Miracle-dz/UniFAR-FTUs huggingface dataset:
The standard protein mix database: a diverse data set to assist in the production of improved Peptide and protein identification software tools.

Tandem mass spectrometry (MS/MS) is frequently used in the identification of peptides and proteins. Typical proteomic experiments rely on algorithms such as SEQUEST and MASCOT to compare thousands of tandem mass spectra against the theoretical fragment ion spectra of peptides in a database. The probabilities that these spectrum-to-sequence assignments are correct can be determined by statistical software such as PeptideProphet or through estimations based on reverse or decoy databases. However, many of the software applications that assign probabilities for MS/MS spectra to sequence matches were developed using training data sets from 3D ion-trap mass spectrometers. Given the variety of types of mass spectrometers that have become commercially available over the last 5 years, we sought to generate a data set of reference data covering multiple instrumentation platforms to facilitate both the refinement of existing computational approaches and the development of novel software tools. We analyzed the proteolytic peptides in a mixture of tryptic digests of 18 proteins, named the "ISB standard protein mix", using 8 different mass spectrometers. These include linear and 3D ion traps, two quadrupole time-of-flight platforms (qq-TOF), and two MALDI-TOF-TOF platforms. The resulting data set, which has been named the Standard Protein Mix Database, consists of over 1.1 million spectra in 150+ replicate runs on the mass spectrometers. The data were inspected for quality of separation and searched using SEQUEST. All data, including the native raw instrument and mzXML formats and the PeptideProphet validated peptide assignments, are available at http://regis-web.systemsbiology. net/PublicDatasets/.
Production of radionuclides and their migration in groundwater: a Fermilab case history model

Particle accelerators that are buried underground like those at Fermilab create a condition where soil can be activated. Naturally percolating groundwater becomes contaminated by leaching out some of the radioactivity as it migrates through the soil to the underlying aquifer. The Fermilab Concentration Model was formulated to account for and combine the fundamental processes of production, leaching, and migration. Its general features are described, then site-specific data from one of the target stations are used to make calculations and compare them to regulatory limits and DOE guidelines.
Towards certifiable reconfigurable real-time mission critical software systems

This thesis makes a contribution towards the certification of reconfigurable real-time mission critical software systems. In highly reconfigurable software systems it is possible for a situation to arise where the system expends most or all of its resoun;:es on reconfiguring, and thus cannot provide sufficient resources to conduct intended computing functions. This anomaly has been termed "configuration thrashing" by the author due to its loose analogy to memory thrashing. If configuration thrashing is not eliminated, or at least minimised, then it is possible for circumstance to occur where reconfigurable systems cannot be certified due to potential failure to meet deadlines caused by configuration thrashing. The elimination of reconfiguration thrashing is a step towards certifiable dynamic reconfigurable systems capable of enforcing deadlines. The elimination of reconfiguration thrashing is necessary, though not sufficient, for this goal. In order to restrict configuration thrashing it is necessary to understand the possibilities available within reconfigurable software. A VDM-SL model is presented to explore the options available for reconfigurable architectures, and has allowed many operators to be formally specified providing a much greater understanding of the tasks involved in reconfiguration. The thesis demonstrates how model checkers can be used to check software processes for configuration thrashing using predefined CSP models, thus allowing system programmers to engineer configuration thrashing out of systems. However, model checkers are susceptible to state space explosion, particularly if models are large and / or complex, which may make the use of the model checkers impractical or even impossible for some systems. The thesis therefore also explores potential run-time solutions to configuration thrashing. These solutions allow developers to include additional logic / processes within their systems in order to eliminate configuration thrashing (without the use of model checkers). Several options are explored in-depth, from providing mechanisms for developers to choose when reconfiguration can / cannot occur, to a rule based solution. The exploration of the rule based solution explores issues such as rule expression, rule predictability, as well as potential core rules. The two approaches taken within this thesis to eliminate, or at least restrict sufficiently, configuration thrashing form a basis which would allow for the certification of reconfigurable real-time mission critical software systems.
Naturopathic Physicians: Holistic Primary Care and Integrative Medicine Specialists

