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Along with a wide range of applications, the surface-enhanced Raman spectroscopy (SERS) is a prominent analytical technique to recognize and detect molecules and materials even at an extremely low molar concentration. In this work, a unique hybrid SERS platform is demonstrated by the incorporation of molybdenum disulfate (MoS2) nanoparticles (NPs) onto the core-shell AuPt hybrid NPs (HNPs) for the enhanced molecular Raman vibration of crystal violet (CV). The hybrid platform takes the advantage of both the electromagnetic mechanism (EM) offered by the AuPt HNPs and chemical mechanism (CM) owing to the MoS2 NPs. The distinctive core-shell morphology of AuPt HNPs with the high-density background Au NPs is attained by a unique two-step solid-state dewetting method, which can offer a high concentration of electromagnetic hot spots. At the same time, the MoS2 NPs can provide an ample charge transfer with abundant active sites. Through the hybrid SERS approach, a dramatic SERS enhancement of CV Raman vibration is demonstrated, and the SERS capability is thoroughly studied. In addition, the finite-difference time-domain (FDTD) simulations provide a deeper understanding of the electromagnetic field distributions for various configurations of nanostructures and their hybrid combinations: i.e., HNPs, alloy NPs, MoS2/HNPs configurations.

Sharply improved photoresponse characteristics are demonstrated by the multi-metallic AgCu, AuCu and AgAuCu NP based UV-PDs through the superior photo carrier injection by the strong elemental composition-dependent hot electrons and localized surface plasmon resonance (LSPR).

In this work, a nanoscale device architecture is demonstrated for a UV photodetector application on sapphire (0001), incorporating the plasmonic hybrid nanoparticles (HNPs), graphene quantum dots (GQDs), and titanium oxide (TiO2) for the first time. The hybrid GQDs/TiO2/HNPs photodetector exhibits the photocurrent of 1.58 × 10-5 A under the 1.64 mW/mm2 of 275 nm illumination at 10 V, which is around two order increase from the bare TiO2 device. The proposed architecture demonstrates a low dark current of ∼1 × 10-10 A at 10 V and thus the device demonstrates an excellent photo to dark current ratio along with the improved rise and fall time on the order of several hundred millisecond. The enhanced performance of device architecture is attributed to the efficient utilization of localized surface plasmon resonance (LSPR) induced hot carriers as well as scattered photons from the plasmonic HNPs that are fully encapsulated by the photoactive TiO2 layers. Furthermore, the addition of GQDs on the TiO2 can offer an additional photon absorption pathway. The proposed hybrid architecture of GQDs/TiO2/HNPs demonstrates the integration of the photon absorption and carrier transfer properties of plasmonic HNPs, GQDs, and TiO2 for an enhanced ultraviolet (UV) photoresponse. The photocurrent enhancement mechanisms of the hybrid device architecture are thoroughly investigated based on the finite-difference time domain (FDTD) simulation along with the energy band analysis. This work demonstrates a great potential of the hybrid device architecture for high-performance UV photodetectors.

FAM21 (family with sequence similarity 21) is a component of the Wiskott–Aldrich syndrome protein and SCAR homologue (WASH) protein complex that mediates actin polymerization at endosomal membranes to facilitate sorting of cargo-containing vesicles out of endosomes. To study the function of FAM21in vivo, we generated conditional knockout (cKO) mice in the C57BL/6 background in which FAM21 was specifically knocked out of CD11c-positive dendritic cells. Bone marrow-derived dendritic cells (BMDC) from those mice displayed enlarged early endosomes, and altered cell migration and morphology relative to wildtype (WT) cells. FAM21-cKO cells were less competent in phagocytosis and antigen processingin vitro, though antigen presentation was not affected. More importantly, we identified the TLR2/CLEC4E signaling pathway as being downregulated in FAM21-cKO BMDCs when challenged with its specific ligandCandida albicans. Moreover, FAM21-cKO mice were more susceptible toC. albicansinfection than WT mice. Reconstitution of WT BMDCs in FAM21-cKO mice rescued them from lethalC. albicansinfection. Thus, our study highlights the importance of FAM21 in a host immune response against a significant pathogen.

