Artificial Mixture Methods for Correlated Nominal Responses and Discrete Failure Time.

Multinomial logit model with random effects is a common choice for modeling correlated nominal responses. But due to the presence of random effects and the complex form of the multinomial probabilities, the computation is often costly. We generalize the artificial mixture method for independent nominal response to correlated nominal responses. Our method transforms the complex multinomial likelihood to Poisson-type likelihoods and hence allows for the estimates to be obtained iteratively solving a set of independent low-dimensional problems. The methodology is applied to real data and studied by simulations. For discrete failure time data in large data sets, there are often many ties and a large number of distinct event time points. This poses a challenge of a high-dimensional model. We explore two ideas with the discrete proportional odds (PO) model due to its methodological and computational convenience. The log-likelihood function of discrete PO model is the difference of two convex functions; hence difference convex algorithm (DCA) carries over and brings computational efficiency. An alternative method proposed is a recursive procedure. As a result of simulation studies, these two methods work better than Quasi-Newton method in terms of both accuracy and computational time. The results from the research on the discrete PO model motivate us to develop artificial mixture methods to discrete failure time data. We consider a general discrete transformation model and mediate the high-dimensional optimization problem by changing the model form at the “complete-data” level (conditional on artificial variables). Two complete data representations are studied: proportional hazards (PH) and PO mixture frameworks. In the PH mixture framework, we reduce the high-dimensional optimization problem to many one-dimensional problems. In the PO mixture framework, both recursive solution and DCA can be synthesized into the M-step of EM algorithm leading to simplification in the optimization. PO mixture method is recommended due to its simplicity. It is applied to real data sets to fit a discrete PH and PHPH models. Simulation study fitting discrete PH model shows that the advocated PO mixture method outperforms Quasi-Newton method in terms of both accuracy and speed.Ph.D.BiostatisticsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/91531/1/sfwang_1.pd

Postharvest handling systems assessment for vegetables in China and Australia

The needs of industry are increasingly being targeted when planning research programs. This is frequently done informally by individual researchers or research groups, but often lacks a comprehensive study of the systems and people in the system. This may result in misdirected, inappropriate, or inadequate research programs that do not meet the needs of the industry groups concerned. A component of the ACIAR project PHT/1994/016 “Shelf-life extension of leafy vegetables” was the assessment of postharvest handling systems for a range of vegetables in China and Australia. The assessment methodology selected was an adaptation of ‘A commodity systems assessment methodology for program and project identification’ developed by J. La Gra of the University of Idaho, USA. We used the methodology in a series of case studies reflecting the main postharvest handling systems. Crops assessed were Chinese cabbage, oriental bunching onion, pak choi (in China), and broccoli (in China and Australia). We assessed: • fresh and stored, and domestic and export, Chinese cabbage; • stored oriental bunching onion; • fresh pak choi; and • fresh domestic and exported broccoli. We also included in the assessment peri-urban production and product transported long distances to market. This paper discusses the methodology used and its advantages and limitations

DGR mutagenic transposition occurs via hypermutagenic reverse transcription primed by nicked template RNA.

Diversity-generating retroelements (DGRs) are molecular evolution machines that facilitate microbial adaptation to environmental changes. Hypervariation occurs via a mutagenic retrotransposition process from a template repeat (TR) to a variable repeat (VR) that results in adenine-to-random nucleotide conversions. Here we show that reverse transcription of the Bordetella phage DGR is primed by an adenine residue in TR RNA and is dependent on the DGR-encoded reverse transcriptase (bRT) and accessory variability determinant (Avd ), but is VR-independent. We also find that the catalytic center of bRT plays an essential role in site-specific cleavage of TR RNA for cDNA priming. Adenine-specific mutagenesis occurs during reverse transcription and does not involve dUTP incorporation, indicating it results from bRT-catalyzed misincorporation of standard deoxyribonucleotides. In vivo assays show that this hybrid RNA-cDNA molecule is required for mutagenic transposition, revealing a unique mechanism of DNA hypervariation for microbial adaptation

Isolation of Thiobacillus spp. and its application in the removal of heavy metals from activated sludge

Two strains of Thiobacillus isolated from native excess activated sludge were identified as Acidithiobacillus ferrooxidans and Acidithiobacillus thiooxidans by 16S rRNA gene sequencing and physiological-biochemical characteristics. Single and mixed cultures of the strains were used to carry out bioleaching for 9 days in order to remove heavy metals from activated sludge. The changes in pH, oxidation-reduction potential, and contents of heavy metals were measured. The results show that the bioleaching effect of the mixed culture was best in all runs, and that the final removals of As, Cr, Cu, Ni, and Zn were 96.09, 93.47, 98.32, 97.88, and 98.60%, respectively, whereas the removals of Cd and Pb decreased rapidly after six days. In addition, we demonstrate for the first time that bioleaching can reduce the pathogenicity of sludge by detecting fecal coliforms before and after bioleaching in order to ensure that the sludge was suitable for agricultural land application.Key words: Acidithiobacillus ferrooxidans, Acidithiobacillus thiooxidans, excess activated sludge, removing heavy metals, sludge pathogenicity

Neural Dysfunction Underlying Working Memory Processing at Different Stages of the Illness Course in Schizophrenia:A Comparative Meta-analysis

