Growth at moderately elevated temperature alters the physiological response of the photosynthetic apparatus to heat stress in pea (Pisum sativum L.) leaves

The impact of heat stress on the functioning of the photosynthetic apparatus was examined in pea (Pisum sativum L.) plants grown at control (25 °C; 25 °C-plants) or moderately elevated temperature (35 °C; 35 °C-plants). In both types of plants net photosynthesis (Pn) decreased with increasing leaf temperature (LT) and was more than 80% reduced at 45 °C as compared to 25 °C. In the 25 °C-plants, LTs higher than 40 °C could result in a complete suppression of Pn. Short-term acclimation to heat stress did not alter the temperature response of Pn. Chlorophyll a fluorescence measurements revealed that photosynthetic electron transport (PET) started to decrease when LT increased above 35 °C and that growth at 35 °C improved the thermal stability of the thylakoid membranes. In the 25 °C-plants, but not in the 35 °C-plants, the maximum quantum yield of the photosystem II primary photochemistry, as judged by measuring the Fv/Fm ratio, decreased significantly at LTs higher than 38 °C. A post-illumination heat-induced reduction of the plastoquinone pool was observed in the 25 °C-plants, but not in the 35 °C-plants. Inhibition of Pn by heat stress correlated with a reduction of the activation state of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). Western-blot analysis of Rubisco activase showed that heat stress resulted in a redistribution of activase polypeptides from the soluble to the insoluble fraction of extracts. Heat-dependent inhibition of Pn and PET could be reduced by increasing the intercellular CO2 concentration, but much more effectively so in the 35 °C-plants than in the 25 °C-plants. The 35 °C-plants recovered more efficiently from heat-dependent inhibition of Pn than the 25 °C-plants. The results show that growth at moderately high temperature hardly diminished inhibition of Pn by heat stress that originated from a reversible heat-dependent reduction of the Rubisco activation state. However, by improving the thermal stability of the thylakoid membranes it allowed the photosynthetic apparatus to preserve its functional potential at high LTs, thus minimizing the after-effects of heat stress.

A review of the cost effectiveness of bisphosphonates in the treatment of post-menopausal osteoporosis in Switzerland

The economic burden associated with osteoporosis is considerable. As such, cost-effectiveness analyses are important contributors to the diagnostic and therapeutic decision-making process. The aim of this study was to review the cost effectiveness of treating post-menopausal osteoporosis with bisphosphonates and identify the key factors that influence the cost effectiveness of such treatment in the Swiss setting. A systematic search of databases (MEDLINE, EMBASE and the Cochrane Library) was conducted to identify published literature on the cost effectiveness of bisphosphonates in post-menopausal osteoporosis in the Swiss setting. Outcomes were compared with similar studies in Western European countries. Three cost-effectiveness studies of bisphosphonates in this patient population were identified; all were from a healthcare payer perspective. Outcomes showed that, relative to no treatment, treatment with oral bisphosphonates was predicted to be cost saving for most women aged ≥70 years with osteoporosis or at least one risk factor for fracture, and cost effective for women aged ≥75 years without prior fracture when used as a component of a population-based screen-and-treat programme. Results were most sensitive to changes in fracture risk, cost of fractures, cost of treatment, nursing home admissions and adherence with treatment. Swiss results were generally comparable to those in other European settings. Assuming similar clinical efficacy, lowering treatment cost (through the use of price-reduced brand-name or generic drugs) and/or improving adherence should both contribute to further improving the cost effectiveness of bisphosphonates in women with post-menopausal osteoporosis. Published evidence indicates that bisphosphonates are estimated to be similarly cost effective or cost saving in most treatment scenarios of post-menopausal osteoporosis in Switzerland and in neighbouring European countries.

