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An environmentally sustainable strategy for the chemoselective heterocyclization of bromoenynes through a transition-metal-free sulfuration/cyclization process is reported. Using inexpensive and sa...

BACKGROUND To explore the TEM8 expression in patients with lung cancer and its relationship with clinical pathology and prognosis, and to analyze the diagnostic value of TEM8. METHODS A total of 204 patients with lung cancer diagnosed and treated in Zhongmeng Hospital Zhalantun and the First Affiliated Hospital of Jinzhou Medical University from March 2013 to February 2016 were enrolled in the study group, and 203 healthy subjects in the control group. qRT-PCR technique was applied to detect the TEM8 expression. Combined with clinical information, the diagnostic value of TEM8 for lung cancer and the correlation of clinical characteristics of TEM8 were analyzed. The 3-year survival curves of patients with low and high TEM8 expressions were compared. RESULTS The expression in the study group was significantly higher than that in the control group (P

Three types of silane-based impregnation agent (short for SIA) are used to treat the concrete surface, and the influence of water/binder (W/B) ratio, mineral admixtures, curing methods, the type and dosage of SIA on the capillary water absorption and electric flux of concretes is examined. Results show that the penetration depth of SIA increases with the increasing of the W/B ratio and SIA dosage, and is related to the type of SIA. Surface treatment by SIA can reduce capillary water absorption and electric flux of concretes, the W/B ratio and curing methods are no longer the main factor, the increasing of the SIA dosage can further improve the surface protection effect of concrete. Mineral admixtures improve the compactness of concretes, and the combined effects of surface treatment and admixtures can evidently enhance the impermeability of concrete. Different types of SIAs have different mechanisms of action on the surface treatment of concrete, and thus have different impacts on the permeability of concrete. The concrete treated by SIA2 with the effects of the penetration and the formation of surface film layer has lower permeability.

An environmentally sustainable strategy for the chemoselective heterocyclization of bromoenynes through a transition-metal-free sulfuration/cyclization process is reported. Using inexpensive and safe EtOCS

Traceability of honey is highly required by consumers and food administration with the consideration of food safety and quality. In this study, a technique named laser-induced breakdown spectroscopy (LIBS) was used to fast trace geographical origins of acacia honey and multi-floral honey. LIBS emissions from elements of Mg, Ca, Na, and K had significant differences among different geographical origins. The clusters of honey from different geographical origins were visualized with principal component analysis. In addition, support vector machine (SVM) and linear discrimination analysis (LDA) were used to quantitively classify the origins. The results indicated that SVM performed better than LDA, and the discriminant results of multi-floral honey were better than acacia honey. The accuracy and mean average precision for multi-floral honey were 99.7% and 99.7%, respectively. This study provided a fast approach for geographical origin classification, and might be helpful for food traceability.

Vapor-liquid-solid (VLS) growth of nanoscale or subwavelength scale semiconductor wires (nanowires) has been proven to be an important and effective approach to producing high-quality, substrate insensitive photonic materials with a flexible and ever-expanding coverage of wavelengths for lasing and other photonic applications. However, the materials and lasing demonstrations have so far been limited to mostly ultraviolet to visible wavelengths, with a few exceptions in the short-wavelength infrared range. A further extension to longer wavelengths (such as mid-infrared, MIR) using narrower band gap semiconductors encounters severe challenges: the ever decreasing radiative efficiency due to the Auger and other nonradiative channels with wavelengths demands extremely high material quality and significantly narrows the material choices. This situation is very unsatisfactory, given many important applications that demand materials and lasers of subwavelength scales for MIR wavelengths in an integrated platform, especially on silicon. Here we report our results on lasing demonstration in MIR (3-4 μm) based on a unique combination of high-quality material growth on a silicon substrate and the choice of an intrinsically strong MIR material in lead sulfide (PbS). Lasing is demonstrated from single wires both on the original silicon substrate and on the sapphire substrates after transferring, with sizes of lasing wires down to below half of the normalized volume (volume of wires divided by the wavelength cubed) and operating temperature up to 180 K. Such subwavelength wire lasers could be important for a wide range of MIR applications on silicon-based integrated photonic platforms, such as chemical and environmental sensing, free-space communications, and many others.

