Broadband double-layered coplanar patch antennas with adjustable CPW feeding structure

In this paper, we have presented the double-layered coplanar patch antennas of enhanced impedance bandwidth and adjustable conductor-backed coplanar waveguide feed lines. The proposed structure retains the advantage of laying the coplanar patch and coplanar waveguide (CPW) feed line on the same surface, which makes direct integration with other devices easier. In addition, the substrate thickness of the radiating patch can be adjusted to achieve a wider impedance bandwidth while the dimensions of the CPW feed line are kept unchanged. Simulation has been done by using commercial electromagnetic (EM) simulation software. Four testing antennas, which have centre frequency at about 10 GHz, were designed. The four testing antennas had the same total thickness, but different thickness combinations. From the measured return loss, gain, and radiation patterns of the antennas, it was demonstrated that different thickness combinations do not affect the characteristics of the antennas seriously. Therefore, the dimensions of the CPW feed structure of the antennas can be adjusted individually and can be selected for different applications

Activation of RHOA–VAV1 signaling in angioimmunoblastic T-cell lymphoma

Somatic G17V RHOA mutations were found in 50–70% of angioimmunoblastic T-cell lymphoma (AITL). The mutant RHOA lacks GTP binding capacity, suggesting defects in the classical RHOA signaling. Here, we discovered the novel function of the G17V RHOA: VAV1 was identified as a G17V RHOA-specific binding partner via high-throughput screening. We found that binding of G17V RHOA to VAV1 augmented its adaptor function through phosphorylation of 174Tyr, resulting in acceleration of T-cell receptor (TCR) signaling. Enrichment of cytokine and chemokine-related pathways was also evident by the expression of G17V RHOA. We further identified VAV1 mutations and a new translocation, VAV1–STAP2, in seven of the 85 RHOA mutation-negative samples (8.2%), whereas none of the 41 RHOA mutation-positive samples exhibited VAV1 mutations. Augmentation of 174Tyr phosphorylation was also demonstrated in VAV1–STAP2. Dasatinib, a multikinase inhibitor, efficiently blocked the accelerated VAV1 phosphorylation and the associating TCR signaling by both G17V RHOA and VAV1–STAP2 expression. Phospho-VAV1 staining was demonstrated in the clinical specimens harboring G17V RHOA and VAV1 mutations at a higher frequency than those without. Our findings indicate that the G17V RHOA–VAV1 axis may provide a new therapeutic target in AITL

Durvalumab as monotherapy and in combination therapy in patients with lymphoma or chronic lymphocytic leukemia: The FUSION NHL 001 trial.

BACKGROUND: Studies suggest that immune checkpoint inhibitors may represent a promising strategy for boosting immune responses and improving the antitumor activity of standard therapies in patients with relapsed/refractory hematologic malignancies. AIMS: Phase 1/2 FUSION NHL 001 was designed to determine the safety and efficacy of durvalumab, an anti-programmed death ligand 1 (PD-L1) antibody, combined with standard-of-care therapies for lymphoma or chronic lymphocytic leukemia (CLL). METHODS AND RESULTS: The primary endpoints were to determine the recommended phase 2 dose of the drugs used in combination with durvalumab (durvalumab was administered at the previously recommended dose of 1500 mg every 4 weeks) and to assess safety and tolerability. Patients were enrolled into one of four arms: durvalumab monotherapy (Arm D) or durvalumab in combination with lenalidomide ± rituximab (Arm A), ibrutinib (Arm B), or rituximab ± bendamustine (Arm C). A total of 106 patients with relapsed/refractory lymphoma were enrolled. All but two patients experienced at least one treatment-emergent adverse event (TEAE); those not experiencing a TEAE were in Arm C (diffuse large B-cell lymphoma [DLBCL]) and Arm D (DLBCL during the durvalumab monotherapy treatment period). No new safety signals were identified, and TEAEs were consistent with the respective safety profiles for each study treatment. Across the study, patients with follicular lymphoma (FL; n = 23) had an overall response rate (ORR) of 59%; ORR among DLBCL patients (n = 37) was 18%. Exploratory biomarker analysis showed that response to durvalumab monotherapy or combination therapy was associated with higher interferon-γ signature scores in patients with FL (p = .02). CONCLUSION: Durvalumab as monotherapy or in combination is tolerable but requires close monitoring. The high rate of TEAEs during this study may reflect on the difficulty in combining durvalumab with full doses of other agents. Durvalumab alone or in combination appeared to add limited benefit to therapy