COVID-19 in humans is caused by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that belongs to the beta family of coronaviruses. SARS-CoV-2 causes severe respiratory illness in 10-15% of infected individuals and mortality in 2-3%. Vaccines are urgently needed to prevent infection and to contain viral spread. Although several mRNA- and adenovirus-based vaccines are highly effective, their dependence on the “cold chain” transportation makes global vaccination a difficult task. In this context, a stable lyophilized vaccine may present certain advantages. Accordingly, establishing additional vaccine platforms remains vital to tackle SARS- CoV-2 and any future variants that may arise. Vaccinia virus (VACV) has been used to eradicate smallpox disease, and several attenuated viral strains with enhanced safety for human applications have been developed. We have generated two candidate SARS-CoV-2 vaccines based on two vaccinia viral strains, MVA and v-NY, that express full-length SARS-CoV-2 spike protein. Whereas MVA is growth-restricted in mammalian cells, the v-NY strain is replication-competent. We demonstrate that both candidate recombinant vaccines induce high titers of neutralizing antibodies in C57BL/6 mice vaccinated according to prime-boost regimens. Furthermore, our vaccination regimens generated TH1-biased immune responses in mice. Most importantly, prime-boost vaccination of a Syrian hamster infection model with MVA-S and v-NY-S protected the hamsters against SARS-CoV-2 infection, supporting that these two vaccines are promising candidates for future development. Finally, our vaccination regimens generated neutralizing antibodies that partially cross-neutralized SARS-CoV-2 variants of concern.

A unique ultraviolet (UV) photodetector architecture of MoS2/ZnO/HNP is explored and significantly increased photocurrent (Iph) of 4 × 10−3 A is demonstrated under the 385 nm illumination of 54.9 mW/mm2 at 10 V. This leads to the superior device performance factors: i.e., photoresponsivity of 21,111 mA/W, detectivity of 7.9 × 1011 jones and EQE of 6,800 %. These device performance factors confirm that the proposed photodetector configuration is superior as compared to the similar versions of ZnO-based UV photodetectors. The hybrid MoS2/ZnO/HNP architecture is constructed by the 2-D transition metal dichalcogenide MoS2 nanoflakes, wide-bandgapZnO quantum dots (QDs) and plasomonic PdAg hybrid nanoparticles (HNPs). The increased Iph is related to the hot carrier injection through the strongly improved localized surface plasmon resonance (LSPR) by the PdAg HNPs and additional photo carriers from the 2-D MoS2 nanoflakes on top of the original photo-induced carriers in the ZnO QD layer. The PdAg HNPs are fabricated by a unique two-step solid-state dewetting (SSD) technique, having the core-shelled PdAg NPs with the high-density small background Ag NPs. This HNP configuration offers very high-density hot spots and significantly improved LSPR. The photocurrent enhancement of MoS2/ZnO/HNP architecture is systematically studied by the finite-difference time-domain (FDTD) simulations.

In this work, an innovative and simple growth approach of two-step solid state dewetting (SSD) has been introduced for the fabrication of bimetallic and core-shell nanoparticle (NP) configurations. A significant surface-enhanced Raman spectroscopy (SERS) enhancement on the hybrid Pd@Ag core-shell NP substrate is systematically demonstrated by a unique hybrid approach of mixing the graphene quantum dots (GQDs) and Rhodamine 6G (R6G). Due to the substantially increased electromagnetic hotspots in the hybrid Pd@Ag core-shell NP configuration and also the charge transfer enhancement by the addition of GQDs through the chemical enhancement mechanism, over 100 times of SERS signal enhancement is observed for the detection of R6G. The hybrid Pd@Ag core-shell NPs with the background Ag NPs and fully alloyed bi-metallic AgPd NPs without the background Ag NPs are demonstrated on sapphire (0001). The bimetallic and core-shell NPs demonstrate much enhanced localized surface plasmon resonance (LSPR) and thus significantly improved SERS responses. In specific, the hybrid Pd@Ag core-shell NPs demonstrate a gradual blue-shift and narrowing of LSPR peaks while the fully alloyed bi-metallic AgPd NPs show a continuing redshift and broadening of LSPR peaks.

