Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effect of Mycophenolate Mofetil on Disease Development in the gld.apoE −/− Mouse Model of Accelerated Atherosclerosis and Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is characterized by autoantibody production and inflammatory disease involving multiple organs. Premature atherosclerosis is a common complication of SLE and results in substantial morbidity and mortality from cardiovascular disease (CVD). The reasons for the premature atherosclerosis in SLE are incompletely understood, although chronic inflammation is thought to play an important role. There is currently no known preventative treatment of premature atherosclerosis in SLE. Mycophenolate mofetil (MMF) is an immunosuppressive agent that is commonly used for treatment of patients with SLE. In order to study the impact of this drug on murine lupus disease including premature atherosclerosis development, we treated gld.apoE−/− mice, a model of SLE and accelerated atherosclerosis, with MMF. We maintained seven-week old gld.apoE−/− mice on a high cholesterol Western diet with or without MMF. After 12 weeks on diet, mice receiving MMF showed decreased atherosclerotic lesion area compared to the control group. MMF treatment also improved the lupus phenotype, indicated by a significant decrease circulating autoantibody levels and ameliorating lupus nephritis associated with this model. This data suggests that the effects of MMF on the immune system may not only be beneficial for lupus, but also for inflammation driving lupus-associated atherosclerosis.
Sequential H(2)(15)O PET studies in baboons: before and after amphetamine.

UNLABELLED PET and (11)C-raclopride have been used to assess dopamine activity in vivo using a paradigm that involved d-amphetamine (AMPH)-induced endogenous dopamine release that led to reductions (relative to baseline) in the (11)C-raclopride-specific binding parameter (binding potential). A common assumption in bolus injection PET studies of this type is that cerebral blood flow (CBF) does not vary during the scan. The goal of this work was to examine the effect of AMPH administration on sequential PET measures of CBF. METHODS Eight dynamic H(2)(15)O PET scans were acquired with arterial blood sampling in 6 baboons: 4 scans before AMPH (over 60 min) and 4 scans after AMPH (over 60 min) (0.6 mg/kg AMPH). Magnetic resonance images (coregistered to PET) were used to define regions of interest that included cortex, striatum (including subregions), and cerebellum. Data were analyzed using a 1-tissue compartment model. CBF was assessed through K(1) (mL/mL/min). RESULTS Temporal patterns of the CBF alterations were similar across regions for each baboon. For 5 of 6 baboons, a general pattern of an initial increase in K(1) was observed after AMPH that gradually declined toward baseline, after minimizing anesthesia-induced variability in the in vivo measures. Although these alterations after AMPH were statistically significant in particular subcortical regions and cerebellum, such changes would not likely influence measures of (11)C-raclopride binding potential to a significant extent. CONCLUSION These data support previous PET studies for which constant blood flow was assumed during the bolus PET (11)C-raclopride/AMPH experiment across striatal subregions, while underscoring the importance of considering effects of anesthesia when interpreting in vivo imaging parameters.
Hyperactivation of L-type voltage-gated Ca2+ channels in Caenorhabditis elegans striated muscle can result from point mutations in the IS6 or the IIIS4 segment of the α1 subunit

Several human diseases, including hypokalemic periodic paralysis and Timothy syndrome, are caused by mutations in voltage-gated calcium channels. The effects of these mutations are not always well understood, partially because of difficulties in expressing these channels in heterologous systems. The use of Caenorhabditis elegans could be an alternative approach to determine the effects of mutations on voltage-gated calcium channel function because all the main types of voltage-gated calcium channels are found in C. elegans, a large panel of mutations already exists and efficient genetic tools are available to engineer customized mutations in any gene. In this study, we characterize the effects of two gain-of-function mutations in egl-19, which encodes the L-type calcium channel α1 subunit. One of these mutations, ad695, leads to the replacement of a hydrophobic residue in the IIIS4 segment. The other mutation, n2368, changes a conserved glycine of IS6 segment; this mutation has been identified in patients with Timothy syndrome. We show that both egl-19 (gain-of-function) mutants have defects in locomotion and morphology that are linked to higher muscle tone. Using in situ electrophysiological approaches in striated muscle cells, we provide evidence that this high muscle tone is due to a shift of the voltage dependency towards negative potentials, associated with a decrease of the inactivation rate of the L-type Ca2+ current. Moreover, we show that the maximal conductance of the Ca2+ current is decreased in the strongest mutant egl-19(n2368), and that this decrease is correlated with a mislocalization of the channel.
Identification of Conversion from Mild Cognitive Impairment to Alzheimer's Disease Using Multivariate Predictors