ABSTRACT The use of Complimentary and Alternative Medicine (CAM) is increasing in the United States; there is a need for physician level practitioners who possess extensive training in both CAM and conventional medicine. Naturopathic physicians possess training that allows integration of modern scientific knowledge and the age-old wisdom of natural healing techniques. Naturopathic philosophy provides a framework to implement CAM in concert with conventional therapies. The naturopathic physician's expertise in both conventional medicine and CAM allows a practice style that provides excellent care through employing conventional and CAM modalities while utilizing modern research and evidence-based medicine.
Single-chain protein mimetics of the N-terminal heptad-repeat region of gp41 with potential as anti–HIV-1 drugs

Significance The envelope subunit gp41 is an attractive target for therapeutic intervention against HIV-1. Interfering with the interaction between the heptad-repeat regions of gp41 is a promising approach to inhibit HIV-1 fusion to the host cell membrane. Here, we present an alternative rational design and protein-engineering approach to produce highly stable single-chain proteins that accurately mimic the trimeric coiled-coil surface of the gp41 N-terminal heptad repeat. This approach has a strong potential for development to HIV-1 drugs, vaccines, or microbicides and could be extendable to the design of proteins interfering with other types of coiled-coil interactions. During HIV-1 fusion to the host cell membrane, the N-terminal heptad repeat (NHR) and the C-terminal heptad repeat (CHR) of the envelope subunit gp41 become transiently exposed and accessible to fusion inhibitors or Abs. In this process, the NHR region adopts a trimeric coiled-coil conformation that can be a target for therapeutic intervention. Here, we present an approach to rationally design single-chain protein constructs that mimic the NHR coiled-coil surface. The proteins were built by connecting with short loops two parallel NHR helices and an antiparallel one with the inverse sequence followed by engineering of stabilizing interactions. The constructs were expressed in Escherichia coli, purified with high yield, and folded as highly stable helical coiled coils. The crystal structure of one of the constructs confirmed the predicted fold and its ability to accurately mimic an exposed gp41 NHR surface. These single-chain proteins bound to synthetic CHR peptides with very high affinity, and furthermore, they showed broad inhibitory activity of HIV-1 fusion on various pseudoviruses and primary isolates.
Diagnosis makes a difference: Perceptions of older persons with dementia symptoms

ABSTRACT Background/Study Context: Employing the stereotype content model and terror management theory, we examined whether stereotypes and feelings about persons with dementia vary depending on the type of dementia diagnosis and purported causes of the dementia. Methods: Participants were randomly assigned to read one of four vignettes that depicted a man who consulted his doctor because of memory problems. All vignettes described the same symptoms and diagnostic tests, but each of four groups read a different result: all tests normal (Normal); Alzheimer’s disease (AD); Wernicke–Korsakoff Syndrome (WKS) associated with alcohol abuse; and chronic traumatic encephalopathy (CTE) associated with head injuries from playing football in high school and college. Measures included a word fragment completion task, a stereotype content scale, and an emotions scale. Results: Results showed no differences in the number of death-related words generated in the word fragment completion task and no differences in assessment of competence across the four groups. Those in the Normal, AD, and CTE groups evaluated the man as warmer than those in the WKS group. Participants in the AD condition showed more empathy than those in the WKS group. There were no differences in pity or fear but the CTE condition produced more envy and admiration and the WKS condition produced more contempt. Conclusion: These results suggest that different forms of dementia elicit varying emotional and cognitive responses.
Rapamycin Potentiates Transforming Growth Factor β-Induced Growth Arrest in Nontransformed, Oncogene-Transformed, and Human Cancer Cells

