164 research outputs found
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Calculation of airborne radioactivity hazard from machining volume-activated materials
When evaluating a task involving the machining of volume-activated materials, accelerator health physicists must consider more than the surface contamination levels of the equipment and containment of loose shavings, dust or filings. Machining operations such as sawing, routing, welding, and grinding conducted on volume-activated material may pose a significant airborne radioactivity hazard to the worker. This paper presents a computer spreadsheet notebook that conservatively estimates the airborne radioactivity levels generated during machining operations performed on volume-activated materials. By knowing (1) the size and type of materials, (2) the dose rate at a given distances, and (3) limited process knowledge, the Derived Air Concentration (DAC) fraction can be estimated. This tool is flexible, taking into consideration that the process knowledge available for the different materials varies. It addresses the two most common geometries: thick plane and circular cylinder. Once the DAC fraction has been estimated, controls can be implemented to mitigate the hazard to the worker
Submitted ta Health Physics Society
Abstract When evaluating a task involving the machining of volume-activated materials, accelerator health physicists must consider more than the surface contamination levels of the equipment and containment of loose shavings, dust or filings. Machining operations such as sawing, routing, welding, and grinding conducted on volume-activated material may pose a significant airborne radioactivity hazard to the worker. This paper presents a computer spreadsheet notebook that conservatively estimates the airborne radioactivity levels generated during machining operations performed on volume-activated materials. By knowing (1) the size and type of materials, (2) the dose rate at a given distances, and (3) limited process knowledge, the Derived Air Concentration (DAC) fraction can be estimated. This tool is flexible, taking into consideration that the process knowledge available for the different materials varies. It addresses the two most common geometries: thick plane and circular cylinder. Once the DAC fraction has been estimated, controls can be implemented to mitigate the hazard to the worker
Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations
Objective: The phenotype associated with heterozygous HNF4A gene mutations has recently been extended to include diazoxide responsive neonatal hypoglycemia in addition to maturity-onset diabetes of the young (MODY). To date, mutation screening has been limited to patients with a family history consistent with MODY. In this study, we investigated the prevalence of HNF4A mutations in a large cohort of patients with diazoxide responsive hyperinsulinemic hypoglycemia (HH).
Subjects and methods: We sequenced the ABCC8, KCNJ11, GCK, GLUD1, and/or HNF4A genes in 220 patients with HH responsive to diazoxide. The order of genetic testing was dependent upon the clinical phenotype.
Results: A genetic diagnosis was possible for 59/220 (27%) patients. KATP channel mutations were most common (15%) followed by GLUD1 mutations causing hyperinsulinism with hyperammonemia (5.9%), and HNF4A mutations (5%). Seven of the 11 probands with a heterozygous HNF4A mutation did not have a parent affected with diabetes, and four de novo mutations were confirmed. These patients were diagnosed with HI within the first week of life (median age 1 day), and they had increased birth weight (median +2.4 SDS). The duration of diazoxide treatment ranged from 3 months to ongoing at 8 years.
Conclusions: In this large series, HNF4A mutations are the third most common cause of diazoxide responsive HH. We recommend that HNF4A sequencing is considered in all patients with diazoxide responsive HH diagnosed in the first week of life irrespective of a family history of diabetes, once KATP channel mutations have been excluded
Bulk and Boundary Critical Behavior at Lifshitz Points
Lifshitz points are multicritical points at which a disordered phase, a
homogeneous ordered phase, and a modulated ordered phase meet. Their bulk
universality classes are described by natural generalizations of the standard
model. Analyzing these models systematically via modern
field-theoretic renormalization group methods has been a long-standing
challenge ever since their introduction in the middle of the 1970s. We survey
the recent progress made in this direction, discussing results obtained via
dimensionality expansions, how they compare with Monte Carlo results, and open
problems. These advances opened the way towards systematic studies of boundary
critical behavior at -axial Lifshitz points. The possible boundary critical
behavior depends on whether the surface plane is perpendicular to one of the
modulation axes or parallel to all of them. We show that the semi-infinite
field theories representing the corresponding surface universality classes in
these two cases of perpendicular and parallel surface orientation differ
crucially in their Hamiltonian's boundary terms and the implied boundary
conditions, and explain recent results along with our current understanding of
this matter.Comment: Invited contribution to STATPHYS 22, to be published in the
Proceedings of the 22nd International Conference on Statistical Physics
(STATPHYS 22) of the International Union of Pure and Applied Physics (IUPAP),
4--9 July 2004, Bangalore, Indi
A high activity index of stearoyl-CoA desaturase is associated with increased risk of fracture in men
Idiopathic Male Infertility Is Strongly Associated with Aberrant Promoter Methylation of Methylenetetrahydrofolate Reductase (MTHFR)
Abnormal germline DNA methylation in males has been proposed as a possible mechanism compromising spermatogenesis of some men currently diagnosed with idiopathic infertility. Previous studies have been focused on imprinted genes with DNA methylation in poor quality human sperms. However, recent but limited data have revealed that sperm methylation abnormalities may involve large numbers of genes or shown that genes that are not imprinted are also affected.Using the methylation-specific polymerase chain reaction and bisulfite sequencing method, we examined methylation patterns of the promoter of methylenetetrahydrofolate reductase (MTHFR) gene (NG_013351: 1538-1719) in sperm DNA obtained from 94 idiopathic infertile men and 54 normal fertile controls. Subjects with idiopathic infertility were further divided into groups of normozoospermia and oligozoospermia. Overall, 45% (41/94) of idiopathic infertile males had MTHFR hypermethylation (both hemimethylation and full methylation), compared with 15% of fertile controls (P<0.05). Subjects with higher methylation level of MTHFR were more likely to have idiopathic male infertility (P-value for trend = 0.0007). Comparing the two groups of idiopathic infertile subjects with different sperm concentrations, a higher methylation pattern was found in the group with oligozoospermia.Hypermethylation of the promoter of MTHFR gene in sperms is associated with idiopathic male infertility. The functional relevance of hypermathylation of MTHFR to male fertility warrants further investigation
Restoring assembly and activity of cystathionine β-synthase mutants by ligands and chemical chaperones
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An update on vitamin B12-related gene polymorphisms and B12 status.
