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Raman shift of the C–H symmetric stretching band (v1) of methane can be used to calculate the pressure and density of methane in fluid inclusions. However, previous numerical functions for Raman band shifts and methane density are only suitable for methane with densities lower than 0.3 g/cm3. In this study, Raman shifts for pure CH4 were systematically measured at 25 °C and pressures up to 150 MPa. Parameters of the long range attractive forces were fitted, and Raman shifts of CH4 were calculated with hard sphere model for density up to 0.55 g/cm3. Based on experimental data and theoretical calculation, a unified equation was established to calculate the density of methane gas from Raman shifts over a wide density ranges up to 0.55 g/cm3: D = v d − v o = 211.3 ρ 4 − 73.238 ρ 3 + 24.477 ρ 2 − 29.0632 ρ where ρ represents the density of methane in g/cm3; D(cm-1) is the difference between the measured peak position of methane in the fluid inclusion (vd) and the known peak position of methane at quite low density (vo). The equation will work regardless of which machine the measurements of Raman shifts are done on, as long as the user knows or finds the zero-density peak position.

Based on the new all-covering 3D seismic data and the drilling-logging data, we established the sequence stratigraphic framework for Dongying Depression and identified two kinds of structural systems in Palaeogene, i.e. the extensional structural system and the transtensional structural system. The extensional structural system consists of different normal faults that predominantly trend NE, EW, and NW. The attitudes of the normal faults vary in different tectonic settings. However, the transtensional structural system consists of some strike–slip faults and some normal faults. According to the analysis of the relationships between the faults and the sedimentary sequences of Dongying Depression, we considered that the extensional structural system was developed mainly from the Palaeocene to the middle Eocene, whereas the transtensional structural system was mostly developed from the middle Eocene to the Oligocene. In addition, we found that the structural systems had transformed since 43.5 Ma, whe...

A randomized, partial‐blind, repeat‐dose, 3‐period crossover study (NCT02027454) assessed the effect of cabotegravir on QT interval in healthy subjects. To achieve a supratherapeutic dose, each subject received cabotegravir 150 mg (30 mg × 5 tablets) every 12 hours for a total of 3 doses over 2 days, matching placebo (every 12 hours) over 2 days, or a single open‐label 400‐mg dose of the positive control moxifloxacin, with a 21‐day washout between treatments. Blood samples for pharmacokinetic analyses were collected up to 24 hours after the third dose on day 2. QT interval data were obtained by continuous Holter monitoring for approximately 24 hours at baseline (day ‐1) and from 2 hours before to 24 hours after the third dose on day 2. Plasma cabotegravir exposure was approximately 3‐fold above clinically relevant doses. After 3 doses of 150 mg of cabotegravir administered every 12 hours, all upper limits of 2‐sided 90% confidence intervals for ΔΔQTcF (difference in time‐matched change from baseline for QTcF between cabotegravir and placebo) were 450 milliseconds. There were no serious or grade 3 or 4 adverse events or clinically significant changes in laboratory values, vital signs, or electrocardiogram results. These data demonstrate that cabotegravir at a supratherapeutic dose had no effect on cardiac repolarization.

Improved critical current density in Y0.5Gd0.5 Ba2Cu3O7−δ films is achieved by a controlled study of substrate surface modifications with nano-sized second-phase pre-formed Dy2O3 particles. Nanoparticles were applied to buffered Hastelloy substrates using metal organic deposition techniques prior to YGdBCO film growth. With the introduction of Dy2O3 nanoparticles, YGdBCO films showed more robust field dependence and higher flux pinning force at intermediate fields, indicating Dy2O3 surface decoration with metal organic deposition process is a promising method for enhancement of current-carrying capability of YGdBCO film.

Retroperitoneal liposarcoma is a rare malignancy derived from adipocytes. They can grow to large sizes before inducing clinical symptoms. Giant retroperitoneal liposarcoma with a diameter over 30 centimeters is extremely rare. So far, only 13 cases of giant retroperitoneal liposarcoma with a diameter greater than 30 cm have been reported. There is very little experience in the treatment of these bulky tumors. Herein, we report a 65-year-old male patient diagnosed with giant retroperitoneal liposarcoma. The patient underwent successful complete surgical resection. The tumor was found to occupy almost the entire abdominal cavity, measuring 37.0 cm × 32.0 cm × 26.5 cm in size and 21.0 kg in weight. Histopathological analysis indicated a grade I, well-differentiated liposarcoma. The patient was discharged uneventfully, and no sign of recurrence was observed at 12-month follow-up. Moreover, we reviewed 13 literatures in English published on PubMed database regarding retroperitoneal liposarcoma greater than 30 cm in diameter. The analysis suggests that size alone should not be considered as a contraindication to surgical resection. Combined resection of adjacent organs is necessary if local invasion is confirmed. The role of adjuvant radio or chemotherapy remains controversial. Thorough evaluation on the extent of resection should be made to minimize post-surgery decline in quality of life.

Enhancing the catalytic activity of manganese oxide in oxygen reduction reaction (ORR) is a key issue for its large-scale application in metal-air fuel cells. Ag-doped [Formula: see text]-MnO2 nanowires without Ag or Ag2O have been successfully synthesized via a facile hydrothermal method, and the changes in both the structure and electrochemical catalytic performances after Ag doping are investigated. Compared with the pristine [Formula: see text]-MnO2, the as-prepared Ag-doped MnO2 exhibits a significantly enhanced catalytic activity in both ORR and Mg-air fuel cell application. With Ag/Mn ratio of 1:25, Ag-doped MnO2 exhibits a typical 4e-reaction pathway and presents a 163 mV higher half-wave potential than that of the pristine [Formula: see text]-MnO2. Furthermore, it demonstrates a power density of 75.1[Formula: see text]mW[Formula: see text]cm[Formula: see text] at current density of 134.5[Formula: see text]mA[Formula: see text]cm[Formula: see text] in the Mg-air fuel cells. The enhanced ORR performances are considered to be contributed from the activation of surface lattice oxygen, the improvement in conductivity and the increase in oxygen vacancies of [Formula: see text]-MnO2. These findings provide new understanding for developing high-performance manganese oxide catalysts.

