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Chemically synthesized, small peptides that bind with high affinity and specificity to CD8-expressing (CD8+) tumor-infiltrating T cells, yet retain the desirable characteristics of small molecules, hold valuable potential for diagnostic molecular imaging of immune response. Here, we report the development of 18F-labeled peptides targeting human CD8α with nanomolar affinity via the strain-promoted sydnone-alkyne cycloaddition with 4-[18F]fluorophenyl sydnone. The 18F-sydnone is produced in one step, in high radiochemical yield, and the peptide labeling proceeds rapidly. A hydrophilic chemical linker results in a tracer with favorable pharmacokinetic properties and improved image contrast, as demonstrated by in vivo PET imaging studies.

Objective: Chemotherapy-induced nausea and vomiting (CINV) are common with doxorubicin-cyclophosphamide (AC) chemotherapy. Recommended antiemetic regimens incorporate neurokinin-1 receptor antagonist (NK1RA), 5-hydroxytryptamine type-3 receptor antagonist (5HT3RA), corticosteroid, and dopamine antagonists. This post-hoc analysis compared results of 3 prospective antiemetic studies conducted among Chinese breast cancer patients who received (neo)adjuvant AC, in order to identify optimal antiemetic prophylaxis. Methods: A total of 304 patients were included: Group 1, ondansetron/dexamethasone (D1); Group 2, aprepitant/ondansetron/dexamethasone (D1); Group 3, aprepitant/ondansetron/dexamethasone (D1–3); Group 4, aprepitant/ondansetron/dexamethasone (D1–3)/olanzapine; and Group 5, netupitant/palonosetron/dexamethasone (D1–3). Antiemetic efficacies of Groups 3, 4, and 5 during cycle 1 of AC were individually compared with Group 1. In addition, emesis outcomes of patients in Groups 3 and 5, and those of Groups 2 and 3, were compared. Results: When comparing efficacies of a historical doublet (5HT3RA/dexamethasone) with triplet antiemetic regimens (NK1RA/5HT3RA/dexamethasone) with/without olanzapine, complete response (CR) percentages and quality of life (QOL) in overall phase of cycle 1 AC were compared between Group 1 and the other groups: Group 1 vs. 3, 41.9% vs. 38.3% (P = 0.6849); Group 1 vs. 4, 41.9% vs. 65.0% (P = 0.0107); and Group 1 vs. 5, 41.9% vs. 60.0% (P = 0.0460). Groups 4 and 5 achieved a better QOL. When comparing netupitant-based (Group 3) with aprepitant-based (Group 5) triplet antiemetics, CR percentages were 38.3% vs. 60.0%, respectively (P = 0.0176); Group 5 achieved a better QOL. When comparing 1 day (Group 2) vs. 3 day (Group 3) dexamethasone, CR percentages were 46.8% and 38.3%, respectively (P = 0.3459); Group 3 had a worse QOL. Conclusions: Aprepitant-containing triplets were non-superior to doublet antiemetics. Netupitant-containing triplets and adding olanzapine to aprepitant-containing triplets were superior to doublets. Netupitant/palonosetron/dexamethasone was superior to aprepitant/ondansetron/dexamethasone. Protracted administration of dexamethasone provided limited additional benefit.

High-performance pentace organic thin-film transistors (OTFTs) with room-temperature-processed Hf0.13 La0.87O as gate dielectric and Pd as gate electrode have been fabricated on both rigid Si and flexible polymide (PI) substrates. The OTFT on PI (Si) can achieve a high carrier mobility of 10.3 cm2V−1s−1 (12.5 cm2V−1s−1), and has a negligible hysteresis of −0.17 V (−0.08 V), small sub-threshold swing of 0.12 V/dec (0.11 V/dec) and low threshold voltage of −0.65 V (−0.86 V). After the devices have been exposed to the air for 30 days without encapsulation, their carrier mobilities degrade by less than 10%, indicating that the devices have good stability in the air.

Per- and polyfluoroalkyl substances (PFASs) are a class of environmentally persistent industrial compounds that disrupt various metabolic pathways. Among the protein receptors to which PFASs bind, the human pregnane X receptor (hPXR) is found to be a host for a variety of long- and short-chain PFASs that lead to its overactivation. Overactivation of hPXR is linked to potential endocrine disruption, oxidative stress, hepatic steatosis, and adverse drug interactions. In this study, molecular dynamics (MD) is used to study the binding between hPXR and a number of PFAS compounds, including alternatives whose activity on hPXR has not been experimentally tested. This is the first-time MD is used to study the interactions between PFASs and hPXR, showing how relative binding free energies of PFASs relate to hPXR agonism. Binding free energy calculations, hydrogen bond analysis, per-residue decomposition calculations, and alanine scanning studies are done to provide further insight. Activities on hPXR for several short-chain and alternative PFAS compounds to long-chain PFASs that have yet to be reported will also be considered. These short-chain and alternative species include perfluorobutane sulfonic acid (PFBS), Gen-X (trade name for 2,3,3,3-tetrafluoro-2-heptafluoropropoxy propanoic acid), ADONA (trade name for 4,8-dioxa-3H-perfluorononanoic acid), and 6:2 fluorotelomer carboxylic acid (6:2 FTCA). The study shows key aspects of PFAS recognition on the hPXR, the link between PFAS binding to hPXR and the hPXR activity change observed upon the PFAS exposure, and the potential effects of alternative PFASs on hPXR activity.

An organic thin-film transistor (OTFT)-based hydrogen sensor with palladium (Pd) source/drain (S/D) electrodes as the sensing medium is fabricated, and the effects of operating temperature on its sensing performance are investigated. The sensor exhibits a current decrease upon exposure to hydrogen, and a rapid and reversible H2 response upon the introduction and removal of hydrogen is observed. Heating the sensor changes its electrical characteristics and thus its hydrogen sensitivity. It is found that the effects of temperature on the hydrogen solubility and sticking coefficient of the Pd electrodes are important factors determining the sensitivity at a high temperature of 90 °C, but the temperature dependences of carrier mobility and threshold voltage of the OTFT become dominant at lower temperatures of 60 °C and 30 °C. Moreover, shorter response time is realized at higher operating temperature because higher temperature accelerates the diffusion of H atoms in the Pd electrode. However, the recovery time does not show the same trend due to a reconstruction of the pentacene layer at high operating temperature.

