Miracle-dz/UniFAR-FTUs huggingface dataset:
CASK interacts with PMCA4b and JAM‐A on the mouse sperm flagellum to regulate Ca2+ homeostasis and motility

Deletion of the highly conserved gene for the major Ca2+ efflux pump, Plasma membrane calcium/calmodulin‐dependent ATPase 4b (Pmca4b), in the mouse leads to loss of progressive and hyperactivated sperm motility and infertility. Here we first demonstrate that compared to wild‐type (WT), Junctional adhesion molecule‐A (Jam‐A) null sperm, previously shown to have motility defects and an abnormal mitochondrial phenotype reminiscent of that seen in Pmca4b nulls, exhibit reduced (P < 0.001) ATP levels, significantly (P < 0.001) greater cytosolic Ca2+ concentration ([Ca2+]c) and ∼10‐fold higher mitochondrial sequestration, indicating Ca2+ overload. Investigating the mechanism involved, we used co‐immunoprecipitation studies to show that CASK (Ca2+/calmodulin‐dependent serine kinase), identified for the first time on the sperm flagellum where it co‐localizes with both PMCA4b and JAM‐A on the proximal principal piece, acts as a common interacting partner of both. Importantly, CASK binds alternatively and non‐synergistically with each of these molecules via its single PDZ (PDS‐95/Dlg/ZO‐1) domain to either inhibit or promote efflux. In the absence of CASK–JAM‐A interaction in Jam‐A null sperm, CASK–PMCA4b interaction is increased, resulting in inhibition of PMCA4b's enzymatic activity, consequent Ca2+ accumulation, and a ∼6‐fold over‐expression of constitutively ATP‐utilizing CASK, compared to WT. Thus, CASK negatively regulates PMCA4b by directly binding to it and JAM‐A positively regulates it indirectly through CASK. The decreased motility is likely due to the collateral net deficit in ATP observed in nulls. Our data indicate that Ca2+ homeostasis in sperm is maintained by the relative ratios of CASK–PMCA4b and CASK–JAM‐A interactions. J. Cell. Physiol. 227: 3138–3150, 2012. © 2011 Wiley Periodicals, Inc.
The Predictability and Abstractness of Language: A Study in Understanding and Usage of the English Language through Probabilistic Modeling and Frequency

Accounts of language acquisition differ significantly in their treatment of the role of prediction in language learning. In particular, nativist accounts posit that probabilistic learning about words and word sequences has little to do with how children come to use language. The accuracy of this claim was examined by testing whether distributional probabilities and frequency contributed to how well 3-4 year olds repeat simple word chunks. Corresponding chunks were the same length, expressed similar content, and were all grammatically acceptable, yet the results of the study showed marked differences in performance when overall distributional frequency varied. It was found that a distributional model of language predicted the empirical findings better than a number of other models, replicating earlier findings and showing that children attend to distributional probabilities in an adult corpus. This suggested that language is more prediction-and-error based, rather than on abstract rules which nativist camps suggest. Keywords—Abstractness, Child psychology, Language acquisition, Prediction and error
Path Integration Using a Model of e-Vector Orientation Coding in the Insect Brain: Reply to Vickerstaff and Di Paolo

In their response to our article (Haferlach, Wessnitzer, Mangan, & Webb, 2007), Vickerstaff and Di Paolo correctly note that the response function of input units used to evolve our network was the same cos(ha – hp) as that used by Vickerstaff and Di Paolo (2005), and resembles the POL neuron arrangement in insects (Labhart & Meyer, 2002) only in the use of three instead of two such units. However it is important to note that our evolved network structure—which maintains a population encoding of the home vector over a set of memory neurons that integrate the input coming from the direction cells—is in fact generalizable to a wide range of direction cell response functions. To demonstrate this point, we here show the results of integrating this network with a very recent model of e-Vector orientation coding in the central complex of the insect brain (Sakura, Lambrinos, & Labhart, 2008)
90Y‐ibritumomab tiuxetan radiotherapy as first‐line therapy for early stage low‐grade B‐cell lymphomas, including bulky disease