ABSTRACT Transforming growth factor β (TGF-β) induces cell cycle arrest of most nontransformed epithelial cell lines. In contrast, many human carcinomas are refractory to the growth-inhibitory effect of TGF-β. TGF-β overexpression inhibits tumorigenesis, and abolition of TGF-β signaling accelerates tumorigenesis, suggesting that TGF-β acts as a tumor suppressor in mouse models of cancer. A screen to identify agents that potentiate TGF-β-induced growth arrest demonstrated that the potential anticancer agent rapamycin cooperated with TGF-β to induce growth arrest in multiple cell lines. Rapamycin also augmented the ability of TGF-β to inhibit the proliferation of E2F1-, c-Myc-, and V12H-Ras-transformed cells, even though these cells were insensitive to TGF-β-mediated growth arrest in the absence of rapamycin. Rapamycin potentiation of TGF-β-induced growth arrest could not be explained by increases in TGF-β receptor levels or rapamycin-induced dissociation of FKBP12 from the TGF-β type I receptor. Significantly, TGF-β and rapamycin cooperated to induce growth inhibition of human carcinoma cells that are resistant to TGF-β-induced growth arrest, and arrest correlated with a suppression of Cdk2 kinase activity. Inhibition of Cdk2 activity was associated with increased binding of p21 and p27 to Cdk2 and decreased phosphorylation of Cdk2 on Thr160. Increased p21 and p27 binding to Cdk2 was accompanied by decreased p130, p107, and E2F4 binding to Cdk2. Together, these results indicate that rapamycin and TGF-β cooperate to inhibit the proliferation of nontransformed cells and cancer cells by acting in concert to inhibit Cdk2 activity.
Requirement for the Amino-Terminal Domain of Sindbis Virus nsP4 during Virus Infection

ABSTRACT The Sindbis virus RNA-dependent RNA polymerase nsP4 possesses an amino-terminal region that is unique to alphaviruses and is predicted to be disordered. To determine the importance of this region during alphavirus replication, 29 mutations were introduced, and resultant viruses were assessed for growth defects. Three small plaque mutants, D41A, G83L, and the triple mutant GPG(8-10)VAV, had defects in subgenome synthesis, minus-strand synthesis, and overall levels of viral RNA synthesis, respectively. Large plaque viruses were selected following passage in BHK-21 cells, and the genomes of these were sequenced. Suppressor mutations in nsP1, nsP2, and nsP3 that restored viral RNA synthesis were identified. An nsP2 change from M282 to L and an nsP3 change from H99 to N corrected the D41A-induced defect in subgenomic RNA synthesis. Three changes in nsP1, I351 to V, I388 to V, or the previously identified change, N374 to H (C. L. Fata, S. G. Sawicki, and D. L. Sawicki, J. Virol. 76:8641-8649, 2002), suppressed the minus-strand synthetic defect. A direct reversion back to G at position 8 reduced the RNA synthesis defect of the GPG(8-10)VAV virus. These results imply that nsP4's amino-terminal domain participates in distinct interactions with other nsPs in the context of differentially functioning RNA synthetic complexes, and flexibility in this domain is important for viral RNA synthesis. Additionally, the inability of the mutant viruses to efficiently inhibit host protein synthesis suggests a role for nsP4 in the regulation of host cell gene expression.
ABA-Hypersensitive Germination3 Encodes a Protein Phosphatase 2C (AtPP2CA) That Strongly Regulates Abscisic Acid Signaling during Germination among Arabidopsis Protein Phosphatase 2Cs1[W]

The phytohormone abscisic acid (ABA) regulates physiologically important developmental processes and stress responses. Previously, we reported on Arabidopsis (Arabidopsis thaliana) L. Heynh. ahg mutants, which are hypersensitive to ABA during germination and early growth. Among them, ABA-hypersensitive germination3 (ahg3) showed the strongest ABA hypersensitivity. In this study, we found that the AHG3 gene is identical to AtPP2CA, which encodes a protein phosphatase 2C (PP2C). Although AtPP2CA has been reported to be involved in the ABA response on the basis of results obtained by reverse-genetics approaches, its physiological relevance in the ABA response has not been clarified yet. We demonstrate in vitro and in vivo that the ahg3-1 missense mutation causes the loss of PP2C activity, providing concrete confirmation that this PP2C functions as a negative regulator in ABA signaling. Furthermore, we compared the effects of disruption mutations of eight structurally related PP2C genes of Arabidopsis, including ABI1, ABI2, HAB1, and HAB2, and found that the disruptant mutant of AHG3/AtPP2CA had the strongest ABA hypersensitivity during germination, but it did not display any significant phenotypes in adult plants. Northern-blot analysis clearly showed that AHG3/AtPP2CA is the most active among those PP2C genes in seeds. These results suggest that AHG3/AtPP2CA plays a major role among PP2Cs in the ABA response in seeds and that the functions of those PP2Cs overlap, but their unique tissue- or development-specific expression confers distinct and indispensable physiological functions in the ABA response.
Depressive Symptoms and Mortality Risk in a National Sample: Confounding Effects of Health Status

