A miniaturized silicon based device for nucleic acids electrochemical detection

In this paper we describe a novel portable system for nucleic acids electrochemical detection. The core of the system is a miniaturized silicon chip composed by planar microelectrodes. The chip is embedded on PCB board for the electrical driving and reading. The counter, reference and work microelectrodes are manufactured using the VLSI technology, the material is gold for reference and counter electrodes and platinum for working electrode. The device contains also a resistor to control and measuring the temperature for PCR thermal cycling. The reaction chamber has a total volume of 20 μL. It is made in hybrid silicon–plastic technology. Each device contains four independent electrochemical cells.Results show HBV Hepatitis-B virus detection using an unspecific DNA intercalating redox probe based on metal–organic compounds. The recognition event is sensitively detected by square wave voltammetry monitoring the redox signals of the intercalator that strongly binds to the double-stranded DNA. Two approaches were here evaluated: (a) intercalation of electrochemical unspecific probe on ds-DNA on homogeneous solution (homogeneous phase); (b) grafting of DNA probes on electrode surface (solid phase).The system and the method here reported offer better advantages in term of analytical performances compared to the standard commercial optical-based real-time PCR systems, with the additional incomes of being potentially cheaper and easier to integrate in a miniaturized device. Keywords: Electrochemical detection, Real time PCR, Unspecific DNA intercalato

Novel analytical tool for a univocal flavor and fragrance identification: Gas chromatography coupled with condensed-phase FTIR and TOF mass spectrometry

The correct identification of flavor and fragrance (F&F) compounds in real samples is still a challenge despite the huge number of different instruments available. Only a slight structural difference can cause a very different sensory profile, for example in the case of geometric isomers, it is generally considered that (Z)-isomers have a more pleasant and natural odor than (E) ones.                The most frequently used instrument for the analysis of volatiles is gas chromatography (GC) coupled with mass spectrometry (MS). MS may still fail to adequately identify compounds because of the lack of specificity of spectra (terpenes, isomers). MS spectral searches can be supported with linear retention index (LRI) information which, although not in all cases, could resolve the problem of possible misidentification of target molecules.                Condensed phase FTIR can be a complementary detection system to MS, and its application could allow a very detailed structural elucidation. The novelty of this instrument is that the separated compounds are condensed in small, singular spots on a rotating disc, thus the distortion of spectra is eliminated, giving an excellent spectral resolution. Through the specificity of the “fingerprint” region around 1100 cm-1, even positional isomers and diastereomers could be distinguished.                Coupling condensed-phase FTIR after a simple post-column split to a GC-TOF MS, three independent analytical information can be obtained about the target compound: retention behavior (LRI), MS and FTIR spectra. Exploiting the enhanced resolution of the TOF MS and discriminating power of FTIR a unique TOF MS/FTIR spectral library with more than 1500 F&F compounds was developed, including also experimental LRI. Boosting this comprehensive information collection, a universal post-run software, namely CromatoPlus Spectra, performs the library search using the FTIR spectral similarity and LRI filter, simultaneously. A GC-TOF MS/FTIR method was optimized for the analysis of real essential-oil and perfume samples. Using the F&F library with embedded LRI, a reliable peak assignment was obtained for each separated compound

Cannabis terpene profiling in therapeutic products by means of gas chromatography coupled with mass spectrometry

