Current evidence of integrative oncology modalities for managing adverse effects and survivorship issues among adolescents and young adult (AYA) cancer patients and survivors.

PURPOSE OF REVIEW: Symptom burden of cancer diagnosis and treatment has led adolescents and young adult cancer patients (AYAC) and survivors to seek different self-management strategies including integrative oncology (IO) modalities. IO holds great promise to improve survivorship issues in adolescents and young adult (AYA) cancer survivors. This review aims to encompass the current evidence of IO modalities and to analyze the efficacy of IO for managing survivorship issues among AYA cancer patients and survivors. RECENT FINDINGS: Nineteen randomized controlled trials included in this review evaluated mind and body modalities including both physical and psychological (74%) and psychological only (26%) modalities. Most assessed IO modalities were physical activity (PA) (37%) and structured exercise (10%). Most effective IO modalities found were PA, massage, mindfulness-based stress reduction (MBSR) and light therapy for treating AYA symptom burden. The Cochrane risk of bias (RoB-2) concluded 21% studies had high risk, 58% possessed some concerns and 21% had low risk. SUMMARY: Although evidence has shown that a number of IO modalities may improve survivorship among AYA cancer survivors, more rigorous study designs are needed in order for these modalities to be routinely recommended for use in clinical practice.

Prediction of gastrointestinal symptoms trajectories using omega-3 and inflammatory biomarkers in early-stage breast cancer patients receiving chemotherapy.

PURPOSE: Gastrointestinal (GI) symptoms are common among breast cancer patients undergoing chemotherapy, negatively impacting treatment outcomes and quality of life. Evidence points to inflammatory processes as the underlying cause of chemotherapy-associated GI symptoms. Relatedly, omega-3 (n-3) has been linked to anti-inflammatory processes. The primary objective of this study was to examine the associations between baseline n-3, baseline inflammatory markers and GI symptom progression in early-stage breast cancer patients receiving chemotherapy. METHODS: In this secondary analysis of a prospective cohort study, we analyzed baseline levels of inflammatory biomarkers (measured using a Luminex bead-immunoassay) and plasma levels of DHA, EPA, and FFA (measured using enzyme-linked immunosorbent assay). GI symptoms were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire in Cancer Patients (EORTC QLQ-C30) symptom scale scores at baseline (T1) and at least 6 weeks after, during chemotherapy (T2). Inferential statistics were used to analyze associations between the variables of interest. RESULTS: The analysis included 31 female breast cancer patients (mean age ± SD = 50.5 ± 8.8; 89.6% receiving anthracycline-based chemotherapy). Higher levels of docosahexaenoic acid (DHA) and interleukin-8 (IL-8) predicted increases in appetite loss. Similarly, higher IL-8 predicted worsened nausea and vomiting. CONCLUSION: Baseline IL-8 and DHA predicted GI symptom progression in early-stage breast cancer patients undergoing chemotherapy. Future studies are required to evaluate how therapeutic intervention targeting these biomarkers may mitigate gastrointestinal symptoms in cancer patients.

Targeting novel inhibitory receptors in cancer immunotherapy.

T cells play a critical role in promoting tumor regression in both experimental models and humans. Yet, T cells that are chronically exposed to tumor antigen during cancer progression can become dysfunctional/exhausted and fail to induce tumor destruction. Such tumor-induced T cell dysfunction may occur via multiple mechanisms. In particular, immune checkpoint inhibitory receptors that are upregulated by tumor-infiltrating lymphocytes in many cancers limit T cell survival and function. Overcoming this inhibitory receptor-mediated T cell dysfunction has been a central focus of recent developments in cancer immunotherapy. Immunotherapies targeting inhibitory receptor pathways such as programmed cell death 1 (PD-1)/programmed death ligand 1 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), alone or in combination, confer significant clinical benefits in multiple tumor types. However, many patients with cancer do not respond to immune checkpoint blockade, and dual PD-1/CTLA-4 blockade may cause serious adverse events, which limits its indications. Targeting novel non-redundant inhibitory receptor pathways contributing to tumor-induced T cell dysfunction in the tumor microenvironment may prove efficacious and non-toxic. This review presents preclinical and clinical findings supporting the roles of two key pathways-T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) and T cell immunoreceptor with Ig and ITIM domain (TIGIT)/CD226/CD96/CD112R-in cancer immunotherapy.

