Block Transmission Research Articles

Cooperative Spectrum Sharing in Spectrum Domain with Discrete Time Energy Harvesting for Primary User

In this paper, we propose a spectrum sharing protocol for cognitive radio networks with an energy-constraint primary transmitter (PT), which performs energy harvesting from the received radio frequency (RF) signals broadcasting by two secondary users (SUs). After the amount of harvested energy at the PT is sufficient for data transmission, a SU will cooperatively forward PT's signal using amplify-and-forward (AF) scheme along with transmitting its own signal to increase the spectrum efficiency of the system. To be specific, the data transmission block can be divided into two phases. During the first phase, the PT will optimally select a relay from nodes S1 and S2 in order to further improve the overall throughput, then the PT transmits primary signal to the selected SU and primary receiver (PR), respectively, while the non-selected SU transmits signal to secondary receiver (SR). In the second phase, the selected SU transmits signals of both the primary and secondary systems simultaneously. A discrete Markov chain is used to simulate the charging and discharging processes of the PT's battery. In order to avoid mutual interference between the primary and secondary systems, a fraction of spectrum is used to transmit primary data and the residual spectrum is served for data transmission of the secondary system. An appropriate bandpass filter (BF) is deployed at the receive front-end of each receiver to extract the desired signals from assigned bandwidth. Based on this, the exact expressions of the outage probabilities for both the primary and secondary systems are derived. Moreover, the optimal bandwidth allocation coefficient is determined by utilizing convex optimization to maximize the achievable rate of the secondary system while guaranteeing the achievable rate of the secondary system in information transmission mode. Numerical results show that the proposed spectrum sharing protocol outperforms to other scheme and non-cooperative scenario in terms of average spectrum efficiency.

Performance Analysis of OCDM for Wireless Communications

Orthogonal chirp division multiplexing (OCDM) was recently introduced as a new multi-carrier scheme based on the chirp spread spectrum (CSS) and shown to be more robust to interference caused by insufficient guard intervals. However, a thorough analysis of OCDM for wireless channels has not been conducted. Thus, this paper investigates the performance of OCDM affected by different impairments that are typical in a wireless channel and shows that uncoded OCDM performs better than OFDM and similar to single carrier block transmissions in multipath channels. Building on previous results, this study also shows that OCDM is more robust to time-burst interference (TBI) than its competitors and to narrow band interference (NBI) than OFDM because of spreading. However, OCDM is shown to suffer because of the loss of orthogonality caused by carrier frequency offset (CFO) and is analytically shown to have the same peak-to-average power ratio (PAPR) as OFDM.

Synthesis and biological evaluation of benzhydryl-based antiplasmodial agents possessing Plasmodium falciparum chloroquine resistance transporter (PfCRT) inhibitory activity.

Due to the surge in resistance to common therapies, malaria remains a significant concern to human health worldwide. In chloroquine (CQ)-resistant (CQ-R) strains of Plasmodium falciparum, CQ and related drugs are effluxed from the parasite's digestive vacuole (DV). This process is mediated by mutant isoforms of a protein called CQ resistance transporter (PfCRT). CQ-R strains can be partially re-sensitized to CQ by verapamil (VP), primaquine (PQ) and other compounds, and this has been shown to be due to the ability of these molecules to inhibit drug transport via PfCRT. We have previously developed a series of clotrimazole (CLT)-based antimalarial agents that possess inhibitory activity against PfCRT (4a,b). In our endeavor to develop novel PfCRT inhibitors, and to perform a structure-activity relationship analysis, we synthesized a new library of analogues. When the benzhydryl system was linked to a 4-aminoquinoline group (5a-f) the resulting compounds exhibited good cytotoxicity against both CQ-R and CQ-S strains of P.falciparum. The most potent inhibitory activity against the PfCRT-mediated transport of CQ was obtained with compound 5k. When compared to the reference compound, benzhydryl analogues of PQ (5i,j) showed a similar activity against blood-stage parasites, and a stronger invitro potency against liver-stage parasites. Unfortunately, in the invivo transmission blocking assays, 5i,j were inactive against gametocytes.

Switchable Coupled Relays Aid Massive Non-Orthogonal Multiple Access Networks with Transmit Antenna Selection and Energy Harvesting.

