scholarly journals A Quantitative Ultrastructural Study of Oocytes During the Early Stages of Ovarian Follicular Development in Booroola and Wild-Type Sheep

2021 ◽  
Author(s):  
◽  
Karen Lee Reader
Keyword(s):  
Granulosa Cells ◽  
Follicular Development ◽  
Cell Junctions ◽  
Wild Type ◽  
Cortical Granules ◽  
Surface Areas ◽  
Stage Of Development ◽  
Type 3

<p>In the sheep ovary, primordial follicles are formed as an oocyte surrounded by either a single layer of flattened granulosa cells (type 1) or a mixture of flattened and cuboidal granulosa cells (type 1a). Booroola sheep have a mutation in the growth factor receptor, activin-like kinase receptor 6 (ALK6) which is expressed in oocytes of follicles at the type 1 stage of development. In Booroola ewes homozygous for the ALK6 mutation (BB), oocytes undergo precocious maturation that appears to be initiated during the preantral growth phase. The aim of this study was to quantify the ultrastructural features of oocytes of ovarian follicles at the types 1/1a, 2 and 3 stages of development, from BB and wild-type (++) ewes. Ovaries from 6 ++ and 5 BB 4 week old ewe lambs were processed for both light microscopy (LM) and electron microscopy (EM). LM and stereological methods were used to estimate the mean volume of the oocytes of each follicular type and genotype. EM images and point counting or linear intercept counting were used to estimate the volume of smooth endoplasmic reticulum (SER), Golgi, mitochondria, vesicles, lipid, ribosomes, zona pellucida (ZP) and cortical granules (CG), and the surface area of the outer and inner mictochondrial membranes, microvilli and cell junctions. Oocytes of type 1/1a follicles of BB animals had a greater diameter than that in ++ animals (BB: 29.76 ± 0.58 μm vs ++: 27.05 ± 0.30 μm; P < 0.01) but there were no significant genotype differences in the oocyte diameters of type 2 or 3 follicles. As the follicles of ++ animals developed from the type 1 through to the type 3 stage, the volume and 3 surface areas of all sub-cellular structures measured within oocytes increased (P < 0.05). In oocytes of type 1/1a follicles of BB animals, the SER, mitochondria and ZP volumes were greater than in ++ animals (P < 0.05) as were the surface areas of the outer mitochondrial membranes, oocyte membrane, and zonula adherens type junctions (P < 0.05). At the type 2 stage of development the lipid volume was greater in oocytes of ++ animals, and at the type 3 stage of development the ribosomal volume was greater in oocytes of BB animals. These results suggest that the ALK6 mutation in BB animals has influenced the ultrastructural properties of oocytes in the type 1/1a follicle. This early genotype difference in follicular characteristics may influence the rate of follicular development during the early developmental stages.</p>

scholarly journals A Quantitative Ultrastructural Study of Oocytes During the Early Stages of Ovarian Follicular Development in Booroola and Wild-Type Sheep

2021 ◽  
Author(s):  
◽  
Karen Lee Reader
Keyword(s):  
Granulosa Cells ◽  
Follicular Development ◽  
Cell Junctions ◽  
Wild Type ◽  
Cortical Granules ◽  
Surface Areas ◽  
Stage Of Development ◽  
Type 3

