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Monitoring groundwater storage is essential for sustainable groundwater management. Storage can be quantified by considering the two main components through which storage change is expressed: saturation changes and deformation of aquifer materials. Here, these components were quantified using a selected area in California's San Joaquin Valley (USA). First, this involved following existing observational approaches: quantifying the component expressed through saturation changes by identifying head measurements from shallow wells and scaling by specific yield. In the San Joaquin Valley, existing approaches to estimate the deformation component are to ignore it or approximate it with a simple linear relation to measured head. However, head and deformation measurements made at extensometers revealed that assuming a linear relationship between deformation and head might provide a poor estimate, particularly during periods in which measured head is rising. Instead, InSAR-derived surface deformation measurements were used to quantify the deformation component of storage changes. This showed that the two components—saturation and deformation—accounted for storage declines of equal magnitude over 2015–2021, suggesting that the deformation component should not be neglected when estimating storage changes in regions with subsidence. Summing the two calculated components gave a new estimate of the total storage change that captured the major trends seen in independent estimates, while better accounting for the deformation component. An additional benefit is that this method accounts for the deformation component in the unconfined aquifer. This method to quantify total storage change can be a practical and effective tool to support groundwater management. [ABSTRACT FROM AUTHOR]

Purpose: This study sought to investigate the diagnostic sensitivity of diffusion-weighted imaging (DWI) in variant Creutzfeldt-Jakob disease (vCJD), a prion disease with significant public health implications on account of its transmissibility. The importance of this research stemmed from the first neuropathologically confirmed vCJD case in a PRNP heterozygous individual in 2016, which displayed DWI features typical of sporadic CJD (sCJD). The case was classified as 'probable' sCJD in life, predominantly based on these imaging findings. While DWI has proven valuable in diagnosing sCJD, its utility in vCJD diagnosis remains unclear. Methods: DWI and Fluid-attenuated inversion recovery (FLAIR) images from probable and definite vCJD cases referred to the National CJD Research and Surveillance Unit (NCJDRSU) were independently analysed by an expert neuroradiologist. Scans were reviewed within a mixed cohort of CJD cases including definite sCJD and non-CJD controls. Results: FLAIR sequences demonstrated greater sensitivity in identifying the pulvinar sign in vCJD compared to DWI (73% vs 41%, p-value <0.001). Basal ganglia hyperintensities were more prevalent in DWI (84%) than FLAIR (64%), and cortical hyperintensities were exclusive to DWI (24%). The pulvinar sign showed a specificity of 98% for vCJD and was rare in sCJD. Conclusion: DWI showed reduced sensitivity compared to FLAIR imaging in detecting the pulvinar sign in vCJD. Conversely, DWI can more distinctively identify basal ganglia and cortical hyperintensities, thus leading to imaging patterns more characteristic of sCJD. Therefore, DWI should be cautiously interpreted in vCJD diagnosis, with axial FLAIR potentially providing a more precise evaluation of the pulvinar sign. [ABSTRACT FROM AUTHOR]

The online version of the original article can be found at https://doi.org/10.1007/s10040-023-02705-7.Correction to: Hydrogeology Journalhttps://doi.org/10.1007/s10040-023-02705-7In Fig. 9 of the original article, the legend incorrectly describes the deformation and saturation components. In the corrected figure, the descriptions have been reversed.The original article has been corrected.Publisher's NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.By M. Lees and R. KnightReported by Author; Author [Extracted from the article]

We prove a conjecture of Reinhold: that a finite lattice is isomorphic to an interval in the lattice of topologies on some set if and only if it is isomorphic to an interval in the lattice of topologies on a finite set. [ABSTRACT FROM AUTHOR]

The planning of IMRT treatments requires a compromise between dose conformity (complexity) and deliverability. This study investigates established and novel treatment complexity metrics for 122 IMRT beams from prostate treatment plans. The Treatment and Dose Assessor software was used to extract the necessary data from exported treatment plan files and calculate the metrics. For most of the metrics, there was strong overlap between the calculated values for plans that passed and failed their quality assurance (QA) tests. However, statistically significant variation between plans that passed and failed QA measurements was found for the established modulation index and for a novel metric describing the proportion of small apertures in each beam. The 'small aperture score' provided threshold values which successfully distinguished deliverable treatment plans from plans that did not pass QA, with a low false negative rate. [ABSTRACT FROM AUTHOR]

Lenalidomide is the approved treatment for patients with red blood cell (RBC) transfusion-dependent lower-risk myelodysplastic syndromes (MDS) and chromosome 5q deletion (del(5q)). We report the long-term outcomes (median follow-up 3.2 years) in patients treated with lenalidomide in the MDS-003 trial. RBC transfusion independence (TI) ≥ 8 weeks was achieved in 97 of 148 treated patients (65.5%), with a median response duration of 2.2 years. Partial or complete cytogenetic response was achieved by 63 of 88 evaluable patients (71.6%). Median overall survival (OS) was longer in patients achieving RBC-TI ≥ 8 weeks (4.3 vs 2.0 years in non-responders; P<0.0001) or cytogenetic response (4.9 vs 3.1 years in non-responders; P=0.010). Time to acute myeloid leukemia (AML) progression was longer in patients achieving RBC-TI ≥ 8 weeks or any cytogenetic response versus non-responders (P=0.001 and P=0.0002, respectively). In a landmark multivariate analysis, RBC-TI ≥ 8 weeks was associated with prolonged OS (P<0.001) and a trend toward reduced relative risk of AML progression (P=0.080). Among these lower-risk MDS patients with del(5q), lenalidomide was associated with prolonged RBC-TI and cytogenetic responses, which were linked to improved OS and reduced risk of AML progression. [ABSTRACT FROM AUTHOR]