The article proposes a new switchable coupled relay model for massive MIMO-NOMA networks. The model equips a much greater number of antennas on the coupled relays to dramatically improve capacity and Energy Efficiency (EE). Each relay in a coupled relay is selected and delivered into a single transmission block to serve multiple devices. This paper also plots a new diagram of two transmission blocks which illustrates energy harvesting and signal processing. To optimize the system performance of a massive MIMO-NOMA network, i.e., Outage Probability (OP) and system throughput, this paper deploys a Transmit Antenna Selection (TAS) protocol to select the best received signals from the pre-coding channel matrices. In addition, to achieve better EE, Simultaneously Wireless Information Power Transmit (SWIPT) is implemented. Specifically, this paper derives the novel theoretical analysis in closed-form expressions, i.e., OP, system throughput and EE from a massive MIMO-NOMA network aided by switchable coupled relays. The theoretical results obtained from the closed-form expressions show that a massive MIMO-NOMA network achieves better OP and greater capacity and expends less energy than the MIMO technique. Finally, independent Monte Carlo simulations verified the theoretical results.

Plasmodium oocysts respond with dormancy to crowding and nutritional stress

Malaria parasites develop as oocysts in the mosquito for several days before they are able to infect a human host. During this time, mosquitoes take bloodmeals to replenish their nutrient and energy reserves needed for flight and reproduction. We hypothesized that these bloodmeals are critical for oocyst growth and that experimental infection protocols, typically involving a single bloodmeal at the time of infection, cause nutritional stress to the developing oocysts. Therefore, enumerating oocysts disregarding their growth and differentiation state may lead to erroneous conclusions about the efficacy of transmission blocking interventions. Here, we examine this hypothesis in Anopheles coluzzii mosquitoes infected with the human and rodent parasites Plasmodium falciparum and Plasmodium berghei, respectively. We show that oocyst growth and maturation rates decrease at late developmental stages as infection intensities increase; an effect exacerbated at very high infection intensities but fully restored with post infection bloodmeals. High infection intensities and starvation conditions reduce RNA Polymerase III activity in oocysts unless supplemental bloodmeals are provided. Our results suggest that oocysts respond to crowding and nutritional stress with a dormancy-like strategy, which urges the development of alternative methods to assess the efficacy of transmission blocking interventions.

A review of malaria elimination in Minhang District, Shanghai

Objective To analyze the malaria epidemic situation and prevention and control process, and we summarize and assess the malaria elimination work in Minhang District, Shanghai, so as to provide the evidence for maintaining the eradication of malaria. Methods The data of control work, reports, documents, work plans, strategies and measures of malaria in Minhang District from 1950 to 2019 were collected and analyzed, to indicate its epidemiological characteristics and preventive procedure by descriptive epidemiological methods. And we summarized and evaluated the process of eliminating malaria in Minhang District. Results Malaria used to be the most dangerous infectious disease in Minhang District. Two outbreaks occurred in 1954 and 1961 respectively, with the highest annual incidence of 7 824.98/100 000, with P. vivax as the dominant vector and Anopheles sinensis as the only vector. Through comprehensive prevention and control, the incidence of malaria gradually decreased to 10 per 100 000 in 1980, and the standard of basically eliminating malaria was met in 1985. In 2010, Minhang District launched the Action Plan for Eliminating Malaria, and implemented comprehensive technical measures focusing on eliminating the source of infection and blocking transmission. By 2015, there had been no local infection cases for five consecutive years, meeting the assessment standards for eliminating malaria. The malaria eradication maintenance phase began after 2016. According to the characteristics of malaria epidemic in different periods, Minhang District adopted targeted prevention and control measures, which experienced different stages of malaria epidemic, control, monitoring, elimination and post-elimination maintenance. After 2013, all the cases were imported from abroad, and the majority of them were middle-aged and young migrating population. There were no obvious characteristics of the infected species and onset time of the cases. The focus of prevention and control is to timely detect and deal with malaria cases to prevent further transmission. Conclusion Maintaining surveillance networks and surveillance capabilities, and preventing the risk of retransmission of imported cases has become a new challenge after malaria eradication has been entered the maintenance phase. 摘要：目的 分析上海市闵行区不同时期疟疾流行状况和防治历程, 总结闵行区消除疟疾工作, 为维持消除疟疾 状态提供依据。 方法 收集闵行区1950—2019年疟疾防治疫情相关报表、工作计划总结、防治文件和策略等资料, 采 用描述流行病学方法分析闵行区疟疾流行特征与防治措施, 总结评估闵行区消除疟疾历程。 结果 疟疾曾是闵行区 危害最大的传染病, 1954年和1961年先后发生过2次暴发流行, 年发病率最髙达7 824.98/10万, 以间日疟为主, 中华按 蚊为唯一传播媒介。经过综合防治, 1980年疟疾发病率逐步降低至10/10万, 1985年达到了基本消灭疟疾的标准;2010 年启动闵行区消除疟疾行动计划 , 实施以清除传染源、阻断传播为重点的综合技术措施 , 至2015年连续5年无本地感 染病例, 达到了消除疟疾考核标准;2016年后进人消除疟疾维持阶段。闵行区根据不同时期疟疾流行特点采取了针对 性防控措施, 经历疟疾流行、控制、监测、消除和消除后维持的不同阶段。2013年后病例均为境外输人性病例, 以中青 年流动人口为主, 感染虫种和病例发病时间无明显特征, 防控重点是及时发现和处置疟疾病例, 防止引起续发传播。 结论 达到消除疟疾标准后, 维持疟疾监测网络和监测能力, 防止输人性病例再传播风险成为面临的新挑战。