<p>In the sheep ovary, primordial follicles are formed as an oocyte surrounded by either a single layer of flattened granulosa cells (type 1) or a mixture of flattened and cuboidal granulosa cells (type 1a). Booroola sheep have a mutation in the growth factor receptor, activin-like kinase receptor 6 (ALK6) which is expressed in oocytes of follicles at the type 1 stage of development. In Booroola ewes homozygous for the ALK6 mutation (BB), oocytes undergo precocious maturation that appears to be initiated during the preantral growth phase. The aim of this study was to quantify the ultrastructural features of oocytes of ovarian follicles at the types 1/1a, 2 and 3 stages of development, from BB and wild-type (++) ewes. Ovaries from 6 ++ and 5 BB 4 week old ewe lambs were processed for both light microscopy (LM) and electron microscopy (EM). LM and stereological methods were used to estimate the mean volume of the oocytes of each follicular type and genotype. EM images and point counting or linear intercept counting were used to estimate the volume of smooth endoplasmic reticulum (SER), Golgi, mitochondria, vesicles, lipid, ribosomes, zona pellucida (ZP) and cortical granules (CG), and the surface area of the outer and inner mictochondrial membranes, microvilli and cell junctions. Oocytes of type 1/1a follicles of BB animals had a greater diameter than that in ++ animals (BB: 29.76 ± 0.58 μm vs ++: 27.05 ± 0.30 μm; P < 0.01) but there were no significant genotype differences in the oocyte diameters of type 2 or 3 follicles. As the follicles of ++ animals developed from the type 1 through to the type 3 stage, the volume and 3 surface areas of all sub-cellular structures measured within oocytes increased (P < 0.05). In oocytes of type 1/1a follicles of BB animals, the SER, mitochondria and ZP volumes were greater than in ++ animals (P < 0.05) as were the surface areas of the outer mitochondrial membranes, oocyte membrane, and zonula adherens type junctions (P < 0.05). At the type 2 stage of development the lipid volume was greater in oocytes of ++ animals, and at the type 3 stage of development the ribosomal volume was greater in oocytes of BB animals. These results suggest that the ALK6 mutation in BB animals has influenced the ultrastructural properties of oocytes in the type 1/1a follicle. This early genotype difference in follicular characteristics may influence the rate of follicular development during the early developmental stages.</p>

scholarly journals Poliomyelitis surveillance in England and Wales, 1969–1975

1978 ◽  
Vol 80 (1) ◽  
pp. 155-167 ◽  
Author(s):  
J. W. G. Smith ◽  
P. J. Wherry
Keyword(s):  
Reproductive Capacity ◽  
Paralytic Poliomyelitis ◽  
Test Results ◽  
Wild Type ◽  
England And Wales ◽  
Marker Test ◽  
Type 3 ◽  
Temperature Test

SUMMARYPoliomyelitis continued to be a rare disease in England and Wales in the period 1969–75. Only 31 paralytic and 44 cases of possible non-paralytic poliomyelitis were recorded during the 7 years.Of the 31 paralytic cases approximately one third were vaccine-associated; 3 were patients who had recently received oral poliovaccine and 7 had been in contact with a vaccinated person. Five of these 7 patients were parents of recently vaccinated children. The rate of vaccine-associated poliomyelitis was estimated in recipients to be 0·2 and in contacts 0·4 per million doses of vaccine given.Marker test results were reported on 555 strains of poliomyelitis virus isolated during 1969–75, using the reproductive capacity temperature test. Forty-eight (8·6%) resembled wild virus in this property, 15 strains being type 1, 8 type 2 and 25 type 3. Most of these isolations of apparently wild virus were from excreters with no symptoms of poliomyelitis, although 3 of the 15 type 1 strains were from patients with paralytic poliomyelitis and 3 from possible cases of non-paralytic poliomyelitis. None of the 8 apparently wild type 2 viruses was from a case of paralytic illness and only 1 of the 39 type 3 strains.Eleven of the 31 paralytic cases were in patients in whom the infection was likely to have been acquired abroad.