Vitamin B12 is an essential micronutrient in humans needed for health maintenance. Deficiency of vitamin B12 has been linked to dietary, environmental and genetic factors. Evidence for the genetic basis of vitamin B12 status is poorly understood. However, advancements in genomic techniques have increased the knowledge-base of the genetics of vitamin B12 status. Based on the candidate gene and genome-wide association (GWA) studies, associations between genetic loci in several genes involved in vitamin B12 metabolism have been identified. The objective of this literature review was to identify and discuss reports of associations between single-nucleotide polymorphisms (SNPs) in vitamin B12 pathway genes and their influence on the circulating levels of vitamin B12. Relevant articles were obtained through a literature search on PubMed through to May 2017. An article was included if it examined an association of a SNP with serum or plasma vitamin B12 concentration. Beta coefficients and odds ratios were used to describe the strength of an association, and a < 0.05 was considered as statistically significant. Two reviewers independently evaluated the eligibility for the inclusion criteria and extracted the data. From 23 studies which fulfilled the selection criteria, 16 studies identified SNPs that showed statistically significant associations with vitamin B12 concentrations. Fifty-nine vitamin B12-related gene polymorphisms associated with vitamin B12 status were identified in total, from the following populations: African American, Brazilian, Canadian, Chinese, Danish, English, European ancestry, Icelandic, Indian, Italian, Latino, Northern Irish, Portuguese and residents of the USA. Overall, the data analyzed suggests that ethnic-specific associations are involved in the genetic determination of vitamin B12 concentrations. However, despite recent success in genetic studies, the majority of identified genes that could explain variation in vitamin B12 concentrations were from Caucasian populations. Further research utilizing larger sample sizes of non-Caucasian populations is necessary in order to better understand these ethnic-specific associations
Tissue distribution and differential expression of melanocortin 1 receptor, a malignant melanoma marker
The melanocortin 1 receptor is a G-protein-coupled receptor, described to be expressed on melanomas and melanocytes. Subsequent RT–PCR studies demonstrated the presence of melanocortin 1 receptor mRNA in other tissues such as pituitary gland and testis. Previously, we have demonstrated that three HLA-A2 binding nonamer peptides derived from melanocortin 1 receptor can elicit peptide-specific CTL which can recognize target cells transfected with the melanocortin 1 receptor gene and MHC class I matched melanoma lines. The potential of targeting melanocortin 1 receptor in therapy and diagnosis will depend on a preferential expression of this receptor in the majority of primary and metastatic melanomas vs normal tissues. We tested a panel of melanomas, carcinomas and other cell lines for the presence of melanocortin 1 receptor, using two monoclonal antibodies. The receptor was detected in 83% of the tested melanoma cell lines but not in other carcinoma lines. Immunohistochemistry revealed a strong expression of melanocortin 1 receptor in all tested primary and metastatic melanomas, but also demonstrated low levels of expression in adrenal medulla, cerebellum, liver and keratinocytes. Flow cytometry studies showed that melanocortin 1 receptor was expressed in in vitro activated monocytes/macrophages and in the THP-1 monocytic leukaemia line at levels of about 1 in 3 to 1 in 5 of that found in melanomas. Peripheral blood-derived dendritic cells, also express melanocortin 1 receptor in vitro. This extensive analysis of melanocortin 1 receptor tissue distribution may be of relevance not only for melanoma immunology, but also for research on the pathogenicity of inflammatory conditions in the skin and neurologic tissues. It remains to be seen if the over-expression of melanocortin 1 receptor in melanomas is sufficiently high to allow a ‘therapeutic window’ to be exploited in cancer immunotherapy
Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency
BACKGROUND: Remethylation defects are rare inherited disorders in which impaired remethylation of homocysteine to methionine leads to accumulation of homocysteine and perturbation of numerous methylation reactions.
OBJECTIVE: To summarise clinical and biochemical characteristics of these severe disorders and to provide guidelines on diagnosis and management.
DATA SOURCES: Review, evaluation and discussion of the medical literature (Medline, Cochrane databases) by a panel of experts on these rare diseases following the GRADE approach.
KEY RECOMMENDATIONS: We strongly recommend measuring plasma total homocysteine in any patient presenting with the combination of neurological and/or visual and/or haematological symptoms, subacute spinal cord degeneration, atypical haemolytic uraemic syndrome or unexplained vascular thrombosis. We strongly recommend to initiate treatment with parenteral hydroxocobalamin without delay in any suspected remethylation disorder; it significantly improves survival and incidence of severe complications. We strongly recommend betaine treatment in individuals with MTHFR deficiency; it improves the outcome and prevents disease when given early
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