The protein catalyzed capture agent (PCC) method is a powerful combinatorial screening strategy for discovering synthetic macrocyclic peptide ligands, called PCCs, to designated protein epitopes. The foundational concept of the PCC method is the use of in situ click chemistry to survey large combinatorial libraries of peptides for ligands to designated biological targets. State-of-the-art PCC screens integrate synthetic libraries of constrained macrocyclic peptides with epitope-specific targeting strategies to identify high-affinity (

This study aimed to examine how probiotics affect autophagy and interleukin-1β (IL-1β) expression in Salmonella-infected intestinal epithelial cells (IECs). The original Caco-2 cells and ATG16L1 siRNA-transfected Caco-2 cells were pretreated or left untreated with probiotics, including Lactobacillus rhamnosus GG (LGG; ATCC 53103) and Bifidobacterium longum (BL; ATCC15697), and these cells were infected with wild-type Salmonella enterica serovar Typhimurium (S. Typhimurium strain, SL1344). Western blot analysis was used to detect the conversion of microtubule-associated proteins 1A/1B light chain 3B (LC3)-I to LC3-II. Immunofluorescence was used to analyse LC3+ autophagosomes. Membrane proteins were analysed by western blot for protein (ATG16L1, NOD2), and total RNA by RT-PCR for mRNA expression [ATG16L1, vitamin D receptor (VDR)]. We demonstrated that probiotics enhanced both VDR mRNA, and nucleotide-binding oligomerisation domain-containing protein 2 (NOD2) and autophagy-related protein 16-like 1 (ATG16L1) protein expression. The enhanced expression resulted in autophagic LC3-II protein expression and formation of LC3 punctae in Salmonella-infected Caco-2 cells. It was observed that ATG16L1 siRNA could attenuate this mechanism, and ATG16L1-mediated IL-1β expression was suppressed by probiotics. These results suggest that probiotics enhance autophagy and also suppress inflammatory IL-1β expression in Salmonella-infected IECs via membrane ATG16L1 protein expression. Probiotics may enhance autophagic clearance of Salmonella infection and modulate inflammatory responses to protect the hosts. Hence, we can assume that probiotics could treat infectious and autoimmune diseases through mechanisms involving ATG16L1.

Different lanthanide oxynitrides (LaON, NdON, CeON, and GdON) are applied as the interfacial passivation layers (IPLs) for GaAs metal–oxide–semiconductor (MOS) capacitors with HfO2 as the gate dielectric. The measurement results show that all the IPLs can improve the quality of the HfO2/GaAs interface by suppressing the in-diffusions of Hf and O toward the GaAs surface from the gate dielectric, and thus the growth of unstable Ga/As oxides as proved by the atomic force microscope (AFM) and X-ray photoelectron spectroscopy (XPS) analysis. Among the IPLs, the LaON IPL shows the best passivating effect on the GaAs surface, and so the relevant MOS capacitor exhibits the lowest interface-state density ( ${8} \times {10}^{{11}}$ cm−2eV−1), smallest flat-band voltage (0.65 V), negligible hysteresis (33 mV), lowest gate leakage ( ${1.08} \times {10}^{-{{6}}}$ A/cm2 at ${V}_{\text {fb}} + {1}$ V), smallest frequency dispersion (2.85% in accumulation region), and good high-field reliability. NdON exhibits slightly less performance improvement than LaON, but its lower cost and higher moisture resistance can enhance its potential for GaAs surface passivation.

Background There is limited work on the impact of chemotherapy‐induced nausea and vomiting (CINV) on quality of life (QoL) in adriamycin‐cyclophosphamide (AC)–treated patients with breast cancer. The objectives of the study were the following: (a) to confirm if symptoms of CINV led to lower QoL during AC; (b) to evaluate the pattern of changes in patients’ QoL during multiple cycles of AC; and (c) to assess if the QoL in an earlier cycle affected the QoL in subsequent cycles of AC. Materials and Methods This is a secondary pooled data analysis that included 303 Chinese patients with breast cancer who received 1,177 cycles of adjuvant AC in three prospective antiemetic studies. QoL data were based on Functional Living Index–emesis (FLIE) scored over three to four AC cycles. CINV symptoms assessed included “no significant nausea” (NSN), “significant nausea” (SN), “no vomiting” (NoV), “vomiting” (V), and complete response (CR). Results Across all AC cycles, the mean scores for the FLIE nausea domain for patients who experienced NSN versus SN were 10.92 versus 53.92, respectively (p, This article focuses on chemotherapy‐induced nausea and vomiting and quality of life of breast cancer patients through multiple cycles of treatment.

Evasion of immunosurveillance is critical for cancer initiation and development. The expression of “don’t eat me” signals protects cancer cells from being phagocytosed by macrophages, and the blockade of such signals demonstrates therapeutic potential by restoring the susceptibility of cancer cells to macrophage-mediated phagocytosis. However, whether additional self-protective mechanisms play a role against macrophage surveillance remains unexplored. Here, we derived a macrophage-resistant cancer model from cells deficient in the expression of CD47, a major “don’t eat me” signal, via a macrophage selection assay. Comparative studies performed between the parental and resistant cells identified self-protective traits independent of CD47, which were examined with both pharmacological or genetic approaches in in vitro phagocytosis assays and in vivo tumor models for their roles in protecting against macrophage surveillance. Here we demonstrated that extracellular acidification resulting from glycolysis in cancer cells protected them against macrophage-mediated phagocytosis. The acidic tumor microenvironment resulted in direct inhibition of macrophage phagocytic ability and recruitment of weakly phagocytic macrophages. Targeting V-ATPase which transports excessive protons in cancer cells to acidify extracellular medium elicited a pro-phagocytic microenvironment with an increased ratio of M1-/M2-like macrophage populations, therefore inhibiting tumor development and metastasis. In addition, blockade of extracellular acidification enhanced cell surface exposure of CD71, targeting which by antibodies promoted cancer cell phagocytosis. Our results reveal that extracellular acidification due to the Warburg effect confers immune evasion ability on cancer cells. This previously unrecognized role highlights the components mediating the Warburg effect as potential targets for new immunotherapy harnessing the tumoricidal capabilities of macrophages.