A super-porous hybrid platform can offer significantly increased number of reaction sites for the analytes and thus can offer advantages in the biosensor applications. In this work, a significantly improved sensitivity and selectivity of hydrogen peroxide (H2O2) detection is demonstrated by a super-porous hybrid CuO/Pt nanoparticle (NP) platform on Si substrate as the first demonstration. The super-porous hybrid platform is fabricated by a physiochemical approach combining the physical vapor deposition of Pt NPs and electrochemical deposition of super-porous CuO structures by adopting a dynamic hydrogen bubble technique. Under an optimized condition, the hybrid CuO/Pt biosensor demonstrates a very high sensitivity of 2,205 &micro, A/mM∙cm2 and a low limit of detection (LOD) of 140 nM with a wide detection range of H2O2. This is meaningfully improved performance as compared to the previously reported CuO-based H2O2 sensors as well as to the other metal oxide-based H2O2 sensors. The hybrid CuO/Pt platform exhibits an excellent selectivity against other interfering molecules such as glucose, fructose, dopamine, sodium chloride and ascorbic acid. Due to the synergetic effect of highly porous CuO structures and underlying Pt NPs, the CuO/Pt architecture offers extremely abundant active sites for the H2O2 reduction and electron transfer pathways.

The calcineurin-NFAT signaling pathway regulates cell proliferation, differentiation, and development in diverse cell types and organ systems. Deregulation of calcineurin-NFAT signaling has been reported in leukaemias and few solid tumors such as breast and colon. In the present study, we found elevated calcineurin protein levels and phosphatase activity in cervical cancer cell lines and depletion of the same attenuated cell proliferation. Additionally, nuclear levels of NFAT2, a downstream target of calcineurin, viz, was found elevated in human papillomavirus (HPV) infected cells, HeLa and SiHa, compared to the HPV negative cells, HaCaT and C33A, indicative of its higher DNA binding activity. The nuclear levels of both NFAT1 and NFAT3 remain unaltered implicating they have little role in cervical carcinogenesis. Similar to the in vitro studies, the HPV infected human squamous cell carcinoma specimens showed higher NFAT2 levels compared to the normal cervical epithelium. Depletion of NFAT2 by RNAi attenuated growth of SiHa cells. Overexpression of HPV16 oncoproteins viz, E6 and E7 increased NFAT2 expression levels and DNA binding activity, while knockdown of E6 by RNAi decreased the same. Briefly, we now report an activation of calcineurin-NFAT2 axis in cervical cancer and a novel role of HPV oncoprotein in facilitating NFAT2 dependent cell proliferation.

The paper introduces an adaptive optimization framework that is used to calibrate and optimize multiple intelligent transportation strategies such as high occupancy toll (HOT), ramp metering, and variable speed limits. The framework is capable of estimating the OD (origin–destination) matrix, calibrating the model with the experimental data, and conducting system optimization in transportation. This capability is shown with simulation experiments based on the public data of I-95 Florida. The preliminary results show that the revenue increases with target speed up to a point, after which the revenue drops. Also, the throughput on the HOT increases with decreasing target speed. So, to maximize revenue and throughput together, the optimal values are observed at moderate levels of the feasible range. Also, in the presence of accidents, the total throughput is improved by decreasing the toll rate. Optimal level of vehicles on the HOT lanes is examined to minimize vehicle emissions.

Managed lanes, or high-occupancy toll (HOT) lanes, have been implemented across the United States to improve the utility of existing road facilities. The pricing algorithm in managed lanes is the critical component in ensuring that the desired level of service metrics is met. Some pricing algorithms currently in use are static algorithms, and others adopt a dynamic strategy. Static pricing algorithms do not account for the changes in real-time traffic conditions. However, dynamic pricing algorithms are reactive in nature and do not account for the potential demand for actual future time intervals for which the toll is determined. The HOT-lane system is nonlinear and complex in nature; this complexity leads to high levels of instability in such a system. The complexity has been increasing because of the growth in demand as well as incorporation of other, noninteracting strategies that are implemented to address this demand. Therefore, more sophisticated designs of the pricing algorithm are needed for HOT-lane pricing control. A model-based pricing algorithm is proposed for determining the toll rate dynamically to maximize the throughput on the HOT lanes while maintaining a desired level of service. It consists of both proactive and reactive components to achieve fast response to real-time changes and maintain a steady, maximal traffic flow. The controller structure also incorporates active bottleneck management to maintain optimal traffic flow under stressed conditions. Implementation of this controller has shown high utilization of HOT lanes while ensuring the desired level of service.

With the advancement and use of low cost cameras, video-based remote vital-monitoring technologies have drawn more and more attention. However, many of the previously proposed techniques rely on the assumption that the video is acquired under well-controlled conditions. There has been no study reported around how various acquisition factors and/or noise will affect the estimation accuracy. In this paper, we describe a systematic approach in understanding the challenges of extending the technology beyond a well-controlled environment and share the solution paths in making the technology robust in one specific application. The systematic approach involves first understanding the data analysis process, identifying key factors that affect the algorithms and then estimating the bounds of the factors and metrics that explain the variations in these vitals. As part of the solution paths, our paper goes into the details of how the algorithms were improved to address the findings of the current state. The refinement in the algorithms includes getting stronger signals in less controlled setting.

A new class of potent PI3Kα inhibitors is identified based on aryl substituted morpholino-triazine scaffold. The identified compounds showed not only a high level of enzymatic and cellular potency in nanomolar range but also high oral bioavailability. The three lead molecules (based on their in vitro potency) when evaluated further for in vitro metabolic stability as well as pharmacokinetic profile led to the identification of 26, as a candidate for further development. The IC50 and EC50 value of 26 is 60 and 500 nM, respectively, for PI3Kα enzyme inhibitory activity and ovarian cancer (A2780) cell line. The identified lead also showed a high level of microsomal stability and minimal inhibition activity for CYP3A4, CYP2C19, and CYP2D6 at 10 μM concentrations. The lead compound 26, demonstrated excellent oral bioavailability with an AUC of 5.2 μM at a dose of 3 mpk in mice and found to be well tolerated in mice when dosed at 30 mpk BID for 5 days.

The present study was conducted to evaluate the effect of selection for egg production traits in White Leghorn chicken based upon the semen quality. Males of 3 pure lines of White Leghorn, namely IWH, IWI, and IWK, along with a pedigree random-bred control (IWC) population, were selected and housed in individual cages. The semen collected from individual birds was evaluated for different physical and biochemical parameters. There was significant (P ≤ 0.013) difference in semen quality parameters studied between the lines. High egg-producing lines IWH and IWI had poor semen quality in comparison with that of the control line (IWC). Thus, it can be concluded that selection for higher egg production affects the semen quality of males in the selected lines.

Print supply chain includes document design, material procurement, document creation, production, warehousing and delivery. Several small and medium scale industry players are involved in this supply chain process. Thus the print supply chain network is a loosely coupled system of spatially dispersed independent companies, working together for delivering value to the customer. This network consists of specialists in printing and complementary players such as packaging companies, logistics providers, IT companies, etc. Our focus in this paper is to design an orchestrator for the governance of end to end print service chain network in consumer oriented sectors such as banking, retail and insurance for small and medium enterprises (SMEs). The orchestrator typically does three functions: partner selection, supply chain planning and supply chain execution. In this paper, we concentrate on the second step - the supply chain planning and scheduling and develop a mixed integer programming model, illustrating it with an example.

An important print quality attribute of digital printing equipment deals with the absolute position of the printed image relative to the page. Historically, the most precise method of measuring image to paper (IOP) registration is by scanning a printed sheet on a flatbed scanner. These measurements have been limited to sheets smaller than the full capacity of the printer. In addition, the precision of the measurement has been limited by the accuracy of the scanner itself and the measurement of a few (~4) points on the page have limited the information that can be gathered. The new method proposed in this paper measures IOP registration throughout the sheet in a more precise manner. In a similar fashion, the relative position of the image on both the simplex and duplex side of the print can be determined. In addition, the new method helps link the source of registration errors to individual sub-systems. By generating the individual error sources from a printed sheet enables the understanding of the percentage contribution of each sub-system, prioritizes efforts to obtain better IOP performance, finds initial IOP setup errors of a printing engine, compares different technologies affecting IOP registration in sub-systems and potentially acts as a diagnostic tool for individual sub-systems.