Multiple clinical studies have correlated gene expression with survival outcome in cancer on a genome-wide scale. However, in many cases, no obvious correlation between expression of well-known tumour-related genes (that is, p53, p73 and p21) and survival rates of patients has been observed. This can be mainly explained by the complex molecular mechanisms involved in cancer, which mask the clinical relevance of a gene with multiple functions if only gene expression status is considered. As we demonstrate here, in many such cases, the expression of the gene interaction partners (gene 'interactome') correlates significantly with cancer survival and is indicative of the role of that gene in cancer. On the basis of this principle, we have implemented a free online datamining tool (http://www.bioprofiling.de/PPISURV). PPISURV automatically correlates expression of an input gene interactome with survival rates on >40 publicly available clinical expression data sets covering various tumours involving about 8000 patients in total. To derive the query gene interactome, PPISURV employs several public databases including protein-protein interactions, regulatory and signalling pathways and protein post-translational modifications. [ABSTRACT FROM AUTHOR]

ΔNp63 is a transcription factor that is critical for the development of stratified epithelia and is overexpressed or amplified in >80% of squamous cell carcinomas (SCCs). We identified the RING finger E3 ubiquitin ligase PIR2/Rnf144b as a direct transcriptional target of ΔNp63α and showed that its expression parallels that of ΔNp63α in keratinocytes, SCC cell lines and SCCs. We used primary keratinocytes as a model system to investigate the function of PIR2/Rnf144b in stratified epithelia. Depletion of PIR2/Rnf144b severely impaired keratinocyte proliferation and differentiation, associated with accumulation of p21WAF1/CIP1; a known target of PIR2/Rnf144b. More importantly, we found that PIR2/Rnf144b binds and mediates proteasomal degradation of ΔNp63α, generating a hitherto unknown auto-regulatory feedback loop. These findings substantiate PIR2/Rnf144b as a potentially critical component of epithelial homeostasis, acting downstream of ΔNp63α to regulate cellular levels of p21WAF1/CIP1 and ΔNp63α. [ABSTRACT FROM AUTHOR]

Plerixafor augments PBSC collection, but the optimal approach for incorporating it into mobilization is uncertain. Forty-nine consecutive patients mobilized with G-CSF alone were analyzed, and a day 4 peripheral blood CD34+ cell count of 0.015/ml was found to predict for a day 5 apheresis yield of 2 × 106 CD34+ progenitors/kg, our institutional minimum necessary for a single autologous transplant. On the basis of this relationship, a clinical guideline was developed which recommended pre-emptive use of plerixafor if the day 4 peripheral blood CD34+ cell count was between 0.005 and 0.015/ml. A total of 166 consecutive subjects with lymphoma or plasma cell dyscrasias underwent G-CSF mobilization after adoption of this care pathway, and the mobilization failure rate was only 7% in patients managed per guideline. The median PBSC yield was 6.3 × 106 CD34+ progenitors/kg with G-CSF (day 4 peripheral blood CD34+ cell>0.015/ml) and 4.9 × 106 CD34+ progenitors/kg with G-CSF+plerixafor (day 4 peripheral blood CD34+ cell 0.005-0.015/ml). The median number of days of apheresis was 2 in both groups. This clinical guideline is an effective mobilization algorithm that minimizes mobilization failures, reduces poor apheresis yields, does not require risk factor identification and is simple to implement. [ABSTRACT FROM AUTHOR]

Two pivotal, phase III, randomised, placebo-controlled, registration trials (MM-009 and MM-010) showed that lenalidomide plus dexamethasone was more effective than placebo plus dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma. This pooled, retrospective subanalysis of MM-009 and MM-010 analysed outcomes according to patient age. A total of 704 patients (390 aged <65 years, 232 aged 65-74 years, and 82 aged ≥75 years) received lenalidomide or placebo, both in combination with dexamethasone. The overall response rate (ORR) was significantly higher in patients treated with lenalidomide plus dexamethasone versus placebo plus dexamethasone in all age groups (P < 0.0001 for all). Median progression-free survival (PFS) and median time-to-progression (TTP) were similar, and both were significantly longer with lenalidomide plus dexamethasone in all age groups (P < 0.001 for all). Median overall survival (OS) favoured lenalidomide plus dexamethasone in all age groups, although the difference was not statistically significant. Adverse events of anaemia, febrile neutropenia, deep-vein thrombosis, neuropathy, and gastrointestinal disorders increased with age. Lenalidomide combined with dexamethasone improved the ORR and prolonged PFS, TTP, and OS compared with placebo plus dexamethasone, irrespective of age. This finding was consistent with the overall MM-009 and MM-010 populations. [ABSTRACT FROM AUTHOR]

Replication-dependent histone gene expression is a fundamental process occurring in S-phase under the control of the cyclin-E/CDK2 complex. This process is regulated by a number of proteins, including Flice-Associated Huge Protein (FLASH) (CASP8AP2), concentrated in specific nuclear organelles known as HLBs. FLASH regulates both histone gene transcription and mRNA maturation, and its downregulation in vitro results in the depletion of the histone pull and cell-cycle arrest in S-phase. Here we show that the transcription factor p73 binds to FLASH and is part of the complex that regulates histone gene transcription. Moreover, we created a novel gene trap to disrupt FLASH in mice, and we show that homozygous deletion of FLASH results in early embryonic lethality, owing to arrest of FLASH−/− embryos at the morula stage. These results indicate that FLASH is an essential, non-redundant regulator of histone transcription and cell cycle during embryogenesis. [ABSTRACT FROM AUTHOR]

In 2009, the Nomenclature Committee on Cell Death (NCCD) proposed a set of recommendations for the definition of distinct cell death morphologies and for the appropriate use of cell death-related terminology, including 'apoptosis', 'necrosis' and 'mitotic catastrophe'. In view of the substantial progress in the biochemical and genetic exploration of cell death, time has come to switch from morphological to molecular definitions of cell death modalities. Here we propose a functional classification of cell death subroutines that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic apoptosis, regulated necrosis, autophagic cell death and mitotic catastrophe. Moreover, we discuss the utility of expressions indicating additional cell death modalities. On the basis of the new, revised NCCD classification, cell death subroutines are defined by a series of precise, measurable biochemical features. [ABSTRACT FROM AUTHOR]

