Here we present a method to extract the underlying state sequences from experimental SM time-series. Taking into account empirical error and the finite sampling of the time-series, the method extracts a steady-state network which provides an approximation of the underlying effective free energy landscape. The core VE-821 of the method is the application of rate-distortion theory from information theory, allowing the individual

data points to be assigned to multiple states simultaneously. We demonstrate the method’s proficiency in its application to simulated trajectories as well as to experimental SM fluorescence resonance energy transfer (FRET) trajectories obtained from isolated agonist binding domains of the AMPA receptor, an ionotropic glutamate receptor that is prevalent in the central nervous system.”
“Hyponatremia may be a risk factor for fracture. To NSC23766 mw determine the relationship between hyponatremia and fracture we conducted cross-sectional and longitudinal analyses using data from the Osteoporotic Fractures in Men (MrOS) study. The MrOS study enrolled 5122 community dwelling men aged 65 years from six centers across the United States.

We excluded men taking bisphosphonates, those with unknown medication history, those without serum sodium measures, or those with out of range assays for serum sodium. Serum sodium was measured at study entry. Subjects were followed for fractures (nonspine [including hip], hip, incident morphometric, and prevalent morphometric) for up to 9 years. We used Cox proportional hazards models to analyze the association between serum sodium levels ( smaller than 135mmol/L versus 135mmol/L) and risk of nonspine and hip fractures, with results presented as hazard ratios (HRs) and 95% confidence intervals (CIs). We examined the association between morphometric vertebral fractures and serum sodium using logistic regression models, presented as odds ratios (ORs) and 95% CI. Hyponatremia was observed in 64 men (1.2% of the cohort). After adjusting

for age, BMI, study center, and other covariates, we found that, compared to men with serum sodium 135mmol/L, those with serum sodium smaller than 135mmol/L, had an increased risk of hip fracture (HR=3.04; 95% CI, 1.37 to SNX-5422 nmr 6.75), prevalent morphometric spine fracture (OR=2.46; 95% CI, 1.22 to 4.95), and incident morphometric spine fracture (OR=3.53; 95% CI, 1.35 to 9.19), but not nonspine fracture (OR=1.44; 95% CI, 0.85 to 2.44). Adjusting for bone mineral density (BMD) did not change our findings. Our data show that hyponatremia is associated with up to a doubling in the risk of hip and morphometric spine fractures, independent of BMD. Further studies, to determine how hyponatremia causes fractures and if correction of hyponatremia decreases fractures, are needed. (c) 2014 American Society for Bone and Mineral Research.

septempunctata and H. axyridis exhibited a type II functional

response for predation toward adult soybean aphids at 26 +/- 1 degrees C. In C. septempunctata, the functional response curve of adult males differed from those of third instars and adult females, but see more there was no difference between third instars and adult females. In H. axyridis,, the functional response curves of larvae, adult females, and adult males all differed significantly. Third instars and adult females consumed significantly more soybean aphids than did adult males at prey densities of 150 and 180 aphids per arena for C. septempunctata and at prey densities of 60, 90, 120, 150, and 180 aphids per arena for H. axyridis. The theoretical maximum daily predation rate of adult aphids by C. septempunctata was predicted to be 204 per third instar, 277 per adult female, and 166 per adult male, and 244, 156, and 73, respectively, for H. axyridis. Third instars and adult females of both species consumed significantly more aphids than did adult males on soybean plants with the recommended action threshold of 250 soybean aphids per plant. Both C. septempunctata and H. axyridis have high predation capacities and are important in suppressing soybean aphid populations.”
“Metastasis is the main cause of cancer-related death. It is surprising then that the exact nature of metastasisthe process by which cancer cells leave the primary tumor to reach

distant organs, and resume proliferation-is not fully understood. Moreover, the different conditions under OSI-906 nmr which the immune system can either promote or suppress metastasis are only now beginning to be uncovered. In recent years, our understanding of metastasis as a genocentric, cell-autonomous process has shifted toward a systemic model in which interactions between cancer cells and their surrounding microenvironments lead to dissemination and metastasis. In silico modeling of the various steps involved in metastasis can help provide an understanding of how tumor properties emerge from the complex interplays between tumor cells and their microenvironment. In silico models can also be useful in identifying the selective

forces that SB525334 favor the outcomes of cancer cells with metastatic potential.”
“Norovirus is a major cause of viral gastroenteritis and a common cause of foodborne and waterborne outbreaks. Norovirus outbreaks are responsible for economic losses, most notably to the public health and food industry field. Norovirus has characteristics such as low infectious dose, prolonged shedding period, strong stability, great diversity, and frequent genome mutations. Besides these characteristics, they are known for rapid and extensive spread in closed settings such as hospitals, hotels, and schools. Norovirus is well known as a major agent of food-poisoning in diverse settings in South Korea. For these reasons, nationwide surveillance for norovirus is active in both clinical and environmental settings in South Korea.

