Subclassified Acutely Dissociated Cells of Rat DRG: Histochemistry and Patterns of Capsaicin-, Proton-, and ATP-Activated Currents

2000 ◽  
Vol 84 (5) ◽  
pp. 2365-2379 ◽  
Author(s):  
Jeffrey C. Petruska ◽  
Jintana Napaporn ◽  
Richard D. Johnson ◽  
Jianguo G. Gu ◽  
Brian Y. Cooper
Keyword(s):  
Cell Types ◽  
Long Duration ◽  
Calcitonin Gene ◽  
Dissociated Cells ◽  
Type 3 ◽  
Current Signatures ◽  
Current Signature

We used a “current signature” method to subclassify acutely dissociated dorsal root ganglion (DRG) cells into nine subgroups. Cells subclassified by current signature had uniform properties. The type 1 cell had moderate capsaicin sensitivity (25.9 pA/pF), powerful, slowly desensitizing (τ = 2,300 ms), ATP-activated current (13.3 pA/pF), and small nondesensitizing responses to acidic solutions (5.6 pA/pF). Type 1 cells expressed calcitonin gene–related peptide immunoreactivity (CGRP-IR), manifested a wide action potential (7.3 ms), long duration afterhyperpolarization (57.0 ms), and were IB4 positive. The type 2 cell exhibited large capsaicin activated currents (134.9 pA/pF) but weak nondesensitizing responses to protons (15.3 pA/pF). Currents activated by ATP and αβ-m-ATP (51.7 and 44.6 pA/pF, respectively) had fast desensitization kinetics (τ = 214 ms) that were distinct from all other cell types. Type 2 cells were IB4 positive but did not contain either substance P (SP) or CGRP-IR. Similar to capsaicin-sensitive nociceptors in vivo, the afterhyperpolarization of the type 2 cell was prolonged (54.7 ms). The type 3 cell expressed, amiloride-sensitive, rapidly desensitizing (τ = 683 ms) proton-activated currents (127.0 pA/pF), and was insensitive to ATP or capsaicin. The type 3 cell was IB4 negative and contained neither CGRP nor SP-IR. The afterhyperpolarization (17.5 ms) suggested nonnociceptive function. The type 4 cell had powerful ATP-activated currents (17.4 pA/pF) with slow desensitization kinetics (τ = 2,813 ms). The afterhyperpolarization was prolonged (46.5 ms), suggesting that this cell type might belong to a capsaicin-insensitive nociceptor population. The type 4 cell did not contain peptides. The type 7 cell manifested amiloride-sensitive, proton-activated currents (45.8 pA/pF) with very fast desensitization kinetics (τ = 255 ms) and was further distinct from the type 3 cell by virtue of a nondesensitizing amiloride-insensitive component (6.0 pA/pF). Capsaicin and ATP sensitivity were relatively weak (4.3 and 2.9 pA/pF, respectively). Type 7 cells were IB4 positive and contained both SP and CGRP-IR. They exhibited an exceptionally long afterhyperpolarization (110 ms) that was suggestive of a silent (mechanically insensitive) nociceptor. We concluded that presorting of DRG cells by current signatures separated them into internally homogenous subpopulations that were distinct from other subclassified cell types.

Electrophysiological and Chemical Properties in Subclassified Acutely Dissociated Cells of Rat Trigeminal Ganglion by Current Signatures

2010 ◽  
Vol 104 (6) ◽  
pp. 3451-3461 ◽  
Author(s):  
Shenghong Xu ◽  
Kentaro Ono ◽  
Kiyotoshi Inenaga
Keyword(s):  
Trigeminal Ganglion ◽  
Chemical Properties ◽  
Input Resistance ◽  
Cell Types ◽  
Whole Cell Patch Clamp ◽  
Long Duration ◽  
Cell Groups ◽  
Dissociated Cells ◽  
Induced Currents ◽  
Current Signatures

