Miracle-dz/UniFAR-FTUs huggingface dataset:
Viscoelastic Behavior of Human Lamin A Proteins in the Context of Dilated Cardiomyopathy

Lamins are intermediate filament proteins of type V constituting a nuclear lamina or filamentous meshwork which lines the nucleoplasmic side of the inner nuclear membrane. This protein mesh provides a supporting scaffold for the nuclear envelope and tethers interphase chromosome to the nuclear periphery. Mutations of mainly A-type lamins are found to be causative for at least 11 human diseases collectively termed as laminopathies majority of which are characterised by aberrant nuclei with altered structural rigidity, deformability and poor mechanotransduction behaviour. But the investigation of viscoelastic behavior of lamin A continues to elude the field. In order to address this problem, we hereby present the very first report on viscoelastic properties of wild type human lamin A and some of its mutants linked with Dilated cardiomyopathy (DCM) using quantitative rheological measurements. We observed a dramatic strain-softening effect on lamin A network as an outcome of the strain amplitude sweep measurements which could arise from the large compliance of the quasi-cross-links in the network or that of the lamin A rods. In addition, the drastic stiffening of the differential elastic moduli on superposition of rotational and oscillatory shear stress reflect the increase in the stiffness of the laterally associated lamin A rods. These findings present a preliminary insight into distinct biomechanical properties of wild type lamin A protein and its mutants which in turn revealed interesting differences.
Effect of Chronic Stress on Immune Function and Health in the Elderly

Cunningham-Rundles, S. (1993). Nutrient modulation 01' the immune response. New York: Marcel Dekker. Gillis, S. , Kozak, R. , Durante, M. , & Weksler, M. (1981). Immunological studies of aging. Decreased production and response to T cell growth factor by lymphocytes from aged humans. Journal 01' Clinical lnvestigation, 67. 937-942. Hulstaerr, F" Hanner, L Deneys, V" Munhyeshuli, Y, Reichert, T. De Bruyere, M" & Strauss. K. (1994). Age-related changes in human blood lymphocytes subpopulations. II. Varying kinetics of percentage and absolute count measurements. Clinical Immunology and Immunopathology. 70. 152-158. Mariotti, S" Sansoni, P" Barbesino, G. , Caturegli, P., Monti, D. , Cossarizza, A. , Giacomelli, T, Passeri, G. , Fagiolo, U. , Pinchera, A. , & Franceschi, C. (1992). Thyroid and other organ-specific autoantibodies in healthy centenarians, Lancet. 1.1506-1508. Murasko, D. M. , Gold, M. J., Hessen, M. T, & Kaye, D. (1990). Immune reactivity, morbidity, and mortality of elderly humans, Aging: Immunology and Infectious Disease, 3. 171-179, Murasko, D. M. , Weiner, P, & Kaye, D. (1988). Association of lack of mitogen-induced lymphocyte proliferation with increased mortality in the elderly. Aging: lmmunologv and lniectious Disease. I. 1--6. Nagel, J. E. , Chopra, R, K. , Chrest, E J., McCoy, M, T, Schneider, E, L. , Holbrook, N. J" & Adler, W, H. (1988). Decreased proliferation, interleukin-2 synthesis, and interleukin-2 receptor expression are accompanied by decreased mRNA expression in PHA stimulated cells from elderly donors. Journal ofClinical Investigation, 81. 1096-1102. Thoman, M. L. , & Weigle, W.O. (1982), Cell mediated immunity in aged mice: An underlying lesion in IL-2 synthesis, Journal of Immunology, 128. 2358-2361. 6
Estimating the apparent transverse relaxation time (R2*) from images with different contrasts (ESTATICS) reduces motion artifacts

