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Background： Patients implanted with pacemakers frequently develop atrial fibrillation. Pacemaker-detected atrial high-rate episodes or AHREs, where one AHRE is defined as ≥ 160beats/min lasting ≥ 5 minutes, may identify patients at increased risk for stroke and death. In this study, we sought to observe whether patients with sinus node dysfunction or atria-ventricular block are more likely to develop AHREs. Methods: A total of 103 patients (age 69.4±13.5 years，58% female) with DDD/DDDR pacemakers were enrolled for the study. These pacemakers were equipped with features that enabled the detection and storage of information such as the dates, durations and sequential episodes of AHRE. Patients were followed up for 2 years and the time of the first occurrence of AHRE was determined at follow-up visit. Other data such as age, gender, structural heart disease, concomitant non-cardiac diseases, the cumulative percentage of atrial pacing (Cum% AP) and ventricular pacing (Cum% VP) were also collected. Results: Atrial fibrillation developed frequently after the dual-chamber pacemaker implantation. AHRE occurred more often in patients with sinus node disease (SND) than those with atrioventricular block (AVB) （OR, 2.553; 95%CI, 1.122-5.814；P=0.045）. Conclusions: AHRE developed frequently after dual-chamber pacemaker implantation. Patients with SND are more likely to develop AF compared to the patients with AVB.

The development of a blood-stage malaria vaccine has largely focused on the subunit approach. However, the limited success of this strategy, mainly due to antigenic polymorphism and the failure to maintain potent parasite-specific immune responses, indicates that other approaches must be considered. Whole parasite (WP) vaccines offer many advantages over sub-units; they represent every antigen on the organism, thus limiting the effects of antigenic polymorphism, and similarly they compensate for individual Immune-Response (Ir) gene-regulated non-responsiveness to any particular antigen. From a development perspective, they negate the need to identify and compare the relative efficacies of individual candidate antigens. WP vaccines induce protective immunity that is largely cell-mediated. However, WP blood-stage vaccines present a number of challenges for the development pathway. Key issues are cryopreservation and storage and the possible induction of antibodies against red blood cell surface antigens, even if the parasites are grown in blood group O, Rh negative blood. Here, we used a novel adaptation of an immunomagnetic method from STEMCELL™ Technologies to remove the red cell membranes from human red blood cells parasitized with P. falciparum. We then used these antigens to construct liposomes which were modified to present mannose on their membrane to target the liposome to antigen presenting cells. We then compared the immunogenicity of freshly prepared and lyophilized liposome vaccines. Following vaccination of mice, liposomes induced significantly lower antibody responses to human red cells but potent strain- and species-transcending cell-mediated immune responses to parasite antigens. These data support transitioning the P. falciparum liposomal vaccine into clinical studies.

© 2019 IEEE In this work, an on-chip bandpass filter (BPF) with ultra-wideband, low insertion loss, sharp selectivity and excellent in-band flatness is achieved using a novel design approach based on a quasi-lumped-element method. This approach simply utilizes folded metal strip lines with metal-insulator-metal (MIM) capacitors. To understand the principle of the presented design approach, theoretical analysis is given by means of a simplified equivalent LC-circuit model. Using the analyzed results with a full-wave electromagnetic (EM) simulator to guide the design, a BPF is implemented and fabricated in a standard 0.13-µm (Bi)-CMOS technology. The measurements show that a return loss of better than 10 dB is obtained from 13.5 to 32 GHz. Furthermore, the insertion loss of less than 2.3 dB is achieved with less than 0.1 dB in-band magnitude ripple. The BPF size without measurement pads is only 0.148 mm2 (0.37 × 0.4 mm2).

