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Factor XI (FXI) inhibition offers the promise of hemostasis‐sparing anticoagulation for the prevention and treatment of thromboembolic events. Abelacimab (MAA868) is a novel fully human monoclonal antibody that targets the catalytic domain and has dual activity against the inactive zymogen Factor XI and the activated FXI. To investigate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of single dose intravenous and multiple dose subcutaneous administration of abelacimab in healthy volunteers and patients with atrial fibrillation, respectively. In study ANT‐003, healthy volunteers were administered single intravenous doses of abelacimab (30–150 mg) or placebo. The ANT‐003 study also included a cohort of obese but otherwise healthy subjects. In study ANT‐004, patients with atrial fibrillation were administered monthly subcutaneous doses of abelacimab (120 mg and 180 mg), or placebo, for 3 months. Key PK and PD parameters, including activated partial thromboplastin time (aPTT) and free FXI levels, as well as anti‐drug antibodies (ADA) were assessed. Following intravenous administration of abelacimab, the terminal elimination half‐life ranged from 25 to 30 days. One hour after the start of the intravenous infusion greater than 99% reductions in free FXI levels were observed. Following once monthly subcutaneous administration, marked reductions from baseline in free FXI levels were sustained. Parenteral administration of abelacimab demonstrated a favorable safety profile with no clinically relevant bleeding events. Intravenous and multiple subcutaneous dose administration of abelacimab were safe and well tolerated. The safety, PK, and PD data from these studies support the clinical development of abelacimab.

Factor XI (FXI) inhibition offers the promise of hemostasis‐sparing anticoagulation for the prevention and treatment of thromboembolic events. Abelacimab (MAA868) is a novel fully human monoclonal antibody that targets the catalytic domain and has dual activity against the inactive zymogen Factor XI and the activated FXI.

Chemically protected sodium butyrate (CSB) is a new kind of sodium butyrate. Our previous study found that 1,000 mg/kg of CSB had the potential capacity of improving growth performance and promoting early development of small intestine in broilers. This study aimed to investigate the effect of long-term antibiotics or CSB supplementation for intestinal microflora dynamical regulation in broilers. One hundred ninety-two 1-day-old Arbor Acres male broilers were randomly allocated into 3 dietary treatment (8 replicates per treatment) and fed with a basal diet (CON), a diet supplemented with the antibiotics (enramycin, 8 mg/kg and aureomycin, 100 mg/kg) (ANT), or a diet supplemented with 1,000 mg/kg of CSB, respectively. Results showed that dietary supplementation of CSB or ANT treatment elevated the weight gain and feed conversion ratio (FCR; P< 0.05), as compared with control (CON) group. Additionally, CON, CSB, or ANT administration dynamically altered the gut microbiota composition as time goes on. The increased presence of potential pathogens, such as Romboutsiaand Shuttleworthia, and decreased beneficial bacteria such as Alistipes, Akkermansia, and Bacteroideswere verified in new gut homeostasis reshaped by long-term antibiotics treatment, which has adverse effects on intestinal development and health of broilers. Conversely, CSB supplementation could dynamically enhance the relative abundance of Bacteroides, and decrease Romboutsiaand Shuttleworthiain new microflora, which has positive effects on intestinal bacteria of broilers compared with CON group. Meanwhile, CSB supplementation was significantly increased the concentration of propionic acid and total short chain fatty acids (total SCFA; P< 0.05) in comparison with CON and ANT groups. Moreover, CSB treatment significantly increased anti-inflammatory and antioxidative capacities (P< 0.05) of broilers compared with ANT group. Taken together, we revealed characteristic structural changes of gut microbiota throughout long-term CSB or ANT supplementation in broilers, which provided a basic data for evaluating the mechanism of action affecting intestinal health by CSB or ANT administration and CSB as an alternative to antibiotics in the broilers industry.

OBJECTIVE: To investigate the effects of β-(3,4-dihydroxyphenyl)lactic acid on oxidative stress stimulated by high glucose levels in human peritoneal mesothelial cells (HPMCs) in vitro. METHODS: HPMCs were incubated with 100 mol/l glucose followed by 0.625 – 20 mg/ml β-(3,4-dihydroxyphenyl)lactic acid. Reactive oxygen species (ROS) were quantified by flow cytometry. Relative levels of fibronectin-1 (FN1), collagen-I α1(COL1A1), endothelin-1 (EDN1) and haem oxygenase-1 (HMOX1) mRNA and protein were quantified by real-time reverse transcription—polymerase chain reaction and Western blotting, respectively. Absolute levels of FN1 and COLIA1 were quantified by enzyme-linked immunosorbent assay. RESULTS: β-(3,4-Dihydroxyphenyl)lactic acid significantly decreased ROS levels, and EDN1 mRNA and protein levels, in dose- and time-dependent manners. HMOX1 mRNA and protein levels were significantly increased by β-(3,4-dihydroxyphenyl)lactic acid in dose-dependent manners. COL1A1 and FN1 mRNA and protein levels were significantly decreased by β-(3,4-dihydroxyphenyl)lactic acid in dose- and time-dependent manners. CONCLUSIONS: β-(3,4-Dihydroxyphenyl)lactic acid inhibited oxidative stress and reversed increases in FN1 and COLIA1 induced by high glucose levels in HPMCs. This may contribute to a protective role in peritoneal fibrosis.