Relaxation rates provide important information about tissue microstructure. Multi-parameter mapping (MPM) estimates multiple relaxation parameters from multi-echo FLASH acquisitions with different basic contrasts, i.e., proton density (PD), T1 or magnetization transfer (MT) weighting. Motion can particularly affect maps of the apparent transverse relaxation rate R2*, which are derived from the signal of PD-weighted images acquired at different echo times. To address the motion artifacts, we introduce ESTATICS, which robustly estimates R2* from images even when acquired with different basic contrasts. ESTATICS extends the fitted signal model to account for inherent contrast differences in the PDw, T1w and MTw images. The fit was implemented as a conventional ordinary least squares optimization and as a robust fit with a small or large confidence interval. These three different implementations of ESTATICS were tested on data affected by severe motion artifacts and data with no prominent motion artifacts as determined by visual assessment or fast optical motion tracking. ESTATICS improved the quality of the R2* maps and reduced the coefficient of variation for both types of data—with average reductions of 30% when severe motion artifacts were present. ESTATICS can be applied to any protocol comprised of multiple 2D/3D multi-echo FLASH acquisitions as used in the general research and clinical setting.
Working When No One Is Watching: Motivation, Test Scores, and Economic Success

This paper provides evidence that scores on simple, low-stakes tests are associated with future economic success because the scores also reflect test takers' personality traits associated with their level of intrinsic motivation. To establish this, I use the coding speed test that was administered without incentives to participants in the National Longitudinal Survey of Youth (NLSY). I show that, controlling for cognitive ability, the coding speed scores are correlated with future earnings of male NLSY participants. I provide evidence that the coding speed scores relate to intrinsic motivation. I show that the scores of the highly motivated, though less educated, group (potential recruits to the U.S. military), are higher than the NLSY participants' scores. I use controlled experiments to show directly that intrinsic motivation is an important component of the unincentivized coding speed scores and that it relates to test takers' personality traits. This paper was accepted by Teck Ho, behavioral economics.
Agent-Based Cloud Computing

Agent-based cloud computing is concerned with the design and development of software agents for bolstering cloud service discovery, service negotiation, and service composition. The significance of this work is introducing an agent-based paradigm for constructing software tools and testbeds for cloud resource management. The novel contributions of this work include: 1) developing Cloudle: an agent-based search engine for cloud service discovery, 2) showing that agent-based negotiation mechanisms can be effectively adopted for bolstering cloud service negotiation and cloud commerce, and 3) showing that agent-based cooperative problem-solving techniques can be effectively adopted for automating cloud service composition. Cloudle consists of 1) a service discovery agent that consults a cloud ontology for determining the similarities between providers' service specifications and consumers' service requirements, and 2) multiple cloud crawlers for building its database of services. Cloudle supports three types of reasoning: similarity reasoning, compatibility reasoning, and numerical reasoning. To support cloud commerce, this work devised a complex cloud negotiation mechanism that supports parallel negotiation activities in interrelated markets: a cloud service market between consumer agents and broker agents, and multiple cloud resource markets between broker agents and provider agents. Empirical results show that using the complex cloud negotiation mechanism, agents achieved high utilities and high success rates in negotiating for cloud resources. To automate cloud service composition, agents in this work adopt a focused selection contract net protocol (FSCNP) for dynamically selecting cloud services and use service capability tables (SCTs) to record the list of cloud agents and their services. Empirical results show that using FSCNP and SCTs, agents can successfully compose cloud services by autonomously selecting services.
Genetic structure of populations of the human hookworm, Necator americanus, in China

Twenty‐one to 58 individual Necator americanus were sampled from each of four villages in south‐western China. Each nematode was sequenced for 588 bp of the mitochondrial cytochrome oxidase I gene. Allelic and nucleotide diversity varied two‐fold among villages. Overall FST among populations was ≈ 0.28, but this large value resulted from one low‐diversity population that had a large genetic distance to the other three populations (FST = 0.10 without that population). There was no correlation between geographical and genetic distance among sites. Thus, the genetic structure of this species in China may be characterized by variable effective sizes and uneven movement among sites. We discuss the implications of this genetic structure for vaccine development and the spread of drug resistance in human hookworms, and compare the genetic structure of hookworms with that of other nematodes.
Membrane-Localized Extra-Large G Proteins and Gβγ of the Heterotrimeric G Proteins Form Functional Complexes Engaged in Plant Immunity in Arabidopsis1[OPEN]

