We examine the effects of bank M&As on small business lending using data on over 6000 recent U.S. bank M&As. We are the first to decompose the impact of M&As into the static effects from simply ...melding the antecedent institutions and the dynamic effects associated with post-M&A refocusing of the consolidated institution. We are also the first to estimate the dynamic reactions of other local banks. We find that the static effects of consolidation reduce small business lending, but are mostly offset by the reactions of other banks, and in some cases also by refocusing efforts of the consolidating institutions themselves.
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive enlargement of kidney cysts, leading to chronic kidney disease. Since the available treatment for ADPKD is ...limited, there is emerging interest for natural compounds as potential therapeutic candidates. The aim of our study was to investigate whether an olive leaf extract may be able to counteract the cyst growth in an
in vitro
model of ADPKD. We treated WT9-12 cells with an olive leaf extract (OLE). In monolayer culture we evaluated cell viability by the MTT assay, protein expression by western-blot analysis and apoptosis by DNA laddering and TUNEL assays. For functional studies we used transient transfection and ChIP assays. Intracellular calcium measurement was performed with a spectrofluorimeter using a fluorescent probe. 3D-cell-culture was used for cyst growth studies. OLE reduced the WT9-12 cell growth rate and affected intracellular signaling due to high c-AMP levels, as OLE reduced PKA levels, enhanced p-AKT, restored B-Raf-inactivation and down-regulated p-ERK. We elucidated the molecular mechanism by which OLE,
via
Sp1, transactivates the p21
WAF1/Cip1
promoter, whose levels are down-regulated by mutated PKD1. We demonstrated that p-AKT up-regulation also played a crucial role in the OLE-induced anti-apoptotic effect and that OLE ameliorated intracellular calcium levels, the primary cause of ADPKD. Finally, using a 3D-cell-culture model we observed that OLE reduced the cyst size. Therefore, multifaceted OLE may be considered a new therapeutic approach for ADPKD treatment.
-Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive enlargement of kidney cysts, leading to chronic kidney disease.
A new hadron-therapy facility implementing an active beam scanning technique has been developed at the Italian National Center of Oncological Hadron-therapy (CNAO). This paper presents the design and ...the characterization of the beam monitor detectors developed for the on-line monitoring and control of the dose delivered during a treatment at CNAO. The detectors are based on five parallel-plate transmission ionization chambers with either a single large electrode or electrodes segmented in 128 strips (strip chambers) and 32×32pixels (pixel chamber). The detectors are arranged in two independent boxes with an active area larger than 200×200mm2 and a total water equivalent thickness along the beam path of about 0.9mm. A custom front-end chip with 64 channels converts the integrated ionization channels without dead-time.
The detectors were tested at the clinical proton beam facility of the Paul Scherrer Institut (PSI) which implements a spot scanning technique, each spot being characterized by a predefined number of protons delivered with a pencil beam in a specified point of the irradiation field. The short-term instability was measured by delivering several identical spots in a time interval of few tenths of seconds and is found to be lower than 0.3%. The non-uniformity, measured by delivering sequences of spots in different points of the detector surface, results to be lower than 1% in the single electrode chambers and lower than 1.5% in the strip and pixel chambers, reducing to less than 0.5% and 1% in the restricted 100×100mm2 central area of the detector.
Cardiogenic shock is a dreadful complication of myocardial infarction. Despite widespread use and availability, intra‐aortic balloon pump (IABP) does not reduce mortality nor improves outcomes. ...Advanced mechanical circulatory support with IMPELLA system can substantially support hemodynamics and improve short‐term prognosis in patients with myocardial infarction and cardiogenic shock.
Cardiogenic shock is a dreadful complication of myocardial infarction. Despite widespread use and availability, intra‐aortic balloon pump (IABP) does not reduce mortality nor improves outcomes. Advanced mechanical circulatory support with IMPELLA system can substantially support hemodynamics and improve short‐term prognosis in patients with myocardial infarction and cardiogenic shock.