Peptides from natural plant proteins have been observed to show various bioactivities in many studies. In this paper, oxidation resistance and anti-inflammatory effect of three millet prolamins peptides (MPP) was evaluated, including peptides with molecular weight below 1kDa obtained from hydrolysate by alcalase and two other peptides: Pro-Phe-Leu-Phe (PFLF) and Ile-Ala-Leu-Leu-Ile-Pro-Phe (IALLIPF), in human keratinocyte HaCaT cells and RAW264.7 murine macrophages. As a result, MPP effectively reduced the production of reactive oxygen species (ROS) as well as malondialdehyde (MDA) but increased the level of glutathione (GSH) in H2O2-induced HaCaT cells, showing anti-oxidant bioactivity in cells. To be specific, IALLIPF could more effectively both decrease the ROS and increase GSH than the other two peptides. And PFLF had better activity to reduce MDA production. In addition, MPP were able to significantly alleviate inflammation by inhibiting the yield of nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, interleukin IL-6 and IL-1β) in (lipopolysaccharide) LPS-stimulated RAW264.7 murine macrophages. Moreover, these findings suggested that MPP pre-treatment lowered the level of p-IκB and p65 by suppressing the translocation of NF-kB to cell nucleus. Besides, this effect might be related to the inhibition of MAPK pathway as well. Therefore, this study suggested that MPP could be a possible anti-inflammatory alternative for the therapy of inflammatory related illness.

The abuse of antibiotics has led to the enhancement of bacterial drug resistance, which has aroused widespread concern. In our study, an unusual polymer (PADAAC) with aldehyde, vinyl and azo groups was obtained by copolymerization of allyl diazoacetate (ADA) and acrolein (AC). We fabricated a series of hydrogels (PA0AM, PA5AM, PA10AM and PA20AM) by incorporation PADAAC into the acrylamide and N, N′-methylene bis(acrylamide) networks, which can suppress bacterial growth and kill the bacteria with >95%. All the hydrogels possessed low cytotoxicity. More remarkably, the aldehyde groups were protected amino groups via a simple imine reaction. Protected PA20AM had no effect on the bacteria, while deprotected PA20AM recovered its antimicrobial property against Staphylococcus aureus (killing efficiency: 96.1%), Escherichia coli (killing efficiency: 98.3%) and methicillin-resistant Staphylococcus aureus (MRSA) (killing efficiency: 95.0%) after removing the amino groups. PA20AM and deprotected PA20AM also exhibited good antimicrobial property in vivo.

Failure of stent retrieval and periprocedural embolization of plaque are rare complications of carotid artery stenting, which need emergency surgical treatment. In Video 1, we demonstrate failed stent retrieval with acute middle cerebral artery occlusion that was treated with carotid endarterectomy and stent-assisted thrombectomy in a hybrid operating room. A 65-year-old man underwent carotid artery stenting for symptomatic left internal carotid artery stenosis with severe calcification. Immediately after placement of the open-cell carotid stent, left middle cerebral artery M1 segment occlusion was detected. A self-expanding retrievable intracranial stent was used for mechanical thrombectomy. However, the retrievable stent was blocked by the carotid stent and could not be retrieved. We attempted various ways to retrieve the device to avoid embolic complications, including neck rotation and neck compression, but they all failed. Therefore, we decided to perform surgical retrieval. Surgery was performed in a hybrid operating room under general anesthesia, and intraoperative neuromonitoring was used. The surgical field was deployed according to standard procedure. A longitudinal incision was then made through the adventitia on the anterolateral surface of the carotid artery. We pulled both stents out of the vessel and mobilized the plaque from the adventitia. The arteriotomy was closed with a double 6/0 monofilament suture. Angiogram was performed after vessel suturing to confirm there was not vessel wall damage or flow problems. After carotid endarterectomy, the stent-assisted thrombectomy was performed. Postoperative digital subtraction angiography confirmed the recanalization of the middle cerebral artery. The patient's neurologic function dramatically improved after hybrid treatment.

In the present study, an extraction method, combining extraction by ethyl acetate + ethanol and purification by HPD400 resin, was established to obtain huangjiu polyphenol extract (HPE). After extraction and purification, the polyphenol yield was 22.57%, and 90.57% protein and 97.99% sugar were removed. HPLC analysis indicated that (+)-catechin (91.33 μg mL−1) was the predominant phenolic compound among the 11 detected polyphenols. In LPS-stimulated RAW264.7 cells, HPE exhibits anti-inflammatory effects by inhibiting the production of NO and pro-inflammatory cytokines (TNF-α, interleukin IL-6 and IL-1β). The anti-inflammatory effect of HPE is associated with the inhibition of iNOS expression, the suppression of NF-κB translocation to the nucleus, and the inhibition of the phosphorylation of IκB and the MAPK family proteins, e.g. p-38, Erk 1/2, and JNK. Moreover, the activation of Nrf2 and HO-1 is also related to the anti-inflammatory effect of HPE.

Background Danirixin (DNX), a selective and reversible CXC chemokine receptor 2 antagonist, inhibits neutrophil transmigration and activation. This study assessed the safety, tolerability, and clinical effect of DNX with and without oseltamivir (OSV) in adults with acute, uncomplicated influenza. Methods This was a placebo-controlled, double-blind, Phase IIa study. Participants (18–64 years) with influenza-like symptoms (onset ≤48 hours) and positive influenza rapid antigen test were randomized 2:1:2:1 to DNX, placebo, DNX+OSV, or OSV (75 mg each, administered twice daily for 5 days) and followed for 28 days. Primary endpoints included frequency of adverse events (AEs) and serious AEs (SAEs). The effect of DNX on virologic response and clinical effect on influenza symptoms were secondary endpoints. Results A total of 45 participants were enrolled, 35 of whom were confirmed influenza positive by polymerase chain reaction analysis. The highest incidence of AEs was in the placebo group (4 of 7, 57%), followed by the DNX+OSV (7 of 16, 44%), DNX (3 of 15, 20%), and OSV (0 of 7, 0%) groups. One SAE (T-wave abnormality) was reported in the DNX group (unrelated to treatment). No differences in viral load assessments were observed among treatment groups. Conclusions Danirixin treatment was well tolerated and did not impede viral clearance.