Arabidopsis immunity against multiple pathogens depends on unconventional G protein complexes. In animals, heterotrimeric G proteins, comprising Gα, Gβ, and Gγ subunits, are molecular switches whose function tightly depends on Gα and Gβγ interaction. Intriguingly, in Arabidopsis (Arabidopsis thaliana), multiple defense responses involve Gβγ, but not Gα. We report here that the Gβγ dimer directly partners with extra-large G proteins (XLGs) to mediate plant immunity. Arabidopsis mutants deficient in XLGs, Gβ, and Gγ are similarly compromised in several pathogen defense responses, including disease development and production of reactive oxygen species. Genetic analysis of double, triple, and quadruple mutants confirmed that XLGs and Gβγ functionally interact in the same defense signaling pathways. In addition, mutations in XLG2 suppressed the seedling lethal and cell death phenotypes of BRASSINOSTEROID INSENSITIVE1-associated receptor kinase1-interacting receptor-like kinase1 mutants in an identical way as reported for Arabidopsis Gβ-deficient mutants. Yeast (Saccharomyces cerevisiae) three-hybrid and bimolecular fluorescent complementation assays revealed that XLG2 physically interacts with all three possible Gβγ dimers at the plasma membrane. Phylogenetic analysis indicated a close relationship between XLGs and plant Gα subunits, placing the divergence point at the dawn of land plant evolution. Based on these findings, we conclude that XLGs form functional complexes with Gβγ dimers, although the mechanism of action of these complexes, including activation/deactivation, must be radically different form the one used by the canonical Gα subunit and are not likely to share the same receptors. Accordingly, XLGs expand the repertoire of heterotrimeric G proteins in plants and reveal a higher level of diversity in heterotrimeric G protein signaling.
Simulation for Anesthesiology Milestones

The new Milestones requirement for all Accreditation Council for Graduate Medical Education (ACGME)-approved residency training was introduced by the ACGME with the goal of changing program assessment from process-oriented to outcomes-oriented measures in the Next Accreditation System (NAS). No longer are residencies approved on the basis of their curriculum, faculty, facilities, or case-mix; instead, residency programs are expected to shepherd residents through training with a goal of achieving the desired competencies for each subspecialty based on defined Milestones leading to Entrustable Professional Activities (EPAs). Subspecialty medical boards have worked with the ACGME to develop Milestones that capture the progression of skills expected to be developed during residency training. The NAS rolled out Milestones for 7 subspecialties in 2013: diagnostic radiology, emergency medicine, internal medicine, neurological surgery, orthopedic surgery, pediatrics, and urology. The original 6 competencies (patient care, medical knowledge, systems-based practice, practice-based learning and improvement, communication, and professionalism) are each broken down into 5 development levels on the basis of the Dreyfus model of skill acquisition that encompass the commonly expected progress of most residents for each particular specialty. The competencies are further divided into subcompetencies (between 12 and 41 in the first cohort) for each subspecialty. Anesthesiology residencies began to use Milestones in July 2014, with 25 defined subcompetencies developed by the Anesthesiology Milestone Working Group. This group included 9 anesthesiologists chosen by the Anesthesiology Residency Review Committee (RRC) who worked in conjunction with the American Board of Anesthesiology, the
Workshop/conference report—Quantitative bioanalytical methods validation and implementation: Best practices for chromatographic and ligand binding assays

ConclusionFor quantitative bioanalytical method validation procedure and requirements, there was a relatively good agreement between chromatographic assays and ligand-binding assays. It was realized that the quantitative and qualitative aspects of bioanalytical method validation should be reviewed and applied appropriately.1. Some of the major concerns between the 2 methodologies related to the acceptable total error for precision and accuracy determination and acceptance criteria for an analytical run. The acceptable total error for precision and accuracy for both the methodologies is less than 30. The 4–6–15 rule for accepting an analytical run by a chromatographic method remained acceptable while a 4–6–20 rule was recommended for ligand-binding methodology.2. The 3rd AAPS/FDA Bioanalytical Workshop clarified the issues related to placement of QC samples, determination of matrix effect, stability considerations, use of internal standards, and system suitability tests.3. There was a major concern and issues raised with respect to stability and reproducibility of incurred samples. This should be addressed for all analytical methods employed. It was left to the investigators to use their scientific judgment to address the issue.4. In general, the 3rd AAPS/FDA Bioanalytical Workshop provided a forum to discuss and clarify regulatory concerns regarding bioanalytical method validation issues.
The unimodal distribution of sub–threshold, ongoing activity in cortical networks