MicroRNA-21 enhances estradiol production by inhibiting WT1 expression in granulosa cells

2021 ◽  
Author(s):  
Renee Emily Hilker ◽  
Bo Pan ◽  
Xiaoshu Zhan ◽  
Julang Li
Keyword(s):  
Granulosa Cells ◽  
Follicular Development ◽  
Negative Control ◽  
Luciferase Reporter ◽  
Wild Type ◽  
Aromatase Expression ◽  
Antral Follicles ◽  
Porcine Granulosa Cells ◽  
In The Wild ◽  
Type 3

In antral follicles, transition of proliferative granulosa cells to estradiol-producing is critical for proper oocyte maturation. MicroRNAs are noncoding RNAs that play important roles in ovarian follicular development, however this has yet to be fully characterized. MicroRNA-21 is significantly higher in granulosa cells isolated from large antral follicles compared to those from small antral follicles. To investigate the function of miR-21, porcine granulosa cells were transfected with miR-21 mimic or miR-21 targeted siRNA. Cells with the miR-21 mimic had higher aromatase expression and estradiol production but decreased WT1 expression. Conversely, cells with the miR-21 siRNA secreted less estradiol and had higher WT1 expression. We hypothesized miR-21 promotes estradiol production by inhibiting WT1 protein synthesis. We found a potential miR-21 binding site in the 3’UTR of the WT1 transcript and performed a dual luciferase reporter assay using the wild-type and mutated 3’UTR. Compared to the negative control, the miR-21 mimic induced a significant decrease in luciferase activity in the wild-type 3’UTR. This decrease was reversed when the 3’UTR was mutated, suggesting miR-21 targets this site to inhibit WT1 expression. We next transfected porcine granulosa cells with WT1 targeted siRNA and observed a significant increase in aromatase expression and estradiol secretion. We propose that miR-21 represses WT1 expression in granulosa cells to potentially promote aromatase expression and estradiol production. This study offers the first report of a microRNA regulating WT1 expression in granulosa cells and reveals the role of miR-21 in WT1’s regulation of estradiol production.

The development of cell pattern in the root epidermis

1995 ◽  
Vol 350 (1331) ◽  
pp. 95-99 ◽  
Keyword(s):  
Hair Cells ◽  
Asymmetric Cell Division ◽  
Wild Type ◽  
Cell Type ◽  
Root Epidermis ◽  
Cell Pattern ◽  
Differential Exposure ◽  
Type 3

The root epidermis of most angiosperms is composed of a patterned array of hair and non-hair cells. Hair cells may develop randomly in any location in the epidermis (type 1), from specialized cells that form as result of an asymmetric cell division in a mother cell (type 2) or cells may be arranged in files of one cell type or the other (type 3). The development of the epidermis in Arabidopsis has been examined in detail and corresponds to type 3 epidermal development. A combination of physiological and genetic observations indicates that ethylene is a positive regulator of root hair differentiation. Differential exposure of epidermal cells to ethylene as a result of the cellular geometry of the root may account for the wild-type epidermal pattern.

scholarly journals Natural Genetic Exchanges between Vaccine and Wild Poliovirus Strains in Humans

2000 ◽  
Vol 74 (18) ◽  
pp. 8434-8443 ◽  
Author(s):  
Sophie Guillot ◽  
Valérie Caro ◽  
Nancy Cuervo ◽  
Ekaterina Korotkova ◽  
Mariana Combiescu ◽  
...  
Keyword(s):  
Paralytic Poliomyelitis ◽  
Nucleotide Sequencing ◽  
Wild Type ◽  
Coding Region ◽  
Wild Poliovirus ◽  
Type 3 ◽  
Recombinant Genome ◽  
Natural Means

ABSTRACT In a previous study of poliovirus vaccine-derived strains isolated from patients with vaccine-associated paralytic poliomyelitis (VAPP) (9, 11), we reported that a high proportion (over 50%) of viruses had a recombinant genome. Most were intertypic vaccine/vaccine recombinants. However, some had restriction fragment length polymorphism (RFLP) profiles different from those of poliovirus vaccine strains. We demonstrate here that five such recombinants, of 88 VAPP strains examined, carried sequences of wild (nonvaccine) origin. To identify the parental wild donor of these sequences, we used RFLP profiles and nucleotide sequencing to look for similarity in the 3D polymerase-coding region of 61 wild, cocirculating poliovirus isolates (43 type 1, 16 type 2, and 2 type 3 isolates). In only one case was the donor identified, and it was a wild type 1 poliovirus. For the other four vaccine/wild recombinants, the wild parent could not be identified. The possibility that the wild sequences were of a non-poliovirus-enterovirus origin could not be excluded. Another vaccine/wild recombinant, isolated in Belarus from a VAPP case, indicated that the poliovirus vaccine/wild recombination is not an isolated phenomenon. We also found wild polioviruses (2 of 15) carrying vaccine-derived sequences in the 3′ moiety of their genome. All these results suggest that genetic exchanges with wild poliovirus and perhaps with nonpoliovirus enteroviruses, are also a natural means of evolution for poliovirus vaccine strains.

