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Pulmonary fibrosis is a serious respiratory disease, with limited therapeutic options. Since TGF-β is a critical factor in the fibrotic process, downregulation of this cytokine has been considered a potential approach for disease treatment. Herein, we designed a new lung-targeted delivery technology based on the complexation of polymeric antisense oligonucleotides (pASO) and dimeric human β-defensin 23 (DhBD23). Antisense oligonucleotides targeting TGF-β mRNA were polymerized by rolling circle amplification and complexed with DhBD23. After complexation with DhBD23, pASO showed improved serum stability and enhanced uptake by fibroblasts in vitro and lung-specific accumulation upon intravenous injection in vivo. The pASO/DhBD23 complex delivered into the lung downregulated target mRNA, and subsequently alleviated lung fibrosis in mice, as demonstrated by western blotting, quantitative reverse-transcriptase PCR (qRT-PCR), immunohistochemistry, and immunofluorescence imaging. Moreover, as the complex was prepared only with highly biocompatible materials such as DNA and human-derived peptides, no systemic toxicity was observed in major organs. Therefore, the pASO/DhBD23 complex is a promising gene therapy platform with lung-targeting ability to treat various pulmonary diseases, including pulmonary fibrosis, with low side effects.

Although considerable research has focused on the relationship between working hours and stress, few cross-cultural studies have examined this relationship with job control. This study investigated...

Delivery of apoptosis-associated proteins is an attractive approach to treat cancer, but their large molecular sizes and membrane-impermeability require the use of a suitable delivery carrier. As a versatile drug carrier, mesoporous silica nanoparticles (MSNs) have been utilized to transport a variety of therapeutic molecules. However, the use of MSNs for protein delivery has been limited because their conventionally obtainable pore size (ca. 2–3 nm in diameter) is too small to load large-sized biomolecular cargos. In this article, we present surface erosion of MSNs by hydrolytic degradation as a new strategy to obtain a mesoporous colloidal carrier for effective delivery of a bulky apoptosis-inducible protein, cytochrome c (CYT). A series of physicochemical properties of particles were analyzed before and after the hydrolytic surface erosion of pristine small-pored MSNs and the subsequent CYT loading. The results showed that hydrolytic degradation of MSNs imparts beneficial structural features for CYT loading and release, i.e., enlarged pores (up to ~10 nm in diameter) and roughened surface texture, leading to significantly enhanced intracellular delivery of CYT over conventional small-pored MSNs. The present results may offer a useful insight into silica degradability for tuning the internal/external surface characteristics of MSN-based colloidal particles to open a wide range of biomedical applications.

There is an increased need of drugs with multifunctional properties for visualization of β-amyloid (Aβ) plaques for early diagnosis and treatment of Alzheimer's disease (AD). Curcumin (Cur) is a potent antiamyloid, antiinflammatory, and antiapoptotic natural product that has been used to treat several neurodegenerative diseases, including AD. Curcumin can reduce amyloid burden, rescue neuronal damage, and restore normal cognitive and sensory motor functions in AD. Curcumin is a promising natural product theranostic because it fluoresces and preferentially binds to misfolded Aβ. However, poor water solubility, limited bioavailability, and inability to cross the blood-brain barrier (BBB) limit curcumin use for biological applications. In this work, ultrasmall (~ 11 nm) curcumin encapsulated Pluronic F127 nanoparticles (FCur NPs) were developed and optimized to enhance bioavailability, facilitate circulation in the bloodstream, and improve BBB penetration. We compare BBB crossing ability of FCur NPs and free curcumin using an in vitro BBB model, and we demonstrate brain accumulation following intravenous administration to healthy mice. FCur NPs display 6.5-fold stronger fluorescent intensity in the brain than those from free curcumin. In addition, in vitro comparison with Congo red, a marker for Aβ plaques, revealed that encapsulated curcumin maintains its ability to bind to Aβ plaques. FCur NPs exhibited antioxidant and antiapoptotic activity when compared to free curcumin. The combination of in vitro and in vivo results suggest potential utility of the inexpensive FCur NPs as a theranostic agent for AD.