Schizophrenia (SCZ), as a chronic and persistent disorder, exhibits working memory deficits across various stages of the disorder, yet the neural mechanisms underlying these deficits remain elusive with inconsistent neuroimaging findings. We aimed to compare the brain functional changes of working memory in patients at different stages: clinical high risk (CHR), first-episode psychosis (FEP), and long-term SCZ, using meta-analyses of functional magnetic resonance imaging (fMRI) studies. Following a systematic literature search, fifty-six whole-brain task-based fMRI studies (15 for CHR, 16 for FEP, 25 for long-term SCZ) were included. The separate and pooled neurofunctional mechanisms among CHR, FEP and long-term SCZ were generated by Seed-based d Mapping toolbox. The CHR and FEP groups exhibited overlapping hypoactivation in the right inferior parietal lobule, right middle frontal gyrus, and left superior parietal lobule, indicating key lesion sites in the early phase of SCZ. Individuals with FEP showed lower activation in left inferior parietal lobule than those with long-term SCZ, reflecting a possible recovery process or more neural inefficiency. We concluded that SCZ represent as a continuum in the early stage of illness progression, while the neural bases are inversely changed with the development of illness course to long-term course

Relationship between the Montreal Cognitive Assessment and Mini-mental State Examination for assessment of mild cognitive impairment in older adults

BACKGROUND: The Montreal Cognitive Assessment (MoCA) was developed to enable earlier detection of mild cognitive impairment (MCI) relative to familiar multi-domain tests like the Mini-Mental State Exam (MMSE). Clinicians need to better understand the relationship between MoCA and MMSE scores. METHODS: For this cross-sectional study, we analyzed 219 healthy control (HC), 299 MCI, and 100 Alzheimer's disease (AD) dementia cases from the Alzheimer's Disease Neuroimaging Initiative (ADNI)-GO/2 database to evaluate MMSE and MoCA score distributions and select MoCA values to capture early and late MCI cases. Stepwise variable selection in logistic regression evaluated relative value of four test domains for separating MCI from HC. Functional Activities Questionnaire (FAQ) was evaluated as a strategy to separate dementia from MCI. Equi-percentile equating produced a translation grid for MoCA against MMSE scores. Receiver Operating Characteristic (ROC) analyses evaluated lower cutoff scores for capturing the most MCI cases. RESULTS: Most dementia cases scored abnormally, while MCI and HC score distributions overlapped on each test. Most MCI cases scored ≥ 17 on MoCA (96.3%) and ≥ 24 on MMSE (98.3%). The ceiling effect (28-30 points) for MCI and HC was less using MoCA (18.1%) versus MMSE (71.4%). MoCA and MMSE scores correlated most for dementia (r = 0.86; versus MCI r = 0.60; HC r = 0.43). Equi-percentile equating showed a MoCA score of 18 was equivalent to MMSE of 24. ROC analysis found MoCA ≥ 17 as the cutoff between MCI and dementia that emphasized high sensitivity (92.3%) to capture MCI cases. The core and orientation domains in both tests best distinguished HC from MCI groups, whereas comprehension/executive function and attention/calculation were not helpful. Mean FAQ scores were significantly higher and a greater proportion had abnormal FAQ scores in dementia than MCI and HC. CONCLUSIONS: MoCA and MMSE were more similar for dementia cases, but MoCA distributes MCI cases across a broader score range with less ceiling effect. A cutoff of ≥ 17 on the MoCA may help capture early and late MCI cases; depending on the level of sensitivity desired, ≥ 18 or 19 could be used. Functional assessment can help exclude dementia cases. MoCA scores are translatable to the MMSE to facilitate comparison

An insight into the mechanism and evolution of shale reservoir characteristics with over-high maturity

AbstractOver-high maturity is one of the most vital characteristics of marine organic-rich shale reservoirs from the Lower Paleozoic in the south part of China. The organic matter (OM) in shale gas reservoirs almost went through the entire thermal evolution. During this wide span, a great amount of hydrocarbon was available and numerous pores were observed within the OM including kerogen and solid bitumen/pyrobitumen. These nanopores in solid bitumen/pyrobitumen can be identified using SEM. The imaging can be dissected and understood better based on the sequence of diagenesis and hydrocarbon charge with the shape of OM and pores. In terms of the maturity process showed by the various typical cases, the main effects of the relationship between the reservoir porosity and organic carbon abundance are interpreted as follows: the change and mechanism of reservoirs properties due to thermal evolution are explored, such as gas carbon isotope from partial to complete rollover zone, wettability alteration from water-wet to oil-wet and then water-wet pore surface again, electrical resistivity reversal from the increasing to decreasing stage, and nonlinearity fluctuation of rock elasticity anisotropy. These indicate a possible evolution pathway for shale gas reservoirs from the Lower Paleozoic in the southern China, as well as the general transformation processes between different shale reservoirs in thermal stages

Total ginsenosides suppress monocrotaline-induced pulmonary hypertension in rats: involvement of nitric oxide and mitogen-activated protein kinase pathways

AbstractBackgroundGinsenosides have been shown to exert beneficial pharmacological effects on the central nervous, cardiovascular, and endocrine systems. We sought to determine whether total ginsenosides (TG) inhibit monocrotaline (MCT)-induced pulmonary hypertension and to elucidate the underlying mechanism.MethodsMCT-intoxicated rats were treated with gradient doses of TG, with or without NG-nitro-l-arginine methyl ester. The levels of molecules involving the regulation of nitric oxide and mitogen-activated protein kinase pathways were determined.ResultsTG ameliorated MCT-induced pulmonary hypertension in a dose-dependent manner, as assessed by the right ventricular systolic pressure, the right ventricular hypertrophy index, and pulmonary arterial remodeling. Furthermore, TG increased the levels of pulmonary nitric oxide, endothelial nitric oxide synthase, and cyclic guanosine monophosphate. Lastly, TG increased mitogen-activated protein kinase phosphatase-1 expression and promoted the dephosphorylation of extracellular signal-regulated protein kinases 1/2, p38 mitogen-activated protein kinase, and c-Jun NH2-terminal kinase 1/2.ConclusionTG attenuates MCT-induced pulmonary hypertension, which may involve in part the regulation of nitric oxide and mitogen-activated protein kinase pathways