Mani, seine Lehre und seine Schriften : ein Beitrag zur Geschichte des Manichäismus : aus dem Fihrist des Abûʼlfaradsch Muḥammad ben Isḥaḳ al-Warrâḳ, bekannt unter dem Namen Ibn Abî Jaʻḳûb an-Nadîm /

Mode of access: Internet.

Dei fidecommessi a famiglie e a chiese e luoghi pii : in proposito del termine di mani-morte introdotto a questi ultimi tempi nell'economia nazionale libri due /

"Copia di lettera scritta addi 29 gennajo 1785, ai signori novellisti letterarj di Firenze"; p. 396-400.

S. Ephraim's prose refutations of Mani, Marcion, and Bardaisan, of which the greater part has been transcribed from the palimpsest B.M. add. 14623 and is now first published,

Title varies: v.2 ... Completed by A. A. Bevan and F. C. Burkitt.

Concepciones alternativas que, referentes al comportamiento variaciones de funciones, manifiestan profesores de bachillerato

En este artículo se reportan los resultados de una investigación que explora las concepciones alternativas de profesores de matemáticas de bachillerato acerca del comportamiento de funciones. Para tal exploración se diseñó un cuestionario en el que se usan los sistemas de representación verbal, gráfico y analítico. En especial se exploraron concepciones relativas al comportamiento variacional de funciones [v. gr: Para qué x, f'(x)>0], comportamiento variacional y signo simultáneamente [v. gr: Para qué x se cumple que: f'(x)>0 y f(x)<0] y las relativas a los procesos de reversibilidad: [v. gr: Dada f(x) esbozar f(x) y viceversa]. Los resultados indican que una cantidad significativa de profesores, creen que f(x)<0 si su gráfica está en el semieje negativo de las x; consideran a f'(x) como asociada a un punto y no al comportamiento de fix); la mayoría se muestra imposibilitado para transferir información variacional de la gráfica de f"(x) a f(x).

BSTA Promotes mTORC2-Mediated Phosphorylation of Akt1 to Suppress Expression of FoxC2 and Stimulate Adipocyte Differentiation

Phosphorylation and activation of Akt1 is a crucial signaling event that promotes adipogenesis. However, neither the complex multistep process that leads to activation of Akt1 through phosphorylation at Thr308 and Ser473 nor the mechanism by which Akt1 stimulates adipogenesis is fully understood. We found that the BSD domain–containing signal transducer and Akt interactor (BSTA) promoted phosphorylation of Akt1 at Ser473 in various human and murine cells, and we uncovered a function for the BSD domain in BSTA-Akt1 complex formation. The mammalian target of rapamycin complex 2 (mTORC2) facilitated the phosphorylation of BSTA and its association with Akt1, and the BSTA-Akt1 interaction promoted the association of mTORC2 with Akt1 and phosphorylation of Akt1 at Ser473 in response to growth factor stimulation. Furthermore, analyses of bsta gene-trap murine embryonic stem cells revealed an essential function for BSTA and phosphorylation of Akt1 at Ser473 in promoting adipocyte differentiation, which required suppression of the expression of the gene encoding the transcription factor FoxC2. These findings indicate that BSTA is a molecular switch that promotes phosphorylation of Akt1 at Ser473 and reveal an mTORC2-BSTA-Akt1-FoxC2–mediated signaling mechanism that is critical for adipocyte differentiation.

FOXC2 expression links epithelial-mesenchymal transition and stem cell properties in breast cancer

Resistance to chemotherapy and metastases are the major causes of breast cancer-related mortality. Moreover, cancer stem cells (CSC) play critical roles in cancer progression and treatment resistance. Previously, it was found that CSC-like cells can be generated by aberrant activation of epithelial–mesenchymal transition (EMT), thereby making anti-EMT strategies a novel therapeutic option for treatment of aggressive breast cancers. Here, we report that the transcription factor FOXC2 induced in response to multiple EMT signaling pathways as well as elevated in stem cell-enriched factions is a critical determinant of mesenchymal and stem cell properties, in cells induced to undergo EMT- and CSC-enriched breast cancer cell lines. More specifically, attenuation of FOXC2 expression using lentiviral short hairpin RNA led to inhibition of the mesenchymal phenotype and associated invasive and stem cell properties, which included reduced mammosphere-forming ability and tumor initiation. Whereas, overexpression of FOXC2 was sufficient to induce CSC properties and spontaneous metastasis in transformed human mammary epithelial cells. Furthermore, a FOXC2-induced gene expression signature was enriched in the claudin-low/basal B breast tumor subtype that contains EMT and CSC features. Having identified PDGFR-β to be regulated by FOXC2, we show that the U.S. Food and Drug Administration-approved PDGFR inhibitor, sunitinib, targets FOXC2-expressing tumor cells leading to reduced CSC and metastatic properties. Thus, FOXC2 or its associated gene expression program may provide an effective target for anti-EMT-based therapies for the treatment of claudin-low/basal B breast tumors or other EMT-/CSC-enriched tumors.