The characterization of the subthreshold, ongoing activity in cortical neurons has been the focus of numerous studies. This activity, described as spontaneous slow waves in membrane potential, has been observed in a span of species in diverse cortical and subcortical areas. We here characterized membrane potential fluctuations in motor and the frontal association cortices cortical neurons of ketamine–xylazine anesthetized rats. We recorded from 95 neurons from a range of cortical depths to unravel the network and cellular mechanisms that shape the subthreshold ongoing spontaneous activity of these neurons. We define a unitary event that generates the subthreshold ongoing activity: giant synaptic potentials (GSPs). These events have a duration of 87 ± 50 ms and an amplitude of 19 ± 6.4 mV. They occur at a frequency of 3.7 ± 0.8 Hz and involve an increase in conductance change of 22 ± 21%. GSPs are mainly due to excitatory activity that occurs throughout all cortical layers, unaffected by the intrinsic properties of the cells. Indeed, blocking the GABAA receptors, a procedure that had a profound effect on cortical activity, did not alter these unitary events. We propose that this unitary event is composed of individual, excitatory synaptic potentials that appear at different levels of synchrony and that the level of synchrony determines the shape of the subthreshold activity.
PP2ACdc55 regulates G1 cyclin stability

Maintaining accurate progression through the cell cycle requires the proper temporal expression and regulation of cyclins. The mammalian D-type cyclins promote G1-S transition. D1 cyclin protein stability is regulated through its ubiquitylation and resulting proteolysis catalyzed by the SCF E3 ubiquitin ligase complex containing the F-box protein, Fbx4. SCF E3-ligase-dependent ubiquitylation of D1 is trigged by an increase in the phosphorylation status of the cyclin. As inhibition of ubiquitin-dependent D1 degradation is seen in many human cancers, we set out to uncover how D-type cyclin phosphorylation is regulated. Here we show that in S. cerevisiae, a heterotrimeric protein phosphatase 2A (PP2ACdc55) containing the mammalian PPP2R2/PR55 B subunit ortholog Cdc55 regulates the stability of the G1 cyclin Cln2 by directly regulating its phosphorylation state. Cells lacking Cdc55 contain drastically reduced Cln2 levels caused by degradation due to cdk-dependent hyperphosphorylation, as a Cln2 mutant unable to be phosphorylated by the yeast cdk Cdc28 is highly stable in cdc55-null cells. Moreover, cdc55-null cells become inviable when the SCFGrr1 activity known to regulate Cln2 levels is eliminated or when Cln2 is overexpressed, indicating a critical relationship between SCF and PP2A functions in regulating cell cycle progression through modulation of G1-S cyclin degradation/stability. In sum, our results indicate that PP2A is absolutely required to maintain G1-S cyclin levels through modulating their phosphorylation status, an event necessary to properly transit through the cell cycle.
Transplanted Adipose‐Derived Stem Cells Ameliorate Testicular Dysfunction In A D‐Galactose–Induced Aging Rat Model

