Total synthesis of natural disaccharide sambubiose

A practical and robust synthetic method to obtain the natural disaccharide sambubiose (2O-β-D-xylopyranosyl-D-glucopyranose) is reported, exploring the key step in the synthesis, i.e., stereoselective O-glycosylation. Specifically, the best combinations of glycoside donors and acceptors were identified, stereospecific control of the reaction was achieved by screening several catalysts and protection/deprotection steps were evaluated and improved. The best result was obtained by coupling allyl 3,5,6-tri-O-benzyl-β-D-glucofuranoside with 2,3,4-tri-O-acetyl-Dxylopiranosyl-α-trichloro acetimidate in the presence of trimethylsilyl triflate as a catalyst giving the corresponding protected target compound as a correct single isomer. The latter was transformed accordingly into the desired final product by deprotection steps (deallylation, deacetylation, and debenzylation). Sambubiose was synthesized into a satisfactory and higher overall yield than previously reported and was also characterized

Radiation-free Microwave Technology for Breast Lesion Detection using Supervised Machine Learning Model

Mammography is the gold standard technology for breast screening, which has been demonstrated through different randomized controlled trials to reduce breast cancer mortality. However, mammography has limitations and potential harms, such as the use of ionizing radiation. To overcome the ionizing radiation exposure issues, a novel device (i.e. MammoWave) based on low-power radio-frequency signals has been developed for breast lesion detection. The MammoWave is a microwave device and is under clinical validation phase in several hospitals across Europe. The device transmits non-invasive microwave signals through the breast and accumulates the backscattered (returned) signatures, commonly denoted as the S21 signals in engineering terminology. Backscattered (complex) S21 signals exploit the contrast in dielectric properties of breasts with and without lesions. The proposed research is aimed to automatically segregate these two types of signal responses by applying appropriate supervised machine learning (ML) algorithm for the data emerging from this research. The support vector machine with radial basis function has been employed here. The proposed algorithm has been trained and tested using microwave breast response data collected at one of the clinical validation centres. Statistical evaluation indicates that the proposed ML model can recognise the MammoWave breasts signal with no radiological finding (NF) and with radiological findings (WF), i.e., may be the presence of benign or malignant lesions. A sensitivity of 84.40% and a specificity of 95.50% have been achieved in NF/WF recognition using the proposed ML model

Exploring the ecology of bifidobacteria and their genetic adaptation to the mammalian gut

The mammalian gut is densely inhabited by microorganisms that have coevolved with their host. Amongst these latter microorganisms, bifidobacteria represent a key model to study host–microbe interaction within the mammalian gut. Remarkably, bifidobacteria naturally occur in a range of ecological niches that are either directly or indirectly connected to the animal gastrointestinal tract. They constitute one of the dominant bacterial members of the intestinal microbiota and are among the first colonizers of the mammalian gut. Notably, the presence of bifidobacteria in the gut has been associated with several health-promoting activities. In this review, we aim to provide an overview of current knowledge on the genetic diversity and ecology of bifidobacteria. Furthermore, we will discuss how this important group of gut bacteria is able to colonize and survive in the mammalian gut, so as to facilitate host interactions

K Index in cerebrospinal fluid: a valid tool in multiple sclerosis diagnosis

Detection of oligoclonal IgG bands in cerebrospinal fluid by isoelectrocfocusing and immunodetection is the current gold standard to detect an inflammatory process in the central nervous system. It has been proposed that the presence of free light chains (FLCs) in CSF was associated with recent demyelination activity in MS and might be used as a prognosis marker. Our study’s objective is assessing the diagnostic accuracy of a new highly sensitive latex-enhanced nephelometric assay for k free light chain (kFLC) determination in CSF/serum as an alternative to traditional tests and its clinical application. Methods. kFLCs were measured in CSF/serum pairs from 80 patients by the use of a new highly sensitive latex-enhanced nephelometric automated immunoassay for detection of immunoglobulin FLC. The eighty patients were split into three groups according to the neurological diagnosis. In this study we confirm even more the use of the k Index as a diagnostic aid in multiple sclerosis. Results. kFLC Index seems to be more accurate parameter respect the determination of oligoclonal immunoglobulin bands (OCBs). We recalculate the K Index sensitivity and specificity respect the precedent published result. Two patients previously diagnosed with leukoencephalopathy have gone to group 3 as confirmed the diagnosis of MS. Conclusions. These new data reinforce even more the use of the k Index to diagnose MS in comparison to classical methods and to the reference method, the OCBs

Fluid-Assisted Strain Localization in Quartz at the Brittle/Ductile Transition

A mylonitic quartzite with conjugate and synthetic shear bands was investigated by Electron Backscatter Diffraction and optical microscopy to obtain insights on recrystallization mechanisms and strain localization in quartz at plastic to semibrittle conditions close to the brittle-ductile transition. The mylonitic quartzite deformed during late Miocene thrusting coeval with contact metamorphism in the high-strain domains of the Calamita Schists (Elba Island, Italy). Mylonitic deformation occurred from amphibolite to lower greenschist facies conditions during cooling of the aureole. Dynamic recrystallization, dominated by the activity of dislocation creep by prism slip, produced recrystallized quartz layers mantling relic large quartz porphyroclasts. Under decreasing temperature and fluid-rich conditions, quartz porphyroclasts acted as relatively rigid bodies and fractured along synthetic and conjugate C′ shear bands. Shear bands developed along kinematically favored orientations, just locally assisted by weak crystallographic planes in quartz. Fracturing along shear bands was assisted by cataclasis and fluid infiltration enhancing fracture propagation and healing by recrystallization and authigenesis of new quartz and phyllosilicate grains. The process enhanced the propagation of and strain localization in shear bands, with the development of bands of weak phyllosilicates. Furthermore, we observed the development of a c axis preferred orientation (CPO) related to dissolution and precipitation of new grains with their c axis oriented parallel to shear bands. This study highlights the importance of the interplay between brittle and crystal-plastic processes and fluid ingress in the semibrittle regime to understand deformation partitioning and strain localization

