Electrostatic Adsorption Behaviors of Polymer Plates to a Droplet.

Electrostatic transfer and adsorption of electrically conductive polymer-coated poly(ethylene terephthalate) plates from a particle bed to a water droplet were studied, with the influence of plate thickness and shape observed. After synthesis and confirmation of the particles' properties using stereo and scanning electron microscopies, elemental microanalysis, and water contact angle measurement, the electric field strength and droplet-bed separation distance required for transfer were measured. An electrometer and high-speed video footage were used to measure the charge transferred by each particle, and its orientation and adsorption behavior during transfer and at the droplet interface. The use of plates of consistent square cross section allowed the impact of contact-area-dependent particle cohesion and gravity on the electrostatic transfer of particles to be decoupled for the first time. The electrostatic force required to extract a plate was directly proportional to the plate mass (thickness), a trend very different from that previously observed for spherical particles of varied diameter (mass). This reflected the different relationship between mass, surface area, and cohesive forces for spherical and plate-shaped particles of different sizes. Thicker plates transferred more charge to the droplet, probably due to their remaining at the bed at higher field strengths. The impact of plate cross-sectional geometry was also assessed. Differences in the ease of transfer of square, hexagonal, and circular plates seemed to depend only on their mass, while other aspects of their comparative behavior are attributed to the more concentrated charge distribution present on particles with sharper vertices.

24-Hour Rest-Activity Rhythm in Middle-Aged and Older Persons with Depression.

Changes in rest or active states were clinically observed in persons with depression. However, the association between symptoms of depression and 24 h rest-activity rhythm (RAR) components that can be measured using wearable devices was not clarified. This preliminary cross-sectional study aimed to clarify the 24 h RAR components associated with symptoms of depression in middle-aged and older persons. Participants were recruited from among inpatients and outpatients requiring medical treatment at Akita University Hospital for the group with depression and from among healthy volunteers living in Akita prefecture, Japan, for the healthy control group. To assess RAR parameters including inter-daily stability (IS), intra-daily variability (IV), relative amplitude (RA), and average physical activity level for the most active 10 h span (M10) or for the least active 5 h span (L5), all the participants were instructed to wear an Actiwatch Spectrum Plus device on their non-dominant wrist for seven days. Twenty-nine persons with depression and 30 controls were included in the analysis. The results of a binomial regression analysis showed that symptoms of depression were significantly associated with a high IS value (odds ratio [OR], 1.20; 95% confidence interval [95% CI], 1.01-1.44; p = 0.04) and a low M10 value (OR, 0.85; 95% CI, 0.74-0.96; p = 0.01). Our findings suggest potential components of 24 h RAR are associated with depression.

A Comprehensive Study of the Immunophenotype and its Clinicopathologic Significance in Adult T-Cell Leukemia/Lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell tumor caused by human T-lymphotropic virus type 1 (HTLV-1). The typical ATLL immunophenotypes are described in the 2017 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (positive: CD2, CD3, CD5, CD4, and CD25; negative: CD7, CD8, and cytotoxic markers; and partially positive: CD30, CCR4, and FOXP3). However, limited studies are available on the expression of these markers, and their mutual relationship remains unknown. Furthermore, the expression status of novel markers associated with T-cell lymphomas, including Th1 markers (T-bet and CXCR3), Th2 markers (GATA3 and CCR4), T follicular helper markers (BCL6, PD1, and ICOS), and T-cell receptor (TCR) markers, and their clinicopathologic significance is unclear. In this study, we performed >20 immunohistochemical stains in 117 ATLL cases to determine the comprehensive immunophenotypic profile of ATLL, which were compared on the basis of clinicopathologic factors, including morphologic variants (pleomorphic vs anaplastic), biopsy locations, treatments, Shimoyama classification-based clinical subtype, and overall survival. CD3+/CD4+/CD25+/CCR4+ was considered a typical immunophenotype of ATLL, but approximately 20% of cases did not conform to this pattern. Simultaneously, the following new findings were obtained: (1) most cases were negative for TCR-ß and TCR-δ (104 cases, 88.9%), indicating the usefulness of negative conversion of TCR expression to provide differentiation from other T-cell tumors; (2) the positivity of CD30 and CD15 and the negativity of FOXP3 and CD3 were significantly associated with anaplastic morphology; and (3) atypical cases, such as T follicular helper marker-positive (12 cases, 10.3%) and cytotoxic molecule-positive cases (3 cases, 2.6%), were identified. No single markers could predict the overall survival among patients with acute/lymphoma subtypes of ATLL. The results of this study illustrate the diversity of ATLL phenotypes. In T-cell tumors occurring in HTLV-1 carriers, the possibility of ATLL should not be eliminated even when the tumor exhibits an atypical phenotype, and the confirmation of HTLV-1 in the tissue is recommended.

