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Autism (or autism spectrum disorder [ASD]) is an often disabling childhood neurologic condition of mostly unknown cause. It is commonly diagnosed at 3 or 4 years of age. We explored whether there was an association of any analytes measured by newborn screening tests with a later diagnosis of ASD. A database was compiled of 3–5 year‐old patients with any ASD diagnosis in the Texas Medicaid system in 2010–2012. Two controls (without any ASD diagnosis) were matched to each case by infant sex and birth year/month. All study subjects were linked to their 2007–2009 birth and newborn screening laboratory records, including values for 36 analytes or analyte ratios. We examined the association of analytes/ratios with a later diagnosis of ASD. Among 3,258 cases and 6,838 controls, seven analytes (e.g., 17‐hydroxyprogesterone, acylcarnitines) were associated with a later ASD diagnosis. In this exploratory study, an ASD diagnosis was associated with 7 of 36 newborn screening analytes/ratios. These findings should be replicated in other population‐based datasets.

The strain response of both acrylate and polyimide-coated optical fiber strain sensors bonded to aluminum specimens with AE-10, AE-15 and M-Bond 200 strain gage adhesives was investigated with both axial and cantilever beam tests. These results were compared to both the strain response of conventional strain gages and to model predictions. The results indicate that only approximately 82.6% of the known strain in the specimen was transferred through the glue line and fiber coating into the fiber. Thus, multiplying by a strain transfer factor of 1.21 was sufficient to correct the optical fiber strain output. This effect was found to be independent of the optical fiber coating, as well as the adhesive type and the 3D profile of the glue line used to attach the optical fiber. [ABSTRACT FROM AUTHOR]

The article focuses on the planned development and establishment of Marine Corps Forces Special Operations Command (MarSOC) in the U.S. It notes that the establishment of MarSOC which is in line with the roles and missions assigned by Congress to the Marine Corps will yield both tangible and vital benefits for the group. MarSOC will strengthen and improves the quality of the country's armed forces through unique modes of employment, tactical techniques, and training.

This study examined the effect of dietary consumption of carbohydrates (CHO) on the blood lactate to rating of perceived exertion (La:RPE) ratio during an intense micro-cycle of exercise training. This ratio is a proposed biomarker of exercise training stress and potential indicator for under- or overtraining in athletes. Sixteen male athletes were randomly assigned into two groups; high CHO (H-CHO; 60% of daily caloric intake) and low CHO (L-CHO; 30% of daily caloric intake). Diets were controlled the day before and for the three days of the micro-cycle. The micro-cycle consisted of three successive days of 60 minutes of intense cycling (∼70% of VO2peak). Blood samples were obtained immediately before and after exercise (post) on each day of exercise training (D1, D2, D3) and were analyzed for blood lactate. Rating of perceived exertion (RPE) scores were taken at the end of each exercise session and combined with the post exercise lactate value to form the La:RPE ratio. An analysis of variance (ANOVA) showed a significant difference between the La:RPE ratio for the H-CHO and L-CHO groups at D3 even though the exercise intensity was not significantly different between the groups. Specifically, the ratio was significantly (p < 0.02) lower on D3 in the L-CHO group (∼31% lower) than in the H-CHO group. From these findings it is recommended that diet needs to be monitored when using the La:RPE ratio as an exercise training biomarker to determine whether an athlete is truly under-training or overtraining. Athletes or coaches that use the La:RPE ratio as a training biomarker, but do not monitor dietary CHO intake need to interpreted their findings carefully.

Aggrecan is responsible for the mechanical properties of cartilage. One of the earliest changes observed in arthritis is the depletion of cartilage aggrecan due to increased proteolytic cleavage within the interglobular domain. Two major sites of cleavage have been identified in this region at Asn(341)-Phe(342) and Glu(373)-Ala(374). While several matrix metalloproteinases have been shown to cleave at Asn(341)-Phe(342), an as yet unidentified protein termed "aggrecanase" is responsible for cleavage at Glu(373)-Ala(374) and is hypothesized to play a pivotal role in cartilage damage. We have identified and cloned a novel disintegrin metalloproteinase with thrombospondin motifs that possesses aggrecanase activity, ADAMTS11 (aggrecanase-2), which has extensive homology to ADAMTS4 (aggrecanase-1) and the inflammation-associated gene ADAMTS1. ADAMTS11 possesses a number of conserved domains that have been shown to play a role in integrin binding, cell-cell interactions, and extracellular matrix binding. We have expressed recombinant human ADAMTS11 in insect cells and shown that it cleaves aggrecan at the Glu(373)-Ala(374) site, with the cleavage pattern and inhibitor profile being indistinguishable from that observed with native aggrecanase. A comparison of the structure and expression patterns of ADAMTS11, ADAMTS4, and ADAMTS1 is also described. Our findings will facilitate the study of the mechanisms of cartilage degradation and provide targets to search for effective inhibitors of cartilage depletion in arthritic disease.

