We further categorized the inpatient population into those who had VCE placed within 3 days and after 3 days of admission and examined the association between time of placement and detection of active bleeding and active bleeding with angioectasia via t tests

of proportions. We similarly examined the relationship between successful therapeutic intervention and comorbidities and timing of VCE placement. Additionally, we compared timing of VCE placement with length of stay through t tests of means. In all instances, a P < .05 was considered to be statistically significant. Finally, we conducted post-hoc power calculations on key outcomes of interest to assess whether lack of significance was likely click here because of low power or to a truly small effect. All statistical analyses were conducted by using SAS 9.2

software (SAS Institute Inc., Cary, North Carolina, USA), whereas post-hoc power calculations were performed by using Power Analysis and Sample Size (PASS 11.0, NCSS LLC, Kaysville, Utah, USA). Because this was a retrospective study, with data collected from previously recorded data, the study was waived for Ku-0059436 cost a full review by the Institutional Review Board of the University of Massachusetts Medical Center and received expedited approval. The study design, including distribution of the patients, is showed in Figure 1, and patient demographics are presented in Table 1. A positive result was defined as active bleeding, angioectasia, red spot, tumor, ulcer, or bleeding outside of the small intestine (stomach or colon). The overall yield of VCE was 65.9% (95 of 144) for the inpatient population versus 53.4% (62 of 116) for the outpatient population Morin Hydrate (P = .054).

Red spots were included in the list of positive findings but were not included in the analysis. Findings of VCE for inpatients are presented in Table 2. The mean hematocrit on admission was 26.8% ± 6%. The inpatient population was further divided into those who had VCE placed within 3 days of admission (n = 90) and those who had VCE placed after 3 days of admission (n = 54) for OOGIB. We were interested in lesions in which endoscopic intervention was potentially feasible. We therefore looked specifically at patients with either active bleeding or angioectasia. Active bleeding was found in 28.9% of the <3-day cohort (26 of 90) compared with 13.0% of the >3-day cohort (7 of 54) (P = .028) ( Fig. 2). The yield to find either an active bleed and/or an angioectasia was 44.4% in the <3-day cohort (40 of 90) versus 27.8% in the >3-day cohort (15 of 54) (P = .046) ( Fig. 2). Two VCEs from each cohort showed evidence of both an active bleed and one or more angioectasia. Detection of active bleeding declined progressively for each day after admission (Fig. 3) as did the detection of active bleeding and angioectasia for each day after admission (Fig. 4) for the inpatient population.

The introduction of CNIs in the 1980s resulted in lower rejection rates and improved short-term patient and allograft survival rates, with 1-year graft survival rates of around 90% and acute rejection rates below 20% being achieved.

find more Despite these impressive 1-year rates, long-term improvements in graft survival have been more difficult to achieve with CNIs. Indeed, the reduction in acute rejection with these drugs has not directly translated to improvements in allograft survival, and suggests that CNI-based immunosuppression may not improve long-term graft survival [1]. The main reason for this observation is that long-term CNI use gives rise to nephrotoxicity, which is an important cause of long-term

graft failure [3]. Indeed, nephrotoxicity is present in 96.8% of kidney allograft biopsies by 10 years [4]. CNIs initially protect the renal transplant ALK inhibitor against immunologic injury but may subsequently cause damage as a result of long-term nephrotoxicity. This helps, at least partly, to explain why the low early acute rejection rates achieved using CNIs are not accompanied by improvements in long-term outcomes [4]. As a consequence, CNI-sparing/withdrawal strategies are employed to minimize CNI nephrotoxicity under the protection of additional immunosuppressant drugs [1] and [4]. One approach is to use 2-stage immunosuppression, with stage 1 using CNIs to minimize immunogenic injury and stage 2 using long-term “nonnephrotoxic” immunosuppression [4]. The emergence of powerful nonnephrotoxic agents such as the mammalian target of rapamycin (mTOR) inhibitors has facilitated CNI reduction/withdrawal early posttransplantation [1]. The need to reduce nephrotoxicity, however, must be weighed against the increased risk of acute rejection or chronic why antibody-mediated rejection [5] that presents with suboptimal CNI exposure [6]. The mTOR inhibitors, sirolimus (SRL) and everolimus (EVR), have an immunosuppressive mode of action complementary to that of CNIs, which provides