Purpose: There is increasing concern that environmental chemicals have a direct effect on fertility. Heavy metals such as mercury have been shown to affect various organ systems in humans including nervous system and skin, however they could also act as endocrine disrupting chemicals adversely affecting fertility. Metals such as zinc and selenium are essential micronutrients with diverse functions that may be important for reproductive outcomes. We measured mercury, zinc and selenium levels in the hair, a reliable reflection of long term environmental exposure and dietary status, to correlate with the outcome of ovarian hyperstimulation for in vitro fertilisation (IVF) treatment. Methods: We analysed the hair of 30 subfertile women for mercury, zinc and selenium using inductively coupled mass spectrometry. Each woman underwent one cycle of IVF treatment. Correlation between the levels of these trace metals and treatment outcomes was investigated. Results: Thirty women were recruited with mean (±SD) age of 32.7(4.4) years and BMI of 25.4(5.0)kg/m. Hair mercury concentration showed a negative correlation with oocyte yield ( p < 0.05,βcoefficient 0.38) and follicle number ( p = 0.03,β coefficient0.19) after ovarian stimulation. Zinc and selenium levels in hair correlated positively with oocyte yield after ovarian stimulation ( p < 0.05,β coefficient0.15) and ( p = 0.03,β coefficient0.21) respectively. Selenium levels in hair correlated significantly with follicle number following stimulation ( p = 0.04, βcoefficient0.22). There was no correlation between mercury, zinc and selenium in hair and their corresponding serum levels. Conclusion: These data suggest that mercury had a deleterious effect whilst there was a positive effect for zinc and selenium in the ovarian response to gonadotrophin therapy for IVF. Hair analysis offers a novel method of investigating the impact of long-term exposure to endocrine disruptors and nutritional status on reproductive outcomes. [ABSTRACT FROM AUTHOR]

Eucaryotic cell nuclei contain a number of different organelles that are highly dynamic structures and respond to a variety of stimuli. Here we investigated the effect of UV irradiation on a recently identified group of organelles, Histone Locus Bodies. Histone Locus Bodies contain at least two main proteins, FLASH and NPAT, and have been shown to be involved in replication-dependent histone gene transcription. We show that these organelles are disrupted after sublethal irradiation and both FLASH and NPAT are degraded, which in turn results in cell-cycle arrest at the S/G2 transition. The effect on the cell cycle is due to reduced transcription of histone genes and restoring normal histone protein levels by stabilizing histone mRNA allows cells to progress through the cell cycle. This provides a novel mechanism of S-phase arrest in response to DNA damage that potentially allows DNA repair before cells continue into mitosis, and thus prevents transmission of genomic alterations. [ABSTRACT FROM AUTHOR]

We present a pooled update of two large, multicenter MM-009 and MM-010 placebo-controlled randomized phase III trials that included 704 patients and assessed lenalidomide plus dexamethasone versus dexamethasone plus placebo in patients with relapsed/refractory multiple myeloma (MM). Patients in both studies were randomized to receive 25 mg daily oral lenalidomide or identical placebo, plus 40 mg oral dexamethasone. In this pooled analysis, using data up to unblinding (June 2005 for MM-009 and August 2005 for MM-010), treatment with lenalidomide plus dexamethasone significantly improved overall response (60.6 vs 21.9%, P<0.001), complete response rate (15.0 vs 2.0%, P<0.001), time to progression (median of 13.4 vs 4.6 months, P<0.001) and duration of response (median of 15.8 months vs 7 months, P<0.001) compared with dexamethasone-placebo. At a median follow-up of 48 months for surviving patients, using data up to July 2008, a significant benefit in overall survival (median of 38.0 vs 31.6 months, P=0.045) was retained despite 47.6% of patients who were randomized to dexamethasone-placebo receiving lenalidomide-based treatment after disease progression or study unblinding. Low β2-microglobulin and low bone marrow plasmacytosis were associated with longer survival. In conclusion, these data confirm the significant response and survival benefit with lenalidomide and dexamethasone. [ABSTRACT FROM AUTHOR]

Different types of cell death are often defined by morphological criteria, without a clear reference to precise biochemical mechanisms. The Nomenclature Committee on Cell Death (NCCD) proposes unified criteria for the definition of cell death and of its different morphologies, while formulating several caveats against the misuse of words and concepts that slow down progress in the area of cell death research. Authors, reviewers and editors of scientific periodicals are invited to abandon expressions like ‘percentage apoptosis’ and to replace them with more accurate descriptions of the biochemical and cellular parameters that are actually measured. Moreover, at the present stage, it should be accepted that caspase-independent mechanisms can cooperate with (or substitute for) caspases in the execution of lethal signaling pathways and that ‘autophagic cell death’ is a type of cell death occurring together with (but not necessarily by) autophagic vacuolization. This study details the 2009 recommendations of the NCCD on the use of cell death-related terminology including ‘entosis’, ‘mitotic catastrophe’, ‘necrosis’, ‘necroptosis’ and ‘pyroptosis’.Cell Death and Differentiation (2009) 16, 3–11; doi:10.1038/cdd.2008.150; published online 10 October 2008 [ABSTRACT FROM AUTHOR]

High velocity oxy-fuel (HVOF) combustion spraying has previously been shown to be a viable method for depositing polymer and polymer/ceramic composite coatings. The addition of hard particulate reinforcing phases to soft polymeric matrices should improve their durability and sliding wear performance. Nanosized diamond is an ideal reinforcing phase, owing to its high hardness, low coefficient of friction, and desirable thermal properties. Composite coatings comprising a Nylon-11 matrix reinforced with nanodiamonds have been successfully produced by HVOF. An important challenge is preserving the structure of the nanoparticles after thermal spray deposition and achieving their uniform dispersion within the polymeric matrix. Raman spectroscopy and x-ray diffraction were used to confirm the presence and retention of nanodiamonds after HVOF deposition. Understanding of the role of process parameters, including the content of reinforcing phase in the matrix and powder preparation route is necessary. Nanoindentation studies demonstrated an improvement in creep behavior and recovery of the HVOF Nylon-11/nanodiamond composites subjected to deformation. [ABSTRACT FROM AUTHOR]

