cssi/SciSciGPT-SciSciNet huggingface dataset:
"In the driver's seat": Parent perceptions of choice in a participant-directed medicaid waiver program for young children with autism.

This study investigated families’ experience of choice within a participant-directed Medicaid waiver program for young children with autism. Fourteen parents or grandparents participated in in-depth interviews about their experience of choosing personnel, directing in-home services, and managing the $25,000 annual allocation. Key findings included families’ preference to hire providers with whom they have a prior relationship, parent empowerment and differences of opinion about parents as teachers. Professionals implementing participant directed service models could benefit from understanding the strong value parents’ placed on the personalities and interpersonal skills of providers. Parents’ descriptions of directing rather than merely accepting autism services revealed increased confidence in their ability to choose and manage the multiple components of their children’s HCBS autism waiver program.
Novel resistant potato starches on glycemia and satiety in humans.

This study was designed to determine the efficacy of two novel type-four resistant starches (RS4) on postprandial glycemia and ratings of fullness. Volunteers (n=10) completed completed five interventions designed to determine the glycemic and satiety (fullness) effects of the starches (38 g,) alone and when added on top of available carbohydrate. The dose of the starches provided 30 g of resistant starch per treatment. The treatments were: commercial resistant starch added to water (PF−), noncommercial resistant starch added to water (PR−), dextrose solution (DEX, 50 g), and DEX with PenFibe starch (PF
Elemental diet alters macrophage function in mice

Administration of a chemically defined liquid elemental diet (ED) induces spontaneous bacterial translocation to mesenteric lymph nodes (MLN) in animal models. The influence of this process on host immunity is unclear. This study evaluated the effects of ED on peritoneal macrophage (PM phi) antimicrobial functions. Conventional C57/BL6 mice and endotoxin-resistant C3H/HeJ mice (n = 60) were randomized to be pair-fed either an ED or regular chow diet (RD) for 14 days. Blood, spleen, liver, and MLN were cultured for bacteria. PM phi were harvested for: percentage Candida albicans (CA) phagocytosis, percentage killing of CA, PM phi superoxide anion (O2-) production, and TNF-dependent macrophage cytotoxicity. Enteral feeding of ED in conventional C57/BL6 mice caused significant bacterial translocation to MLN but not other organs. Significant impairment of CA killing by PM phi occurred in the ED group and was associated with reduced O2- production. Tumor necrosis factor (TNF)-dependent cytotoxicity of PM phi was also decreased. In endotoxin-resistant C3H/HeJ mice, bacterial translocation was not observed and PM phi antifungal functions remained similar in both RD and ED groups. Thus, enteral feeding of an elemental diet downregulates host oxidative and antimicrobial mechanisms and TNF-dependent cytotoxicity in conventional mice which may be secondary to elemental diet-induced bacterial translocation.
Expression of bacteriophage T4 genes 45, 44, and 62. I. Discoordinate synthesis of the T4 45- and 44-proteins.

Abstract T4 genes 45, 44, and 62 code for proteins that play essential roles in phage DNA replication. These three genes map as a cluster on the T4 chromosome and are thought to be transcribed into one polycistronic mRNA. We reexamined the possibility that these three genes are cotranscribed and obtained results which suggested that the protein products of genes 44 and 62 are translated from one mRNA species, but that the protein products of genes 45 and 44 are translated from different mRNA species. Cotranscription of T4 genes 44 and 62 was implied by polar effects that two amber mutations in gene 44 exhibited on the synthesis of the protein product of gene 62. In contrast, an amber mutation in T4 gene 45 did not affect the synthesis of the protein products of genes 44 and 62, and the protein products of genes 45 and 44 were found to be disproportionately synthesized under more than one type of growth condition. In the accompanying paper, Bowles and Karam present genetic evidence for the existence of a regulatory site for gene 44 that does not service gene 45. This also suggests that genes 45 and 44 belong to different operons. The T4 gene 45 amber mutation that we used in our studies exhibited a cis-dominant effect on the biological activity (although not on the synthesis ) of a partially defective protein product of gene 44. The results suggest that the protein products of genes 45 and 44 are more likely to interact with each other in vivo when they are coded for by the same genome than when they are synthesized from genotypically different coinfecting genomes.
Cover Picture: Trimeric Perfluoro‐ortho‐phenylenemercury: A Versatile Lewis Acidic Host (Chem. Eur. J. 21/2003)

The cover picture shows how trimeric perfluoro-ortho-phenylene mercury (center), one of the simplest trifunctional Lewis acidic hosts, interacts with organic molecules to afford various adducts. The planarity of this trinuclear complex as well as its overall polarizability compounded with relativistic effects at mercury permits the occurrence of noncovalent interactions and accounts for the tendency of this compound to form cofacial dimers as observed in the structure of the acetone adduct (top left). With a triply coordinated acetone molecule, the structure of this adduct also substantiates the cooperative effects that arise from the proximity and accessibility of the mercury centers. The complexation of arenes, such as benzene (bottom left) and naphthalene (bottom right), also occurs and leads to the formation of binary stacks in which the arene establishes multiple linkages with the mercury centers of the trifunctional Lewis acids. In addition to displaying unusual coordination environment, the arene units present in those stacks exhibit remarkable phosphorescent properties. For more details, see the paper by F. P. Gabbai, R. E. Taylor, and M. R. Haneline on p. 5188 ff.
Combining T-cell immunotherapy and anti-androgen therapy for prostate cancer