Seed loss caused by pod-shatter during harvesting is one of the main problems in rapeseed production worldwide. Quantitative trait loci (QTLs) for pod-shatter based on genetic mapping would help breeders develop cultivars resistant to pod-shatter. In this study, we constructed a genetic map of Brassica napus containing 107 simple sequence repeat (SSR) markers and 68 sequence-related amplified polymorphism (SRAP) markers using a doubled-haploid (DH) population of 276 lines derived from the cross H155×Qva. This map covered 1382.8cM with an average marker interval of 7.9cM. In total, 13QTLs for pod-shatter resistance were identified in this DH population at two experimental sites (in Wuhan and Zhengzhou); three of the QTLs were present at both locations. At Zhengzhou, nine QTLs, identified in linkage groups A1, A7, A8, C5, and C8, together explained 49.0% of the phenotypic variation. At Wuhan, four QTLs were mapped on the A1, A4, A7, and C8 linkage groups. These QTLs explained 38.6% of the phenotypic variation. These results may serve as a valuable basis for further molecular dissection of pod-shatter resistance in B. napus, and for development of the markers related to QTLs that may be useful for marker-assisted selection of pod-shatter resistant cultivars.

The purpose of this study was to analyze inter- and intra-fractional changes in tumor volume with respect to both spatial and volumetric parameters among patients treated by SBRT for lung cancer. Twelve patients (13 tumors) were treated by SBRT with abdominal compression in 3–5 fractions over a 2 week period to a median dose of 60 Gy (range, 48 to 60 Gy). Kilovoltage cone-beam CT (CBCT) was obtained prior to the delivery of each fraction as well as intra-fractionally yielding a total of 55 CBCT scans. All CBCT scans were registered with the planning CT for target alignment and shifts were recorded and analyzed. Retrospectively, gross tumor volume (GTV) was contoured on all CBCT images and compared to initial planning volumes; positional differences were evaluated utilizing directional and vector analysis. Shifts greater than 5 mm were applied inter-fractionally in 6.8% (lateral), 29.5% (longitudinal), and 6.8% (vertical) of all delivered treatments. Using a 10 mm threshold, the corresponding percentages were 2.3%, 13.6%, and 2.3%, respectively. Across all fractions, the calculated inter-fractional shift vectors ranged from 0 to 31.2 mm, with 40.9%, 15.9%, and 11.4% of all fractions having shift vectors =5 mm, =10 mm, and =20 mm, respectively. Intra-fractional shifts were also evaluated and found negligible in a small portion of patients evaluated. The mean overall reduction in GTV was 21.1% during SBRT. Significant changes in both position and volume occur during SBRT for lung cancer. Shifts (particularly in the superior-inferior axis) may exceed applied margins and compromise target coverage. Due to the extreme hypofractionation associated with SBRT, inter-fractional image guidance is necessary.

This paper presents a simple and reliable pumpless methanol feeding (PLMF) method for application in direct methanol fuel cell (DMFC) systems. The primary feature and advantage of the PLMF is as follows: it employs an approach that allows the cathode gas pressure to be connected with a fuel container for supplying the methanol fuel into the anode fuel loop, instead of using any feeding pump or other specially designed apparatuses. The PLMF has been used in a portable 25 W DMFC system and realised feeding methanol in real time for meeting the requirements of the system. The PLMF method not only is suitable for the DMFC system, but also can be used in other liquid‐feeding fuel cell systems.