Prediction of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) is of major interest in AD research. A large number of potential predictors have been proposed, with most investigations tending to examine one or a set of related predictors. In this study, we simultaneously examined multiple features from different modalities of data, including structural magnetic resonance imaging (MRI) morphometry, cerebrospinal fluid (CSF) biomarkers and neuropsychological and functional measures (NMs), to explore an optimal set of predictors of conversion from MCI to AD in an Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. After FreeSurfer-derived MRI feature extraction, CSF and NM feature collection, feature selection was employed to choose optimal subsets of features from each modality. Support vector machine (SVM) classifiers were then trained on normal control (NC) and AD participants. Testing was conducted on MCIc (MCI individuals who have converted to AD within 24 months) and MCInc (MCI individuals who have not converted to AD within 24 months) groups. Classification results demonstrated that NMs outperformed CSF and MRI features. The combination of selected NM, MRI and CSF features attained an accuracy of 67.13%, a sensitivity of 96.43%, a specificity of 48.28%, and an AUC (area under curve) of 0.796. Analysis of the predictive values of MCIc who converted at different follow-up evaluations showed that the predictive values were significantly different between individuals who converted within 12 months and after 12 months. This study establishes meaningful multivariate predictors composed of selected NM, MRI and CSF measures which may be useful and practical for clinical diagnosis.
Auditory Phase Opponency: A Temporal Model for Masked Detection at Low Frequencies

Summary We present a model for tone-in-noise detection at low frequencies that includes a physiologically realistic mechanism for processing the information in neural discharge times. The proposed model exploits the frequencydependent phase properties of the tuned filters in the auditory periphery and uses cross-auditory-nerve-fiber coincidence detection to extract temporal cues. Information in the responses of model coincidence detectors is quantified and compared to human performance in a masked detection task. The responses of some crossfrequency coincidence detectors are reduced when a low-frequency tone is added to a noise because of phase differences between fibers tuned to different frequencies. We refer to this response reduction as “phase opponency. ” For super-critical masker bandwidths, the PO model succeeds in predicting detection of low-frequency tones in roving-level maskers, a psychophysical task for which the classical energy model fails. The PO model describes a physiologically realistic mechanism for extracting spatio-temporal information that can be applied to other sensory systems in which spatially overlapping and partially correlated temporal information is important.
Capacity scaling of cognitive networks: Beyond interference-limited communication

The capacity scaling laws of two overlaid networks sharing the same wireless resources with different priorities are investigated. The primary network is assumed to operate in an order-optimal fashion to achieve its standalone capacity scaling law. The secondary “cognitive” network must keep its interference to the primary network below a certain threshold while at the same time maximizing its own throughput scaling law based on cognition information. The existing scaling results for cognitive networks inherently assume multihop communication treating all other signals except from a single intended transmitter as noise. By contrast, in this paper, a general coding model is considered without any specific physical layer coding assumptions. Therefore, this paper provides a general framework for comprehensive understanding of fundamental limits on the capacity scaling laws of cognitive networks. For the extended network model, the capacity scaling laws of both the primary and secondary networks are completely characterized. For the dense network model, an improved throughput scaling law is achieved by inducing cooperation within the secondary network. In both cases, it turns out that the conventional multihop approach is in general quite suboptimal.
Tracing entire operation cycles of molecular motor hepatitis C virus helicase in structurally resolved dynamical simulations

Hepatitis C virus helicase is a molecular motor that splits duplex DNA while actively moving over it. An approximate coarse-grained dynamical description of this protein, including its interactions with DNA and ATP, is constructed. Using such a mechanical model, entire operation cycles of an important protein machine could be followed in structurally resolved dynamical simulations. Ratcheting inchworm translocation and spring-loaded DNA unwinding, suggested by experimental data, were reproduced. Thus, feasibility of coarse-grained simulations, bridging a gap between full molecular dynamics and reduced phenomenological theories of molecular motors, has been demonstrated.
Polo-like kinase 1 inhibits DNA damage response during mitosis