A protective role of HTLV-1 gp46-specific neutralizing and antibody-dependent cellular cytotoxicity-inducing antibodies in progression to adult T-cell leukemia (ATL).

Human T-cell leukemia virus type-1 (HTLV-1) establishes a long-term persistent infection in humans and causes malignant T-cell leukemia, adult T-cell leukemia (ATL). HTLV-1-specific cytotoxic T lymphocytes have been suggested to play a major role in the immunosurveillance of HTLV-1-infected T cells. However, it remains unclear whether HTLV-1-specific functional antibodies are also involved in the host defense. To explore the role of antibodies in the course of HTLV-1 infection, we quantitated HTLV-1-specific neutralizing and antibody-dependent cellular cytotoxicity (ADCC)-inducing antibody levels in plasma from asymptomatic carriers (ACs) and ATL patients. The levels of neutralizing antibodies, as determined by a syncytium inhibition assay, were significantly lower in acute and chronic ATL patients than in ACs. The levels of ADCC-inducing activity were tested using an autologous pair of HTLV-1-producing cells and cultured natural killer (NK) cells, which showed that the ADCC-inducing activity of IgG at a concentration of 100 µg/ml was comparable between ACs and acute ATL patients. The anti-gp46 antibody IgG levels, determined by ELISA, correlated with those of the neutralizing and ADCC-inducing antibodies. In contrast, the proviral loads did not correlate with any of these antibody levels. NK cells and a monoclonal anti-gp46 antibody reduced the number of HTLV-1 Tax-expressing cells in cultured peripheral blood mononuclear cells from patients with aggressive ATL. These results suggest a protective role for HTLV-1 neutralizing and ADCC-inducing antibodies during the course of HTLV-1 infection.

Learning from mistakes-Assessing the performance and uncertainty in process-based models.

Typical applications of process- or physically-based models aim to gain a better process understanding or provide the basis for a decision-making process. To adequately represent the physical system, models should include all essential processes. However, model errors can still occur. Other than large systematic observation errors, simplified, misrepresented, inadequately parametrised or missing processes are potential sources of errors. This study presents a set of methods and a proposed workflow for analysing errors of process-based models as a basis for relating them to process representations. The evaluated approach consists of three steps: (1) training a machine-learning (ML) error model using the input data of the process-based model and other available variables, (2) estimation of local explanations (i.e., contributions of each variable to an individual prediction) for each predicted model error using SHapley Additive exPlanations (SHAP) in combination with principal component analysis, (3) clustering of SHAP values of all predicted errors to derive groups with similar error generation characteristics. By analysing these groups of different error-variable association, hypotheses on error generation and corresponding processes can be formulated. That can ultimately lead to improvements in process understanding and prediction. The approach is applied to a process-based stream water temperature model HFLUX in a case study for modelling an alpine stream in the Canadian Rocky Mountains. By using available meteorological and hydrological variables as inputs, the applied ML model is able to predict model residuals. Clustering of SHAP values results in three distinct error groups that are mainly related to shading and vegetation-emitted long wave radiation. Model errors are rarely random and often contain valuable information. Assessing model error associations is ultimately a way of enhancing trust in implemented processes and of providing information on potential areas of improvement to the model.

Elevation of the Plasma Levels of TNF Receptor 2 in Association with Those of CD25, OX40, and IL-10 and HTLV-1 Proviral Load in Acute Adult T-Cell Leukemia.