The sulfonated poly(ether ether ketone) (SPEEK) / polytetrafluoroethylene (PTFE) composite membranes were produced to aid the swelling properties. The PTFE porous films were used as reinforcing material for the SPEEK/PTFE composite membranes. Scanning electron micrographs showed that SPEEK resin was distributed uniformly in the composite membrane and completely plugged the micropores; there is a continuous thin SPEEK film present on the PTFE surface. The dimensional stability and mechanical strength of the composite membranes were apparently improved. The composite membrane had a smaller oxygen permeability than the Nafion® membrane despite it being larger than that of the SPEEK homogenous membrane. The performance and stability of the PEMFC with SPEEK/PTFE composite membranes were also tested. Results showed that the fuel cell had a larger resistance than the SPEEK homogenous membrane or the Nafion® membrane, but these disadvantages are compensated for with the thinner composite membrane, because of its low gas permeability and high mechanical strength. Stability testing showed that the cell performance could be kept steady for more than 150 hours. The structure of the composite membrane didn't undergo any change and a tight bond remained between the composite membrane and the catalyst layers of electrode after more than 300 hours of intermittent operation.

This paper describes a PEM Fuel Cell Engine (FCE) with 40 kW stacks designed for a car. This was developed by DICP and Sunrise Power and is funded by the Chinese “863” key project. The FCE system construction, stack performance, specifications, and operating characteristics are explained. The efficiency of the FCE is analyzed. The net power output for this FCE is 27 kW and the efficiency is 35–38%. The utilization of air and hydrogen are more than 50% and 97%, respectively.

The development of key materials for proton exchange membrane fuel cells including electrocatalysts, electrodes, proton exchange membranes and bipolar plates in DICP are introduced in this paper. The basic fundamentals and the most recent progress in the key materials have been discussed. The preparation methods of electrocatalysts have been reviewed. Characteristics of various electrode preparation methods are also introduced. A new electrode design and prospective manufacturing methods are indicated. The disadvantages of the present exchange membrane are presented. The results of proton exchange membrane degradation mechanisms are given. Studies of the Nafion/PTFE membrane, blending membrane and PBI membrane are reviewed. Developmental trends of the membrane in both the medium and long term are previewed. Different bipolar plates are compared.

The development of key materials for proton exchange membrane fuel cells including electrocatalysts, electrodes, proton exchange membranes and bipolar plates in DICP are introduced in this paper. The basic fundamentals and the most recent progress in the key materials have been discussed. The preparation methods of electrocatalysts have been reviewed. Characteristics of various electrode preparation methods are also introduced. A new electrode design and prospective manufacturing methods are indicated. The disadvantages of the present exchange membrane are presented. The results of proton exchange membrane degradation mechanisms are given. Studies of the Nafion/PTFE membrane, blending membrane and PBI membrane are reviewed. Developmental trends of the membrane in both the medium and long term are previewed. Different bipolar plates are compared.

This paper describes a PEM Fuel Cell Engine (FCE) with 40 kW stacks designed for a car. This was developed by DICP and Sunrise Power and is funded by the Chinese “863” key project. The FCE system construction, stack performance, specifications, and operating characteristics are explained. The efficiency of the FCE is analyzed. The net power output for this FCE is 27 kW and the efficiency is 35–38%. The utilization of air and hydrogen are more than 50% and 97%, respectively.

A series of dendritic ligands with a chiral diphosphine located at the focal point have been synthesized through coupling of pyrphos 2 with Fréchet-type polyether dendron 3. The relationship between the primary structure of the dendrimer and its catalytic properties was established in the Rh-catalyzed asymmetric hydrogenation of α-acetamido cinnamic acid 4. A remarkable structural effect on catalytic activity was observed.

Drug discovery is dependent on finding a very small number of biologically active or potent compounds among millions of compounds stored in chemical collections. Quantitative structure−activity relationships suggest that potency of a compound is highly related to that compound's chemical makeup or structure. To improve the efficiency of cell-based analysis methods for high throughput screening, where information of a compound's structure is used to predict potency, we consider a number of potentially influential factors in the cell-based approach. A fractional factorial design is implemented to evaluate the effects of these factors, and lift chart results show that the design scheme is able to find conditions that enhance hit rates.

The analysis of 35,312 cannabis preparations confiscated in the USA over a period of 18 years for delta-9-tetrahy-drocannabinol (Δ9-THC) and other major cannabinoids is reported. Samples were identified as cannabis, hashish, or hash oil. Cannabis samples were further subdivided into marijuana (loose material, kilobricks and buds), sinsemilla, Thai sticks and ditchweed. The data showed that more than 82% of all confiscated samples were in the marijuana category for every year except 1980 (61%) and 1981 (75%). The potency (concentration of Δ9-THC) of marijuana samples rose from less than 1.5% in 1980 to approximately 3.3% in 1983 and 1984, then fluctuated around 3% till 1992. Since 1992, the potency of confiscated marijuana samples has continuously risen, going from 3.1% in 1992 to 4.2% in 1997. The average concentration of Δ9-THC in all cannabis samples showed a gradual rise from 3% in 1991 to 4.47% in 1997. Hashish and hash oil, on the other hand, showed no specific potency trends. Other major cannabinoids [cannabidiol (CBD), cannabinol (CBN), and cannabichromene (CBC)] showed no significant change in their concentration over the years.