Two new rocaglamides, 8b-O-5-oxohexylrocaglaol (1) and elaeagnin (2), together with twelve known compounds, were isolated from the bark of Aglaia elaeagnoidea and the whole tree of A. odorata. Their structures were determined using spectroscopic methods, mainly 1D and 2D NMR. Cytotoxic activity against HepG2 human liver cancer cells of the isolated compounds was evaluated in vitro using the SRB assay. Three rocaglamide derivatives, dehydroaglaiastatin (13), 8b-O-5-oxohexylrocaglaol (1) and rocaglaol (5), exhibited significant effects with IC50 values of 0.69, 4.77 and 7.37 µM, respectively.

The outbreak of the 2019-nCoV coronavirus causing severe acute respiratory syndrome which can be fatal, especially in elderly population, has been declared a pandemic by the World Health Organization. Many biotechnology laboratories are rushing to develop therapeutic antibodies and antiviral drugs for treatment of this viral disease. The viral CoV spike (S) glycoprotein is one of the main targets for pharmacological intervention. Its receptor-binding domain (RBD) interacts with the human ACE2 receptor ensuring the entry of the viral genomes into the host cell. In this work, we report on the differences in the binding of the RBD of the previous coronavirus SARS-CoV and of the newer 2019-nCoV coronavirus to the human ACE2 receptor using atomistic molecular dynamics techniques. Our results show major mutations in the 2019-nCoV RBD with respect to the SARS-CoV RBD occurring at the interface of RBD-ACE2 complex. These mutations make the 2019-nCoV RBD protein backbone much more flexible, hydrophobic interactions are reduced and additional polar/charged residues appear at the interface. We observe that higher flexibility of the 2019-nCoV RBD with respect to the SARS-CoV RBD leads to a bigger binding interface between the 2019-nCoV RBD and ACE2 and to about 20% more contacts between them in comparison with SARS-CoV. Taken together, the 2019-nCoV RBD shows more stable binding interface and higher binding affinity for the ACE2 receptor. The mutations not only stabilize the binding interface, they also lead to overall more stable 2019-nCoV RBD protein structure, even far from the binding interface. Our results on the molecular differences in the binding between the two viruses can provide important inputs for development of appropriate antiviral treatments of the new viruses, addressing the necessity of ongoing pandemics.

In this study, a comparative analysis of the instabilities and degradation routes of organic solar cell (OSCs) employing the three benchmarked donor polymers namely poly(3-hexylthiophene) (P3HT), poly[N-900- hepta-decanyl-2,7-carbazole-alt-5,5-(40,70-di-2-thienyl-20,10,30-benzothiadiazole)] (PCDTBT) and Poly[[4,8-bis[(2-ethylhexyl)oxy]benzo[1,2- b:4,5-b']dithiophene-2,6-diyl][3-fluoro-2-[(2 ethylhexyl)carbonyl] thieno[3,4-b]thiophenediyl]] (PTB7) along with [6,6]-phenylC71 butyric acid methyl-ester (PC71BM) acceptor have been conducted using the extracted photovoltaic parameters in conjunction with the X-ray photoelectron spectroscopy (XPS), optical and morphological analysis. During the 14 days air stability test, the power conversion efficiency (PCE) decreased by 78.85%, 65.83% and 83.36% for P3HT:PC71BM, PCDTBT:PC71BM and PTB7:PC71BM based devices, respectively. However, the degradation study of the bulk heterojunction (BHJ) films was prolonged to 28 days in order to further elucidate the degradation factors affecting the device performance. XPS, optical and morphological studies enabled detailed information on the device degradation mechanisms and confirmed the oxidation of photoactive layer after ageing, morphological deterioration and fall in absorbance, particularly, the PTB7:PC71BM blend that showed the rapid degradation among all three. The results obtained in the current study advance the understanding of the stability/degradation mechanisms pertaining to the three most commonly used BHJ materials and hence, will help to improve the OSCs for longer lifetime.

The effects of source/drain (S/D) electrode material (Ni, Pt and Pd) and deposition method (electron-beam evaporation and sputtering) on the performance of pentacene organic thin-film transistor (OTFT) are studied. Experimental results show that the OTFT with Pd S/D electrodes deposited by sputtering exhibits the best electrical performance. This should be due to the small charge-injection barrier at the pentacene/electrode interface and small thermal load generated during the metal deposition. Besides, through varying the Pd S/D electrode thickness, it is found that increasing the electrode thickness results in performance degradation due to degraded pentacene/electrode interface, which is caused by higher thermal stress developed during longer deposition time.

An investigation on the incorporation of two different kinds of high-κ dielectrics (HfO2 and Ta2O5) in the dielectric of Pd-WO3-SiC Schottky diode is presented. It is found that while the surface morphology of the WO3 and WHfO films is almost the same, the WTaO film has the smoothest surface due to suppression of oxygen vacancies in WO3 by the Ta incorporation, as supported by XPS analysis. The current-voltage characteristics are examined under a wide range of temperature and hydrogen concentration. Upon exposure to 10,000 ppm H2/air, the diodes based on WHfO and WTaO show a maximum hydrogen response of 89 and 147 respectively, both higher than that (31) of the control sample with WO3. From the kinetics analysis, it is demonstrated that more hydrogen atoms are accumulated at the Pd/WHfO and Pd/WTaO interfaces than their Pd/WO3 counterpart due to larger enthalpy change for hydrogen adsorption on passivated surface, resulting in a greater barrier-height variation at the interface and thus better sensing performance for the two devices with ternary oxide.