Adult T-cell leukemia/lymphoma (ATL) cells express TNF receptor type-2 (TNFR2) on their surface and shed its soluble form (sTNFR2). We previously reported that sTNFR2 levels were highly elevated in the plasma of patients with acute ATL. To investigate whether its quantitation would be helpful for the diagnosis or prediction of the onset of acute ATL, we examined the plasma levels of sTNFR2 in a large number of specimens obtained from a cohort of ATL patients and asymptomatic human T-cell leukemia virus type 1 (HTLV-1) carriers (ACs) and compared them to those of other candidate ATL biomarkers (sCD25, sOX40, and IL-10) by enzyme-linked immunosorbent assays (ELISA) and HTLV-1 proviral loads. We observed that sTNFR2 levels were significantly elevated in acute ATL patients compared to ACs and patients with other types of ATL (chronic, smoldering, and lymphoma). Importantly, sTNFR2 levels were significantly correlated with those of sCD25, sOX40, and IL-10, as well as proviral loads. Thus, the present study confirmed that an increase in plasma sTNFR2 levels is a biomarker for the diagnosis of acute ATL. Examination of plasma sTNFR2 alone or in combination with other ATL biomarkers may be helpful for the diagnosis of acute ATL.

Molecular epidemiological features of SARS-CoV-2 in Japan, 2020-1.

There were five epidemic waves of coronavirus disease 2019 in Japan between 2020 and 2021. It remains unclear how the domestic waves arose and abated. To better understand this, we analyzed the pangenomic sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and characterized the molecular epidemiological features of the five epidemic waves in Japan. In this study, we performed deep sequencing to determine the pangenomic SARS-CoV-2 sequences of 1,286 samples collected in two cities far from each other, Tokyo Metropolis and Nagoya. Then, the spatiotemporal genetic changes of the obtained sequences were compared with the sequences available in the Global Initiative on Sharing All Influenza Data (GISAID) database. A total of 873 genotypes carrying different sets of mutations were identified in the five epidemic waves. Phylogenetic analysis demonstrated that sharp displacements of lineages and genotypes occurred between consecutive waves over the 2 years. In addition, a wide variety of genotypes were observed in the early half of each wave, whereas a few genotypes were detected across Japan during an entire wave. Phylogenetically, putative descendant genotypes observed late in each wave displayed regional clustering and evolution in Japan. The genetic diversity of SARS-CoV-2 displayed uneven dynamics during each epidemic wave in Japan. Our findings provide an important molecular epidemiological basis to aid in controlling future SARS-CoV-2 epidemics.

First molecular detection of Hemolivia and Hepatozoon parasites in reptile-associated ticks on Iriomote Island, Japan.

Hepatozoon and Hemolivia are members of the haemogregarines and are reported in reptiles and reptile-associated ticks. However, no studies have reported on Hepatozoon and Hemolivia in Japanese reptile-associated ticks. This study aimed to molecularly identify and to characterize Hepatozoon and Hemolivia in Japanese reptile-associated ticks, Amblyomma geoemydae (Cantor, 1847) and Amblyomma nitidum (Hirst & Hirst, 1910). A total of 41 and 75 DNA samples from A. geoemydae and A. nitidum ticks, respectively, were used for screening of Hepatozoon and Hemolivia with polymerase chain reaction targeting 18S rDNA. As a result, Hemolivia and Hepatozoon were detected in two A. geoemydae and one A. nitidum, respectively. The sequences of Hemolivia spp. showed a 99.5% (1,050/1,055 bp) identity with Hemolivia parvula (KR069083), and the Hemolivia spp. were located in the same clade as H. parvula in the phylogenetic tree. The sequences of Hepatozoon sp. showed a 98.4% (1,521/1,545 bp) identity with Hepatozoon colubri (MN723844), and the Hepatozoon sp. was distinct from validated Hepatozoon species in the tree. Our findings highlight the first molecular record of Hemolivia in Japan and present the first detection of Hepatozoon in A. nitidum. Further investigations on these tick-borne protozoa are required to understand their life cycle and pathogenicity.

Clinicopathological features of adult T-cell leukemia/lymphoma with HTLV-1-infected Hodgkin and Reed-Sternberg-like cells.