Therapeutic effectiveness of bisphosphonates (BP) on bone metastases in patients with cancers including those of the breast and prostate has been well documented. However, there are still many important questions that remain unsolved or controversial. To obtain answers for these questions that are not readily addressed in a well-controlled manner in clinical studies, we have developed two animal models of bone metastasis (orthotopic and experimental). Using these models, we studied the effects of BP alone or in combination with anti-cancer agents on the metastasis of breast cancer to bone and visceral organs. In addition, we also determined the effects of BP on osteosclerotic metastases. We found that BP impaired the progression of bone metastases primarily through enhancing apoptosis in osteoclasts and breast cancer cells colonized in bone. In some situations, however, BP alone increased metastases in visceral organs including liver and adrenal glands. However, combination of BP with anti-cancer agents enhanced the suppression of tumour in both bone and visceral organs, leading to prolonged survival of tumour-bearing animals. Of potential importance, preventative administration of BP inhibited the development of eventual osteosclerotic bone metastases. These results suggest that BP exhibits diverse beneficial effects on osteolytic and osteoblastic bone metastasis and non-bone organ metastasis in breast cancer when administered appropriately. They also suggest that the animal models of bone metastasis described here allow us to produce clinically- relevant information that is useful for the design of optimal regimens of BP for the treatment of breast cancer patients with bone and visceral metastases.

Abstract: The hydrological analysis of one of the old meanders of the french upper Rhne, called the ‘Lne des Pcheurs’, is carried out from September 1976 to November 1977. The principal components analysis of the physico-chemical characteristics of the water shows an ecological tripartition along the longitudinal axe of the ‘lne’, according to the mixing processus of two types of waters, the one influenced by the lateral underflow, the other flowing in from the Rhne, and related with the overflow. Partitional analogies are also noted between the structure of phytoplanctonic community and the hydrological environment.

In this study, an optimal design of a 2 degree-of-freedom anthropomorphic robot module is performed. A composite design index is employed to deal with multi-criteria based design in a systematic manner. The results from kinematic optimization based on two different composite indices are compared with respect to the global design indices, operational performance indices, and optimal actuator sizes. It is found that incorporating the gradient properties of the design indices into the composite design index yields even distribution of operational performances throughout the workspace and reduces the sizes of the system actuators.

The difficult in making stainless steel is decarburization and chromium conservation. Although the traditional AOD (Argon-Oxygen Decarburization) process was proved to be effective on decarburization and loss is minimized, the effect of the refractories on molten steel at high temperature still needs to be taken into account. However, application of CO2 in decarbonization during steel refining is a potential way to retain valuable alloy elements. Nevertheless, there are few reports about CO2 refining Fe-Cr-C alloy under vacuum levitation. In the present work, experimental data was collected for levitated stainless droplets exposed with Ar-CO2 mixture gas. The result shows that: (1) Stainless steel was refined by CO2 under electromagnetic levitation, the carbon content loss to 0.043 wt%; (2) Variation of gas flow rate and CO2 partial pressure has ignorable effect of chromium in the sample, and the effect of chromium conservation is obvious.

This research focuses on studying levitating forces of droplets by utilizing a refining process known as electromagnetic levitation(EML). With the mathematical predictions, the levitating forces were described by a mathematical model in this article. Combined with theory analysis, the balancing phenomenon was also investigated in silicon-iron systems. The research found that the relationship between droplets position and levitation forces was linear. As EML system was a multi-induction, the levitating forces generation was affected by the properties of droplet, quality and size. The electromagnetic properties of the droplets were mainly the reasons for the levitation force to change from heating process before melting. EML droplet getting its melting point, electromagnetic properties of EML droplet were fixed due to the droplets absorbing latent heat. The results of this investigation will be used for vacuum electromagnetic levitation technology, and solar grade silicon samples will be prepared from relative inexpensive raw material, metallurgical grade silicon.

Four kinds of composite membranes were prepared by the solution-cast method with Nafion resin, poly(tetrafluoroethylene), and different types of SiO2. They are SiO2sulfonated by 1,3-propane sultone (denoted as SiO2–1,3PS), SiO2sulfonated by H2SO4(denoted as SiO2–SO3H), and pure SiO2. The SiO2content was controlled at 5% in the composite membranes. Combined with the results of the electrochemical impedance spectroscopy, water uptake, and fuel cell performance of different membranes, it suggested the organically modified SiO2has a weak water uptake ability due to the organic molecule chain.