A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis

BACKGROUND: Mycograb (NeuTec Pharma) is a human recombinant monoclonal antibody against heat shock protein 90 that, in laboratory studies, was revealed to have synergy with amphotericin B against a broad spectrum of Candida species. METHODS: A double-blind, randomized study was conducted to determine whether lipid-associated amphotericin B plus Mycograb was superior to amphotericin B plus placebo in patients with culture-confirmed invasive candidiasis. Patients received a lipid-associated formulation of amphotericin B plus a 5-day course of Mycograb or placebo, having been stratified on the basis of Candida species (Candida albicans vs. non-albicans species of Candida). Inclusion criteria included clinical evidence of active infection at trial entry plus growth of Candida species on culture of a specimen from a clinically significant site within 3 days after initiation of study treatment. The primary efficacy variable was overall response to treatment (clinical and mycological resolution) by day 10. RESULTS: Of the 139 patients enrolled from Europe and the United States, 117 were included in the modified intention-to-treat population. A complete overall response by day 10 was obtained for 29 (48%) of 61 patients in the amphotericin B group, compared with 47 (84%) of 56 patients in the Mycograb combination therapy group (odds ratio [OR], 5.8; 95% confidence interval [CI], 2.41-13.79; P<.001). The following efficacy criteria were also met: clinical response (52% vs. 86%; OR, 5.4; 95% CI, 2.21-13.39; P<.001), mycological response (54% vs. 89%; OR, 7.1; 95% CI, 2.64-18.94; P<.001), Candida-attributable mortality (18% vs. 4%; OR, 0.2; 95% CI, 0.04-0.80; P = .025), and rate of culture-confirmed clearance of the infection (hazard ratio, 2.3; 95% CI, 1.4-3.8; P = .001). Mycograb was well tolerated. CONCLUSIONS: Mycograb plus lipid-associated amphotericin B produced significant clinical and culture-confirmed improvement in outcome for patients with invasive candidiasis.

Myoblast-seeded biodegradable scaffolds to prevent post-myocardial infarction evolution toward heart failure

OBJECTIVE(S): Even though the mechanism is not clearly understood, direct intramyocardial cell transplantation has demonstrated potential to treat patients with severe heart failure. We previously reported on the bioengineering of myoblast-based constructs. We investigate here the functional outcome of infarcted hearts treated by implantation of myoblast-seeded scaffolds. METHODS: Adult Lewis rats with echocardiography-confirmed postinfarction reduced ejection fraction (48.3% +/- 1.1%) were randomized to (1) implantation of myoblast-seeded polyurethane patches at the site of infarction (PU-MyoB, n = 11), (2) implantation of nonseeded polyurethane patches (PU, n = 11), (3) sham operation (Sham, n = 12), and (4) direct intramyocardial myoblast injection (MyoB, n = 11). Four weeks later, the functional assessment by echocardiography was repeated, and we additionally performed left ventricular catheterization plus histologic studies. RESULTS: The ejection fraction significantly decreased in the PU (39.1% +/- 2.3%; P = .02) and Sham (39.9% +/- 3.5%; P = .04) groups, whereas it remained stable in the PU-MyoB (48.4% +/- 3.1%) and MyoB (47.9% +/- 3.0%) groups during the observation time. Similarly, left ventricular contractility was significantly higher in groups PU-MyoB (4960 +/- 266 mm Hg/s) and MyoB (4748 +/- 304 mm Hg/s) than in groups PU (3909 +/- 248 mm Hg/s, P = .01) and Sham (4028 +/- 199 mm Hg/s, P = .01). Immunohistology identified a high density of myoblasts within the seeded scaffolds without any migration toward the host cardiac tissue and no evidence of cardiac cell differentiation. CONCLUSIONS: Myoblast-seeded polyurethane scaffolds prevent post-myocardial infarction progression toward heart failure as efficiently as direct intramyocardial injection. The immunohistologic analysis suggests that an indirect mechanism, potentially a paracrine effect, may be assumed.

Post-mortem forensic neuroimaging: correlation of MSCT and MRI findings with autopsy results