This has implications for workforce planning FK506 inhibitor and the future provision of cancer services.\n\nMethod: In an attempt to establish a baseline of the workforce a census

was taken. Data was collected via an Excel spreadsheet by Cancer Network Nurse Directors and Lead Nurses across England and Northern Ireland and a lead nurse in Wales. Scotland, Palliative Care and Chemotherapy posts were excluded at levels other than Consultant as these are collected via other mechanisms.\n\nResults & conclusions: The census recorded 2309.4 specialist and advanced practice posts in England (89% response rate), 204 posts in Wales (66% response rate) and 43.4 posts in Northern Ireland (100% response rate).\n\nThere is a variation HDAC activity assay in terms of distribution of specialist nurses across the Networks both in number and in cancer type.1800 adult CNS posts were recorded in England and 1 in 5 of these were breast cancer posts. The range of job titles is very wide with 17 different titles being used. In England the extent of support for posts from Macmillan Cancer Support was considerable. Around a third (31%) of all adult cancer specialist posts in England are supported by Macmillan Cancer Support (n = 671.2) 607.2 of these are CNS posts equating to 34% of all CNS posts in

England. 34% of all NI CNS posts and 32.5% in Wales. (C) 2009 Elsevier Ltd. All rights reserved.”
“Pesticide coated seeds are commonly used in agriculture, and may be an important source of food for some birds in times of scarcity,

as well as a route of pesticide ingestion. We tested the lethal and sub-lethal effects of treated seed ingestion by the red-legged partridge (Alectoris rufa), a game bird of high socio-economic value in Spain. One year-old partridges (n = 42 pairs) were fed for 10 days in spring (prior to breeding) with wheat treated with difenoconazole (fungicide), thiram (fungicide) or imidacloprid (insecticide), using two doses for each pesticide (the one recommended, and S3I-201 its double to represent potential cases of abuse of pesticides). We investigated the direct and indirect effects on the body condition, physiology, immunology, coloration and subsequent reproduction of exposed partridges. For the latter, eggs were collected, measured and incubated and the growth and survival of chicks were monitored. Thiram and imidacloprid at high exposure doses produced mortalities of 41.6 and 58.3 %, respectively. The first death was observed at day 3 for imidacloprid and at day 7 for thiram. Both doses of the three pesticides caused sublethal effects, such as altered biochemical parameters, oxidative stress and reduced carotenoid-based coloration. The high exposure doses of imidacloprid and thiram also produced a decrease in cellular immune response measured by the phytohemagglutinin test in males.

Simulations show a direct correlation between the void nucleation stress and the ability of a grain boundary to plastically deform by emitting dislocations, during shock compression. Plastic response of a GB, affects the development

of stress concentrations believed to be responsible for void nucleation by acting as a dissipation mechanism for the applied stress.”
“In this article, the anatomical and morphological features of the acetabulum in infancy and childhood are presented. The pathology and treatment of older children and adolescents is deliberately not covered, because the fracture morphology and treatment GANT61 price of patients aged 13 to 15 years is based on the criteria of adult medicine. Especially in the younger child, the anatomical differences are of particular importance. The younger the child is, the more

difficult the diagnosis. Therefore today, MRI examinations should be generous used, even if anesthesia is necessary. If the injured child is hemodynamic stable, anesthesia can be electively used for a more complex diagnosis. Acetabular fractures are particularly problematic in infancy because even with optimal treatment and perfect reduction growth disturbances can occur. These manifest as so-called secondary dysplasia. During treatment, care should be taken to Ulixertinib ensure that a surgical team having experience with the infant and juvenile skeleton is available and that appropriate implants are available.”
“Aims: Studies in adults have identified evidence of

