Miracle-dz/UniFAR-FTUs huggingface dataset:
Deterministic Formulization of End-to-End Delay and Bandwidth Efficiency for Multicast Systems

End-System multicasting (ESM) is a promising application-layer scheme that has been recently proposed for implementing multicast routing in the application layer as a practical alternative to the IP multicasting. Moreover, ESM is an efficient application layer solution where all the multicast functionality is shifted to the end users. However, the limitation in bandwidth and the fact that the message needs to be forwarded from host-to-host using unicast connection, and consequently incrementing the end-to-end delay of the transmission process, contribute to the price to pay for this new approach. Therefore, supporting high-speed real-time applications such as live streaming multimedia, videoconferencing, distributed simulations, and multiparty games require a sound understanding of these multicasting schemes such as IP multicast and ESM and the factors that might affect the end-user requirements. In this paper, we present both the analytical and the mathematical models for formalizing the end-to-end delay and the bandwidth efficiency of both IP and ESM multicast system. For the sake of the experimental verifications of the proposed models, numerical and simulation results are presented in this paper. Finally, the proposed formulization can be used to design and implement a more robust and efficient multicast systems for the future networks.
Laws of order: expensive synchronization in concurrent algorithms cannot be eliminated

Building correct and efficient concurrent algorithms is known to be a difficult problem of fundamental importance. To achieve efficiency, designers try to remove unnecessary and costly synchronization. However, not only is this manual trial-and-error process ad-hoc, time consuming and error-prone, but it often leaves designers pondering the question of: is it inherently impossible to eliminate certain synchronization, or is it that I was unable to eliminate it on this attempt and I should keep trying? In this paper we respond to this question. We prove that it is impossible to build concurrent implementations of classic and ubiquitous specifications such as sets, queues, stacks, mutual exclusion and read-modify-write operations, that completely eliminate the use of expensive synchronization. We prove that one cannot avoid the use of either: i) read-after-write (RAW), where a write to shared variable A is followed by a read to a different shared variable B without a write to B in between, or ii) atomic write-after-read (AWAR), where an atomic operation reads and then writes to shared locations. Unfortunately, enforcing RAW or AWAR is expensive on all current mainstream processors. To enforce RAW, memory ordering--also called fence or barrier--instructions must be used. To enforce AWAR, atomic instructions such as compare-and-swap are required. However, these instructions are typically substantially slower than regular instructions. Although algorithm designers frequently struggle to avoid RAW and AWAR, their attempts are often futile. Our result characterizes the cases where avoiding RAW and AWAR is impossible. On the flip side, our result can be used to guide designers towards new algorithms where RAW and AWAR can be eliminated.
A fluorescent imaging method for analyzing the biodistribution of therapeutic monoclonal antibodies that can distinguish intact antibodies from their breakdown products

Many monoclonal antibodies have been developed for therapy over the last 2 decades. In the development of therapeutic antibodies, the preclinical assessment of an antibody's biodistribution is important for the prediction of the antibody's efficacy and safety. For imaging analyses of such biodistributions, radioisotope (RI) labeling and fluorescence labeling methods are typically used, but the resulting data are limited because these methods cannot distinguish breakdown products from intact antibodies. To resolve this problem, we developed a novel method using fluorescent resonance energy transfer (FRET)-type labeling and a spectral unmixing tool. With FRET-type labeling (labeling with 2 species of fluorophore), different fluorescence properties of labeled intact antibodies and their breakdown products (the hydrolyzed/digested type of breakdown products) are made visible. With the spectral unmixing tool, the fluorescence of a solution containing the intact antibody and its breakdown products could be unmixed in proportion to their contents. Moreover, when labeled antibodies that targeted either human epidermal growth factor receptor-2 or epidermal growth factor receptor were injected into nude mice implanted subcutaneously with tumor cells, the accumulation of the injected labeled antibodies and their breakdown products in the tumor could be separately analyzed by both whole-mouse imaging and a tumor homogenate analysis. These results suggest that our method using FRET-type labeling and a spectral unmixing tool could be useful in distinguishing breakdown products from intact antibodies.
Desensitization of Catecholamine Release