For efficacious gene therapeutics, cytosolic transport of the endocytosed siRNA is crucial, not to mention a non-toxic delivery carrier composition. In this paper, we report facile achievement of amine-free loading and lysosomolytic delivery of siRNA in an unconventional way by using calcium (Ca2+)-doped mesoporous silica nanoparticles (CMSNs) as a host material along with a pore-loaded endosomal disruptor, chloroquine (CQ). It is demonstrated that CMSNs are capable of direct siRNA loading through Ca2+-incorporated larger pores, as well as efficient release of the loaded siRNA under pH control thanks to the high degradability of the Ca2+-doped silica backbone. A therapeutic performance of siRNA-loaded CMSNs is exemplified in vitro with SKOV3 human ovarian cancer cells, which underwent distinct knockdown of a target anti-apoptotic Bcl-2 gene and consequent apoptosis after incubation with those particles. When co-loaded with CQ, particles were shown to substantially promote the cytosolic delivery of the endocytosed siRNA via endo/lysosomal escape for more effective induction of cell apoptosis. The results suggest that a variety of target-genes can be applicable to the presented delivery system on demand, providing a highly versatile feature of our nanocarrier for many gene-therapeutic applications with higher efficacy.

This study aims to develop a reservoir operation rule adding downstream environmental flow release (EFR) to the exclusive use of irrigation water supply (IWS) from agricultural reservoirs through canals to rice paddy areas. A reservoir operation option was added in the Soil and Water Assessment Tool (SWAT) to handle both EFR and IWS. For a 366.5 km2 watershed including three agricultural reservoirs and a rice paddy irrigation area of 4744.7 ha, the SWAT was calibrated and validated using 21 years (1998–2018) of daily reservoir water levels and downstream flow data at Gongdo (GD) station. For reservoir water level and streamflow, the average root means square error (RMSE) ranged from 19.70 mm to 19.54 mm, and the coefficient of determination (R2) and Nash–Sutcliffe efficiency (NSE) had no effect on the improved SWAT. By applying the new reservoir option, the EFR amount for a day was controlled by keeping the reservoir water level up in order to ensure that the IWS was definitely satisfied in any case. The downstream mean wet streamflow (Q95) decreased to 5.70 m3/sec from 5.71 m3/sec and the mean minimum flow (Q355) increased to 1.05 m3/sec from 0.94 m3/sec. Through the development of a SWAT reservoir operation module that satisfies multiple water supply needs such as IWR and EFR, it is possible to manage agricultural water in the irrigation period and control the environmental flow in non-irrigation periods. This study provides useful information to evaluate and understand the future impacts of various changes in climate and environmental flows at other sites.

Since oxidative stress has been recognized as a major factor contributing to the progression of several neurodegenerative disorders, reactive oxygen species (ROS) including superoxide have received great attention as a representative molecular marker for the diagnosis of Alzheimer's disease (AD). Here, superoxide-sensitive fluorogenic molecular probes, benzenesulfonylated resorufin derivatives (BSRs), were newly devised for optical bioimaging of oxidative events in neurodegenerative processes. BSRs, fluorescence-quenched benzenesulfonylated derivatives of resorufin, were designed to recover their fluorescence upon exposure to superoxide through a selective nucleophilic uncaging reaction of the benzenesulfonyl cage. Among BSRs, BSR6 presented the best sensitivity and selectivity to superoxide likely due to the optimal reactivity matching between the nucleophilicity of superoxide and its electrophilicity ascribed to the highly electron-withdrawing pentafluoro-substitution on the benzenesulfonyl cage. Fluorescence imaging of inflammatory cells and animal models presented the potential of BSR6 for optical sensing of superoxide in vitro and in vivo. Furthermore, microglial cell (Bv2) imaging with BSR6 enabled the optical monitoring of intracellular oxidative events upon treatment with an oxidative stimulus (amyloid beta, Aβ) or the byproduct of oxidative stress (4-hydroxynonenal, HNE).

This article proposes a deep-learning-based underground object classification technique that uses triplanar ground-penetrating radar images consisting of B-, C-, and D-scan images. Although multichannel ground-penetrating radar (GPR) systems provide three-dimensional (3-D) information about underground objects, there is currently no suitable technique available for processing 3-D data as opposed to 2-D images. In this article, a triplanar deep convolutional neural network technique is proposed for use in processing 3-D GPR data for use in automatized underground object classification. The proposed method was validated experimentally using 3-D GPR road scanning data obtained from urban roads in Seoul, South Korea. In addition, the classification performance of the method was compared to that of a conventional method that uses only B-scan-images. The results of the validation and comparison tests reveal that the classification performance of the proposed technique is notably better than that of the conventional B-scan-image-based method and that its use results in decrease misclassification ratios.