Hodgkin and Reed-Sternberg (HRS) cells, a hallmark of classic Hodgkin lymphoma (CHL), are occasionally detected in non-Hodgkin lymphomas, including adult T-cell leukemia/lymphoma (ATLL), a lymphoid neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1). HRS-like cells associated with ATLL have been described to be of B-cell lineage and infected with Epstein-Barr virus (EBV), not HTLV-1. We herein describe clinicopathological findings in 8 cases (4 males and 4 females; median age, 73 years [range, 55-81 years]) of ATLL with HTLV-1-infected HRS-like cells identified by ultrasensitive RNA in situ hybridization for HTLV-1 basic leucine zipper factor (HBZ-ISH), a specific viral transcript of HTLV-1. All patients showed nodal or mediastinal lesions, and 5 of the 8 patients were at an advanced disease stage. HRS-like cells were positive for CD30, CD15, MUM1, CD25, and HBZ-ISH and negative for B-cell markers, including PAX5, pan-T-cell antigens, and EBV in all cases. Five cases were positive for CD4, and 6 cases were positive for fascin. HBZ was identified in both HRS-like cells and surrounding lymphoid cells in 1 case with an aggressive clinical course and only HRS-like cells in 7 cases, most of whom showed a clinical response regardless of the chemotherapeutic regimen. Even though the definitive lineage typing of the HTLV-1-infected HRS cells is one of the limitations of this study in the absence of single-cell microdissection for polymerase chain reaction analysis, the combination of diffuse HBZ-ISH positivity and negativity for PAX5 and EBV deemed these cases distinct from CHL arising in HTLV-1 carriers.

Genetic profile of adult T-cell leukemia/lymphoma in Okinawa: Association with prognosis, ethnicity, and HTLV-1 strains.

Genetic alterations in adult T-cell leukemia/lymphoma (ATLL), a T-cell malignancy associated with HTLV-1, and their clinical impacts, especially from the perspective of viral strains, are not fully elucidated. We employed targeted next-generation sequencing and single nucleotide polymorphism array for 89 patients with ATLL in Okinawa, the southernmost islands in Japan, where the frequency of HTLV-1 tax subgroup-A (HTLV-1-taxA) is notably higher than that in mainland Japan, where most ATLL cases have HTLV-1-taxB, and compared the results with previously reported genomic landscapes of ATLL in mainland Japan and the USA. Okinawan patients exhibited similar mutation profiles to mainland Japanese patients, with frequent alterations in TCR/NF-ĸB (eg, PRKCB, PLCG1, and CARD11) and T-cell trafficking pathways (CCR4 and CCR7), in contrast with North American patients who exhibited a predominance of epigenome-associated gene mutations. Some mutations, especially GATA3 and RHOA, were detected more frequently in Okinawan patients than in mainland Japanese patients. Compared to HTLV-1-taxB, HTLV-1-taxA was significantly dominant in Okinawan patients with these mutations (GATA3, 34.1% vs 14.6%, P = .044; RHOA, 24.4% vs 6.3%, P = .032), suggesting the contribution of viral strains to these mutation frequencies. From a clinical viewpoint, we identified a significant negative impact of biallelic inactivation of PRDM1 (P = .027) in addition to the previously reported PRKCB mutations, indicating the importance of integrated genetic analysis. This study suggests that heterogeneous genetic abnormalities in ATLL depend on the viral strain as well as on the ethnic background. This warrants the need to develop therapeutic interventions considering regional characteristics.

Rock glaciers and related cold rocky landforms: Overlooked climate refugia for mountain biodiversity.

Mountains are global biodiversity hotspots where cold environments and their associated ecological communities are threatened by climate warming. Considerable research attention has been devoted to understanding the ecological effects of alpine glacier and snowfield recession. However, much less attention has been given to identifying climate refugia in mountain ecosystems where present-day environmental conditions will be maintained, at least in the near-term, as other habitats change. Around the world, montane communities of microbes, animals, and plants live on, adjacent to, and downstream of rock glaciers and related cold rocky landforms (CRL). These geomorphological features have been overlooked in the ecological literature despite being extremely common in mountain ranges worldwide with a propensity to support cold and stable habitats for aquatic and terrestrial biodiversity. CRLs are less responsive to atmospheric warming than alpine glaciers and snowfields due to the insulating nature and thermal inertia of their debris cover paired with their internal ventilation patterns. Thus, CRLs are likely to remain on the landscape after adjacent glaciers and snowfields have melted, thereby providing longer-term cold habitat for biodiversity living on and downstream of them. Here, we show that CRLs will likely act as key climate refugia for terrestrial and aquatic biodiversity in mountain ecosystems, offer guidelines for incorporating CRLs into conservation practices, and identify areas for future research.

A new diagnostic algorithm using biopsy specimens in adult T-cell leukemia/lymphoma: combination of RNA in situ hybridization and quantitative PCR for HTLV-1.