Vaccination and Non-Pharmaceutical Interventions: When Can the UK Relax About COVID-19?

Background: The announcement of efficacious vaccine candidates against SARS-CoV-2 has been met with worldwide acclaim and relief. Many countries already have detailed plans for vaccine targeting based on minimising severe illness, death and healthcare burdens. Normally, relatively simple relationships between epidemiological parameters, vaccine efficacy and vaccine uptake predict the success of any immunisation programme. However, the dynamics of vaccination against SARS-CoV-2 is made more complex by age-dependent factors, changing levels of infection and the potential relaxation of non-pharmaceutical interventions (NPIs) as the perceived risk declines. Methods: In this study we use an age-structured mathematical model, matched to a range of epidemiological data, which also captures the roll-out of a two-dose vaccination programme targeted at specific age groups. Findings: We consider the interaction between the UK vaccination programme and future re- laxation (or removal) of NPIs. Our predictions highlight the population-level risks of early relaxation leading to a pronounced wave of infection, hospital admissions and deaths. Only vaccines that offer high transmission-blocking efficacy with high uptake in the general population allow relaxation of NPIs without a huge surge in deaths. Interpretation: While the novel vaccines against SARS-CoV-2 offer a potential exit strategy for this outbreak, this is highly contingent on the transmission blocking action of the vaccine and the population uptake, both of which need to be carefully monitored as vaccine programmes are rolled out in the UK and other countries.Funding Statement: This research was funded by the National Institute for Health Research (NIHR) [Policy Research Programme, Mathematical & Economic Modelling for Vaccination and Immunisation Evaluation, and Emergency Response; NIHR200411], the Medical Research Council through the COVID- 19 Rapid Response Rolling Call [grant number MR/V009761/1] and through the JUNIPER modelling consortium [grant number EP/V030477/1]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Declaration of Interests: All authors declare that they have no competing interests.Ethics Approval Statement: The data were supplied from the CHESS database after anonymisation under strict data protection protocols agreed between the University of Warwick and Public Health England. The ethics of the use of these data for these purposes was agreed by Public Health England with the Government’s SPI-M(O) / SAGE committees.

Identification and Assessment of Plasmodium berghei Merozoites and Cell Cycle by Flow Cytometry.