The glucocorticoid receptor (GR) interacts specifically with glucocorticoids, whereas its closest relative, the mineralocorticoid receptor (MR), interacts with both glucocorticoids and mineralocorticoids, such as aldosterone. To investigate the mechanism underlying the glucocorticoid/mineralocorticoid specificity of the GR, we used a yeast model system to screen for GR ligand-binding domain mutants, substituted with MR residues in the segment 565-574, that can be efficiently activated by aldosterone. In all such increased activity mutants, valine 571 was replaced by methionine, even though most mutants also contained substitutions of other residues with their MR counterparts. Further analysis in yeast and COS-7 cells has revealed that the identity of residue 571 determines the behavior of other MR substituted residues in the 565-574 segment. Generally, MR substitutions in this region are only consistent with aldosterone binding if residue 571 is also replaced with methionine (MR conformation). If residue 571 is valine (GR conformation), most other MR substitution mutants drastically reduce interaction with both mineralocorticoid and glucocorticoid hormones. Based on these functional data, we hypothesize that residue 571 functions as a regional organizer involved in discriminating between glucocorticoid and mineralocorticoid hormones. We have used a molecular model of the GR ligand-binding domain in an attempt to interpret our functional data in structural terms.

At scales appropriate to the National Ignition Facility, calculations indicate double shell capsules reach ignition conditions with room temperature fuel. Los Alamos is laying the groundwork for these double shell ignition targets with a preliminary campaign on Nova. The target design features a 260 μm O.D. inner glass capsule with an I.D. of approximately 200 μm, containing deuterium gas, centered inside a machined polymer shell. The central capsule was supported either with a 30 mg/cc foam or with two polymer films, each less than 0.1 μm in thickness. The materials, machining, assembly, and characterization of the targets are discussed.

The outcome of women with adenosquamous carcinoma of the cervix has been a controversial issue. To assess the prognostic significance of this cell type, the medical records of 29 patients with stage IB primary adenosquamous carcinoma of the cervix were reviewed. Twenty-six had cervical tumors measuring 3 cm or less. With a median follow-up of 60 months, the overall disease-free 5-year survival was 85. Pelvic lymph node metastases were found in three of 19 patients (16) with stage IB, and periaortic lymph nodes were negative in eight. A log-likelihood x2test comparing lymphatic spread, recurrence rate, and 5-year disease-free survival in patients with stage IB disease and tumors less than 3 cm versus a similar group of 58 patients with pure squamous cell carcinoma of equivalent stage and comparable size treated during the same time disclosed no significant differences in any of the indicators analyzed. We conclude that stage IB adenosquamous carcinoma of the cervix does not differ in its metastatic potential or outcome from the more common pure squamous cell carcinoma.

Purified rat liver glucocorticoid receptor was covalently charged with [3H]glucocorticoid by photoaffinity labeling (UV irradiation of [3H]triamcinolone acetonide-glucocorticoid receptor) or affinity labeling (incubation with [3H]dexamethasone mesylate). After labeling, separate samples of the denatured receptor were cleaved with trypsin (directly or after prior succinylation), chymotrypsin, and cyanogen bromide. Labeled residues in the peptides obtained were identified by radiosequence analysis. The peaks of radioactivity corresponded to Met-622 and Cys-754 after photoaffinity labeling with [3H]triamcinolone acetonide and Cys-656 after affinity labeling with [3H]dexamethasone mesylate. The labeled residues are all positioned within hydrophobic segments of the steroid-binding domain. The patterns of hydropathy and secondary structure for the glucocorticoid receptor are highly similar to those for the progestin receptor and similar but less so to those for the estrogen receptor and to those for c-erb A.

We have defined and characterized a region upstream of the bovine prolactin gene that confers repression by glucocorticoids. This 'negative glucocorticoid response element' (nGRE) contains multiple footprinting sites for purified glucocorticoid receptor protein between -51 and -562 bp. A strong consensus sequence for receptor binding within the nGRE has not yet been defined, but it is apparent that nGRE sequences differ from the GRE consensus elements that confer positive glucocorticoid regulation. Unlike 'positive' GREs, the nGRE enhances promoter activity in the absence of glucocorticoids or receptor, presumably through the action of a protein that binds in the same region and activates transcription. The hormone-receptor complex appears to negate this enhancement by competing or inactivating the second factor. As with positive GREs, nGRE sequences confer hormonal regulation upon linked heterologous promoters within various cell types; a 34-bp subfragment containing a single receptor binding site is sufficient for nGRE activity. We speculate that nGRE sequences might alter the structure of bound receptor, thereby preventing it from functioning as a positive regulator when bound at those sites.