The effects of La content in HfLaO gate dielectric on the performance of pentacene organic thin-film transistor (OTFT) fabricated on Si have been studied. The OTFT with Hf0.103La0.897O y gate dielectric shows high performance such as high carrier mobility of 3.45 cm $^{\textsf {2}}\cdot \textsf {V}^{-\textsf {1}}\cdot \textsf {s}^{-\textsf {1}}$ (132 times and 40 times higher than those of devices using Hf oxide and La oxide, respectively), small threshold voltage of −2.09 V, and negligible hysteresis of −0.029 V. Binding-energy shift of Hf 4f peak in the X-ray photoelectron spectroscopy spectrum indicates that La incorporation can passivate the oxygen vacancies in HfO2. Atomic force microscope reveals that the La incorporation can reduce the surface roughness of the gate dielectric by suppressing the crystallization of HfO2. Therefore, by using Hf0.103La0.897O y as gate dielectric, OTFT with high carrier mobility and small threshold voltage can be obtained.

The electrochemical reactions of SiC film with Li+ have been investigated by electrochemical characterization and X-ray photoelectron spectroscopy. The SiC film is prepared by inductively-coupled-plasma chemical-vapor-deposition (ICP-CVD) technique and displays an amorphous state due to the low processing temperature (∼350 °C). An irreversible reaction of SiC with Li+ occurs with the formation of lithium silicon carbide (LixSiyC) and elemental Si, followed by a reversible alloying/dealloying reaction of the elemental Si with Li+. The 500 nm SiC film shows an initial reversible specific capacity of 917 mA h g−1 with a capacity retention of 41.0% after 100 cycles at 0.3C charge/discharge current, and displays much better capacity retention than the Si film (5.2%). It is found that decreasing the SiC thickness effectively improves the specific capacity by enhancing the reaction kinetics but also degrades the capacity retention (for 250 nm SiC, its initial capacity is 1427 mA h g−1 with a capacity retention of 25.7% after 100 cycles). The better capacity retention of the 500 nm SiC anode is mainly because residual SiC exists in the film due to its incomplete reaction caused by its lower reaction kinetics, and it has high hardness and can act as a buffer matrix to alleviate the anode volume change, thus improving the mechanical stability and capacity retention of the SiC anode.

GaAs metal–oxide–semiconductor capacitors with NdTaON as gate dielectric and NdAlON, NdON or AlON as interfacial passivation layer (IPL) are fabricated, and their interfacial and electrical properties are compared with their counterpart without IPL. Experimental results show that owing to the suppressed hygroscopicity of NdON by Al incorporation, best improvements in electrical properties and reliability are achieved for the sample with NdAlON IPL (low interface-state density ( $8 \times 10^{11}$ cm−2/eV), small flatband voltage (0.72 V), negligible hysteresis (43 mV), small frequency dispersion, and low gate leakage current density ( $2.56 \times 10^{-6}$ A/cm2 at Vfb + 1 V). These should be attributed to suppressed growth of unstable Ga and As oxides on the GaAs surface and reduced in-diffusion of elements from the gate dielectric to the GaAs surface by the NdAlON IPL during gate-dielectric annealing.

A hydrogen sensor based on pentacene organic thin-film transistor (OTFT) with palladium (Pd) source and drain (S/D) electrodes is analyzed in detail. When exposed to H2 with different concentrations, the sensor shows a clear change in drain current due to three reasons: 1) work-function change of the source electrode induced by hydrogen absorption; 2) reduced carrier mobility; and 3) increased S/D series resistance both caused by the expansion of the S/D electrodes after absorbing hydrogen. Analysis of the data demonstrates that the first two are the dominant mechanisms. Without the need of heating, rapid, reversible, and concentration-dependent response of the OTFT is observed upon introduction and removal of H2 with concentration ranging from 200 to 17 000 ppm.

Bottom-gate pentacene organic thin-film transistors (OTFTs) with HfLaO gate dielectric have been fabricated on different substrates with different gate materials (namely, Ti- or Al-coated vacuum tape, n-Si wafer, and ITO-coated glass) and the effects of the gate material on device performance have been studied. Although the dielectric surface and pentacene grain on the Ti- and Al-coated vacuum tapes are much rougher and much smaller, respectively, than those on the n-Si wafer, the OTFTs fabricated on the two vacuum tapes have much higher carrier mobility than that fabricated on the n-Si wafer, implying that the gate material can greatly affect the device performance. Like the case for MOSFET, the possible reason is that metal gate can screen the remote phonon scattering of HfLaO and avoid the remote Coulomb scattering of silicon gate, thus resulting in higher carrier mobility for the OTFTs with Al and Ti gate electrodes. As a result, a high-performance OTFT with a carrier mobility of 4.95 cm $^{2}\text{V}^{-1}\text{s}^{-1}$ and threshold voltage of −1.31 V was successfully fabricated on vacuum tape by using Ti gate.

The origin of positive-gate-bias-stress (PGBS)-induced instability and the effects of fluorine treatment on the instability of an InGaZnO thin-film transistor (TFT) are investigated. The fluorine treatments on the dielectric/InGaZnO interface and InGaZnO back channel of the device can effectively modulate their electrical properties. By characterizing the TFTs with various fluorine treatments, it is found that the back channel rather than the dielectric/InGaZnO interface dominates the PGBS instability. Electrons induced by moisture absorption near the back channel migrate from the back channel to the interface under PGBS at room temperature, thus resulting in a threshold-voltage decrease. Moreover, the fluorine treatment on the back channel effectively suppresses the PGBS instability due to reduced moisture absorption caused by the fluorine passivation.

Pentacene organic thin-film transistors (OTFTs) using La x Nb(1– x )O y as gate dielectric with ${x}= \mathsf {1}$ , 0.946, 0.850, and 0.648 have been fabricated on vacuum tape at a temperature of 200 °C. Among them, the OTFT with La0.850Nb0.150O y as gate dielectric has the highest carrier mobility of 4.63 cm $^{\mathsf {2}}\text{V}^{\mathsf {-1}}\text{s}^{\mathsf {-1}}$ , negligible hysteresis of −0.032 V, small subthreshold swing of 0.174 V/decade, and small threshold voltage of −1.90 V. AFM and X-ray photoelectron spectroscopy reveal that Nb incorporation can alleviate the hygroscopicity of La oxide, resulting in a smoother dielectric surface. Pentacene grain size first increases with Nb content due to smoother dielectric surface, and then decreases due to Nb-induced traps acting as nucleation sites for the growth of pentacene grains on the dielectric surface. Therefore, there exists an optimal Nb content in La x Nb(1– x )O y that can result in the largest grain size and, hence, the highest carrier mobility.