Optimization of optical and structural properties of Al2O3/TiO2 nano-laminates deposited by atomic layer deposition for optical coating.

Optimizing the atomic layer deposition (ALD) process of films is particularly important in preparing multilayer interference films. In this work, a series of Al2O3/TiO2 nano-laminates with a fixed growth cycle ratio of 1:10 were deposited on Si and fused quartz substrates at 300 °C by ALD. The optical properties, crystallization behavior, surface appearance and microstructures of those laminated layers were systematically investigated by spectroscopic ellipsometry, spectrophotometry, X-ray diffraction, atomic force microscope and transmission electron microscopy. By inserting Al2O3 interlayers into TiO2 layers, the crystallization of the TiO2 is reduced and the surface roughness becomes smaller. The TEM images show that excessively dense distribution of Al2O3 intercalation leads to the appearance of TiO2 nodules, which in turn leads to increased roughness. The Al2O3/TiO2 nano-laminate with a cycle ratio 40:400 has relatively small surface roughness. Additionally, oxygen-deficient defects exist at the interface of Al2O3 and TiO2, leading to evident absorption. Using O3 as an oxidant instead of H2O for depositing Al2O3 interlayers was verified to be effective in reducing absorption during broadband antireflective coating experiments.

Low polarization-sensitive ultra-broadband anti-reflection coatings with improved reliability.

Broader spectra, lower reflectivity and higher reliability are the performance requirements for broadband antireflective (BBAR) films. In this work, a BBAR film structure was proposed, which maintains extremely low reflectivity, ultra-wide spectra, low polarization sensitivity and practical reliability. The BBAR film consists of a dense multilayer interference stack on the bottom and a nano-grass-like alumina (NGLA) layer with a gradient low refractive index distribution on the top. The film was deposited by atomic layer deposition, while the NGLA layer was formed by means of a hot water bath on Al2O3 layer. The top NGLA layer has extremely high porosity and ultra-low refractive index, along with extremely fragile structure. To surmount the fragility of NGLA layer, a sub-nano layer of SiO2 was grown by atomic layer deposition to solidify its structure and also to adjust the refractive index with different thicknesses of SiO2. Finally, in the wide wavelength range of 400-1100 nm, the average transmittance of the double-sided coated fused quartz reaches 99.2%. The absorption, light scattering, reliability and polarization characteristics of BBAR films were investigated. An optimized BBAR film with low polarization-sensitivity and improved reliability was realized, which should be potentially promising for application in optical systems.

Ground-to-satellite quantum teleportation.

An arbitrary unknown quantum state cannot be measured precisely or replicated perfectly. However, quantum teleportation enables unknown quantum states to be transferred reliably from one object to another over long distances, without physical travelling of the object itself. Long-distance teleportation is a fundamental element of protocols such as large-scale quantum networks and distributed quantum computation. But the distances over which transmission was achieved in previous teleportation experiments, which used optical fibres and terrestrial free-space channels, were limited to about 100 kilometres, owing to the photon loss of these channels. To realize a global-scale 'quantum internet' the range of quantum teleportation needs to be greatly extended. A promising way of doing so involves using satellite platforms and space-based links, which can connect two remote points on Earth with greatly reduced channel loss because most of the propagation path of the photons is in empty space. Here we report quantum teleportation of independent single-photon qubits from a ground observatory to a low-Earth-orbit satellite, through an uplink channel, over distances of up to 1,400 kilometres. To optimize the efficiency of the link and to counter the atmospheric turbulence in the uplink, we use a compact ultra-bright source of entangled photons, a narrow beam divergence and high-bandwidth and high-accuracy acquiring, pointing and tracking. We demonstrate successful quantum teleportation of six input states in mutually unbiased bases with an average fidelity of 0.80 ± 0.01, well above the optimal state-estimation fidelity on a single copy of a qubit (the classical limit). Our demonstration of a ground-to-satellite uplink for reliable and ultra-long-distance quantum teleportation is an essential step towards a global-scale quantum internet.

Using machine learning to develop a clinical prediction model for SSRI-associated bleeding: a feasibility study.