Aim This study was conducted to determine a more accurate imaging method for the diagnosis of cesarean scar diverticulum (CSD) and to identify the parameters of CSD strongly associated with prolonged menstrual bleeding. Methods We enrolled 282 women with a history of cesarean section (CS) who presented with prolonged menstrual bleeding between January 2012 and May 2015. Transvaginal ultrasound, general magnetic resonance imaging (MRI) and contrast-enhanced MRI were used to diagnose CSD. Five parameters were compared among the imaging modalities: length, width, depth and thickness of the remaining muscular layer (TRM) of CSD and the depth/TRM ratio. Correlation between the five parameters and days of menstrual bleeding was performed. Finally, multivariate analysis was used to determine the parameters associated with menstrual bleeding longer than 14 days. Results Contrast-enhanced MRI yielded greater length or width or thinner TRM of CSD compared with MRI and transvaginal ultrasound. CSD size did not significantly differ between women who had undergone one and two CSs. Correlation analysis revealed that CSD (P = 0.038) and TRM (P = 0.003) lengths were significantly associated with days of menstrual bleeding. Longer than 14 days of bleeding was defined by cut-off values of 2.15 mm for TRM and 13.85 mm for length. TRM and number of CSs were strongly associated with menstrual bleeding longer than 14 days. Conclusions CE-MRI is a relatively accurate and efficient imaging method for the diagnosis of CSD. A cut-off value of TRM of 2.15 mm is the most important parameter associated with menstrual bleeding longer than 14 days.

Pim kinases have been targets of interest for a number of therapeutic areas. Evidence of durable single-agent efficacy in human clinical trials validated Pim kinase inhibition as a promising therapeutic approach for multiple myeloma patients. Here, we report the compound optimization leading to GDC-0339 (16), a potent, orally bioavailable, and well tolerated pan-Pim kinase inhibitor that proved efficacious in RPMI8226 and MM.1S human multiple myeloma xenograft mouse models and has been evaluated as an early development candidate.

Based on the Fourier transform (FT) of surface plasmon polaritons (SPPs), the relation between the displacement of the plasmonic field and the spatial frequency of the excitation light is theoretically established. The SPPs&rsquo, field shifts transversally or longitudinally when the spatial frequency components f x or f y are correspondingly changed. The SPPs&rsquo, focus and vortex field can be precisely located at the desired position by choosing the appropriate spatial frequency. Simulation results are in good agreement with the theoretical analyses. Dynamically tailoring the plasmonic field based on the spatial frequency modulation can find potential applications in microparticle manipulation and angular multiplexed SPP focusing and propagation.

A mesoscale coupled atmosphere-ocean model has been developed based on the GRAPES (Global and Regional Assimilation and Prediction System) regional typhoon model (GRAPES_TYM) and ECOM-si (estuary, coast and ocean model (semi-implicit)). Coupling between the typhoon and ocean models was conducted by exchanging wind stress, heat, moisture fluxes, and sea surface temperatures (SSTs) using the coupler OASIS3.0. Numerical prediction experiments were run with and without coupling for the case of Typhoon Muifa in the western North Pacific. To investigate the impact of using more accurate SST information on the simulation of the track and the intensity of Typhoon Muifa, experiments were also conducted using increased SST resolution in the initial condition field of the control test. The results indicate that increasing SST resolution in the initial condition field somewhat improved the intensity forecast, and use of the coupled model improved the intensity forecast significantly, with mean absolute errors in maximum wind speed within 48 and 72 h reduced by 32% and 20%, respectively. Use of the coupled model also resulted in less pronounced over-prediction of the intensity of Typhoon Muifa by the GRAPES_TYM. Moreover, the effects of using the coupled model on the intensity varied throughout the different stages of the development of Muifa owing to changes in the oceanic mixed layer depth. The coupled model had pronounced effects during the later stage of Muifa but had no obvious effects during the earlier stage. The SSTs predicted by the coupled model decreased by about 5–6°C at most after the typhoon passed, in agreement with satellite data. Furthermore, based on analysis on the sea surface heat flux, wet static energy of the boundary layer, atmospheric temperature, and precipitation forecasted by the coupled model and the control test, the simulation results of this coupled atmosphere-ocean model can be considered to reasonably reflect the primary mechanisms underlying the interactions between tropical cyclones and oceans.

The structure activity relationship of the prime region of conformationally restricted hydroxyethylamine (HEA) BACE inhibitors is described. Variation of the P1′ region provided selectivity over Cat-D with a series of 2,2-dioxo-isothiochromanes and optimization of the P2′ substituent of chromane–HEA(s) with polar substituents provided improvements in the compound’s in vitro permeability. Significant potency gains were observed with small aliphatic substituents such as methyl, n-propyl, and cyclopropyl when placed at the C-2 position of the chromane.

