Oil-Isolated Hydrogel Microstructures for Sensitive Bioassays On-Chip

Multiplexed, sensitive, and on-chip molecular diagnostic assays are essential in both clinical and research settings. In past work, running reactions in nanoliter- to femtoliter-sized volumes such as microwells or droplets has led to significant increases in detection sensitivities. At the same time, hydrogels have emerged as attractive scaffolds for bioassays due to their nonfouling, flexible, and aqueous properties. In this paper, we combine these concepts and develop a novel platform in which hydrogel compartments are used as individually confined reaction volumes within a fluorinated oil phase. We fabricate functional and versatile hydrogel microstructures in microfluidic channels that are physically isolated from each other using a surfactant-free fluorinated oil phase, generating picoliter- to nanoliter-sized immobilized aqueous reaction compartments that are readily functionalized with biomolecules. In doing so, we achieve monodisperse reaction volumes with an aqueous interior while exploiting the unique chemistry of a hydrogel, which provides a solid and porous binding scaffold for biomolecules and is impenetrable to oil. Furthermore, our lithographically defined reaction volumes are readily customized with respect to geometry and chemistry within the same channel, allowing rational tuning of the confined reaction volume on a post-to-post basis without needing to use surfactants to maintain stability. We design and implement a multiplexed signal amplification assay in which gel-bound enzymes turn over small molecule substrate into fluorescent product in the oil-confined gel compartment, providing significant signal enhancement. Using short (20 min) amplification times, the encapsulation scheme provides up to 2 orders of magnitude boost of signal in nucleic acid detection assays relative to direct labeling and does not suffer from any cross-talk between the posts. We ultimately demonstrate up to 57-fold increase in nucleic acid detection sensitivity compared to a direct labeling scheme.National Institutes of Health (U.S.). Center for Future Technologies in Cancer Care (U54-EB-015403-01)National Institutes of Health (U.S.) (Interdepartmental Biotechnology Training Grant T32 GM08334)National Science Foundation (U.S.) (Grant CMMI-1120724

Metastasis-inducing proteins are widely expressed in human brain metastases and associated with intracranial progression and radiation response

Background:Understanding the factors that drive recurrence and radiosensitivity in brain metastases would improve prediction of outcomes, treatment planning and development of therapeutics. We investigated the expression of known metastasis-inducing proteins in human brain metastases.Methods:Immunohistochemistry on metastases removed at neurosurgery from 138 patients to determine the degree and pattern of expression of the proteins S100A4, S100P, AGR2, osteopontin (OPN) and the DNA repair marker FANCD2. Validation of significant findings in a separate prospective series with the investigation of intra-tumoral heterogeneity using image-guided sampling. Assessment of S100A4 expression in brain metastatic and non-metastatic primary breast carcinomas.Results:There was widespread staining for OPN, S100A4, S100P and AGR2 in human brain metastases. Positive staining for S100A4 was independently associated with a shorter time to intracranial progression after resection in multivariate analysis (hazard ratio for negative over positive staining=0.17, 95% CI: 0.04-0.74, P=0.018). S100A4 was expressed at the leading edge of brain metastases in image guided sampling and overexpressed in brain metastatic vs non-brain metastatic primary breast carcinomas. Staining for OPN was associated with a significant increase in survival time after post-operative whole-brain radiotherapy in retrospective (OPN negative 3.43 months, 95% CI: 1.36-5.51 vs OPN positive, 11.20 months 95% CI: 7.68-14.72, Log rank test, P<0.001) and validation populations.Conclusions:Proteins known to be involved in cellular adhesion and migration in vitro, and metastasis in vivo are significantly expressed in human brain metastases and may be useful biomarkers of intracranial progression and radiosensitivity

Diet Self-efficacy and Physical Self-concept of College Students at Risk for Eating Disorders

Background: Both eating disorders and body image dissatisfaction affect a high proportion of college students. Self-esteem and self-efficacy may be protective factors for eating disorders. The aim of this study was to evaluate diet self-efficacy, the confidence to maintain or lose weight, and its association with physical selfconcept using data from an online survey of health literacy, body image, and eating disorders. Study Population and Methods: This cross-sectional study collected online survey data from college students within the United States. The inclusion criteria allowed for 1612 college students, ages 17-35 years (597 males, 1015 females) belonging to the following racial/ethnic categories: Black (187); White, non-Hispanic (244), Hispanic (1035), and other (146). Specifically, the study aimed to examine (a) whether and to what degree diet self-efficacy and physical self-concept were associated with risk of eating disorders; (b) the interaction of gender by ethnicity on diet self-efficacy, physical self-concept and risk of eating disorders; and, (c) the relationship of diet self-efficacy with physical self-description and body mass index (BMI) in college students. Results:Low diet self-efficacy was associated with a lower score on physical self-concept (B = −0.52 [−0.90, −0.15], P = 0.007). Males had a higher physical self-concept as compared to females (B = 14.0 [8.2, 19.8], P Conclusion: College students in this study who had a poor body image were less confident with diet control. Poorer body image and low diet selfefficacy were associated with higher BMI. These findings suggest lifestyle management interventions may be of value to improve physical self-concept and lower risk of eating disorders for college students

Modeling and Simulation of Multi-Lane Traffic Flow

A most important aspect in the field of traffic modeling is the simulation of bottleneck situations. For their realistic description a macroscopic multi-lane model for uni-directional freeways including acceleration, deceleration, velocity fluctuations, overtaking and lane-changing maneuvers is systematically deduced from a gas-kinetic (Boltzmann-like) approach. The resulting equations contain corrections with respect to previous models. For efficient computer simulations, a reduced model delineating the coarse-grained temporal behavior is derived and applied to bottleneck situations.Comment: For related work see http://www.theo2.physik.uni-stuttgart.de/helbing.htm