scholarly journals Roles of Type 1, 2, and 3 Innate Lymphoid Cells in Herpes Simplex Virus 1 InfectionIn VitroandIn Vivo

2019 ◽  
Vol 93 (13) ◽  
Author(s):  
Satoshi Hirose ◽  
Shaohui Wang ◽  
Kati Tormanen ◽  
Yizhou Wang ◽  
Jie Tang ◽  
...  
Keyword(s):  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Wild Type ◽  
Herpes Simplex Virus 1 ◽  
Type 3 ◽  
Deficient Mice ◽  
Hsv 1

ABSTRACTInnate lymphoid cells (ILCs) play important roles in host defense and inflammation. They are classified into three distinct groups based on their cytokine and chemokine secretion patterns and transcriptome profiles. Here, we show that ILCs isolated from mice can be infected with herpes simplex virus 1 (HSV-1) but that subsequent replication of the virus is compromised. After infection, type 2 ILCs expressed significantly higher levels of granulocyte colony-stimulating factor (G-CSF), interleukin 1α (IL-1α), IL-6, IL-9, RANTES, tumor necrosis factor alpha (TNF-α), CXCL1, CXCL2, CXCL10, CCL3, and CCL4 than infected type 1 or type 3 ILCs. Transcriptome-sequencing (RNA-seq) analysis of the ILCs 24 h after HSV-1 infection revealed that 77 herpesvirus genes were detected in the infected type 3 ILCs, whereas only 11 herpesvirus genes were detected in infected type 1 ILCs and 27 in infected type 2 ILCs. Compared with uninfected cells, significant upregulation of over 4,000 genes was seen in the HSV-1-infected type 3 ILCs, whereas 414 were upregulated in the infected type 1 ILCs and 128 in the infected type 2 ILCs. In contrast, in all three cell types, only a limited number of genes were significantly downregulated. Type 1, type 2, and type 3 ILC-deficient mice were used to gain insights into the effects of the ILCs on the outcome of ocular HSV-1 infection. No significant differences were found on comparison with similarly infected wild-type mice or on comparison of the three strains of deficient mice in terms of virus replication in the eyes, levels of corneal scarring, latency-reactivation in the trigeminal ganglia, or T-cell exhaustion. Although there were no significant differences in the survival rates of infected ILC-deficient mice and wild-type mice, there was significantly reduced survival of the infected type 1 or type 3 ILC-deficient mice compared with type 2 ILC-deficient mice. Adoptive transfer of wild-type T cells did not alter survival or any other parameters tested in the infected mice. Our results indicate that type 1, 2, and 3 ILCs respond differently to HSV-1 infectionin vitroand that the absence of type 1 or type 3, but not type 2, ILCs affects the survival of ocularly infected mice.IMPORTANCEIn this study, we investigated for the first time what roles, if any, innate lymphoid cells (ILCs) play in HSV-1 infection. Analysis of isolated ILCsin vitrorevealed that all three subtypes could be infected with HSV-1 but that they were resistant to replication. The expression profiles of HSV-1-induced cytokines/chemokines and cellular and viral genes differed among the infected type 1, 2, and 3 ILCsin vitro. While ILCs play no role or a redundant role in the outcomes of latency-reactivation in infected mice, absence of type 1 and type 3, but not type 2, ILCs affects the survival of infected mice.

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.

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