Herein, we describe our strategy to design metabolically stable γ-secretase inhibitors which are selective for inhibition of Aβ generation over Notch. We highlight our synthetic strategy to incorporate diversity and chirality. Compounds 30 (ELND006) and 34 (ELND007) both entered human clinical trials. The in vitro and in vivo characteristics for these two compounds are described. A comparison of inhibition of Aβ generation in vivo between 30, 34, Semagacestat 41, Begacestat 42, and Avagacestat 43 in mice is made. 30 lowered Aβ in the CSF of healthy human volunteers.

This study was conducted to determine a more accurate imaging method for the diagnosis of cesarean scar diverticulum (CSD) and to identify the parameters of CSD strongly associated with prolonged menstrual bleeding.We enrolled 282 women with a history of cesarean section (CS) who presented with prolonged menstrual bleeding between January 2012 and May 2015. Transvaginal ultrasound, general magnetic resonance imaging (MRI) and contrast-enhanced MRI were used to diagnose CSD. Five parameters were compared among the imaging modalities: length, width, depth and thickness of the remaining muscular layer (TRM) of CSD and the depth/TRM ratio. Correlation between the five parameters and days of menstrual bleeding was performed. Finally, multivariate analysis was used to determine the parameters associated with menstrual bleeding longer than 14 days.Contrast-enhanced MRI yielded greater length or width or thinner TRM of CSD compared with MRI and transvaginal ultrasound. CSD size did not significantly differ between women who had undergone one and two CSs. Correlation analysis revealed that CSD (P = 0.038) and TRM (P = 0.003) lengths were significantly associated with days of menstrual bleeding. Longer than 14 days of bleeding was defined by cut-off values of 2.15 mm for TRM and 13.85 mm for length. TRM and number of CSs were strongly associated with menstrual bleeding longer than 14 days.CE-MRI is a relatively accurate and efficient imaging method for the diagnosis of CSD. A cut-off value of TRM of 2.15 mm is the most important parameter associated with menstrual bleeding longer than 14 days.

The preparation of novel tetrahydro-1H-pyrazolo[4,3-c]pyridines is reported. Pivotal to the synthesis of these compounds was the development of mild reaction conditions to generate a highly functionalized nitrilimine capable of undergoing an intramolecular cycloaddition with a tethered alkyne. The desired cycloadduct was formed as an equal mixture of diastereomers.

The structure–activity relationship (SAR) of a novel, potent and metabolically stable series of sulfonamide-pyrazoles that attenuate β-amyloid peptide synthesis via γ-secretase inhibition is detailed herein. Sulfonamide-pyrazoles that are efficacious in reducing the cortical Aβx-40 levels in FVB mice via a single PO dose, as well as sulfonamide-pyrazoles that exhibit selectivity for inhibition of APP versus Notch processing by γ-secretase, are highlighted.

We demonstrate a novel top-down approach for fabricating nanowires with unprecedented complexity and optical quality by taking advantage of a nanoscale self-masking effect. We realized vertical arrays of nanowires of 20-40 nm in diameter with 16 segments of complex longitudinal InGaAsP/InP structures. The unprecedented high quality of etched wires is evidenced by the narrowest photoluminescence linewidth ever produced in similar wavelengths, indistinguishable from that of the corresponding wafer. This top-down, mask-free, large scale approach is compatible with the established device fabrication processes and could serve as an important alternative to the bottom-up approach, significantly expanding ranges and varieties of applications of nanowire technology.

Significant improvement in metabolic stability on the pyrazolopiperidine scaffold over the original series were achieved and this stability improvement translated in an improved in vivo efficacy.

We have reported the growth of p-type As-doped ZnO nanorod (NR) arrays and their electrical and electroluminescence (EL) properties. Well-directed ZnO NR arrays were grown on the Si substrate. The GaAs wafer was employed as an arsenic resource. Thermal anneal was performed to diffuse an As element into a ZnO NR. The As content increased with the increase in annealing time and temperature, which was measured utilizing energy dispersive x-ray spectroscopy in transmission electron microscopy (TEM). When enough As was doped, ZnO NR arrays began to show p-type behaviour and formed good p–n heterojunctions with the n-type Si substrate. The high-resolution TEM (HRTEM) was employed to measure the lattice structure change in the ZnO NR before and after As doping. The ultraviolet EL spectrum of the n-Si/p-ZnO NR arrays' light emitting diode device was measured at room temperature and a peak at a wavelength of about 380 nm was observed in the spectrum.