Self-assembly of peptides containing both l- and d-isomers often results in nanostructures with enhanced properties compared to their enantiomeric analogues, such as faster kinetics of formation, higher mechanical strength, and enzymatic stability. However, occurrence and consequences of the heterochiral assembly in the cellular microenvironment are unknown. In this study, we monitored heterochiral assembly of amphiphilic peptides inside the cell, specifically mitochondria of cancer cells, resulting in nanostructures with refined morphological and biological properties owing to the superior interaction between the backbones of opposite chirality. We have designed a mitochondria penetrating tripeptide containing a diphenyl alanine building unit, named as Mito-FF due to their mitochondria targeting ability. The short peptide amphiphile, Mito-FF co-assembled with its mirror pair, Mito-ff, induced superfibrils of around 100 nm in diameter and 0.5-1 μm in length, while enantiomers formed only narrow fibers of 10 nm in diameter. The co-administration of Mito-FF and Mito-ff in the cell induced drastic mitochondrial disruption both

Objective: The purpose of this study was to evaluate the clinical outcome of surgical decompression and rehabilitation therapy in dogs with thoracolumbar intervertebral disk herniation (IVDH). Materials and Methods: After surgery, physiotherapeutic rehabilitation was performed by a combination of electrotherapy, infrared therapy, training for standing, deep tendon reflex, and aquatic treadmill exercise. A total of 186 dogs were selected from the hospital records and included in two groups: the rehabilitated group (RG, n = 96) and non-rehabilitated group (NRG, n = 90). Dogs in each group were subdivided into three groups based on a pre-operative clinical severity grading system and those in grades 24 were included in this study. Post-operative neurologic functions, unassisted standing, walking, and the success rate of both groups were evaluated and compared Results: Overall, 86.46% (83/96) of dogs had a successful neurologic outcome in the RG group, which was significantly (p < 0.01) higher than the NRG group 52.22% (47/90). Interestingly, the success rate differed when the preoperative grading system was considered. The success rates of grades 2, 3, and 4 were 97.14% (34/35), 97.33% (42/45), and 43.75% (7/16), respectively, in the rehabilitated groups, whereas in the non-rehabilitated groups, success rates were 82.35% (28/34), 51.85% (14/27), and 17.24% (5/29), respectively. The differences in success rates among the groups according to grading were 14.79%, 41.48%, and 26.51%, respectively, indicating that the proposed rehabilitation therapy is remarkably advantageous for increasing the success rate. Conclusion: Rehabilitation therapy after surgical decompression of thoracolumbar IVDH improves neurologic functions and increases the success rate, especially when the preoperative pathological condition is severe. [J Adv Vet Anim Res 2019; 6(3.000): 394-402]

Dual-emissive systems showing color-specific photoswitching are promising in bioimaging and super-resolution microscopy. However, their switching efficiency has been limited because a delicate manipulation of all the energy transfer crosstalks in the systems is unfeasible. Here, we report a perfect color-specific photoswitching, which is rationally designed by combining the complete off-to-on fluorescence switching capability of a fluorescent photochromic diarylethene and the frustrated energy transfer to the other fluorescent dye based on the excited-state intramolecular proton transfer (ESIPT) process. Upon alternation of UV and visible light irradiations, the system achieves 100% switching on/off of blue emission from the diarylethene while orange emission from the ESIPT dye is unchanged in the polymer film. By fabricating this system into biocompatible polymer nanoparticles, we demonstrate microscopic imaging of RAW264.7 macrophage cells with reversible blue-color specific fluorescence switching that enables super-resolution imaging with a resolution of 70 nm., Photoswitchable nanoparticles can be used for selective imaging in biological systems but usually have only one color. Here the authors develop a two-color fluorescent emissive system that allows full on-off switching of one component color of the system while the other color is unaffected, which has implications for super-resolution imaging.

