Fast on-wafer electrical, mechanical, and electromechanical characterization of piezoresistive cantilever force sensors

Validation of a technological process requires an intensive characterization of the performance of the resulting devices, circuits, or systems. The technology for the fabrication of micro and nanoelectromechanical systems (MEMS and NEMS) is evolving rapidly, with new kind of device concepts for applications like sensing or harvesting are being proposed and demonstrated. However, the characterization tools and methods for these new devices are still not fully developed. Here, we present an on-wafer, highly precise, and rapid characterization method to measure the mechanical, electrical, and electromechanical properties of piezoresistive cantilevers. The setup is based on a combination of probe-card and atomic force microscopy technology, it allows accessing many devices across a wafer and it can be applied to a broad range of MEMS and NEMS. Using this setup we have characterized the performance of multiple submicron thick piezoresistive cantilever force sensors. For the best design we have obtained a force sensitivity ℜ_F = 158μV/nN, a noise of 5.8 μV (1 Hz–1 kHz) and a minimum detectable force of 37 pN with a relative standard deviation of σ_r ≈ 8%. This small value of σr, together with a high fabrication yield >95%, validates our fabrication technology. These devices are intended to be used as bio-molecular detectors for the measurement of intermolecular forces between ligand and receptor molecule pairs

Synthesis and complexing properties of cyclic benzylopeptoids-a new family of extended macrocyclic peptoids

An efficient protocol for the solid-phase synthesis of six members of a new class of extended macrocyclic peptoids (based on ortho-, meta- and para-N-(methoxyethyl)aminomethyl phenylacetyl units) is described. Theoretical (DFT) and experimental (NMR) studies on the free and Na+-complexed cyclic trimers (3\u20135) and tetramers (6\u20138) demonstrate that annulation of the rigidified peptoids can generate new hosts with the ability to sequestrate one or two sodium cations with the affinities and stoichiometries defined by the macrocycle morphology. Ion transport studies have been also performed in order to better appreciate the factors promoting transmembrane cation translocation

Role of Lipophilicity in the Activity of Hexameric Cyclic Peptoid Ion Carriers

Two families of hexameric cyclic peptoids decorated with linear N-alkyl and alternated N-alkyl/N-benzyl side chains (2 a\u2013d and 3 a\u2013c, respectively) were designed and synthesized in order to correlate their logP values (from 2.55 to 6.83) to their ionophoric activities. The present contribution confirms the general ability of hexameric cyclic peptoids to behave as efficient cation carriers, corroborates their preference for Na+ ion, among the tested alkali metals, and suggests a Na+/H+ antiport transport mechanism (rate limited by the transport of the proton) for these new ionophores. Our observations indicate that in order to attain an efficient ionophoric activity, a narrow range of liphophilicity is required (4<5). Moreover, to gain information on the solid state stucture of ionophoric cyclic peptoids with linear N-side chains, X-ray crystallographic studies were performed on exemplar compound 2 a. Crystal structure of compound 2 a confirms the tendency of ionophoric cyclopeptoids with linear N-side chains to form layered assemblies

Distinctive features of tumor-infiltrating gd T lymphocytes in human colorectal cancer

gd T cells usually infiltrate many different types of cancer, but it is unclear whether they inhibit or promote tumor progression. Moreover, properties of tumor-infiltrating gd T cells and those in the corresponding normal tissue remain largely unknown. Here we have studied features of gd T cells in colorectal cancer, normal colon tissue and peripheral blood, and correlated their levels with clinicopathologic hallmarks. Flow cytometry and transcriptome analyses showed that the tumor comprised a highly variable rate of TILs (5-90%) and 4%gd T cells on average, with the majority expressing Vd1. Most Vd1 and Vd2 T cells showed a predominant effector memory phenotype and had reduced production of IFN-g which was likely due to yet unidentified inhibitory molecules present in cancer stem cell secretome. Transcriptome analyses revealed that patients containing abundant gd T cells had significantly longer 5-year disease free survival rate, suggesting their efficacy in controlling tumor at very early stage

Pancreatic cancer intrinsic PI3Kα activity accelerates metastasis and rewires macrophage component.

Pancreatic ductal adenocarcinoma (PDAC) patients frequently suffer from undetected micro-metastatic disease. This clinical situation would greatly benefit from additional investigation. Therefore, we set out to identify key signalling events that drive metastatic evolution from the pancreas. We searched for a gene signature that discriminate localised PDAC from confirmed metastatic PDAC and devised a preclinical protocol using circulating cell-free DNA (cfDNA) as an early biomarker of micro-metastatic disease to validate the identification of key signalling events. An unbiased approach identified, amongst actionable markers of disease progression, the PI3K pathway and a distinctive PI3Kα activation signature as predictive of PDAC aggressiveness and prognosis. Pharmacological or tumour-restricted genetic PI3Kα-selective inhibition prevented macro-metastatic evolution by hindering tumoural cell migratory behaviour independently of genetic alterations. We found that PI3Kα inhibition altered the quantity and the species composition of the produced lipid second messenger PIP3 , with a selective decrease of C36:2 PI-3,4,5-P3 . Tumoural PI3Kα inactivation prevented the accumulation of pro-tumoural CD206-positive macrophages in the tumour-adjacent tissue. Tumour cell-intrinsic PI3Kα promotes pro-metastatic features that could be pharmacologically targeted to delay macro-metastatic evolution