To explore the clinical effect of transvaginal repair of cesarean scar diverticulum (CSD).Totally 64 patients of CSD in the First Maternity and Infant Hospital, Tongji University between Mar. 2013 and Sept. 2014 underwent transvaginal repair of CSD were reviewed retrospectively and followed.All the patients had a prolonged period, and the duration was (14.8 ± 3.5) days; all the patients were received the transvaginal repair of CSD, there was no intra-operative complications, the procedures were successfully performed in all patients. The mean operation time was (67 ± 12) minutes, the mean blood loss was (53 ± 32) ml, and the mean length of hospital stay was (4.0 ± 1.1) days. All patients were followed after the operation, the duration of menstruation was (8.1 ± 3.5) days shorter in average, which was statistically significant (P0.01); the operation effective rate was 94% (60/64) to assess the clinic syptoms, the operation effective rate was 95% (61/64) for anatomic assessment. The distance of the CSD from the serosa became thicker after surgery significantly, the distance was thicker (3.4 ± 0.4) mm compared with preoperation (P0.01).Transvaginal repair of CSD offers minimal invasiveness, good exposure and accurate resection. It is worth to be popularized in the treatment of patients with CSD.

Time-dependent inhibition (TDI) of cytochrome P450 (CYP) enzymes may incur serious undesirable drug-drug interactions and in rare cases drug-induced idiosyncratic toxicity. The reactive metabolites are often generated through multiple sequential biotransformations and form adducts with CYP enzymes to inactivate their function. The complexity of these processes makes addressing TDI liability very challenging. Strategies to mitigate TDI are therefore highly valuable in discovering safe therapies to benefit patients. In this Letter, we disclose our simplified approach toward addressing CYP3A TDI liabilities, guided by metabolic mechanism hypotheses. By adding a methyl group onto the α carbon of a basic amine, TDI activities of both the truncated and full molecules (7a and 11) were completely eliminated. We propose that truncated molecules, albeit with caveats, may be used as surrogates for full molecules to investigate TDI.

The aim of this study was to validate melanin-concentrating hormone (MCH)-1 receptor antagonism as a potential treatment of mood disorders. We attempted to replicate the effects previously reported with SNAP-7941 and expanded the investigation to three other orally bioavailable MCH-1 receptor antagonists with good brain penetration. SNAP-7941 (3–30 mg/kg, i.p.) and T-226296 (5–60 mg/kg, p.o.) (± racemate), were evaluated in the rat forced swim and mouse tail suspension tests. (+)SNAP-7941 (3–10 mg/kg, p.o.) was also tested in a modified 5-min rat forced swim protocol as previously reported. A-665798 (3–30 mg/kg, p.o.) and A-777903 (3–30 mg/kg, p.o.) were tested in mouse tail suspension and rat Vogel tests. None of the compounds showed meaningful efficacy in the paradigms tested. The lack of efficacy with four structurally different MCH-1 receptor antagonists does not support a role for therapeutic treatment of depression/anxiety via this mechanism of action.

As part of our efforts to identify potent HIV-1 protease inhibitors that are active against resistant viral strains, structural modification of the azacyclic urea (I) was undertaken by incorporating acyl groups as P1′ ligands. The extensive SAR study has yielded a series of N-acyl azacyclic ureas (II), which are highly potent against both wild-type and multiple PI-resistant viral strains.

The effects of a thermal-rate treatment technique on the critical thickness of glass formation for an Al85Ni10Ce5 alloy melt have been investigated. The amorphous ribbon of the alloy with a thickness of 300 μm is obtained using a single-roller melt-spinning technique by the thermal-rate treatment, while that of 50 μm is obtained at conventional melt superheating condition. The experiment shows that the coordination numbers of the Al85Ni10Ce5 alloy melt decreases from 12 to 9 with increasing melt temperature from 900 to 1200 °C. The relationship between the coordination numbers, the first position of the main peak of the alloy melt and the critical cooling rate for getting amorphous alloys has been discussed.

