The reduced expression of the HADH2 protein causes X-linked mental retardation, choreoathetosis, and abnormal behavior

Recently, we defined a new syndromic form of X-linked mental retardation in a 4-generation family with a unique clinical phenotype characterized by mild mental retardation, choreoathetosis, and abnormal behavior (MRXS10). Linkage analysis in this family revealed a candidate region of 13.4 Mb between markers DXS1201 and DXS991 on Xp11; therefore, mutation analysis was performed by direct sequencing in most of the 135 annotated genes located in the region. The gene (HADH2) encoding L-3-hydroxyacyl-CoA dehydrogenase II displayed a sequence alteration (c.574 C-->A; p.R192R) in all patients and carrier females that was absent in unaffected male family members and could not be found in 2,500 control X chromosomes, including in those of 500 healthy males. The silent C-->A substitution is located in exon 5 and was shown by western blot to reduce the amount of HADH2 protein by 60%-70% in the patient. Quantitative in vivo and in vitro expression studies revealed a ratio of splicing transcript amounts different from those normally seen in controls. Apparently, the reduced expression of the wild-type fragment, which results in the decreased protein expression, rather than the increased amount of aberrant splicing fragments of the HADH2 gene, is pathogenic. Our data therefore strongly suggest that reduced expression of the HADH2 protein causes MRXS10, a phenotype different from that caused by 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency, which is a neurodegenerative disorder caused by missense mutations in this multifunctional protein.

Advances in population surveillance for physical activity and sedentary behavior : reliability and validity of time use surveys

Many countries conduct regular national time use surveys, some of which date back as far as the 1960s. Time use surveys potentially provide more detailed and accurate national estimates of the prevalence of sedentary and physical activity behavior than more traditional self-report surveillance systems. In this study, the authors determined the reliability and validity of time use surveys for assessing sedentary and physical activity behavior. In 2006 and 2007, participants (n = 134) were recruited from work sites in the Australian state of New South Wales. Participants completed a 2-day time use diary twice, 7 days apart, and wore an accelerometer. The 2 diaries were compared for test-retest reliability, and comparison with the accelerometer determined concurrent validity. Participants with similar activity patterns during the 2 diary periods showed reliability intraclass correlations of 0.74 and 0.73 for nonoccupational sedentary behavior and moderate/vigorous physical activity, respectively. Comparison of the diary with the accelerometer showed Spearman correlations of 0.57-0.59 and 0.45-0.69 for nonoccupational sedentary behavior and moderate/vigorous physical activity, respectively. Time use surveys appear to be more valid for population surveillance of nonoccupational sedentary behavior and health-enhancing physical activity than more traditional surveillance systems. National time use surveys could be used to retrospectively study nonoccupational sedentary and physical activity behavior over the past 5 decades.

An MRI study of pituitary volume and parasuicidal behavior in teenagers with first-presentation borderline personality disorder

This structural magnetic resonance imaging study examined the relationship between pituitary gland volume (PGV) and lifetime number of parasuicidal behaviors in a first-presentation, teenage borderline personality disorder (BPD) sample with minimal exposure to treatment. Hierarchical regression analysis revealed that age and number of parasuicidal behaviors were significant predictors of PGV. These findings indicate that parasuicidal behavior in BPD might be associated with greater activation of the hypothalamic-pituitary-adrenal (HPA) axis. Further studies are required using direct neuroendocrine measures and exploring other parameters of self-injurious behavior, such as recency of self-injurious behavior, intent to die and medical threat.

Ratcheting and wear behavior of Australian rail steel: Experimental investigation of material properties and sampling method

To The ratcheting behavior of high-strength rail steel (Australian Standard AS1085.1) is studied in this work for the purpose of predicting wear and damage to the rail surface. Historically, researchers have used circular test coupons obtained from the rail head to conduct cyclic load tests, but according to hardness profile data, considerable variation exists across the rail head section. For example, the induction-hardened rail (AS1085.1) shows high hardness (400-430 HV100) up to four-millimeters into the rail head’s surface, but then drops considerably beyond that. Given that cyclic test coupons five millimeters in diameter at the gauge area are usually taken from the rail sample, there is a high probability that the original surface properties of the rail do not apply across the entire test coupon and, therefore, data representing only average material properties are obtained. In the literature, disks (47 mm in diameter) for a twin-disk rolling contact test machine have been obtained directly from the rail sample and used to validate rolling contact fatigue wear models. The question arises: How accurate are such predictions? In this research paper, the effect of rail sampling position on the ratcheting behavior of AS1085.1 rail steel was investigated using rectangular shaped specimens. Uniaxial stress-controlled tests were conducted with samples obtained at four different depths to observe the ratcheting behaviour of each. Micro-hardness measurements of the test coupons were carried out to obtain a constitutive relationship to predict the effect of depth on the ratcheting behaviour of the rail material. This work ultimately assists the selection of valid material parameters for constitutive models in the study of rail surface ratcheting.