In the present study, we subclassified acutely dissociated trigeminal ganglion (TRG) cells of rats using a current signature method in whole cell patch-clamp recordings. Using modified criteria for cell classification for the dorsal root ganglion (DRG), TRG cells were subclassified into nine cell types: 1–5, 7–9, and 13. Types 1, 3, and 7 were in the small cell groups (15–24 μm); types 4, 5, and 8–13 were in the medium cell groups (25–38 μm); and type 2 was a mixed group of both cell sizes. Types 1–3, 5, and 7 showed high-input resistance and types 1, 2, and 7 showed more depolarized resting membrane potentials. Types 1, 2, and 5–13 expressed long-duration action potentials (APs), but types 3 and 4 expressed short-duration APs. Sensitivities to capsaicin, protons, and adenosine 5′-triphosphate (ATP) in TRG cell types largely corresponded to DRG cell types. However, different from the matched DRG types, half of TRG type 1 cells were capsaicin insensitive, showing desensitizing proton-induced currents, and types 5, 7, and 9 exhibited slow-desensitizing ATP-induced currents. Types 4, 5, and 8–13 had nicotine sensitivity, but the other cell types were insensitive. These results indicate that the “current signatures” classification is a useful means to separate TRG cells into internally homogeneous subpopulations that were distinct from other cell types. Furthermore, the data suggest some specific differences in the chemical responsiveness of some cell types between the TRG and DRG.

New Fine Structure within the Adult Hematopoietic Stem Cell Compartment Revealed by Longterm Analysis of Mice Repopulated with Single Cells or Their In Vitro Generated Clonal Progeny.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1720-1720
Author(s):  
Brad Dykstra ◽  
David Kent ◽  
Lindsay McCaffrey ◽  
Kristin Lyons ◽  
Merete Kristiansen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Single Cells ◽  
Myeloid Cells ◽  
Hematopoietic Stem ◽  
Type 3

Abstract Assessments of hematopoietic stem cell (HSC) repopulating activity in vivo have historically relied on calculated average longterm (12–16 wk) progeny outputs using non-purified transplants, thereby precluding definitive clonal assignments of donor-derived cells. Viral marking circumvents this problem, but has not been used for large scale surveys. Heterogeneity observed in the repopulation patterns has generally been inferred to reflect stochastic processes. We now report the in vivo repopulation kinetics of 89 individual longterm repopulating cells (LTRCs) before (n=49) and after (n=40) 4 days of clonal growth in vitro. LTRCs were defined here as cells whose WBC progeny could be detected at levels of ≥1% for at least 16 wk in sublethally irradiated Ly5-congenic W41/W41 hosts. Recipients were transplanted with either freshly isolated, single lin−Rho−SP LTRCs or 4-day clones generated from similar cells in serum-free cultures (+ 300 ng/ml SF, 20 ng/ml IL-11 & 1ng/ml Flt3-L). 4, 8, 12, 16, and 24 wk post-transplant, blood samples were stained for donor-derived B, T, and myeloid cells using a procedure that identifies donor/recipient doublets and Ly6g/Mac1low cells (which have features of lymphoid rather than myeloid WBCs) to exclude false-positive myeloid events. Four distinct patterns of repopulation were revealed. Type 1 showed a delayed production of predominantly myeloid WBCs (low or undetectable before 12 wk) that increased progressively (reaching 0.4–15% of all WBCs by 16 wk). Type 2 showed a robust multilineage repopulation that remained stable or increased over time (6–84% of all WBCs at 16 wk). Type 3 also showed an initially robust pattern of multilineage repopulation (peak numbers of WBCs at 8–12 wk and 1–51% at 16 wk), but the contribution of donor-derived myeloid cells was transient (<0.5% by 16 wk). Type 4 showed a lymphoid-restricted pattern (myeloid contribution <0.5% at all time points), with repopulation levels peaking at 8 wk and decreasing thereafter (1–22% at 16 wk). Persisting granulopoiesis, indicated by a high proportion of donor-derived cells in the Ly6g/Mac1+SSChi population at 16–24 wk, clearly distinguished the type 1 and 2 patterns from types 3 and 4 which showed near or complete cessation of donor-derived granulopoiesis beyond 12 wk. Preliminary secondary transplant experiments show that donor-derived LTRCs (with and without longterm granulopoietic activity) were exclusively generated in primary recipients with type 1 and 2 repopulation patterns. Amongst the freshly isolated LTRCs, 18% (9/49) were type 1, 41% (20/49) were type 2, 22% (11/49) were type 3, and 18% (9/49) were type 4. In contrast, 4-day clones derived from cells of the same phenotype and containing LTRC activity showed a marked decrease in type 1 and type 2 activity with a corresponding increase in type 3 and type 4 activity: type 1 = 5% (2/41), type 2 = 18% (7/40), type 3 = 28% (11/40) and type 4 = 50% (20/40). Collectively, these data identify a new hierarchy of four biologically discrete states within the compartment of cells currently defined as LTRCs. Proliferation of LTRCs either in vitro or in vivo appears to induce an irreversible transition from one state to another (from Type 1 to 2 to 3 to 4), suggesting the existence of intrinsic molecular correlates for each of these states and specific mechanisms that underlie their sequential appearance.

Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Refractory Patient-Derived Multiple Myeloma Cells, Growing in a Novel Humanized Mouse MM Model

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 940-940
Author(s):  
Willy A Noort ◽  
Richard W.J. Groen ◽  
Reinier Raymakers ◽  
Linda Aalders ◽  
Frans M Hofhuis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Tumor Cells ◽  
Research Funding ◽  
Humanized Mouse ◽  
Myeloma Cells ◽  
Tumor Load ◽  
Type 3

Abstract Abstract 940 The evolution of multiple myeloma (MM) is a multi-step process during which mature B cells acquire genetic mutations in multiple genes, which typically takes place in the bone marrow (BM) microenvironment. This, together with the difficulty to culture MM in vitro or to grow MM in vivo in animal models has been the main reason during past decades for poor progress in preclinical research with patient-derived myeloma (pMM) cells. Recently, we developed a unique human-mouse hybrid model that allows engraftment and outgrowth of pMM cells by implementing a technology that is based on first generating a human bone environment in immune deficient mice (Groen et al. 2012) and that is subsequently capable of supporting growth of injected pMM cells. The model offers the opportunity (1) to study the pathobiology of myeloma, and (2) to evaluate, preclinically, new therapeutics for MM treatment, including antibody testing against pMM cells, obtained from patients who acquired resistance to conventional and novel drugs. Daratumumab (DARA) is a human CD38 antibody with broad-spectrum killing activity. Daratumumab induces effective killing of MM tumor cells via complement dependent cytolysis (CDC), ADCC (antibody dependent cellular cytolysis) and ADCP (antibody-dependent phagocytosis). DARA represents a novel promising treatment for MM and other hematological malignancies and is currently tested in Phase I/II clinical trials. In these clinical studies the adverse events have been manageable and marked reductions in paraprotein and bone marrow plasma cells have been observed. In the current study, we asked whether DARA was able to inhibit growth of refractory tumor cells in our human-mouse hybrid model. To this end, immune-deficient RAG2−/−gc−/−-mice were implanted subcutaneously with biphasic calcium phosphate (BCP) particles (2–3 mm) loaded with culture expanded human mesenchymal stromal cells (MSCs). Eight weeks later, the humanized scaffolds in mice (n=45) were injected with 0.5–5×106 pMM cells obtained from different refractory, MM patients. The pMM cells were gene-marked with a GFP-luciferase lentiviral construct for imaging of viable tumor cells. Bioluminescent imaging (BLI) was used to follow myeloma outgrowth in time and to visualize the effect of treatment. The pMM cells were obtained from patients at diagnosis (type 1); at end stage disease, after a history of MPT (melphalan, prednisone, thalidomide, type 2); or from a patient refractory to chemotherapy with bortezomib (BORT), adriamycine and dexamethasone (DEX) (type 3). Mice carrying the pMM cells received similar treatment as the patients or were treated with DARA in a dose range of 1x 50 μg (low dose (LD)) or 2 to 3x 200 μg/mouse (high dose (HD)). BLI showed that the type 1 pMM-bearing mice responded well to all treatments, including DARA; type 2-bearing pMM mice showed no reduction in tumor growth after chemotherapy, but DARA treatment (LD) resulted in an almost complete elimination of circulating MM cells, as assessed with a CD138 antibody, in blood and BM. In a second experiment, type 2-pMM bearing mice were treated with a high DARA dose early (day 34, 50 and 72, 3 times HD, tumor size/BLI signal <200 cmp/cm2) or late (day 50 and 72, 2 times HD, tumor size/BLI signal >8000 cpm/cm2). A significant reduction of overall tumor load, as measured with BLI was observed, which interestingly did not differ between the high and low tumor load group. A reduction of circulating tumor cells (CD138+) was observed for both conditions, which was most obvious in the early treated mice and in agreement with the observations in the first experiment. Type 3 (resistant) pMM-bearing mice showed only a minor response to DEX and BORT, but were highly sensitive to melphalan. When DEX- and BORT-treated mice were treated with a single injection of DARA, this resulted in a complete remission in 3 out of 4 mice and a reduction of the tumor load by 50% in the fourth BORT-treated mouse. In conclusion, our results demonstrate that DARA is effective against multiple myeloma cells derived from therapy- naïve or -refractory patients grafted in a humanized mouse model. In addition, this humanized MM model can be used to study the potential and mechanism of action of DARA in vivo. This novel MM model might be used to predict responsiveness of myeloma patients to particular treatments. Disclosures: Groen: Genmab BV: Research Funding. Raymakers:Novartis: Consultancy. Lammerts van Bueren:Genmab BV: Employment. Parren:genmab: Employment. Mutis:genmab: Research Funding. Martens:Genmab BV: Research Funding.