The epidermis, the outer layer of the skin composed of keratinocytes, is a stratified epithelium that functions as a barrier to protect the organism from dehydration and external insults. The epidermis develops following the action of the transcription factor p63, amember of the p53 family of transcription factors. The Trp63 gene contains two promoters driving the production of distinct proteins, one with an N-terminal transactivation domain (TAp63) and one without (ΔNp63), although their relative contribution to epidermal development is not clearly established. Trp63 mutations are involved in the pathogenesis of several human diseases, phenotypically characterized by ectodermal dysplasia. In this review, we summarize the current advances that have been made in understanding the role of p63 in epidermal morphogenesis. [ABSTRACT FROM AUTHOR]

The Brn-3a/POU4F1 POU transcription factor is critical for the survival and differentiation of specific sensory neurons during development or upon injury; by regulating expression of target genes, either directly or indirectly upon interaction with other proteins. In this study, we demonstrated the physical interaction of Brn-3a with different p73 isoforms and showed co-localization in sensory neurons arising from the neural crest. The biological effects of p73/ Brn-3a interaction depend on the particular p73 isoform, because co-expression of Brn-3a with TAp73 enhanced cell cycle arrest, whereas Brn-3a and ΔNp73 cooperated to increase protection from apoptosis. Brn-3a antagonized TAp73 transactivation of pro-apoptotic Bax, but co-operated to increase transcription of the cell cycle regulator p21CIP1/Waf1. The region 425–494 amino acids within the TAp73 C terminus were critical for Brn-3a to repress Bax transactivation, but not for cooperation on the p21CIP1/Waf1 promoter. Our results suggest that co-factors binding to the p73 C terminus facilitate maximal activation on the Bax but not p21CIP1/Waf1 promoter and that Brn-3a modulates this interaction. Thus, the physical interaction of Brn-3a with specific p73 isoforms will be critical for determining cell fate during neuronal development or in injured neurons expressing both factors.Cell Death and Differentiation (2008) 15, 1266–1278; doi:10.1038/cdd.2008.45; published online 18 April 2008 [ABSTRACT FROM AUTHOR]

The p73 protein, a member of the p53 family, has both developmental and tumorigenic functions. Here we show that p73 is cleaved by caspase-3 and -8 both in vitro and in vivo during apoptosis elicited by DNA-damaging drugs and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor ligation. TAp73 and some of its cleavage products are localized to mitochondria. siRNA-mediated downregulation of p73 expression induced a small but significant change in the susceptibility of HCT116 cells to TRAIL-induced apoptosis. A transcription-deficient mutant of TAp73 enhanced TRAIL-induced apoptosis suggesting that p73 protein has transcription-independent functions during death receptor-mediated apoptosis. Additionally, recombinant p73 protein induced cytochrome c release from isolated mitochondria providing evidence that nonnuclear p73 may have additional functions in the progression of apoptosis.Oncogene (2008) 27, 4363–4372; doi:10.1038/onc.2008.64; published online 24 March 2008 [ABSTRACT FROM AUTHOR]

The HECT-type E3 ubiquitin ligase (E3) Itch is absent in the non-agouti-lethal 18H or Itchy mice, which develop a severe immunological disease, including lung and stomach inflammation and hyperplasia of lymphoid and hematopoietic cells. The involvement of Itch in multiple signaling pathways and pathological conditions is presently an area of extensive scientific interest. This review aims to bring together a growing body of work exploring Itch-regulated biological processes, and to highlight recent discoveries on the regulatory mechanisms modulating its catalytic activity and substrate recognition capability. Our contribution is also an endeavor to correlate Itch substrate specificity with the pathological defects manifested by the mutant Itchy mice.Cell Death and Differentiation (2008) 15, 1103–1112; doi:10.1038/cdd.2008.60 [ABSTRACT FROM AUTHOR]

The epidermis, the outer layer of the skin composed of keratinocytes, is a stratified epithelium that functions as a barrier to protect the organism from dehydration and external insults. The epidermis develops depending on the transcription factor p63, a member of the p53 family of transcription factors. p63 is strongly expressed in the innermost basal layer where epithelial cells with high clonogenic and proliferative capacity reside. Deletion of p63 in mice results in a dramatic loss of all keratinocytes and loss of stratified epithelia, probably due to a premature proliferative rundown of the stem and transient amplifying cells. Here we report that microRNA (miR)-203 is induced in vitro in primary keratinocytes in parallel with differentiation. We found that miR-203 specifically targets human and mouse p63 3′-UTRs and not SOCS-3, despite bioinformatics alignment between miR-203 and SOCS-3 3′-UTR. We also show that miR-203 overexpression in proliferating keratinocytes is not sufficient to induce full epidermal differentiation in vitro. In addition, we demonstrate that miR-203 is downregulated during the epithelial commitment of embryonic stem cells, and that overexpression of miR-203 in rapidly proliferating human primary keratinocytes significantly reduces their clonogenic capacity. The results suggest that miR-203, by regulating the ΔNp63 expression level, is a key molecule controlling the p63-dependent proliferative potential of epithelial precursor cells both during keratinocyte differentiation and in epithelial development. In addition, we have shown that miR-203 can regulate ΔNp63 levels upon genotoxic damage in head and neck squamous cell carcinoma cells, thus controlling cell survival.Cell Death and Differentiation (2008) 15, 1187–1195; doi:10.1038/cdd.2008.69; published online 16 May 2008 [ABSTRACT FROM AUTHOR]