Combinatorial and structure-based medicinal chemistry strategies were used together to advance a lead compound with an activity of K(i) = 58 microM via a potency enhancement of70 000-fold to an analogue with an activity of K(i) = 0.8 nM against influenza neuraminidase (A/Tokyo/67). Lead optimization was initiated using molecular modeling and combinatorial chemistry. Protein crystal structures revealed that inconsistent structure-activity relationship (SAR) data resulted from different binding orientations of the inhibitor core five-membered rings from one series to another. Binding modes for a series of compounds showed up to a 180 degrees variation in orientation of the five-membered ring within the active site. Potent analogues were only achieved with chemical series that were observed to bind in the same orientation and yielded consistent SAR. In one series, consistent binding was obtained by an unprecedented occupation of a negatively charged binding pocket by a neutral methyl ester unit. The structural rationale for this novel SAR variation, based on protein crystallographic data, is given.

Objective This work aims to explore the effects of adaptive statistical iterative reconstruction (ASiR) and model-based iterative reconstruction (MBIR) algorithms in reducing computed tomography (CT) radiation dosages in abdominal imaging. Methods CT scans on a standard male phantom were performed at different tube currents. Images at the different tube currents were reconstructed with the filtered back-projection (FBP), 50% ASiR and MBIR algorithms and compared. The CT value, image noise and contrast-to-noise ratios (CNRs) of the reconstructed abdominal images were measured. Volumetric CT dose indexes (CTDIvol) were recorded. Results At different tube currents, 50% ASiR and MBIR significantly reduced image noise and increased the CNR when compared with FBP. The minimal tube current values required by FBP, 50% ASiR, and MBIR to achieve acceptable image quality using this phantom were 200, 140, and 80 mA, respectively. At the identical image quality, 50% ASiR and MBIR reduced the radiation dose by 35.9% and 59.9% respectively when compared with FBP. Conclusions Advanced iterative reconstruction techniques are able to reduce image noise and increase image CNRs. Compared with FBP, 50% ASiR and MBIR reduced radiation doses by 35.9% and 59.9%, respectively.

The electrochemical deposition and dissolution of lead on gold electrodes immersed in an aqueous solution of lead nitrate were studied in situ using a biasing liquid cell by transmission electron microscopy (TEM). We investigate in real time the growth mechanisms of lead dendrites as deposited on the electrodes under an applied potential. TEM images reveal that lead dendrites are developed by the fast protrusion of lead branches in the electrolyte and tip splitting. And, the fast growing tip of the dendritic branch is composed of polycrystalline nanograins and it develops into a single crystalline branch eventually. This study demonstrated unique electrochemical growth of single crystal dendrites through nucleation, aggregation, alignment and attachment of randomly oriented small grains. Additionally, we found the lead concentration in the electrolyte drastically influences the morphology of dendritic formation.

Herein, we describe our strategy to design metabolically stable γ-secretase inhibitors which are selective for inhibition of Aβ generation over Notch. We highlight our synthetic strategy to incorporate diversity and chirality. Compounds 30 (ELND006) and 34 (ELND007) both entered human clinical trials. The in vitro and in vivo characteristics for these two compounds are described. A comparison of inhibition of Aβ generation in vivo between 30, 34, Semagacestat 41, Begacestat 42, and Avagacestat 43 in mice is made. 30 lowered Aβ in the CSF of healthy human volunteers.

Title compounds (V) are evaluated in the cellular assay but, unfortunately, possess APP selectivity of less than 100-fold.

We report mid-infrared lasing around 3 μm from a single PbS subwavelength wire, with a cavity volume less than the wavelength cubed at 0.44 λ3. The maximal lasing temperature is 180 K under pulse operation.

The preparation of novel tetrahydro-1H-pyrazolo[4,3-c]pyridines is reported. Pivotal to the synthesis of these compounds was the development of mild reaction conditions to generate a highly functionalized nitrilimine capable of undergoing an intramolecular cycloaddition with a tethered alkyne. The desired cycloadduct was formed as an equal mixture of diastereomers.

Surface states in semiconductor nanowires (NWs) are detrimental to the NW optical and electronic properties and to their light emission-based applications, due to the large surface-to-volume ratio of NWs and the congregation of defects states near surfaces. In this paper, we demonstrated an effective approach to eliminate surface states in InAs NWs of zinc-blende (ZB) and wurtzite (WZ) structures and a dramatic recovery of band edge emission through surface passivation with organic sulfide octadecylthiol (ODT). Microphotoluminescence (PL) measurements were carried out before and after passivation to study the dominant recombination mechanisms and surface state densities of the NWs. For WZ-NWs, we show that the passivation removed the surface states and recovered the band-edge emission, leading to a factor of ∼19 reduction of PL linewidth. For ZB-NWs, the deep surface states were removed and the PL peaks width became as narrow as ∼250 nm with some remaining emission of near band-edge surface states. The passivated NWs showed excellent stability in atmosphere, water, and heat environments. In particular, no observable changes occurred in the PL features from the passivated NWs exposed in air for more than five months.