Photovoltaic devices, electrochemical cells, catalysis processes, light emitting diodes, scanning tunneling microscopes, molecular electronics, and related devices have one thing in common: open quantum systems where energy and matter are not conserved. Traditionally quantum chemistry is confined to isolated and closed systems, while quantum dissipation theory studies open quantum systems. The key quantity in quantum dissipation theory is the reduced system density matrix. As the reduced system density matrix is an O(M! × M!) matrix, where M is the number of the particles of the system of interest, quantum dissipation theory can only be employed to simulate systems of a few particles or degrees of freedom. It is thus important to combine quantum chemistry and quantum dissipation theory so that realistic open quantum systems can be simulated from first-principles. We have developed a first-principles method to simulate the dynamics of open electronic systems, the time-dependent density functional theory for open systems (TDDFT-OS). Instead of the reduced system density matrix, the key quantity is the reduced single-electron density matrix, which is an N × N matrix where N is the number of the atomic bases of the system of interest. As the dimension of the key quantity is drastically reduced, the TDDFT-OS can thus be used to simulate the dynamics of realistic open electronic systems and efficient numerical algorithms have been developed. As an application, we apply the method to study how quantum interference develops in a molecular transistor in time domain. We include electron-phonon interaction in our simulation and show that quantum interference in the given system is robust against nuclear vibration not only in the steady state but also in the transient dynamics. As another application, by combining TDDFT-OS with Ehrenfest dynamics, we study current-induced dissociation of water molecules under scanning tunneling microscopy and follow its time dependent dynamics. Given the rapid development in ultrafast experiments with atomic resolution in recent years, time dependent simulation of open electronic systems will be useful to gain insight and understanding of such experiments. This Account will mainly focus on the practical aspects of the TDDFT-OS method, describing the numerical implementation and demonstrating the method with applications.

PURPOSE The aim of this study was to evaluate the role of gated myocardial perfusion SPECT (GMPS) phase parameters (phase SD and histogram bandwidth) in predicting the short-term response to cardiac resynchronization therapy (CRT) as left ventricle (LV) remodeling and the long-term effect as all-cause mortality or cardiac transplantation and hospitalization for heart failure. PATIENTS AND METHODS This prospective observational study included 63 consecutive patients undergoing CRT from May 2008 to April 2014. Before CRT, patients underwent evaluation of New York Heart Association functional class, standard 12-lead ECG, Tc-MIBI GMPS, and 2-dimensional echocardiography. The patients were grouped according to complete left bundle-branch block (CLBBB). Follow-up was done every 6 months after pacemaker implantation. The short-term end point was reverse LV remodeling in 6 to 12 months follow-up, and the long-term primary end point was all-cause mortality or cardiac transplantation. The secondary end point was hospitalization for heart failure. RESULTS Reverse LV remodeling showed in 60.9% (39/63) patients (74.5% CLBBB [35/47] vs 25.0% non-CLBBB [4/16], P < 0.001). Phase SD less than 55 degrees, CLBBB, and left atrium diameter were independent predictive factors for reverse LV remodeling. At a median follow-up of 39.76 months, there were 17 deaths and 2 transplantations (17.0% CLBBB vs 68.8% non-CLBBB, P < 0.001). Seventeen patients required hospitalization more than once for heart failure, and 2 underwent heart transplantation (14.9% CLBBB vs 62.5% non-CLBBB, P < 0.001). Multivariate logistic regression showed that only CLBBB was an independent predictive factor for both end points. CONCLUSIONS The GMPS parameters were not independent predictive factors for all-cause mortality or cardiac transplantation and hospitalization for heart failure.

Observations from Aerosol Robotic Network (AERONET) radiometers during 2003–2012 in Beijing are assessed and used to characterize a series of aerosol properties and their variations. Some distinctive features are found. (1) Aerosol optical depth contributed by fine particles at 440 nm (AOD440-F) in spring showed a decreasing trend in the decade; compared with 2003 it decreased about 54 % in the spring of 2012. The annual averaged AOD440-F increased from 2003 to 2007 and decreased after Beijing Olympics (2008). (2) The spectrum of single-scattering albedo (SSA) followed a rapid increasing pattern from 440 to 675 nm and a slow decreasing or neutral pattern from 675 to 1020 nm, but in summer it was nearly wavelength independent. After Beijing Olympics, in addition to summer in which the SSA remained almost unchanged, in the other seasons the SSA increased, this suggests the decline of absorbing aerosols loading. (3) The imaginary part of aerosol refractive indices k(λ) showed a wintertime maximum and summertime minimum associated with the variation of black carbon content. After Beijing Olympics k(λ) significantly decreased. A good correlation between k(λ) and SSA was observed. However, different from the electromagnetic theory predicted, high (low) real part n(λ) sometimes corresponded to low (high) SSA. (4) The volume median radius of fine mode (Rvf) and aerosol optical depth (AOD) showed a good correlation, but the volume median radius of coarse mode (Rvc) and AOD exhibited a minor and negative correlation which different from previous studies.

Background: Dolutegravir (DTG; Tivicay; ViiV Healthcare, Research Triangle Park, NC) is an HIV-1-unboosted integrase inhibitor with no cytochrome P450 or uridine 5′diphosphate-glucuronosyltransferase inhibition or induction. As DTG is administered to HIV-1–infected women receiving oral contraceptives, assessing the potential for drug interactions was warranted. Objective: To determine the impact of DTG on the pharmacokinetics (PK) and pharmacodynamics (PD) of a common oral contraceptive, norgestimate/ethinyl estradiol (NGM/EE; Ortho-Cyclen; Ortho-McNeil-Janssen Pharmaceuticals, Inc, Raritan, NJ). Methods: This randomized, 2-period, double-blind, placebo-controlled study was conducted within 1 menstrual cycle at 1 clinical center in the United States; 16 women were enrolled. Participants received NGM 0.25 mg/EE 0.035 mg throughout the study. During days 1 to 10, they were randomized to receive twice-daily DTG 50 mg or matching placebo with food and switched to the other treatment during days 12 to 21. Results: Ratios of area under the concentration-time curve from time 0 until end of the dosage interval (AUC0-τ), maximum plasma concentration, and concentration at the end of the dosage interval of norelgestromin with DTG treatment to the same PK parameters with placebo treatment were 0.975, 0.890, and 0.932, respectively; for EE, ratios were 1.03, 0.99, and 1.02, respectively. No significant differences in luteinizing hormone, follicle-stimulating hormone, and progesterone were detected on days 1, 10, 11, 21, and 22. DTG steady-state AUC0-τ was similar to historical data. No severe or grade 3/4 adverse events occurred. Conclusions: DTG had no effect on NGM/EE PK or PD. NGM/EE can be administered with DTG without dose adjustment.

Quantum interference in cross-conjugated molecules can be utilized to construct molecular quantum interference effect transistors. However, whether its application can be achieved depends on the survivability of the quantum interference under real conditions such as nuclear vibration. We use two simulation methods to investigate the effects of nuclear vibration on quantum interference in a meta-linked benzene system. The simulation results suggest that the quantum interference is robust against nuclear vibration not only in the steady state but also in its transient dynamics, and thus the molecular quantum interference effect transistors can be realized.