Polymer and polymer/ceramic composite coatings were produced by ball-milling 60 μm Nylon-11 together with nominal 10 vol.% of nano and multiscale ceramic reinforcements and by HVOF spraying these composite feedstocks onto steel substrates to produce semicrystalline micron and nanoscale reinforced polymer matrix composites. Room temperature dry sliding wear performance of pure Nylon-11, Nylon-11 reinforced with 7 nm silica, and multiscale Nylon-11/silica composite coatings incorporating 7-40 nm and 10 μm ceramic particles were characterized using a pin-on-disk tribometer. Coefficient of friction and wear rate were determined as a function of applied load and coating composition. Surface profilometry and scanning electron microscopy were used to characterize and analyze the coatings and wear scars. The pure Nylon-11 coating experienced less wear than the composites due to the occurrence of two additional wear mechanisms: abrasive and fatigue wear. [ABSTRACT FROM AUTHOR]

The analysis of markers in the cerebrospinal fluid (CSF) is useful in the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). However, the time at which the study of these markers is most sensitive remains controversal. To assess the influence of time of sampling on the value of CSF tests in the diagnosis of sCJD. In the framework of a multinational European study, we studied the results of 14-3-3, S100b, neurone specific enolase (NSE) and tau protein in 833 CSF samples from sCJD patients at different stages of disease and in 66 sequentially repeated lumbar punctures (LP). 14-3-3 and tau protein tended to increase in sensitivity from onset (88%, 81%) to the advanced stage (91%, 90%). This was significant only in the methionine-valine (MV) heterozygous group of patients at codon 129. The absolute levels of S100b (p < 0.05), NSE and tau protein increased in the last stage of disease. High levels of tau protein, NSE and S100b were associated with shorter survival times (p < 0.01). Sixty-six sCJD patients underwent repeated LP. These sCJD patients were younger, had longer disease durations and were more frequently MV at codon 129 (p < 0.001) than the whole group. 14-3-3 sensitivity increased from 64% to 82% in the second LP (p = 0.025) and 88% sCJD patients had at least one positive result. Sensitivity and absolute levels of CJD markers increased with disease progression and were modulated by the codon 129 genotype. Early negative results should be inter-preted with caution, especially in young patients or those who are MV at codon 129. [ABSTRACT FROM AUTHOR]

A three-dimensional model of particle splatting on rough surfaces has been developed for high-velocity oxyfuel (HVOF) sprayed polymer particles and related to experimentally observed polymer splats. Fluid flow and particle deformation were predicted using a volume of fluid (VoF) method using Flow-3D software. Splatting behavior and final splat shapes were simulated on a realistic rough surface, generated by optical interferometry of an actual grit-blasted steel surface. Predicted splat shapes were compared with scanning electron microscopy images of nylon 11 splats deposited onto grit-blasted steel substrates. Rough substrates led to the formation of fingers and other asymmetric three-dimensional instabilities that are seldom observed in simulations of polymer splatting on smooth substrates. [ABSTRACT FROM AUTHOR]

The high-velocity oxyfuel (HVOF) combustion spraying of dry ball-milled nylon-11/ceramic composite powders is an effective, economical, and environmentally sound method for producing semicrystalline micron and nanoscale reinforced polymer coatings. Composite coatings reinforced with multiple scales of ceramic particulate material are expected to exhibit improved load transfer between the reinforcing phase and the matrix due to interactions between large and small ceramic particles. An important step in developing multiscale composite coatings and load transfer theory is determining the effect of reinforcement size on the distribution of the reinforcement and the properties of the composite coating. Composite feedstock powders were produced by dry ball-milling nylon-11 together with 7, 20, and 40 nm fumed silica particles, 50 and 150 nm fumed alumina particles, and 350 nm, 1, 2, 5, 10, 20, 25, and 50 µm white calcined alumina at 10 vol.% overall ceramic phase loadings. The effectiveness of the ball-milling process as a function of reinforcement size was qualitatively evaluated by scanning electron microscopy+energy dispersive x-ray spectroscopy (SEM+EDS) microanalysis and by characterizing the behavior of the powder during HVOF spraying. The microstructures of the sprayed coatings were characterized by optical microscopy, SEM, EDS, and x-ray diffraction (XRD). The reinforcement particles were found to be concentrated at the splat boundaries in the coatings, forming a series of interconnected lamellar sheets with good three-dimensional distribution. The scratch resistance of the coatings improved consistently and logarithmically as a function of decreasing reinforcement size and compared with those of HVOF sprayed pure nylon-11. [ABSTRACT FROM AUTHOR]

Epidermal development requires the transcription factor p63, as p63−/− mice are born dead, without skin. The gene expresses two proteins, one with an amino-terminal transactivation domain (TAp63) and one without (ΔNp63), although their relative contribution to epidermal development is unknown. To address this issue, we reintroduced TAp63α and/or ΔNp63α under the K5 promoter into p63−/− mice by in vivo genetic complementation. Whereas p63−/− and p63−/−;TA mice showed extremely rare patches of poorly differentiated keratinocytes, p63−/−;ΔN mice showed significant epidermal basal layer formation. Double TAp63α/ΔNp63α complementation showed greater patches of differentiated skin; at the ultrastructural level, there was clear reformation of a distinct basal membrane and hemidesmosomes. At the molecular level, ΔNp63 regulated expression of genes characteristic of the basal layer (K14), interacting (by Chip, luc assay) with the third p53 consensus site. Conversely, TAp63 transcribed the upper layer's genes (Ets-1, K1, transglutaminases, involucrin). Therefore, the two p63 isoforms appear to play distinct cooperative roles in epidermal formation.Cell Death and Differentiation (2006) 13, 1037–1047. doi:10.1038/sj.cdd.4401926; published online 7 April 2006 [ABSTRACT FROM AUTHOR]