It is well-known that cannabinoids provide non-toxic medical benefits and have an effective role in the treatment of chronic pain due to their interaction with the endocannabinoid system. Recently, in addition to the “classical” therapeutic usage, like inhalation or ingestion of cannabis, newer ways of cannabinoid-based products utilization are also being developed. The skin application of topicals including balms, lotions, and oils that are infused with active cannabinoids is a minimally invasive method for the medical cannabis use and allows them to be absorbed directly into the affected area for faster and more focused relief.                According to the terpene profile, the medicinal effect of cannabinoids can change significantly. Terpenes, in fact, have various roles: can make the adsorption of cannabinoids faster, or lessen their effect, interact with cannabinoids, decrease the side-effects of the cannabinoid therapy, and help to relax and calm the patient.                Gas chromatography-mass spectrometric (GC-MS) analysis is a powerful analytical tool for detailed characterization of the volatile fractions of any kind of complex sample. For the identification, mass spectral databases are used, but in many cases, misidentification could occur due to the high spectral similarity of terpenes. The Linear Retention Index (LRI) approach combined with conventional mass spectral search provide a more reliable solution for peak assignment. The FFNSC 4.0 (Flavour and Fragrance Natural and Synthetic Compounds), a dedicated MS Library with embedded LRI information, including almost all of the 140 known cannabis terpenes can be a great support in terpene profiling, thereby also in the optimization of the therapy.                Aroma constituents of cannabinoid-containing medicinal products were analyzed by GC-MS. To obtain the characteristic volatile fraction, sample preparation method was optimized for each sample type. Terpenes were identified using FFNSC 4.0 database

Tuberomics: a molecular profiling for the adaption of edible fungi (Tuber magnatum Pico) to different natural environments

Background: Truffles are symbiotic fungi that develop underground in association with plant roots, forming ectomycorrhizae. They are primarily known for the organoleptic qualities of their hypogeous fruiting bodies. Primarily, Tuber magnatum Pico is a greatly appreciated truffle species mainly distributed in Italy and Balkans. Its price and features are mostly depending on its geographical origin. However, the genetic variation within T. magnatum has been only partially investigated as well as its adaptation to several environments. Results: Here, we applied an integrated omic strategy to T. magnatum fruiting bodies collected during several seasons from three different areas located in the North, Center and South of Italy, with the aim to distinguish them according to molecular and biochemical traits and to verify the impact of several environments on these properties. With the proteomic approach based on two-dimensional electrophoresis (2-DE) followed by mass spectrometry, we were able to identify proteins specifically linked to the sample origin. We further associated the proteomic results to an RNA-seq profiling, which confirmed the possibility to differentiate samples according to their source and provided a basis for the detailed analysis of genes involved in sulfur metabolism. Finally, geographical specificities were associated with the set of volatile compounds produced by the fruiting bodies, as quantitatively and qualitatively determined through proton transfer reaction-mass spectrometry (PTR-MS) and gas-chromatography mass spectrometry (GC-MS). In particular, a partial least squares-discriminant analysis (PLS-DA) model built from the latter data was able to return high confidence predictions of sample source. Conclusions: Results provide a characterization of white fruiting bodies by a wide range of different molecules, suggesting the role for specific compounds in the responses and adaptation to distinct environments

Irinotecan- vs. Oxaliplatin-Based Doublets in KRASG12C-Mutated Metastatic Colorectal Cancer-A Multicentre Propensity-Score-Matched Retrospective Analysis