INTRODUCTION: Adverse drug events (ADEs) are associated with poor outcomes and increased costs but may be prevented with prediction tools. With the National Institute of Health All of Us (AoU) database, we employed machine learning (ML) to predict selective serotonin reuptake inhibitor (SSRI)-associated bleeding. METHODS: The AoU program, beginning in 05/2018, continues to recruit ≥ 18 years old individuals across the United States. Participants completed surveys and consented to contribute electronic health record (EHR) for research. Using the EHR, we determined participants who were exposed to SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vortioxetine). Features (n = 88) were selected with clinicians' input and comprised sociodemographic, lifestyle, comorbidities, and medication use information. We identified bleeding events with validated EHR algorithms and applied logistic regression, decision tree, random forest, and extreme gradient boost to predict bleeding during SSRI exposure. We assessed model performance with area under the receiver operating characteristic curve statistic (AUC) and defined clinically significant features as resulting in > 0.01 decline in AUC after removal from the model, in three of four ML models. RESULTS: There were 10,362 participants exposed to SSRIs, with 9.6% experiencing a bleeding event during SSRI exposure. For each SSRI, performance across all four ML models was relatively consistent. AUCs from the best models ranged 0.632-0.698. Clinically significant features included health literacy for escitalopram, and bleeding history and socioeconomic status for all SSRIs. CONCLUSIONS: We demonstrated feasibility of predicting ADEs using ML. Incorporating genomic features and drug interactions with deep learning models may improve ADE prediction.

Sociodemographic characteristics differ across routine adult vaccine cohorts: An All of Us descriptive study.

BACKGROUND: The National Institutes of Health All of Us (AoU) Research Program is currently building a database of 1million+ adult subjects. With it, we describe the characteristics of those with documented vaccinations. OBJECTIVES: To describe the sociodemographic, health status, and lifestyle factors associated with vaccinations. METHODS: This is a retrospective study involving data from the AoU program (R2020Q4R2, N = 315,297). Five vaccine cohorts [influenza, hepatitis B (HBV), pneumococcal <65 years old, pneumococcal ≥65 years old, and human papillomavirus (HPV)] were generated based on vaccination history. The influenza cohort comprised participants with documented influenza vaccinations in electronic health records (EHRs) from September 2017 to May 2018. Other vaccine cohorts comprised participants with ≥1 lifetime record(s) of vaccination documented in the EHR by December 2018. The vaccine cohorts were compared to the overall AoU cohort. Descriptive statistics were generated using EHR- and survey-based sociodemographic, health, and lifestyle information. The SAMBA (0.9.0) R package was utilized to adjust for EHR selection and outcome misclassification biases to infer sources of disparity for pneumococcal vaccinations in older adults. RESULTS: Cohort counts were as follows: influenza (n = 15,346), HBV (n = 6323), pneumococcal <65 (n = 15,217), pneumococcal ≥65 (n = 15,100), and HPV (n = 2125). All vaccine cohorts had higher proportions of White and non-Hispanic/Latino participants compared to the overall AoU cohort. The largest differences were found in pneumococcal age ≥65, with 80.2% White participants compared to 52.9% in the overall study population. Multivariable analysis revealed that race/ethnic disparities in pneumococcal vaccination among older adults were explained by biological sex, income, health insurance, and education-related variables. CONCLUSION: Racial, ethnic, education, and income characteristics differ across the vaccine cohorts among AoU participants. These findings inform future utilization of large health databases in vaccine epidemiology research and emphasize the need for more targeted interventions that address differences in vaccine uptake.

Transcellular Transport Behavior of the Intact Polymeric Mixed Micelles with Different Polymeric Ratios.

