Superswelling Microneedle Arrays for Dermal Interstitial Fluid (Prote)Omics

The noninvasive sampling of dermal interstitial fluid (ISF) for the monitoring of clinical biomarkers is a greatly appealing area of research. The identification of molecular biomarkers in biological fluids has been accelerated with -omics analyses but remains limited in ISF because of its time-consuming and complex extraction process. Here, the generation of microneedle (MN) patches made of superabsorbent acrylate-based hydrogels for the rapid sampling of dermal ISF is described to explore its proteome. In depth, iterative optimization allows the identification of novel acrylate-based compositions with the required chemical, mechanical, and biocompatibility properties allowing proteomic analysis of the extracted ISF for the first time after sampling with swelling MNs. The generated MN arrays show no cytotoxic effect, successfully cross the stratum corneum, and can collect up to 6 µL of dermal ISF in 10 min in vivo. Proteomics lead to the detection of 176 clinically relevant biomarkers in the collected samples validating the use of ISF as a relevant bodily fluid for disease monitoring and diagnostic. Importantly, it is discovered that extraction fingerprint is strongly dependent on the MNs chemistry, and thus specific biomarkers could be selectively extracted by tuning the composition of the patch, making the system versatile and specific.     

Differences in PARP Inhibitors for the Treatment of Ovarian Cancer: Mechanisms of Action,Pharmacology, Safety,and Efficacy

Poly(ADP-ribose) polymerases (PARP) are proteins responsible for DNA damage detection and signal transduction. PARP inhibitors (PARPi) are able to interact with the binding site for PARP cofactor (NAD+) and trapping PARP on the DNA. In this way, they inhibit single-strand DNA damage repair. These drugs have been approved in recent years for the treatment of ovarian cancer. Although they share some similarities, from the point of view of the chemical structure and pharmacodynamic, pharmacokinetic properties, these drugs also have some substantial differences. These differences may underlie the different safety profiles and activity of PARPi.     

High-temperature fibre Bragg grating thermometer

The use of gratings written in tin-doped silica fibres as a thermometer for high-temperature applications is described. Measurements up to ~800°C show a significant advantage over conventional fibre gratings. A considerable blue-shift has been observed at high temperatures. If corrections for blue-shift are taken into account, the errors are smaller than ~2°C     

Fabrication of optical fibre nanowires and their optical and mechanical characterisation

It is demonstrated for the first time that long nanowires with radii as small as 30 nm can be manufactured with a conventional coupler fabrication rig. The temporal deterioration of nanowire optical properties has been studied and correlated with its mechanical behaviour. The original transmission properties have been restored by a post-fabrication treatment.     

Deep-MEG: spatiotemporal CNN features and multiband ensemble classification for predicting the early signs of Alzheimer’s disease with magnetoencephalography

Neural Computing and Applications - In this paper, we present the novel Deep-MEG approach in which image-based representations of magnetoencephalography (MEG) data are combined with ensemble...     

Aromatic bisphenol A-based elastomers via hydrosilylation chemistry

The preparation of highly aromatic elastomers from a bisphenol A-based divinyl-terminated resin and polymerization with various aromatic silane containing compounds utilizing a room temperature hydrosilylation reaction is demonstrated. The polymers exhibit high thermal and oxidative stability with 5% weight losses around 430 and 350°C and char yields ranging from 35% to 40%. The thermosets maintained their elastomeric properties with good hardness and mechanical properties as measured by elongation measurements. The toughness of the thermosets was not improved with the inclusion of aromatic moieties but the hardness did appear to increase with the addition of more aromatic groups.     

Acetals as nucleating agents for polypropylene

Nucleating agents increase the impact strength, tensile strength, and tensile elasticity modulus of semicrystalline polymers. Nucleating agents also decrease product cycle times, resulting in a cost savings per product unit. We have synthesized and tested 15 compounds as nucleactors for polypropylene. Of these, trinapthylidene sorbitol, tri-(4-methyl-1-naphthylidene)sorbitol, tri-(4-methoxy-1-naphthylidene) sorbitol, and dibenzylidene xylitol are efficient nucleators of polypropylene. Trinaphthylidene sorbitol (tns) has two major diastereomers: The “S” diastereomer yields a faster crystallization rate for polypropylene than does the commercial nucleator dibenzylidene sorbitol (Millad 3905). Crystallization rates are 208 and 88, respectively (t min^?1 × 1000). The “R” diastereomer, however, is a poor nucleator and interferes with the nucleating activity of the “S” diastereomer. A 52/48 mixture of diastereomers does not nucleate polypropylene, even at twice the concentration. This is first time that the importance of stereochemistry has been demonstrated in the nucleating action. © 1994 John Wiley & Sons, Inc.     

Comparison of molecular changes in lung cancers in HIV-positive and HIV-indeterminate subjects

CONTEXT: Human immunodeficiency virus (HIV) infection has been associated with an increasing incidence of malignancy, and HIV-infected persons have an increased incidence of primary lung carcinoma compared with the general population. OBJECTIVE: To investigate the molecular changes present in HIV-associated lung tumors and compare them with those present in lung carcinomas arising in HIV-indeterminate subjects ("sporadic tumors"). DESIGN: Convenience sample. SUBJECTS: Archival tissues from 11 HIV-positive persons and from 35 persons of indeterminate HIV status. SETTING: University-based medical centers and affiliated hospitals. MAIN OUTCOME MEASURES: Analysis of frequency of loss of heterozygosity (LOH) and microsatellite alteration (MA) using polymerase chain reaction and 16 polymorphic microsatellite markers at 8 chromosomal regions frequently deleted in lung cancer. Presence of HIV and human papillomavirus (HPV) sequences. RESULTS: The overall frequency of LOH at all chromosomal regions tested and the frequencies at most of the individual regions were similar in the 2 groups. Frequency of MA present in the HIV-associated tumors (0.18) was 6-fold higher than in sporadic tumors (0.03) (P<.001). At least 1 MA was present in 10 (91%) of 11 HIV-associated tumors vs 17 (48%) of 35 sporadic tumors (P=.02). Molecular changes were independent of tumor stage and gender. HIV and HPV sequences were not detected in the HIV-associated lung carcinomas. CONCLUSIONS: Microsatellite alterations, which reflect widespread genomic instability, occur at greatly increased frequency in HIV-associated lung carcinomas. Although the mechanism underlying the development of increased MAs is unknown, it may play a crucial role in the development of many HIV-associated tumors.