Nicotinic cholinergic receptors undergo desensitization upon repeated or prolonged exposure to agonist. We investigated the effects of a novel chromogranin A catecholamine release-inhibitory fragment, catestatin (chromogranin A344–364), on agonist-induced desensitization of catecholamine release from pheochromocytoma cells. In a dose-dependent fashion, the nicotinic antagonist catestatin blocked agonist desensitization of both catecholamine release (IC50 ∼ 0.24 μm) and22Na+ uptake (IC50 ∼ 0.31 μm), the initial step in nicotinic cationic signal transduction; both secretion inhibition and blockade of desensitization were noncompetitive with agonist. Desensitizing effects of the nicotinic agonists nicotine and epibatidine were blocked. This antagonist action was specific to desensitization by nicotinic agonists, since catestatin did not block desensitization of catecholamine release induced by agents which bypass the nicotinic receptor. Hill plots with slopes near unity suggested noncooperativity for catestatin effects on both nicotinic responses (secretory antagonism and blockade of desensitization). Human, bovine, and rat catestatins (as well as substance P) had similar potencies. IC50 values for secretion inhibition and blockade of desensitization paralleled each other (r = 0.76,n = 10 antagonists, p = 0.01) for several noncompetitive nicotinic antagonists. Peptide nicotinic antagonists (catestatins, substance P) were far more potent inhibitors of both secretion (p = 0.019) and desensitization (p = 0.005) than nonpeptide antagonists (trimethaphan, hexamethonium, procaine, phencyclidine, cocaine, or clonidine), and the peptides displayed enhanced selectivity to block desensitization versus secretion (p = 0.003). We conclude that catestatin is a highly potent, dose-dependent, noncompetitive, noncooperative, specific inhibitor of nicotinic desensitization, an effect which may have implications for control of catecholamine release.
A SEMIDISCRETE APPROXIMATION SCHEME FOR NEUTRAL DELAY-DIFFERENTIAL EQUATIONS

We consider an approximation scheme for systems of linear delay-differential equations of neutral type. The finite dimensional approximating systems are constructed with basis functions defined using linear splines, extending to neutral equations a scheme which had previously been defined only for retarded equations. A Trotter-Kato semigroup convergence result is proved, and numerical results are given to illustrate the qualitative behavior of the scheme.
Age-Dependent Decline in Mouse Lung Regeneration with Loss of Lung Fibroblast Clonogenicity and Increased Myofibroblastic Differentiation

While aging leads to a reduction in the capacity for regeneration after pneumonectomy (PNX) in most mammals, this biological phenomenon has not been characterized over the lifetime of mice. We measured the age-specific (3, 9, 24 month) effects of PNX on physiology, morphometry, cell proliferation and apoptosis, global gene expression, and lung fibroblast phenotype and clonogenicity in female C57BL6 mice. The data show that only 3 month old mice were fully capable of restoring lung volumes by day 7 and total alveolar surface area by 21 days. By 9 months, the rate of regeneration was slower (with incomplete regeneration by 21 days), and by 24 months there was no regrowth 21 days post-PNX. The early decline in regeneration rate was not associated with changes in alveolar epithelial cell type II (AECII) proliferation or apoptosis rate. However, significant apoptosis and lack of cell proliferation was evident after PNX in both total cells and AECII cells in 24 mo mice. Analysis of gene expression at several time points (1, 3 and 7 days) post-PNX in 9 versus 3 month mice was consistent with a myofibroblast signature (increased Tnc, Lox1, Col3A1, Eln and Tnfrsf12a) and more alpha smooth muscle actin (αSMA) positive myofibroblasts were present after PNX in 9 month than 3 month mice. Isolated lung fibroblasts showed a significant age-dependent loss of clonogenicity. Moreover, lung fibroblasts isolated from 9 and 17 month mice exhibited higher αSMA, Col3A1, Fn1 and S100A expression, and lower expression of the survival gene Mdk consistent with terminal differentiation. These data show that concomitant loss of clonogenicity and progressive myofibroblastic differentiation contributes to the age-dependent decline in the rate of lung regeneration.
Mutational analysis of glucose transport regulation and glucose‐mediated virulence gene repression in Listeria monocytogenes