In order to better promote the application of the polymeric mixed micelles (PMMs) in oral delivery, in addition to focusing on the improvement of micellar structural stability, it is necessary to obtain the absorption characteristics of the intact micellar particles. In this work, the transport behavior across Caco-2 cells of FS/PMMs composed of Pluronic F127 and Solutol HS15 was tracked by encapsulating an environment-responsive probe into the particles. The specific property of the probe is the water-initiated aggregation-caused quenching (ACQ) ability, by which integral particles can be identified accurately. The influence of polymeric ratios (FS) on the transcellular behavior of FS/PMMs was explored and the single pass intestinal perfusion experiment was used to further illustrate it. Moreover, pharmacokinetics parameters were detected to analyze the relationship among FS ratios, transport behavior, and pharmacokinetic parameters. FS ratios were found to hardly affect the endocytosis pathways and intracellular itinerary of FS/PMMs, but do affect the proportion of each path. FS/PMMs with high HS15 content, namely System-I, were found to primarily undergo receptor-mediated endocytosis pathway and be less susceptible to lysosomal degradation, which would lead to more absorption and higher Cmax and AUC than drug suspension. In contrast, despite System-II with high F127 content cannot contribute to drug plasma concentration, it can prolong the in vivo retention time. These findings provided evidence for the role of polymeric ratios in modulating the transcellular absorption and pharmacokinetic parameters of the drug-loaded PMMs, and would be a step forward in helping PMMs' design to enhance oral drug delivery.

Discovery of a novel 2-spiroproline steroid mimetic scaffold for the potent inhibition of 11ß-HSD1.

11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) has been identified as the primary enzyme responsible for the activation of hepatic cortisone to cortisol in specific peripheral tissues, resulting in the concomitant antagonism of insulin action within these tissues. Dysregulation of 11ß-HSD1, particularly in adipose tissues, has been associated with a variety of ailments including metabolic syndrome and type 2 diabetes mellitus. Therefore, inhibition of 11ß-HSD1 with a small nonsteroidal molecule is therapeutically desirable. Implementation of a scaffold-hopping approach revealed a 3-point pharmacophore for 11ß-HSD1 that was utilized to design a 2-spiroproline derivative as a steroid mimetic scaffold. Reiterative optimization provided valuable insight into the bioactive conformation of our novel scaffold and led to the discovery of several leads, such as compounds 39 and 51. Importantly, deleterious hERG inhibition and pregnane X receptor induction were mitigated by the introduction of a 4-hydroxyl group to the proline ring system.

Discovery of 1'-(1-phenylcyclopropane-carbonyl)-3H-spiro[isobenzofuran-1,3'-pyrrolidin]-3-one as a novel steroid mimetic scaffold for the potent and tissue-specific inhibition of 11ß-HSD1 using a scaffold-hopping approach.

11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) has been identified as the primary enzyme responsible for the activation of hepatic cortisone to cortisol in specific peripheral tissues resulting in the concomitant antagonism of insulin action within these tissues. Dysregulation of 11ß-HSD1, particularly in adipose tissues, has been associated with metabolic syndrome and type 2 diabetes mellitus. Therefore, inhibition of 11ß-HSD1 with a small nonsteroidal molecule is therapeutically desirable. Implementation of a scaffold-hopping approach revealed a three-point pharmacophore for 11ß-HSD1 that was utilized to design a steroid mimetic scaffold. Reiterative optimization provided valuable insight into the bioactive conformation of our novel scaffold and led to the discovery of INCB13739. Clinical evaluation of INCB13739 confirmed for the first time that tissue-specific inhibition of 11ß-HSD1 in patients with type 2 diabetes mellitus was efficacious in controlling glucose levels and reducing cardiovascular risk factors.

