Efficacy and Safety of Generic Dasatinib as a Second-line Treatment for Patients with Chronic Myeloid Leukemia:a Multicenter Retrospective Study in Hubei Province,China

Dasatinib is a second-generation tyrosine kinase inhibitor (TKI)and it could be used as a second-line treatment for patients with chronic myeloid leukemia (CML).Yinishu,a generic dasatinib made in China,was approved by the China Food and Drug Administration in 2013 and it costs much less than the patented dasatinib SPRYCEL.The present study aimed to examine the efficacy and safety of Yinishu as a second-line treatment for CML by comparing the baseline clinical characteristics,rates of adverse events and efficacy between Yinishu and SPRYCEL groups. The results showed that there were no significant differences in the rates of optimal response between Yinishu and SPRYCEL for patients who started second-line treatment because of treatment failure.For patients who started second-line treatment because of intolerance of first-line treatment, their levels of BCR-ABL1/ABL1 on the international scale (BCR-ABL^IS)was maintained very low throughout the course of Yinishu treatment.Drug-related adverse events occurred with the same frequency in these two groups.It was confirmed that Yinishu was effective and safe as a second- line treatment for CML patients.Yinishu may be more suitable for patients who are economically unable to pay for the patented dasatinib SPRYCEL.

Homing Guidance Law with Falling Angle and Flying Time Control

In this paper,a new homing guidance method is used to control the flying time and falling angle for guided missiles. Through this approach,it finds the approximate solution to the quadratic equation of time-togo,which is used for the formula derivation of the flying time control command. In this guidance law design,the acceleration rate control command is adopted. The guidance law is composed of a PN guidance command and a flying time control command. Firstly,it obtains a desired falling angle with accurate guidance. Secondly,it introduces to satisfy the constraint of flying time. The flying time control requires an assumption on the future evolution of missile,which is called time-to-go. To cope with the time-varying speed of missiles,a method of compensating the estimation of time-to-go is presented. The new guidance law is evaluated by using a simulation of typical terminal guidance for rocket-propelled torpedo. The simulation results show that the guidance achieves excellent control performance and exhibits insensitivity to initial trajectory parameter over a widen flight envelope.

Adaptive Sliding Mode BTT Autopilot for Cruise Missiles with Variable-Swept Wings

In this paper,an adaptive sliding mode method was proposed for BTT autopilot of cruise missiles with variable-swept wings. To realize the whole state feedback,the roll angle,normal overloads and angular rates were considered as state variables of the autopilot,and a parametric sliding mode controller was designed via feedback linearization. A novel parametric adaptation law was put forward to estimate the nonlinear timevarying parameter perturbations in real time based on Lyapunov stability theory. A sliding mode boundary layer theory was adopted to smooth the discontinuity of control variables and eliminate the control chattering. The simulation was presented for the roll angle and overload commands tracking in different configuration schemes. The results indicated that the controlled system has robust dynamic tracking performance in condition of the large-scale aerodynamic parametric variety resulted from variable-swept wings.

Telomere-to-telomere haplotype-resolved reference genome reveals subgenome divergence and disease resistance in triploid Cavendish banana

Banana is one of the most important crops of the world.Cavendish-type bananas,which have a monospecific Musa acuminata origin(AAA),account for around half of the global banana production,thereby are of great significance for human societies.However,until now,the high-quality haplotype-resolved reference genome was still undecoded for banana cultivars.Here,we reported the telomere-to-telomere(T2T)and haplotype-resolved reference genome of‘Baxijiao’(Cavendish)consisting of three haploid assemblies.The sizes of the three haploid assemblies were estimated to be 477.16 Mb,477.18 Mb,and 469.57 Mb,respectively.Although with monospecific origins,the three haploid assemblies showed great differences with low levels of sequence collinearity.Several large reciprocal translocations were identified among chromosomes 1,4,and 7.An expansion of gene families that might affect fruit quality and aroma was detected,such as those belonging to sucrose/disaccharide/oligosaccharide catabolic processes,sucrose metabolic process,starch metabolic process,and aromatic compound biosynthetic process.Besides,an expansion of gene families related to anther and pollen development was observed,which could be associated with parthenocarpy and sterility of the Cavendish cultivar.Finally,much fewer resistance genes were identified in‘Baxijiao’than in M.acuminata,particularly in the gene clusters in chromosomes 3 and 10,providing potential targets to explore for molecular analysis of disease resistance in banana.This T2T haplotype-resolved reference genome will thus be a valuable genetic resource for biological studies,molecular breeding,and genetic improvement of banana.

Development of RF windows for 650 MHz multibeam klystron

Radio frequency windows are developed and evaluated for a 650 MHz continuous-wave multibeam klystron.Thin-pillbox windows with alumina and beryllia disks are designed with an average RF power of CW 400 kW.Results of a cold test and tuning procedures are described.The final measured S11 curves under the required bandwidth are less than-32.0 and-26.9 dB for alumina and beryllia windows,respectively.The windows are tested up to CW 143 kW for traveling waves and CW 110 kW for standing waves using a solid-state amplifier as an RF power source.Multipactor simulations for windows and benchmark studies for the thermal analysis of ceramic disks are introduced.