Listeria monocytogenes transports glucose/mannose via non‐PTS permeases and phosphoenolpyruvate:carbohydrate phosphotransferase systems (PTS). Two mannose class PTS are encoded by the constitutively expressed mpoABCD and the inducible manLMN operons. The man operon encodes the main glucose transporter because manL or manM deletion significantly slows glucose utilization, whereas mpoA deletion has no effect. The PTSMpo mainly functions as a constitutively synthesized glucose sensor controlling man operon expression by phosphorylating and interacting with ManR, a LevR‐like transcription activator. EIIBMpo plays a dual role in ManR regulation: P∼EIIBMpo prevailing in the absence of glucose phosphorylates and thereby inhibits ManR activity, whereas unphosphorylated EIIBMpo prevailing during glucose uptake is needed to render ManR active. In contrast to mpoA, deletion of mpoB therefore strongly inhibits man operon expression and glucose consumption. A ΔptsI (EI) mutant consumes glucose at an even slower rate probably via GlcU‐like non‐PTS transporters. Interestingly, deletion of ptsI, manL, manM or mpoB causes elevated PrfA‐mediated virulence gene expression. The PTSMan is the major player in glucose‐mediated PrfA inhibition because the ΔmpoA mutant showed normal PrfA activity. The four mutants showing PrfA derepression contain no or only little unphosphorylated EIIABMan (ManL), which probably plays a central role in glucose‐mediated PrfA regulation.
Evaluating theories of drought-induced vegetation mortality using a multimodel-experiment framework.

SUMMARY Model-data comparisons of plant physiological processes provide an understanding of mechanisms underlying vegetation responses to climate. We simulated the physiology of a piñon pine-juniper woodland (Pinus edulis-Juniperus monosperma) that experienced mortality during a 5 yr precipitation-reduction experiment, allowing a framework with which to examine our knowledge of drought-induced tree mortality. We used six models designed for scales ranging from individual plants to a global level, all containing state-of-the-art representations of the internal hydraulic and carbohydrate dynamics of woody plants. Despite the large range of model structures, tuning, and parameterization employed, all simulations predicted hydraulic failure and carbon starvation processes co-occurring in dying trees of both species, with the time spent with severe hydraulic failure and carbon starvation, rather than absolute thresholds per se, being a better predictor of impending mortality. Model and empirical data suggest that limited carbon and water exchanges at stomatal, phloem, and below-ground interfaces were associated with mortality of both species. The model-data comparison suggests that the introduction of a mechanistic process into physiology-based models provides equal or improved predictive power over traditional process-model or empirical thresholds. Both biophysical and empirical modeling approaches are useful in understanding processes, particularly when the models fail, because they reveal mechanisms that are likely to underlie mortality. We suggest that for some ecosystems, integration of mechanistic pathogen models into current vegetation models, and evaluation against observations, could result in a breakthrough capability to simulate vegetation dynamics.
Gene products that promote mRNA turnover in Saccharomyces cerevisiae

We showed previously that the increased rate of mRNA turnover associated with premature translational termination in the yeast Saccharomyces cerevisiae requires a functional UPF1 gene product. In this study, we show that the UPF1 gene codes for a 109-kDa primary translation product whose function is not essential for growth. The protein contains a potential zinc-dependent nucleic acid-binding domain and a nucleoside triphosphate-binding domain. A 300-amino-acid segment of the UPF1 protein is 36% identical to a segment of the yeast SEN1 protein, which is required for endonucleolytic processing of intron-containing pre-tRNAs. The same region is 32% identical to a segment of Mov-10, a mouse protein of unknown function. Dominant-negative upf1 mutations were isolated following in vitro mutagenesis of a plasmid containing the UPF1 gene. They mapped exclusively at conserved positions within the sequence element common to all three proteins, whereas the recessive upf1-2 mutation maps outside this region. The clustering of dominant-negative mutations suggests the presence of a functional domain in UPF1 that may be shared by all three proteins. We also identified upf mutations in three other genes designated UPF2, UPF3, and UPF4. When alleles of each gene were screened for effects on mRNA accumulation, we found that the recessive mutation upf3-1 causes increased accumulation of mRNA containing a premature stop codon. When mRNA half-lives were measured, we found that excess mRNA accumulation was due to mRNA stabilization. On the basis of these results, we suggest that the products of at least two genes, UPF1 and UPF3, are responsible for the accelerated rate of mRNA decay associated with premature translational termination.
Recombinant infectious hematopoietic necrosis virus and viral hemorrhagic septicemia virus glycoprotein epitopes expressed in Aeromonas salmonicida induce protective immunity in rainbow trout (Oncorhynchus mykiss)