For the bad accuracy and high costs of the transit passenger traffic statistics, we propose a machine vision-based algorithm. As the body parts of the human often occur overlap in congested conditions, the algorithm in this study uses the overhead image of the passengers as the statistic targets. The Histogram of Oriented Gradient (HOG) combined with the Support Vector Machine (SVM) is adopted in this study. Compared with the traditional methods, the accuracy and the speed of the detection stage have been greatly improved. The algorithm can be divided into three steps: the target detection, target tracking and statistics. Based on the machine learning methods, it first extracts the head HOG feature, and then uses the SVM algorithm to train feature sets to get a classifier based on passenger heads. We choose the Camshift as the tracking algorithm. In order to improve the correct trajectory, it must be fuse the target detection and the target tracking. Through the rules of the passengers to alight, we can get the number of passengers automatically.

Gastrointestinal (GI) malignancies are the most prevalent tumors worldwide, with increasing incidence and mortality. Although surgical resection, chemotherapy, radiotherapy, and molecular targeted therapy have led to significant advances in the treatment of GI cancer patients, overall survival is still low. Therefore, alternative strategies must be identified to improve patient outcomes. In the tumor microenvironment, tumor cells can escape the host immune response through the interaction of PD-1 and PD-L, which inhibits the function of T cells and tumor-infiltrating lymphocytes while increasing the function of immunosuppressive T regulatory cells. The use of an anti-PD-1/PD-L blockade enables reprogramming of the immune system to efficiently identify and kill tumor cells. In recent years, the efficacy of PD-1/PD-L blockade has been demonstrated in many tumors, and this treatment is expected to be a pan-immunotherapy for tumors. Here, we review the signaling pathway underlying the dysregulation of PD-1/PD-L in tumors, summarize the current clinical data for PD-1/PD-L inhibitors in GI malignancies, and discuss road toward precision immunotherapy in relation to PD-1/PD-L blockade. The preliminary data for PD-1/PD-L inhibitors are encouraging, and the precision immunotherapy of PD-1/PD-L inhibitors will be a viable and pivotal clinical strategy for GI cancer therapy.

This paper demonstrates an 8 × 8 Butler Matrix design that does not employ cross-overs. The Butler Matrix was manufactured on a single side of Printed Circuit Board (PCB) and is intended for use with a low-profile C-band directional antenna array. This solution provides an effective methodology for electronically switching beam states of a planner distributed array where typical applications of active phase shifters would either be cost prohibitive or are unnecessary to meet the technical requirements. This design makes use of a series of quadrature hybrid couplers made up of microstrip line circuit board. Test results show that the Matrix efficiently produces the necessary power and phase distribution to each output port allowing the antenna array to show 8 distinct beam states.

BACKGROUND: GSK1265744 (744) is an HIV-1 integrase inhibitor in clinical development as a long-acting (LA) injectable formulation. This study evaluated plasma and tissue pharmacokinetics after single-dose administration of 744 LA administered by intramuscular (IM) or subcutaneous injections. METHODS: This was a phase I, open-label, 9-cohort, parallel study of 744 in healthy subjects. 744 was administered as a 200 mg/mL nanosuspension at doses of 100-800 mg IM and 100-400 mg subcutaneous. RESULTS: Eight (6 active and 2 placebo) male and female subjects participated in each of the first 7 cohorts. All 8 subjects, 4 males and 4 females, received active 744 LA in cohorts 8 and 9 and underwent rectal and cervicovaginal tissue sampling, respectively. Plasma pharmacokinetic sampling was performed for a minimum of 12 weeks or until 744 concentrations were ≤0.1 μg/mL. Rectal and cervicovaginal tissue biopsies were performed at weeks 2 and 8 (cohort 8) and weeks 4 and 12 (cohort 9). 744 LA was generally safe and well tolerated after single injections. A majority of subjects reported injection site reactions, all graded as mild in intensity. Plasma concentration-time profiles were prolonged with measureable concentrations up to 52 weeks after dosing. 744 LA 800 mg IM achieved mean concentrations above protein adjusted-IC90 for approximately 16 weeks. Rectal and cervicovaginal tissue concentrations ranged from

Aims The aim was to evaluate the effect of boceprevir and telaprevir on dolutegravir pharmacokinetics (PK); the effect of dolutegravir on boceprevir and telaprevir PK was assessed through comparison with historical data for each hepatitis C virus (HCV) drug's prescribing information alone. Methods This was a single-centre, randomized, open-label, two-cohort, two-period, one-way study in healthy adult subjects. Dolutegravir 50 mg once daily was administered for 5 days in Period 1, and dolutegravir 50 mg once daily was coadministered with either boceprevir 800 mg every 8 h (Cohort 1) or telaprevir 750 mg every 8 h (Cohort 2) for 10 days in Period 2. Results No deaths or serious adverse events were reported during the study. Four subjects were withdrawn from the study because of adverse events (elevated alanine aminotransferase, cellulitis, increased serum creatinine and dizziness). One subject became pregnant during the study. Coadministration of dolutegravir with boceprevir had no effect on dolutegravir area under the plasma concentration–time curve (AUC) and maximal plasma concentration (Cmax) and caused a small increase in concentration at the end of the dosing interval (Cτ; 8%). Coadministration of dolutegravir with telaprevir resulted in increased dolutegravir plasma exposures compared with those after administration of dolutegravir alone; AUC0–τ, Cmax and Cτ increased by 25, 19 and 37%, respectively. Coadministration of boceprevir or telaprevir with dolutegravir had no clinically significant effect on dolutegravir PK. Plasma boceprevir and telaprevir PK data for either combined treatment were similar to historical data, indicating no effect of dolutegravir on boceprevir or telaprevir exposure. Conclusions Dolutegravir can be coadministered with boceprevir or telaprevir in patients coinfected with HIV and HCV with no dose adjustment.

Mesocarbon microbeads (MCMBs) were synthesized by pyrolyzing the hexane insoluble (HI) extracted from the coal-tar pitch in the dimethyl silicone dispersant. Structural development of product thus prepared was investigated by X-ray diffractometer, scanning electron microscope and particle size analyzer. Experimental results indicated that the HI-derived MCMBs possessed well-graphitized structure, excellent spherical morphology and even particle size due to preprocessing of the pitch raw material. It was suggested that structural improvement benefited from homogenous nucleation and good fluidity of the mesophase spherules.