For siRNA therapeutics, the use of positively charged amine-rich delivery vectors has been indispensable, but the amine-associated toxicological responses remain a clinical conundrum. Herein, we report a new strategy of harnessing a biocompatible, biodegradable and well-tolerated nanomaterial as an amine-free non-positive carrier for siRNA delivery. By employing mesoporous silica nanoparticles (MSNs) as a biocompatible vector, siRNA is loaded nonconventionally through calcium ion (Ca2+)-mediated interconnection (calcium gluing) between phosphates of siRNA and surface silicates of MSNs in a sequential, cumulative and directional way. The "one-pot" gluing process utilizing endogenously abundant Ca2+ ions offers a simple but robust means of siRNA loading on the non-positive bare surface of MSNs without the aid of multi-amine functionalization, and thus minimizes the risk of amine-associated cytotoxicity and immunogenicity while keeping the intrinsic biocompatibility of MSNs. As demonstrated with loading of an anticancer siRNA, this strategy allows stable in vivo delivery of siRNA for targeted gene silencing, and capitalizes on the unique structural versatility of MSNs by simultaneously delivering a pore-loaded chemodrug to synergistically enhance the treatment efficacy. Therefore, the Ca2+-glued MSNs as a general siRNA carrier platform provide a less toxic, less laborious and more utilitarian delivery tool for more effective and safer siRNA therapeutics.

Purpose The purpose of this paper is to investigate gender differences in the relationships between job demands, job control and distress with the moderation effects of family status (i.e. marriage and parenthood) in the patriarchal cultural context of Korea. Design/methodology/approach The authors formulated hypotheses on the grounds of stress and role theories and tested them using a hierarchical regression analysis. A sample of 403 Korean employees (230 males; 173 females) was used for the analysis. Findings Family status moderated the relationship between job demands and distress for both males and females, whereas family status significantly moderated the effect of job control on distress for only males. Regardless of gender, marriage and parenthood were associated with distress affected by job demands, while only males exhibited significant distress in interactions between family status and job control. Originality/value This exploratory study is one of few that explicitly addresses the concepts of the job demands-control model dealing with the unique characteristics of demographic groups. By incorporating data from the single, the married and parents, this study identified applications of the conservation of resources and role theory for various family statuses in a non-Western culture. Particularly, this study is meaningful in that it highlighted the impacts of family roles on distress that can be observed in any culture, but is salient in a highly hierarchal, patriarchal and work-centered culture, like Korea.

Despite the wide use of the term workaholism, universally defined as an addiction to work, there is little consensus on this concept and how people become workaholics. This article critically reviews the workaholism literature to reframe the concept of workaholism and to provide implications for human resource development (HRD). Through a literature review, four perspectives were found based on assumptions about behavioral motivation. The motivation and addiction processes in workaholism are discussed, focusing on the theories and characteristics of the workplace. The gaps and omissions are identified in the reviewed research, and a workaholism framework is suggested that emphasizes contextual and behavioral inclusiveness. This review contributes to literature on workaholism by illuminating current divergent opinions on workaholism and guiding future research. The recommendations can also enhance the practical development of individuals and organizations that currently or potentially face excessive work issues.

In theranostics, peptide-based platforms have widely been exploited owing to their unique biological functions and chemical versatilities. As a tumor-homing ligand, internalizing RGD peptide (iRGD), composed of a tumor-targeting sequence (RGD) and a cell-penetrating C-end Rule (CendR) motif, is known to facilitate the tumor-specific delivery of payloads that are covalently conjugated on its N-terminal fragment or co-administered without any covalent linkages. However, theranostic uses of the iRGD-based platform remain in its infancy with its full potential unexplored; for instance, detailed mechanism of iRGD fragmentation during internalization, strategies for the tumor-specific release of payloads from iRGD and the role of the C-terminal iRGD fragment in delivery have yet to be revealed. In this study, we designed a dual-channel fluorescent cyclic iRGD (TAMRA-iRGDC-Cy5.5) to track each of the N- and C-terminal fragments separately during the tumor internalization process. It turned out that both fragments undergo translocation into cancer cells together and are localized within endosomal-lysosomal compartments. The resulting co-internalization of both iRGD fragments allowed us to develop a new theranostic peptide platform (Cy5.5-iRGDC-Pt(IV)) by conjugating a fluorescent dye and a cisplatin prodrug on each terminus of cyclic iRGD for simultaneous cancer-targeted imaging and therapy. Compared to a control peptide having a non-iRGD sequence, the Cy5.5-iRGDC-Pt(IV) did not only provide a better tumor imaging contrast but also induced tumor-specific apoptosis leading to efficacious tumor suppression. Besides the outstanding cancer imaging and therapeutic performance, the Cy5.5-iRGDC-Pt(IV) revealed negligible systemic toxicity, holding potential to be applied for theranostic uses.