The asexual blood stages of the Plasmodium berghei life cycle including merozoites are attractive targets for transmission blocking vaccines and drugs. Improved understanding of P. berghei life cycle stage growth and development would provide new opportunities to evaluate antimalarial vaccines and drugs. Blood stage samples from C57BL/6 albino mice infected with P. berghei sporozoites were singly stained with a high binding affinity deoxyribonucleic acid dye, YOYO-1, and measured by flow cytometry (FCM). Duplicate slides were made from samples and stained with diluted Giemsa's and YOYO-1, respectively. Correlated results were compared by FCM, light microscopy, and fluorescent microscopy. Complete life cycle stage determination and analysis by FCM is reported to include merozoites, ring forms, trophozoites, immature, and mature schizonts. FCM demonstrated a clear separation between each stage using their unique fluorescence distribution. When compared to light microscopy, a strong correlation (r 2 = 0.925 to 0.974) was observed in determining the ring forms, trophozoites, and schizonts phases, but only a moderate correlation (r 2 = 0.684 to 0.778) was observed for merozoites. The identification and measurement of merozoites suggest that FCM is a useful technique to monitor the entire life stage of the parasite. Initial stage-specific data demonstrated that mefloquine has a mode of action on mature parasite forms, and artesunic acid was rapidly effective against merozoites and other immature and mature parasite forms with higher killing. Blood stage parasites in each individual life stage, including merozoites, are reliably identified and quantified quickly by FCM, making this technique an ideal alternative to microscopy. This integrated whole life stage model, particularly with confirmed determination of merozoite population, could widely be used for drug and vaccine research in malaria therapy and prophylaxis.

Model-informed COVID-19 vaccine prioritization strategies by age and serostatus.

Limited initial supply of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine raises the question of how to prioritize available doses. We used a mathematical model to compare five age-stratified prioritization strategies. A highly effective transmission-blocking vaccine prioritized to adults ages 20 to 49 years minimized cumulative incidence, but mortality and years of life lost were minimized in most scenarios when the vaccine was prioritized to adults greater than 60 years old. Use of individual-level serological tests to redirect doses to seronegative individuals improved the marginal impact of each dose while potentially reducing existing inequities in COVID-19 impact. Although maximum impact prioritization strategies were broadly consistent across countries, transmission rates, vaccination rollout speeds, and estimates of naturally acquired immunity, this framework can be used to compare impacts of prioritization strategies across contexts.

Characterization of the Temporal Pattern of Blood Protein Digestion in Rhodnius prolixus: First Description of Early and Late Gut Cathepsins.

Rhodnius prolixus is one important vector for the parasite Trypanosoma cruzi in Latin America, where Chagas disease is a significant health issue. Although R. prolixus is a model for investigations of vector–parasite interaction and transmission, not much has been done recently to further comprehend its protein digestion. In this work, gut proteolysis was characterized using new fluorogenic substrates, including optimum pH, inhibition profiles, and tissue and temporal expression patterns. Each protease possessed a particular tissue prevalence and activity cycle after feeding. Cathepsin L had a higher activity in the posterior midgut lumen, being characterized by a plateau of high activities during several days in the intermediate phase of digestion. Cathepsin D showed high activity levels in the tissue homogenates and in the luminal content of the posterior midgut, with a single peak 5 days after blood feeding. Aminopeptidases are highly associated with the midgut wall, where the highest activity is located. Assays with proteinaceous substrates as casein, hemoglobin, and serum albumin revealed different activity profiles, with some evidence of biphasic temporal proteolytic patterns. Cathepsin D genes are preferentially expressed in the anterior midgut, while cathepsin L genes are mainly located in the posterior portion of the midgut, with specific sets of genes being differently expressed in the initial, intermediate, or late phases of blood digestion.Significance StatementThis is the first description in a non-dipteran hematophagous species of a sequential protease secretion system based on midgut cathepsins instead of the most common insect digestive serine proteases (trypsins and chymotrypsins). The midgut of R. prolixus (Hemiptera) shows a different temporal expression of proteases in the initial, intermediate, and late stages of blood digestion. In this respect, a different timing in protease secretion may be an example of adaptative convergence in blood-sucking vectors from different orders. Expanding the knowledge about gut physiology in triatomine vectors may contribute to the development of new control strategies, aiming the blocking of parasite transmission.

A Reproducible and Scalable Process for Manufacturing a Pfs48/45 Based Plasmodium falciparum Transmission-Blocking Vaccine.