Loss of breast epithelial marker hCLCA2 promotes epithelial to mesenchymal transition and indicates higher risk of metastasis

Transition between epithelial and mesenchymal states is a feature of both normal development and tumor progression. We report that expression of chloride channel accessory protein hCLCA2 is a characteristic of epithelial differentiation in the immortalized MCF10A and HMLE models, while induction of epithelial-to-mesenchymal transition by cell dilution, TGFβ or mesenchymal transcription factors sharply reduces hCLCA2 levels. Attenuation of hCLCA2 expression by lentiviral small hairpin RNA caused cell overgrowth and focus formation, enhanced migration and invasion, and increased mammosphere formation in methylcellulose. These changes were accompanied by downregulation of E-cadherin and upregulation of mesenchymal markers such as vimentin and fibronectin. Moreover, hCLCA2 expression is greatly downregulated in breast cancer cells with a mesenchymal or claudin-low profile. These observations suggest that loss of hCLCA2 may promote metastasis. We find that higher-than-median expression of hCLCA2 is associated with a one-third lower rate of metastasis over an 18-year period among breast cancer patients compared with lower-than-median (n=344, unfiltered for subtype). Thus, hCLCA2 is required for epithelial differentiation, and its loss during tumor progression contributes to metastasis. Overexpression of hCLCA2 has been reported to inhibit cell proliferation and is accompanied by increases in chloride current at the plasma membrane and reduced intracellular pH (pHi). We found that knockdown cells have sharply reduced chloride current and higher pHi, both characteristics of tumor cells. These results suggest a mechanism for the effects on differentiation. Loss of hCLCA2 may allow escape from pHi homeostatic mechanisms, permitting the higher intracellular and lower extracellular pH that are characteristic of aggressive tumor cells.

Design, implementation and multisite evaluation of a system suitability protocol for the quantitative assessment of instrument performance in liquid chromatography-multiple reaction monitoring-MS (LC-MRM-MS)

Multiple reaction monitoring (MRM) mass spectrometry coupled with stable isotope dilution (SID) and liquid chromatography (LC) is increasingly used in biological and clinical studies for precise and reproducible quantification of peptides and proteins in complex sample matrices. Robust LC-SID-MRM-MS-based assays that can be replicated across laboratories and ultimately in clinical laboratory settings require standardized protocols to demonstrate that the analysis platforms are performing adequately. We developed a system suitability protocol (SSP), which employs a predigested mixture of six proteins, to facilitate performance evaluation of LC-SID-MRM-MS instrument platforms, configured with nanoflow-LC systems interfaced to triple quadrupole mass spectrometers. The SSP was designed for use with low multiplex analyses as well as high multiplex approaches when software-driven scheduling of data acquisition is required. Performance was assessed by monitoring of a range of chromatographic and mass spectrometric metrics including peak width, chromatographic resolution, peak capacity, and the variability in peak area and analyte retention time (RT) stability. The SSP, which was evaluated in 11 laboratories on a total of 15 different instruments, enabled early diagnoses of LC and MS anomalies that indicated suboptimal LC-MRM-MS performance. The observed range in variation of each of the metrics scrutinized serves to define the criteria for optimized LC-SID-MRM-MS platforms for routine use, with pass/fail criteria for system suitability performance measures defined as peak area coefficient of variation <0.15, peak width coefficient of variation <0.15, standard deviation of RT <0.15 min (9 s), and the RT drift <0.5min (30 s). The deleterious effect of a marginally performing LC-SID-MRM-MS system on the limit of quantification (LOQ) in targeted quantitative assays illustrates the use and need for a SSP to establish robust and reliable system performance. Use of a SSP helps to ensure that analyte quantification measurements can be replicated with good precision within and across multiple laboratories and should facilitate more widespread use of MRM-MS technology by the basic biomedical and clinical laboratory research communities.