Multislice-computed tomography (MSCT) and magnetic resonance imaging (MRI) are increasingly used for forensic purposes. Based on broad experience in clinical neuroimaging, post-mortem MSCT and MRI were performed in 57 forensic cases with the goal to evaluate the radiological methods concerning their usability for forensic head and brain examination. An experienced clinical radiologist evaluated the imaging data. The results were compared to the autopsy findings that served as the gold standard with regard to common forensic neurotrauma findings such as skull fractures, soft tissue lesions of the scalp, various forms of intracranial hemorrhage or signs of increased brain pressure. The sensitivity of the imaging methods ranged from 100% (e.g., heat-induced alterations, intracranial gas) to zero (e.g., mediobasal impression marks as a sign of increased brain pressure, plaques jaunes). The agreement between MRI and CT was 69%. The radiological methods prevalently failed in the detection of lesions smaller than 3mm of size, whereas they were generally satisfactory concerning the evaluation of intracranial hemorrhage. Due to its advanced 2D and 3D post-processing possibilities, CT in particular possessed certain advantages in comparison with autopsy with regard to forensic reconstruction. MRI showed forensically relevant findings not seen during autopsy in several cases. The partly limited sensitivity of imaging that was observed in this retrospective study was based on several factors: besides general technical limitations it became apparent that clinical radiologists require a sound basic forensic background in order to detect specific signs. Focused teaching sessions will be essential to improve the outcome in future examinations. On the other hand, the autopsy protocols should be further standardized to allow an exact comparison of imaging and autopsy data. In consideration of these facts, MRI and CT have the power to play an important role in future forensic neuropathological examination.

Proteomic alterations in heat shock protein 27 and identification of phosphoproteins in ascending aortic aneurysm associated with bicuspid and tricuspid aortic valve

Whether or not there are molecular differences, at the intra- and extracellular level, between aortic dilatation in patients with bicuspid (BAV) and those with a tricuspid aortic valve (TAV) has remained controversial for years. We have performed 2-dimensional gel electrophoresis and mass spectrometry coupled with dephosphorylation and phosphostaining experiments to reveal and define protein alterations and the high abundant structural phosphoproteins in BAV compared to TAV aortic aneurysm samples. 2-D gel patterns showed a high correlation in protein expression between BAV and TAV specimens (n=10). Few proteins showed significant differences, among those a phosphorylated form of heat shock protein (HSP) 27 with significantly lower expression in BAV compared to TAV aortic samples (p=0.02). The phosphoprotein tracing revealed four different phosphoproteins including Rho GDP dissociation inhibitor 1, calponin 3, myosin regulatory light chain 2 and four differentially phosphorylated forms of HSP27. Levels of total HSP27 and dually phosphorylated HSP27 (S78/S82) were investigated in an extended patient cohort (n=15) using ELISA. Total HSP27 was significantly lower in BAV compared to TAV patients (p=0.03), with no correlation in levels of phospho-HSP27 (S78/S82) (p=0.4). Western blots analysis showed a trend towards lower levels of phospho-HSP27 (S78) in BAV patients (p=0.07). Immunohistochemical analysis revealed that differences in HSP27 occur in the cytoplasma of VSMC's and not extracellularly. Alterations in HSP27 may give early evidence for intracellular differences in aortic aneurysm of patients with BAV and TAV. Whether HSP27 and the defined phosphoproteins have a specific role in BAV associated aortic dilatation remains to be elucidated.

Livelihoods in Transition: Changing Land Use Strategies and Ecological Implications in a Post Soviet Setting (Kyrgyzstan)

The sudden independence of Kyrgyzstan from the Soviet Union in 1991 led to a total rupture of industrial and agricultural production. Based on empirical data, this study seeks to identify key land use transformation processes since the late 1980s, their impact on people's livelihoods and the implication for natural resources in the communes of Tosh Bulak and Saz, located in the Sokuluk River Basin on the northern slope of the Kyrgyz Range. Using the concept of the sustainable livelihood approach as an analytical framework, three different livelihood strategies were identified: (1) An accumulation strategy applied by wealthy households where renting and/or buying of land is a key element; they are the only household category capable of venturing into rain fed agriculture. (2) A preserving strategy involving mainly intermediate households who are not able to buy or rent additional agricultural land; very often they are forced to return their land to the commune or sell it to wealthier households. (3) A coping strategy including mainly poor households consisting of elderly pensioners or headed by single mothers; due to their limited labour and economic power, agricultural production is very low and hardly covers subsistence needs; pensions and social allowances form the backbone of these livelihoods. Ecological assessments have shown that the forage productivity of remote high mountain pastures has increased from 5 to 22 per cent since 1978. At the same time forage productivity on pre-mountain and mountain pastures close to villages has generally decreased from 1 to 34 per cent. It seems that the main avenues for livelihoods to increase their wealth are to be found in the agricultural sector by controlling more and mainly irrigated land as well as by increasing livestock. The losers in this process are thus those households unable to keep or exploit their arable land or to benefit from new agricultural land. Ensuring access to land for the poor is therefore imperative in order to combat rural poverty and socio-economic disparities in rural Kyrgyzstan.

Hsp90 transcriptionally and post-translationally regulates the expression of NDRG1 and maintains the stability of its modifying kinase GSK3beta

N-myc downstream-regulated gene 1 (NRDG1) is a stress-induced protein whose putative function is suppression of tumor metastasis. A recent proteonomic study showed NDRG1 interacts with the molecular chaperone heat shock protein 90 (Hsp90). From their reported association, we investigated if NDRG1 is dependent on Hsp90 for its stability and is therefore a yet unidentified Hsp90 client protein. Here, we demonstrate that endogenous NDRG1 and Hsp90 physically associate in hepatocellular cancer cell lines. However, geldanamycin (GA)-mediated inhibition of Hsp90 did not disrupt their interaction or result in NDRG1 protein destabilization. On the contrary, inhibition of Hsp90 led to a transcriptional increase of NDRG1 protein which was associated with cell growth arrest. We also observed that GA inhibited the phosphorylation of NDRG1 by targeting its regulating kinases, serum- and glucocorticoid-induced kinase 1 (SGK1) and glycogen synthase kinase 3 beta (GSK3beta). We demonstrate that in the presence of GA, GSK3beta protein and activity were decreased thus indicating that Hsp90 is necessary for GSK3beta stability. Taken together, our data demonstrate that NDRG1 is not a classic client protein but interacts with Hsp90 and is still dually regulated by Hsp90 at a transcriptional and post-translational level. Finally, we suggest for the first time GSK3beta as a new client protein of Hsp90.

A specific expression profile of heat-shock proteins and glucose-regulated proteins is associated with response to neoadjuvant chemotherapy in oesophageal adenocarcinomas

BACKGROUND Oesophageal adenocarcinomas often show resistances to chemotherapy (CTX), therefore, it would be of high interest to better understand the mechanisms of resistance. We examined the expression of heat-shock proteins (HSPs) and glucose-regulated proteins (GRPs) in pretherapeutic biopsies of oesophageal adenocarcinomas to assess their potential role in CTX response. METHODS Ninety biopsies of locally advanced adenocarcinomas before platin/5-fluorouracil (FU)-based CTX were investigated by reverse phase protein arrays (RPPAs), immunohistochemistry (IHC) and quantitative RT-PCR. RESULTS CTX response strongly correlated with survival (P=0.001). Two groups of tumours with specific protein expression patterns were identified by RPPA: Group A was characterised by low expression of HSP90, HSP27 and p-HSP27((Ser15, Ser78, Ser82)) and high expression of GRP78, GRP94, HSP70 and HSP60; Group B exhibited the inverse pattern. Tumours of Group A were more likely to respond to CTX, resulting in histopathological tumour regression (P=0.041) and post-therapeutic down-categorisation from cT3 to ypT0-T2 (P=0.040). High HSP60 protein (IHC) and mRNA expression were also associated with tumour down-categorisation (P=0.016 and P=0.004). CONCLUSION Our findings may enhance the understanding of CTX response mechanisms, might be helpful to predict CTX response and might have translational relevance as they highlight the role of potentially targetable cellular stress proteins in the context of CTX response.

Repression, Anpassung, Neuorientierung: Islamische Bildung im sowjetischen und post- sowjetischen Raum