A global survey on the utilization of cryotherapy and compression therapy for the prevention of chemotherapy-induced peripheral neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect that is highly prevalent among cancer patients undergoing chemotherapy. There is a growing use of cryotherapy (CryTx) and compression therapy (ComTx) to prevent CIPN at cancer centers worldwide. In this study, we examined the awareness and recommendation of these modalities and evaluated factors associated with awareness. In addition, we investigated the type of technology utilized, barriers to implementation, and perceived adverse events of CryTx and ComTx. METHODS: Active members of the Multinational Association of Supportive Care of Cancer (MASCC) were invited to complete an electronic survey that was sent via SurveyMonkey between September and October 2021. The survey assessed participants' awareness, recommendation, usage, barriers to utilization, and perceived adverse events of CryTx and ComTx. Descriptive statistics and multiple logistic regression were utilized to analyze findings. RESULTS: Out of 184 participants, 70.1% were physicians, 73.4% had over 10 years of practice, and 49.5% were practicing in an outpatient setting. While more than half (63.3%) of participants indicated awareness of CryTx for taxane-induced peripheral neuropathy, less than a quarter (22.8%) indicated recommendation in their practice setting. Factors associated with higher awareness of CryTx for patients receiving taxanes include living in Europe (OR = 2.69, 95% CI [1.28-5.64], p = 0.009), not practicing in an inpatient setting (OR = 3.15, 95% CI [1.45-6.85], p = 0.004), and self-identifying as non-physician (OR = 2.40, 95% CI [1.03-4.37], p = 0.041). Commercial cooling (31.5%) and compression (16.8%) gloves and socks were the most used modalities for CryTx and ComTx, respectively. The most identified barriers to CryTx and ComTx utilization include insufficient evidence (53.5%), logistics (34.8%), and patient discomfort (23.4%). Redness/irritation of skin (27.7%) and numbness/tingling (24.5%) accounted for about half of the perceived adverse events associated with use of CryTx and ComTx. CONCLUSION: Results of our global survey illustrated that there are varying modes in the delivery of CryTx and ComTx among cancer centers around the world. Education of the utilization of CryTx and ComTx, in addition to efficacy and implementation studies, is needed to close the gap between awareness and implementation in clinical practice.

Double-sided optical coating of strongly curved glass by atomic layer deposition.

A reaction chamber of atomic layer deposition (ALD) was developed for simultaneous coating on the inner and outer surfaces of a large-size and strongly curved glass bowl. The inner surface ALD process was in a showerhead reaction mode and the outer surface ALD process was in a cross-flow reaction mode. Blue reflection (BR) film of 400 nm wavelength and broadband antireflection (BBAR) film of 400-700 nm wavelength were coated on different glass bowls by ALD. The spectral uniformity of both coated bowls was studied. The measured spectra at multiple positions of the glass bowl with the BBAR coating show better spectral uniformity along the circumference than the depth. The spectral deviation is mainly caused by the non-uniformity of the film on the outer surface (<±3%), and the film on the inner surface has good uniformity along both the circumference and the depth (<±0.7%). The growth rate of the outer film was reduced by 10% on average compared to that of the inner film due to the different gas flow mode.

Understanding the Synergistic Correlation between the Spatial Distribution of Drug-Loaded Mixed Micellar Systems and In Vitro Behavior via Experimental and Computational Approaches.

To better promote the application of polymeric mixed micelles (PMMs), a coarse-grained molecular dynamics simulation (CGMD) has been employed to investigate the factors controlling the spatial distribution within the PMMs and predict their drug-loading properties, meanwhile, combined with experimental methods to validate and examine it. In this study, the snapshots obtained from CGMD and the results of proton nuclear magnetic resonance (1H NMR) and transmission electron microscopy (TEM) provide new insights into the distribution principle that the spatial distribution depends on the hydrophobic compatibility of drugs with the regions within PMMs. Docetaxel (DTX) is located within the interior or near the core-corona interface of the HS15 hydrophobic core inside FS/PMMs (PMMs fabricated from a nonionic triblock copolymer (F127)) and a nonionic surfactant (HS15), and therefore, the system with a high HS15 ratio, such as system I, is more suitable for loading DTX. In contrast, the more water-soluble puerarin (PUE) is more likely to be solubilized in the "secondary hydrophobic area," mainly formed by the hydrophobic part of F127 within FS/PMMs. However, when the initial feeding concentration of the drug is increased or the FS mixing ratios are changed, an inappropriate distribution would occur and hence influence the drug-loading stability. Also, this impact was further elucidated by the calculated parameters (solvent-accessible surface area (SASA), the radius of gyration (Rg), and energy landscape), and the analysis of the drug leakage, concluding that inappropriate distribution of the drug would lower the stability of the drug in the PMMs. These results combined together provide new insights into the distribution principle that the spatial distribution of drugs within PMMs depends on the hydrophobic compatibility of drugs with the regions formed by micellar materials. Additionally, in vitro drug release yielded a consistent picture with the above conclusions and provides evidence that both the location of the drug within the systems and the stability of the drug-loading system have a great influence on the drug release behavior. Accordingly, this work demonstrates that we can tune the drug-loading stability and drug release behavior via the drug-PMM interaction and drug location study, and CGMD technology would be a step forward in the search for suitable drug-delivery PMMs.