Taxonomy and redescription of the Atherton Antechinus, Antechinus godmani (Thomas) (Marsupialia: Dasyuridae)

We provide a taxonomic redescription of the dasyurid marsupial Atherton Antechinus, Antechinus godmani (Thomas). A. godmani is only rarely encountered and limited to wet tropical rainforests of north-east Queensland, Australia, between the towns of Cardwell and Cairns (a distribution spanning 135 kilometres from north to south). The distinctive species occurs at altitudes of over 600 meters asl, in all major rainforest types, and can be found with both the northern subspecies of the Yellow-footed Antechinus, A. flavipes rubeculus Van Dyck and the Rusty Antechinus, A. adustus (Thomas). A. god-mani is clearly separated from all congeners on the basis of both morphometrics and genetics. A. godmani can be distin-guished from all extant congeners based on external morphology by a combination of large size, naked-looking tail and reddish fur on the face and head. A. godmani skulls are characteristically large, with a suite of long features: basicranium, palate, upper premolar tooth row, inter-palatal vacuity distance and dentary. Phylogenies generated from mt- and nDNA data position Antechinus godmani as monophyletic with respect to other members of the genus; A. godmani is strongly supported as the sister-group to a clade containing all other antechinus, but excluding the south-east Australian Dusky An-techinus, A. swainsonii (Waterhouse) and Swamp Antechinus, A. minimus (Geoffroy). Antechinus godmani are genetically very divergent compared to all congeners (mtDNA: range 12.9–16.3%).

The Mobile Application Rating Scale (MARS): A new tool to measure the quality of health mobile applications

Smartphone technology provides free or inexpensive access to mental health and wellbeing resources. As a result the use of mobile applications for these purposes has increased significantly in recent years. Yet, there is currently no app quality assessment alternative to the popular ‘star’-ratings, which are often unreliable. This presentation describes the development of the Mobile Application Rating Scale (MARS) a new measure for classifying and rating the quality of mobile applications. A review of existing literature on app and web quality identified 25 published papers, conference proceedings, and online resources (published since 1999), which identified 372 explicit quality criteria. Qualitative analysis identified five broad categories of app quality rating criteria: engagement, functionality, aesthetics, information quality, and overall satisfaction, which were refined into the 23-item MARS. Independent ratings of 50 randomly selected mental health and wellbeing mobile apps indicated the MARS had excellent levels of internal consistency (α = 0.92) and inter-rater reliability (ICC = 0.85). The MARS provides practitioners and researchers with an easy-to-use, simple, objective and reliable tool for assessing mobile app quality. It also provides mHealth professionals with a checklist for the design and development of high quality apps.

Epithelial mesenchymal transition traits in human breast cancer cell lines parallel the CD44HI/CD24lO/-stem cell phenotype in human breast cancer

We review here the recently emerging relationship between epithelial-mesenchymal transition (EMT) and breast cancer stem cells (BCSC), and provide analyses of published data on human breast cancer cell lines, supporting their utility as a model for the EMT/BCSC state. Genome-wide transcriptional profiling of these cell lines has confirmed the existence of a subgroup with mesenchymal tendencies and enhanced invasive properties ('Basal B'/Mesenchymal), distinct from subgroups with either predominantly luminal ('Luminal') or mixed basal/luminal ('Basal A') features (Neve et al. Cancer Cell, 2006). A literature-derived EMT gene signature has shown specific enrichment within the Basal B subgroup of cell lines, consistent with their over-expression of various EMT transcriptional drivers. Basal B cell lines are found to resemble BCSC, being CD44highCD24low. Moreover, gene products that distinguish Basal B from Basal A and Luminal cell lines (Basal B Discriminators) showed close concordance with those that define BCSC isolated from clinical material, as reported by Shipitsin et al. (Cancer Cell, 2007). CD24 mRNA levels varied across Basal B cell lines, correlating with other Basal B Discriminators. Many gene products correlating with CD24 status in Basal B cell lines were also differentially expressed in isolated BCSC. These findings confirm and extend the importance of the cellular product of the EMT with Basal B cell lines, and illustrate the value of analysing these cell lines for new leads that may improve breast cancer outcomes. Gene products specific to Basal B cell lines may serve as tools for the detection, quantification, and analysis of BCSC/EMT attributes.