Histopathological distinction between adult T-cell leukemia/lymphoma (ATLL) and other T-cell neoplasms is often challenging. The current gold standard for the accurate diagnosis of ATLL is the Southern blot hybridization (SBH) assay, which detects clonal integration of human T-cell leukemia virus type I (HTLV-1) provirus. However, SBH cannot be performed with small biopsy or formalin-fixed paraffin-embedded (FFPE) tissue samples because this assay requires a large amount of DNA without degradation. Here we developed a new diagnostic algorithm for the accurate diagnosis of ATLL using FFPE samples. This method combines two HTLV-1 detection assays, namely, ultrasensitive RNA in situ hybridization using RNAscope for HTLV-1 bZIP factor (HBZ-RNAscope), and quantitative PCR targeting the tax gene (tax-qPCR). We analyzed 119 FFPE tissue specimens (62 ATLL, and 57 non-ATLL, including 41 HTLV-1 carriers) and compared them with the SBH results using the corresponding fresh-frozen samples. As a result, tax-qPCR had a higher ATLL identification rate than HBZ-RNAscope (88% [52/59], and 63% [39/62], respectively). However, HBZ-RNAscope clearly visualized the localization of HTLV-1-infected tumor cells and its identification rate increased to 94% (17/18) when the analysis was limited to samples up to 2 years old, indicating its usefulness in the daily diagnosis. The diagnostic algorithm combining these two assays successfully evaluated 94% (112/119) of samples and distinguished ATLL from non-ATLL cases including HTLV-1 carriers with 100% sensitivity and specificity. This method is expected to replace SBH and increase the accuracy of the diagnosis of ATLL.

Rickettsia spp. and Ehrlichia spp. in Amblyomma ticks parasitizing wild amphibious sea kraits and yellow-margined box turtles in Okinawa, Japan.

Recently, several tick-borne pathogens were detected in reptile-associated ticks. However, studies on the microorganisms in reptile-associated ticks in Japan are limited. This molecular survey thus aimed to identify and characterize tick-borne pathogens (Rickettsiaceae and Anaplasmataceae) in reptile-associated ticks in Japan. In total, 77 Amblyomma nitidum and 104 Amblyomma geoemydae were collected from wild amphibious sea kraits (Laticauda semifasciata, Laticauda colubrina, and Laticauda laticaudata) and from yellow-margined box turtles (Cuora flavomarginata evelynae), respectively. Conventional polymerase chain reaction was performed using the DNA extracted from the ticks to detect the selected pathogens. Sequencing analysis of four Rickettsia genes (gltA, ompA, ompB, and sca4) led to the identification of a putative novel Rickettsia sp. and Rickettsia aeschlimannii-like rickettsia in A. nitidum and A. geoemydae, respectively. Sequencing analysis of gltA and groEL of Anaplasmataceae revealed that the Ehrlichia spp. in these ticks were novel and related to Candidatus Ehrlichia occidentalis. This is the first study on the microorganisms in A. nitidium and the first record of Rickettsia and Ehrlichia in A. geoemydae. Further studies are required to understand their pathogenicity to humans and animals and their life cycle in the wild.

[Improvement of Analytical Method of PCBs by GC-MS/MS Using an Accelerated Solvent Extractor and Expansion of Target Food Products].

We examined the expansion of target food products for the analysis of polychlorinated biphenyls (PCBs). From our studies in fish using an accelerated solvent extractor (ASE) and GC-MS/MS, we found that recovery of low-chlorinated PCBs (some isomer of 3 or 4 chlorinated PCBs) in specific food products was low. Therefore, we attempted to improve the analytical method. In Japanese sea perch (Suzuki) and milk, freeze drying before extracting with ASE did not sufficiently improve the recovery of low-chlorinated PCBs; however, it was significantly improved by changing the column to a silica gel/H2SO4 silica gel multilayer column. To evaluate this method for other food products, PCBs in fish, meat, eggs, milk, and dairy products were analyzed. The samples were extracted using ASE at 125℃ with n-hexane, cleaned up using a silica gel/H2SO4 silica gel multilayer column, and analyzed by GC-MS/MS for 3-7 chlorinated PCBs. The limit of quantification for this method was was 0.03-0.16 µg/kg for the 3-7 chlorinated PCBs. The recovery and the coefficient of variation of 3-7 chlorinated PCBs from each of the food products (n=5) was in the range of 84%-112% and 1%-9%, respectively.

Hydrogeological characterization of an alpine aquifer system in the Canadian Rocky Mountains.