High quality stoichiometric lead sulfide (PbS) wires were synthesized by a simple chemical vapor deposition (CVD) process using pure PbS powder as the material source. Growth mechanisms were systematically investigated under various growth conditions, with three modes of growth identified: direct vapor-liquid-solid (VLS) wire growth nucleating from the substrate surface, bulk PbS crystallites by vapor-solid (VS) deposition, and subsequent VLS growth nucleating on top of the bulk deposition through spontaneously formed catalyst particles. Furthermore, we found that these growth modes can be organized in terms of different levels of supersaturation, with VS bulk deposition dominating at high supersaturation and VLS wire growth on the substrate dominating at low supersaturation. At intermediate supersaturation, the bulk VS deposition can form larger crystallites with domains of similarly oriented wires extending from the flat facets. Both predeposited catalysts and spontaneously formed Pb particles were observed as nucleation catalysts, and their interplay leads to various interesting growth scenarios such as reversely tapered growth with increasing diameter. The VLS growth mechanism was confirmed by the presence of Pb-rich caps revealed in an elaborate cross-sectional transmission electron microscopy (TEM) experiment after focused ion beam milling in a modified lift-out procedure. Temperature-dependent photoluminescence (PL) of PbS wires was performed in the mid-infrared wavelength range for the first time, demonstrating strong light emission from band edge, blue-shifted with increasing temperature. The high optical quality of PbS wires may lead to important applications in mid-infrared photonics. The substrate growth temperature as low as 400 °C allows for silicon-compatible processing for integrated optoelectronics applications.

We report on synthesis of single crystal erbium chloride silicate nanowires, which exhibit superior optical property than erbium silicate, providing a new Si-compatible material for light emission and amplification at1.53 μm wavelength.

We demonstrated a general methodology of growing spatially composition-controlled alloys by combining spatial source reagent gradient with a temperature gradient. Using this dual gradient method, we achieved for the first time a continuous spatial composition grading of single-crystal quaternary Zn(x)Cd(1-x)S(y)Se(1-y) alloy nanowires over the complete band gap range along the length of a substrate. The band gap grading spans between 3.55 eV (ZnS) and 1.75 eV (CdSe) on a single substrate, with the corresponding light emission over the entire visible spectrum. We also showed that the dual gradient method can be extended to achieve alloy composition control in two spatial dimensions. The unique material platform achieved will open a wide range of applications from color engineered display and lighting, full spectrum solar cells, multispectral detectors, or spectrometer on-a-chip to superbroadly tunable nanolasers. The growth methodology can be extended more generally to other alloy systems.

A new histamine H3 receptor (H3R) antagonist chemotype 1 was designed by combining key pharmacophoric elements from two different precursor structural series and then simplifying and optimizing the resulting combined structural features. First, analogues were made based on a previously identified conessine-based H3R antagonist series. While the first analogues 11 and 15 showed no antagonistic activity to H3R, the mere addition of a key moiety found in the reference compound 7 (ABT-239) elevated the series to high potency at H3R. The hybrid structure (16b) was judged too synthetically demanding to enable an extensive SAR study, thus forcing a strategy to simplify the chemical structure. The resulting (3aR,6aR)-5-alkyl-1-aryl-octahydropyrrolo[3,4-b]pyrrole series proved to be highly potent, as exemplified by 17a having a human H3 K(i) of 0.54 nM, rat H3 K(i) of 4.57 nM, and excellent pharmacokinetics (PK) profile in rats (oral bioavailability of 39% and t(1/2) of 2.4 h).

We used an improved cothermal evaporation route for the first time to achieve quaternary semiconductor nanostructured alloys, using an example of Zn(x)Cd(1-x)S(y)Se(1-y) nanobelts. The PL (bandgap) of these as-grown nanostructured alloys can be continuously tunable across the entire visible spectrum through experimentally controlling their compositions. Such widely controlled alloy nanostructures via composition/light emission provide a new material platform for applications in wavelength-tunable lasers, multicolor detectors, full-spectrum solar cells, LEDs, and color displays.