Research on the iterative method for model updating based on the frequency response function

Model reduction technique is usually employed in model updating process. In this paper, a new model updat- ing method named as cross-model cross-frequency response function （CMCF） method is proposed and a new iterative method associating the model updating method with the mo- del reduction technique is investigated. The new model up- dating method utilizes the frequency response function to avoid the modal analysis process and it does not need to pair or scale the measured and the analytical frequency re- sponse function, which could greatly increase the number of the equations and the updating parameters. Based on the traditional iterative method, a correction term related to the errors resulting from the replacement of the reduction ma- trix of the experimental model with that of the finite element model is added in the new iterative method. Comparisons be- tween the traditional iterative method and the proposed itera- tive method are shown by model updating examples of solar panels, and both of these two iterative methods combine the CMCF method and the succession-level approximate reduc- tion technique. Results show the effectiveness of the CMCF method and the proposed iterative method .

Early Detection of Myelodysplastic Syndrome/Leukemia-associated Mutations Using NGS Is Critical in Treating Aplastic Anemia

Distinguishing between aplastic anemia(AA)and hypoblastic myelodysplastic syndrome(hMDS)with a low percentage of bone marrow(BM)blasts(<5%)can be difficult due to the overlap in clonality and a spectrum of genetic alternations between the two subtypes of diseases.However,due to recent advances in DNA sequencing technology,both spectnim and frequency of mutations can be accurately determined and monitored by next-generation sequencing(NGS)at initial diagnosis and during immunosuppressive therapy(1ST)in patients with AA or hMDS.This improvement in acquiring a patient's genetic status and clonal evolution can provide more proper,precise,and on-time information to guide disease management,which is especially helpful in the absence of traditional morphologic/cytogenetic evidence.

Occupational burnout in nurses:a concept analysis

Objective:This paper aims to clarify the concept of occupational burnout(OB)as well as develop appropriate methods to relieve or prevent OB in the nursing profession.Methods:Walker and Avant's eight-step approach of concept analysis was applied.Results:OB was defined as a chronic form of work-related stress.Accurately,it was characterized by emotional exhaustion,depersonalization/cynicism,and reduced personal accomplishment/inefficacy.Antecedents of burnout included(a)demographic characteristics;(b)chronic exposure to work-related stressors;(c)quantitative and qualitative job demands;(d)lack of job resources;and(e)personality traits.Consequences involved(a)individual’s unfavorable quality of life;(b)negative impact on the organization;and(c)poor services quality.Although the Maslach Burnout Inventory(MBI)is perceived as an ideal tool to measure burnout and hence,it is used worldwide,whether this instrument fits to measure this concept for nurses has still not yet been verified and thus further research is needed.Conclusions:By proposing a comprehensive definition of the concept,this analysis contributes to recognition of the process of OB of nurses.All nurses are vulnerable to OB.Hence,burnout in nursing needs to be recognized as a critical factor in the delivery of safe patient care.It proposes that the prevention of OB would be achieved through team communication training,mindfulness group,education,etc.

Bile salt derivatives with novel skeleton from sea lamprey function as putative pheromone

OBJECTIVE The invasive sea lamprey(Petromyzon marinus)has devastated the ecosystem of the Laurentian Great Lakes.Application of pheromones to manipulate adult sea lamprey behavior is among the options considered for alternative sea lamprey control techniques.The male sea lamprey sex pheromone is hypothesized to be possess multiple functions through actions of multiple components,some of which have yet to be characterized.Our objective is to isolate and characterize the bioactive components from water conditioned with sexually mature male sea lamprey.METHODS The water conditioned with sexually mature male sea lamprey was extracted by solid phase extraction and concentrated in vacuo.The compounds were isolated by liquid chromatography and elucidated by spectrometry and spectroscopy.Their biological activities were evaluated by electro-olfactogram recordings and two-choice maze behavioral assays.RESULTS Five novel bile salts,petromyzene A and B and petromyzone A-C,have been characterized.Petromyzene A and B featured either a unique,rearranged side chain or a rare cis-11,12-diol on the steroidal B-ring.Petromyzone A-C represented three novel highly oxidized sulfated bile alcohols possessing different hydroxylation,oxidation,and double bond patterns,which exemplify the chemical diversity of bile salts.These five bile salts were potent odorants that stimulated the adult sea lamprey olfactory epithelium in a concentration dependent manner and showed detection thresholds between 10–13mol·L^(-1) and 10^(–11)mol·L^(-1)(paired t-test,P<0.05).Experiments in the two-choice maze showed that all isolated compounds induced behavioral responses in ovulated females.CONCLUSION The five novel compounds are likely additional components of pheromones released by sexually mature male sea lamprey,and may provide useful behavioral manipulation tools to be implemented with the integrated management of the destructive and invasive sea lamprey in the Laurentian Great Lakes.