Penetrating particle ANalyzer (PAN)

PAN is a scientific instrument suitable for deep space and interplanetary missions. It can precisely measure and monitor the flux, composition, and direction of highly penetrating particles ($> \sim$100 MeV/nucleon) in deep space, over at least one full solar cycle (~11 years). The science program of PAN is multi- and cross-disciplinary, covering cosmic ray physics, solar physics, space weather and space travel. PAN will fill an observation gap of galactic cosmic rays in the GeV region, and provide precise information of the spectrum, composition and emission time of energetic particle originated from the Sun. The precise measurement and monitoring of the energetic particles is also a unique contribution to space weather studies. PAN will map the flux and composition of penetrating particles, which cannot be shielded effectively, precisely and continuously, providing valuable input for the assessment of the related health risk, and for the development of an adequate mitigation strategy. PAN has the potential to become a standard on-board instrument for deep space human travel. PAN is based on the proven detection principle of a magnetic spectrometer, but with novel layout and detection concept. It will adopt advanced particle detection technologies and industrial processes optimized for deep space application. The device will require limited mass (~20 kg) and power (~20 W) budget. Dipole magnet sectors built from high field permanent magnet Halbach arrays, instrumented in a modular fashion with high resolution silicon strip detectors, allow to reach an energy resolution better than 10\% for nuclei from H to Fe at 1 GeV/n

Radial Basis Function for Breast Lesion Detection from MammoWave Clinical Data

Recently, a novel microwave apparatus for breast lesion detection (MammoWave), uniquely able to function in air with 2 antennas rotating in the azimuth plane and operating within the band 1-9 GHz has been developed. Machine learning (ML) has been implemented to understand information from the frequency spectrum collected through MammoWave in response to the stimulus, segregating breasts with and without lesions. The study comprises 61 breasts (from 35 patients), each one with the correspondent output of the radiologist's conclusion (i.e., gold standard) obtained from echography and/or mammography and/or MRI, plus pathology or 1-year clinical follow-up when required. The MammoWave examinations are performed, recording the frequency spectrum, where the magnitudes show substantial discrepancy and reveals dissimilar behaviours when reflected from tissues with/without lesions. Principal component analysis is implemented to extract the unique quantitative response from the frequency response for automated breast lesion identification, engaging the support vector machine (SVM) with a radial basis function kernel. In-vivo feasibility validation (now ended) of MammoWave was approved in 2015 by the Ethical Committee of Umbria, Italy (N. 6845/15/AV/DM of 14 October 2015, N. 10352/17/NCAV of 16 March 2017, N 13203/18/NCAV of 17 April 2018). Here, we used a set of 35 patients. According to the radiologists conclusions, 25 breasts without lesions and 36 breasts with lesions underwent a MammoWave examination. The proposed SVM model achieved the accuracy, sensitivity, and specificity of 91%, 84.40%, and 97.20%. The proposed ML augmented MammoWave can identify breast lesions with high accuracy

Synthesis and Properties of Sucrose- and Lactose-Based Aromatic Ester Surfactants as Potential Drugs Permeability Enhancers

The delivery of therapeutics across biological membranes (e.g., mucosal barriers) by avoiding invasive routes (e.g., injection) remains a challenge in the pharmaceutical field. As such, there is the need to discover new compounds that act as drug permeability enhancers with a favorable toxicological profile. A valid alternative is represented by the class of sugar-based ester surfactants. In this study, sucrose and lactose alkyl aromatic and aromatic ester derivatives have been synthesized with the aim to characterize them in terms of their physicochemical properties, structure–property relationship, and cytotoxicity, and to test their ability as permeability enhancer agents across Calu-3 cells. All of the tested surfactants showed no remarkable cytotoxic effect on Calu-3 cells when applied both below and above their critical micelle concentration. Among the explored molecules, lactose p-biphenyl benzoate (URB1420) and sucrose p-phenyl benzoate (URB1481) cause a reversible ~30% decrease in transepithelial electrical resistance (TEER) with the respect to the basal value. The obtained result matches with the increased in vitro permeability coefficients (Papp) calculated for FTIC-dextran across Calu-3 cells in the presence of 4 mM solutions of these surfactants. Overall, this study proposes sucrose- and lactose-based alkyl aromatic and aromatic ester surfactants as novel potential and safe permeation enhancers for pharmaceutical applications

The infant gut microbiome as a microbial organ influencing host well-being

Initial establishment of the human gut microbiota is generally believed to occur immediately following birth, involving key gut commensals such as bifidobacteria that are acquired from the mother. The subsequent development of this early gut microbiota is driven and modulated by specific dietary compounds present in human milk that support selective colonization. This represents a very intriguing example of host-microbe co-evolution, where both partners are believed to benefit. In recent years, various publications have focused on dissecting microbial infant gut communities and their interaction with their human host, being a determining factor in host physiology and metabolic activities. Such studies have highlighted a reduction of microbial diversity and/or an aberrant microbiota composition, sometimes referred to as dysbiosis, which may manifest itself during the early stage of life, i.e., in infants, or later stages of life. There are growing experimental data that may explain how the early human gut microbiota affects risk factors related to adult health conditions. This concept has fueled the development of various nutritional strategies, many of which are based on probiotics and/or prebiotics, to shape the infant microbiota. In this review, we will present the current state of the art regarding the infant gut microbiota and the role of key commensal microorganisms like bifidobacteria in the establishment of the first microbial communities in the human gut