inherited cardiovascular diseases in up to 53% of families, but data on the prevalence of familial disease in children are scarce. The aim of this study was to evaluate the yield of clinical screening in pediatric first-degree relatives of victims of SADS using a systematic and comprehensive protocol. Methods: Patients referred for family screening after sudden cardiac death (SCD) of a family member were, retrospectively, enrolled into the study. Systematic evaluation of the children included selleck clinical examination, family history, electrocardiogram (ECG), echocardiogram, 24-hour tape, and signal-averaged ECG. Older patients also underwent exercise testing, cardiac magnetic resonance imaging, and ajmaline provocation testing. Results: A total of 90 children from 52 consecutive families were included in the study. An inherited cardiac disease was identified in seven first-degree children from seven (13.5%) families (five children were diagnosed with Brugada syndrome, one with long QT syndrome, and one with catecholaminergic polymorphic ventricular tachycardia). Two further children had late potentials on signal-averaged ECGs with no other abnormalities. Conclusions: These data show a high prevalence of inherited heart disease in pediatric first-degree relatives of SADS victims.

“
“Duloxetine is a balanced serotonin-norepinephrine reuptake inhibitor. Duloxetine-induced liver injury in patients with preexisting liver disease or chronic alcohol use is known. However, we have found that duloxetine can also induce liver injury in cases without those risk factors. We recommend that clinicians should monitor liver function carefully following duloxetine treatment. Psychiatry Investig 2011;8:269-271″
“PURPOSE\n\nWe aimed to investigate clinical and radiologic manifestations of pulmonary cryptococcosis in immunocompetent patients and their outcomes

after treatment.\n\nMATERIALS AND METHODS\n\nWe retrospectively reviewed the medical records, initial and follow-up Selleck MK 1775 chest computed tomography scans and/or radiographs for initial clinical and radiologic manifestations and outcomes following antifungal treatment of 12 immunocompetent patients diagnosed with pulmonary cryptococcosis between 1990 and 2012.\n\nRESULTS\n\nTwelve patients (age range, 21-62 years; males, eight patients [66.7%]) were included. Nine (75%) patients were symptomatic, eight of whom had disseminated infection with central nervous system

involvement. Initial pulmonary abnormalities consisted of single nodules/masses (n=5), single segmental or lobar mass-like consolidation (n=3), multiple cavitary and noncavitary nodules (n=1), and multifocal consolidation plus nodules (n=3). These PD-1/PD-L1 Inhibitor 3 cost lesions ranged from less than 1 cm to 15 cm in greatest diameter. Distinct subpleural and lower lung predominance

was observed. Seven patients (58.3%) had one or more atypical/aggressive findings, namely endobronchial obstruction (n=4), calcified (n=1) or enlarged (n=4) mediastinal/hilar lymph nodes, vascular compression (n=1), pericardial involvement (n=1), and pleural involvement (n=2). Following antifungal therapy, radiologic resolution was variable within the first six months of eight nonsurgical cases. Substantial (>75%) improvement with some residual abnormalities, bronchiectasis, cavitation, and/or fibrotic changes were frequently observed after 12-24 months of treatment (n=6).\n\nCONCLUSION\n\nPulmonary cryptococcosis in immunocompetent patients frequently causes disseminated KPT-8602 infection with atypical/aggressive radiologic findings that are gradually and/or incompletely resolved after treatment. The presence of nonenhanced low-attenuation areas within subpleural consolidation or mass and the absence of tree-in-bud appearance should raise concern for pulmonary cryptococcosis, particularly in patients presenting with meningitis.”
“Umeclidinium (UMEC) is an inhaled long-acting muscarinic antagonist approved in the US and EU for the once-daily (QD) treatment of chronic obstructive pulmonary disease (COPD); it is not indicated for the treatment of asthma.