Objective: We examined the association between depressive symptoms and all-cause mortality in a population sample. Published findings on the relation between depressive symptoms and mortality risk point to an inconsistent association and one that is likely influenced by health status. Few studies have assessed this relation in randomly selected population samples. Methods: Participants were 3617 noninstitutionalized adults, age 25 years or older, from the Americans’ Changing Lives Study, an ongoing longitudinal study of a nationally representative sample. Depressive symptoms were measured by the 11-item version of the Center for Epidemiological Studies Depression Scale (CES-D). Cox proportional hazards models estimated the relative risk of mortality as a function of the CES-D scores at baseline. Results: In 7.5 years of follow-up, 542 deaths occurred. Each 1-standard unit increase on the CES-D predicted a 21% increased risk of all-cause mortality, adjusting for age, gender, and race (hazard ratio = 1.21, 95% confidence interval = 1.08 to 1.36, p = .001). This association was weakened somewhat following adjustment for education, income, body mass index, smoking and alcohol consumption (hazard ratio = 1.13, 95% confidence interval = 0.99 to 1.28, p = .06). However, control for self-reported functional limitations or chronic health conditions at baseline effectively eliminated the relationship. Analyses limited to participants with good to excellent health or no functional impairments at baseline showed no association between depressive symptoms and subsequent mortality risk. Secondary analyses showed no association between depressive symptoms and cardiovascular mortality. Conclusions: These findings from a randomly selected, nationally representative sample do not support the hypothesis that depressive symptoms are independently related to mortality in the general population, after adequate adjustment for the confounding effects of physical health status. ACL = Americans’ Changing Lives Study; CES-D = Center for Epidemiological Studies Depression Scale; CHD = coronary heart disease; CI = confidence interval; HR = hazard ratio.
SpamCloud: A MapReduce based anti-spam architecture

From a computing perspective and context, Spam can be described as an Internet scale problem. A potential approach for tackling Spam is consequently via the application of Internet scale algorithms and techniques. A number of approaches exist which are pitched to tackle this type of challenge in such fashion, including MapReduce. This research evaluates the degree of feasibility and applicability of Hadoop's Map Reduce Framework when applied to spam filtering.
The contribution of haploids, diploids and clones to fine‐scale population structure in the seaweed Cladophoropsis membranacea (Chlorophyta)

Local populations of Cladophoropsis membranacea exist as mats of coalesced thalli composed of free‐living haploid and diploid plants including clonally reproduced plants of either phase. None of the phases are morphologically distinguishable. We used eight microsatellite loci to explore clonality and fine‐scale patch structure in C. membranacea at six sites on the Canary Islands. Mats were always composites of many individuals; not single, large clones. Haploids outnumbered diploids at all sites (from 2:1 to 10:1). In both haploid and diploid plants, genetic diversity was high and there was no significant difference in allele frequencies. Significant heterozygote deficiencies were found in the diploid plants at five out of six sites and linkage disequilibrium was associated with the haploid phase at all sites. Short dispersal distances of gametes/spores and small effective population sizes associated with clonality probably contribute to inbreeding. Spatial autocorrelation analysis revealed that most clones were found within a radius of ≈ 60 cm and rarely further than 5 m. Dominance of the haploid phase may reflect seasonal shifts in the relative frequencies of haploids and diploids, but may alternatively reflect superiority of locally adapted and competitively dominant, haploid clones; a strategy that is theoretically favoured in disturbed environments. Although sexual reproduction may be infrequent in C. membranacea, it is sufficient to maintain both life history phases and supports theoretical modelling studies that show that haploid–diploid life histories are an evolutionarily stable strategy.
OUTCOMES FOR SURGICAL AND ENDOVASCULAR MANAGEMENT OF INTRACRANIAL ANEURYSMSUSING A COMPREHENSIVE GRADING SYSTEM