Highly pure Ba0.5Sr0.5Co0.8Fe0.2O3 − δ (BSCF) perovskite nanocompound was synthesized via glycine-nitrate process (GNP) and coprecipitation-azeotropic distillation method (ADM), respectively. Compared to ADM, GNP was proved to facilitate the synthesis of BSCF powder with small crystal and particle sizes as well as large surface area. BSCF material was employed as the cathode of solid oxide fuel cell (SOFC) incorporating with Sm0.2Ce0.8O1.9 (SDC) electrolyte. Linear sweep voltammetry (LSV) and electrochemical impedance spectroscopy (EIS) tests indicated that the GNP powder-based cathode not only exhibited high electrocatalytic activity but also possessed low oxygen diffusion resistance due to the high porosity. As a result, the cell with GNP powder-based cathode showed a power density of 0.35 W cm−2 when the voltage was 0.7 V at 650 °C. Furthermore, the cathode performance was significantly improved at the high current density condition.

Understanding and controlling the shape of materials has attracted considerable attention over the past few decades. Taking a typical transition metal chalcogenide NiSe2 as an example, we have figured out the role of chemical potential in the equilibrium shape of materials by a combined theoretical and experimental study. The theoretical equilibrium shape evolution of NiSe2 with chemical potential has been investigated using ab initio atomistic thermodynamics and Wulff construction. Moreover, in order to confirm our theoretical results, a series of NiSe2 crystals with different morphologies were also synthesized via a solvothermal route in mixed solvents of hydrazine hydrate, ethylenediamine and reactant. X-ray powder diffraction (XRD) and field emission scanning electron microscopy (FESEM) were used to analyze the products. Our results indicated that the theoretical equilibrium shapes of NiSe2 change from pyritohedron enclosed by (210) facet, truncated octahedron to perfect octahedron occupied by (111) facet, which agrees with the experimental shapes of NiSe2 synthesized with different volume ratios of mixed solvents. The present theory and experimental work indicates that controlling the chemical potential is a general and efficient way to tailor the shape of materials.

Supercapacitor with high energy density and super-long cyclic durability is attractive for the rechargeable energy storage devices. The combination of multiple pseudo-capacitive materials is favorable for improving the energy density of supercapacitor, but the rationally designed electrode structures are highly desirable for achieving the super-long cyclic durability. Here we realize a novel hierarchical NiS/NiTe/Ni positive electrode for supercapacitor, and the assembled asymmetric supercapacitor using the positive electrode demonstrates a super-long cycle life exceeding 200 000 cycles. In the positive electrode, a porous NiTe inner layer acts as the volumetric stain buffer layer between a rigid Ni substrate and a spongy NiS outer layer. In particular, the initiation of volumetric expansion from NiTe inner layer to NiS outer layer, along with the proceeding of volumetric shrinkage from the outer to the inner layer occurring in sequence on the positive electrode play crucial roles in the super-long cycle life, for which sheds a new light on the design/synthesis of multiple pseudo-capacitive materials to achieve the outstanding cyclic stability of supercapacitors.

Rationale The inferior parathyroid glands derive from the third branchial pouch and seldom ectopically migrate to thyroid grand, mediastinum, thymus. Ectopic intrathyroidal parathyroid grand (ETPG) is rare and it cannot be consistently detected by any imaging examinations. The unusual ETPG is easily resected during thyroidectomy, which might cause postoperative hypoparathyroidism. Auto-transplantation of even a parathyroid gland can restore parathyroid function to some extent. Until now, there are not any guidelines on the management of ETPG. Patient concerns Without any symptoms, a 27-year-old female patient was admitted to our hospital for a thyroid nodule. Thyroid ultrasonography demonstrated a hypoechoic nodule, measuring 0.6 cm × 0.6 cm × 0.7 cm, with multiple punctate micro-calcifications within the right thyroid lobe. Thyroid function tests were normal. The invasive fine needle aspiration cytology for the thyroid nodule was rejected by patient. Diagnoses The patient was firstly diagnosed as right thyroid hypoechoic nodule, which was pathologically proved to be papillary thyroid carcinoma (PTC) finally. Interventions The patient underwent right thyroidectomy, central compartment neck dissection, parathyroid exploration, and auto-transplantation of the normal ETPG. Outcomes The right thyroid hypoechoic nodule was diagnosed as PTC by pathological examination. The inferior parathyroid gland could not found in normal locations. On the cut surface of excised thyroid lobe, a yellow and soft nodule was discovered and it was pathologically diagnosed as a normal parathyroid grand. In the end, auto-transplantation of the normal ETPG was conducted. Postoperative follow-ups found both serum calcium and parathyroid hormone tests were normal. Lessons ETPG in a patient with PTC is easily overlooked and unexpectedly excised for its rarity. ETPG brings about a failed parathyroid exploration. However, within the thyroid parenchyma, it might be occasionally discovered by cutting a thyroid lobe into slices. Auto-transplantation of normal ETPG is necessary.

Dolutegravir (DTG) and GSK1265744 are HIV integrase inhibitors (INIs) in clinical development. The oral formulation of rilpivirine (RPV), a nonnucleoside reverse transcriptase inhibitor (NNRTI), has been approved for treatment-naive HIV infection. Long-acting depot injections of GSK1265744 and RPV are also being developed. This study evaluated the potential for drug interactions between RPV and these INIs. This phase 1, open-label, two-cohort, three-period, single-sequence crossover study evaluated oral coadministration of RPV with DTG or GSK1265744. Healthy subjects received DTG (50 mg every 24 h for 5 days) or GSK1265744 (30 mg every 24 h for 12 days) in period 1 followed by a washout, RPV (25 mg every 24 h for 11 or 12 days) in period 2, immediately followed by RPV (25 mg every 24 h) plus DTG (50 mg every 24 h) for 5 days or GSK1265744 (30 mg every 24 h) for 12 days in period 3. Steady-state pharmacokinetic (PK) parameters were estimated using noncompartmental analysis of data collected on the last day of each period. The combinations of RPV and DTG ( n = 16) and of RPV and GSK1265744 ( n = 11) were well tolerated; no grade 3 or 4 adverse events (AEs) or AE-related discontinuations were observed. The 90% confidence intervals for the area under the curve from time zero until the end of the dosage interval [AUC 0–τ ] and maximum concentration of drug in serum ( C max ) geometric mean ratios were within 0.8 to 1.25. Following administration of DTG + RPV, DTG and RPV C τ increased by 22% and 21%, respectively. Following administration of GSK1265744 + RPV, RPV C τ decreased 8%. DTG and GSK1265744 can be administered with RPV without dosage adjustment for either agent. These results support coadministration of RPV with DTG or GSK1265744 as either oral or long-acting depot injection regimens. (This study has been registered at ClinicalTrials.gov under registration no. NCT01467531.)