Prostate cancer remains a significant health problem for men in the Western world. Although treatment modalities are available, these do not confer long-term benefit and are accompanied by substantial side effects. Adoptive immunotherapy represents an attractive alternative to conventional treatments as a means to control tumor growth. To selectively target the tumor-expressed form of Muc1 we constructed a retroviral vector encoding a chimeric antigen receptor (CAR) directed against the aberrantly-expressed extracellular portion of Muc1 called the ‘variable number of tandem repeats’. We now demonstrate that T cells can be genetically engineered to express a CAR targeting the tumor-associated antigen Muc1. CAR-Muc1 T cells were able to selectively kill Muc1-expressing human prostate cancer cells. However, we noted that heterogeneous expression of the Muc1 antigen on tumor cells facilitated immune escape and the outgrowth of target-antigen loss variants of the tumor. Given the importance of androgen ablation therapy in the management of metastatic prostate cancer, we therefore also tested the value of combining conventional (anti-androgen) and experimental (CAR-Muc1 T cells) approaches. We show that CAR-Muc1 T cells were not adversely impacted by anti-androgen therapy and subsequently demonstrate the feasibility of combining the approaches to produce additive anti-tumor effects in vitro. Adoptive transfer of CAR-Muc1 T cells alone or in combination with other luteinizing hormone-releasing hormone analogs or antagonists should be tested in human clinical trials.
Totally percutaneous aortic aneurysm repair: Experience and prudence

Objective Totally percutaneous aortic aneurysm repair has been shown to be technically feasible, with low morbidity. Complications from percutaneous arterial closure are not insignificant, however, and can be fatal. We sought to evaluate our experience with this technique, compare it with the published literature, and identify factors associated with conversion to open repair and complications. Methods A retrospective review of a prospectively collected database was performed. All patients who underwent percutaneous closure of large-bore-sheath (>12F) access sites with off-label use of a suture-mediated closure device (Prostar XL) between December 2002 and August 2005 were reviewed. Outcome measures evaluated were rates of technical success, conversion to open femoral arterial repair, and complications. Axial diameter measurements of the accessed vessels were assessed with computed tomographic (CT) angiography both before and after the procedure. Patient variables were compared by using χ 2 , Fisher exact, and paired and independent samples t tests where appropriate. The mean follow-up interval was 1.5 years. Results During the study period, 49 patients underwent percutaneous closure of 79 large-bore-sheath access sites after successful endovascular aneurysm repair. Seven patients (14%) were morbidly obese (body mass index >35 kg/m 2 ). Successful closure was achieved in 74 access sites (93.7%). Percutaneous closure was unsuccessful in five access sites (6.3%), all of which required open femoral repair at the same setting. Two converted patients experienced complications (4.1%): one retroperitoneal hematoma requiring transfusion of blood products and one iliac artery injury leading to death from myocardial infarction. Both of these patients were morbidly obese. Both complications occurred after closure of larger than 20F sheath sites. Morbid obesity and sheath size greater than 20F were associated with a significantly increased complication rate ( P = .02 and P = .01, respectively). No thrombotic or infectious complications occurred in this series. Upon comparison of preoperative and postoperative CT angiograms, one (1.3%) small pseudoaneurysm was detected. No arteriovenous fistulas or hematomas larger than 3 cm were detected. The pseudoaneurysm occurred after closure of a 20F sheath access site. There were no significant differences in minimum intraluminal (7.38 ± 1.8 vs 7.48 ± 1.8) or maximum extraluminal (11.25 ± 2.8 vs 12.02 ± 2.7) diameters between preoperative and postoperative CT angiograms, respectively. Conclusions Totally percutaneous aortic aneurysm repair is technically feasible in most cases, with no effect on the luminal diameter of the accessed femoral artery. Complications occur more often in morbidly obese patients and with sheaths larger than 20F. These complications can be minimized with meticulous technique and good patient selection. The capability for expeditious open femoral arterial repair is mandatory with this approach.
"This Is Our Land": Collective Violence, Property Law, and Imagining the Geography of Palestine

This study seeks to explain the origins of two types of violence occurring on the Palestinian landscape, the erasure of Palestinian farms and the demolition of Palestinian homes. Such violence has two sources. One source derives from an enduring practice of meaning-making about geographical places that has inspired groups with territorial ambitions to seize control of the landscapes they covet and is referred to by Edward Said as the crafting of “imaginative geographies.” The second source focuses on changes in property rights that follow when groups with territorial ambitions succeed in seizing control of coveted land. It is the imagined geography of Palestine as a homeland for the Jewish people, first framed by Zionists of the late 19th century and absorbed into the practices of Israeli state-building, and the changes in property rights inscribed into the Palestinian landscape following Zionist and Israeli military conquests in 1948 and 1967, that lie at the core of violence directed against the Palesti...
Perturbation theory in the LSZ-formalism

Abstract The theory of a real, scalar, local field satisfying the LSZ-axioms is considered. A perturbative expansion of its retarded functions solving the unitarity equations of Glaser, Lehmann, and Zimmermann rigorously in every finite order of perturbation theory is constructed. The calculations involve only mathematically well defined quantities. No divergences enter at any step. The procedure works for nonrenormalizable theories as well as for renormalizable ones. No essential difference between these two types of theories, which would allow to exclude the former from consideration, has been found.
Morphine and HIV-Tat increase microglial-free radical production and oxidative stress: possible role in cytokine regulation.

