The importance of the RET gene in thyroid cancer and therapeutic implications

Since the discovery of the RET receptor tyrosine kinase in 1985, alterations of this protein have been found in diverse thyroid cancer subtypes. RET gene rearrangements are observed in papillary thyroid carcinoma, which result in RET fusion products. By contrast, single amino acid substitutions and small insertions and/or deletions are typical of hereditary and sporadic medullary thyroid carcinoma. RET rearrangements and mutations of extracellular cysteines facilitate dimerization and kinase activation, whereas mutations in the RET kinase coding domain drive dimerization-independent kinase activation. Thus, RET kinase inhibition is an attractive therapeutic target in patients with RET alterations. This approach was initially achieved using multikinase inhibitors, which affect multiple deregulated pathways that include RET kinase. In clinical practice, use of multikinase inhibitors in patients with advanced thyroid cancer resulted in therapeutic efficacy, which was associated with frequent and sometimes severe adverse effects. However, remarkable progress has been achieved with the identification of novel potent and selective RET kinase inhibitors for the treatment of advanced thyroid cancer. Although expanded clinical validation in future trials is needed, the sustained antitumoural activity and the improved safety profile of these novel compounds is opening a new exciting era in precision oncology for RET-driven cancers

Estimulación vagal en el tratamiento de la epilepsia

The vagal nerve stimulation is a new technique for the treatment of drug resistant epilepsies. DEVELOPMENT: In 1997, it was approved in United States by the FDA to be used in adults with refractory focal epilepsies not candidates for epilepsy surgery. Its mechanism of action is unknown. The results in the controlled studies indicated a decrease of 30 50% in the seizure frequency in around 50% of the patients. Although more experience is needed to corroborate these results, it seems reasonable as a treatment for patients with difficult epilepsies, especially when the response to the antiepileptic drugs is poor or they are producing secondary effects, and the resection of the focus is not possible

ROCK SURFACE CHARACTERIZATION BY IMMERSION CALORIMETRY: WETTABILITY AND SPECIFIC SURFACE AREA

ABSTRACT Petrophysical properties such as wettability and surface area control hydrocarbon storage and transport properties. In the work being reported in this paper, we present the theoretical aspects as well as experimental technique and results of testing and validating a proposed calorimetry technique for specific surface area and wettability characterization. Identical immersion calorimetry experiments with slightly different initial conditions of the sample are analyzed to obtain these two properties of a core sample. Validation of the experimental technique is an important step, which is performed in this work by comparing the surface areas of the samples obtained by the proposed technique with the surface area obtained by the well-known Brunauer-EmmettTaylor (BET) gas-adsorption technique. Surface area measurements are performed on a set of core plugs and reference samples, including hydrophilic and hydrophobic powders of pure substances, minerals, and clays

Paresia poscrítica durante estudios de monitorización de vídeo-EEG

To know the frequency of Todd s paralysis during the video EEG monitoring studies, to investigate in its pathophysiology, and to confirm its value to localise the epileptic focus. PATIENTS AND METHODS: We reviewed 114 monitoring studies, in 102 patients. RESULTS: Sixty patients had epileptic seizures. An obvious paresis was noted in four seizures of two patients (3 and 1, respectively). Both patients had frontal epilepsy. During the paralysis, in the first patient the EEG showed ictal discharges on the contralateral centrotemporal area. In the second patient, the EEG demonstrated slow waves in the contralateral frontal region. The ictal onset was contralateral to the paresis in all cases. No patient with pseudoseizures had paralysis. CONCLUSIONS: Postconvulsive paralysis are not frequent in video EEG monitoring studies. However, if present it points out to a contralateral seizure onset. In our series it happened in patients with frontal seizures. The EEG may help to clarify if it correspond to a true postictal phenomenon or to a ictal paralysis

Justice Stevens: The First Three Terms

This Special Project undertakes an examination of Justice Stevens\u27 Supreme Court opinions in an effort to identify his philosophical orientations, to evaluate the consistency of his views, and to determine the extent to which he has developed workable analytical methods. To achieve these goals, Justice Stevens\u27 opinions are examined in three contexts: first, the area of federal-state relations,including commerce clause and supremacy clause questions; second, the individual rights area, emphasizing criminal constitutional and first amendment issues, and problems of fifth and fourteenth amendment analysis; and third, questions concerning the proper role of the Supreme Court in the constitutional scheme. Even though any vote cast by a Supreme Court Justice may illustrate a significant aspect of his ideology, this Special Project limits attention to opinions authored by Justice Stevens on the assumption that they most accurately represent his views.\u2

Deciphering interplay between Salmonella invasion effectors

Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a ‘signaling hub’ during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cis binary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen–host interaction

The effects of concentration and salinity on polymer adsorption isotherm at sandstone rock surface

Adsorption of hydrolyzed polyacrylamide (HPAM) polymers on sandstone rock surface was studied by static adsorption experiments. Total of 10 Runs of static experiments were conducted in test tubes by mixing the desired solution with crushed rock sample, at temperature of 25 °C, and salinity range from 0-4 wt%. The results are in conformity with Langmuir's isotherm. Ten different isotherms were generated at each Run. The initial polymer concentration was varied from 0.3-2.1 g/l. The effects of salinity have been studied by observation on Langmuir adsorption coefficients (Y and K). The results show that the adsorption coefficient (Y) was found to have linear relationship with salinity. The adsorption coefficient (K) was found to be related to salinity by a quadratic relationship

Scaling of Transport Coefficients of Porous Media under Compaction

Porous sediments in geological systems are exposed to stress by the above-laying mass and consequent compaction, which may be significantly nonuniform across the massif. We derive scaling laws for the compaction of sediments of similar geological origin. With these laws, we evaluate the dependence of the transport properties of a fluid-saturated porous medium (permeability, effective molecular diffusivity, hydrodynamic dispersion, electrical and thermal conductivities) on its porosity. In particular, we demonstrate that the assumption of a uniform geothermal gradient is not adequate for systems with nonuniform compaction and show the importance of the derived scaling laws for mathematical modelling of methane hydrate deposits; these deposits are believed to have potential for impact on global climate change and Glacial-Interglacial cycles.Comment: 6 pages, 2 figure