scholarly journals A mathematical model of rat ascending Henle limb. III. Tubular function

2010 ◽  
Vol 298 (3) ◽  
pp. F543-F556 ◽  
Author(s):  
Alan M. Weinstein
Keyword(s):  
Mathematical Model ◽  
Tubular Function ◽  
Proton Secretion ◽  
Luminal Membrane ◽  
Catalytic Role ◽  
Type 3

K+ plays a catalytic role in AHL Na+ reabsorption via Na+-K+-2Cl− cotransporter (NKCC2), recycling across luminal K+ channels, so that luminal K+ is not depleted. Based on models of the ascending Henle limb (AHL) epithelium, it has been hypothesized that NH4+ may also catalyze luminal Na+ uptake. This hypothesis requires that luminal NH4+ not be depleted, implying replenishment via either direct secretion of NH4+, or NH3 in parallel with a proton. In the present work, epithelial models of rat medullary and cortical AHL (Weinstein AM, Krahn TA. Am J Physiol Renal Physiol 298: F000–F000, 2009) are configured as tubules and examined in simulations of function in vitro and in vivo to assess the feasibility of a catalytic role for NH4+ in Na+ reabsorption. Modulation of Na+ transport is also examined by peritubular K+ concentration and by Bartter-type transport defects in NKCC2 (type 1), in luminal membrane K+ channels (type 2), and in peritubular Cl− channels (type 3). It is found that a catalytic role for NH4+, which is significant in magnitude (relative to K+), is quantitatively realistic, in terms of uptake via NKCC2, and in terms of luminal membrane ammonia backflux. Simulation of a 90% NKCC2 defect is predicted to double distal Na+ delivery; it is also predicted to increase distal acid delivery (principally as NH4+). With doubling of medullary K+, the model predicts a 30% increase in distal Na+ delivery, but in this case there is a decrease in AHL acidification. This effect of peritubular K+ on proton secretion appears to be akin to type 3 Bartter's pathophysiology, in which there is decreased peritubular HCO3− exit, cytosolic alkalinization, and a consequent decrease in luminal proton secretion by NHE3. One consequence of overlapping and redundant roles for K+ and NH4+, is a blunted impact of luminal membrane K+ permeability on overall Na+ reabsorption, so that type 2 Bartter pathophysiology is not well captured by the model.