Microbubbles are clinically used as an imaging agent for contrast-enhanced ultrasound image. Beyond the preformed microbubbles, nanoscale gas-generating chemical systems that are capable of stimulu...

Deposition of crystalline titanium dioxide (TiO2) on gold nanostructures has been considered as a promising strategy for near-infrared (NIR) light-activated photocatalysis. A typical route comprises pre-deposition of amorphous TiO2 on the gold surface and its ensuing crystallization by high-temperature annealing. Such condition, however, is not compatible with highly plasmonic but thermally unstable sharp-tipped gold nanostructures, causing structural disruption and plasmonic decline. Herein, we report a hybridization method excluding high-temperature annealing, i.e., direct deposition of anatase TiO2 onto sharp-tipped gold nanobipyramid (Au NBP/a-TiO2) with conserving their morphology without agglomeration via low-temperature hydrothermal reaction. In addition to keeping the plasmonic photothermal performance, Au NBP/a-TiO2 exhibits enhanced photocatalytic generation of reactive oxygen species in response to the NIR excitation, evidencing the efficient injection of hot electrons from the Au NBP to the anatase shell. In vitro and in vivo studies revealed that the efficient photocatalytic/photothermal responses of Au NBP/a-TiO2, along with dispersion stability in biological media and minimal toxicity, hold potential for synergistic photothermal and photodynamic therapy. We believe that the low-temperature synthetic method introduced here might offer a general way of crystalline deposition of TiO2 on a variety of gold nanostructures, broadening the spectrum of NIR-responsive photocatalytic hybrid nanostructures for biomedical applications.

Molecular design concepts are described for the preparation of azobenzene polymers capable of showing a tunable response to the rat liver microsome-induced side-chain self-immolation process under hypoxic conditions. It is shown that azobenzene nuclei carrying a donor/acceptor substitution pattern are the most active system towards the enzymatically triggered azobenzene cleavage reaction (half-life = t1/2 = 6 min). Their activity is followed by azobenzene nuclei carrying donor/donor (t1/2 = 20 min), electronically non-substituted (t1/2 = 72 min), and acceptor (t1/2 = 78 min) systems. This trend is preserved when a chemical stimulus, sodium dithionite, replaces the biological reducing conditions and demonstrates generality of the findings, and their potential in proteomics procedures. Furthermore, the established design concepts also permit for variation in polymer structure and topology while still maintaining the electronic substitution pattern. The steric constraints or the inherent character (hydrophilic/hydrophobic) of the azobenzene, however, does not alter the fate of the scission reaction. In all cases, the self-immolation process allows the polymer chain to convert from a chemically neutral to a cationic state. This structural transformation can be used as an activation mechanism (in vitro) to gain entry into cells through electrostatic interactions with the oppositely charged cell membrane and to deliver an anticancer drug. Interestingly, polymer structure now plays a role and bottlebrush-like copolymer show higher selectivity and faster cellular uptake. Finally, the best performing polymer allows for structural modulation into a fluorescent imaging probe. In vivo application to mice suffering from colitis confirms accumulation of the imaging probe in the diseased colon and cecum parts of the body where the endogenous microbial flora is known to produce the activation enzyme. This work, therefore, establishes general principles for the molecular design of biologically activatable and cleavable azobenzene-based polymeric scaffolds applicable to delivery and imaging applications.