Fragments of the glycoprotein genes of viral hemorrhagic septicemia virus (VHSV) and infectious hematopoietic necrosis virus (IHNV) were cloned into a bacterial broad-host-range expression vector under the control of the plac promoter. Western blot (immunoblot) analysis with monoclonal antibodies specific to the glycoproteins demonstrated the inducible expression of the fusion proteins in Escherichia coli. Aeromonas salmonicida is the causative agent of furunculosis in salmonid fish. It was confirmed that an avirulent strain of A. salmonicida, A440, which contains a deletion in the structural gene for the paracrystalline surface protein array, will provide protective immunity against furunculosis when used as a live attenuated vaccine. The plasmid-encoded viral epitopes were then mobilized into A440 for use as a shuttle system for the expression of fragments of the glycoprotein genes of IHNV and VHSV. Vaccination of rainbow trout with A440 containing the viral epitopes resulted in the development of protective immunity against both VHSV and IHNV. This indicates that the use of cloned fragments of the glycoproteins and the use of A. salmonicida as a shuttle system constitute a feasible approach to fish vaccine development.
New Insights into Molecular Basis of Glioblastoma Multiforme and Associated Immunosuppression Acta Facultatis Medicae Naissensis

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults and carries the poorest prognosis despite aggressive multimodal therapy. The majority of GBMs develop de novo (primary) with a short clinical history, while secondary GBMs develop through progression from preexisting lowergrade precursor gliomas and show distinct genetic and expression profiles including the high frequency of isocitrate dehydrogenase 1 (IDH1) mutations, already present in precursor lesions. Large-scale integrative genomic studies provided the new view that GBMs are remarkable molecularly heterogeneous tumors and identified distinct molecular entities that may lead to different therapeutic approaches. Although being restricted to the intracranial compartment, GBMs are associated with global immunosuppression. Better understanding of the immune response to GBMs growing in the immunologically distinct microenvironment in the brain and mechanisms by which they may escape the response and even suppress it will accelerate the development of more effective immunotherapies. This review summarizes the current knowledge regarding genetic alterations and signaling pathways critical to the biology of GBMs, few mechanisms of developing local and systemic GBM-induced immunosuppression, and the role of GBM stem cells.
Three Large-Scale Functional Brain Networks from Resting-State Functional MRI in Subjects with Different Levels of Cognitive Impairment

Normal aging and to a greater degree degenerative brain diseases such as Alzheimer's disease (AD), cause changes in the brain's structure and function. Degenerative changes in brain structure and decline in its function are associated with declines in cognitive ability. Early detection of AD is a key priority in dementia services and research. However, depending on the disease progression, neurodegenerative manifestations, such as cerebral atrophy, are detected late in course of AD. Functional changes in the brain may be an indirect indicator of trans-synaptic activity and they usually appear prior to structural changes in AD. Resting-state functional magnetic resonance imaging (RS-fMRI) has recently been highlighted as a new technique for interrogating intrinsic functional connectivity networks. Among the majority of RS-fMRI studies, the default mode network (DMN), salience network (SN), and central executive network (CEN) gained particular focus because alterations to their functional connectivity were observed in subjects who had AD, who had mild cognitive impairment (MCI), or who were at high risk for AD. Herein, we present a review of the current research on changes in functional connectivity, as measured by RS-fMRI. We focus on the DMN, SN, and CEN to describe RS-fMRI results from three groups: normal healthy aging, MCI and AD.
Dominant Negative Dimerization of a Mutant Homeodomain Protein in Axenfeld-Rieger Syndrome