90Y‐ibritumomab‐tiuxetan (90YIT) was used as a first‐line therapy for patients with early‐stage follicular lymphoma (FL) or marginal zone B‐cell lymphoma (MZL). Thirty‐one patients were treated, with an overall 3‐month response rate of 100% (68% complete response, 29% unconfirmed complete response and 3% partial response). At a median follow‐up of 56 months, ten patients (32%) had disease relapse or progression. The progression‐free rates at 3 and 5 years were lower in males, patients with FL, stage II diseaseand non‐bulky disease, although they did not reach statistical significance. Grade 3–4 neutropenia, thrombocytopenia and anaemia were 61%, 35%, and 3%, respectively. 90YIT was well tolerated, including in those patients over 60 years old, and achieved high response rates in patients with early‐stage low‐grade B‐cell lymphomas. Bulky disease did not adversely affect tumour response.
The need for minimization strategies: current problems of immunosuppression

New immunosuppressants and the better use of immunosuppressant combination therapy have led to significant improvements in renal allograft outcomes over the last decades. Yet, despite dramatic reduction in rejection rates and improvement in 1‐year graft survival, long‐term graft attrition rates remained rather constant. Current immunosuppressant combinations are frequently leading to overimmunosuppression and are increasing cardiovascular risk. Importantly, calcineurin inhibitors are nephrotoxic, contribute to cardiovascular risk and chronic allograft dysfunction. Furthermore, immunosuppressant‐associated toxicities aggravate immune‐mediated nephron injury and side effects lead to nonadherence, an identified important reason for late acute and chronic antibody‐mediated rejections. The frequent development of a chronic humoral response indicates rather insufficient immunosuppression of current combinations than simple under‐immunosuppression. While there is no evidence that increasing immunosuppressive doses will improve outcomes or reduce de novo HLA‐antibody formation, there is clear evidence that adequate minimization strategies will reduce side effect burden. Because of low rejection risk, but frequent side effects, drug minimization is particularly relevant for the many maintenance patients. In summary, new therapeutic strategies need to be developed from adequately powered clinical trials for reduction of the many side effects of immunosuppressants. Such evidence‐based and time‐dependent immunosuppressive minimization strategies are needed to achieve better long‐term outcomes in the future.
Design of MIMO relay systems with interference cancellation under perfect CSI

This paper describes a design method of two-hop single and multiple relay systems in which sources, relays, and destination are equipped with multiple antenna. The existence of interference signal and perfect CSI (channel state information) condition are assumed, and the design is carried out based on the maximum SINR (signal to interference plus noise ration) criterion. For multiple relay case, array weights are designed independently between first and second hops by adopting separable weight matrices in relays. Through computer simulations, the effectiveness of the proposed methods is verified.
Déclinaison d'exigences de sécurité, du niveau système vers le niveau logiciel, assistée par des modèles formels

Les turbomoteurs d'helicoptere incluent des logiciels de controle de plus en plus elabores et complexes. Pour repondre aux exigences de securite de ce type de systeme, il convient de decliner precisement les exigences systeme en exigences logicielles. Nos travaux ont porte sur l'amelioration de cette phase de declinaison d'exigences. Nous proposons une demarche en deux etapes. La premiere consiste a modeliser, en language AltaRIca, les propagations de pannes potentielles de composants du systeme, en integrant des hypotheses de modes de defaillance sur les parties materielles et logicielles. L'analyse de ce modele permet d'evaluer la surete de l'architecture du systeme envisagee, et de deduire des exigences elementaires, en particulier sur les fonctions logicielles. Ces exigences imposent que certains comportements logiciels ne se produisent pas. La seconde etape porte sur le raffinement de ces exigences afin de les rendre verifiables sur le modele de conception SCADE du logiciel.
In Patas monkey, glutamic acid decarboxylase‐67 and reelin mRNA coexpression varies in a manner dependent on layers and cortical areas