the rationale for their combined clinical use [7], [8] and [9]. CNIs act early after T-cell activation, preventing transcriptional activation of early T-cell-specific genes. By blocking calcineurin, the production of proinflammatory cytokines (e.g. interleukin-2 [IL-2]) and, subsequently, T-cell activation are inhibited. By contrast, mTOR inhibitors reduce T-cell activation later in the cell cycle by blocking growth-factor-mediated cell proliferation in the cellular response to alloantigen [3], [8] and [10]. The distinct mechanism of action and favorable nephrotoxicity profile has led to mTOR-inhibitor-containing regimens being developed with the aim of minimizing, eliminating, or avoiding exposure to CNIs.

Similarly, a post hoc analysis of patients (n = 8) who had anemia at baseline showed a mean increase of 1.9 and 1.7 g/dL in absolute hemoglobin concentrations by study end for the Selleck U0126 taliglucerase alfa 30-U/kg and 60-U/kg groups, respectively (Table 4). Six (75%) of the 8 patients no longer had anemia at study end; the 2 patients (25%) who had anemia at study end were in the 30-U/kg group and had achieved hemoglobin

concentrations that approached normal by study end (11.2 and 11.8 g/dL, respectively). From baseline to 12 months, improvements were observed in organ volumes and platelet counts (Table 2, Fig. 2). Mean spleen volumes were reduced from 22.2 MN at baseline to 14.0 MN at 12 months and 29.4 MN at baseline to 12.9 MN at 12 months for taliglucerase alfa 30 U/kg and 60 U/kg, respectively (Fig. 2A). At 12 months, mean absolute spleen volume

(calculated by volume in mL) decreased by 28.6% and 41.1% from baseline for patients receiving taliglucerase alfa 30 U/kg and 60 U/kg, respectively FLT3 inhibitor (Fig. 2B). Mean liver volumes were reduced from 1.8 MN at baseline to 1.5 MN at 12 months and 2.2 MN at baseline to 1.7 MN at 12 months, for the taliglucerase alfa 30-U/kg and 60-U/kg groups, respectively (Fig. 2C). Mean absolute liver volume (calculated by volume in mL) was reduced from baseline to 12 months by 6.3% and 14.0%, for the taliglucerase alfa 30-U/kg and 60-U/kg groups, respectively (Fig. 2D). After 12 months of

treatment, mean percent change in platelet counts improved by 30.9% (from 162,667 to 208,167/mm3) for the 30-U/kg dose group and by 73.7% (from 99,600 to 172,200/mm3) for the 60-U/kg dose group (Table 2, Fig. 2E). Mean chitotriosidase activity was reduced by 58.5% and 66.1% after 12 months of treatment with taliglucerase alfa 30 U/kg and 60 U/kg, respectively (Fig. 2F). Individual patient data medroxyprogesterone for these parameters are reported in Table 3. Increases in height and weight were seen at the end of the study in both dose groups, with increases in mean (± SD) height of 4.2% (± 2.2) and 7.6% (± 2.1) and mean increases in weight of 9.6% (± 7.0) and 14.7% (± 5.7) in the 30-U/kg and 60-U/kg treatment groups, respectively. Post hoc analysis of height velocity showed that the taliglucerase alfa 30-U/kg group had a mean growth of 5.1 cm/year and the 60-U/kg treatment group had a mean growth of 8.0 cm/year after 12 months’ treatment of taliglucerase alfa. There was no change in puberty (Tanner stage) in 4/5 patients from baseline to study end in the 60-U/kg dose group (data not available for 1 patient; all patients ≤ 10 years of age and at stage I at baseline). Of the 6 patients treated with taliglucerase alfa 30 U/kg, 2 patients (14 and 11 years of age) had a change in Tanner stage from I to II, 1 patient remained at Tanner stage III, and the other 3 patients remained at Tanner stage I.