Opiate abuse alters the progression of human immunodeficiency virus and may increase the risk of neuroAIDS. As neuroAIDS is associated with altered microglial reactivity, the combined effects of human immunodeficiency virus-Tat and morphine were determined in cultured microglia. Specifically, experiments determined the effects of Tat and morphine on microglial-free radical production and oxidative stress, and on cytokine release. Data show that combined Tat and morphine cause early and synergistic increases in reactive oxygen species, with concomitant increases in protein oxidation. Furthermore, combined Tat and morphine, but not Tat or morphine alone, cause reversible decreases in proteasome activity. The effects of morphine on free radical production and oxidative stress are prevented by pre-treatment with naloxone, illustrating the important role of opioid receptor activation in these phenomena. While Tat is well known to induce cytokine release from cultured microglia, morphine decreases Tat-induced release of the cytokines tumor necrosis factor-α and interleukin-6, as well as the chemokine monocyte chemoattractant protein-1 (MCP-1). Finally, experiments using the reversible proteasome inhibitor MG115 show that temporary, non-cytotoxic decreases in proteasome activity increase protein oxidation and decrease tumor necrosis factor-α, interleukin-6, and MCP-1 release from microglia. Taken together, these data suggest that oxidative stress and proteasome inhibition may be involved in the immunomodulatory properties of opioid receptor activation in microglia.
What works (or doesn't) in a DUI court? An example of expedited case processing

Abstract Purpose A number of policy efforts have aimed to reduce drunk driving, including deterrence-based policies and specialized treatment courts. This study examines the impact of expedited court processing on the county-wide rate of DUI offenses. It also examines the links between sanction swiftness, certainty, and severity and changes in DUI rates over time. Methods This study uses interrupted time series analysis to assess changes in DUI rates in one county over a time period including the introduction of a full-coverage, expedited court docket for DUI. Additionally, the three components of deterrence were examined. Result Findings reveal that the program implementation corresponded with a lower rate of DUI case filings, but not with a general reduction in alcohol-involved collisions in the county. Additionally, only sanction swiftness improved over time, while certainty remained stable and severity declined. Conclusions Results indicate that the introduction of the expedited court docket does not appear to have produced a deterrent effect on DUI. It may be that DUI offenders require more than expedited processing to overcome the issues that precipitate their offending. Future research and policy should explore both the impact of swiftness of punishment and the provision of appropriate treatment services in addressing DUI offending.
Decision tree parsing using a hidden derivation model

Parser development is generally viewed as a primarily linguistic enterprise. A grammarian examines sentences, skillfully extracts the linguistic generalizations evident in the data, and writes grammar rules which cover the language. The grammarian then evaluates the performance of the grammar, and upon analysis of the errors made by the grammar-based parser, carefully refines the rules, repeating this process, typically over a period of several years.
Phosphorylation of p21 in G2/M Promotes Cyclin B-Cdc2 Kinase Activity

Little is known about the posttranslational control of the cyclin-dependent protein kinase (CDK) inhibitor p21. We describe here a transient phosphorylation of p21 in the G2/M phase. G2/M-phosphorylated p21 is short-lived relative to hypophosphorylated p21. p21 becomes nuclear during S phase, prior to its phosphorylation by CDK2. S126-phosphorylated cyclin B1 binds to T57-phosphorylated p21. Cdc2 kinase activation is delayed in p21-deficient cells due to delayed association between Cdc2 and cyclin B1. Cyclin B1-Cdc2 kinase activity and G2/M progression in p21-/- cells are restored after reexpression of wild-type but not T57A mutant p21. The cyclin B1 S126A mutant exhibits reduced Cdc2 binding and has low kinase activity. Phosphorylated p21 binds to cyclin B1 when Cdc2 is phosphorylated on Y15 and associates poorly with the complex. Dephosphorylation on Y15 and phosphorylation on T161 promotes Cdc2 binding to the p21-cyclin B1 complex, which becomes activated as a kinase. Thus, hyperphosphorylated p21 activates the Cdc2 kinase in the G2/M transition.
Improving Ductility in Nanostructured Materials and Metallic Glasses: Three Laws

Nanostructured materials and bulk metallic glasses are relatively new classes of engineering materials that have promise for unique metals applications. However, both these materials suffer from limited room temperature ductility in unconfined loading geometries. In this work, we present three experimental rules that we have observed to be necessary to toughen bulk metallic glasses. We reason that adaptations to these rules may provide the solution for toughening nanostructured composites and other brittle materials.
The effect of sediment redox potential and soil acidity on nitrogen uptake, anaerobic root respiration, and growth of rice (Oryza sativa)