In nonhuman and human primates, reelin immunoreactivity is expressed consistently in γ‐aminobutyric acid (GABA)‐ergic interneurons of the three upper cortical layers (Impagnatiello et al. [1998] Proc. Natl. Acad. Sci. U S A 95:15718–15723; Rodriguez et al. [2000] Proc. Natl. Acad. Sci. U S A 97:3550–3555). To understand in detail the pattern of reelin synthesis in GABAergic interneurons of primate neocortex, a quantitative analysis of reelin and of glutamic acid decarboxylase‐67 (GAD67) mRNA‐positive neurons as well as a quantitative analysis of total neuronal density measured by neuron‐specific nuclear protein (NeuN) immunoreactivity was carried out in Patas monkey neocortex (Brodmann's areas 2, 3, 4, 6, 9, 17, 18, and 24). Reelin mRNA is expressed in every cortical area and layer studied, but layer II of each cortical area consistently revealed the largest neuronal population expressing reelin mRNA compared with other layers. The percentages of GAD67‐positive neurons in each layer of the eight cortical areas were 83–98% in layer I, 55–64% in layer II, 37–49% in layer III, 71–89% in layer IV, 54–68% in layer V, and 71–85% in layer VI. The percentages of GABAergic neurons expressing reelin were 86–100% in layer I, 76–84% in layer II, 52–96% in layer III, 23–33% in layer IV, 33–57% in layer V, and 34–54% in layer VI. These findings suggest that there may be two classes of GABAergic neurons that can be differentiated by their ability to express reelin mRNA and reelin protein. This differentiation may have a functional significance, considering that reelin is secreted into the extracellular matrix, where it plays a putative role in the maturation of newly formed dendritic spines and binds selectively to dendritic shafts and to spine postsynaptic densities and presumably to integrin receptors, including α3 subunits (Rodriguez et al. [2000]). J. Comp. Neurol. 451:279–288, 2002. © 2002 Wiley‐Liss, Inc.
Entry Level Technology Positions: No Degree Required

Employers demand for skilled technology workers has never been higher. Opportunities for individuals interested in working in technology to acquire the requisite skills have expanded to meet the increased demand. The expansion of training offerings calls into question the quality of new ventures such as coding academies and the necessity of traditional academic pathways. This research addresses concerns by exploring how employers value different forms of skill acquisition within the information technology environment defined as: academic degrees, certifications, and work experience. IT executives and HR managers surveyed give insight into how they relatively value the various sources for their new and experienced employees. Using non-parametric methods and correspondence analysis, an overall picture of employers’ valuations were obtained. Additionally, subsections were analyzed across employer size and industry type. Results from the analysis identified expected general valuations by the employers. However, employer responses to the valuations identified unexpected actions that have potential negative impacts on institutions of higher education.
Etude par RMN et modélisation moléculaire des structures de la séquence ARN initiant la dimérisation chez VIH-1Lai et de son analogue ADN

Le genome du virus de l'immunodeficience humaine (VIH) est constitue, comme tous les retrovirus, de deux copies identiques d'ARN genomique. Celles-ci sont liees de maniere non covalente au niveau de leur region 5'-terminale. Ce phenomene de dimerisation interfere avec differentes etapes cles du cycle retroviral. C'est pourquoi, l'inhibition de la dimerisation represente une nouvelle voie de traitement potentiel du VIH. La premiere partie de ce travail porte sur la sequence d'ARN SL1 initiant la dimerisation chez VIH-1Lai. Nous nous sommes interesses a la determination structurale, par RMN et modelisation moleculaire, des especes presentes dans le processus de dimerisation sous forme instable. Apres avoir isole les deux differents dimere d'ARN, nous avons mis en evidence la structure du dimere stable qui permet d'avancer des hypotheses quant a leur stabilite relative. La seconde partie de ce travail porte sur l'etude du fragment desoxyribose de SL1. La encore, deux conformeres de stabilite differente sont isolables. Le dimere instable s'organise sous forme de “kissing-complex” et represente la premiere structure de ce type elucidee pour un ADN. La structure du dimere stable demeure de type “kissing-complex” bien que presentant des differences a l'origine du changement de stabilite. La presence du groupement hydroxyle distinguant l'ADN de l'ARN explique cette difference de comportement. Ces investigations structurales constituent une solide base d'etude dans les strategies de “drug-design” impliquant le developpement d'inhibiteurs susceptibles d'interferer avec le phenomene de dimerisation.
RNA polymerase II subunit RPB4 is essential for high- and low-temperature yeast cell growth