Osmotic regulation and osmotically induced changes in the neurosecretory cells of the pulmonate snail Helisoma

1979 ◽  
Vol 57 (7) ◽  
pp. 1371-1383 ◽  
Author(s):  
Hamidur R. Khan ◽  
A. S. M. Saleuddin
Keyword(s):  
Sea Water ◽  
Cell Types ◽  
Neurosecretory Cells ◽  
Distilled Water ◽  
Osmotic Concentration ◽  
Helisoma Duryi ◽  
Induced Changes ◽  
Type 3

Helisoma duryi and H. trivolvis are hyperosmotic regulators within a range from distilled water to 20% sea water (0.5–200 mosmol/L). Ultrastructurally three types of neurosecretory cells can be recognized in the visceral and left parietal ganglia. Type 1 and 2 cells correspond to the paraldehyde fuchsin (PAF) positive group 1 cells of visceral and medium sized parietal cells of left parietal ganglia. Type 3 cells are located in the visceral ganglion; they are PAF negative. Type 1 and 2 cells stain intensely with PAF in snails kept in distilled water but stain faintly in snails kept in isosmotic saline. Perikarya and axon endings of type 2 cells contain more granules and appear synthetically active when snails are kept in distilled water but less synthetically active when snails are kept in isosmotic saline. The response of type 1 cells is comparable with that of type 2 cells but less pronounced. The response of type 3 cells to media of different osmotic concentration is opposite to that found in type 2 cells. The possible roles of the cell types are discussed, and it is suggested that type 2 cells may be involved in diuresis.

FUNCTIONAL STATUS AND ADAPTIVE POTENTIAL IN FOREIGN STUDENTS WITH DIFFERENT TYPES OF VEGETATIVE REGULATION DURING TUITION

2020 ◽  
pp. 118-126
Author(s):  
A.M. Satarkulova
Keyword(s):  
Heart Rate ◽  
Foreign Students ◽  
Autonomic Regulation ◽  
The Body ◽  
Functional Changes ◽  
Different Types ◽  
Type 3 ◽  
Adaptive Abilities

The assessment and dynamic control over students’ status is a very important task. It allows timely detection of prenosological status prior to pathology and health maintenance in students. The objective of the paper is to assess the adaptive abilities of the body, to analyze changes in heart rate variability indicators in students with various types of autonomic regulation, to identify prenosological status and precursory pathological symptoms. Materials and Methods. The study enrolled 302 students from India, aged 21.54±1.43. Programming complex «Psychophysiologist» was used to register the main HRV parameters within 5 minutes. Health status was evaluated according to the index of functional changes and the scale of functional states. Results. N.I. Shlyk (2009) distinguished two groups of students with different types of autonomic regulation: type 1 (53 %) with moderate and type 2 (5 %) with marked characteristics of central regulation profile, type 3 (35 %) with moderate and type 4 (7 %) with marked characteristics of autonomous regulation profile. Main parameters of HRV and adaptation potential were defined for each student.All the parameters characterized functional and health status. Conclusions. It was shown that 82 % of trial subjects (type 1), 53 % (type 2), 94 % (type 3) and 95 % (type 4) demonstrated satisfactory adaptation and their physiological processes were at an optimal level. 18 % of students (type 1) demonstrated reduced adaptive abilities of the body. Moreover, they were under moderate stress. 47 % of subjects (type 2) were also under a significant stress, which was proven by excessively high SI, low SDNN and TP, and an increased index of functional changes. 5 % of students (type 4) revealed dysfunctional characteristics in the heart rhythm, peculiar to pathology. Keywords: foreign students, heart rate variability, types of autonomic regulation, adaptation potential, functional status. Оценка состояния студентов и динамический контроль за ним является важной задачей, поскольку позволяет своевременно выявлять у студентов донозологические состояния, предшествующие патологии, и способствовать сохранению здоровья. Цель. Оценка адаптивных возможностей организма, анализ изменений показателей вариабельности сердечного ритма у студентов с различными типами вегетативной регуляции, выявление донозологических состояний и ранних признаков патологии. Материалы и методы. В исследовании участвовало 302 студента в возрасте 21,54+1,43 года из Индии. Регистрировались основные параметры ВСР в течение 5 мин с использованием программно-аппаратного комплекса «Психофизиолог». Состояние и уровень здоровья оценивались по индексу функциональных изменений и шкале функциональных состояний. Результаты. По способу, предложенному Н.И. Шлык, выделены группы студентов с различными типами вегетативной регуляции: I (53 %) и II типы (5 %) – с умеренным и выраженным преобладанием центрального контура регуляции соответственно, III (35 %) и IV типы (7 %) – с умеренным и выраженным преобладанием автономного контура регуляции соответственно. У каждого из студентов определены основные параметры ВСР и адаптационного потенциала, характеризующие функциональное состояние и уровень здоровья. Выводы. Показано, что для 82 % обследуемых с I типом, 53 % со II типом, 94 % c III типом и 95 % с IV типом регуляции характерно состояние удовлетворительной адаптации, физиологические процессы сохраняются на оптимальном уровне. В группе студентов I типа у 18 % студентов адаптивные возможности организма снижены, выявлено состояние умеренного напряжения. У 47 % обследуемых II типа также зафиксировано состояние резко выраженного напряжения, индикатором которого является чрезмерно высокое значение SI, низкие величины SDNN и ТP, повышенное значение индекса функциональных изменений. В группе студентов с IV типом у 5 % учащихсяв регуляции ритма сердца выявлены дисфункциональные признаки, характерные для патологии. Ключевые слова: иностранные студенты, вариабельность сердечного ритма, типы вегетативной регуляции, адаптационный потенциал, функциональное состояние.