Oryza sativa Loisel cultivar Mars., a common lowland rice variety was grown under controlled soil redox conditions (Eh) and acidity (pH). The effect of two variables (Eh and pH) on growth, anaerobic root respiration, and uptake of added labelled nitrogen, was investigated. Plant growth, estimated by dry weight showed significantly higher growth under reducing sediment redox potentials (−200 mV and 0 mV) and at a soil pH of 6.5 Using the activity of the inducible enzyme alcohol dehydrogenase (ADH) as an indicator of anaerobic root respiration, a decrease in redox potential resulted in an increase in root ADH. However, growth paralled increases in anaerobic root respiration suggesting nitrogen transformation in the soil to be a primary parameter governing growth. Labelled nitrogen uptake which was greater under anaerobic conditions apparently led to greater growth of lowland rice in the highly reduced or anaerobic soil treatments.
Photometric Error Analysis. IX: Optimum Use of Photomultipliers.

A critical study of photomultipliers leads to the following conclusions: (1) the dark current observed in tubes with alkali-antimonide cathodes at room temperature is primarily due to gas ions, not thermionic emission; (2) deviation from idealized (simple Poisson) pulse-height distributions is primarily due to secondary electron loss, particularly in Venetian blind multipliers; (3) pulse-counting provides better signal-to-noise ratio than any other simple detection scheme, and is not far from optimum detection in most cases. However, dc methods can approach pulse-counting quite closely if digital readout is used. A convenient method for determining optimum discriminator levels is presented, with examples.
Surveillance of patients with prostate cancer after treatment: The roles of serologic and imaging studies

The asymptomatic patient who has been treated with a curative intent by surgery or irradiation for cancer of the prostate needs only a PSA and a baseline bone scan for his initial (post-treatment) follow-up. Rising serum PSA levels which still remain in the moderate range may signal a local recurrence, but this must be documented histologically. The therapeutic options to consider for a documented local recurrence include pelvic irradiation for the previously operated patient, or surgery for a post-irradiation recurrence. A serum PSA which rises to high levels following treatment will often be associated with distant metastases, and this is more certain if the original tumor was locally advanced and/or the histology was poorly differentiated or aneuploid. A newly elevated serum acid phosphatase in a treated patient with prostate cancer will usually signify disseminated disease also. Whether to wait until a patient becomes symptomatic from a recurrence or to initiate endocrine treatment solely on the basis of a rising serum marker still remains a point of controversy. The overall survival of Stage D2 patients has not been prolonged by endocrine manipulations which were instituted before symptoms of widespread dissemination appeared. The routine use of periodic imaging studies to follow asymptomatic patients with prostate cancer after they have received treatment cannot be justified for clinical decision-making purposes. On the other hand, in treated patients who develop new symptoms suggesting bone metastases, radionuclide scans which are correlated carefully with the patient's symptoms and with radiographs of "hot" areas on the scans are indicated. When a suspected diagnosis of metastatic disease still remains in doubt, elevated serum tumor markers may provide additional evidence. Imaging studies can also be used to guide percutaneous biopsies of suspected metastases in bones (radionuclide scans and radiographs), or of persistent tumor in an irradiated prostate gland or at the urethro-vesical junction after surgery (TRUS). Since cancer of the prostate often progresses slowly and disseminated disease remains incurable at this time, some degree of uncertainty about the presence of metastases or of recurrent local disease might be safer and less costly than the use of multiple diagnostic studies and aggressive treatment (including endocrine manipulations) in nonsymptomatic patients.
Methodology for protein-ligand binding studies: application to a model for drug resistance, the HIV/FIV protease system.

A protocol for the rapid energetic analysis of protein-ligand complexes has been developed. This protocol involves the generation of protein-ligand complex ensembles followed by an analysis of the binding free energy components. We apply this methodology toward understanding the origin of binding specificity within the human immunodeficiency virus/feline immunodeficiency virus (HIV/FIV) protease system, a model system for drug resistance studies. A distinct difference in the internal strain of an inhibitor within each protein environment clearly favors the HIV protease complex, as observed experimentally. Our analysis also predicts that residues within the S2-S3 pockets of the FIV protease active site are responsible for this strain. Close examination of the active site residue contributions to interaction energy and desolvation energy identifies specific amino acids that may also play a role in determining the binding preferences of these two enzymes. Proteins 1999;36:318-331.
Overlapping control structures and security in large scale systems

The problem of decision making in a large-scale C3 system is addressed. The system has a hierarchical structure imposed by constraints on the flow of information and the command and control functions of the various military subsystems. A mathematical framework for the decision problem is presented and these ideas are related to the functional integrity of the system in the midst of random disturbances and failures.
Azelastine desensitization of transient receptor potential vanilloid 1: a potential mechanism explaining its therapeutic effect in nonallergic rhinitis

BackgroundCapsaicin, a prototypic transient receptor potential vanilloid 1 (TRPV1) agonist, has been shown to be more clinically effective in the treatment of nonallergic rhinitis (NAR) compared wi...
Validity of DSM-IV ADHD predominantly inattentive and combined types: relationship to previous DSM diagnoses/subtype differences.