RPB4 encodes the fourth-largest RNA polymerase II subunit in Saccharomyces cerevisiae. The RPB4 gene was cloned and sequenced, and its identity was confirmed by amino acid sequence analysis of tryptic peptides from the purified subunit. The RPB4 DNA sequence predicted a protein of 221 amino acids with a molecular mass of 25,414 daltons. The central 100 amino acids of the RPB4 protein were found to be similar to a segment of the major sigma subunit in Escherichia coli RNA polymerase. Deletion of RPB4 produced cells that were heat and cold sensitive but could grow, albeit slowly, at intermediate temperatures. RNA polymerase II lacking the RPB4 subunit exhibited markedly reduced activity in crude extracts in vitro. The RPB4 subunit, although not essential for mRNA synthesis or enzyme assembly, was essential for normal levels of RNA polymerase II activity and indispensable for cell viability over a wide temperature range.
EVALUATION OF ABAMECTIN TOXICITY ON SOME BIOCHEMICAL CONSTITUENTS AND OSMOREGULATION IN FRESHWATER FISH Oreochromis niloticus ( Tilapia niloticus )

Indiscriment use of pesticides have been elevated the risk of contamination in environment and aquatic organisms. Considering to the previous fact, the present study was done to investigate the alterations of some blood constituents and ionic regulation; as well as the histopathological alterations in tissues of gills and kidneys of freshwater fish, Oreochromis niloticus, following prolonged exposure to sub-lethal concentrations of abamectin insecticide at 14 days. The obtained results showed that abamectin treatment caused hypotriglyceridemia and hyperglycemia in fish exposed to the high concentration (103.68μgL). In addition, hypercholesterolemia was detected in abamectin-exposed fish (by 50.48 and 103. 68μgL) after 14 days of exposure. Also, a marked increase in the creatinine level was observed in abamectin-exposed fish by 103. 68μgL on day 14, with a significant decline in the level of sodium ions (Na) and a significant elevation in the level of chloride ions (Cl) in fish exposed to low concentration (50.48μgL) of abamectin. In contrast, a significant decrease in the level of chloride ions (Cl) was detected in the high concentration of abamectin. Marked decrease in the level of plasma bound calcium (B.Ca) with hypoproteinemia and hypophosphatemia were recorded in fish exposed to low concentration (50.48μgL) of abamectin. On the contrary, a marked enhancement in the triiodothyronine level (T3) was noticed in fish following exposure to 50.48μgL of abamectin. The histopathological studies on the gills and kidneys revealed necrosis of lamella and infiltration of acidophils leukocyte in gills with degenerative changes in kidney tubules were observed at both concentrations of abamectin.
The Evaluation of the Relationship Between the Level of Disclosure of Cancer in Terminally Ill Patients With Cancer and the Quality of Terminal Care in These Patients and Their Families Using the Support Team Assessment Schedule

Aims: To examine the relationship between informing patients of cancer and the quality of terminal care. Methods: This was a study of 87 consecutive terminally ill cancer patients who died during the last 27-month period. Notification of cancer was classified into 4 groups (A, B, C, and D, respectively): “nondisclosure,” “disclosure of cancer diagnosis,” “disclosure of life threatening,” and “disclosure of poor prognosis. ” We evaluated the quality of palliative care using Support Team Assessment Schedule–Japanese (STAS-J). Results: A, B, C, and D groups included 8, 22, 37, and20 cases, respectively. Regarding physical symptoms, no marked difference was noted. Anxiety was significantly reduced, and the recognition of disease conditions and the level of communication were significantly higher in the groups that received specific information (P < .001). Conclusions: Informing patients of more specific information will increase the quality of terminal care.
Finite-Frequency Tomography Reveals a Variety of Plumes in the Mantle

We present tomographic evidence for the existence of deep-mantle thermal convection plumes. P-wave velocity images show at least six well-resolved plumes that extend into the lowermost mantle: Ascension, Azores, Canary, Easter, Samoa, and Tahiti. Other less well-resolved plumes, including Hawaii, may also reach the lowermost mantle. We also see several plumes that are mostly confined to the upper mantle, suggesting that convection may be partially separated into two depth regimes. All of the observed plumes have diameters of several hundred kilometers, indicating that plumes convey a substantial fraction of the internal heat escaping from Earth.
Modélisations et analyses de réseaux de capteurs