Activation of the reflex results in an increase in efferent sympathetic nerve activity and a withdrawal of parasympathetic nerve activity. These actions result in the precise alterations in cardiovascular hemodynamics requisite to meet the metabolic demands of working skeletal muscle. Coordinated activity by this reflex is altered after the development of cardiovascular disease, generating exaggerated increases in sympathetic nerve activity, blood pressure, heart rate, and vascular resistance. The basic components and operational characteristics

of the reflex, the techniques used in human and animals to study the reflex, and the emerging evidence describing the dysfunction of the reflex Pevonedistat chemical structure with the advent of cardiovascular disease are highlighted in this review.”
“Soybean genotypes resistant CCI-779 solubility dmso to stink bugs are derived from complex breeding processes obtained through indirect selection. The aim of the present work was to estimate genetic parameters for guiding selection strategies towards resistant genotypes, based on those traits associated with responses to pod-attacking

stink bugs, such as the grain filling period (GFP), leaf retention (LR), percentage index of pod damage (PIPD) and percentage of spotted seeds (PSS). We assessed the parental lines IAC-100 (resistant) and FT-Estrela (susceptible), the progenies F(2) and F(4), 30 progenies F(2:3), 30 progenies BC(1)F(2:3) and 30 progenies BC(2)F(2:3), besides the cultivars BRS Celeste and MGBR-46 (Conquista). Three field experiments, using randomized complete block design with three replications, were installed in Goiania-GO, in the 2002/03 season. Each experiment consisted of 36 treatments (6 common and 30 regular). Heritability estimates were:

74.6 and 36.1 (GFP); 51.9 and 19.9 (LR); 49.6 and 49.6 (PIPD) and 55.8 and 20.3 (PSS), in both the broad and narrow senses, respectively. Based on these results, we concluded that the best strategy for obtaining stink bug-resistant genotypes consists of selecting the PIPD trait in early generations (F(3) or F(4)), followed by selection for the GFP, LR and PSS traits in generations with higher endogamy levels.”
“Understanding the origin of pallasites, AZD8186 stony-iron meteorites made mainly of olivine crystals and FeNi metal, has been a vexing problem since their discovery. Here, we show that pallasite olivines host minute magnetic inclusions that have favorable magnetic recording properties. Our paleointensity measurements indicate strong paleomagnetic fields, suggesting dynamo action in the pallasite parent body. We use these data and thermal modeling to suggest that some pallasites formed when liquid FeNi from the core of an impactor was injected as dikes into the shallow mantle of a similar to 200-kilometer-radius protoplanet. The protoplanet remained intact for at least several tens of millions of years after the olivine-metal mixing event.

The results suggest

that group II mGluRs regulate both fast glutamatergic and GABAergic synaptic transmission in the ICC, probably through a presynaptic mechanism due to reduction of transmitter release. (C) 2010 Elsevier B.V. All rights reserved.”
“Few genes are known to be involved in renal cell carcinoma (RCC) development and progression. The cell-specific transcription factor hepatocyte nuclear factor 4 alpha (HNF4 alpha) is down-regulated in RCC and we have shown that HNF4 alpha inhibits cell proliferation in the embryonic kidney cell line HEK293. To clarify the possible tumor suppressor activity of HNF4 alpha we analyzed the whole human expression profile in HEK293 cells upon HNF4 alpha induction. By comparing selleck products induced and unincluced cells, we identified 1411 differentially expressed genes. Using RNA interference, we screened 56 HNF4 alpha-regulated genes for their possible role in mediating inhibition of cell proliferation triggered by HNF4 alpha. We demonstrate that 14 of these regulated genes are able to contribute to the inhibitory effect of HNF4 alpha on cell proliferation, including well-known cancer genes, such as CDKN1A(p21), TGFA, MME (NEP) and ADAMTS1. In addition, the genes SEPP1, THEM2, BPHL, DSC2,

ANK3, ALDH6A1, EPHX2, NELL2, EFHD1 and PROS1 are also part www.selleckchem.com/products/mrt67307.html of the network of HNF4 LY2090314 cell line alpha target genes that regulate proliferation in HEK293 cells. Therefore, we postulate that HNF4 alpha orchestrates, at least, these 14 genes to regulate cell proliferation in HEK293 cells and that down-regulation of HNF4 alpha could contribute to the progression of kidney cancer.”
“PURPOSE. Here, we examined the development, composition, and structural organization of the ciliary zonule of the mouse. Fibrillin 1, a large glycoprotein enriched in force-bearing tissues, is a prominent