ABSTRACT Since 1980, three different diagnostic nomenclatures have been published regarding attention-deficit hyperactivity disorder (ADHD). These changing conceptualizations and diagnostic criteria have generated considerable confusion. Objective To examine the multidimensional DSM-IV ADHD criteria in relation to how children and adolescents with a previous DSM-III ADD diagnosis or a DSM-III-R ADHD diagnosis are diagnosed according to DSM-IV criteria. Method: Children whose original diagnoses were according to DSM-III and DSM-III-R criteria received retrospective diagnoses according to DSM-IV criteria. Results: Predominantly inattentive ( n = 30) and combined types ( n = 26) were compared on their previous DSM-III and DSM-III-R diagnoses and on demographic, behavioral, cognitive, and comorbidity variables. Predominantly inattentive and combined type diagnoses corresponded with DSM-III ADD/WO and ADD/H diagnoses, respectively. The DSM-III-R ADHD diagnosis did not correspond with either DSM-IV subtype. Children with the combined type diagnosis had more externalizing codiagnoses, and their parents reported more externalizing, delinquent, and aggressive behaviors. Children with the predominantly inattentive type had more math learning disability codiagnoses. Conclusion: Results support a multidimensional conceptualization of ADHD. There exists close correspondence between the DSM-III ADD/H type and the DSM-IV predominantly inattentive type and between the DSM-III ADD/H type and the DSM-IV combined type. J. Am. Acad. Child Adolesc. Psychiatry , 1996, 35(3):325–333.
Experimental Campylobacter jejuni infection of adult mice.

HA-ICR adult mice were studied to develop an animal model for Campylobacter jejuni enteritis in humans. Fecal and ileal cultures made by selective and nonselective methods showed that C. jejuni and related organisms are not bowel commensals. Intragastric feeding of 108 CFU of three different strains of C. jejuni produced infection in 100% of the animals, and infection rates were dose dependent. Pretreatment with antibiotics or opiates was not necessary to induce infection. Fresh isolates and strains passed on artificial media yielded similar infection rates. Infected mice did not show signs of illness, but transient bacteremia within 10 min of oral infection was observed in nearly 100%. The small intestine was the principal target organ, with epithelial inflammation seen 48 h after infection. Control mice of four species had undetectable serum immunoglobulin G antibody specific for the infecting strain, but infected mice showed peak titers at 1 week with rapid decline. Immunoglobulin M titers rose minimally, and immunoglobulin A titers did not rise. Infected mice uniformly became chronic asymptomatic excretors, shedding 104 to 106 CFU/g of feces; a minority were biliary carriers. Intestine carriage was most pronounced in the stomach and proximal small intestine. Because this experimental infection led to bacteremia, transient pathological changes, and immunoglobulin G titer rises, this model may be useful for evaluating the effects of prophylactic and therapeutic interventions. Images
Superoinferior ventricles: Report of six cases

5. Shrestha NK, Moreno FL, Narciso FV, Torres L, Calleja HB. Two-dimensional echocardiographic diagnosis of left atria1 thrombus in rheumatic heart disease. A clinicopathologic study. Circulation 1983;67:341-7. Inoue K, Hung JS. Percutaneous transvenous mitral commissurotomy (PTMC): the Far East experience. In: Top01 EJ, ed. Textbook of interventional cardiology. Philadelphia: W.B. Saunders Co, 1990:887-99. Vahanian A, Michel PL, Cormier B, Vitoux B, Michel X, Slama M, Sarano LE, Trabelsi S, Ismail MB, Acar J. Results of percutaneous mitral commissurotomy in 200 patients. Am J Cardiol 1989;63:847-52. Hung JS, Lin FC, Chiang CW. Successful percutaneous transvenous catheter balloon mitral commissurotomy after warfarin therapy and resolution of left atria1 thrombus. Am J Cardiol 1989;64:126-8. Aschenberg W, Schliiter M, Kremer P, Schrbder E, Siglow V, Bleifeld W. Transesophageal two-dimensional echocardiography for the detection of left atria1 appendage thrombus. J Am Co11 Cardiol 1986;7:163-6.
A zebrafish model of congenital disorders of glycosylation with phosphomannose isomerase deficiency reveals an early opportunity for corrective mannose supplementation