Recarga artificial en Bajos Submeridionales

Se presenta la experiencia en desarrollo en un sector de Bajos Submeridionales próximo a Tostado, para monitorear los efectos de la recarga artificial de acuíferos. El objetivo del estudio es mejorar la disponibilidad de agua en calidad y cantidad para uso ganadero y evaluar una obra de recarga a partir de un pozo doble propósito recarga – bombeo para mejorar su eficiencia, y difundir estas prácticas.El área piloto se ubica en un paleocauce arenoso del río Salado. En el mismo se han realizado numerosos estudios geoeléctricos, de infiltración, sedimentológicos, químicos recuperación de niveles, de suelos y de recarga. Además se dispone de una estación meteorológica automática, caudalímetro y freatímetros. Se realizó un análisis de eventos de recarga y su efecto sobre el sistema natural y en la obra. Se concluye que ha resultado exitosa y puede ser transferida a otros ambientes de paleocauces del chaco-santafesino.This work describes an artificial recharge experience of groundwater as source for animal beverage, de veloped on a livestock demonstrative unit, placed in Bajos Submeridionales, Santa Fe province, Argentina. The aim of this study is to improve quality and quantity of water for livestock use, analyze a recharge-pumping well efficiency, and finally to spread this practice in the region. The study area is located in a antique sandy channel of the Salado river, where have been conducted geoelectric studies, sedimentologic, soil and water analysis, pumping and recharge, and infiltration tests. Additionally, it counts with metheorological on-line data from an automatic station, flowmeter, and water-level measurements from digital and analogical devises. An analysis of a recharge event has been conducted in order to assess environmental changes and response of facilities. This successful experience suggests that these kinds of facilities could be applied in similar environments of chaco-santafesino region.Universidad Nacional de La Plat

The prognostic impact of anti-cancer immune response: a novel classification of cancer patients

Until now, the anatomic extent of tumor (TNM classification) has been, by far, the most important factor to predict the prognosis of colorectal cancer patients. However, in recent years, data collected from large cohorts of human cancers demonstrated that the immune contexture of the primary tumors is an essential prognostic factor for patients' disease-free and overall survival. Global analysis of tumor microenvironment showed that the nature, the functional orientation, the density, and the location of adaptive immune cells within distinct tumor regions influence the risk of relapse events. An immune classification of the patients was proposed based on the density and the immune cell location within the tumor. The immune classification has a prognostic value that is superior to the TNM classification, and tumor invasion is statistically dependent on the host immune reaction. Tumor and immunological markers predicted by systems biology methods are involved in the shaping of an efficient immune reaction and can serve as targets for novel therapeutic approaches. Thus, the strength of the immune reaction could advance our understanding of cancer evolution and have important consequences in clinical practice

Th17 Cells Are Involved in the Local Control of Tumor Progression in Primary Intraocular Lymphoma

BACKGROUND: Th17 cells play an important role in the pathogenesis of many autoimmune diseases, but despite some reports of their antitumor properties, too little is known about their presence and role in cancers. Specifically, knowledge is sparse about the relation of Th17 to lymphoma microenvironments and, more particularly, to the microenvironment of primary intraocular B-cell lymphoma (PIOL), an aggressive lymphoma with a poor prognosis. METHODS AND PRINCIPAL FINDINGS: In this work, we investigated the presence of Th17 cells and their related cytokines in a syngeneic model of PIOL, a subtype of non-Hodgkin lymphoma. The very small number of lymphocytes trafficking in normal eyes, which represent a low background as compared to tumor-bearing eyes, allows us to develop the present model to characterize the different lymphocyte subsets present when a tumor is developing. IL-21 mRNA was expressed concomitantly with IL-17 mRNA in tumor-bearing eyes and intracellular expression of IL-17A and IL-21 in infiltrating CD4(+) T lymphocytes. Interestingly, IL-17A production by T cells was negatively correlated with tumor burden. We also showed that IL-21 but not IL-17 inhibits tumor cell proliferation in vitro. CONCLUSIONS: These data demonstrate that IL-17A and IL-21-producing CD4(+) T cells, referred as Th17 cells, infiltrate this tumor locally and suggest that Th17-related cytokines may counteract tumor progression via IL-21 production. Thus, Th17 cells or their related cytokines could be considered to be a new therapeutic approach for non-Hodgkin B-cell lymphomas, particularly those with an ocular localization

Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer

The prognosis of colon cancer (CC) is dictated by tumor-infiltrating lymphocytes, including follicular helper T (TFH) cells and the efficacy of chemotherapy-induced immune responses. It remains unclear whether gut microbes contribute to the elicitation of TFH cell-driven responses. Here, we show that the ileal microbiota dictates tolerogenic versus immunogenic cell death of ileal intestinal epithelial cells (IECs) and the accumulation of TFH cells in patients with CC and mice. Suppression of IEC apoptosis led to compromised chemotherapy-induced immunosurveillance against CC in mice. Protective immune responses against CC were associated with residence of Bacteroides fragilis and Erysipelotrichaceae in the ileum. In the presence of these commensals, apoptotic ileal IECs elicited PD-1+ TFH cells in an interleukin-1R1- and interleukin-12-dependent manner. The ileal microbiome governed the efficacy of chemotherapy and PD-1 blockade in CC independently of microsatellite instability. These findings demonstrate that immunogenic ileal apoptosis contributes to the prognosis of chemotherapy-treated CC