The sensitivity to chemotherapy of KRASG12C-mutated colorectal cancer has been investigated to verify whether the combination of chemotherapy plus a KRASG12C-inhibitor might become the standard of care in the near future. To this aim, the present retrospective study was designed to assess the performance of irinotecan vs. oxaliplatin in the first-line treatment of KRASG12C-mutated mCRC patients and provide support for first-line decision making. In this setting of patients treated with FOLFIRI or FOLFOX +/ bevacizumab, irinotecan and oxaliplatin were compared using a propensity-score-matched analysis. the survival superiority of irinotecan was demonstrated over oxaliplatin in KRASG12C-mutated patients, while no differences were observed in a control cohort of KRASG12D-mutated patients. this should be considered when investigating chemotherapy plus targeted agent combinations.background: KRAS(G12C)-mutated metastatic colorectal cancer (mCRC) has recently been recognized as a distinct druggable molecular entity; however, there are limited data on its sensitivity to standard chemotherapy. In the near future, the combination of chemotherapy plus a KRAS(G12C)inhibitor might become the standard of care; however, the optimal chemotherapy backbone is unknown. methods: a multicentre retrospective analysis was conducted including KRASG12C-mutated mCRC patients treated with first-line FOLFIRI or FOLFOX +/ bevacizumab. Both unmatched and propensity-score-matched analysis (PSMA) were conducted, with PSMA controlling for: previous adjuvant chemotherapy, ECOG PS, use of bevacizumab in first line, timing of metastasis appearance, time from diagnosis to first-line start, number of metastatic sites, presence of mucinous component, gender, and age. Subgroup analyses were also performed to investigate subgroup treatment-effect interactions. KRAS(G12D)-mutated patients were analysed as control. results: one hundred and four patients treated with irinotecan-(N = 47) or oxaliplatin-based (N = 57) chemotherapy were included. In the unmatched population, objective response rate (ORR) and median (m) progression-free and overall survival (mPFS and mOS) were comparable between the treatment arms. however, a late (>12 months) PFS advantage was observed with irinotecan (HR 0.62, p = 0.02). In the PSMA-derived cohort, a significant improvement with irinotecan vs. oxaliplatin was observed for both PFS and OS: 12- and 24-month PFS rates of 55% vs. 31% and 40% vs. 0% (HR 0.40, p = 0.01) and mOS 37.9 vs. 21.7 months (HR 0.45, p = 0.045), respectively. According to the subgroup analysis, interaction effects between the presence of lung metastases and treatment groups were found in terms of PFS (p for interaction = 0.08) and OS (p for interaction = 0.03), with a higher benefit from irinotecan in patients without lung metastases. no difference between treatment groups was observed in the KRASG12D-mutated cohort (N = 153). Conclusions: First-line irinotecan-based regimens provided better survival results in KRAS(G12C)-mutated mCRC patients and should be preferred over oxaliplatin. These findings should also be considered when investigating chemotherapy plus targeted agent combinations

Interrupting the nitrosative stress fuels tumor-specific cytotoxic T lymphocytes in pancreatic cancer

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest tumors owing to its robust desmoplasia, low immunogenicity, and recruitment of cancer-conditioned, immunoregulatory myeloid cells. These features strongly limit the success of immunotherapy as a single agent, thereby suggesting the need for the development of a multitargeted approach. The goal is to foster T lymphocyte infiltration within the tumor landscape and neutralize cancer-triggered immune suppression, to enhance the therapeutic effectiveness of immune-based treatments, such as anticancer adoptive cell therapy (ACT). METHODS: We examined the contribution of immunosuppressive myeloid cells expressing arginase 1 and nitric oxide synthase 2 in building up a reactive nitrogen species (RNS)-dependent chemical barrier and shaping the PDAC immune landscape. We examined the impact of pharmacological RNS interference on overcoming the recruitment and immunosuppressive activity of tumor-expanded myeloid cells, which render pancreatic cancers resistant to immunotherapy. RESULTS: PDAC progression is marked by a stepwise infiltration of myeloid cells, which enforces a highly immunosuppressive microenvironment through the uncontrolled metabolism of L-arginine by arginase 1 and inducible nitric oxide synthase activity, resulting in the production of large amounts of reactive oxygen and nitrogen species. The extensive accumulation of myeloid suppressing cells and nitrated tyrosines (nitrotyrosine, N-Ty) establishes an RNS-dependent chemical barrier that impairs tumor infiltration by T lymphocytes and restricts the efficacy of adoptive immunotherapy. A pharmacological treatment with AT38 ([3-(aminocarbonyl)furoxan-4-yl]methyl salicylate) reprograms the tumor microenvironment from protumoral to antitumoral, which supports T lymphocyte entrance within the tumor core and aids the efficacy of ACT with telomerase-specific cytotoxic T lymphocytes. CONCLUSIONS: Tumor microenvironment reprogramming by ablating aberrant RNS production bypasses the current limits of immunotherapy in PDAC by overcoming immune resistance

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV

Measurement of the top quark mass using charged particles in pp collisions at root s=8 TeV

Peer reviewe

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe