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A highly functionalized BCDE model ring system of aconitine has been synthesized for the first time via a strategy involving oxidative dearomatization/IMDA, Wagner–Meerwein rearrangement, Michael addition and reductive cyclization.

There is a lack of literature on effective theories to assist couples with childbearing decision conflict. Authors address the ways how Narrative Therapy could serve as a helpful framework to address this particular problem. The literature will review the topic of childbearing conflict amongst couples, and provide background on Narrative Therapy with a focus on Narrative Couple Therapy. A case example is presented to demonstrate the ways Narrative Therapy deals with a couple's conflict on childbearing decision, showing how its techniques can be used to navigate the decision-making process.

Intelligent reflecting surface (IRS) is considered as an enabling technology for millimeter wave (mmWave) communications since it can provide an extra reflection link to increase the macrodiversity gains and improve the transmission performance. These advantages principally rely on the assumption that the blocking of direct and reflection links is mutually independent. However, due to the nonnegligible sizes of blockages in some practical cases, both links may be simultaneously blocked by the same blockage, which is the so-called blockage correlation. To this end, in this work we investigate the impact of blockage correlation in the IRS-assisted mmWave communication systems. Firstly, we provide a new joint line-of-sight/non-line-of-sight (LOS/NLOS) probability model with blockage correlation. The correlation coefficient of direct and reflection link states is also derived. Secondly, we study the effects of blockage correlation on the system performance of IRS-assisted mmWave communication systems by deriving the expression of transmission success probability. Moreover, we provide a deployment optimization algorithm for IRS when blockage correlation is considered. Finally, simulations verify our theoretical results and validate the IRS deployment optimization algorithm. It is shown that the widelyused independent blocking assumption not only always incur an overestimation of the performance of IRS-assisted mmWave communication systems, but also misdirect the optimal deployment of IRS.

We consider a wireless-powered ad hoc network with clustered Power Beacons (PBs). The wireless-powered transmitters (WP-Txs) only activate stochastically deployed PBs within the circles centered at their locations. The PBs transmit radio frequency (RF) signals, which are harvested by the WP-Txs to transmit information to their target receivers. The nodes are modeled as following $\beta $ -Ginibre Point Processes ( $\beta $ -GPP), which incorporate repulsion among PBs or active WP-Txs. Lacking analytical mathematical tools to describe the distribution of clustered PBs, we establish lower and upper bounds on the energy outage probability, as well as an approximated expression of it. We then derive the information outage probability, an approximate expression of it by approximating the reduced Palm distribution of $\beta $ -GPP as an inhomogeneous Poisson point process (IPPP), and an analytical approximate expression of it by further ignoring the small-scale fading of interfering WP-Tx links. Finally, the transmission capacity is obtained based on the overall outage probability. The simulation results show that the derived theoretical expressions accurately reflect the performance of the wireless-powered ad hoc networks and the performance gap introduced by approximations is negligible. Transmission capacity optimization based on the derived expressions is also possible and demonstrated.

Subcellular organelle targeted imaging and therapy are of enormous interest in cancer theranostics. However, the lack of tumor-selective organelle targeting has compromised their efficacy and safety. In this work, we found that the near-infrared (NIR) fluorophore hemicyanine (CyNH2) can selectively target mitochondria with strong cytotoxicity through decreasing the mitochondrial membrane potential and increasing the intracellular reactive oxygen species (ROS) levels. A macrotheranostic probe (denoted as PLCy) based on conjugating CyNH2 with an acetylated lysine group was developed with masked fluorescence and cytotoxicity, which could both be unmasked through sequential activation by cancer cells overexpressing histone deacetylases (HDACs) and cathepsin L (CTSL) enzymes for selective cancer cell mitochondria-targeted imaging and therapy. In vitro and in vivo studies confirmed that the specific fluorescence turn-on and toxicity were restored in cancer cells and efficiently inhibited tumor growth. This macrotheranostic probe with sequential enzyme activation and mitochondrial targeting is expected to have promising applications in imaging-guided cancer therapy with high specificity and efficiency. Statement of significance To improve the targeting efficiency and enhance the anti-cancer activities of macrotheranostic probe. We designed macrotheranostic probe PLCy that can be activated via sequential enzymes for selective tumor mitochondria targeting. More importantly, the activated CyNH2 can decrease the mitochondrial membrane potential and elevate the reactive oxygen species level in cancer cells without light irradiation, which can further induce apoptosis of tumor cells for chemotherapy. Therefore, the use of sequential enzyme activation and mitochondria targeting strategies in the context of enzymatic activation may provide a general strategy for organelle-targeted imaging and therapy with high specificity and efficiency.

Determination of whether multidrug nanocarriers can deliver and release loaded drugs at a predefined synergistic ratio to target cancer cells is crucial. Although there are many successful applications for delivery of multiple drugs, most current carriers are unable to achieve coordinated loading and release, leading to a drug release ratio that disagrees with the predefined loading ratio. In this work, a simple dual-drug delivery system with a flexible and controllable drug release ratio was constructed to deliver two anticancer drugs, doxorubicin (DOX) and curcumin (CUR). The drug ratio of DOX and CUR can be easily tuned for an enhanced synergistic effect, and the drugs can be released at predesigned ratios due to synchronous drug activation and nanoparticle collapse. Drug release at predefined ratios for synergistic anticancer therapy was demonstrated via in vitro and in vivo experiments. Therefore, the dual drug delivery system developed here provides a simple and efficient strategy for combination chemotherapy.

Folate receptor (FR) is a typical tumor-associated antigen that has been widely used as a biomarker for the determination of cancer. A biosensing platform functionalized with folic acid (FA) is essential to FR detection because FA specifically binds FR. We demonstrate an MgZnO dual-gate thin-film transistor (MZO DGTFT) based biosensor for the sensitive determination of FA derivative, hexadecyl alkynated folic acid (HAFA). The receptor is an MZO nanostructure (MZO $_{\mathrm {nano}}$ ) modified sensing pad which electrically connects to the top gate of DGTFT. The bottom gate of DGTFT is used to bias the device to its optimum operation point, enabling high sensitivity. First, 11-azidoundecanoic acid (AA) was bond onto the MZO $_{\mathrm {nano}}$ surface as the linker layer, resulting in negative charges to MZO $_{\mathrm {nano}}$ due to carboxylic acid binding chemistry. HAFA was then immobilized on MZO $_{\mathrm {nano}}$ via click reaction with AA. HAFA is a polar molecule with the positive end adjacent to AA/MZO $_{\mathrm {nano}}$ , and therefore, the electrostatic condition of MZO $_{\mathrm {nano}}$ is impacted again. Such changes were detected by DGTFT that displayed significant drain current variations. Fourier-transform infrared spectroscopy (FTIR) imaging confirms such successful chemical processes. This MZO DGTFT biosensor with HAFA is promising for potential applications in the detection of FR overexpressed cancer cells.

We demonstrate the negative capacitance thin-film transistor (NC-TFT) on glass substrate using the multifunctional MgZnO (MZO). The Mg0.03Zn0.97O semiconductor layer acts as the TFT channel for stable operation while the Ni-doped MZO, i.e. Ni0.02Mg0.15Zn0.83O (NMZO) serves as the ferroelectric layer in the NMZO/SiO2 stacking gate dielectric structure. The subthreshold swing ( SS ) value is significantly reduced over the reference TFT without ferroelectric layer. The minimum SS value of the NC-TFT reaches 52 mV/dec while the on/off ratio of drain current ${I}_{D}$ reaches $10^{{9}}$ .

The codelivery of drugs at specific optimal ratios to cancer cells is vital for combination chemotherapy. However, most of the current strategies are unable to coordinate the loading and release of drug combinations to acquire precise and controllable synergistic ratios. In this work, we designed an innovative dual-drug backboned and reduction-sensitive polyprodrug PEG-P(MTO-ss-CUR) containing the anticancer drugs mitoxantrone (MTO) and curcumin (CUR) at an optimal synergistic ratio to reverse drug resistance. Due to synchronous drug activation and polymer backbone degradation, drug release at the predefined ratio with a synergistic anticancer effect was demonstrated by in vitro and in vivo experiments. Therefore, the dual-drug delivery system developed in this work provides a novel and efficient strategy for combination chemotherapy.

The CRISPR/Cas9 system is a technology for genome engineering, which has been applied to indel mutations in genes as well as targeted gene deletion and replacement. Here, we describe paired gRNA deletions along the PIGA locus on the human X chromosome ranging from 17 kb to 2 Mb. We found no compelling linear correlation between deletion size and the deletion efficiency, and there is no substantial impact of topologically associating domains on deletion frequency. Using this precise deletion technique, we have engineered a series of designer deletion cell lines, including one with deletions of two X-chromosomal counterselectable (negative selection) markers, PIGA and HPRT1, and additional cell lines bearing each individual deletion. PIGA encodes a component of the glycosylphosphatidylinositol (GPI) anchor biosynthetic apparatus. The PIGA gene counterselectable marker has unique features, including existing single cell level assays for both function and loss of function of PIGA and the existence of a potent counterselectable agent, proaerolysin, which we use routinely for selection against cells expressing PIGA. These designer cell lines may serve as a general platform with multiple selection markers and may be particularly useful for large scale genome engineering projects such as Genome Project-Write (GP-write).

High voltage thin film transistor (HVTFT) built on glass can be used for distributed micro-inverters in the emerging applications, such as the building-integrated photovoltaics (BIPV) and smart glass. We report an HVTFT with a center-symmetric circular configuration which is built on a glass substrate at low temperature. The device is composed of a magnesium zinc oxide (MZO) based channel and a high- $\kappa $ stacked gate dielectric layer of aluminum oxide/silicon dioxide (Al2O3/SiO2). This MZO HVTFT enables a blocking voltage of 900 volts. The high blocking capability is attributed to the lower gate leakage current through the stacked dielectric layer. The device under 10V drain bias shows an on/off current ratio over 109.

Linear polyethylenimine (L-PEI), a standard for nonviral gene delivery, is usually prepared by hydrolysis from poly(2-oxazoline)s. Lately, anionic polymerization of sulfonamide-activated aziridines had been reported as an alternative pathway toward well-defined L-PEI and linear polyamines. However, desulfonylation of the poly(sulfonyl aziridine)s typically relied on harsh conditions (acid, microwave) or used a toxic solvent (e.g., hexamethylphosphoramide). In addition, the drastic change of polarity requires solvents, which keep poly(sulfonyl aziridine)s as well as L-PEI in solution, and only a limited number of strategies were reported. Herein, we prepared 1-(4-cyanobenzenesulfonyl) 2-methyl-aziridine (

We are motivated by a common dilemma that exists when coupling new mobility services with existing transportation systems — the unbalanced nature of operations with regard to efficiency and equity objectives. To address this issue, we study the joint routing and resource allocation problem. Vehicles need to repeatedly and simultaneously choose the route and the resource (i.e., capacity) allocation policy with unknown demand. Efficiency is measured by the total travel distance, and equity is measured by the minimum service level. We propose a two-phase heuristic that solve the learn-and-optimize problem iteratively with small cumulative regret. In Phase 1, the algorithm selects the best demand estimator; In Phase 2, it finds the near optimal operational plan. We examine the effectiveness of the algorithm in a case study from the Miami Dade County that uses idle shuttle vehicles to deliver packages during off-peak hours. The results show that we can improve the minimum service level from 33% to approximately 68% while maintaining small incremental travel costs. This heuristic can provide a general guidance for practitioners and researchers on operating new mobility services in a stochastic network.

Adolescence is a pivotal developmental stage for establishing patterns of behaviors that can last a lifetime. Adolescents’ choices have a significant impact on future opportunities. Education can have tremendous influence on the overall success of an individual. For example, a quality education can affect employability, which indirectly influences economic status; therefore, influencing access to health care and community resources. This literature review will examine the effect of family, peers, and teachers as it relates to adolescent motivation to achieve academically. The authors have investigated adolescent academic motivation from a cross-cultural prospective, exploring four diverse ethnic groups: European Americans, African Americans, Asian Americans, and Hispanic Americans. The research indicates that though developmentally, adolescents share common characteristics, unique dynamics are considered by counselors when addressing academic motivation within ethnic groups.

A soft Poly(Methyl-Meth-Acrylate)(PMMA)-polymerbased V-shaped cantilever probe is proposed for atomic force microscopy (AFM), and the first well-functioning, visually-flat prototype fabricated using a simple, but novel low-cost process and bio-compatible materials is demonstrated. With the prototype, for the first time, AFM nanoindentation was performed on live mammalian cells—human cervical adenocarcinoma cells in liquid. Results obtained using the prototype were compared to those obtained using a commercial Si 3 N 4 cantilever probe. Minimal or no versus severe deformation and/or distortion of the cell membrane was observed when using the prototype versus the Si 3 N 4 probe.

A fully-polymeric nano-electro-mechanical (NEM) relay based on a conductive polymer, Poly(3,4-Ethylenedi oxythiophene):Polystyrene-Sulfonate (PEDOT:PSS) and dielectric polymers is proposed for the first time to enable flexible, transparent, ultralow-power electronics and sensors, and the first functional prototype fabricated using a five-mask low-thermal-budget process is demonstrated. The prototype shows zero off-state leakage current, abrupt on/off switching, complementary switching behavior, and relatively high on/off current ratio. Exploiting the water-absorption behavior of the polymers, the potential use of the relay as a biochemical sensor is also demonstrated.

Larry Golden started the marriage and family therapy program at Our Lady of the Lake University and was founding chair of the Department of Counseling at the University of Texas at San Antonio. He has contributed substantially to the literature in marriage and family counseling. This interview secured his unique perspective on developments in the field.

Micromachined polymer-based cantilever probes have been proposed for atomic force microscopes (AFMs) in order to enable noninvasive, rapid high-resolution topography imaging and mechanical measurements of live biological samples. Polymer-based probes developed to date still consist of a rather stiff cantilever with a relatively high spring constant prone to causing deformation and/or distortion of biological sample surfaces during scanning and a rather blunt tip that limits high-resolution topography imaging. This paper reports the design, fabrication, and characterization of soft polymer-based AFM probes. The proposed probe design and fabrication process utilize an acrylic polymer as the structural material, sequential depositions of low and high viscosity acrylic polymers, and a properly patterned optical reflection coating in order to achieve low effective spring constants (less than 0.01 N/m), relatively small tip radii (as small as 40 nm), and relatively low strain gradient (around 10−4/μm). The fabr...

However, the particularity of the alimentary track restricts the utilization of the current available examine techniques. The upper gastrointestinal tract can be examined by Gastroscopy. The bottom 2 meters makes up the colon and rectum, and can be examined by Colonoscopy. In between, lays the rest of the digestive tract, which is the small intestine characterised by being very long (average 7 meters) and very convoluted. However, this part of the digestive tract lies beyond the reach of the two previously indicated techniques. To diagnose the small intestine diseases, the special imaging techniques like CT scan or MRI are less useful in this circumstance.