The cysteine-rich Pfs48/45 protein, a Plasmodium falciparum sexual stage surface protein, has been advancing as a candidate antigen for a transmission-blocking vaccine (TBV) for malaria. However, Pfs48/45 contains multiple disulfide bonds, that are critical for proper folding and induction of transmission-blocking (TB) antibodies. We have previously shown that R0.6C, a fusion of the 6C domain of Pfs48/45 and a fragment of PfGLURP (R0), expressed in Lactococcus lactis, was properly folded and induced transmission-blocking antibodies. Here we describe the process development and technology transfer of a scalable and reproducible process suitable for R0.6C manufacturing under current Good Manufacturing Practices (cGMP). This process resulted in a final purified yield of 25 mg/L, sufficient for clinical evaluation. A panel of analytical assays for release and stability assessment of R0.6C were developed including HPLC, SDS-PAGE, and immunoblotting with the conformation-dependent TB mAb45.1. Intact mass analysis of R0.6C confirmed the identity of the product including the three disulfide bonds and the absence of post-translational modifications. Multi-Angle Light Scattering (MALS) coupled to size exclusion chromatography (SEC-MALS), further confirmed that R0.6C was monomeric (~70 kDa) in solution. Lastly, preclinical studies demonstrated that the R0.6C Drug Product (adsorbed to Alhydrogel®) elicited functional antibodies in small rodents and that adding Matrix-M™ adjuvant further increased the functional response. Here, building upon our past work, we filled the gap between laboratory and manufacturing to ready R0.6C for production under cGMP and eventual clinical evaluation as a malaria TB vaccine.

Analysis of the Potential Efficacy and Timing of COVID-19 Vaccine on Morbidity and Mortality

Background: A first generation COVID-19 vaccine is expected to be approved and made available by the end of 2020. While questions of vaccine allocation strategies have received significant attention among scientific and professional healthcare communities, important questions remain regarding the potential impact of the vaccine given uncertainties regarding efficacy against transmission, availability, timing, and durability.Methods: We adapted a susceptible-exposed-infectious-recovered (SEIR) model to examine the potential impact on hospitalization and mortality assuming increasing rates of vaccine efficacy. Specifically, though vaccine efficacy is typically evaluated as reduction in disease, we also evaluated efficacy against infectiousness given the uncertainty of the vaccine to prevent infectiousness as well as potential effects of waning immunity. Furthermore, we evaluated these potential vaccine properties in three US states at different stages of the epidemic to assess the impact on outcomes from distribution timing.Findings: Increased vaccine efficacy against disease reduces hospitalizations and deaths from COVID-19; however, the relative benefit of transmission blocking varied depending on the timing of vaccine distribution. Early in an outbreak, a vaccine that reduces transmission will be relatively more effective than one introduced later in the outbreak. Results from analysis of selected US states further suggest that earlier implementation of a less effective vaccine is more impactful than later implementation of a more effective vaccine. These findings are magnified when considering the durability of the vaccine. Vaccination in the spring will be less impactful when immunity is less durable. Interpretation: Policy choices regarding non-pharmaceutical interventions, such as social distancing and face mask use, will need to remain in place longer if the vaccine is less effective at reducing transmission. In addition, the stage of the local outbreak greatly impacts the overall effectiveness of the vaccine in a region and should be considered when allocating vaccines.Funding: Centers for Disease Control and Prevention (CDC) MInD-Healthcare Program (U01CK000589, 1U01CK000536), James S. McDonnell Foundation 21st Century Science Initiative Collaborative Award in Understanding Dynamic and Multiscale Systems, National Science Foundation (CNS-2027908), National Science Foundation Expeditions (CCF1917819), C3.ai Digital Transformation Institute (AWD1006615), and Google, LLC.Declaration of Interests: The authors declare no competing interests.

Restricted genetic heterogeneity of the Plasmodium vivax transmission-blocking vaccine (TBV) candidate Pvs48/45 in a low transmission setting: Implications for the Plasmodium vivax malaria vaccine development.