Antibiotic resistant infections are projected to cause over 10 million deaths by 2050, yet the development of new antibiotics has slowed. This points to an urgent need for methodologies for the rapid development of antibiotics against emerging drug resistant pathogens. We report on a generalizable combined computational and synthetic approach, called antibody-recruiting protein-catalyzed capture agents (AR-PCCs), to address this challenge. We applied the combinatorial protein catalyzed capture agent (PCC) technology to identify macrocyclic peptide ligands against highly conserved surface protein epitopes of carbapenem-resistant Klebsiella pneumoniae, an opportunistic Gram-negative pathogen with drug resistant strains. Multi-omic data combined with bioinformatic analyses identified epitopes of the highly expressed MrkA surface protein of K. pneumoniae for targeting in PCC screens. The top-performing ligand exhibited high-affinity (EC50 ∼50 nM) to full-length MrkA, and selectively bound to MrkA-expressing K. pneumoniae, but not to other pathogenic bacterial species. AR-PCCs that bear a hapten moiety promoted antibody recruitment to K. pneumoniae, leading to enhanced phagocytosis and phagocytic killing by macrophages. The rapid development of this highly targeted antibiotic implies that the integrated computational and synthetic toolkit described here can be used for the accelerated production of antibiotics against drug resistant bacteria., Antibody-recruiting protein-catalyzed capture agent (AR-PCCs) are a new class of all-synthetic and highly targeted antibiotics that recruit endogenous immune responses to eliminate drug-resistant microbes.

In this work, we have shown that betagallium oxide (Ga2O3) thin films of differing thickness could be obtained by physical vapor deposition method, employing proper annealing conditions. These enable us to compare the variation of optical properties like transparency, band gap in these phases. Apart from these, our analysis of transmittance spectra of beta-Ga2O3 indicated the reduction of structural disorders (amorphous to crystalline) with increase in annealing temperature. The calculated band gap based on Density Functional Theory (DFT) for bulk beta-Ga2O3 thin films ~ 4.9 eV (direct) at room temperature is in excellent agreement with our experimentally measured values. This work will serve as design guidance for the new Ga2O3 based thin film electronics.

Improvement in the performance of pentacene organic thin-film transistor has been demonstrated by using fluorine plasma-treated or ion-implanted HfO 2 as its gate dielectric. The carrier mobility of the OTFT on HfO 2 with 900-s plasma treatment can reach a carrier mobility of 0.662 cm2/Vs, about 7 times higher than that of the control sample without fluorine incorporation. The reason is larger pentacene grains due to trap passivation, smoother surface and higher surface energy. On the other hand, the carrier mobility of the OTFT on HfO 2 with a fluorine implant dose of (1 ×10)14/cm2 is improved to 0.251 cm2/Vs, about 2.7 times higher than that of the control sample. The smoother surface of the gate dielectric with fluorine implant results in the growth of larger pentacene grains, leading to an increase of carrier mobility. However, excessive fluorine implant dose or plasma treatment time could cause damage to the gate dielectric, thus decreasing the carrier mobility of the device.

Carrier mobility of MoS 2 transistor can be greatly improved by screening the Columbic scattering by a high-k gate dielectric. In this work, different TiO 2 amounts are incorporated into HfO 2 to form Hf 1-x Ti x O gate dielectrics to investigate its effects on the electrical properties of MoS 2 transistor. It is found that enhanced carrier mobility and decreased gate leakage current can be achieved by optimizing the Ti content, i.e. with ${\rm{Hf}}_{0.9}{\rm{Ti}}_{0.1}O (x\ =\ 0.1)$ as the gate dielectric, the device exhibits the highest carrier mobility of 31.5 ${\rm{cm}}^{2}/Vs$, which is $ 1.3\times$ improvement as compared to the sample with HfO 2 as gate dielectric $(24.1\ {\rm{cm}}^{2}/Vs)$. The main mechanism lies in that Hf 1-x Ti x O has higher k value than HfO 2 to increase the Coulomb screening effect and thus carrier mobility. However, with further increase of Ti content, e.g. ${\rm{Hf}}_{0.85}{\rm{Ti}}_{0.15}O (x=\ 0.15)$, the device exhibits larger off current and degraded subthreshold swing. This is probably attributed to Ti-related oxide traps, a decreased conduction-band offset between ${\rm{Hf}}_{0.85}{\rm{Ti}}_{0.15}{\rm{O}}$ and MoS 2 , and degraded $MoS_{2}/{\rm{Hf}}_{1-x}{\rm{Ti}}_{x}{\rm{O}}$ interface quality.

4H-SiC n-channel MOSFET at 300 K has been studied by using SILVACO TCAD simulation. Based on the good agreements between measured and simulated output characteristics, the components of channel mobility versus gate voltage are clearly illustrated. From the simulation results, the channel mobility degradations due to interface traps under low gate voltage and surface roughness under high gate voltage are analyzed numerically.

Protein-catalyzed capture agents (PCCs) are synthetic and modular peptide-based affinity agents that are developed through the use of single generation in situ click chemistry screens against large peptide libraries. In such screens, the target protein, or a synthetic epitope fragment of that protein, provides a template for selectively promoting the non-copper catalyzed azide-alkyne dipolar cycloaddition click reaction between either a library peptide and a known ligand, or a library peptide and the synthetic epitope. The development of epitope-targeted PCCs was motivated by the desire to fully generalize pioneering work from the Sharpless and Finn groups in which in situ click screens were used to develop potent, divalent enzymatic inhibitors. In fact, a large degree of generality has now been achieved. Various PCCs have demonstrated utility for selective protein detection, as allosteric or direct inhibitors, as modulators of protein folding, and as tools for in vivo tumor imaging. We provide a historical context for PCCs, and place them within the broader scope of biological and synthetic aptamers. The development of PCCs is presented as: (i) Generation I PCCs, which are branched ligands engineered through an iterative, non-epitope targeted process, and (ii) Generation II PCCs, which are typically developed from macrocyclic peptide libraries and are precisely epitope targeted. We provide statistical comparisons of Generation II PCCs relative to monoclonal antibodies in which the protein target is the same. Finally, we discuss current challenges and future opportunities of PCCs.