ABSTRACT Axenfeld-Rieger syndrome is an autosomal-dominant disorder caused by mutations in the PITX2 homeodomain protein. We have studied the mechanism underlying the dominant negative K88E mutation, which occurs at position 50 of the homeodomain. By using yeast two-hybrid and in vitro pulldown assays, we have documented that PITX2a can form homodimers in the absence of DNA. Moreover, the K88E mutant had even stronger dimerization ability, primarily due to interactions involving the C-terminal region. Dimerization allowed cooperative binding of wild-type (WT) PITX2a to DNA containing tandem bicoid sites in a head-to-tail orientation (Hill coefficient, 1.73). In contrast, the WT-K88E heterodimer bound the tandem sites with greatly reduced cooperativity and decreased transactivation activity. To further explore the role of position 50 in PITX2a dimerization, we introduced a charge-conservative mutation of lysine to arginine (K88R). The K88R protein had greatly reduced binding to a TAATCC element and did not specifically bind any other TAATNN motif. Like K88E, K88R formed relatively stronger dimers with WT. As predicted by our model, the K88R protein acted in a dominant negative manner to suppress WT PITX2a activity. These results suggest that the position 50 residue in the PITX2 homeodomain plays an important role in both DNA binding and dimerization activities.
Influence of Dietary Sodium Modulation on Electrocardiographic Voltage Criteria for Left Ventricular Hypertrophy in Normotensive Individuals

Objective Dietary sodium intake and left ventricular hypertrophy (LVH) on electrocardiogram (ECG) are both independent determinants of cardiovascular risk. Prior studies demonstrated that acute dietary sodium modulation significantly altered LVH-specific ECG voltage in hypertensive individuals, thus modifying cardiovascular risk prediction; but whether this phenomenon exists in normotensive individuals is not known. We evaluated the influence of dietary sodium intake on ECG voltage and ECG criteria for LVH in normotensive individuals. Methods Retrospective evaluation of ECGs of healthy normotensive individuals (n = 39) who were prospectively randomized to a dietary study protocol of 1 week of high-sodium diet (>200 mmol of sodium per day) and 1 week of low-sodium diet (<10 mmol/d) was conducted. Electrocardiogram voltage amplitudes and biochemical assessments were performed at the end of each dietary intervention. Results As expected, blood pressure declined and measures of circulating renin-angiotensin-aldosterone system activity rose significantly with low-sodium diet. No significant changes in specific LVH voltage criteria or overall precordial or limb lead ECG voltage amplitudes were detected between diets. Conclusion Although immediate dietary sodium modulation has been shown to significantly alter LVH-specific ECG voltage and the detection of LVH in hypertensive individuals, dietary sodium intake did not influence ECG voltage in normotensive individuals. Healthy normotensive individuals may exhibit adaptive measures that dampen ECG voltage fluctuations in response to dietary sodium modulation. More specific cardiac imaging studies may provide additional insight into this observation and the influence of dietary sodium in cardiac health.
A new self-adaptive fusion algorithm based on DST and DSmT

A new self-adaptive fusion algorithm based on DST and DSmT is proposed. In the new algorithm, part of the conflicting information is normalized according to DST, while the other part is processed by DSmT. A controlling factor is used to control the quantity of information dealt by the two different methods adaptively, which is a new method avoiding setting for the threshold of conflict. The simulation results indicate that the new self-adaptive fusion algorithm based on DST and DSmT can deal with any conflicting situation with a good performance of convergence.
The Internal Structure of Macroporous Membranes and Transport of Surface-Modified Nanoparticles

Abstract Understanding the morphological structure of membranes is essential to improve performance of membrane-based applications. In this paper, macroporous membranes were investigated and two methods introduced as an alternative for characterization of stereo-structure of the membranes. We combined the use of synchrotron X-ray nanotomography and small-angle X-ray scattering to examine the internal structure of cellulose acetate membranes with studies of the capture of surface-modified gold nanoparticles within these membranes. Finally, the morphological structures of macroporous membranes were visualized and their relationships with penetration tendency of surface-modified gold nanoparticles were explained.