Plasmodium vivax is the most widespread malaria species parasitizing humans outside Africa, with approximately 100 million cases reported per year. Most human cases of P. vivax are asymptomatic with low parasitemia, making active case detection-based elimination programme challenging and less effective. Despite the widespread distribution of P. vivax, no effective vaccines are currently available. Transmission blocking vaccines have recently emerged as potential vaccine candidates to reduce transmission rates to below the essential levels required for the maintenance of the parasite life cycle. Here, we demonstrated that P. vivax was the predominant species found in a malaria-endemic area, although P. vivax/P. falciparum co-infections were also common. Through genomic sequence analysis and neighbor-joining algorithms, we demonstrated limited genetic heterogeneity in the P. vivax transmission-blocking vaccine candidate Pvs48/45 among clinical isolates of P. vivax. Restricted genetic polymorphism occurred at both nucleotide and amino acid levels. The most frequent mutation was A→G at nucleotide position 77 (46.7%), whereas the least frequent was C→T at nucleotide position 1230 (3.3%). The occurrence of single nucleotide polymorphisms (SNPs) distribution at 6/8 positions (75%) led to changes in amino acid sequences in the Pvs48/45 loci, whereas 2/8 (25%) of SNPs resulted in no amino acid sequence variations. Consistently, the nucleotide diversity in the Pvs48/45 locus among the P. vivax population studied was extremely low (π=0.000525). Changes in amino acid sequences in the Pvs48/45 protein did not result in substantial conformational modifications in the tertiary structures of these proteins. Unveiling the population genetic structure and genetic heterogeneity of vaccine target antigens are necessary for rational design of transmission-blocking antibody vaccines and to monitor the vaccine efficacy in clinical trials in endemic areas for malaria.

COVID-19: advance in laboratory diagnostic strategy and technology.

SARS-CoV-2 is one of the beta-coronaviruses with the spike protein. It invades host cells by binding to angiotensin converting enzyme 2 (ACE2). This newly discovered virus can result in excessive inflammation and immune pathological damage, as shown by a decreased number of peripheral lymphocytes, increased levels of cytokines, and damages of lung, heart, liver, kidney, and other organs. Effective therapeutic modalities such as new antiviral drugs and vaccines against this emerging virus need to be thoroughly studied and developed. However, so far the only recognized but mild progress in this area is the screening of old drugs for new uses. Therefore, rapid and accurate laboratory SARS-CoV-2 testing approaches are the important basis of identification and blockage of COVID-19 transmission. For COVID-19 patients with different clinical classifications (mild, common, severe, and critically severe), dynamic monitoring of functional indicators of susceptible and vital organs is an important strategy for evaluating therapeutic efficacy and prognosis. In this review, we summarized SARS-CoV-2 laboratory diagnostic schemes, pathophysiological indices of tissues and organs of COVID-19 patients, and laboratory diagnostic strategies for distinct disease stages. Further, we discussed the importance of hierarchical management and dynamic observation in SARS-CoV-2 laboratory diagnostics. We then summed up the advance in SARS-CoV-2 testing technology and described the prospect of intelligent medicine in the prevention of infectious disease outbreaks.Graphic abstract Supplementary InformationThe online version of this article (10.1007/s11010-020-04004-1) contains supplementary material, which is available to authorized users.

Coded-MPMC: One-to-Many Transfer Using Multipath Multicast With Sender Coding

One-to-many transfers in a fast and efficient manner are essential to meet the growing need for duplicating, migrating, or sharing bulk data among servers in a datacenter and across geographically distributed datacenters. Some existing works utilize multiple multicast trees for a one-to-many transfer request to increase network link utilization and its transfer throughput. However, since those schemes do not fully utilize the max-flow value of transmission from a single sender to each recipient, there is room for each recipient to retrieve data more quickly. Therefore, assuming fully-controlled networks with full-duplex links, we pose a problem to find a set of multicast flows with an allocation of block-wise transmissions by which each of multiple recipients with diverse max-flow values from the sender can utilize its own max-flow value. Based on that, assuming a sender-side coding capability on file blocks, we design a schedule of block transmissions over multiple phases by which each recipient can achieve a lower-bound of its file retrieval completion time, i.e., the file size divided by its own max-flow value. This paper presents the coded Multipath Multicast (Coded-MPMC) for one-to-many transfers with heuristic procedures to find a desired set of multicast flows on which block transmissions are scheduled. Through extensive simulations on large-scale real-world network topologies and different types of randomly-generated synthetic topologies, the proposed method is shown to design a desired schedule efficiently. A preliminary implementation on OpenFlow is also reported to show the fundamental feasibility of Coded-MPMC.

Isolation and Electrophysiology of Murine Sympathetic Postganglionic Neurons in the Thoracic Paravertebral Ganglia.