Individuals with congenital disorders of glycosylation (CDG) have recessive mutations in genes required for protein N-glycosylation, resulting in multi-systemic disease. Despite the well-characterized biochemical consequences in these individuals, the underlying cellular defects that contribute to CDG are not well understood. Synthesis of the lipid-linked oligosaccharide (LLO), which serves as the sugar donor for the N-glycosylation of secretory proteins, requires conversion of fructose-6-phosphate to mannose-6-phosphate via the phosphomannose isomerase (MPI) enzyme. Individuals who are deficient in MPI present with bleeding, diarrhea, edema, gastrointestinal bleeding and liver fibrosis. MPI-CDG patients can be treated with oral mannose supplements, which is converted to mannose-6-phosphate through a minor complementary metabolic pathway, restoring protein glycosylation and ameliorating most symptoms, although liver disease continues to progress. Because Mpi deletion in mice causes early embryonic lethality and thus is difficult to study, we used zebrafish to establish a model of MPI-CDG. We used a morpholino to block mpi mRNA translation and established a concentration that consistently yielded 13% residual Mpi enzyme activity at 4 days post-fertilization (dpf), which is within the range of MPI activity detected in fibroblasts from MPI-CDG patients. Fluorophore-assisted carbohydrate electrophoresis detected decreased LLO and N-glycans in mpi morphants. These deficiencies resulted in 50% embryonic lethality by 4 dpf. Multi-systemic abnormalities, including small eyes, dysmorphic jaws, pericardial edema, a small liver and curled tails, occurred in 82% of the surviving larvae. Importantly, these phenotypes could be rescued with mannose supplementation. Thus, parallel processes in fish and humans contribute to the phenotypes caused by Mpi depletion. Interestingly, mannose was only effective if provided prior to 24 hpf. These data provide insight into treatment efficacy and the broader molecular and developmental abnormalities that contribute to disorders associated with defective protein glycosylation.
The diffuse ensemble filter

A new class of ensemble filters, called the Dif- fuse Ensemble Filter (DEnF), is proposed in this paper. The DEnF assumes that the forecast errors orthogonal to the first guess ensemble are uncorrelated with the latter ensemble and have infinite variance. The assumption of infinite variance corresponds to the limit of "complete lack of knowledge" and differs dramatically from the implicit assumption made in most other ensemble filters, which is that the forecast er- rors orthogonal to the first guess ensemble have vanishing errors. The DEnF is independent of the detailed covariances assumed in the space orthogonal to the ensemble space, and reduces to conventional ensemble square root filters when the number of ensembles exceeds the model dimension. The DEnF is well defined only in data rich regimes and involves the inversion of relatively large matrices, although this bar- rier might be circumvented by variational methods. Two al- gorithms for solving the DEnF, namely the Diffuse Ensemble Kalman Filter (DEnKF) and the Diffuse Ensemble Trans- form Kalman Filter (DETKF), are proposed and found to give comparable results. These filters generally converge to the traditional EnKF and ETKF, respectively, when the en- semble size exceeds the model dimension. Numerical exper- iments demonstrate that the DEnF eliminates filter collapse, which occurs in ensemble Kalman filters for small ensemble sizes. Also, the use of the DEnF to initialize a conventional square root filter dramatically accelerates the spin-up time for convergence. However, in a perfect model scenario, the DEnF produces larger errors than ensemble square root filters that have covariance localization and inflation. For imperfect forecast models, the DEnF produces smaller errors than the ensemble square root filter with inflation. These experiments suggest that the DEnF has some advantages relative to the ensemble square root filters in the regime of small ensemble size, imperfect model, and copious observations.
Using a deformable surface model to obtain a shape representation of the cortex

This paper examines the problem of obtaining a mathematical representation of the outer cortex of the human brain, which is a key problem in several applications, including morphological analysis of the brain, and spatial normalization and registration of brain images. A parameterization of the outer cortex is first obtained using a deformable surface algorithm which, motivated by the structure of the cortex, is constructed to find the central layer of thick surfaces. Based on this parameterization, a hierarchical representation of the outer cortical structure is proposed through its depth map and its curvature maps at various scales. Various experiments on magnetic resonance data are presented.
Systematic Review: Effective Management Strategies for Lactose Intolerance

This systematic review provides background for the NIH consensus statement on lactose intolerance. The review includes evidence from 36 trials that evaluated a variety of dietary, behavioral, and p...
Broader dynamic load balancing for hybrid/multi-level parallel programming models

Recently, Hybrid/Multi-Level Parallel Programming Models have begun gaining lots of momentum basically because they have proven to provide better scalability, speedup and utilisation than any single parallel programming model alone. In such models, load balancing should not only mean balancing the computational loads (as it has always been perceived), but also balancing I/O imbalance as well as synchronisation imbalance. In this paper, we propose a broader generic application/language/model independent multi-agent framework for dynamic load balancing. It takes most of the load-balancing burden away from programmers. It is not a library but a runtime support system that is not hardwired to the parallel applications. The framework is intended to handle varying levels of load changes in computations, I/O and/or synchronisation throughout the application run and it is an open architecture that currently supports four multi-level parallel programming models. It has a clean interface to the application, runs in parallel and provides additional functionality such as determination of when to load balance, and provide interface to end users. The proposed framework has been deployed in four hybrid/multi-level parallel programming models and its capabilities of issuing corrective actions against emerging imbalances were tested in the context of an adaptive mesh refinement application. Experimental results show that the framework is effective in monitoring, tuning and rebalancing emerging computational, I/O and synchronisation sources of load imbalance.
Periodic paralysis associated with thyrotoxicosis: a case report.