DJ-1 is a multifunctional protein that plays roles in transcriptional regulation and antioxidative stress, and loss of its function is thought to result in the onset of Parkinson's disease (PD). Here, we report that DJ-1 was sumoylated on a lysine residue at amino-acid number 130 (K130) by PIASxα or PIASy. The K130 mutation abrogated all of the functions of DJ-1, including ras-dependent transformation, cell growth promotion and anti-UV-induced apoptosis activities. Sumoylation of DJ-1 was increased after UV irradiation concomitant with a pI shift to an acidic point of DJ-1. Furthermore, L166P, a mutant DJ-1 found in PD patients, and K130RX, an artificial mutant containing four mutations in DJ-1, were improperly sumoylated, and they became insoluble, partly localized in the mitochondria and degraded by the proteasome system. Both L166P-expressing cells and DJ-1-knockdown cells were found to be highly susceptible to UV-induced cell apoptosis.Cell Death and Differentiation (2006) 13, 96–108. doi:10.1038/sj.cdd.4401704; published online 24 June 2005 [ABSTRACT FROM AUTHOR]

Discusses the many different models of cell death. Number of different mechanisms of programmed cell death exist; Role of caspases in apoptosis by cleaving a large number of substrates; Summary of the similarities and differences between cornification and apoptosis; Importance of interaction with the extracellular matrix through integrins.

Reports on the proposal of a unified criteria for the definition of cell death and of different cell death morphologies by the Nomenclature Committee on Cell Death (NDCC). Suggestion of NDCC that it is important to discriminate between dying as a process and death as an endpoint; Definition of different cell death types by morphological criteria without a clear reference to precise biochemical mechanisms; Form of death occurring in neurons when excitatory aminoacids.

High-velocity oxyfuel (HVOF) sprayed polyimide/WC-Co functionally graded (FGM) coatings with flame-sprayed WC-Co topcoats have been investigated as solutions to improve the solid-particle erosion and oxidation resistance of polymer matrix composites (PMCs) in the gas flow path of advanced turbine engines. Porosity, coating thickness, and volume fraction of the WC-Co phase retained in the graded coating architecture were determined using standard metallographic techniques and computer image analysis. The adhesive bond strength of three different types of coatings was evaluated according to ASTM D 4541. Adhesive/cohesive strengths of the FGM coating were measured and compared with those of pure polyimide and polyimide/WC-Co composite coatings and also related to the tensile strength of the uncoated PMC substrate perpendicular to the thickness. The FGM coatings exhibited lower adhesive bond strengths (∼6.2 MPa) than pure polyimide coatings (∼8.4 MPa), and in all cases these values were lower than the tensile strength (∼17.6 MPa) of the reference uncoated PMC substrate. The nature and locus of the failures were characterized according to the percent adhesive and/or cohesive failure, and the interfaces tested and layers involved were analyzed by scanning electron microscopy. [ABSTRACT FROM AUTHOR]

Yonelinas et al. (2002) found that hypoxic patients exhibited deficits in recollection that left familiarity relatively unaffected. In contrast, Manns, Hopkins, Reed, Kitchener, and Squire (2003) studied a group of hypoxic patients who suffered severe and equivalent deficits in recollection and familiarity. We reexamine those studies and argue that the discrepancy in results is likely due to differences in the hypoxic groups that were tested (i.e., differences in amnestic severity, subject sampling methods, and patient etiology). Yonelinas et al. examined memory in 56 cardiac arrest patients who suffered a brief hypoxic event, whereas Manns et al. examined a group of severely amnesic patients that consisted of 2 cardiac arrest patients, 2 heroin overdose patients, 1 carbon monoxide poisoning patient, and 2 patients with unknown etiologies. We also consider an alternative explanation proposed by Wixted and Squire (2004), who argued that the two patient groups suffered similar deficits, but that statistical or methodological artifacts distorted the results of each of Yonelinas et al.'s experiments. A consideration of those results, however, indicates that such an explanation does not account for the existing data. All of the existing evidence indicates that recollection, but not familiarity, is disrupted in mild hypoxic patients. In more severe cases of hypoxia, or those with more complex etiologies such as heroin overdose, more profound deficits may be observed. [ABSTRACT FROM AUTHOR]

Explicitly defining large-scale heterogeneity is a necessary step of groundwater model calibration if accurate estimates of flow and transport are to be made. In this work, neural networks are used to estimate radar facies probabilities from ground penetrating radar (GPR) images, yielding stochastic facies-based models that honour the large-scale architecture of the subsurface. For synthetic GPR images, a neural network was able to correctly identify radar facies with an accuracy of approximately 90%. Manual interpretation of a set of 450 MHz GPR field data from the Borden aquifer resulted in the identification of four radar facies. Of these, a neural network was able to identify two facies with an accuracy of near 80% and one with an accuracy of 44%. The neural network was not able to identify the fourth facies, likely due to the choice of defining facies characteristics. Sequential indicator simulation was used to generate facies realizations conditioned to the radar facies probabilities. Numerical simulations indicate that significant improvements in the prediction of solute transport are possible when GPR is used to constrain the facies model compared to using well data alone, especially when data are sparse. [ABSTRACT FROM AUTHOR]

Objective: Sensory symptoms are a prominent feature of variant Creutzfeldt-Jakob disease (vCJD), occurring at an early stage of the illness. They are persistent and can be troublesome. Here, they are described in detail and a possible anatomical basis is discussed. Methods: The first 50 cases of vCJD confirmed by the National CJD Surveillance Unit (NCJDSU) were reviewed. Where possible the patients and their relatives were interviewed and case notes were examined. The presence and nature of sensory symptoms and signs were noted. Results of investigation and types of treatment offered were also reviewed. Results: Of 50 definite cases, 64 % had persistent sensory symptoms, 16 % had no sensory symptoms and 18 % were uncertain. In 2 % there was insufficient information. Of the 32 with definite symptoms, 31 % were symptomatic from the onset of the illness. The symptoms were varied and some patients complained of more than one type of symptom. Limb pain was described in 63 % cases. This was the most common symptom and was often non-specific and poorly localised, usually occurring in the lower limbs. Other symptoms included cold feelings (25 % patients), dysaesthesia (28 % patients), paraesthesia (31 % patients) and numbness (25 % patients). The symptoms were lateralised in 31 % of patients. Conclusions: Sensory symptoms are a prominent feature of vCJD, occurring in nearly two thirds of cases. They may help distinguish variant from sporadic CJD. They are likely to be of thalamic origin but the recognised MRI changes in vCJD do not correlate with the presence or absence of sensory symptoms. Neuropathological changes in the thalamus, however, show marked astrocytosis and neuronal loss. [ABSTRACT FROM AUTHOR]