Previous studies showed that LAPTM4B*2 allele was associated with increased susceptibility of lung cancer [20], gastric cancer [21], colorectal cancers

[22], lymphoma [26], cervical cancer [23] and breast cancer [24]. The risk of developing these cancers were increased to 1.720, 1.710, 1.512, buy NVP-BGJ398 1.610, 1.490, and 1.301 fold in individuals carrying allele *2 in comparison with *1, respectively. In this study, the LAPTM4B *2 carrier had a 1.457-fold risk of suffering melanoma than LAPTM4B *1 carrier. Our result was consistent with previous findings. The two sequence alleles of the LAPTM4B are in homology, with the exception of a 19-bp difference in the first exon. Shao [8] showed that LAPTM4B *1 was predicted to encode a 35 kD protein. In allele *2, the extra 19-bp sequence changed open reading frame of LAPTM4B gene and made LAPTM4B*2 encode one more protein isoform, a 40-kD protein, than LAPTM4B*1 ( Figure 3). The N-terminal sequence of LAPTM4B is crucial for its functions, such as enhancing cell proliferation and signal transduction [19] and [27]. The two different protein isoforms may influence physiological activities and functions of the cancer cell [22]. Moreover, the 19-bp sequence may act as a cis-acting element

to participate in genetic transcriptional regulation. The gene mutation status of melanoma patients were also observed in this study. C-KIT and BRAF are the most common mutated genes in Asian melanomas [28] and [29]. It has been reported Selleck Trametinib that the incidence of somatic mutations within the C-KIT, BRAF, NRAS and PDGFRA genes was 10.1% (58/573), 25.9% (121/468), 7.2% (33/459) and 4.8% (17/352), respectively in Chinese melanoma cases [28] and [29]. The frequencies of C-KIT and BRAF mutation were 6.4% (11/171) and 20.5% (35/171) in this study, closing to previous studies. There was no difference between *2 allele carrier and *1 allele

carrier in C-KIT and BRAF gene mutation, nor in other clinicopathological features. Therefore, we believed that LAPTM4B was an independent risk factor in melanoma developing. To our knowledge, this is the first case-control study focusing on the possible role of LAPTM4B*2 in melanoma. We concluded that LAPTM4B*2 is likely contributing Branched chain aminotransferase to a higher risk of melanoma. Carrying LAPTM4B *2 is a susceptible factor to melanoma in Chinese patients. This work was supported by the National Natural Science Foundation of China (No. 81071422). We would like to thank all people and patients who participated in this study. “
“The majority of patients with pancreatic cancer present with unresectable locally advanced disease. Standard of care therapy for locally advanced pancreatic cancer includes a combination of chemotherapy and radiation therapy [1]. A challenge in the management of pancreatic cancer is the early assessment of treatment response.

[9, 22 and 23]) and Trichostatin A molecular weight once elevated stress levels have subsided. Previous work on intergroup conflict has shown that losing groups might be prevented from using certain areas because of exclusion by winners [9 and 23] or may avoid areas of agonistic interaction if prior experience reliably predicts future conflict [22]. This reduced involvement in agonistic interactions parallels the “loser effect” often found in dyadic contests, whereby individuals become less likely to escalate future conflicts following a defeat (reviewed in [24]). Even where loser effects are not found, previous fights can reduce aggression and discourage home-range overlap [25 and 26]. Here, however, we found the opposite

effect: the woodhoopoe groups in our study used roosts in zones of conflict more often following intergroup conflicts, especially conflicts that were lost, and arrived at roost sites earlier on such occasions. This greater usage may represent defense of a limiting resource; as in many other species [ 23, 27 and 28], there is a risk that highly productive or important parts of a territory will be annexed by successful rival groups [ 29]. Despite this risk, groups may continue to use other roosts outside the zone of conflict if they provide greater thermoregulatory benefits [ 13], provide more protection from predators

[ 29], or are less likely BMS354825 to accumulate water on rainy nights [ 30], or if switching roosts is important for minimizing the buildup of parasites [ 31]. Occasions when members of the same group roost in different

places probably reflect unresolved between-individual conflicts of interest over group decisions [32 and 33]. Our results suggest that an earlier conflict with a rival group enhances the likelihood that a consensus will be reached later on, i.e., that all group members roost together. Since all adult woodhoopoe group members contribute Rucaparib to the majority of IGIs [1] and the outcome of extended IGIs is strongly determined by relative group size [15], an increased need for collective defense may override within-group disagreements about roost site. Previous work on the factors influencing group fissions has focused on environmental variability and uncertainty, as well as within-group factors such as individual energetic state, the social relationships between group members, and the ways in which information is gathered and shared [34, 35 and 36]. Our study suggests that external factors—in this case, intergroup conflict—also play an important role and should be considered in future work on consensus decision-making. Extended intergroup conflicts appear to cause short-term increases in stress, which may be responsible for previously documented changes in allopreening and other behavior in the immediate aftermath [7 and 37].