POLIOMYELITIS IN CANADIAN ESKIMOS: LABORATORY STUDIES. V. TYPE 1 AND TYPE 3 POLIOMYELITIS ANTIBODY LEVELS IN BAFFIN ISLAND ESKIMOS

1954 ◽  
Vol 32 (1) ◽  
pp. 119-125
Author(s):  
W. Wood ◽  
Eina M. Clark ◽  
F. T. Shimada ◽  
A. J. Rhodes
Keyword(s):  
Medical Records ◽  
Baffin Island ◽  
Tissue Cultures ◽  
Laboratory Studies ◽  
Poliomyelitis Virus ◽  
Antibody Titers ◽  
Antibody Levels ◽  
Type 3

Studies on the basic immunology of poliomyelitis in Canadian Eskimos have been continued. Some 87 sera collected from Eskimos at Pangnirtung, Baffin Island, have been examined for the presence of Type 1 and Type 3 poliomyelitis antibody by quantitative tests in tissue cultures. The same sera were previously examined for Type 2 antibody by quantitative tests in mice. The results of the three determinations are now presented together for comparison. These sera came from Eskimos aged 2 to 72 years of age. None of the Eskimos showed any evidence of paralysis. Examination of the medical records did not suggest that any paralytic disease had been present in this part of Baffin Island. Very few of the sera showed the presence of poliomyelitis antibody; thus, Type 1 antibody was demonstrated in the sera of 8%, Type 2 antibody in the sera of 9%, and Type 3 antibody in the sera of 14%. No significant number of Eskimos below the age of 45 years had acquired poliomyelitis antibody. The antibody titers mostly ranged between 10−1.0 and 10−2.0, and were significantly lower than the titers customarily found in recently paralyzed cases. These findings suggest that poliomyelitis infection occurred in Pangnirtung Eskimos many years before the date on which the samples were taken (1951). These results point to the worldwide prevalence of the three types of poliomyelitis virus.

Toward Personalized Treatment for Patients with Low von Willebrand Factor and Quantitative von Willebrand Disease

2021 ◽  
Vol 47 (02) ◽  
pp. 192-200
Author(s):  
James S. O'Donnell
Keyword(s):  
Von Willebrand Factor ◽  
Bleeding Risk ◽  
Von Willebrand Disease ◽  
Personalized Treatment ◽  
Treatment Plans ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractThe biological mechanisms involved in the pathogenesis of type 2 and type 3 von Willebrand disease (VWD) have been studied extensively. In contrast, although accounting for the majority of VWD cases, the pathobiology underlying partial quantitative VWD has remained somewhat elusive. However, important insights have been attained following several recent cohort studies that have investigated mechanisms in patients with type 1 VWD and low von Willebrand factor (VWF), respectively. These studies have demonstrated that reduced plasma VWF levels may result from either (1) decreased VWF biosynthesis and/or secretion in endothelial cells and (2) pathological increased VWF clearance. In addition, it has become clear that some patients with only mild to moderate reductions in plasma VWF levels in the 30 to 50 IU/dL range may have significant bleeding phenotypes. Importantly in these low VWF patients, bleeding risk fails to correlate with plasma VWF levels and inheritance is typically independent of the VWF gene. Although plasma VWF levels may increase to > 50 IU/dL with progressive aging or pregnancy in these subjects, emerging data suggest that this apparent normalization in VWF levels does not necessarily equate to a complete correction in bleeding phenotype in patients with partial quantitative VWD. In this review, these recent advances in our understanding of quantitative VWD pathogenesis are discussed. Furthermore, the translational implications of these emerging findings are considered, particularly with respect to designing personalized treatment plans for VWD patients undergoing elective procedures.