The human glutamine/neutral amino acid transporter ASCT2 (hASCT2) was over-expressed in Pichia pastoris and purified by Ni2+-chelating and gel filtration chromatography. The purified protein was ...reconstituted in liposomes by detergent removal with a batch-wise procedure. Time dependent 3Hglutamine/glutamine antiport was measured in proteoliposomes which was active only in the presence of external Na+. Internal Na+ slightly stimulated the antiport. Optimal activity was found at pH7.0. A substantial inhibition of the transport was observed by Cys, Thr, Ser, Ala, Asn and Met (≥70%) and by mercurials and methanethiosulfonates (≥80%). Heterologous antiport of 3Hglutamine with other neutral amino acids was also studied. The transporter showed asymmetric specificity for amino acids: Ala, Cys, Val, Met were only inwardly transported, while Gln, Ser, Asn, and Thr were transported bi-directionally. From kinetic analysis of 3Hglutamine/glutamine antiport Km values of 0.097 and 1.8mM were measured on the external and internal sides of proteoliposomes, respectively. The Km for Na+ on the external side was 32mM. The homology structural model of the hASCT2 protein was built using the GltPh of Pyrococcus horikoshii as template. Cys395 was the only Cys residue externally exposed, thus being the potential target of SH reagents inhibition and, hence, potentially involved in the transport mechanism.
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•The human ASCT2 transporter has been over produced in P. pastoris.•The over-expressed protein has been purified and reconstituted in liposomes.•Functional analysis highlighted asymmetric specificity towards neutral amino acids.•Targeting by SH reagents correlated with Cys location in the structural model.
Many proteins are localized at the vacuolar membrane, but most of them are still poorly described, due to the inaccessibility of this membrane from the extracellular environment. This work focused on ...the characterization of the CAT2 transporter from
(
CAT2) that was previously overexpressed in
and reconstituted in proteoliposomes for transport assay as ³HArg uptake. The orientation of the reconstituted transporter has been attempted and current data support the hypothesis that the protein is inserted in the liposome in the same orientation as in the vacuole.
CAT2 activity was dependent on the pH, with an optimum at pH 7.5.
CAT2 transport activity was stimulated by the increase of internal osmolality from 0 to 175 mOsmol while the activity was inhibited by the increase of external osmolality. K⁺, Na⁺, and Mg
present on the external side of proteoliposomes at physiological concentrations, inhibited the transport activity; differently, the cations had no effect when included in the internal proteoliposome compartment. This data highlighted an asymmetric regulation of
CAT2. Cholesteryl hemisuccinate, included in the proteoliposomal membrane, stimulated the
CAT2 transport activity. The homology model of the protein was built using, as a template, the 3D structure of the amino acid transporter
ApcT. Putative substrate binding residues and cholesterol binding domains were proposed. Altogether, the described results open new perspectives for studying the response of
CAT2 and, in general, of plant vacuolar transporters to metabolic and environmental changes.
AbstractBackgroundThe twelve‑lead electrocardiogram (ECG) has become an essential tool for the diagnosis, risk stratification, and management of patients with acute coronary syndromes (ACS). However, ...several areas of residual controversies or gaps in evidence exist. Among them, P-wave abnormalities identifying atrial ischemia/infarction are largely neglected in clinical practice, and their diagnostic and prognostic implications remain elusive; the value of ECG to identify the culprit lesion has been investigated, but validated criteria indicating the presence of coronary occlusion in patients without ST-elevation are lacking; finally, which criteria among the multiple proposed, better define pathological Q-waves or success of revascularisation deserve further investigations. MethodsThe Minimizing Adverse hemorrhagic events via TRansradial access site and systemic Implementation of AngioX (MATRIX) trial was designed to test the impact of bleeding avoidance strategies on ischemic and bleeding outcomes across the whole spectrum of patients with ACS receiving invasive management. The ECG-MATRIX is a pre-specified sub-study of the MATRIX programme which aims at analyzing the clinical value of ECG metrics in 4516 ACS patients (with and without ST-segment elevation in 2212 and 2304 cases, respectively) with matched pre and post-treatment ECGs. ConclusionsThis study represents a unique opportunity to further investigate the role of ECGs in the diagnosis and risk stratification of ACS patients with or without ST-segment deviation, as well as to assess whether the radial approach and bivalirudin may affect post-treatment ECG metrics and patterns in a large contemporary ACS population.
This paper compares the performance of students at a high-performing U.S. public school (n = 64) on the advanced placement (AP) chemistry exam to their performance on the ChemQuery assessment system. ...The AP chemistry exam was chosen because, as the National Research Council acknowledges, it is the “perceived standard of excellence and school quality”. In contrast to the nationally recognized AP chemistry exam, the ChemQuery assessment system is a research tool that uses item-response theory to map student progress on a scale of conceptual understanding in chemistry. Our findings indicate that the two types of assessments, traditional problem-solving skills and conceptual understanding, are highly correlated as measured here. However, student performance on the ChemQuery assessment is disappointingly low. On the basis of the data analysis, this paper discusses the implications of the findings with a focus on the current efforts to redesign the AP chemistry exam.
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