, 2007a, Cohen Kadosh et al., 2007b and Cohen Kadosh et al., 2010). Therefore, it was quite astonishing to discover its total absence

in synesthetic individuals. How can this lack of SiCE be explained? We presume that it might be a matter of shortage in mental resources. In an incompatible condition, the numbers do not match the synesthete’s own conscious representation. This conflict between the mental representation and the concrete visualization necessitates mentally rotating or replacing the numbers’ display to fit their location on the synesthetic number form. This process, which is undoubtedly time and energy consuming, leaves little resources (if any) for processing the numbers’ values. This explanation corroborates previous studies that showed how task difficulty this website (e.g., perceptual load) can influence performance in general and automatic processing in particular when attentional resources were consumed by high load task (for review see Lavie, 2005 and Mattingley et al., 2006). Continuing this line of thought, we suggest two alternatives: One possibility is that synesthetes did perceive the semantic meaning of the numbers to some extent (otherwise there would have been no mistakes at all in this condition), however, the incompatible presentation of the numbers was too difficult for achieving complete automatic processing of the numerical values.

Examination of the RT results along with the ER results in physical judgments of the horizontal task support this suggestion, showing that

a conflict between 4-Aminobutyrate aminotransferase the relevant and irrelevant dimensions was evident in the ER measures but did not fully GSI-IX purchase evolve to be manifested also in terms of response time. Alternatively, it is also possible that when numbers were presented in a “”wrong”" order, synesthetes did not perceive them as symbols that entailed numerical values but rather as asemantic, meaningless forms. After debriefing, synesthete ES (who has a bottom to top number form) described her insights from the experiment as follows: “”When the numbers are ordered incorrectly, each number stands on its own and is not perceived as a part of the numerical sequence, therefore it is not confusing when the digit does not correspond to the physical size”". If this is correct, it would not be farfetched to suggest that for synesthetes, the number-line incompatible condition resembles the neutral condition in the sense that the irrelevant information does not interfere with the relevant information. In the same vein of thought, the congruent condition loses its advantage as a facilitator. Indeed, a closer examination of the facilitation (i.e., neutral RT minus congruent RT) and interference (i.e., incongruent RT minus neutral RT) patterns in the physical block of the vertical task revealed that in the incompatible condition both the interference and facilitation components were eliminated (see Fig. 1B).

The recipient must not have any evidence of clinically significant antibodies, presently or in the past. At least two concordant results of ABO and RhD typing must be on record, including one from the current sample. Additional laboratory information system requirements VX 809 must also be met. When electronic crossmatching is performed neither an immediate spin nor antiglobulin phase crossmatch between recipient plasma and donor red cells is required. Electronic crossmatch has cost–benefits and is safe for most patients. However, it is known that potentially clinically significant antibodies, including antibodies to low incidence antigens may be missed by electronic crossmatch [6].

We report here a case of a clinically significant acute extravascular hemolytic Gamma-secretase inhibitor transfusion reaction mediated by previously unrecognized (and undetected) anti-Kpa antibody in a patient who met all criteria for electronic crossmatch, resulting in the transfusion of an incompatible red cell unit. A 64 year old clinically obese female with diabetes

and previous history of myocardial infarction was admitted for urgent repair of a hiatal hernia. The patient had two previous pregnancies. The patient had remote history of transfusion in the 1980s through which she acquired hepatitis C. The patient had a more recent history of red cell transfusion with one unit of red cells transfused after gastrointestinal bleeding 5 years earlier at which time no antibodies were identified. The patient was blood group O, RhD positive. At the time of current presentation, the antibody screen was negative. The hemoglobin was 82 g/L pre-transfusion. One unit of group O, RhD positive, leukoreduced packed red blood cell (PRBC) unit was issued to the patient after electronic crossmatch indicated compatibility. During the transfusion, the patient experienced an elevation in temperature, from 37.9 °C pre-transfusion to 39.5 °C during transfusion, accompanied by chills/rigors, and soon followed by shortness

of breath. The transfusion was permanently discontinued. At this point the patient had received about 200 mL of PRBCs. Immediately after the transfusion the hemoglobin was 90 g/L. The patient was Ribonucleotide reductase given supplemental oxygen, bronchodilator (salbutamol) and bilevel positive airway pressure (BPAP) ventilatory support for a few hours. The patient’s signs and symptoms resolved within a few hours with no additional intervention. Patient blood cultures and cultures of the remainder of the PRBC unit were negative. Transient elevation of the total bilirubin and lactate dehydrogenase was noted (Fig. 1). Transient elevation of troponin I was observed following the incompatible red cell transfusion, peaking just before the surgery (Fig. 2). EKG performed before the incompatible red cell transfusion showed old anterior myocardial infarct.