Glycation product accumulation during aging of slowly renewing tissues may be an important mechanism underlying aging of the testis. Adipose‐derived stem cells (ADSCs) have shown promise in a novel tissue regenerative technique and may have utility in treating sexual dysfunction. ADSCs have also been found to be effective in antiaging therapy, although the mechanism underlying their effects remains unknown. This study was designed to investigate the anti‐aging effect of ADSCs in a D‐galactose (D‐gal)–induced aging animal model and to clarify the underlying mechanism. Randomly selected 6‐week‐old male Sprague–Dawley rats were subcutaneously injected with D‐gal daily for 8 weeks. Two weeks after completion of treatment, D‐gal–induced aging rats were randomized to receive caudal vein injections of 3 × 106 5‐bromo 2′deoxyuridine–labeled ADSCs or an equal volume of phosphate‐buffered saline. Serum testosterone level, steroidogenic enzymes (3‐β‐hydroxysteroid dehydrogenase), and superoxide dismutase (SOD) activity decreased significantly in aging rats compared with the control group; serum lipid peroxidation, spermatogenic cell apoptosis, and methane dicarboxylic aldehyde (MDA) expression increased significantly. ADSCs increased the SOD level and reduced the MDA level in the aging animal model and restored levels of serum testosterone, steroidogenic enzymes, and spermatogenic cell apoptosis. These results demonstrate that ADSCs can contribute to testicular regeneration during aging. ADSCs also provide functional benefits through glycation suppression and antioxidant effects in a rat model of aging. Although some ADSCs differentiated into Leydig cells, the paracrine pathway seems to play a main role in this process, resulting in the reduction of apoptosis. J. Cell. Physiol. 230: 2403–2414, 2015. © 2015 Wiley Periodicals, Inc.
Differential Phosphoproteome Regulation of Nucleus Accumbens in Environmentally Enriched and Isolated Rats in Response to Acute Stress

Increasing evidence shows that stress contributes to the pathogenesis of major depressive disorder which is a severe neuropsychiatric disorder and influences over 10% of the world's population. Our previous studies revealed that rats reared in an enriched environment display less depression-related behavior compared to rats raised in an isolated environment, which implies that environmental enrichment produces an antidepressant-like behavioral phenotype. However, the molecular mechanisms are not fully understood. Protein phosphorylation rapidly changes signaling pathway function and alters the function of proteins associated with the stress-induced depressive disorder. Thus, in this study, a phosphoproteomic approach was used to uncover differential phosphoprotein regulation in rat nucleus accumbens between isolated (IC) and enriched environmental conditions (EC) under basal conditions, and in response to acute stress. We found 23 phosphoproteins were regulated in EC vs. IC rats under basal conditions; 10 phosphoproteins regulated by stress in IC rats; and 15 regulated by stress in EC rats. Among all significantly regulated phosphoproteins, 11 of them were represented in at least two conditions. The regulated phosphoproteins represent signaling pathway proteins (including ERK2), enzymes, transcriptional regulators, protein translation regulators, transporters, chaperones and cytoskeletal proteins. These findings provide a global view for further understanding the contribution of protein phosphorylation in depression pathogenesis and antidepressant action.
Fabrication and investigation of single-mode highly phosphorus-doped fibers for Raman lasers

A technology has been developed for fabrication of single- mode fibers with a high level of phosphorous doping (10 - 17 mol% P2O5) in the core. Characteristics of such fibers intended for use in Raman lasers operating at 1.24 and 1.48 micrometers are investigated. A reduction of fiber drawing temperature and additional doping of the fiber core with fluorine allowed a reduction of optical losses below 1 dB/km in wavelength range 1.1 - 1.5 micrometers .
Control of Saccharomyces cerevisiaeFilamentous Growth by Cyclin-Dependent Kinase Cdc28

ABSTRACT The ascomycete Saccharomyces cerevisiae exhibits alternative vegetative growth states referred to as the yeast form and the filamentous form, and it switches between the two morphologies depending on specific environmental signals. To identify molecules involved in control of morphologic differentiation, this study characterized mutant S. cerevisiae strains that exhibit filamentous growth in the absence of the normal external signals. A specific amino acid substitution in the cyclin-dependent protein kinase Cdc28 was found to cause constitutive expression of most filamentous growth characteristics. These effects include specifically modified cell polarity characteristics in addition to the defined shape and division cycle alterations typical of the filamentous form. Several other mutations affecting Cdc28 function also had specific effects on filamentous growth. Constitutive filamentous growth resulting from deletion of the protein kinase Elm1 was prevented by modification of Cdc28 such that it could not be phosphorylated on tyrosine residue 19. In addition, various mutations affecting Hsl1 or Swe1, known or presumed components of a protein kinase cascade that mediates Cdc28 phosphorylation on Y19, either prevented or enhanced filamentous growth. The data suggest that a protein kinase cascade involving Elm1, Hsl1, and Swe1 can modulate Cdc28 activity and that Cdc28 in turn exerts global effects that cause filamentous growth.