We report the synthesis of the first stable, solution-processable and photocrosslinkable hybrid organic/\ud inorganic titanium dioxide nanorods as ‘hairy rods’ coated with phosphonate ligands with photoreactive\ud coumarin groups located in a terminal position. The relationships between the chemical structure of the\ud diethyl-u-[(7-oxycoumaryl)-n-alkyl]phosphonate ligands on the ligand exchange rate (LER) and the\ud solubility of the resultant ligand-stabilized titanium dioxide nanorods in organic solvents are elucidated.\ud These TiO2 nanorods, with an organic ligand coating, are short enough (aspect ratio ¼ 5–8) to be\ud dissolved in chlorobenzene at high concentrations, but long enough to form lyotropic nematic liquid\ud crystals. These colloidal solutions are used to deposit a thin, uniform layer of hybrid organic/inorganic\ud TiO2 nanorods with their long axes in the plane of a flat, smooth substrate through a self-organization\ud process. Standard photolithographic patterning creates an insoluble dielectric layer of the desired\ud thickness, smoothness and uniformity and with a dielectric constant of sufficient magnitude, k ¼ 8,\ud suitable for the fabrication of multilayer, plastic electronic devices using solution-based fabrication\ud techniques, such as ink-jet printing, used in roll-to-roll manufacturing.

A model for the dimeric form of the human TSPO (hTSPO) protein is constructed homologically using the RsTSPO dimer template. Then, Molecular dynamics simulation of 1μs is carried out on the model to investigate its stability as well as to study its various physicochemical properties. Our model shows good stability, with various important conserved residues involving in monomer–monomer interactions, in good agreements with available experimental data. Several functioning motifs are well demonstrated. This model hence can serve as a good basis for further study of this system as well as for discoveries of candidate radioligands targeting TSPO protein as a biotracer for medical imaging of brain inflamation.

This work proposes a method for extracting the barrier height, ideality factor, series, and shunt resistances of Schottky diodes with high accuracy and consistency. By defining the voltage boundaries for the three regions of the current–voltage curve that are controlled by shunt resistance, thermal emission, and series resistance, respectively, the method can avoid the problems of traditional methods through nonlinear fitting and iterations. The application on Schottky-diode-type hydrogen sensor with a structure of Pd/WO3/SiC reveals excellent agreement between the extracted voltage boundaries and the turning points on the current–voltage curve under different temperatures and hydrogen concentrations. The average mean-squared error of the model current–voltage data vs. experimental data is 0.371, more than five times smaller than that of traditional methods based on least-squares linear regression.

Thoreliolides A and B, two new polyisoprenylated benzoylphloroglucinol derivatives with a novel carbon skeleton, together with four known compounds, were isolated from the fruits of Calophyllum thorelii and their structures elucidated using spectroscopic methods. Thoreliolide B showed moderate activity against three cancer cell lines, MCF-7, HeLa and NCI-H460, with IC 50 values of 9.7, 16.6 and 24.2 μg/mL, respectively, using the sulforhodamine B assay.

The effects of Al doping on the charge-trapping characteristics of ZrO2 are investigated based on Al/Al2O3/Al-doped ZrO2/SiO2/Si structure. XRD and XPS show that the crystallization of ZrO2 and the formation of silicate interlayer at the ZrO2/SiO2 interface are effectively suppressed by Al incorporation, thus resulting in better electrical performance with larger memory window and better retention for the memory device with Al-doped ZrO2 as the charge-trapping layer (CTL) than the one with pure ZrO2. However, excessive Al doping in ZrO2 severely reduces the dielectric constant and electron traps of the CTL, thus leading to much lower program speed for the device.

Silicon underpins microelectronics but lacks the photonic capability needed for next-generation systems and currently relies on a highly undesirable hybridization of separate discrete devices using direct band gap semiconductors. Rare-earth (RE) implantation is a promising approach to bestow photonic capability to silicon but is limited to internal RE transition wavelengths. Reported here is the fi rst observation of direct optical transitions from the silicon band edge to internal f -levels of implanted REs (Ce, Eu, and Yb); this overturns previously held assumptions about the alignment of RE levels to the silicon band gap. The photoluminescence lines are massively redshifted to several technologically useful wavelengths and modeling of their splitting indicates that they must originate from the REs. Eu-implanted silicon devices display a greatly enhanced electroluminescence effi ciency of 8%. Also observed is the fi rst crystal fi eld splitting in Ce luminescence. Mid-IR silicon photodetectors with specifi c detectivities comparable to existing state-of-theart mid-IR detectors are demonstrated.

Pentacene organic thin-film transistors have been fabricated with their NdTaO gate dielectrics annealed at 200 °C, 400 °C, and 800 °C to study the effects of remote phonon scattering caused by the thermal vibration of the gate dielectric on the carrier transport in the conduction channel. Although the sample annealed at 800 °C can achieve the best dielectric quality (reflected by its lowest oxide-charge density, smallest dielectric surface roughness, and largest pentacene grain size), it shows the lowest carrier mobility of 0.44 cm2/V·s as compared to the highest mobility of 1.69 cm2/V·s for the control sample without dielectric annealing. In addition, this mobility degradation increases with increasing annealing temperature in spite of improving dielectric quality. Transmission electron microscopy shows that higher annealing temperature results in the formation of a thicker Si-gate/gate-dielectric interlayer, which increases the separation between the Si-gate plasmons and the gate-dielectric dipoles to weaken the screening effect of the gate electrode on the remote phonon scattering of the high-k gate dielectric, resulting in a lower carrier mobility. Measurements at high temperatures also support the effects of the interlayer.