© 2018 IEEE. In this paper, two third-order bandpass filters (BPFs) designed for millimeter-wave applications are presented. Unlike previously published ones, the proposed designs use a "cell-based" approach, which utilizes identical broadside-coupled resonators (BCRs) with series and shunt capacitors. The capacitors are mainly used as J -inverters to achieve the desired frequency responses. To fully understand the operational mechanism of the presented approach, both the BCR and BPFs are analyzed using the simplified LC-equivalent circuit models. To prove the concept, both BPFs are implemented in a standard 0.13- μm silicon-germanium bipolar complementary metal-oxide-semiconductor technology. According to the on-wafer measurement results, the BPFs exhibit the excellent performance including flat in-band responses with relatively large harmonic suppression. The first design has a 1-dB bandwidth from 23.9 to 39.7 GHz with an insertion loss of 3.9 dB at the center frequency of 31 GHz. The stopband attenuation is better than 45 dB at 58 GHz. The 1-dB bandwidth of the second design covers from 26.7 to 44.3 GHz with an insertion loss of 3.1 dB at the center frequency of 35 GHz, and stopband attenuation up to 35 dB is achieved at 59 GHz. Both designs occupy an identical area of 0.073 mm 2 (0.248×0.294 mm 2 ), excluding the G-S-G testing pads.

Naturally acquired immunity to malaria is robust and protective against all strains of the same species of Plasmodium. This develops as a result of repeated natural infection, taking several years to develop., Naturally acquired immunity to malaria is robust and protective against all strains of the same species of Plasmodium. This develops as a result of repeated natural infection, taking several years to develop. Evidence suggests that apoptosis of immune lymphocytes due to uncontrolled parasite growth contributes to the slow acquisition of immunity. To hasten and augment the development of natural immunity, we studied controlled infection immunization (CII) using low-dose exposure to different parasite species (Plasmodium chabaudi, P. yoelii, or P. falciparum) in two rodent systems (BALB/c and C57BL/6 mice) and in human volunteers, with drug therapy commencing at the time of initiation of infection. CIIs with infected erythrocytes and in conjunction with doxycycline or azithromycin, which are delayed death drugs targeting the parasite’s apicoplast, allowed extended exposure to parasites at low levels. In turn, this induced strong protection against homologous challenge in all immunized mice. We show that P. chabaudi/P. yoelii infection initiated at the commencement of doxycycline therapy leads to cellular or antibody-mediated protective immune responses in mice, with a broad Th1 cytokine response providing the best correlate of protection against homologous and heterologous species of Plasmodium. P. falciparum CII with doxycycline was additionally tested in a pilot clinical study (n = 4) and was found to be well tolerated and immunogenic, with immunological studies primarily detecting increased cell-associated immune responses. Furthermore, we report that a single dose of the longer-acting drug, azithromycin, given to mice (n = 5) as a single subcutaneous treatment at the initiation of infection controlled P. yoelii infection and protected all mice against subsequent challenge.

Background The continuing morbidity and mortality associated with infection with malaria parasites highlights the urgent need for a vaccine. The efficacy of sub-unit vaccines tested in clinical trials in malaria-endemic areas has thus far been disappointing, sparking renewed interest in the whole parasite vaccine approach. We previously showed that a chemically attenuated whole parasite asexual blood-stage vaccine induced CD4+ T cell-dependent protection against challenge with homologous and heterologous parasites in rodent models of malaria. Methods In this current study, we evaluated the immunogenicity and safety of chemically attenuated asexual blood-stage Plasmodium falciparum (Pf) parasites in eight malaria-naïve human volunteers. Study participants received a single dose of 3 × 107 Pf pRBC that had been treated in vitro with the cyclopropylpyrolloindole analogue, tafuramycin-A. Results We demonstrate that Pf asexual blood-stage parasites that are completely attenuated are immunogenic, safe and well tolerated in malaria-naïve volunteers. Following vaccination with a single dose, species and strain transcending Plasmodium-specific T cell responses were induced in recipients. This included induction of Plasmodium-specific lymphoproliferative responses, T cells secreting the parasiticidal cytokines, IFN-γ and TNF, and CD3+CD45RO+ memory T cells. Pf-specific IgG was not detected. Conclusions This is the first clinical study evaluating a whole parasite blood-stage malaria vaccine. Following administration of a single dose of completely attenuated Pf asexual blood-stage parasites, Plasmodium-specific T cell responses were induced while Pf-specific antibodies were not detected. These results support further evaluation of this chemically attenuated vaccine in humans. Trial registration Trial registration: ACTRN12614000228684. Registered 4 March 2014.