The ionospheric precursor to the 2011 march 11 earthquake as based on the Japan-pacific subionospheric VLF/LF network observation

By using the network observation of subionospheric VLF/LF signals in Japan and in Russia, we have found a significant ionospheric perturbation prior to the recent 2011 March 11 Japan earthquake (EQ) in the off-sea of the Tohoku area, which was an exceptionally huge plate-type EQ. A remarkable anomaly (with decrease in the nighttime amplitude and also with enhancement in dispersion) has been detected on March 5 and 6 on the propagation path from the NLK transmitter (Seattle, USA) to Chofu (together with Kochi and Kasugai), and also we have observed the corresponding VLF anomaly during a prolonged period of March 1–6, with minima in the nighttime amplitude on March 3 and 4 on the path from JJI transmitter (Miyazaki, Kyushu) to Kamchatka, Russia.Используя наблюдения распространения СДВ/ДВ-радиоволн над Тихим океаном на японской и российской сети станций, удалось обнаружить значительное возмущение ионосферы, предшествовавшее последнему мощному землетрясению в Японии 11.03.2011 г. Эпицентр землетрясения находился в море, в области Тохоку, а само событие относится к исключительно мощным землетрясениям, связанным с перемещением тектонических плит. Явно выраженная аномалия (уменьшение ночной амплитуды сигнала при увеличении ее дисперсии) была обнаружена 5 и 6 марта на трассе распространения от передатчика NLK (Сиэтл, США) к наблюдателю в Чофу, Япония (аналогичные явления – на трассах распространения в Кочи и Кацугаи). Аналогичная длительная аномалия в СДВ-распространении регистрировалась с 1 по 6 марта с минимальной ночной амплитудой 3 и 4 марта на трассе от передатчика JJI (Миязаки, Кюсю) до Камчатки, Россия.Використовуючи спостереження поширення СДВ/ДВ-радіохвиль над Тихим океаном на японській і російській мережі станцій, вдалося виявити значне збурення іоносфери, що сталося перед останнім потужним землетрусом у Японії 11.03.2011 р. Епіцентр землетрусу знаходився в морі, в області Тохоку, а сама подія відноситься до виключно потужних землетрусів, пов’язаних з переміщенням тектонічних плит. Явно виражена аномалія (зменшення нічної амплітуди сигналу при збільшенні її дисперсії) було виявлено 5 та 6 березня на трасі від передавача NLK (Сіетл, США) до спостерігача в Чофу, Японія (аналогічні явища – на трасах поширення до Кочі й Кацугаї). Аналогічну тривалу аномалію в СДВ-поширенні реєстрували з 1 по 6 березня з мінімальною нічною амплітудою 3 і 4 березня на трасі від передавача JJI (Міязакі, Кюсю) до Камчатки, Росія

Presence of genes for type III secretion system 2 in Vibrio mimicus strains

<p>Abstract</p> <p>Background</p> <p>Vibrios, which include more than 100 species, are ubiquitous in marine and estuarine environments, and several of them e.g. <it>Vibrio cholerae</it>, <it>V. parahaemolyticus</it>, <it>V. vulnificus </it>and <it>V. mimicus</it>, are pathogens for humans. Pathogenic <it>V. parahaemolyticus </it>strains possess two sets of genes for type III secretion system (T3SS), T3SS1 and T3SS2. The latter are critical for virulence of the organism and be classified into two distinct phylogroups, T3SS2α and T3SS2β, which are reportedly also found in pathogenic <it>V. cholerae </it>non-O1/non-O139 serogroup strains. However, whether T3SS2-related genes are present in other <it>Vibrio </it>species remains unclear.</p> <p>Results</p> <p>We therefore examined the distribution of the genes for T3SS2 in vibrios other than <it>V. parahaemolyticus </it>by using a PCR assay targeting both T3SS2α and T3SS2β genes. Among the 32 <it>Vibrio </it>species tested in our study, several T3SS2-related genes were detected in three species, <it>V. cholerae</it>, <it>V. mimicus </it>and <it>V. hollisae</it>, and most of the essential genes for type III secretion were present in T3SS2-positive <it>V. cholerae </it>and <it>V. mimicus </it>strains. Moreover, both <it>V. mimicus </it>strains possessing T3SS2α and T3SS2β were identified. The gene organization of the T3SS2 gene clusters in <it>V. mimicus </it>strains was fundamentally similar to that of <it>V. parahaemolyticus </it>and <it>V. cholerae </it>in both T3SS2α- and T3SS2β-possessing strains.</p> <p>Conclusions</p> <p>This study is the first reported evidence of the presence of T3SS2 gene clusters in <it>V. mimicus </it>strains. This finding thus provides a new insight into the pathogenicity of the <it>V. mimicus </it>species.</p