Groundwater storage in alpine regions is essential for maintaining baseflows in mountain streams. Recent studies have shown that common alpine landforms (e.g., talus and moraine) have substantial groundwater storage capacity, but the hydrogeological connectivity between individual landforms has not been understood. This study characterizes the hydrogeology of an alpine cirque basin in the Canadian Rocky Mountains that contains typical alpine landforms (talus, meadow, moraines) and hydrological features (tarn, streams, and springs). Geological, hydrological, and hydrochemical observations were used to understand the overall hydrogeological setting of the study basin, and three different geophysical methods (electrical resistivity tomography, seismic refraction tomography, and ground penetrating radar) were used to characterize the subsurface structure and connectivity, and to develop a hydrogeological conceptual model. Geophysical imaging shows that the talus is typically 20-40 m thick and highly heterogeneous. The meadow sediments are only up to 11 m thick but are part of a 30-40-m-thick accumulation of unconsolidated material that fills a bedrock overdeepening (i.e. a closed, subglacial basin). A minor, shallow groundwater system feeds springs on the talus and streams on the meadow, whereas a deep system in the moraine supplies most of the water to the basin outlet springs, thereby serving as a 'gate keeper' of the basin. Although the hydrologic functions of the talus in this study are substantially different from other locations, primarily due to differences in bedrock lithology and geomorphic processes, the general conceptual framework developed in this study is expected to be applicable to other alpine regions.

Dans les régions alpines, le stockage des eaux souterraines est essentiel au maintien du débit de base des cours d'eau de montagne. De récentes études ont montré que les formes de relief alpin courants (par exemple le talus et la moraine) ont une capacité de stockage des eaux souterraines substantielle, mais la connectivité hydrogéologique entre les formes particulières de relief n'a pas été comprise. La présente étude caractérise l'hydrogéologie d'un bassin d'un cirque alpin des Montagnes Rocheuses Canadiennes qui présente des formes typiques de relief (talus, prairie, moraines) et des caractéristiques hydrogéologiques (petits lacs, cours d'eau et sources). Des observations géologiques, hydrologiques et hydrochimiques ont été utilisées pour comprendre le contexte hydrogéologique général du bassin étudié, et trois méthodes géophysiques différentes (tomographie par résistivité électrique, tomographie par sismique réfraction et géoradar) ont été utilisées pour caractériser la structure et la connectivité du sous-sol et pour développer un modèle conceptuel hydrogéologique. L'imagerie géophysique montre que le talus a généralement une épaisseur de 20­40 m et est fortement hétérogène. Les sédiments de la prairie n'ont que 11 m d'épaisseur mais font partie d'une accumulation épaisse de 30­40 m de matériel non consolidé, qui remplit un surcreusement profond dans le substratum (c-à-d, un bassin fermé sous-glaciaire). Un petit système aquifère phréatique nourrit des sources sur le talus et des cours d'eau sur la prairie, tandis que le système profond de la moraine fournit la plus grande partie de l'eau aux sources sortant du bassin, servant ainsi de « portier ¼ du bassin. Bien que les fonctions hydrologiques du talus soient dans cette étude substantiellement différentes de celles d'autres localisations, surtout en raison des différences de lithologie du socle et des processus géomorphologiques, on escompte que le schéma conceptuel général développé ici est applicable à d'autres régions alpines.

El almacenamiento de aguas subterráneas en las regiones alpinas es esencial para mantener los flujos de base en los cursos de agua de las montañas. Estudios recientes han demostrado que las formas de relieve alpino comunes (por ejemplo, el talud y la morena) tienen una capacidad importante de almacenamiento de aguas subterráneas, pero no se ha comprendido la interrelación hidrogeológica entre las distintas formas de relieve. Este estudio caracteriza la hidrogeología de una cuenca de circo alpino en las Rocky Mountains del Canadá que contiene las típicas formas de relieve alpino (talud, pradera, morenas) y características hidrológicas (lagunas, arroyos y manantiales). Se utilizaron observaciones geológicas, hidrológicas e hidroquímicas para comprender el contexto hidrogeológico general de la cuenca de estudio, y se emplearon tres métodos geofísicos diferentes (tomografía de resistividad eléctrica, tomografía de refracción sísmica y georradar) para caracterizar la estructura y la conectividad en el subsuelo, y para elaborar un modelo conceptual hidrogeológico. Las imágenes geofísicas muestran que el talud suele tener un espesor de 20 a 40 m y es muy heterogéneo. Los sedimentos de la pradera sólo tienen un espesor de hasta 11 m, pero forman parte de una acumulación de material no consolidado de 30­40 m de espesor que rellena un basamento sobreexcavado (es decir, una cuenca subglacial cerrada). Un sistema menor de aguas subterráneas poco profundas alimenta los manantiales en el talud y los arroyos en la pradera, mientras que un sistema profundo en la morena suministra la mayor parte del agua a los manantiales de salida de la cuenca, sirviendo, así como "portadora" de la cuenca. Aunque las funciones hidrológicas del talud en este estudio son sustancialmente diferentes de las de otros lugares, principalmente debido a las diferencias en la litología del basamento y los procesos geomórficos, se espera que el marco conceptual general desarrollado en este estudio sea aplicable a otras regiones alpinas.