constituent of the mouse zonule. In humans, mutations in the gene for fibrillin 1 (FBN1) underlie Marfan syndrome (MS), a disorder characterized by lens dislocation and other ocular symptoms.\n\nMETHODS. Fibrillin expression was analyzed by in situ hybridization. The organization of the zonule was visualized using antibodies to Fbn1, Fbn2, and microfibril-associated glycoprotein-1 (Magp1) in conjunction with 5-ethynyl-2′-deoxyuridine (EdU), an S-phase marker.\n\nRESULTS. Microfibrils, enriched in Fbn2 and Magp1, were prominent components of the temporary vascular tunic of the embryonic lens. Fbn2 expression by nonpigmented ciliary epithelial cells diminished postnatally and there was a concomitant increase in Fbn1 expression, especially in cells located in valleys between the ciliary folds. Zonular fibers projected from the posterior pars plicata to the lens in anterior, equatorial, and posterior groupings.

In conclusion, suppression of allergen-specific IgE production in offspring ALK phosphorylation could not be induced by paternal immunisation, and genetic factors were of minor importance. In contrast, we demonstrate the necessity of maternal factors, possibly allergen-specific IgG1, resulting from a functional adaptive immune response, for the IgE-suppressive effect in offspring. These maternal factors

could be induced by immunisation of female mice even before conception.”
“Glomerular podocyte molecules are involved in the pathogenesis of congenital nephrotic syndrome. However, their role in primary nephrotic syndrome is not clear. This study investigated the expression of nephrin, podocin and synaptopodin in primary nephrotic syndrome.\n\nEighty-seven patients with primary nephrotic syndrome including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and membranoproliferative eFT-508 in vivo glomerulonephritis Type I (MPGN) were included in the study. Glomerular expression of nephrin, podocin and synaptopodin was studied in renal biopsies by immunofluorescence and immunohistochemistry. Correlation of expression with clinical and biochemical parameters was performed.\n\nThe pattern of expression for all podocyte proteins in controls was uniform

fine granular along the capillary walls towards the visceral epithelial cell aspect. Glomerular expression of nephrin was present in all renal biopsies and was similar to that in controls. Glomerular synaptopodin expression was seen in all MN and MPGN patients, while it was seen in 74 % (17/23) MCD and 93.5 % (29/31) FSGS. Reduced synaptopodin

expression showed no correlation with clinical and biochemical factors. Podocin expression was present in 5/23 MCD (22 %), 3/31 FSGS (9.6 %), 13/17 MN (76.4 %) and 13/16 MPGN (81 %) patients. The reduced expression of podocin significantly correlated with the degree of proteinuria (p = 0.032). No correlation with age, gender and serum creatinine level was observed.\n\nReduction of glomerular podocin expression found in MCD and FSGS is related to the amount of proteinuria. Our findings suggest that alteration in podocyte phenotype may not be a primary event and may reflect the degree of podocyte injury in primary nephrotic syndrome.”
“A AZD9291 reaction of 2-acyl substituted tetrahydroquinolines, prepared by Lewis acid-catalyzed three-component reaction of alpha-oxo aldehydes, anilines, and dienophiles, with in situ generated arynes afforded 5,6-dihydroindolo[1,2-a]-quinolines in good to excellent yields.”
“Grapevine virus A (GVA) has a quasispecies nature and is closely associated with the rugose-wood disease complex of Vitis vinifera L. In the different growing regions of table grape in Sichuan, southwest China, the incidence of GVA infection was found to be 16.9% by ELISA detection among 178 grape plants ( Vitis vinifera L.

Statistically significant differences were registered for the output variables – changes in width find more of keratinized gingiva, changes in bucco-lingual width, and vertical bone changes at four sites – between the two socket preservation

techniques, with P values of smaller than 0.001, smaller than 0.001, and 0.0105, respectively. Conclusions: A full-thickness mucoperiosteal flap gave significantly more negative results than that of the less-demanding flapless procedure, with an increased width resorption of the postextraction site. Moreover, the increased value of the keratinized gingival width attested to the positive outcome of a flapless procedure in terms of soft tissue preservation and improvement. On the other hand, the flapped technique seemed to show less vertical bone resorption on the buccal aspect than the flapless technique.”
“Outer membrane particles from Gram-negative bacteria are attractive vaccine candidates as they present surface antigens check details in their natural context. We previously developed a high yield production process for genetically derived particles, called