Defective acidification of intracellular organelles, particularly the trans-Golgi network, has been proposed to explain the decreased sialylation and increased sulphation of secreted proteins in cystic fibrosis (CF). To test this hypothesis we compared expression of sulphate and sialic acid on three salivary mucins namely MG1 (MUC-5B), MG2 (MUC-7) and GL. Proteins in whole mouth saliva (WMS) from four individuals were separated by fast protein liquid chromatography (FPLC) on a Superdex 200 column and the partially purified mucins slot-blotted and assayed for sulphate content by staining with Alcian Blue. Sulphation varied with the individual and with the mucin: MG1 was the most sulphated and contributed almost the entire sulphate content of WMS. These results allowed us to test small volumes of WMS from 20 CF patients and age- and sex-matched controls for estimates of sulphate content on MG1. Wherever possible sulphate on MG1 was also visualised by staining washed SDS-PAGE gels with Alcian Blue at pH 1.0. To assess the sialic acid content of salivary mucins, electroblots of SDS-PAGE gels were probed with labelled Triticum vulgaris agglutinin. In summary, our results show MG1 to be the main sulphated protein in whole mouth saliva and there are large differences in the expression of sulphate and of sialic acid on this mucin, both in control and CF groups. CF led neither a decrease in sialylation nor an increase in sulphation and direct comparisons of sialic acid content with sulphate in MG1 failed to reveal any obvious link between the two in health or in disease. Our data thus do not support the hypothesis of defective acidification as the underlying cause of altered glycosylation in CF, but point instead to inter-individual differences in expression/functioning of terminal glycosyltransferases for published observations. We thank the European Union Biomed II programme for support. [ABSTRACT FROM AUTHOR]

Destruction of the lungs as a consequence of recurrent infections with microorganisms such as Pseudomonas aeruginosa remains the underlying cause of most morbidity and mortality in cystic fibrosis (CF). We have hypothesized that changes in the glycosylation of key tracheal mucins such as MUC5B and MUC7 might increase the risk of pulmonary disease in CF patients. However, in preference to sputum we have examined the sugar-chains on these mucins in saliva because in the latter not only can the glycoproteins be collected from controls, but they are essentially free from modifications made following bacterial infection in disease. Proteins in ductal or whole-mouth saliva from 20 CF patients with the ΔF-508 CFTR mutation and age-and sex-matched controls were separated by SDS-PAGE and blotted onto nitrocellulose and then probed with labelled lectins of known specificity. Linkage of terminal sialic acid on the blotted mucins was determined using Sambucus nigra agglutinin (detects the 2→6 linkage) and Maackia amurensis agglutinin (the 2→3 linkage). Fucose was detected by Ulex europaeus agglutinin-1 (1→2 linkage) and Aleuria aurantia agglutinin (1→3 linkage). We found that each mucin shows a characteristic glycosylation pattern and in controls most of the sialic acid is 2→6 linked on MG1 (MUC 5B) and 2→3 linked on MG2 (MUC 7). CF is associated with a shift from a 2→6 linkage to a 2→3 linkage on MG1 with some patients showing almost no 2→6 linkage; 2→3 linkage on MG2 is similarly increased in disease in some individuals. The expression of fucose on these mucins is also raised in CF patients. These shift to a 2→3 linkage of sialic acid, and with increased fucosylation this promotes the formation of sialyl-Lewis X antigen detected on CF mucins in our study. These changes will be tested for their correlation with the severity of lung disease. We gratefully acknowledge support from the European Union Biomed-II Programme. [ABSTRACT FROM AUTHOR]

The distribution of high grade prostate intraepithelial neoplasia (PIN) and cancer was analysed in 18 separate areas from 89 radical prostatectomy specimens that had been sectioned and digitally imaged. When the occurrence of each type of pathology was summated a predilection was demonstrated for both pathologies in the apex of the prostate and a linear relationship was found between the frequency of cancer and high grade PIN (r2=0.744, P<0.05). This relationship was strongest at the apex (r2=0.621, P<0.005), lower in the midgland (r2=0.828, P<0.05) and bordered on significance at the base (r2=0.621, P<0.063). These results support the theory that cancer could obliterate high grade PIN as it over grows the areas once occupied by PIN.Prostate Cancer and Prostatic Diseases (2001) 4, 97–100 [ABSTRACT FROM AUTHOR]

Previous research has linked adult sex offending behavior to a multiplicity of variables, including juvenile delinquency and the experience of childhood abuse. The purpose of this study was to explore developmental pathways among childhood abuse, juvenile delinquency, and personality dimensions possibly conducive to adolescent sexual coercion. Using a retrospective self-report inventory, we measured the extent to which juvenile sexual offenders experienced childhood trauma, engaged in adolescent delinquency, and exhibited particular dispositions and cognitive biases. The effects of childhood and adolescent antecedents on sexual coerciveness were then analyzed through simultaneous multiple regression path analyses. Results suggest that sexual compulsivity and hypermasculinity, through misogynistic fantasy behavior, significantly discriminate verbally and physically coercive juvenile offenders from those offenders who do not report using force in their offenses. Results also suggest that alcohol abuse may play a more salient role in the expression of coercive juvenile sexual coercion than previously hypothesized. [ABSTRACT FROM AUTHOR]