O armazenamento de águas subterrâneas em regiões alpinas é essencial para manter os fluxos de base nos córregos das montanhas. Estudos recentes mostraram que formas de relevo alpinas comuns (por exemplo, tálus e morena) têm capacidade substancial de armazenamento de águas subterrâneas, mas a conectividade hidrogeológica entre formas de relevo individuais não foi compreendida. Este estudo caracteriza a hidrogeologia de uma bacia de circo alpino nas Montanhas Rochosas Canadenses que contém formas de relevo alpinas típicas (talus, prados, morenas) e características hidrológicas (tarn, córregos e nascentes). Observações geológicas, hidrológicas e hidroquímicas foram usadas para entender o cenário hidrogeológico geral da bacia em estudo e três métodos geofísicos diferentes (tomografia de resistividade elétrica, tomografia de refração sísmica e radar de penetração no solo) foram usados ​​para caracterizar a estrutura e a conectividade do subsolo, e desenvolver um modelo conceitual hidrogeológico. As imagens geofísicas mostram que o tálus tem tipicamente 20­40 m de espessura e é altamente heterogêneo. Os sedimentos dos prados têm apenas 11 m de espessura, mas fazem parte de um acúmulo de material não consolidado com 30­40 m de espessura que preenche um afundamento no leito de rocha (isto é, uma bacia subglacial fechada). Um sistema menor de águas subterrâneas rasas alimenta fontes no tálus e córregos no prado, enquanto um sistema profundo na morena fornece a maior parte da água às fontes de saída da bacia, servindo assim como um 'guardião' da bacia. Embora as funções hidrológicas do tálus neste estudo sejam substancialmente diferentes de outros locais, principalmente devido a diferenças na litologia dos leitos de rocha e nos processos geomórficos, espera-se que o quadro conceitual geral desenvolvido neste estudo seja aplicável a outras regiões alpinas.

Allogeneic hematopoietic stem cell transplantation at the first remission for younger adults with FLT3-internal tandem duplication AML: The JALSG AML209-FLT3-SCT study.

In this phase II multicenter study (JALSG AML209-FLT3-SCT), we aimed to prospectively elucidate the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1) for FLT3-internal tandem duplication (ITD)-positive AML. Newly diagnosed de novo AML patients with FLT3-ITD were enrolled at the achievement of CR1 and received allo-HSCT as soon as possible after the first consolidation therapy. Mutations of 57 genes in AML cells at diagnosis were also analyzed. Among 48 eligible patients with a median age of 38.5 (17-49) years, 36 (75%) received allo-HSCT at a median of 108 days after CR1. The median follow-up was 1726 days. The primary end-point, 3-year disease-free survival (DFS) based on an intent to treat analysis, was 43.8% (95% confidence interval [CI], 30%-57%), suggesting the efficacy of this treatment because the lower limit of the 95% CI exceeded the threshold response rate of 20%. The 3-year overall survival, post-transplant DFS, and non-relapse mortality rates were 54.2% (95% CI, 39%-67%), 58.3% (95% CI, 41%-72%), and 25.0% (95% CI, 12%-40%), respectively. The median ITD allelic ratio (AR) was 0.344 (0.006-4.099). Neither FLT3-ITD AR nor cooccurring genetic alterations was associated with a poor DFS. This prospective study indicated the efficacy and safety of allo-HSCT for FLT3-ITD AML patients in CR1. This study was registered at: www.umin.ac.jp/ctr/ as #UMIN000003433.