Finally we observed increase of CD69 gene expression. This molecule is expressed by various cells of hematopoietic lineage, being related to activation and proliferation of these cells. selleck monoclonal antibody Some studies have shown the expression of CD69 in HUVECs after inflammatory stimuli, as action of thrombin (Okada et al., 2006) and TNF-α (Viemann et al., 2006). However, future studies should be performed to better characterize the expression and function of this marker in endothelial cells after

stimulation with jararhagin. Considering the inflammation as a multifactorial, multicellular and complex event as it is (Petri et al., 2008) and some considerations pointed here, it is important to note that endothelial cells when removed from its natural environment, are not influenced by other components present in the vascular milieu (i.e. basement membrane, extracellular matrix, fibroblasts, myoblasts and leukocytes). So the isolated endothelial cells, represented here by HUVECs, seems to have little participation in the effective click here release of cytokines, adhesion molecules and other pro-inflammatory mediators induced directly by jararhagin, although these cells present a complete gene transcription system activated by this SVMP. On the other hand, it is well known that the endothelial cells are of fundamental

importance for the inflammatory response induced any agent. In particular by SVMPs, these toxins directly activate (considering in vivo studies) the interaction Ixazomib manufacturer between leukocyte and endothelium and, thus, results in the local inflammation observed during envenoming ( Clissa et al., 2006; Menezes et al., 2008). It is important to cite also another fundamental role of endothelial cells for a different event of local bothropic envenoming,

the hemorrhage. This occurs very rapidly after venom injection, and nowadays this effect has been mainly attributed to the indirect consequence of the SVMPs action on their primary target, i.e. the basement membrane (BM) of capillary vessels and related extracellular matrix components that provide stability to micro vessel structure (Baldo et al., 2010; Escalante et al., 2011; Serrano et al., 2007). Also, it has been proposed that the rapid in vivo damage of endothelial cells is the result of mechanical hemodynamic forces operating in the microvasculature which distend and disrupt the integrity of these cells after an initial weakening of the stability of the BM occurring as a consequence of proteolytic cleavage of BM components ( Gutiérrez et al., 2005, 2006). In summary, our data indicated that most of the genes up-regulated by treatment of HUVECs with jararhagin are related to the inflammatory response.

, 2004 and Bruce et al., 2005). Based on our findings, we present a new model that could explain the radiation of orbweb spiders. We chose Zosis geniculata (Olivier, 1789; Uloboridae) and Metazygia rogenhoferi (Keyserling, 1878; Araneidae) as representatives of the cribellate and ecribellate orb weavers, respectively.

The choice was based on several criteria that enhance comparability between these species. For example, they have a similar adult body size and overall shape, they spin similar-sized orb webs ( Fig. 1), both species do not show univoltine life cycle and their families are at the base of the sister clades Deinopoidea (cribellate) and Araneoidea (ecribellate), thus minimizing the effects of these characteristics on the variables being analyzed. Furthermore, in order to control for sexual dimorphism and ontogeny we analyzed INK 128 solubility dmso only adult females. We analyzed ten individuals of M. rogenhoferi and twenty individuals of Z. geniculata. Specimens from both species were collected in the city of São Paulo. Adult females were brought to the lab and kept inside individual acrylic boxes (31 cm × 31 cm × 12 cm) selleck in a room with a 12:12 light cycle and small temperature (24–26 °C) and humidity (76–81% UR) variation. Many M. rogenhoferi

specimens died in the first week at the laboratory due to nematoid or fungus parasitism. After this first week precaution period (to exclude parasitized individuals), spiders were not fed for at least three days prior to measurement of oxygen consumption. All spiders were weighted before respirometric measurements. The weight was used to model the allometric parameter in the statistical analysis. We used a flow-through intermittent setup. Spiders were inserted into a cylinder shaped test chamber (80 mL) plugged at both ends with three-way valves and partially covered with humidified filter paper to 4-Aminobutyrate aminotransferase maintain air humidity and to allow the spiders to acquire resting posture. The chambers with spiders were maintained at 25 °C of temperature along all the measurement. The spiders were initially given 1 h to achieve rest condition.