Les reseaux de capteurs sont difficiles a concevoir parce qu'ils sont fortement contraints en energie et que tous les elements influencent potentiellement la duree de vie du systeme. Pour tester les solutions avant le deploiement, nous proposons de construire des modeles analysables. Nous avons concu Glonemo, un modele global et precis du systeme. Programme en ReactiveML, cet outil executable permet de simuler des reseaux de grande taille tout en estimant finement la consommation des nœuds. L'environnement y est modelise de facon realiste. Glonemo beneficie d'une semantique formelle, mais la taille des modeles exclue la possibilite d'effectuer des analyses exhaustives. Nous simplifions donc le modele et, grâce a IF, calculons la duree de vie pire-cas du reseau. Enfin, nous definissons une relation d'abstraction modulaire de modeles de consommation. Les abstractions ainsi definies sont conservatives : les proprietes prouvees sur le modele abstrait sont vraies sur le modele detaille.
Major selected monoterpenes α-pinene and 1,8-cineole found in Salvia lavandulifolia (Spanish sage) essential oil as regulators of cellular redox balance

Abstract Context: Salvia lavandulifolia has been employed in folk medicine for the treatment of memory and dementia problems. This specie contains numerous bioactive terpenes which may contribute to its effectiveness. Objective: To analyze the composition of essential oil of S. lavandulifolia and to investigate the potential in vitro cytoprotective and antioxidant activities of its major compounds, α-pinene and 1,8-cineole, against H2O2-induced oxidative stress in the U373-MG cell line. Materials and methods: Chemical composition was analyzed by gas chromatography; antioxidant capacity was measured using the ORAC assay, and cytoprotective activity was evaluated using the MTT assay (for cell viability) (range of concentrations: 10–400 μM), DCFH-DA assay (for intracellular ROS generation), thiobarbituric acid reactive substances (TBARS) method (for lipid peroxidation), and spectrofometric techniques and Western blot (for enzymatic activity and protein expression, respectively) at 10 and 25 µM. Results: α-Pinene (18.39%) and 1,8-cineole (19.57%) were identified as major compounds in S. lavandulifolia essential oil. Pretreatments with these monoterpenes protected U373-MG cells against H2O2-induced oxidative injury by attenuating the loss of cell viability (IC50 : 79.70 µM to α-pinene and 66.23 µM to 1,8-cineole) and cell morphology, inhibiting ROS production (the most active compound was 1,8-cineole by decreasing the ROS production over 30–45% at 10 and 25 μM) and lipid peroxidation and increasing the endogenous antioxidant status (glutathione levels and CAT, SOD, GR, GPx, and HO-1 activity and protein expression). Conclusions: These findings demonstrate for the first time the effects of the monoterpenes 1,8-cineole and α-pinene identified in S. lavandulifolia essential oil as regulators of cellular redox balance in astrocytes.
Tapping natural variation at functional level reveals allele specific molecular characteristics of potato invertase Pain-1.

Biochemical, molecular and genetic studies emphasize the role of the potato vacuolar invertase Pain-1 in the accumulation of reducing sugars in potato tubers upon cold storage, and thereby its influence on the quality of potato chips and French fries. Previous studies showed that natural Pain-1 cDNA alleles were associated with better chip quality and higher tuber starch content. In this study, we focused on the functional characterization of these alleles. A genotype-dependent transient increase of total Pain-1 transcript levels in cold-stored tubers of six different genotypes as well as allele-specific expression patterns were detected. 3D modelling revealed putative structural differences between allelic Pain-1 proteins at the molecule's surface and at the substrate binding site. Furthermore, the yeast SUC2 mutant was complemented with Pain-1 cDNA alleles and enzymatic parameters of the heterologous expressed proteins were measured at 30 and 4 °C. Significant differences between the alleles were detected. The observed functional differences between Pain-1 alleles did not permit final conclusions on the mechanism of their association with tuber quality traits. Our results show that natural allelic variation at the functional level is present in potato, and that the heterozygous genetic background influences the manifestation of this variation.