficulty of predicting confidently the orchard behavior, for each year, constrains the establishment of fixed "standards" useful for management control. Thus, in the present study, we try to explore causes of deviations around average numbers. In Morocco, a liberal economy is established. However, the overproduction with the idea of selling the citrus fruit as dime a dozen or leaving the Adam Smith invisible hand regulates the market has never been the goal of the Green Morocco Plan. Such plan aims to produce and to export more in order to improve the country's trade balance. Today, we are in a situation of excessive clementine supply aggravated by the difficulty to increase export quantity. This situation pushes each producer to perform well. Regarding the difficulty to regulate prices, the basic mission of the management control is to master at least the production costs. The true solution would to introduce an innovative super-control management of citrus sector. This management would include a provisional plantation freezing waiting for finding new markets. In fact, the feared problem is occurred in 2018. Indeed, high quality clementine has been sold at 10 cts kg-1. on the local market after many investments of the producer. The study aims to give suggestions to producers on how to manage this troubled period and overcome the crisis with minimal damage. Key words: Management control, citrus fruits, Morocc

Learning beyond the classroom: students’ attitudes towards the integration of CLIL and museum-based pedagogies

In the last two decades, several studies have reported on the benefits of Content and Language Integrated Learning (CLIL) on students’ affective and cognitive gains. These studies, however, have mainly concentrated on the implementation of CLIL within the formal (school) context, with very little research on its impact in non-formal (out-of-school) contexts. Thus, the present article addresses this gap by describing an action research project aimed at understanding secondary school students’ attitudes towards the integration of CLIL and museum-based pedagogies. The project involved 284 students (14–16 years old) in northern Italy, who participated in a CLIL museum visit on Animal Classification through English at the Natural History Museum in Venice. A mixed-method research design was implemented and data was collected through students’ questionnaires and focus groups. Results reveal that students showed very positive attitudes towards taking part in a CLIL museum visit based on the interaction among the following dimensions: engagement with museum objects, use of English beyond the classroom, methodology and students’ interests, self-concept and career plans

Histone Acetylation-Mediated Regulation of the Hippo Pathway

The Hippo pathway is a signaling cascade recently found to play a key role in tumorigenesis therefore understanding the mechanisms that regulate it should open new opportunities for cancer treatment. Available data indicate that this pathway is controlled by signals from cell-cell junctions however the potential role of nuclear regulation has not yet been described. Here we set out to verify this possibility and define putative mechanism(s) by which it might occur. By using a luciferase reporter of the Hippo pathway, we measured the effects of different nuclear targeting drugs and found that chromatin-modifying agents, and to a lesser extent certain DNA damaging drugs, strongly induced activity of the reporter. This effect was not mediated by upstream core components (i.e. Mst, Lats) of the Hippo pathway, but through enhanced levels of the Hippo transducer TAZ. Investigation of the underlying mechanism led to the finding that cancer cell exposure to histone deacetylase inhibitors induced secretion of growth factors and cytokines, which in turn activate Akt and inhibit the GSK3 beta associated protein degradation complex in drug-affected as well as in their neighboring cells. Consequently, expression of EMT genes, cell migration and resistance to therapy were induced. These processes were suppressed by using pyrvinium, a recently described small molecule activator of the GSK 3 beta associated degradation complex. Overall, these findings shed light on a previously unrecognized phenomenon by which certain anti-cancer agents may paradoxically promote tumor progression by facilitating stabilization of the Hippo transducer TAZ and inducing cancer cell migration and resistance to therapy. Pharmacological targeting of the GSK3 beta associated degradation complex may thus represent a unique approach to treat cancer. © 2013 Basu et al

Expanding Clinical Presentations Due to Variations in THOC2 mRNA Nuclear Export Factor

Multiple TREX mRNA export complex subunits (e.g., THOC1, THOC2, THOC5, THOC6, THOC7) have now been implicated in neurodevelopmental disorders (NDDs), neurodegeneration and cancer. We previously implicated missense and splicing-defective THOC2 variants in NDDs and a broad range of other clinical features. Here we report 10 individuals from nine families with rare missense THOC2 variants including the first case of a recurrent variant (p.Arg77Cys), and an additional individual with an intragenic THOC2 microdeletion (Del-Ex37-38). Ex vivo missense variant testing and patient-derived cell line data from current and published studies show 9 of the 14 missense THOC2 variants result in

Ready for O4 II: GRANDMA Observations of Swift GRBs during eight-weeks of Spring 2022

We present a campaign designed to train the GRANDMA network and its infrastructure to follow up on transient alerts and detect their early afterglows. In preparation for O4 II campaign, we focused on GRB alerts as they are expected to be an electromagnetic counterpart of gravitational-wave events. Our goal was to improve our response to the alerts and start prompt observations as soon as possible to better prepare the GRANDMA network for the fourth observational run of LIGO-Virgo-Kagra (which started at the end of May 2023), and future missions such as SM. To receive, manage and send out observational plans to our partner telescopes we set up dedicated infrastructure and a rota of follow-up adcates were organized to guarantee round-the-clock assistance to our telescope teams. To ensure a great number of observations, we focused on Swift GRBs whose localization errors were generally smaller than the GRANDMA telescopes' field of view. This allowed us to bypass the transient identification process and focus on the reaction time and efficiency of the network. During 'Ready for O4 II', 11 Swift/INTEGRAL GRB triggers were selected, nine fields had been observed, and three afterglows were detected (GRB 220403B, GRB 220427A, GRB 220514A), with 17 GRANDMA telescopes and 17 amateur astronomers from the citizen science project Kilonova-Catcher. Here we highlight the GRB 220427A analysis where our long-term follow-up of the host galaxy allowed us to obtain a photometric redshift of $z=0.82\pm0.09$, its lightcurve elution, fit the decay slope of the afterglows, and study the properties of the host galaxy

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

On-line losses minimization of induction motor vector control

Conventional field-orientated Induction motor drives operate at rated flux even at low load. To improve the efficiency of the existing motor it is important to regulate the flux of the motor in the desired operating range. In this paper a loss model controller (LMC) based on the real coded genetic algorithm is proposed, it has the straightforward goal of maximizing the efficiency for each given load torque. In order to give more accuracy to the motor model and the LMC a series model of the motor which consider the iron losses as a resistance connected in series with the mutual inductance is considered. Digital computer simulation demonstrates the effectiveness of the proposed algorithm and also simulation results have confirmed that this algorithm yields the optimal efficiency