Parenting and the behavior problems of young children with an intellectual disability: Concurrent and longitudinal relationships in a population-based study

We examined parenting behaviors, and their association with concurrent and later child behavior problems. Children with an intellectual disability (ID) were identified from a UK birth cohort (N  =  516 at age 5). Compared to parents of children without an ID, parents of children with an ID used discipline less frequently, but reported a more negative relationship with their child. Among children with an ID, discipline, and home atmosphere had no long-term association with behavior problems, whereas relationship quality did: closer relationships were associated with fewer concurrent and later child behavior problems. Increased parent-child conflict was associated with greater concurrent and later behavior problems. Parenting programs in ID could target parent-child relationship quality as a potential mediator of behavioral improvements in children.

Ferrocene in conjugation with a Fischer carbene: Synthesis, NLO, and electrochemical behavior of a novel organometallic push-pull system

Using an iterative sequence of Wittig olefination, reduction, oxidation, and condensation of an active methylene group to carbonyl, it was possible to prepare a series of organometallic push-pull molecules [(CO)(5)M=C(OCH3)(-CH=CH-)(n)(C5H4)Fe(C5H5), M = W, Cr, n = 1-4] in which ferrocene is the donor element and a Fisher carbene moeity is the acceptor group. The molecular first hyperpolarizability beta was determined by hyper-Rayleigh scattering experiments. The beta values ranged from 110 x 10(-30) to 2420 x 10(-30) esu in acetonitrile, and they are among the highest reported for organometallic molecules so far. Electrochemical measurements are consistent with the push-pull nature of these compounds.

Dialkyl (3-Aryl- 1,2,4-oxadiazol-5-yl)phosphonates: Synthesis and Thermal Behavior-Evidence for Monomeric Alkyl Metaphosphate

Dialkyl (3-aryl-l,2,4-oxadiazol-5-yl)phosphonate6sa -h have been obtained by 1,3-dipolar cycloaddition of arenenitrile oxides 5a-f to dialkyl phosphorocyanidates (4a and 4b) in yields ranging between 30% and 58%. A standardized method for obtaining cyanidates 4a and 4b has been established. The diethyl thiophosphorocyanidate (4c) is less reactive than 4a and 4b, only the 3-(4'-nitrophenyl) derivative 6i being obtainable. While the IR and NMFt spectra of 6a-i were unexceptional, their UV spectra showed evidence of conjugative interaction in high degrees between the phosphonate and heterocyclic moieties as well as a varying conjugative interaction between the heterocyclic and aryl moieties. The oxadiazoles 6a-h are thermally labile and yield trialkyl phosphates 7 as the only identifiable products. A mechanism based on the intermediacy of monomeric alkyl metaphosphate 11 in the formation of trialkyl phosphate was postulated, and supportive evidence in the form of trapping the metaphosphate with acetophenone has been obtained.

Fluidity, Permeability And Antioxidant Behavior Of Model Membranes Incorporated With Alpha-Tocopherol And Vitamin-E Acetate

Magnetic resonance studies reveal a marked difference between the binding of α-tocopherol and that of the corresponding acetate (vitamin E acetate) with dipalmitoylphosphatidylcholine (DPPC) vesicles. This is reflected in differences in the phase-transition curves of the DPPC vesicles incorporated with the two compounds, as well as in the 13C relaxation times and line widths. A model for the incorporation of these molecules in lipid bilayers has been suggested. α-Tocopherol binds strongly with the lipids, possibly through a hydrogen bond formation between the hydroxyl group of the former and one of the oxygen atoms of the latter. The possibility of such a hydrogen bond formation is excluded in vitamin E acetate, which binds loosely through the normal hydrophobic interaction. The model for lipid-vitamin interaction explains the in vitro decomposition of H2O2 by α-tocopherol. α-Tocopherol in conjuction with H2O2 can also act as a free-radical scavenger in the lipid phase. The incorporation of α-tocopherol and vitamin E acetate in DPPC vesicles enhances the permeability of lipid bilayers for small molecules such as sodium ascorbate.