Eastern oysters have been acknowledged for their important contribution to human well-being by providing goods and services including nitrogen removal from water bodies. In this study, we integrated daily environmental data (2008–2016) and filtration rate model parameter uncertainty to estimate nitrogen removal from denitrification and nitrogen burial services provided by the current extent of oyster (Crassostrea virginica) reefs in Mobile Bay, Alabama. Oyster landing data (2008–2016) in the Bay were also used to estimate nitrogen removal through oyster harvest. A replacement cost method using an engineering solution from wastewater treatment plants was implemented to quantify the economic benefit of the nitrogen removal. The estimated total nitrogen removal services provided by oyster reefs in Mobile Bay was 34,911 ± 5,032 kg N yr−1 (mean ± 1sd), in which 22,095 ± 3,305 kg N yr−1 from denitrification, 11,047 ± 1,652 kg N yr−1 from burial of nitrogen into sediments and 1,769 ± 876 kg N yr−1 by oyster harvest. The mean economic benefit was $76,455 ± 11,020 yr−1 which was estimated as $73.2 ± 11.5 ha−1 yr−1. This method could be used for any time period to estimate the nitrogen removal service in Mobile Bay. With proper modification of model parameters, this method could also be used elsewhere to estimate nitrogen removal services provided by oysters.

Gout is an extremely painful form of inflammatory arthritis, caused by the formation of monosodium urate (MSU) crystals in the joints. MSU crystals are one of the triggers for the activation of nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome (NACHT, LRR and PYD domains-containing protein), which in turn induces caspase-1 activation and a nonspecific immune responses that cause inflammation. Further structural studies and ligand designs are needed to block the interaction of NLRP3 with MSU or allow the interaction without activating caspase-1. This would facilitate the screening of new drugs for the treatment of gout. Using computational methods for homology modeling and molecular dynamics simulations, the structural model of mouse NLRP3 protein with its domains, three potential structural models were consistently constructed and tested to find the most stable structural model. Adenosine triphosphate (ATP) — an activator of NACHT (the central domain of mouse NLRP3 protein) — was docked and simulated. Ligand effects to activate as well as limit this protein were analyzed. This study provides insights to deeper understanding about gout development pathway via the NLRP3 protein.

A flexible hydrogen gas sensor based on pentacene organic thin-film transistor (OTFT) using palladium (Pd) source and drain (S/D) electrodes as the sensing medium is prepared on adhesive vacuum tape. The sensor exhibits a clear, rapid and concentration-dependent response upon hydrogen exposure without the need of heating. In addition, in order to demonstrate the flexibility of the sensor, measurements on a curved surface are performed. The sensor, when attached to the curved surface, shows normal transistor characteristics, which essentially remains the same after one hour of tensile stress.

Pentacene organic thin-film transistors (OTFTs) adopting high-k NdON, HfON and NdHfON as gate dielectrics are fabricated. Their electrical and physical characteristics are compared. With appropriate Nd/Hf ratio in the dielectric, the OTFT with NdHfON gate dielectric can achieve improved performance such as a carrier mobility of $1.1~{\mathrm {cm}}^{2}/{\mathrm {V}}\cdot {\mathrm {s}}$ and a small threshold voltage of-1.20 V. The AFM results of the pentacene layer and the dielectric layer reveal that both improved dielectric and pentacene morphologies lead to the higher carrier mobility ofthe device.

Epithelial ovarian cancer (EOC) is the seventh most common cancer among women worldwide. The 5-year survival rate for women with EOC is only 30%-50%, which is largely due to the typically late diagnosis of this condition. EOC is difficult to detect in its early stage because of its asymptomatic nature. Recently, near-infrared fluorescent (NIRF) imaging has been developed as a potential tool for detecting EOC at the molecular level. In this study, a NIRF-sensitive probe was designed to detect matrix metalloproteinase (MMP) activity in ovarian cancer cells. A cyanine fluorochrome was conjugated to the amino terminus of a peptide substrate with enzymatic specificity for MMP-3. To analyze the novel MMP-3 probe, an in vivo EOC model was established by subcutaneously implanting SKOV3 cells, a serous-type EOC cell line, in mice. This novel MMP-3-sensitive probe specifically reacted with only the active MMP-3 enzyme, resulting in a significantly enhanced NIRF emission intensity. Histological analysis demonstrated that MMP-3 expression and activity were enhanced in the stromal cells surrounding the ovarian cancer cells. These studies establish a molecular imaging reporter for diagnosing early-stage EOC. Additional studies are required to confirm the early-stage activity of MMP-3 in EOC and its diagnostic and prognostic significance.

Charge-trapping characteristics of La2O3 with and without nitrogen incorporation were investigated based on Al/Al2O3/La2O3/SiO2/Si (MONOS) capacitors. The physical properties of the high-k films were analyzed by X-ray diffraction and X-ray photoelectron spectroscopy. Compared with the MONOS capacitor with La2O3 as charge-trapping layer, the one with nitrided La2O3 showed a larger memory window (4.9 V at ±10-V sweeping voltage), higher program speed (4.9 V at 1-ms +14 V), and smaller charge loss (27% after 10 years), due to the nitrided La2O3 film exhibiting less crystallized structure and high trap density induced by nitrogen incorporation, and suppressed leakage by nitrogen passivation.

We report an unusual “symbiotic” behavior of oxygen interstitials acting in concert with Ge and Si interstitials at high temperature inducing morphology changes and autonomous migration of Ge nanocrystallites within SiO2/Si3N4 layers. The Ge nanocrystallites were originally generated by the selective oxidation of SiGe nano-pillars grown and lithographically patterned over buffer Si3N4 layers on Si substrates. The coalescence and movement of these Ge nanocrystallites appear to be very sensitive to the presence and flux of oxygen interstitials especially at the Ge nanocrystallite/buffer Si3N4 interface. A range of different morphologies are observed for Ge nanocrystallites that are directly attributable to the influence of oxygen interstitial concentration and consequently the interstitial Si and Ge concentrations. In combination with Si and Ge interstitials, oxygen interstitials activate the coalescence of sparsely-distributed Ge nanocrystallites and concurrently their migration towards the source of Si interstitials, i.e. the buffer Si3N4 layers, through catalytically-enhanced local decomposition and subsequent oxidation of both the SiO2 and Si3N4 buffer layers. We also show that these symbiotic effects are “tunable” by increasing the Ge content of the SiGe nano-pillars. Dense distributions of Ge nanocrystallites generated from high Ge content SiGe nano-pillars remain static and they show no changes in their morphology possibly because oxygen interstitials are simply unable to penetrate these clusters and consequently incapable of inducing symbiotic Si and Ge interstitial generation.