The genetics of resistance to Ascochyta blight ( Ascochyta fabae f. sp. fabae) was studied in two populations of faba bean ( Vicia faba). Plants of a resistant population, ILB 752, and a susceptible one, NEB 463, were screened for their reaction to the pathogen and the results were quantified on a scale of 0–5. Crosses were made between plants both within and between accessions and the F1 and F2 generations assessed in a field trial 21 and 45 days after inoculation. Disease scores were greater at 45 days than at 21 days and they were not significantly affected by the presence of susceptible spreader rows in part of the trial. ILB 752 carried a major dominant gene conferring resistance while NEB 463 carried the recessive allele for susceptibility. Furthermore, a minority of plants of NEB 463 appeared to carry at least one pair of complementary recessive genes, also conferring resistance. Most of the plants of ILB 752 were homozygous for the dominant resistance gene and a few were heterozygous. Reciprocal crosses behaved identically, indicating the absence of maternal effects in the expression of Ascochyta blight resistance in faba beans. The results show that it is important to confirm the level of heterozygosity for the resistance genes in this partially outbreeding species before crossing is commenced. The major dominant gene for resistance, identified in ILB 752, has clear potential for use in breeding for Ascochyta blight resistance. The minor genes identified in NEB 463 also show the potential for accumulating resistance through mass selection. [ABSTRACT FROM AUTHOR]

A significant, valuable percentage of today's municipal solid wastestream consists of polymeric materials, for which almost no economicrecycling technology currently exists. This polymeric waste is incinerated,landfilled, or recycled via downgraded usage. Thermal plasma treatment is apotentially viable means of recycling these materials by converting themback into monomers or into other useful compounds. The technical, laboratoryscale, feasibility of using an induction-coupled RF plasma (ICP) heatedreactor for this purpose has been demonstrated in the presentstudy. Polyethylene powder was injected axially through the center of anICP torch. Results from the initial set of experiments, analyzed using astatistical design of experiment technique, showed that plasma plate power,central gas flow rate, probe gas flow rate, powder feed rate, and theinteraction between the quench gas flow rate and power input were the keyprocess parameters affecting the yield of ethylene in the product gasstream. The gaseous products obtained were mainly mixtures of ethylene andpropylene. The amount of propylene obtained was significantly higher thananticipated and was believed to be due to β-scission reactionsoccurring at the higher plasma temperatures. [ABSTRACT FROM AUTHOR]

The technical feasibility of using an induction-coupled plasma (ICP) torch to synthesize ozone at atmospheric pressure is explored. Ozone concentrations up to ~250 ppm were achieved using a thermal plasma reactor system based on an ICP torch operating at 2.5 MHz and ~11 kVA with an argon/oxygen mixture as the plasma-forming gas. The corresponding production rate and yield were ~20 g ozone/hr and ~2g ozone/kWh, respectively. A gaseous oxygen quench formed ozone by rapid mixing of molecular oxygen with atomic oxygen produced by the torch. The ozone concentration in the reaction chamber was measured by Fourier Transform infrared (FTIR) spectroscopy over a wide range of experimental conditions and configurations. The geometry of the quench gas flow, the quench flow velocity, and the quench flow rate played important roles in determining the ozone concentration. The ozone concentration was sensitive to the torch RF power, but was insensitive to the torch gas flow rates. These observations are interpreted within the framework of a simple model of ozone synthesis. [ABSTRACT FROM AUTHOR]

Systemic malignant lymphoma rarely produces solitary metastasis to the brain. We report such a case in the cerebellopontine (CP) angle mimicking an acoustic neurinoma. CT scan showed a large, round mass in the CP angle which enhanced homogeneously following contrast infusion. The internal auditory meatus appeared to be eroded. The clinical, radiological, and pathological findings are presented. [ABSTRACT FROM AUTHOR]

Twenty-five accessions of mango were examined for random amplified polymorphic DNA (RAPD) genetic markers with 80 10-mer random primers. Of the 80 primers screened, 33 did not amplify, 19 were monomorphic, and 28 gave reproducible, polymorphic DNA amplification patterns. Eleven primers were selected from the 28 for the study. The number of bands generated was primer- and genotype-dependent, and ranged from 1 to 10. No primer gave unique banding patterns for each of the 25 accessions; however, ten different combinations of 2 primer banding patterns produced unique fingerprints for each accession. A maternal half-sib (MHS) family was included among the 25 accessions to see if genetic relationships could be detected. RAPD data were used to generate simple matching coefficients, which were analyzed phenetically and by means of principal coordinate analysis (PCA). The MHS clustered together in both the phenetic and the PCA while the randomly selected accessions were scattered with no apparent pattern. The uses of RAPD analysis for Mangifera germ plasm classification and clonal identification are discussed. [ABSTRACT FROM AUTHOR]

The effects of β-adrenergic receptor antagonists on psychometric tests including vehicle handling, choice reaction time, and kinetic visual acuity (KVA), are reviewed. The β-Blockers had little effect on the performance tests, with the unexplained but reproducible effect of enhanced KVA performance with atenolol. Although the β-Blockers had little effect on performance tests they were shown to have psychotropic effects in normal volunteers. The reasons for the conflicting evidence concerning the effect of these drugs on performance tests is discussed in relation to the present experiments and to variables that may influence response. It is concluded that one should use tests that are as independent as possible from potentially confounding variables. The use of evoked potentials in the electroencephalogram is one such test. A preliminary study is described in which the effects of β-Blockers were detected using visual evoked responses on the electroencephalogram. [ABSTRACT FROM AUTHOR]

The stratigraphy, tectonic history, petrography and major oxide petrochemistry of the volcanic sequences in the western part of the rift valley in southern Kenya is summarised. Volcanism and rift faulting began 15 and 7 m.y. ago respectively. A recurrent feature of Miocene and Pliocene volcanism was the tendency for salic magmas to be preferentially erupted in the northern part of the area: the accumulation of a northward-thickening Pliocene trachyte pile is particularly notable. Transitional-mildly alkalic basalts and trachytes were erupted only after the onset of rift faulting, from sites within the rift structure, and so can be considered «rift dependent». Nephelinites, melanephelinites, limburgites and phonolites were erupted before and after onset of rift faulting, from sites within and outside the rift structure, and so can be considered «rift independent». [ABSTRACT FROM AUTHOR]