This study used Soil and Water Assessment Tool (SWAT) to investigate the impacts of groundwater abstraction and forest growth on the watershed hydrology of Geum River basin (9,645.5 km2), South Korea. Groundwater abstraction (GA) and forest growth (FG) data from 1976 to 2015 (1980s;1976~1985, 1990s; 1986~1995, 2000s; 1996~2005, 2010s;2006~2015) were prepared with 10-year interval as SWAT input data, respectively. SWAT was calibrated (2006~2015) using daily observation data from two multipurpose dams and three multifunction weirs. The dam and weir calibration result showed coefficient of determination (R2) of 0.78, 0.81, Nash-Sutcliffe efficiency (NSE) of 0.79, 0.76, root mean square error (RMSE) of 1.96 mm/day, 0.55 mm/day, and PBIAS of -5.48%, 8.56%, respectively. The SWAT ran at each decade using corresponding GA and FG information under the same weather condition of the 2010s to evaluate the impact of GA and FG on hydrologic cycle. Influenced by both GA and FG, the streamflow at the watershed outlet showed the decrease of 1.3% (10.1 mm/year), 4.4% (34.2 mm/year), and 7.8% (60.3 mm/year) in the 1990s, the 2000s, and the 2010s, respectively. The hydrologic response of surface runoff, lateral flow, groundwater flow, and soil moisture showed decreasing trend while evapotranspiration and groundwater recharge showed increasing trend. GA imposed bigger influence on the spatial and temporal loss of streamflow than FG. Especially, it was discovered that the agricultural water use from groundwater was the most influential factor that has decreased total runoff in the target watershed for the last four decades.

Hardware performance counters are special registers on processors that track the hardware activities. While the performance counter data are useful for many applications, there are challenges in efficiently collecting many event statistics simultaneously, due to the limited number of performance counters on chip. We propose an efficient hardware performance counter design that uses approximate-counting algorithms to improve the number of events tracked on-chip without incurring significant memory overhead. These counters are more memory efficient because they increment counts according to a dynamic probability and approximate the exact counts. Compared with multiplexed hardware performance counters, our approximate hardware counters have a statistically provable memory-accuracy trade-off and are entirely managed in hardware.

The general practice of photodynamic therapy (PDT) comprises repeated multiple sessions, where photosensitizers are repeatedly administered prior to each operation of light irradiation. To address potential problems arising from the total overdose of photosensitizer by such repeated injections, we here introduce an internalizing RGD peptide (iRGD) derivative (Ppa-iRGDC-BK01) that self-aggregates into an injectable single-component supramolecular depot. Ppa-iRGDC-BK01 is designed as an in situ self-implantable photosensitizer so that it forms a depot by itself upon injection, and its molecular functions (cancer cell internalization and photosensitization) are activated by sustained release, tumor targeting, and tumor-selective proteolytic/reductive cleavage of the iRGD segment. The experimental and theoretical studies revealed that when exposed to body temperature, Ppa-iRGDC-BK01 undergoes thermally accelerated self-assembly to form a supramolecular depot through the hydrophobic interaction of the Ppa pendants and the reorganization of the interpeptide hydrogen bonding. It turned out that the self-aggregation of Ppa-iRGDC-BK01 into a depot exerts a multiple-quenching effect on the photosensitivity to effectively prevent nonspecific phototoxicity and protect it from photobleaching outside the tumor, while enabling autonomous tumor rephotosensitization by long sustained release, tumor accumulation, and intratumoral activation over time. We demonstrate that depot formation through a single peritumoral injection and subsequent quintuple laser irradiations at intervals resulted in complete eradication of the tumor. During the repeated PDT, depot-implanted normal tissues around the tumor exhibited no phototoxic damage under laser exposure. Our approach of single-component photosensitizing supramolecular depot, combined with a strategy of tumor-targeted therapeutic activation, would be a safer and more precise operation of PDT through a nonconventional protocol composed of one-time photosensitizer injection and multiple laser irradiations.

A novel conjugated Schiff base-based chemosensor DAP, N′-((1E,2E)-3-(4-(dimethylamino)phenyl)allylidene)-3-nitrobenzohydrazide, has been synthesized. DAP showed significant selectivity toward mercury ion by color change of pale yellow to orange. Detection limit was 0.11 μM, which is lower than the value (2.48 μM) recommended by Health Canada. DAP could recognize and quantify mercury ion in real water samples. The binding mode of DAP and Hg2+ was demonstrated, based on Job plot, IR spectra and ESI-MS. A novel conjugated Schiff base-based chemosensor DAP was developed for the detection of mercury ion by color change of pale yellow to orange. DAP with low detection limit (0.11 μM) could quantify mercury ion in real water samples.