Purpose Craniofacial venous malformations (VMs) are challenging lesions. Treatment is not routinely indicated unless the benefit and loss have been weighed properly. Therefore it is crucial to predict clinical outcome before treatment. This study was performed to retrospectively determine whether pretreatment magnetic resonance imaging (MRI) findings are predictive of outcome in patients who undergo sclerotherapy for craniofacial VMs. Patients and Methods MRI findings and clinical results of percutaneous sclerotherapy with ethanol and bleomycin A 5 in 69 patients with craniofacial VMs were retrospectively reviewed. Lesions were categorized with MRI based on margins; 51 were limited VMs, and 18 were infiltrating VMs. We performed t test analysis to assess the difference in the number of sclerotherapy sessions between the 2 groups. The Kruskal-Wallis test was used to evaluate differences in symptom improvement and satisfaction level between the groups. The difference in complication rates was assessed by χ 2 analysis. Results The better response to treatment was among the patients with limited VMs. The number of sclerotherapy sessions was 1.9 ± 1.2 for limited VMs and 3.6 ± 1.5 for infiltrating VMs, with a significant difference between the groups ( P = .0001). The patients with limited VMs were significantly more likely to have better symptom improvement ( P = .0001) and a higher satisfaction level ( P = .0001). The complication rates of the limited and infiltrating VMs were 18.2% (18/99) and 32.8% (21/64), respectively. A significant difference was found between the groups ( P = .033). Conclusions The feature of lesion margin on MRI before sclerotherapy is an important predictor of treatment outcome for craniofacial VMs.

We demonstrate CdSxSe1-xnanowire growth with x changing from 0 to 1 continuously within 1-cm substrate corresponding to 200-nm wavelength variation on a single substrate, providing novel full-spectrum materials for high-efficiency solar cell applications.

A new structural series of histamine H3 receptor antagonist was developed. The new compounds are based on a quinoline core, appended with a required basic aminoethyl moiety, and with potency- and property-modulating heterocyclic substituents. The analogs have nanomolar and subnanomolar potency for the rat and human H3R in various in vitro assays, including radioligand competition binding as well as functional tests of H3 receptor-mediated calcium mobilization and GTPgammaS binding. The compounds possessed favorable drug-like properties, such as good PK, CNS penetration, and moderate protein binding across species. Several compounds were found to be efficacious in animal behavioral models of cognition and attention. Further studies on the pharmaceutic properties of this series of quinolines discovered a potential problem with photochemical instability, an issue which contributed to the discontinuation of this series from further development.

A new series of H3 receptor antagonists was discovered with nanomolar and subnanomolar affinities at human and rat H3 receptors. Starting from an earlier, more structurally limited series of benzofurans, the present series of compounds demonstrated increased structural variety and flexibility with greater in vitro potency. One compound in particular, [2-[2-(2-(R)-methylpyrrolidin-1-yl)ethyl]benzofuran-5-yl](5-nitropyridin-2-yl)amine (7h), gave the best binding potency (human K(i) of 0.05 nM, rat K(i) of 0.11 nM), which represented a 9-fold (in human) and an 11-fold (in rat) improvement over ABT-239 (compound 5), a compound previously reported to have excellent in vitro potency and in vivo efficacy. The synthesis, SAR of the H3 binding affinities, in vitro assay for phospholipidosis, and pharmacokinetic properties of the new compounds are described.

The structure-activity relationship (SAR) of a novel hydrophobic binding interaction within a subsite of the influenza neuraminidase (NA) active site was characterized and optimized for a series of trisubstituted pyrrolidine inhibitors modified at the 4-position. Previously, potent inhibitors have targeted this subsite with hydrophilic substituents such as amines and guanidines. Inhibitor-bound crystal structures revealed that hydrophobic substituents with sp(2) hybridization could achieve optimal interactions by virtue of a low-energy binding conformation and favorable pi-stacking interactions with the residue Glu119. From a lead methyl ester, investigation of five-membered heteroaromatic substituents at C-4 produced a 3-pyrazolyl analogue that improved activity by making a targeted hydrogen bond with Trp178. The SAR of substituted vinyl substituents at C-4 produced a Z-propenyl analogue with improved activity over the lead methyl ester. The C-1 ethyl ester prodrugs of the substituted C-4 vinyl analogues gave compounds with excellent oral bioavailability (F > 60%) when dosed in rat.