The thoracic paravertebral sympathetic chain postganglionic neurons (tSPNs) represent the predominant sympathetic control of vascular function in the trunk and upper extremities. tSPNs cluster to form ganglia linked by an interganglionic nerve and receive multisegmental convergent and divergent synaptic input from cholinergic sympathetic preganglionic neurons of the spinal cord (Blackman and Purves, 1969; Lichtman et al., 1980 ). Studies in the past have focused on cervical and lumbar chain ganglia in multiple species, but few have examined the thoracic chain ganglia, whose location and diminutive size make them less conducive to experimentation. Seminal studies on the integrative properties of preganglionic axonal projections onto tSPNs were performed in guinea pig (Blackman and Purves, 1969; Lichtman et al., 1980 ), but as mice have become the accepted mammalian genetic model organism, there is need to reproduce and expand on these studies in this smaller model. We describe an ex vivo approach that enables electrophysiological, calcium imaging, and optogenetic assessment of convergence, divergence, and studies on pre- to postganglionic synaptic transmission, as well as whole-cell recordings from individual tSPNs. Preganglionic axonal connections from intact ventral roots and interganglionic nerves across multiple segments can be stimulated to evoke compound action potential responses in individual thoracic ganglia as recorded with suction electrodes. Chemical block of synaptic transmission differentiates spiking of preganglionic axons from synaptically-recruited tSPNs. Further dissection, including removal of the sympathetic chain, enables whole-cell patch clamp recordings from individual tSPNs for characterization of cellular and synaptic properties.

Challenge and response of imported malaria for preventing malaria re-establishment

Malaria was one of the most serious infectious diseases with the longest epidemic history in China. After decades of unremitting efforts by several generations of malaria workers, the malaria cases from 30 million per year to zero in China, and there have been no indigenes malaria cases for four consecutive years, which has reached the goal of WHO malaria elimination. However, there are thousands of imported malaria cases in China every year, and the malaria vector still exists in the original malaria-endemic areas. Deaths caused by imported malaria cases and secondary imported malaria cases occur somewhile. Imported malaria give rise to new challenge to prevent re-establishment of malaria in China. In this paper, the pathogenic biology of inputted parasite strains, the clinical characteristics and treatment needs of imported malaria cases and the possibility of local transmission through imported case are analyzed. Three countermeasures and suggestions are proposed for early finding and standardized treatment of imported cases as well as accurate blocking of potential local transmission by imported case. 摘要: 疟疾曾是我国流行历史最久远,影响范围最广泛,危害最严重的传染病之一,经过几代疟防工作者几十年不懈的努力,我国成功实现了从年发病例3 000万到0的突破,并已连续4年无本地原发疟疾病例,达到了世界卫生组织消除疟疾的标准。但我国每年仍有数千例境外输人性疟疾,原疟疾流行区的传疟媒介依然存在,因境外输人病例导致的死亡病例和输人继发病例时有发生,境外输人性疟疾对我国巩固消除疟疾成果,防止输人再传播造成新的威胁。本文就境外输人疟原虫虫株的病原生物学特征、境外输人性疟疾病例的临床特点和诊治需求、境外输人病例在本地传播可能性等进行了分析,并提出及时发现输人传染源、规范诊治输人性病例和精准阻断输人再传播三个防止输人再传播的对策建议。

Feature Learning Improved by Location Guidance and Supervision for Object Detection

In recent years, the single-stage detectors have been developed rapidly; however, compared with the multi-stage detectors, their detection precision is still relatively low. Single-stage detectors and multi-stage detectors are analyzes and compared in detail in this paper, which reveals that single-stage detectors suffer from some problems, including feature loss and inaccurate feature extraction. Therefore, this paper proposes a novel detection model, dubbed Optimized Network (OptNet), to alleviate these deficiencies. OptNet consists of three modules: pyramid of attention features, feature alignment and consistency supervision (CS). The pyramid of attention features, based on feature pyramid networks (FPNs), introduces a novel branch named attention FPN (AtFPN), which aggregates the multi-layer features of the backbone network and optimizes the object features by using lightweight attention modules. AtFPN alleviates the loss of the feature pyramid information and the blocking of feature transmission between adjacent layers. Meanwhile, it provides global information for the model. The feature alignment module aligns the anchor box to the feature by using the object location information to guide the network to extract precise object features. Finally, CS accelerates network optimization and reduces semantic differences between the features on different layers. In the detection stage, OptNet optimizes the prediction of the model with the first detection result to improve the accuracy. Experiments on the MS COCO 2017 dataset demonstrate that OptNet yields significant improvement in the detection precision.