How did Islam survive in the Soviet Union, and how did it develop since 1991? In four case studies and four longitudinal surveys, senior specialists from the area and two German junior scholars discuss the transformations of Islam in Tatarstan, Azerbaijan, Daghestan, Uzbekistan and Tajikistan. Several chapters analyze the Bolsheviks’ attack on Islam since the 1920s. Altay Göyüşov and Il’nur Minnullin demonstrate how the Soviets first attempted to draw some groups of Muslim scholars and intellectuals to their side, in Azerbaijan and Tatarstan, respectively. In the early 1930s collectivization and outright state terror made a complete end to the Islamic infrastructure, including mosques and pious foundations, Muslim village courts (as shown by Vladimir Bobrovnikov for Dagestan), Islamic educational institutions (as documented by Aširbek Muminov for Uzbekistan), as well as the Muslim press (analyzed by Dilyara Usmanova for Tatarstan); also Sufi brotherhoods became a main target of violent repression (Šamil‘ Šixaliev, for Dagestan). Repression was followed by the establishment of a modus vivendi between state and religion in the post-war period (Muminov, Bobrovnikov, Šixaliev), and by the instrumentalization of religion for patriotic purposes in the post-Soviet Caucasus and Central Asia (Christine Hunner-Kreisel, Manja Stephan, both based on fieldwork). By the early 2000s Islam was almost everywhere back under full state control; the leading role of the state for defining „good“ and „bad“ Islam is largely taken for granted. While similar forms of state pressure in all regions thus allow us to draw an overall picture of how Islamic traditions were repressed and reanimated, the „archival revolution“ of the early 1990s provides fascinating insights into the specific developments in the individual regions, and into the adaptation strategies of the Muslim scholars and intellectuals on the spot. Still, the Soviet heritage is still very palpable; also the attempts to leapfrog the Soviet period and to link up again with the individual local Islamic traditions from before 1917, and even the negation of the Soviet experience in the form of embracing Islamic trends from abroad, are often still couched in largely Soviet mental frameworks.

Rainer Werner Fassbinder’s "Garbage, The City, and Death". A Four Act Scandal in Post-war Germany

Rainer Werner Fassbinder’s Garbage, The City, and Death. A Four Act Scandal in Post-war Germany The paper explores the dramaturgy of the scandals around the play Garbage, The City and Death (Der Müll, die Stadt und der Tod) by German playwright, theatre and film maker Rainer Werner Fassbinder. Published in 1976, the play immediately caused a scandal in West Germany, because it was accused of reproducing anti-Semitic stereotypes. The presentation sheds light on the different phases of the scandal and their historical and cultural contexts in post-war Germany – starting as a literary scandal in 1976, being transformed into a theatre scandal in the 1980ies and finally being dissolved by the German premiere in 2009. The paper is structured as follows: Act One: The Literary Scandal. Destroying Fassbinder’s Garbage, Act Two: Preventing the Staging of the Play, Act Three: Blocking the Opening Night, Act Four: Performing the Play in Germany. By analysing the dramaturgical structure of this specific scandal, the paper discusses the following hypotheses: 1. Scandals arise through the circulation of decontextualised information in public. This is due to either a lack of information about the actual object or incident being scandalised or a lack of information about the context of the object or incident. This lack is caused by the logic of the scandal itself: Because the play or the performance is prohibited, it has been withdrawn from the public, making it impossible to form a well-founded opinion on the controversy. 2. The scandal is driven forward by an emotionalising rhetoric built around the decontextualised information. 3. Once the gap of information is filled, the scandalising rhetoric turns into a rhetoric of irrelevance: Reviews of the first performance of Garbage, The City and Death in Germany considered the play hardly a matter of public concern.

Intravitreal ranibizumab monotherapy to treat retinopathy of prematurity zone II, stage 3 with plus disease.

BACKGROUND Treatment of retinopathy of prematurity (ROP) stage 3 plus with bevacizumab is still very controversial. We report the outcome of 6 eyes of 4 premature infants with ROP stage 3 plus disease treated with ranibizumab monotherapy. METHODS Six eyes of 4 premature infants with threshold ROP 3 plus disease in zone II, were treated with one intravitreal injection of 0.03 ml ranibizumab. No prior laser or other intravitreal therapy was done. Fundus examination was performed prior to the intervention and at each follow-up visit. Changes in various mean vital parameters one week post intervention compared to one week pre-intervention were assessed. RESULTS The gestational age (GA) of patient 1, 2, 3, and 4 at birth was 24 5/7, 24 5/7, 24 4/7, and 26 1/7 weeks, respectively. The birth weight was 500 grams, 450 grams, 665 grams, and 745 grams, respectively. The GA at the date of treatment ranged from 34 3/7 to 38 6/7 weeks. In one infant, upper air way infection was observed 2 days post injection of the second eye. Three eyes required paracentesis to reduce the intraocular pressure after injection and to restore central artery perfusion. After six months, all eyes showed complete retinal vascularisation without any signs of disease recurrence. CONCLUSIONS Treatment of ROP 3 plus disease with intravitreal ranibizumab was effective in all cases and should be considered for treatment. One infant developed an upper air way infection suspicious for nasopharyngitis, which might be a possible side effect of ranibizumab. Another frequent complication was intraocular pressure rise after injection. More patients with longer follow-up duration are mandatory to confirm the safety and efficacy of this treatment. TRIAL REGISTRATION NUMBER NCT02164604 ; Date of registration: 13.06.2014.