Plasmodium falciparum is the most virulent human malaria parasite because of its ability to cytoadhere in the microvasculature. Nonhuman primate studies demonstrated relationships among knob expression, cytoadherence, and infectivity. This has not been examined in humans. Cultured clinical-grade P. falciparum parasites (NF54, 7G8, and 3D7B) and ex vivo -derived cell banks were characterized. Knob and knob-associated histidine-rich protein expression, CD36 adhesion, and antibody recognition of parasitized erythrocytes (PEs) were evaluated. Parasites from the cell banks were administered to malaria-naive human volunteers to explore infectivity. For the NF54 and 3D7B cell banks, blood was collected from the study participants for in vitro characterization. All parasites were infective in vivo . However, infectivity of NF54 was dramatically reduced. In vitro characterization revealed that unlike other cell bank parasites, NF54 PEs lacked knobs and did not cytoadhere. Recognition of NF54 PEs by immune sera was observed, suggesting P. falciparum erythrocyte membrane protein 1 expression. Subsequent recovery of knob expression and CD36-mediated adhesion were observed in PEs derived from participants infected with NF54. Knobless cell bank parasites have a dramatic reduction in infectivity and the ability to adhere to CD36. Subsequent infection of malaria-naive volunteers restored knob expression and CD36-mediated cytoadherence, thereby showing that the human environment can modulate virulence.

MnxOy, CoxOy, and MnxOy-CoxOy supported on activated carbon (AC) adsorbents have been successfully prepared and characterized by specific surface area (BET), X-ray photoelectron spectroscopy, X-ray...

© 2004-2012 IEEE. Load-variation insensitivity, for impedance matching between power amplifiers (PAs) and transmitting antennas, contributes to challenging the design of millimeter-wave wireless systems. In this paper, a W -band two-way balanced PA based on a compact quadrature coupler with a broadside coupled strip-line (BCSL) as the core is presented to enhance the load-variation insensitivity and stability. The proposed coupler is truly broadband with low amplitude and phase imbalance. The proposed W -band balanced PA achieves higher power-added efficiency (PAE) and unsaturated output power {P} -{\mathrm{ sat}} over wide frequency bandwidth. The W -band balanced PA is implemented in a 0.13- \mu \text{m} SiGe BiCMOS process and achieves a measured {P} -{\mathrm{ sat}} of 16.3 dBm and a peak PAE of 14.1% at 100 GHz (with 1.6-V power supply). The measured {P} -{\mathrm{ sat}} with 1-dB bandwidth is from 91 to 102 GHz. The measured results present the feasibility of the compact quadrature coupler. The total chip surface area (with pads) is 0.64 mm2, where the size of the proposed quadrature coupler area is only 0.04 mm2.

© 1980-2012 IEEE. This letter proposes a compact and broadband quadrature coupler with a center frequency of 55 GHz, which consists of a 90° broadside coupled-line to support the differential signal propagation and two T-type L-C networks to support the common signal propagation. To analyze the proposed coupler, an equivalent circuit model is provided for estimation of the distributed and lumped component values. The measured results of the proposed on-chip quadrature coupler show that the return loss and isolation are greater than 20 dB with a bandwidth of 105%, while the insertion loss is about -0.85 dB. The magnitude imbalances are less than 1 dB within the bandwidth of 56% and the phase differences are with ±1° errors within the bandwidth of 96.9%. The chip size, excluding the test pads, is only 0.31 × 0.22 mm2.

© 1980-2012 IEEE. In this letter, an on-chip miniaturized bandpass filter (BPF) is presented, which is based on a grounded center-Tapped ring resonator (CTRR) with shunt capacitive loading. To analyze the principle of this design, a simple but effective equivalent circuit model is provided. Using this model, it is easy to show that the CTRR-based approach has a potential to generate two transmission poles within the passband. Compared with the conventional single-pole-based approach, this dual-pole design not only possesses a flexibility of controlling the passband width, but also has better flatness of insertion loss in the passband. In addition, this approach is able to significantly improve the stopband performance. To further demonstrate the feasibility of this approach in practice, the structure is implemented and fabricated in a commercial 0.13-μ (Bi)-CMOS SiGe technology. The measured results show that the BPF has a center frequency at 33 GHz with a bandwidth of 42.4%. The minimum insertion loss is 2.6 dB, while the stopband rejection is maintained to be better than 20 dB beyond 58 GHz. The chip, excluding the pads, is very compact at only 0.03 mm2 (0.11 × 0.28 mm2.