We present a facile synthesis of trigonal selenium with butterfly-like microstructure from elemental selenium via a solvothermal and aging route. By using X-ray diffraction and scanning electron microscopy to characterize the products, a possible growth mechanism is proposed. The solvothermal process promotes the dissolution of selenium in ethylenediamine to form a brown homogeneous [Se(en)x] solution. By introducing acetone into this [Se(en)x] solution, amorphous selenium nanoparticles were produced which then transformed into trigonal selenium, which further assembled along the c-axis to form hexagonal rods. Owing to stereo hindrance as well as to development of opposite lateral sides of the hexagonal rod in opposing directions, a butterfly-like microstructure consisting of two long outside rods and a short inner rod was obtained.

Prednisone, a corticosteroid frequently used to treat common AIDS-related illnesses and comorbidities, has been shown to induce drug metabolism. This study was performed to determine whether prednisone coadministration affected the pharmacokinetics of dolutegravir (DTG). In this open-label, repeat-dose study, 12 healthy subjects were administered DTG at 50 mg daily alone for 5 days and then with concomitant prednisone for 10 days (prednisone at 60 mg daily for 5 days, followed by a 5-day taper). Serial blood sampling and safety assessments were performed during the trial. Pharmacokinetic parameters were determined using noncompartmental methods and geometric least-square mean ratios, and 90% confidence intervals were generated. Coadministration of DTG and 5-day high-dose prednisone with a 5-day taper had a modest effect on DTG exposure. The area under the DTG plasma concentration-time curve, maximum observed DTG concentration, and 24-hour postdose DTG concentration were increased by 11%, 6%, and 17%, respectively, on day 10 of the combination. Similar results were observed after 5 days of DTG and prednisone. Dolutegravir and prednisone coadministration was well tolerated. The changes in plasma exposures of DTG in healthy individuals as a result of prednisone dosing were not clinically significant. No dose adjustment is required for DTG coadministered with prednisone. (This study has been registered at ClinicalTrials.gov under registration no. NCT01425099.)

This study evaluated dolutegravir pharmacokinetics (PK) in subjects with moderate hepatic impairment compared to matched, healthy controls. In this open-label, parallel-group study, eight adult subjects with moderate hepatic impairment (Child-Pugh Score 7-9) and eight healthy subjects matched for gender, age, and body mass index received a single dolutegravir 50-mg dose. Following dosing, 72-hour PK sampling was performed to determine total and unbound dolutegravir concentrations. PK parameters were calculated using non-compartmental analysis. Geometric least squares mean ratios (GMR) and 90% confidence intervals (CIs) in subjects with hepatic impairment versus healthy subjects were generated by analysis of variance. Results showed that PK parameters of total plasma dolutegravir were similar between subject groups. The unbound fraction was higher in subjects with moderate hepatic impairment than in healthy subjects with GMR (90% CI) of 2.20 (1.62, 2.99) for unbound fraction at 3 hours post-dose and 1.76 (1.23, 2.51) for unbound fraction at 24 hours post-dose; this correlated with lower serum albumin concentrations and was not considered clinically significant. Dolutegravir was well tolerated in both groups; all adverse events were reported as minor. Although free fraction was increased, no dose adjustment is required for patients treated with dolutegravir who have mild to moderate hepatic impairment.

The pharmacokinetics, metabolism, and excretion of dolutegravir, an unboosted, once-daily human immunodeficiency virus type 1 integrase inhibitor, were studied in healthy male subjects following single oral administration of [ 14 C]dolutegravir at a dose of 20 mg (80 μCi). Dolutegravir was well tolerated, and absorption of dolutegravir from the suspension formulation was rapid (median time to peak concentration, 0.5 h), declining in a biphasic fashion. Dolutegravir and the radioactivity had similar terminal plasma half-lives ( t 1/2 ) (15.6 versus 15.7 h), indicating metabolism was formation rate limited with no long-lived metabolites. Only minimal association with blood cellular components was noted with systemic radioactivity. Recovery was essentially complete (mean, 95.6%), with 64.0% and 31.6% of the dose recovered in feces and urine, respectively. Unchanged dolutegravir was the predominant circulating radioactive component in plasma and was consistent with minimal presystemic clearance. Dolutegravir was extensively metabolized. An inactive ether glucuronide, formed primarily via UGT1A1, was the principal biotransformation product at 18.9% of the dose excreted in urine and the principal metabolite in plasma. Two minor biotransformation pathways were oxidation by CYP3A4 (7.9% of the dose) and an oxidative defluorination and glutathione substitution (1.8% of the dose). No disproportionate human metabolites were observed.

Aim Dolutegravir (DTG; S/GSK1349572) is under clinical development as a once daily, unboosted integrase inhibitor for the treatment of HIV infection. The effect of DTG on glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and creatinine clearance (CLcr) was evaluated in 34 healthy volunteers. Methods Subjects received DTG 50 mg (once daily or twice daily) or placebo for 14 days. GFR was measured by iohexol plasma clearance, ERPF was assessed by para-aminohippurate plasma clearance and CLcr was measured by 24 h urine collection. Results All treatments were generally well tolerated. A modest decrease (10–14%) in CLcr was observed, consistent with clinical study observations. DTG 50 mg once daily and twice daily had no significant effect on GFR or ERPF compared with placebo over 14 days in healthy subjects. Conclusions These findings support in vitro data that DTG increases serum creatinine by the benign inhibition of the organic cation transporter 2, which is responsible for tubular secretion of creatinine.

The majority of HIV-1 integrase amino acid sites are highly conserved, suggesting that most are necessary to carry out the critical structural and functional roles of integrase. We analyzed the 34 most variable sites in integrase (>10% variability) and showed that prevalent polymorphic amino acids at these positions did not affect susceptibility to the integrase inhibitor dolutegravir (S/GSK1349572), as demonstrated both in vitro (in site-directed mutagenesis studies) and in vivo (in a phase IIa study of dolutegravir monotherapy in HIV-infected individuals). Ongoing clinical trials will provide additional data on the virologic activity of dolutegravir across subject viruses with and without prevalent polymorphic substitutions.