PERIODIC paralysis is a rare disease characterized by recurrent attacks of flaccid paralysis in the absence of any gross involvement of the central nervous system. The attacks usually occur at night, frequently following a high carbohydrate meal. They last from a few hours to a few days and subside, leaving no residual muscle dysfunction. The disease may appear as a familial trait or may occur sporadically with a negative family background. Talbott (1), in his exhaustive review of the literature on the subject through 1941, found that 18 per cent of the cases reported were of the sporadic type. He also noted that the sporadic type occurred almost exclusively in young males, whereas in the familial type the ratio of males to females was 3:1. Shinosaki (2), in 1926, first noted the association of periodic paralysis with thyroid disease. He reported a series of 24 cases, 15 of which manifested the clinical characteristics of thyrotoxicosis with associated periodic paralysis. Since this report, an additional ...
Stress-induced structural transformation and shear banding during simulated nanoindentation of a metallic glass

Simulated nanoindentation tests on a three-dimensional model of a binary metallic glass-forming alloy reveal how the stress field and material structure interact to control deformation beneath the indenter. Initially, the stress field follows the Hertzian solution with fluctuations due to heterogeneities. Homogeneous or localized plastic deformation arises, depending on the processing history of the material. In the case of localized deformation, the first shear band initiates sub-surface, relaxing the local shear stress. The subsequent shear band morphology is observed to be rate-dependent. Deformation induced changes in material structure are characterized in terms of short-range ordering and free volume, with the former providing significantly greater signal-to-noise.
Tooth whitening: what we now know.

Abstract Current research about tooth whitening shows that it is safe and effective when manufacturer's protocol is followed, yet there are risks of which the profession and users should be aware. This update provides a summary of current research and assessment of the safety and efficacy of tooth whitening regimens. Background Tooth whitening has become one of the most frequently requested dental procedures by the public. The public has come to demand whiter, more perfect smiles and in response many choices for tooth whitening have been made available. These include home-based products such as toothpastes, gels, and films, as well as in-office based systems where products containing highly concentrated bleaching agents are applied under professional supervision. The profession and public have been aware of certain risks related to tooth whitening such as increased tooth sensitivity and gingival irritation. New research has shown that there are other risks such as tooth surface roughening and softening, increased potential for demineralization, degradation of dental restorations, and unacceptable color change of dental restorations. The new research is also focused on optimizing whitening procedures to reduce tooth sensitivity and to increase the persistence of the whitening. Methods Current reports in the literature are reviewed that are related to the use of peroxide based whitening methods. These reports include in vitro studies for method optimization and mechanism as well as clinical studies on effects of various whitening regimens. Conclusions When manufacturer's instructions are followed, hydrogen peroxide and carbamide peroxide based tooth whitening is safe and effective. Patients should be informed of the risks associated with tooth whitening and instructed on identification of adverse occurrences so that they may seek professional help as needed.
Relationship between Body Surface Potential and Ventricular Excitation in the Dog

The distribution of body surface potential was studied in normal dogs by time normalization of nonsimuitaneously recorded voltages from 200 thoracic electrocardiograms using a digital computer technique. In addition, ventricular excitation data were obtained in the same animals using Scher myo-cardial plunge electrodes. Subsequently, the external surface voltage distribution was correlated spatially and temporally with the process of ventricular activation. It was noted that "dipolar" and "nondipolar" surface voltage patterns were related to the configuration of the instantaneous activation distribution in the ventricles. The reproducibility of the data obtained from the body surface and within the ventricles, and the observed consistent correlations between these two events indicate that there is a predictable relationship between major "inside-outside" activities.
The Independent Auditors’ Assessment and Conveyance of Risk (Preliminary Results)

The independent auditors’ primary objective is to insure the reader (user) of a corporation’s fmancial statements that those financial statements present “fairly” the information that they purport to present. The auditor does that by issuing an audit report to that effect; the audit report then accompanies the financial statements. By necessity, financial statements contain many estimates and judgments (such as the degree of collectibility of the firm’s receivables, the amount of money to be realized from the sale of a company’s inventory, the exposure associated with a lawsuit for which the company is a defendant, etc.). The auditor must evaluate the degree and type of uncertainty associated with the financial statements. If a firm is faced with material unusual circumstances, auditors are presently required to “qualify” their audit report by mentioning the uncertainty in the report. This research will examine how successful auditors are in determining and conveying whether a firm is faced with “material unusual circumstances.”
A genome-wide analysis of common fragile sites: What features determine chromosomal instability in the human genome?