generalized modules for membrane antigens (GMMA), from Shigella. As GMMA are derived from the outer membrane, they contain immunostimulatory components, especially lipopolysaccharide (LPS). We examined ways of reducing their reactogenicity by modifying lipid A, the endotoxic part of LPS, through deletion of late acyltransferase genes, msbB or htrB, in GMMA-producing Shigella sonnei and Shigella flexneri strains. GMMA with resulting penta-acylated lipid A from the msbB mutants

showed a 600-fold Blebbistatin concentration reduced ability, and GMMA from the S. sonnei Delta htrB mutant showed a 60,000-fold reduced ability compared with GMMA with wild-type lipid A to stimulate human Toll-like receptor 4 (TLR4) in a reporter cell line. In human peripheral blood mononuclear cells, GMMA with penta-acylated lipid A showed a marked reduction in induction of inflammatory cytokines (S. sonnei Delta htrB, 800-fold; Delta msbB mutants, 300-fold). We found that the residual activity of these GMMA is largely due to non-lipid A-related TLR2 activation. In contrast, in the S. flexneri Delta htrB mutant, a compensatory lipid A palmitoleoylation resulted in GMMA with hexa-acylated lipid A with similar to 10-fold higher activity to stimulate peripheral blood mononuclear cells than GMMA with penta-acylated lipid A, mostly due to retained TLR4 activity. Thus, for use as vaccines, GMMA will likely require lipid A penta-acylation. The results identify the relative contributions of TLR4 and TLR2 activation by GMMA, which need to be taken into consideration for GMMA vaccine development.”
“Background: Men and women differ in their ability to extinguish fear. Fear extinction requires the activation of brain regions, including the ventromedial prefrontal cortex (vmPFC) and amygdala.

A minority of practitioners relied solely on the published ACR classification criteria for the diagnosis of FM. We also report gender bias with regard to disease classification, because rheurnatologists were

more likely to require a physical finding to support a diagnostic conclusion in male patients. (Gend Med. 2010;7:19-27) (C) 2010 Excerpta Medica Inc.”
“Mitochondrial alterations are critically involved in increased vulnerability to disease during aging. We investigated the contribution of mitochondria-sarcoplasmic reticulum (SR) communication in cardiomyocyte functional alterations during aging. Heart function (echocardiography) and ATP/phosphocreatine 4EGI-1 (NMR spectroscopy) were preserved in hearts from old mice (420 months) with respect to young mice (5-6 months). Mitochondrial membrane BMS-754807 manufacturer potential and resting O-2 consumption were similar in mitochondria from young and old hearts. However, maximal ADP-stimulated O-2 consumption was specifically reduced in interfibrillar mitochondria from aged hearts. Second generation proteomics disclosed an

increased mitochondrial protein oxidation in advanced age. Because energy production and oxidative status are regulated by mitochondrial Ca2+, we investigated the effect of age on mitochondrial Ca2+ uptake. Although no age-dependent differences were found in Ca2+ uptake kinetics in isolated mitochondria, mitochondrial Ca2+ uptake secondary to SR Ca2+ release was significantly reduced in cardiomyocytes from old hearts, and this effect was associated with decreased NAD(P)H regeneration and increased mitochondrial ROS upon increased contractile activity. Immunofluorescence and proximity ligation assay identified the defective communication between mitochondrial voltage-dependent anion channel and SR ryanodine receptor (RyR) in cardiomyocytes from aged hearts associated

with altered Ca2+ handling. Age-dependent alterations in SR Ca2+ transfer to mitochondria and in Ca2+ this website handling could be reproduced in cardiomyoctes from young hearts after interorganelle disruption with colchicine, at concentrations that had no effect in aged cardiomyocytes or isolated mitochondria. Thus, defective SR-mitochondria communication underlies inefficient interorganelle Ca2+ exchange that contributes to energy demand/supply mistmach and oxidative stress in the aged heart.”
“The dynamics of the actin cytoskeleton and its regulation by Rho GTPases are essential to maintain cell shape, to allow cell motility and are also critical during cell cycle progression and mitosis. Rho GTPases and their effectors are involved in cell rounding at mitosis onset, in chromosomes alignment and are required for contraction of the actomyosin ring that separates daughter cells at the end of mitosis. Recent studies have revealed how a number of nucleotide exchange factors and GTPase-activating proteins regulate the activity of Rho GTPases during these processes.