Molecular Consequences of the SERPINH1/HSP47 Mutation in the Dachshund Natural Model of Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a heritable connective tissue disease characterized by bone fragility and increased risk of fractures. Up to now, mutations in at least 18 genes have been associated with dominant and recessive forms of OI that affect the production or post-translational processing of procollagen or alter bone homeostasis. Among those, SERPINH1 encoding heat shock protein 47 (HSP47), a chaperone exclusive for collagen folding in the ER, was identified to cause a severe form of OI in dachshunds (L326P) as well as in humans (one single case with a L78P mutation). To elucidate the disease mechanism underlying OI in the dog model, we applied a range of biochemical assays to mutant and control skin fibroblasts as well as on bone samples. These experiments revealed that type I collagen synthesized by mutant cells had decreased electrophoretic mobility. Procollagen was retained intracellularly with concomitant dilation of ER cisternae and activation of the ER stress response markers GRP78 and phospho-eIF2α, thus suggesting a defect in procollagen processing. In line with the migration shift detected on SDS-PAGE of cell culture collagen, extracts of bone collagen from the OI dog showed a similar mobility shift, and on tandem mass spectrometry, the chains were post-translationally overmodified. The bone collagen had a higher content of pyridinoline than control dog bone. We conclude that the SERPINH1 mutation in this naturally occurring model of OI impairs how HSP47 acts as a chaperone in the ER. This results in abnormal post-translational modification and cross-linking of the bone collagen.

Insights into post-translational processing of beta-galactosidase in an animal model resembling late infantile human G-gangliosidosis

G(M1)-gangliosidosis is a lysosomal storage disorder caused by a deficiency of ss-galactosidase activity. Human GM1-gangliosidosis has been classified into three forms according to the age of clinical onset and specific biochemical parameters. In the present study, a canine model for type II late infantile human GM1-gangliosidosis was investigated 'in vitro' in detail. For a better understanding of the molecular pathogenesis underlying G(M1)-gangliosidosis the study focused on the analysis of the molecular events and subsequent intracellular protein trafficking of beta-galactosidase. In the canine model the genetic defect results in exclusion or inclusion of exon 15 in the mRNA transcripts and to translation of two mutant precursor proteins. Intracellular localization, processing and enzymatic activity of these mutant proteins were investigated. The obtained results suggested that the beta-galactosidase C-terminus encoded by exons 15 and 16 is necessary for correct C-terminal proteolytic processing and enzyme activity but does not affect the correct routing to the lysosomes. Both mutant protein precursors are enzymatically inactive, but are transported to the lysosomes clearly indicating that the amino acid sequences encoded by exons 15 and 16 are necessary for correct folding and association with protective protein/cathepsin A, whereas the routing to the lysosomes is not influenced. Thus, the investigated canine model is an appropriate animal model for the human late infantile form and represents a versatile system to test gene therapeutic approaches for human and canine G(M1)-gangliosidosis.

Radiocarbon dating of modern peat profiles: Pre- and post-bomb C-14 variations in the construction of age-depth models

We present studies of 9 modern (up to 400-yr-old) peat sections from Slovenia, Switzerland, Austria, Italy, and Finland. Precise radiocarbon dating of modern samples is possible due to the large bomb peak of atmospheric 14C concentration in 1963 and the following rapid decline in the 14C level. All the analyzed 14C profiles appeared concordant with the shape of the bomb peak of atmospheric 14C concentration, integrated over some time interval with a length specific to the peat section. In the peat layers covered by the bomb peak, calendar ages of individual peat samples could be determined almost immediately, with an accuracy of 23 yr. In the pre-bomb sections, the calendar ages of individual dated samples are determined in the form of multi-modal probability distributions of about 300 yr wide (about AD 16501950). However, simultaneous use of the post-bomb and pre-bomb 14C dates, and lithological information, enabled the rejection of most modes of probability distributions in the pre-bomb section. In effect, precise age-depth models of the post-bomb sections have been extended back in time, into the wiggly part of the 14C calibration curve.