scholarly journals Optimally growing initial errors of El Niño events in the CESM

2021 ◽  
Author(s):  
Hui Xu ◽  
Lei Chen ◽  
Wansuo Duan
Keyword(s):  
El Niño ◽  
El Nino ◽  
Equatorial Pacific ◽  
Initial Error ◽  
Initial Errors ◽  
El Niño Events ◽  
Type 3 ◽  
El Nino Events

AbstractThe optimally growing initial errors (OGEs) of El Niño events are found in the Community Earth System Model (CESM) by the conditional nonlinear optimal perturbation (CNOP) method. Based on the characteristics of low-dimensional attractors for ENSO (El Niño Southern Oscillation) systems, we apply singular vector decomposition (SVD) to reduce the dimensions of optimization problems and calculate the CNOP in a truncated phase space by the differential evolution (DE) algorithm. In the CESM, we obtain three types of OGEs of El Niño events with different intensities and diversities and call them type-1, type-2 and type-3 initial errors. Among them, the type-1 initial error is characterized by negative SSTA errors in the equatorial Pacific accompanied by a negative west–east slope of subsurface temperature from the subsurface to the surface in the equatorial central-eastern Pacific. The type-2 initial error is similar to the type-1 initial error but with the opposite sign. The type-3 initial error behaves as a basin-wide dipolar pattern of tropical sea temperature errors from the sea surface to the subsurface, with positive errors in the upper layers of the equatorial eastern Pacific and negative errors in the lower layers of the equatorial western Pacific. For the type-1 (type-2) initial error, the negative (positive) temperature errors in the eastern equatorial Pacific develop locally into a mature La Niña (El Niño)-like mode. For the type-3 initial error, the negative errors in the lower layers of the western equatorial Pacific propagate eastward with Kelvin waves and are intensified in the eastern equatorial Pacific. Although the type-1 and type-3 initial errors have different spatial patterns and dynamic growing mechanisms, both cause El Niño events to be underpredicted as neutral states or La Niña events. However, the type-2 initial error makes a moderate El Niño event to be predicted as an extremely strong event.

scholarly journals Successful Aging Perception in Middle-Aged Korean Men: A Q Methodology Approach

2021 ◽  
Vol 18 (6) ◽  
pp. 3095
Author(s):  
Mi Hyeon Seong ◽  
Eunyoung Shin ◽  
Sohyune Sok
Keyword(s):  
Successful Aging ◽  
Q Methodology ◽  
Principal Component ◽  
Middle Aged ◽  
Practice Nurses ◽  
Mature Type ◽  
Type 3 ◽  
Family Centered

The purpose of this study is to identify the types of perception of successful aging in middle-aged men and to analyze and describe the characteristics of each type of successful aging perception of middle-aged men in South Korea. This study uses an exploratory study design, applying the Q methodology, which is a subjective research method. The participants were 25 middle-aged men (40 to 60 years old) living in C, Y, and B cities, which were P-samples that were judged to best reveal the successful aging of middle-aged men. In this study, principal component analysis of the PQ method program was used. The five perception types of successful aging among middle-aged men are Type 1 for the “leisure type”, Type 2 for the “mature type”, Type 3 for the “health-oriented type”, Type 4 for the “patriarchal type”, and Type 5 for the “family-centered type”. The mature type had the highest variance among the five types, and the leisure type was the type that showed the second-highest variance. In nursing practice, nurses need to pay attention to the successful aging perceptions of middle-aged Korean men for their successful aging in the future.

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