Coarse-Grained Molecular Dynamic and Experimental Studies on Self-Assembly Behavior of Nonionic F127/HS15 Mixed Micellar Systems.

The self-assembly of a nonionic triblock copolymer (F127) and a nonionic surfactant (HS15) has been investigated due to favorable changes in properties in their mixtures. The effect of the mixing ratio on the self-assembly process and on the structural stability of the mixtures was studied by coarse-grained molecular dynamic simulation (CGMD) and experimental measurements (transmission electron microscopy, dynamic light scattering measurement, drug loading stability analysis, and fluorescence spectroscopy measurement). The CGMD provided the information on self-assembly behavior. The microstructure and micellar stability are affected by different proportions of F127/HS15. Pure HS15 molecules (system I) can rapidly form stable aggregates driven by strong hydrophobic force, including two steps: the formation of seed clusters and the fusion of them. At low F127 ratio (system II), the self-assembly process is dynamic unstable, and a volatile "coil/cluster-like" aggregate is formed under the single "binding" effect. As the ratio of added F127 increase, such as system III, stable "lotus-seedpod-like" aggregates form under the double effects of "binding plus wrapping". Its dynamic equilibrium can be achieved rapidly. The experimental results approved the assumption of "different mixing ratio with different structural stability" and even different loading stability of F127/HS15 systems for drugs with different log P, such as PUE and DTX, which means different loading area for them in the micellar systems at different mixing ratios because of less hydrophobic microdomains with the increase of F127 molecules.

Effect comparison of three different types of transanal drainage tubes after anterior resection for rectal cancer.

BACKGROUND: Anastomotic leakage (AL) is one of the most severe early complications after rectal cancer surgery. Many studies and meta-analysis results show that the indentation of transanal drainage tubes (TDT) can prevent and reduce the incidence of AL. However, the size and material of drainage tubes are rarely reported. Herein, we compare the effect of three kinds of TDT and analyze the use of TDT material and size to prevent AL, which may better prevent the occurrence of AL. METHODS: The clinical data of 182 patients who underwent laparoscopic anterior resection of rectal cancer were retrospectively analyzed between January 2016 and March 2019. According to the types of indwelling TDT after the operation, they were divided into Fr32 silicone tubes (81 cases), Fr24 silicone tubes (54 cases), Fr24 latex tubes (47 cases). The first drainage, exhaust, defecation, abdominal distension and anastomotic leakage of the patients with three different types of TDT were compared. RESULTS: There was no significant difference in the degree of first exhaust, abdominal distension and anastomotic leakage among three different types of TDT; the time of first drainage and defecation of the Fr32 silicone tube was significantly earlier than that of Fr24 silicone tube and Fr24 latex tube. CONCLUSION: The drainage effect of the Fr32 silicone tube is better than that of Fr24 silicone tube and Fr24 latex tube after anterior resection for rectal cancer, Fr32 silicone may better prevent the occurrence of AL, but randomized controlled studies are needed.

Dissolved Organic Matter or Salts Change the Bioavailability Processes and Toxicity of the Nanoscale Tetravalent Lead Corrosion Product PbO2 to Medaka Fish.

Nanoscale lead dioxide (nPbO2(s)) is a corrosion product formed from the chlorination of lead-containing plumbing materials. This metal oxide nanoparticle (NP) plays a key role in determining lead pollution in drinking water and receiving water bodies. This study uses nPbO2(s) and medaka fish (Oryzias latipes) as surrogates to investigate the aqueous fate and toxicological risk of metal oxide NPs associated with water matrices. The larvae of medaka were treated with solutions containing nPbO2(s) or Pb(II)aq in different water matrices for 7-14 days to investigate the in vivo toxic effects of NPs. Ionic strength enhanced aggregation and sedimentation of nPbO2(s) in water, leading to increased lead contents in fish bodies. However, the presence of dissolved organic matter in water enhanced particle stability and accelerated the lead dissolution, thus changing the bioavailability processes (bioaccessibility) of particles. Oxidative stress response and neurotoxicity in exposed fish was greater for nPbO2(s) solution with increased salinity than dissolved organic matter. We predict the bioavailability processes and toxicity of nPbO2(s) in medaka from the aqueous particle behavior under environmentally relevant exposure conditions. Our investigation suggests a toxicological risk of metal oxide NP pollution in the aquatic environment.