The IL-17 cytokine family is associated with multiple immune and autoimmune diseases and comprises important diagnostic and therapeutic targets. This work reports the development of epitope-targeted ligands designed for differential detection of human IL-17F and its closest homologue IL-17A. Non-overlapping and unique epitopes on IL-17F and IL-17A were identified by comparative sequence analysis of the two proteins. Synthetic variants of these epitopes were utilized as targets for in situ click screens against a comprehensive library of synthetic peptide macrocycles with 5-mer variable regions. Single generation screens yielded selective binders for IL-17F and IL-17A with low cross-reactivity. Macrocyclic peptide binders against two distinct IL-17F epitopes were coupled using variable length chemical linkers to explore the physical chemistry of cooperative binding. The optimized linker length yielded a picomolar affinity binder, while retaining high selectivity. The presented method provides a rational approach towards targeting discontinuous epitopes, similar to what is naturally achieved by many B cell receptors.

A 6-layer continuous and uniform MoS 2 film is successfully grown by thermal chemical vapor deposition (CVD) through optimizing its growth conditions, and is used as channel material to fabricate top-gated transistors by conventional lithography process. Also, the effects of a buffer layer on the electrical performance of the CVD MoS 2 transistor are investigated, and enhanced carrier mobility (0.69 cm2/V·s) is achieved by using Ta 2 O 5 as the buffer layer.

Pentacene organic thin-film transistors (OTFTs) with high-k NdON gate dielectric incorporating different Ti contents are fabricated and their physical and electrical characteristics are studied. With appropriate Ti content, the OTFT with NdTiON as gate dielectric can achieve improved performance, e.g. a carrier mobility of 0.80 cm2/V·s, a small threshold voltage of -1.25 V, and a small sub-threshold swing of 0.13 V/dec. The AFM results of the pentacene layer and the dielectric layer reveal that incorporating Ti into NdON can obtain a smoother dielectric surface, which should be due to the suppressed hygroscopicity of Nd oxide caused by the Ti incorporation. Both the smoother dielectric surface and thus larger pentacene grains grown are responsible for the improved carrier mobility of the device.

Benign prostatic hyperplasia (BPH) is the most common urologic disease among elderly men. A well-established in vitro cell model is required to determine the therapeutic mechanism of BPH inflammation. In this study, we attempted to establish an immortalized human prostate stromal cell line by transfecting with HPV-16 E6/E7 and designated as ihPSC. No significant difference was found in fibroblast-like morphology between primary hPSC and ihPSC. The ihPSC possessed a significantly higher cell proliferation rate than primary hPSC. The prostate-specific markers and proteins including cytoskeleton (α-SMA and vimentin) and smooth muscle (calponin), especially the androgen receptor (AR) were also examined in ihPSC, almost identical to the primary hPSC. To create an in vitro model featuring chronic prostatic inflammation, ihPSC was stimulated with IFN-γ+IL-17 and then treated with the high molecular weight hyaluronic acid hylan G-F 20 as an alternative strategy for inhibiting BPH inflammation. Hylan G-F 20 could dose-dependently diminish the inflammation-induced proliferation in ihPSC. The enhanced expressions of inflammatory molecules including IL-1β, IL-6, IL-8, cyclooxygenase 2 (COX2), inducible nitrogen oxide synthase (iNOS), and Toll-like receptor 4 (TLR4) were all abolished by hylan G-F 20. For inflammatory signaling, hylan G-F 20 can also diminish the IFN-γ+IL-17-increased expression of iNOS and p65 in ihPSC. These findings suggest that ihPSC could provide a mechanism-based platform for investigating prostate inflammation. The hylan G-F 20 showed strong anti-inflammatory effects by decreasing inflammatory cytokines and signalings in the ihPSC, indicating its therapeutic potentials in BPH treatment in the future.

The charge-trapping characteristics of BaTiO3 with and without nitrogen incorporation were investigated based on Al/Al2O3/BaTiO3/SiO2/Si (MONOS) capacitors. The physical properties of the high-k films were analyzed by transmission electron microscopy and X-ray photoelectron spectroscopy. Compared with the MONOS capacitor with BaTiO3 as charge-trapping layer, the one with nitrided BaTiO3 showed higher program speed even at lower operating voltage (4.3 V at +8 V for 100 μs), better endurance property and smaller charge loss (charge loss of 10.6% after 104 s at 85 °C), due to the nitrided BaTiO3 film exhibiting higher charge-trapping efficiency caused by nitrogen incorporation and suppressed leakage induced by nitrogen passivation.

The interfacial and electrical properties of Ge-based metal–oxide–semiconductor (MOS) capacitor with high- \(k\) gate dielectric of HfTiO and passivation interlayer of LaTaON are investigated. Experimental results show the Ge MOS with HfTiO/LaTaON gate-stacked dielectric exhibits low interface-state density ( \(7.8\times 10^{11}\) cm \(^{-2}\) eV \(^{\mathrm {-1}}\) ), small gate-leakage current ( \(7.88\times 10^{\mathrm {-4}}\) A cm \(^{\mathrm {-2}}\) at \(V_{\rm g} - V_{\rm fb}= 1\) V), small capacitance equivalent thickness (1.1 nm), and large equivalent dielectric constant (27.7). X-ray photoelectron spectroscopy and transmission electron microscopy reveal that the improvements should be due to the fact that La/Ta-based oxide/oxynitride has excellent interface properties with Ge, and the LaTaON interlayer can effectively block the in-diffusion of oxygen and the out-diffusion of germanium, thus suppressing the growth of low- \(k\) GeOx and intermixing between Ge and Hf.