Search results for "target [deuteron]"

Concurrent TMS-fMRI for causal network perturbation and proof of target engagement

2021

The experimental manipulation of neural activity by neurostimulation techniques overcomes the inherent limitations of correlative recordings, enabling the researcher to investigate causal brain-behavior relationships. But only when stimulation and recordings are combined, the direct impact of the stimulation on neural activity can be evaluated. In humans, this can be achieved non-invasively through the concurrent combination of transcranial magnetic stimulation (TMS) with functional magnetic resonance imaging (fMRI). Concurrent TMS-fMRI allows the assessment of the neurovascular responses evoked by TMS with excellent spatial resolution and full-brain coverage. This enables the functional ma…

A genome-wide transcriptional study reveals that iron deficiency inhibits the yeast TORC1 pathway

2019

Iron is an essential micronutrient that participates as a cofactor in a broad range of metabolic processes including mitochondrial respiration, DNA replication, protein translation and lipid biosynthesis. Adaptation to iron deficiency requires the global reorganization of cellular metabolism directed to optimize iron utilization. The budding yeast Saccharomyces cerevisiae has been widely used to characterize the responses of eukaryotic microorganisms to iron depletion. In this report, we used a genomic approach to investigate the contribution of transcription rates to the modulation of mRNA levels during adaptation of yeast cells to iron starvation. We reveal that a decrease in the activity…

Value of home blood pressure as predictor of target organ damage in mild arterial hypertension

2001

Implementare le politiche sanitarie a livello regionale per l'eliminazione dell'epatite C ai tempi del COVID-19

2022

Viral hepatitis C is an important public health problem and its elimination by 2030, defined by the World Health Organization, is an ambitious goal. The chance of free screening for HCV infection represents an important achievement that requires a successful State-Regions coordination and an effective regional organisation, that guarantees an interdisciplinary course between local and specialized healthcare. A structured communication program to increase the sensitivity of target populations as well as health professionals is the key for success. The implementation of the proactive screening, defined by the Milleproroghe Law, is crucial because it will define the tracks for the whole HCV co…

Learning a class of regular expressions via restricted subset queries

1992

A wide class of regular expressions non-representable as unions of “smaller” expressions is shown to be polynomial-time learnable via restricted subset queries from arbitrary representative examples “reflecting” the loop structure and a way the input example is obtained from the unknown expression. The corresponding subclass of regular expressions of loop depth at most 1 is shown to be learnable from representative examples via membership queries. A wide class of expressions with loops A+ of arbitrary loop depth is shown to be learnable via restricted subset queries from arbitrary examples.

mTORC1 activation in B cells confers impairment of marginal zone microarchitecture by exaggerating cathepsin activity

2018

Mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cell metabolism and lymphocyte proliferation. It is inhibited by the tuberous sclerosis complex (TSC), a heterodimer of TSC1 and TSC2. Deletion of either gene results in robust activation of mTORC1. Mature B cells reside in the spleen at two major anatomical locations, the marginal zone (MZ) and follicles. The MZ constitutes the first line of humoral response against blood‐borne pathogens and undergoes atrophy in chronic inflammation. In previous work, we showed that mice deleted for TSC1 in their B cells (TSC1(BKO)) have almost no MZ B cells, whereas follicular B cells are minimally affected. To explore potential underl…

Outline for a Relevance Theoretical Model of Machine Translation Post-editing

2018

Translation process research (TPR) has advanced in the recent years to a state which allows us to study “in great detail what source and target text units are being processed, at a given point in time, to investigate what steps are involved in this process, what segments are read and aligned and how this whole process is monitored” (Alves 2015, p. 32). We have sophisticated statistical methods and with the powerful tools to produce a better and more detailed understanding of the underlying cognitive processes that are involved in translation. Following Jakobsen (2011), who suspects that we may soon be in a situation which allows us to develop a computational model of human translation, Alve…

Sensitivity of pancreatic cancer cells to chemotherapeutic drugs, signal transduction inhibitors and nutraceuticals can be regulated by WT-TP53

2020

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic malignancy. Approximately 85% of pancreatic cancers are classified as PDACs. The survival of PDAC patients is very poor and only 5–10% of patients survive 5 years after diagnosis. Mutations at the KRAS and TP53 gene are frequently observed in PDAC patients. The PANC-28 cell line lacks wild-type (WT) TP53. In the following study, we have investigated the effects of restoration of WT TP53 activity on the sensitivity of PANC-28 pancreatic cancer cells to various drugs which are used to treat PDAC patients as well as other cancer patients. In addition, we have examined the effects of signal transduction inhibitors which tar…

Muscle follistatin gene delivery increases muscle protein synthesis independent of periodical physical inactivity and fasting

2020

Blocking of myostatin and activins effectively counteracts muscle atrophy. However, the potential interaction with physical inactivity and fasting in the regulation of muscle protein synthesis is poorly understood. We used blockade of myostatin and activins by recombinant adeno-associated virus (rAAV)-mediated follistatin (FS288) overexpression in mouse tibialis anterior muscle. To investigate the effects on muscle protein synthesis, muscles were collected 7 days after rAAV-injection in the nighttime or in the daytime representing high and low levels of activity and feeding, respectively, or after overnight fasting, refeeding, or ad libitum feeding. Muscle protein synthesis was increased by…

The landscape of epilepsy-related GATOR1 variants

2019

Purpose:\ud \ud To define the phenotypic and mutational spectrum of epilepsies related to DEPDC5, NPRL2 and NPRL3 genes encoding the GATOR1 complex, a negative regulator of the mTORC1 pathway.\ud \ud Methods:\ud \ud We analyzed clinical and genetic data of 73 novel probands (familial and sporadic) with epilepsy-related variants in GATOR1-encoding genes and proposed new guidelines for clinical interpretation of GATOR1 variants.\ud \ud Results:\ud \ud The GATOR1 seizure phenotype consisted mostly in focal seizures (e.g., hypermotor or frontal lobe seizures in 50%), with a mean age at onset of 4.4 years, often sleep-related and drug-resistant (54%), and associated with focal cortical dysplasia…