HIV integrase inhibitors such as raltegravir and elvitegravir halt HIV progression, but treatment-emergent resistance and cross-resistance have been observed. The nonnucleoside reverse transcriptase inhibitor etravirine (ETR) may be used in combination with integrase inhibitors in patients with drug resistance. This single-center, open-label, two-period, single-sequence crossover study evaluated the effects of ETR coadministration on the pharmacokinetic profile of S/GSK1265744, an investigational integrase inhibitor in phase 2 studies. Healthy subjects received 30 mg of S/GSK1265744 alone once daily for 10 days (period 1) and in combination with 200 mg of ETR twice daily for 14 days (period 2). Serial plasma samples for pharmacokinetic analyses were collected on day 10 during period 1 and on day 14 during period 2. All treatments were well tolerated. Etravirine had no effects on S/GSK1265744 geometric mean ratios of the area under the curve from time zero until the end of the dosing interval (1.01; 90% confidence interval [CI], 0.956 to 1.06), of the maximum observed plasma concentration (1.04; 90% CI, 0.987 to 1.09), or of the plasma concentration at the end of the dosing interval (0.999; 90% CI, 0.942 to 1.06). Etravirine pharmacokinetics (PK) parameters observed following coadministration with S/GSK1265744 were in the range of historical values reported for ETR alone in healthy subjects. These results indicate that 30 mg of S/GSK1265744 for 10 days as monotherapy followed by an additional 14 days in combination with ETR was well tolerated in healthy subjects and that no dose adjustment of S/GSK1265744 is required when it is coadministered with ETR.

Background Cotreatment of tuberculosis (TB) and HIV among coinfected patients is now the standard of care. Rifampin (RIF) is a standard part of TB treatment but is a potent inducer of drug metabolizing enzymes. This study evaluated the effect of RIF or rifabutin (RBT) on the pharmacokinetics of the investigational HIV integrase inhibitor, dolutegravir (DTG). Methods Phase I pharmacokinetic drug interaction study. In arm 1, healthy subjects received 50 mg of DTG once daily for 7 days (period 1), then 50 mg of DTG twice daily for 7 days (period 2), then 50 mg of DTG twice daily together with 600 mg of RIF once daily for 14 days (period 3). In arm 2, subjects received 50 mg of DTG once daily for 7 days (period 1) then 50 mg of DTG once daily together with 300 mg of RBT once daily for 14 days (period 2). PK sampling was performed at the end of each period. Results In arm 1, comparing period 3 to period 1, the geometric mean ratio (GMR) for the 24-hour area under the time-concentration curve (AUC0-24) was 1.33 [90% confidence interval (CI): 1.14 to 1.53], and the GMR for the trough (Cτ) was 1.22 (90% CI: 1.01 to 1.48). Comparing period 2 to period 1 in arm 2, the GMR for the AUC0-24 was 0.95 (90% CI: 0.82 to 1.10), and the GMR for the Cτ was 0.70 (90% CI: 0.57 to 0.87). Conclusions Regimens including twice-daily DTG and RIF or once-daily DTG and RBT may represent a new treatment option for patients who require concomitant treatment of HIV and TB.

Background Both lamivudine and adefovir dipivoxil are approved for the treatment of chronic hepatitis B (CHB) and have established safety profiles. A fixed-dose combination (FDC) formulation of lamivudine/adefovir dipivoxil for the treatment of CHB may provide dosing convenience and improve adherence. Objective This study compared the pharmacokinetic profiles of an FDC capsule containing lamivudine/adefovir dipivoxil 100/10 mg and conventional lamivudine 100-mg + adefovir dipivoxil 10-mg tablets to determine bioequivalence. Methods This randomized, open-label, single-dose, 2-period crossover study was conducted in healthy male Chinese subjects. The study included a screening visit, 2 treatment sessions, and a follow-up visit. Subjects who met the inclusion/exclusion criteria were assigned to receive, in randomized order, 1 FDC capsule or 1 tablet each of lamivudine and adefovir dipivoxil. After a 7- to 10-day washout period, alternate treatment was given to the subjects during the second treatment session. Blood samples were collected immediately before and after dosing for 48 hours for plasma drug concentration measurement. Data on adverse events (AEs) were collected from the start of dosing until the follow-up visit. Tolerability assessments included physical examinations with vital sign measurements and clinical laboratory evaluations throughout the study. Results Forty subjects were enrolled into the study (mean age, 22.4 years [range, 19–28 years]; weight, 63.8 kg [range, 54–78 kg]). The pharmacokinetic profiles of lamivudine and adefovir were similar between the FDC and reference formulations. The geometric mean ratios (GMRs) for lamivudine C max and AUC 0–last were 1.02 (90% CI, 0.92–1.12) and 0.99 (90% CI, 0.95–1.04), respectively; adefovir, 0.94 (90% CI, 0.89–0.99) and 0.95 (90% CI, 0.91–1.00). A limited number of mild AEs were reported, with no clinically significant changes in vital signs or laboratory results. Conclusions The FDC capsule was bioequivalent to the concurrent administration of lamivudine + adefovir dipivoxil tablets based on the 90% CIs of the GMRs for C max , AUC 0–∞ , AUC 0–last , and t 1 2 (all were between 0.80 and 1.25). Both treatments were well-tolerated. Clinicaltrial.gov identifier: NCT01353742.

The transient current through an array of as many as 1000 quantum dots is simulated with two newly developed quantum mechanical methods. To our surprise, upon switching on the bias voltage, the current increases linearly with time before reaching its steady state value. And the time required for the current to reach its steady state value is proportional to the length of the array, and more interestingly, is exactly the time for a conducting electron to travel through the array at the Fermi velocity. These quantum phenomena can be understood by a simple analysis on the energetics of an equivalent classical circuit. An experimental design is proposed to confirm the numerical findings.

The synthesis of ammonia and liquid fuel are two important chemical processes in which most of the energy is consumed in the production of H2 /N2 and H2 /CO synthesis gases from natural gas (methane). Here, we report a membrane reactor with a mixed ionic-electronic conducting membrane, in which the nine steps for the production of the two types of synthesis gases are shortened to one step by using water, air, and methane as feeds. In the membrane reactor, there is no direct CO2 emission and no CO or H2 S present in the ammonia synthesis gas. The energy consumption for the production of the two synthesis gases can be reduced by 63 % by using this membrane reactor. This promising membrane reactor process has been successfully demonstrated by experiment.

The article uses content analysis method, using CNKI database as a search tool to retrieve the relevant papers published during the period of 2002-2015.By comparing, analyzing and integrating the research history, research types, research topics, research content and so on ,we think the further development of personalized learning system can not be separated from the support of mobile technology and the integration of subject knowledge, in order to provide reference for the study of personalized learning system.

Systematic shape evolution of hexagonal NiSe crystals is realized via a simple solvothermal route in a mixture of NiCl2·6H2O, elemental selenium, hydrazine hydrate and ethylenediamine. By introducing ammonium chloride as electrolyte and varying the volume ratios of hydrazine hydrate to ethylenediamine, shape evolution of hexagonal NiSe crystals from small hexagonal microdisks to hexagonal microdisks in larger width, microspheres, hexagonal prisms and hexagonal bitowers is successfully achieved. X-ray powder diffraction, field emission scanning electron microscopy, energy dispersion spectrometer, transmission electron microscopy and selected area electron diffraction are performed for the analyses of the products. The ionization and hydrolysis of ammonium chloride decrease the nucleation rate of hexagonal NiSe and the diffusion rate of growth resources, while the adsorption of ethylenediamine at {001} facets of hexagonal NiSe crystals inhibits the crystal growth in directions, thus leading to various novel architectures.