An analysis of theories of search and search behavior

Theories of search and search behavior can be used to glean insights and generate hypotheses about how people interact with retrieval systems. This paper examines three such theories, the long standing Information Foraging Theory, along with the more recently proposed Search Economic Theory and the Interactive Probability Ranking Principle. Our goal is to develop a model for ad-hoc topic retrieval using each approach, all within a common framework, in order to (1) determine what predictions each approach makes about search behavior, and (2) show the relationships, equivalences and differences between the approaches. While each approach takes a different perspective on modeling searcher interactions, we show that under certain assumptions, they lead to similar hypotheses regarding search behavior. Moreover, we show that the models are complementary to each other, but operate at different levels (i.e., sessions, patches and situations). We further show how the differences between the approaches lead to new insights into the theories and new models. This contribution will not only lead to further theoretical developments, but also enables practitioners to employ one of the three equivalent models depending on the data available.

Size dependence and dispersion behavior of the first hyperpolarizability of copper nanoparticles

We have probed the size dependency of the first hyperpolarizability (b) of copper nanoparticles by hyper-Rayleigh scattering (HRS). Our results indicate that second harmonic generation (SHG) originates predominantly at the surface of the nanoparticles as long as the size (d) remains small compared to the wavelength (k). However, volume contribution to the SH response due to the retardation effect becomes important when particle size grows beyond the `small particle limit'. There is a significant dispersion in the b values of copper nanoparticles owing tothe presence of the strong surface plasmon resonance (SPR) band.

Influence of heat-treatment on the strength and fracture-behavior of fe-12cr-6al ferritic stainless-steel

The changes in the tensile properties and fracture mode brought about by heat treatment of Fe-12Cr-6Al ferritic stainless steel have been studied. A favourable combination of high strength and good ductility is obtained by heating the material at 1370 K for 2 h followed by a water quench. The high-temperature treatment results in carbide dissolution as well as an increase in the grain size. The mechanism of strengthening has been evaluated from the apparent activation energy (28 kJ mol–1) and is identified to be the unpinning of dislocations from the atmosphere of carbon atoms. As the heat-treatment temperature is increased, the fracture behaviour changes from ductile to brittle mode and this is related to the changes in grain size and friction stress.

Stochastic kinetics of ribosomes: Single motor properties and collective behavior

Syntheses of protein molecules in a cell are carried out by ribosomes.A ribosome can be regarded as a molecular motor which utilizes the input chemical energy to move on a messenger RNA (mRNA) track that also serves as a template for the polymerization of the corresponding protein. The forward movement, however, is characterized by an alternating sequence of translocation and pause. Using a quantitative model, which captures the mechanochemical cycle of an individual ribosome, we derive an exact analytical expression for the distribution of its dwell times at the successive positions on the mRNA track. Inverse of the average dwell time satisfies a Michaelis-Menten-type'' equation and is consistent with the general formula for the average velocity of a molecular motor with an unbranched mechanochemical cycle. Extending this formula appropriately, we also derive the exact force-velocity relation for a ribosome. Often many ribosomes each synthesizes a copy of the same protein. We extend the model of a single ribosome by incorporating steric exclusion of different individuals on the same track. We draw the phase diagram of this model of ribosome traffic in three-dimensional spaces spanned by experimentally controllable parameters. We suggest new experimental tests of our theoretical predictions.

Fuel conditions and fire behavior characteristics of managed Picea abies and Pinus sylvestris forests in Finland

The objectives of this study were to analyze the impact of structural stand characteristics on ignition potential, surface fuel moisture, and fire behavior in Pinus sylvestris L. and Picea abies (L.) Karst stands in Finland and to explain stand-specific fire danger using the Canadian Fire Weather Index System and the Finnish Fire Risk Index. Additionally, the study analyzes the relationship between observed fire activity and fire weather indices at different stages of growing season. Field experiments were carried out in Pinus sylvestris or Picea abies dominated stands during fire seasons 2001 and 2002. Observations on ignition potential, fuel moisture, and fire behavior were analyzed in relation to stand structure and the outputs of the Finnish and Canadian fire weather indices. Seasonal patterns of fire activity were examined based on national fire statistics 1996 2003, effective temperature sum, and the fire weather indices. Point fire ignition potential was highest in Pinus clear-cuts and lowest in closed Picea stands. Moss-dominated surface fuels were driest in clear-cut and sapling stage stands and presented the highest moisture content under closed Picea canopy. Pinus sylvestris stands carried fire under a wide range of fire weather conditions under which Picea abies stands failed to sustain fire. In the national fire records, the daily number of reported ignitions presented its highest value during late fire season whereas the daily area burned peaked most substantially during early season. The fire weather indices correlated significantly with ignition potential and fuel moisture but were unable to explain fire behavior in the experimental fires. During the initial and final stages of the growing season, fire activity was disconnected from weather-based fire danger ratings. Information on stand structure and season stage would benefit the assessment of fire danger in Finnish forest landscape for fire suppression and controlled burning purposes.