Receiver Energy Efficiency and Transmission Latency Analysis of Outage-Constrained Differential PSK With a Finite Resolution ADC

We consider a power constrained downlink communication scenario where energy efficiency, reliability, and latency take precedence over rate, as in some Internet of Things (IoT) applications. To reduce its receiver power consumption and complexity, we assume that the IoT device has a single RF chain and investigate the finite-resolution analog-to-digital converter (ADC) operation with differential Phase Shift Keying (PSK) modulation. A lower ADC resolution leads to an exponential decrease in power consumption, while adopting differential PSK enables the use of a low-cost detector with no channel state information (CSI) or carrier phase recovery circuitry. Our main goal in this article is to compare, both analytically and numerically using representative IoT system design parameters, the receiver energy efficiency of the proposed differential PSK system with a coherent PSK system that uses estimated CSI under reliability and latency constraints in Rayleigh slow-fading and ADC quantization distortion conditions. To mitigate the ADC finite-resolution effects without requiring CSI at the receiver or transmitter, we propose and analyze a PSK differentially-modulated Alamouti space-time block transmission scheme with only two RF chains at the transmitter while still restricting the IoT device to have a single RF chain. Our results demonstrate that in the considered low-rate, and outage and latency-constrained scenario with stringent power consumption requirements, differentially-modulated Alamouti transmissions to a single RF-chain IoT device with a low-resolution ADC is an attractive choice in terms of receiver energy efficiency, reliability, and transmission latency.

Single Low Dose Tafenoquine Combined with Dihydroartemisinin-Piperaquine to Reduce <i>P. Falciparum</i> Transmission: A Phase 2 Single Blind Randomised Clinical Trial in Ouelessebougou, Mali

Background: Tafenoquine (TQ) was recently approved as prophylaxis and radical cure for P. vivax infection, but its P. falciparum transmission-blocking efficacy is unclear. We determined efficacy and safety of single doses of TQ in combination with dihydroartemisinin-piperaquine (DP) for reducing gametocyte density and transmission to mosquitoes. Methods: In this single-blind, phase 2 randomised clinical trial, participants (12-50 years of age) with asymptomatic P. falciparum microscopy-detected gametocyte carriage (n=80) were randomized to standard treatment with DP, or with DP plus a single dose of TQ (in solution) at a final concentration of 0·42mg/kg, 0·83mg/kg, or 1·66mg/kg. The primary endpoint was percent reduction in mosquito infection rate 7 days after treatment compared to baseline. Safety endpoints included frequency and incidence of adverse events (AE). The final follow-up visit was on the 23 rd December 2021; the trial is registered on ClinicalTrials.gov (NCT04609098). Findings: Participants were enrolled from 29th October to 25th November 2020. Before treatment, 66% (53/80) of individuals were infectious to mosquitoes, infecting on average 12·5% of mosquitoes (Interquartile range [IQR] 3·64-35). Within-arm percent reduction in mosquito infection rate on day 7 was 79·95% (IQR 57·15-100) following DP (p=0·0005 for difference from baseline), 100% (IQR 98·36-100) following DP-TQ 0·42mg/kg (p=0·0005), 100% (IQR 100-100) following DP -TQ 0·83mg/kg (p<0·0001) and 100% (IQR 100-100) following DP-TQ 1·66 mg/kg (p<0·0001). 55/80 participants experienced a total of 94 AE over the course of the trial; 86 categorised as ‘mild’, 7 as ‘moderate’, and 1 as ‘severe’. No serious adverse events (SAE) occurred. No significant differences in the incidence of all AEs (p=0.73) or drug-related AEs (p=0.62) were observed between treatment arms. Interpretation: TQ was well tolerated and accelerated P. falciparum gametocyte clearance. All TQ doses demonstrated improved transmission reduction at day 7 compared to DP alone. These data support the case for further research on TQ as a transmission blocking supplement to standard antimalarials. Trial Registration: ClinicalTrials.gov (NCT04609098). Funding: Bill & Melinda Gates FoundationTrial registration: Declaration of Interest: We have no competing interests. Ethical Approval: Ethical approval was granted by the Ethics Committee of the Faculty of Medicine, Pharmacy, and Dentistry of the University of Science, Techniques, and Technologies of Bamako (Bamako, Mali), and the Research Ethics Committee of the London School of Hygiene and Tropical Medicine (London, UK).