The scent fingerprint of Rosa laevigata Michx., Rosaceae, samples harvested at different periods was investigated. Principal component analysis (PCA) and discriminant factor analysis (DFA) were done on the scent response values measured by an electronic nose (EN) sensor. Statistical quality control (SQC) analysis was also conducted. The R. laevigata samples were clustered into two categories after being analyzed by PCA and DFA. One cluster consisted of samples No. 1 to No. 6, and the other consisted of samples No. 7 to No. 10. The combination of EN, PCA, and DFA for scent analysis can be used for the quality control of traditional Chinese medicines.

Dispersed rhombohedral NiS rods with high aspect ratios and rhombic dodecahedron-like cubic NiS{sub 2} crystals were prepared by solvothermal routes using NiCl{sub 2}.6H{sub 2}O and Na{sub 2}S{sub 2}O{sub 3}.5H{sub 2}O as reagents and ethylenediamine as a solvent, and 3D blossoming flower-like rhombohedral NiS microstructures were synthesized using different sulfur sources of thiourea. The products were characterized by X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, energy dispersion spectrometry and selected area electronic diffraction. All the products were pure and had good single crystalline nature. The synthesis parameters were of great importance on the purity and morphology of the products. The possible growth mechanisms have been discussed based on the analyses of the effects of sulfur sources and solvent on the crystal structures and detailed configurations of the products. The present work is likely to help the phase-controlled synthesis of other metal chalcogenides. - Graphical abstract: Rhombohedral NiS dispersed rods and 3D flower-like microstructures are evolved from dispersed nucleus and aggregate of nucleus, respectively, and the cross-sections of such rods are in equilateral triangle-like shape. Highlights: > 3D blossoming flower-like r-NiS microstructures are obtained. > Equilateral triangle-like cross-sections of r-NiS rods are observed. > Approach based on XRD analysismore » to phase-controlled synthesis is presented.« less

AIMS S/GSK1349572 is an unboosted, once daily, next generation integrase inhibitor with potent activity, low pharmacokinetic (PK) variability and a novel resistance profile. As the primary route of metabolism is via glucuronidation, the effects of atazanavir (ATV, a UGT1A1 inhibitor) and atazanavir/ritonavir (ATV/RTV) on S/GSK1349572 PK were evaluated.

Monoclinic BiVO 4 nanorods and nanoplates were synthesized via the CTAB/water/n-butanol/n-octane microemulsion-mediated hydrothermal process. The physical and photophysical properties of the as-prepared samples were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Raman spectroscopy, and UV–vis diffuse reflectance spectroscopy (UV–vis). It was found that the ratio of H 2 O to CTAB in microemulsion played a key role in the morphology evolution of the products. The possible formation mechanism of BiVO 4 nanostructure with various morphologies was briefly discussed. The Raman results indicated that the symmetry distortions in the local structure of the synthesized BiVO 4 were affected by the morphology of the products. The bandgaps ( E g ) of BiVO 4 nanorods and nanoplates are 2.45 and 2.38 eV, respectively. The synthesized BiVO 4 nanoplates showed superior photocatalytic activity compared with BiVO 4 nanorods due to their higher degree of structural distortion, larger surface area, and thinness.

Objectives: To evaluate the effect of pH-altering agents on S/GSK1349572 exposure in healthy subjects. Methods: S/GSK1349572 is an unboosted, once-daily, next-generation HIV integrase inhibitor. In the first study, 16 subjects received four single-dose treatments: (i) S/GSK1349572 50 mg; (ii) S/GSK1349572 50 mg with a multivitamin (MVI; One A Day Maximum); (iii) S/GSK1349572 50 mg with a liquid antacid (Maalox Advanced Maximum Strength); and (iv) S/GSK1349572 50 mg 2 h before an antacid. In the second study, 12 subjects received a single dose of S/GSK1349572 alone and on day 5 of omeprazole. Results: All treatments were well tolerated. MVI co-administration modestly decreased S/GSK1349572 AUC by 33%. Concurrent antacid co-administration reduced S/GSK1349572 AUC by 74% and staggered antacid dosing significantly diminished this interaction, with a reduction in S/GSK1349572 AUC of 26%. Omeprazole did not significantly affect S/GSK1349572 exposure. Conclusions: S/GSK1349572 can be taken with proton pump inhibitors and MVIs without dose adjustment but should be administered 2 h before or 6 h after antacids.

N-acylhydrazones containing glycine residue 3a-j and 8a-h were synthesized as HIV-1 capsid protein assembly inhibitors. The structures of the novel N-acylhydrazone derivatives were characterized using different spectroscopic methods. Antiviral activity demonstrated that compound 8c bearing 4-methylphenyl moiety was the most active with low cytotoxicity.

Neural network-based first-principles method for predicting heat of formation (HOF) was previously demonstrated to be able to achieve chemical accuracy in a broad spectrum of target molecules [L. H. Hu et al., J. Chem. Phys. 119, 11501 (2003)]. However, its accuracy deteriorates with the increase in molecular size. A closer inspection reveals a systematic correlation between the prediction error and the molecular size, which appears correctable by further statistical analysis, calling for a more sophisticated machine learning algorithm. Despite the apparent difference between simple and complex molecules, all the essential physical information is already present in a carefully selected set of small molecule representatives. A model that can capture the fundamental physics would be able to predict large and complex molecules from information extracted only from a small molecules database. To this end, a size-independent, multi-step multi-variable linear regression-neural network-B3LYP method is developed in this work, which successfully improves the overall prediction accuracy by training with smaller molecules only. And in particular, the calculation errors for larger molecules are drastically reduced to the same magnitudes as those of the smaller molecules. Specifically, the method is based on a 164-molecule database that consists of molecules made of hydrogen and carbon elements. 4 molecular descriptors were selected to encode molecule's characteristics, among which raw HOF calculated from B3LYP and the molecular size are also included. Upon the size-independent machine learning correction, the mean absolute deviation (MAD) of the B3LYP/6-311+G(3df,2p)-calculated HOF is reduced from 16.58 to 1.43 kcal/mol and from 17.33 to 1.69 kcal/mol for the training and testing sets (small molecules), respectively. Furthermore, the MAD of the testing set (large molecules) is reduced from 28.75 to 1.67 kcal/mol.