OBJECTIVEA systematic approach to the consideration of various factors on outcome demands a comprehensive grading system for patients with intracranial aneurysms. We have previously identified potential patient- and lesion-specific factors that correlate strongly with outcome after treatment for intracranial aneurysms, and we have developed a comprehensive grading system based on these factors. In this study, we evaluate this grading system in a large series of aneurysm patients treated by surgery and endovascular therapy. METHODSBetween January 1998 and January 2003, ruptured and unruptured aneurysm patients were prospectively entered into a database. Based on our previous study that showed which factors correlated strongly with outcome, data were collected on patient age, aneurysm size, Hunt and Hess grade, and Fisher scale (if presenting with subarachnoid hemorrhage), and a Massachusetts General Hospital grade was then applied. The modified Glasgow Outcome Scale was used for clinical assessment at follow-up, and a binary analysis classified patients into favorable versus unfavorable outcome. Univariate and multivariate analyses for the predictor variables were performed. RESULTSOne thousand forty-nine aneurysms in 914 patients were identified. Fifty-eight percent (n = 608) of the lesions were unruptured, and 25% (n = 261) were treated endovascularly. For patients treated either surgically or endovascularly, worsening outcome was demonstrated for higher Hunt and Hess grade (surgery, P < 0.001; endovascular, P < 0.001), Fisher scale (surgery, P < 0.001; endovascular, P < 0.001) and for older patients (surgery, P < 0.001; endovascular, P = 0.004). Size of aneurysm had a significant effect on outcome after surgery (P = 0.04), but not after endovascular therapy (P = 0.3). Overall, there was a greater proportion of favorable outcomes for anterior circulation compared with posterior circulation lesions (P < 0.0001). For both the surgical and endovascular subgroups, MGH grade correlated well with clinical outcomes. CONCLUSIONThe MGH grade is a comprehensive grading system that is easily applied and that allows separation of patients with aneurysms into groups with markedly different outcomes. This information can potentially be helpful in making treatment decisions and when discussing projected outcome before surgical or endovascular intervention of both unruptured and ruptured aneurysms.
Biodistribution and Gastrointestinal Drug Delivery of New Lipidic Multilamellar Vesicles

Encapsulation of therapeutic molecules in a new noncationic multilamellar vector (Spherulites ®), composed of phosphatidylcholine, cholesterol, and polyoxyethylene alcohol, is described here. Spherulites with entrapped drugs were prepared by shearing a phospholipidic lyotropic lamellar phase using a recently discovered method. The average size of these vesicles is ~300 nm. Our formulation did not show cytotoxicity to human cells and could be used as a drug delivery system. Our previous experiments showed that this new multilamellar vector is stable in many different buffers such as serum, acidic or basic buffers, and enzymatic buffers and may deliver drugs in vivo. We describe two ways of administration for drug delivery. The tissue biodistribution of radiolabeled Spherulites entrapping 125 I protein A was studied after intravenous injection in Wistar rats using the major organs of the body. Approximately 70% of the radioactivity was found in the spleen 60 min after injection and about half this percentage was found in the liver. By 6 hr, only 52% remained in the spleen. The other tissues accumulated < 30% of the dose throughout the duration of the study. On the other hand, oral administration of Spherulites, entrapping 111 In-NTA, in fasting rats showed a significant increase of radioactivity in blood.
Constrained TV-minimization image reconstruction from sparse-view diagnostic CT data

Advanced diagnostic CT scanners acquire data at a large number of projections. Conventional image reconstruction algorithms, such as FDK algorithm, are analytic-based. Recently, optimization-based algorithms have been under investigation because they may reconstruct images with improved quality, and has the potential and flexibility for image reconstruction from data in non-conventional configurations, such as data collected at sparse views. In this work, using the adaptive-steepest-descent-projection-onto-convex-sets (ASD-POCS) algorithm, we investigate image reconstruction from swine data sets collected by using Toshiba 320-slice CT scanner. We performed ASD-POCS image reconstruction from 1200-, and 600-view data sets and compared them with those obtained with currently used analytic-based algorithm. The results demonstrate that images reconstructed from 1200- and 600-view data sets by use of ASD-POCS algorithm can be comparable or improved over images obtained with conventional algorithms.