Bile Acid-Induced Virulence Gene Expression of Vibrio parahaemolyticus Reveals a Novel Therapeutic Potential for Bile Acid Sequestrants

Vibrio parahaemolyticus, a bacterial pathogen, causes human gastroenteritis. A type III secretion system (T3SS2) encoded in pathogenicity island (Vp-PAI) is the main contributor to enterotoxicity and expression of Vp-PAI encoded genes is regulated by two transcriptional regulators, VtrA and VtrB. However, a host-derived inducer for the Vp-PAI genes has not been identified. Here, we demonstrate that bile induces production of T3SS2-related proteins under osmotic conditions equivalent to those in the intestinal lumen. We also show that bile induces vtrA-mediated vtrB transcription. Transcriptome analysis of bile-responsive genes revealed that bile strongly induces expression of Vp-PAI genes in a vtrA-dependent manner. The inducing activity of bile was diminished by treatment with bile acid sequestrant cholestyramine. Finally, we demonstrate an in vivo protective effect of cholestyramine on enterotoxicity and show that similar protection is observed in infection with a different type of V. parahaemolyticus or with non-O1/non-O139 V. cholerae strains of vibrios carrying the same kind of T3SS. In summary, these results provide an insight into how bacteria, through the ingenious action of Vp-PAI genes, can take advantage of an otherwise hostile host environment. The results also reveal a new therapeutic potential for widely used bile acid sequestrants in enteric bacterial infections

Clinical outcome and risk factors for recurrence in borderline ovarian tumours

We investigated the long-term prognosis of borderline ovarian tumours and determined risk factors for recurrence. One hundred and twenty-one borderline ovarian tumours treated between 1994 and 2003 at the participating institutions in the Tohoku Gynecologic Cancer Unit were retrospectively investigated for clinical stage, histopathological subtype, surgical technique, postoperative chemotherapy, the presence or absence of recurrence, and prognosis. The median follow-up period was 57 months (1–126 months). One hundred and nine cases (90.6%) were at clinical stage I. The histopathological subtypes consisted of 91 cases of mucinous tumour (75.2%), 27 cases of serous tumour (22.3%), and three cases of endometrioid tumour. Conservative surgery was used in 53 cases (43.8%), radical surgery in 68 cases (56.2%), a staging laparotomy in 43 cases (35.5%), and postoperative adjuvant therapy in 30 cases (24.8%). Recurrence was found in eight cases, but no tumour-related deaths were reported. Although no significant difference in disease-free survival rate was seen between different clinical stages, the difference in disease-free survival rate between serous and nonserous (mucinous and endometrioid) types was significant (P<0.05). The 10-year disease-free survival rate was 89.1% for the radical surgery group and 57.4% for the conservative surgery group – this difference was significant (P<0.05). In the conservative surgery group, cystectomy and serous tumour were independent risk factors for recurrence. Although recurrence was observed, the long-term prognosis of borderline ovarian tumour was favourable, without tumour-related deaths. Considering the favourable prognosis, conservative surgery can be chosen as far as the patient has a nonserous tumour and receive adnexectomy. However, in cases of serous type and/or receiving cystectomy special care should be given as relative risk rates of recurrence elevate by 2–4-folds