Improving the accuracy of Laplacian estimation with novel multipolar concentric ring electrodes.

Conventional electroencephalography with disc electrodes has major drawbacks including poor spatial resolution, selectivity and low signal-to-noise ratio that are critically limiting its use. Concentric ring electrodes, consisting of several elements including the central disc and a number of concentric rings, are a promising alternative with potential to improve all of the aforementioned aspects significantly. In our previous work, the tripolar concentric ring electrode was successfully used in a wide range of applications demonstrating its superiority to conventional disc electrode, in particular, in accuracy of Laplacian estimation. This paper takes the next step toward further improving the Laplacian estimation with novel multipolar concentric ring electrodes by completing and validating a general approach to estimation of the Laplacian for an (n + 1)-polar electrode with n rings using the (4n + 1)-point method for n ≥ 2 that allows cancellation of all the truncation terms up to the order of 2n. An explicit formula based on inversion of a square Vandermonde matrix is derived to make computation of multipolar Laplacian more efficient. To confirm the analytic result of the accuracy of Laplacian estimate increasing with the increase of n and to assess the significance of this gain in accuracy for practical applications finite element method model analysis has been performed. Multipolar concentric ring electrode configurations with n ranging from 1 ring (bipolar electrode configuration) to 6 rings (septapolar electrode configuration) were directly compared and obtained results suggest the significance of the increase in Laplacian accuracy caused by increase of n.

An optical monitoring method for depositing dielectric layers of arbitrary thickness using reciprocal of transmittance.

An approach extracting information of both optical monitoring signal and phase thickness of deposited layer on a trace diagram is proposed. Realtime fitting and calculation are performed to get both practical thickness and refractive index of deposited layer with the assist of quartz crystal monitoring for keeping steady rate of deposition. Monitoring error of thickness using this approach is analyzed. It was used to obtain the refractive indices and thickness of Ge layer and SiO layer in in situ measurement mode, and the results were compared with those of ex-situ spectral measurement using infrared spectrometer. The effectiveness of the proposed monitoring method was verified by fabricating narrow bandpass filter consisting of quarter-wave and non-quarter-wave layers.

Bioactive constituents from the green alga Caulerpa racemosa.

Three diterpenoids, including a pair of epimers, racemobutenolids A and B (1 and 2), and 4',5'-dehydrodiodictyonema A (3), an α-tocopheroid, α-tocoxylenoxy (8), and an 28-oxostigmastane steroid, (23E)-3ß-hydroxy-stigmasta-5,23-dien-28-one (11), together with 12 known compounds, were isolated from the green alga Caulerpa racemosa. The structures of the new compounds were elucidated by detailed analysis of spectroscopic data, and by comparison with data for related known compounds. The epimers (1 and 2) are two unusual diterpenoid lactones bearing a ß-methyl-γ-substituted butenolide moiety, and 3 and 8 represent the first naturally occurring natural products with a hematinic acid ester group and 3,5-dimethylphenoxy functionality, respectively. The enzyme inhibitory activities of the isolated compounds were evaluated in vitro against PTP1B and related PTPs (TCPTP, CDC25B, LAR, SHP-1, and SHP-2). Compounds 3, 5, 6, and 9-14 exhibited different levels of PTP1B inhibitory activities with IC50 values ranging from 2.30 to 50.02µM. Of these compounds, 3, 9, and 11 showed the most potent inhibitory activities towards PTP1B with IC50 values of 2.30, 3.85, and 3.80µM, respectively. More importantly, the potent PTP1B inhibitors 3, 9, and 11 also displayed high selectivity over the highly homologous TCPTP and other PTPs. Also, the neuroprotective effects of the isolates against Aß25-35-induced cell damage in SH-SY5Y cells were investigated. Compounds 10, 11, and 14 exhibited significant neuroprotective effects against Aß25-35-induced SH-SY5Y cell damage with 11.31-15.98% increases in cell viability at 10µM. In addition, the cytotoxic activities of the isolated compounds were tested against the human cancer cell lines A-549 and HL-60.