Aluminum tolerant soybean cultivars are needed for deeper rooting and increased drought tolerance in acid subsoils. Fifteen cultivars or plant introductions were screened for Al tolerance by growing them for 33 days in pots of unlimed (pH 4.3) and limed (pH 5.6) Taturn subsoil. Tolerance was based upon plant symptoms on unlimed soil (leaf cupping, chlorosis or necrosis, and petiole collapse), absolute dry-weights of shoots and roots on unlimed soil and relative (unlimed/limed %) shoot and root weights. On unlimed soil, absolute dry weights ranged 4-fold for shoots and 7-fold for roots. Relative weights (unlimed/limed %) ranged 2.7-fold for shoots and 6-fold for roots. Based on these criteria, entries PI248511 (Japan), Perry (USA), PI381674 (Uganda), Amcor (Ohio USA) and Hernon 147 (Zimbabwe, Africa) were judged most tolerant to the acid soil. Most sensitive entries included Sable, Oribi and Duiker, all from Zimbabwe, Africa, and Chief (USA). Santa Rosa (Brazil) was only moderately tolerant. Entries from Zimbabwe, Africa showed a range of acid soil tolerance. Hernon 147 was most tolerant, Oribi and Sable least tolerant and Buffalo and Impala intermediate. None of the introduced gerrnplasm was superior to Perry in acid soil tolerance. Amcor (Ohio, USA), reportedly tolerant to low soil fertility and drought, was more tolerant to acid Tatum soil than Beeson (Indiana USA). Results suggest that Amcor soybean, like some Ohio cultivars of wheat and barley, may have been exposed to Al during its breeding history. Entries producing highest shoot and root dry weights on unlimed soil were also generally more vigorous on limed soil. Thus, overall vigor may contribute to Al tolerance. Similar observations have been made for selections of Ky 31 tall fescue. Our results suggested that shoot growth alone was an adequate index of acid soil tolerance among the soybean entries tested. Mineral element concentrations in plant shoots were not useful in understanding differential acid soil tolerance.

Activated glucocorticoid receptor protein, purified to 40-60% homogeneity from rat liver extracts, binds selectively in vitro to a cloned fragment of murine mammary tumor virus (MTV) DNA. The DNA fragment tested contains about half of the sequences present in intact MTV DNA, and its rate of transcription, like that of the intact viral element, is strongly stimulated by glucocorticoids when it is introduced into the genome of a receptor-containing cell. In contrast, the receptor fails to bind selectively to DNA restriction fragments from E. coli plasmids pBR322 and RSF2124 or from bacteriophages lambda and T4. Preliminary experiments to localize regions within MTV DNA responsible for selective binding have revealed thus far one subfragment that fails to bind the receptor and one selectively bound subfragment that maps far downstream from the 5' terminus of the normal RNA transcript. These studies are consistent with the notion that steroid receptors may modulate rates of transcription by recognizing specific DNA sequences within or near the regulated genes.

Part I presents six years of grading disparities found at one university. Reliable grading differences were found at all levels examined (college, discipline, and instructor). Part II focuses upon three studies which show how these disparities translate into inequitable GPA and honor status. GPAs are compared with GCAs (grade centile averages), the latter a relative measure of achievement used in these studies. The first study examines the different grading experiences encountered by 19 students who graduated with the highest over-all GPAs at the end of one term. The second study found 8 students who earned honor level semester GPAs for statistically unexceptional work, compared to their classmates. The third study monitored 7 semesters of overgrading of groups of students who happened to enroll in the same set of courses. Part III presents a long discussion of grading. Findings from the target university Appalachian State University in North Carolina are related to findings by Goldman at the University of California at Riverside and to those by Prather at Georgia State University in Atlanta. Many generalizations are reviewed, and grading practice is related to Helson's adaptation level phenomenon and to Stouffer's concept of relative deprivation. The antigrading view that traditional grading should be abandoned is considered and rejected. Part IV presents the writer's suggested reforms to increase the validity of grading. GCAs based upon performance in selected courses are proposed to determine honor and rank status, while simplified traditional grading is suggested to determine discipline status and whether or not course credits will be earned. Also considered are means to reform various administrative rules which affect grading, e.g., pass/fail, repeat, transfer, and readmission rules. Envisioned for the future would be a more valid index of academic achievement and higher correlations between the new index and other measures of aptitude and/or achievement.