Proteomic profiling of HTLV-1 carriers and ATL patients reveals sTNFR2 as a novel diagnostic biomarker for acute ATL.

Adult T-cell leukemia/lymphoma (ATL) is a human T-cell leukemia virus type 1 (HTLV-1)-associated T-cell malignancy with generally poor prognosis. Although only ∼5% of HTLV-1 carriers progress to ATL, early diagnosis is challenging because of the lack of ATL biomarkers. In this study, we analyzed blood plasma profiles of asymptomatic HTLV-1 carriers (ACs); untreated ATL patients, including acute, lymphoma, smoldering, and chronic types; and ATL patients in remission. Through SOMAscan, expression levels of 1305 plasma proteins were analyzed in 85 samples (AC, n = 40; ATL, n = 40; remission, n = 5). Using gene set enrichment analysis and gene ontology, overrepresented pathways in ATL vs AC included angiogenesis, inflammation by cytokines and chemokines, interleukin-6 (IL-6)/JAK/STAT3, and notch signaling. In selecting candidate biomarkers, we focused on soluble tumor necrosis factor 2 (sTNFR2) because of its active role in enriched pathways, extreme significance (Welch's t test P < .00001), high discrimination capacity (area under the curve >0.90), and novelty in ATL research. Quantification of sTNFR2 in 102 plasma samples (AC, n = 30; ATL, n = 68; remission, n = 4) using enzyme-linked immunosorbent assay showed remarkable elevations in acute ATL, at least 10 times those of AC samples, and return of sTNFR2 to AC state levels after achieving remission. Flow cytometry and immunostaining validated the expression of TNFR2 in ATL cells. No correlation between sIL-2 and sTNFR2 levels in acute ATL was found, suggesting the possibility of sTNFR2 as an independent biomarker. Our findings represent the first extensive blood-based proteomic analysis of ATL, suggesting the potential clinical utility of sTNFR2 in diagnosing acute ATL.

[Determination of Tributyltin and Triphenyltin in Fish and Shellfish Using Accelerated Solvent Extraction and Liquid Chromatography with Tandem Mass Spectrometry].

A determination method for tributyltin (TBT) and triphenyltin (TPT) in fish and shellfish using an accelerated solvent extractor (ASE) and LC-MS/MS was developed. The chromatographic separation was conducted on a Poroshell 120 EC-C18 column using an isocratic mobile phase of 0.1% formic acid in 70% methanol. Sample preparation was performed using ASE at 125℃ with n-hexane and a cleanup using a Florisil cartridge. Internal calibration curves using deuterium-labeled TBT and TPT were employed for quantification. For both TBT and TPT, the calibration curves were linear in the range of 0.2-250 ng/mL, and the method quantification limits were 0.8 ng/g for both TBT and TPT. A National Institute for Environmental Studies certified reference material, No. 15 (adductor muscle of scallop), was analyzed to assess the performance of the developed method. The trueness, relative standard deviations of repeatability, and within laboratory reproducibility of this method, evaluated using a recovery test with four spiked fish species and one shellfish, ranged from 89.3 to 105.3%, 1.0 to 4.5%, and 1.3 to 7.6%, respectively.

Alpine Hydrogeology: The Critical Role of Groundwater in Sourcing the Headwaters of the World.

Groundwater discharge in alpine headwaters sustains baseflow in rivers originating in mountain ranges of the world, which is critically important for aquatic habitats, run-of-river hydropower generation, and downstream water supply. Groundwater storage in alpine watersheds was long considered negligible, but recent field-based studies have shown that aquifers are ubiquitous in the alpine zone with no soil and vegetation. Talus, moraine, and rock glacier aquifers are common in many alpine regions of the world, although bedrock aquifers occur in some geological settings. Alpine aquifers consisting of coarse sediments have a fast recession of discharge after the recharge season (e.g., snowmelt) or rainfall events, followed by a slow recession that sustains discharge over a long period. The two-phase recession is likely controlled by the internal structure of the aquifers. Spatial extent and distribution of individual aquifers determine the groundwater storage-discharge characteristics in first- and second-order watersheds in the alpine zone, which in turn govern baseflow characteristics in major rivers. Similar alpine landforms appear to have similar hydrogeological characteristics in many mountain ranges across the world, suggesting that a common conceptual framework can be used to understand alpine aquifers based on geological and geomorphological settings. Such a framework will be useful for parameterizing storage-discharge characteristics in large river hydrological models.