The design of peptide-based therapeutics is generally based on the replacement of l-amino acids with d-isomers to obtain improved therapeutic efficiency. However, d-isomers are expensive and frequently induce undesirable immune responses. In the present work, we demonstrate that an intra-mitochondrially self-assembling amphiphilic peptide exhibits analogous activity in both d- and l-isomeric forms. This outcome is in contrast to the general observation considering higher therapeutic efficiencies of d-isomers compared with l-analogues. This suggests that l-peptides overcome proteolytic degradation during intra-mitochondrial self-assembly both in vitro and in vivo.

Current theranostic approaches in cancer therapy demand delivery systems that can carry multiple drugs or imaging agents in a single nanoplatform with uniform biodistribution and improved target specificity. In this study, we have developed amphiphilized poly(ethyleneimine) nanoparticles (aPEI NPs) as a versatile multi-cargo delivery platform. The aPEI NPs were engineered to have the loading capacity for both hydrophobic molecules and negatively charged hydrophilic colloidal cargos through amphiphilic modification, i.e., octadecylation and subsequent PEGylation of poly(ethyleneimine). In the aqueous phase, the resulting aPEIs underwent amphiphilic self-assembly into spherical nanoparticles whose structure is constituted of the hydrophobic core with the positively charged surface and the hydrophilic neutral corona. The high degree of PEGylation resulted in the tiny colloidal size (

Triggered cellular uptake of a synthetic graft copolymer carrying an anticancer drug is achieved through self-immolation of the side-chain azobenzene groups. In this concept, the conjugate is initially chemically neutral and does not possess cell-penetrating function. However, upon cleavage of the azobenzene moieties, a cascade process is initiated that ultimately reveals an ammonium cation in the vicinity of the polymer backbone. Hence, self-immolation results in the transformation of the neutral polymer chain into a polycation. This structural transformation allows the conjugate to be taken up by the cancer cells through favorable electrostatic interactions with the negatively charged phospholipid components of the cell membrane. Once inside the cells, the polymer releases covalently attached doxorubicin in a pristine form through a low pH activated release mechanism. The significance of this approach lies in the sensitivity of the azobenzene group to hypoxic conditions and to the enzyme azoreductase that is secreted by the microbial flora of the human colon and suggests a pathway to targeted drug delivery applications under these conditions.

Two new cyanine-based fluorescent probes 1 and 2 have been developed. Probe 1 bears two cyanine units in a single molecule, and probe 2 contains a bis(trifluoromethyl)benzenethiol moiety. Both are non-fluorescent. The addition of intracellular glutathione (GSH) significantly enhanced the NIR fluorescence of the two probes. Both probes were used to image varying amounts of GSH in living cells. In tumor bearing mice, the in vivo fluorescence intensity of both probes was higher in tumors, where GSH is overexpressed, than in normal tissues. These results suggest that these new fluorogenic probes have potential for GSH-targeting diagnostic imaging.

We document fragile demand for socially responsible investments (SRI) by retail mutual fund investors. Using COVID-19 as an economic shock, we show funds with higher sustainability ratings experienced sharper declines in retail flows during the pandemic, controlling for fund characteristics. Contrasting resilience of institutional SRI fund flows, sharper declines in retail SRI flows to funds marketed in economies hit hardest by COVID-19, recovering SRI fund flows during reopening periods, and falling internet search traffic on sustainability during the pandemic indicate a high sensitivity of demand for SRI by retail investors with respect to income shocks.

Although a continual nationwide drive to develop human resources has enabled Korea to achieve rapid economic growth, Korean society has recently faced several emerging social and economic issues at the national, organizational, and individual levels including a higher unemployment rate, a skill mismatch between job seekers and the market, and the required additional cost of reeducation. To address these issues, the Korean government and private organizations have cooperated to create a new government-private sector collaboration model called a work-learning dual system (WLDS). Our study explored how WLDS functions in the workplace and its influence on learning and performance outcomes at various levels through interviews with multiple stakeholders and documents collected from the organizations that are responsible for the implementation of WLDS. We interviewed twelve employees and analyzed internal and external documents. The findings were presented within the key dimensions of talent development by Garavan, Carbery, and Rock (Eur J Train Dev 36(1):5–24, 2012), and the outcomes were specified from multiple stakeholders at various levels. WLDS provides important implications not only for research on talent development but also HRD practices through public-private partnerships.

This article attempts to (a) identify leadership challenges and opportunities among Korean and Indian women, and (b) explore how women’s leadership differs by generation in India and Korea. We prov...