After this first hour, the chamber was purged with outdoor air and then left closed for 4 h. After this period, the air was drawn from the chambers for 4 min, and passed through carbon dioxide and water absorbers before going into the PA-1 oxygen analyzer (Sable Systems Inc.). The air flow used was 150 mL/min and did not seem to disturb spiders. Oxygen depletion between the initial and final sampling was estimated via integration (DatacanV software from Sable Systems Inc.) and used to calculate metabolic rates over the time interval. The resting metabolism was measured in the lightened period of the day, which is the period of lowest activity for spiders. The oxygen consumption of each animal was recorded three times and only the lowest value for each spider was considered. Spurious values (e.g. values from the same day consistently above the others) were discarded.

The insoluble histones were re-dissolved in 4 ml of unfolding Buffer (7 M Guanidinium-HCl, 20 mM HEPES-KOH pH 7.5, 1 mM EDTA, 1 mM click here DTT) and dialysed into SAU200 Buffer (20 mM sodium acetate pH 5.2, 7 M urea, 200 mM NaCl, 1 mM EDTA, 5 mM β-mercaptoethanol). 0.5 ml of cation exchange resin (SP FF, GE Healthcare) was equilibrated with SAU200 buffer in 10 mL disposable chromatography columns (Bio-Rad). Dialysed histones were bound to the resin, washed twice with 2 mL of SAU200, once with 2 mL of SAU400 (400 mM NaCl), and

eluted in 2 mL of SAU800 (800 mM NaCl). Eluted histones were dialysed into H2O plus 5 mM β-mercaptoethanol and lyophilized. Histones were re-dissolved in unfolding Buffer, quantified by absorbance at 280 nm and mixed in equimolar amounts. The octamer complex was refolded by dialysis into refolding buffer (2 M NaCl, 20 mM HEPES-KOH pH 7.5, 1 mM EDTA, 5 mM β-mercaptoethanol), and purified from mis-folded aggregates by gel filtration on a GL 10/300 column packed with Superdex S200(GE Healthcare). Before gel filtration, 20 mM dithiothrietol was added to the samples and incubated at 25 °C for 30 min to

ensure complete reduction of the histone H3 labeling site. Gel filtration was carried out in Refolding Buffer without β-mercaptoethanol. Immediately after gel filtration, fractions containing the correctly folded histone octamer were concentrated, using an Amicon Ultra-4 selleck products centrifugal concentrator (Millipore) with a molecular weight cut off of 10,000 Da, to ∼25 μM, and spin labeled with a ten-fold excess of non-deuterated (1-Oxyl-2,2,5,5-tetramethylpyrroline-3-methyl) methanethiosulfonate (MTSSL) (Fig. S2) at 25 °C for 3 h. Excess MTSSL was removed by dialysis verses 2 L of refolding buffer without reducing agents at 4 °C for 16 h. Labeled octamer was combined with a 1-fold excess of H2A–H2B dimers,

refolded and purified separately, as our previous work had shown that an excess of dimer stabilizes the octamer complex [10]. H2O in the samples was exchanged for D2O by four rounds of sequential concentration Nintedanib (BIBF 1120) and dilution, with deuterated refolding buffer minus reducing agent (prepared by lyophilisation and re-solvation of buffer with D2O), using Amicon Ultra-4 centrifugal concentrators (Millipore), achieving 99.8% exchange with D2O. The octamer samples were finally concentrated to 50 μM and diluted 1:1 with D8-glycerol (Cambridge Isotope Laboratories Inc.), giving a final spin-pair concentration of approximately 25 μM, and stored at 4 °C until EPR measurements were made. Solvent exchange and subsequent sample preparation steps took approximately 2.5 h at room temperature and subsequently samples were routinely stored at 4 °C for several days. Based on reported hydrogen–deuterium exchange rates in proteins [13] and the inherent structural lability of the core histone octamer, it was expected that almost complete exchange of protons would have been achieved.