Prospects of III-Vs for Logic Applications

The increasing challenges for further scaling down of Si CMOS require the study of alternative channel materials. This paper highlights the significance of III-V compound semiconductor materials in order to face the looming fate of Si CMOS technology. The potential advantages of using III-Vs as channel materials for future III-V CMOS is its outstanding transport properties that have been widely accepted in high frequency RF applications. However, many significant challenges in front of III-V digital technology needs to be overcome before III-V CMOS becomes feasible for next generation high speed and low power logic applications. But it may be that this situation is changing given recent progress in the fabrication of high-mobility III-Vs based heterostructure electronic devices for logic applications to fulfill the needs towards the everyday evolving III-V CMOS technology. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/2778

Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

Variability and anatomical specificity of the orbitofrontothalamic fibers of passage in the ventral capsule/ventral striatum (VC/VS): precision care for patient-specific tractography-guided targeting of deep brain stimulation (DBS) in obsessive compulsive disorder (OCD)

Deep Brain Stimulation (DBS) is a neurosurgical procedure that can reduce symptoms in medically intractable obsessive-compulsive disorder (OCD). Conceptually, DBS of the ventral capsule/ventral striatum (VC/VS) region targets reciprocal excitatory connections between the orbitofrontal cortex (OFC) and thalamus, decreasing abnormal reverberant activity within the OFC-caudate-pallidal-thalamic circuit. In this study, we investigated these connections using diffusion magnetic resonance imaging (dMRI) on human connectome datasets of twenty-nine healthy young-adult volunteers with two-tensor unscented Kalman filter based tractography. We studied the morphology of the lateral and medial orbitofrontothalamic connections and estimated their topographic variability within the VC/VS region. Our results showed that the morphology of the individual orbitofrontothalamic fibers of passage in the VC/VS region is complex and inter-individual variability in their topography is high. We applied this method to an example OCD patient case who underwent DBS surgery, formulating an initial proof of concept for a tractography-guided patient-specific approach in DBS for medically intractable OCD. This may improve on current surgical practice, which involves implanting all patients at identical stereotactic coordinates within the VC/VS region

Factors affecting the ecological habitat of Benthic macro-invertebrate assemblages in Asan wetland, Dehradun in Garhwal Himalaya

The Himalayan region has several freshwater resources, such as rivers, lakes, and wetlands. These freshwater resources have been adversely affected by environmental factors. Freshwater biological systems are defenseless against outcomes of environmental changes that might prompt the irreversible disintegration of these natural surroundings. The present study aimed to investigate the effect of biotic and abiotic factors on the Benthic macro-invertebrate assemblages of the Asan wetland, Dehradun in Garhwal Himalaya. A determination of the physico-chemical health status of the Asan wetland viz., electrical conductivity (EC), total dissolved solids (TDS), biochemical oxygen demand (BOD), and nutrients parameters like nitrogen, potassium, and phosphorus were investigated during this study. Three sampling sites (Site 1, Site 2 and Site 3) of wetland were selected and the water samples were collected seasonally, i.e., summer, winter, and monsoon from April 2021-March 2022. Maximum values of EC(163.75 µS/cm), TDS (232.78 (mg/l),  alkalinity (141.20 mg/l)  and pH(7.8)  were recorded in the monsoon season (June-September) and minimum values of EC( 135.80µS/cm), TDS (196.80 (mg/l),  alkalinity (119.80mg/l)  and pH(7.2) were recorded in the winter season (November–February). An overall total of 18 macrobenthos genera belonging to four classes was identified. Maximum communities of macrobenthos were observed during the winter and minimum communities during the monsoon season. Canonical correspondence analysis (CCA) was used to determine whether microbenthic genera and habitat ecological parameters and showed a positive or negative correlation. Thus, the present study contributed to the status of various factors and their impacts on the Benthic macro-invertebrate structure of the Asan wetland.        

Effect of UV-B radiations on mortality and enzymes level in fish larvae of Tor tor and Schizothorax richardsonii on laboratory scale

Depletion of stratospheric ozone layer is resulting into increase in solar UV-B on earth surface. Ultra violet radiation is well known to cause many detrimental effects in aquatic organisms. The present study was performed to study the effect of solar ultraviolet radiation on fish fingerlings of Tor tor and Schizothorax richardsonii as a model system on laboratory scale. The effect of different intensities of natural solar and artificial UV-B radiation on fish larvae of T. tor and S. richardsonii in a presence of retene was investigated. Solar ultraviolet intensity showed seasonal and altitudinal variations in Garhwal region. Solar UV radiation level was lower (0.390 mw/cm2) in the month of January- February at lower altitude and highest (1.192 mw/cm2) in the month of July-August 2018 at higher altitude. Fish larvae exposed to artificial UV-B (average wavelength 312 nm and intensity of 750 mw/cm2) with retene (50µg/l) showed increase in gills malandialdehyde level and caused larvae mortality as indicating that enhanced solar UV-B exposure could be lethal to fish fauna in aquatic ecosystem. Artificial UV-B had a stronger damaging effect on fish larvae than solar radiation exhibited highly toxic in presence of retene. The larvae of S. richardsonii was found more sensitive than T. tor as indicated by high mortality rate (30%) and high pigmented characteristics on dorsal side. The solar and ultraviolet radiation showed a positive effect on high pigmentation. These results suggest that on a short time scale, UV-B radiation causing developmental stress on fish larvae may contribute to assess the phototoxic behaviour of cold water fishes