This article provides an overview of the history and current status of graduate and undergraduate Human Resource Development (HRD) programs at the University of Minnesota. The HRD program at the UM...

The Problem Although a continual nationwide drive to develop human resources has enabled Korea to achieve rapid economic growth, Korean society has recently faced several emerging social and economic issues at the national, organizational, and individual levels including a higher unemployment rate, a competency mismatch between the skills new employees possess and what employers require, and the required additional cost of reeducation. To address these issues, the Korean government and private organizations have cooperated to create a new government-private sector collaboration model called a work and learning dual system (WLDS). The Solution Our study explored how WLDS functions in the workplace and its influence on learning and performance outcomes at various levels through interviews with multiple stakeholders and documents collected from the organizations responsible for the implementation of WLDS. Twelve employees in the organizations were interviewed, and internal and external documents were analyzed. The findings were presented within the key dimensions of talent development by Garavan, Carbery, and Rock, and the outcomes were specified from multiple stakeholders at various levels. WLDS provides important implications for research on not only talent development but also human resource development (HRD) practices through public–private partnerships. The Stakeholders The findings offer several important practical insights for multiple stakeholders. HRD practitioners and policy makers in emerging markets can learn from this type of combined talent development program with structured off- and on-the-job-training. In terms of national HRD, they can strategically and systematically improve their talent development programs and cooperate with relevant governmental agencies.

Objective: The aim of this paper is to report surgical correction of ureteric rupture due to stenosis induced secondary to accidental injury by placing nephrovesical subcutaneous ureteric bypass in a dog and postoperative long term outcomes. Materials and methods: Imaging techniques revealed multiple bone fractures as well as left proximal ureter injury. The all bone fractures were corrected using standard techniques while left proximal ureter injury was treated as conservation medical therapy. One month later, contrast media were also found in proximal ureter and abdomen which indicated ureter rupture. This rupture was corrected surgically by nephrovesical subcutaneous ureteric bypass (SUB) under fluoroscopy guidance. Results: First day after accidental injury, the serum BUN and CRE were 10.7 mg/dL and 0.9 mg/dL, respectively which indicated kidney injury but by conservative therapy these parameters were lowered gradually. On the 5 th day after considering these parameters, the dog was judged normal. However, on the 31 st day BUN and CRE were 14.3 mg/dL and 0.8 mg/Kg, respectively. The Doppler ultrasonography revealed hydroneprosis, proximal ureter stenosis and high resistive index (0.72±0.02) in the renal arcuate artery indicating renal abnormalities due to ureter obstruction. On re-examination by radiography after one month postoperatively, revealed that patency of the device and normal renal function. The dog was clinically normal with normal urination and no complications were found 6 months postoperatively. Conclusion: In view of the above findings, it is suggested that the SUB system can be a better alternative to preserve the kidney in non-reparable traumatic ureteral damage in dogs. http://doi.org/10.5455/javar.2018.e266

Here, we describe a rapid and efficient synthetic method of peptide-conjugated perylene diimide (P-PDI) using solid-phase peptide synthesis (SPPS). Due to severe insolubility of perylene dianhydride (PDA) as a starting material of perylene diimide (PDI), PDA was initially conjugated with amino acids to obtain soluble PDI derivatives. Target peptides were synthesized on a 2-chlorotrityl chloride resin using the SPPS method and then conjugated with the amino acid-appended PDI. Various conditions such as loading levels, reaction times and solvents were optimized for introducing the peptides to both sides of the amino acid-appended PDI. The final P-PDI was obtained with a maximum yield of 80% in 12 h. Its singlet oxygen-derived phototoxicity on cells was confirmed, which could be applicable to photodynamic therapy.

This article presents a method for evaluating the support condition of bridges. This is done by representing the aging and deteriorated supports as rotation springs with equivalent spring constants. Sensitivity analysis was performed to obtain a relationship between the spring constant and the bridge responses (deflections/slopes). From this relationship, measured bridge responses can be used to estimate the equivalent spring constants through interpolation. Numerical analysis was performed to check whether the method can be used to calculate equivalent spring constants. Then, the method was verified by performing laboratory tests on a scale model bridge and field test on an actual bridge. In both tests, spring constants were estimated using the proposed method and then verified by calculating the displacements and frequencies and comparing them to the measured values.