Chromosomal common fragile sites (CFSs) are unstable genomic regions that break under replication stress and are involved in structural variation. They frequently are sites of chromosomal rearrangements in cancer and of viral integration. However, CFSs are undercharacterized at the molecular level and thus difficult to predict computationally. Newly available genome-wide profiling studies provide us with an unprecedented opportunity to associate CFSs with features of their local genomic contexts. Here, we contrasted the genomic landscape of cytogenetically defined aphidicolin-induced CFSs (aCFSs) to that of nonfragile sites, using multiple logistic regression. We also analyzed aCFS breakage frequencies as a function of their genomic landscape, using standard multiple regression. We show that local genomic features are effective predictors both of regions harboring aCFSs (explaining ∼77% of the deviance in logistic regression models) and of aCFS breakage frequencies (explaining ∼45% of the variance in standard regression models). In our optimal models (having highest explanatory power), aCFSs are predominantly located in G-negative chromosomal bands and away from centromeres, are enriched in Alu repeats, and have high DNA flexibility. In alternative models, CpG island density, transcription start site density, H3K4me1 coverage, and mononucleotide microsatellite coverage are significant predictors. Also, aCFSs have high fragility when colocated with evolutionarily conserved chromosomal breakpoints. Our models are predictive of the fragility of aCFSs mapped at a higher resolution. Importantly, the genomic features we identified here as significant predictors of fragility allow us to draw valuable inferences on the molecular mechanisms underlying aCFSs.
Metabolism, excretion, and pharmacokinetics of ((3,3-difluoropyrrolidin-1-yl)((2S,4S)-4-(4-(pyrimidin-2-yl)piperazin-1-yl)pyrrolidin-2-yl)methanone, a dipeptidyl peptidase inhibitor, in rat, dog and human.

The disposition of 3,3-difluoropyrrolidin-1-yl{(2S,4S)-4-[4-(pyrimidin-2-yl)piperazin-1-yl]pyrrolidin-2-yl}methanone (PF-00734200), a dipeptidyl peptidase IV inhibitor that progressed to phase 3 for the treatment of type 2 diabetes, was examined in rats, dogs, and humans after oral administration of a single dose of [14C]PF-00734200. Mean recoveries of administered radioactivity were 97.1, 92.2, and 87.2% in rats, dogs, and humans, respectively. The majority of radioactive dose was detected in the urine of dogs and humans and in the feces of rats. Absorption of PF-00734200 was rapid in all species, with maximal plasma concentrations of radioactivity achieved within 1 h after the dose. Circulating radioactivity was primarily composed of the parent drug (79.9, 80.2, and 94.4% in rat, dog, and human, respectively). The major route of metabolism was due to hydroxylation at the 5′ position of the pyrimidine ring (M5) in all species. In vitro experiments with recombinant cytochrome P450 isoforms suggested that the formation of M5 was catalyzed both by CYP2D6 and CYP3A4. Molecular docking simulations showed that the 5′ position of the pyrimidine moiety of PF-00734200 can access the heme iron-oxo of both CYP3A4 and CYP2D6 in an energetically favored orientation. Other metabolic pathways included amide hydrolysis (M2), N-dealkylation at the piperazine nitrogen (M3) and an unusual metabolite resulting from scission of the pyrimidine ring (M1). Phase II metabolic pathways included the following: carbamoyl glucuronidation (M9), glucosidation (M15) on the pyrrolidine nitrogen, and conjugation with creatinine to form an unusual metabolite/metabonate (M16). The data from these studies suggest that PF-00734200 is eliminated by both metabolism and renal clearance.
Anti-reflux surgery improves pulmonary function in lung transplant patients

months posttransplant, 23 (40%) had a positive BAL culture for Pseudomonas. In Kaplan-Meier analysis, early colonization with Pseudomonas is associated with decreased survival (p 0.027, by log-rank test), and a fourfold increase risk of death (hazard ratio 4.09, 95% CI 1.05,15.8, by Cox proportional hazards test). Other predictors of survival were donor age 30 yr. old (p 0.04), and more than 2 episodes of acute rejection (p 0.003). Conclusion: Early colonization or infection with Pseudomonas aeruginosa in CF lung transplant recipients is associated with significantly worse long-term survival. Additional research is needed to define the risk factors for early posttransplant infection, mechanisms of colonization in the donor lungs, and independent contribution of colonization to late death through multivariate analyses.
Integrative analysis and variable selection with multiple high-dimensional data sets

In high-throughput -omics studies, markers identified from analysis of single data sets often suffer from a lack of reproducibility because of sample limitation. A cost-effective remedy is to pool data from multiple comparable studies and conduct integrative analysis. Integrative analysis of multiple -omics data sets is challenging because of the high dimensionality of data and heterogeneity among studies. In this article, for marker selection in integrative analysis of data from multiple heterogeneous studies, we propose a 2-norm group bridge penalization approach. This approach can effectively identify markers with consistent effects across multiple studies and accommodate the heterogeneity among studies. We propose an efficient computational algorithm and establish the asymptotic consistency property. Simulations and applications in cancer profiling studies show satisfactory performance of the proposed approach.
Attentional states influence early neural responses associated with motivational processes: Local vs. global attentional scope and N1 amplitude to appetitive stimuli

Positive affects vary in the degree with which they are associated with approach motivation, the drive to approach an object or a goal. High approach-motivated positive affects cause a narrowing of attention, whereas low approach-motivated positive affects causes a broadening of attention. The current study was designed to extend this work by examining whether the relationship between motivation and attentional bias was bi-directional. Specifically, the experiment investigated whether a manipulated local attentional scope would cause greater approach motivational processing than a global attentional scope as measured by neural processes as early as 100 ms. As compared to a global attentional scope, a local attentional scope caused greater neural processing associated with approach motivation as measured by the N1 to appetitive pictures.