In response to genotoxic stress, cells protect their genome integrity by activation of a conserved DNA damage response (DDR) pathway that coordinates DNA repair and progression through the cell cycle. Extensive modification of the chromatin flanking the DNA lesion by ATM kinase and RNF8/RNF168 ubiquitin ligases enables recruitment of various repair factors. Among them BRCA1 and 53BP1 are required for homologous recombination and non-homologous end joining, respectively. Whereas mechanisms of DDR are relatively well understood in interphase cells, comparatively less is known about organization of DDR during mitosis. Although ATM can be activated in mitotic cells, 53BP1 is not recruited to the chromatin until cells exit mitosis. Here we report mitotic phosphorylation of 53BP1 by Plk1 and Cdk1 that impairs the ability of 53BP1 to bind the ubiquitinated H2A and to properly localize to the sites of DNA damage. Phosphorylation of 53BP1 at S1618 occurs at kinetochores and in cytosol and is restricted to mitotic cells. Interaction between 53BP1 and Plk1 depends on the activity of Cdk1. We propose that activity of Cdk1 and Plk1 allows spatiotemporally controlled suppression of 53BP1 function during mitosis.
Antimicrobial activity of Enterococcus Faecium Fair-E 198 against gram-positive pathogens

ABSTRACT This study investigated the antimicrobial activity of Enterococcus faecium FAIR-E 198 against Bacillus cereus, Listeria monocytogenes and Staphylococcus aureus. Using the critical-dilution method, the bacteriocin produced by E. faecium FAIR-E 198 inhibited all L. monocytogenes strains evaluated (1,600 to 19,200 AU mL-1). However, none of the B. cereus and S. aureus strains investigated were inhibited. The maximum activity of this bacteriocin (800 AU mL-1) was observed in MRS broth, while the activity in milk was 100 AU mL-1. In the co-cultivation test in milk, B. cereus K1-B041 was reduced to below the detection limit (1.00 log CFU mL-1) after 48 h. E. faecium reduced the initial L. monocytogenes Scott A population by 1 log CFU mL-1 after 3 h at 35°C, However, the pathogen regained growth, reaching 3.68 log CFU mL-1 after 48 h. E. faecium did not influence the growth of S. aureus ATCC 27154 during the 48 h of co-cultivation, Therefore, it can be concluded that the effectiveness of the antimicrobial activity of E. faecium FAIR-E 198 is strictly related to the species and strain of the target microorganism and to the culture medium,
Oscillator Phase Noise: A Geometrical Approach

We construct a coordinate-independent description of oscillator linear response through a decomposition scheme derived independently of any Floquet theoretic results. Trading matrix algebra for a simpler graphical methodology, the text will present the reader with an opportunity to gain an intuitive understanding of the well-known phase noise macromodel. The topics discussed in this paper include the following: orthogonal decompositions, AM-PM conversion, and nonhyperbolic oscillator noise response.
Facial Expression Recognition Based on Facial Components Detection and HOG Features

—In this paper, an effective method is proposed to handle the facial expression recognition problem. The system detects the face and facial components including eyes, brows and mouths. Since facial expressions result from facial muscle movements or deformations, and Histogram of Oriented Gradients (HOG) is very sensitive to the object deformations, we apply the HOG to encode these facial components as features. A linear SVM is then trained to perform the facial expression classification. We evaluate our proposed method on the JAFFE dataset and an extended Cohn-Kanade dataset. The average classification rate on the two datasets reaches 94.3% and 88.7%, respectively. Experimental results demonstrate the competitive classification accuracy of our proposed method.
Impact of Extended Coherent Integration Times on Weak Signal RTK in an Ultra-Tight Receiver

The use of an ultra-tight GPS/IMU integration strategy has been proposed for carrier phase-based positioning in weak signal environments. The use of IMU-aided tracking allows the carrier tracking loop bandwidths to be narrowed, thereby improving the quality of the carrier phase measurements. To improve tracking sensitivity in GPS receivers it is common to increase the coherent integration time, thereby improving the quality of the measurements when the C/N0 is low. One of the major challenges associated with increasing the coherent integration time is the increased sensitivity to dynamics, a problem which is largely mitigated by the use of INS aiding. Therefore, it would seem possible that ultratight integration coupled with longer coherent integration times could yield a viable solution to the problem of RTK positioning in weak signal environments.
Electoral laws and the 2007 general elections in Nigeria

Credible elections are a salient indicator of democratic consolidation and the principal institutionalised means of forming and changing democratic governments. A central determinant of the success of any election is the institutions which structure the behaviour of participants and the choices available to them, hence their belief in pay-offs to individuals and groups. The guiding principles and regulations of the 2007 general elections in Nigeria are to be found in the 1999 Constitution and in the Electoral Act 2006. These documents not only set out the rules, the enactment of the Electoral Act usually signals the beginning of the electoral contest. The Constitution and the Act together make elaborate provision for voter registration, party and candidate registration, campaign financing and regulation, election observation, ballot design, polling stations, voting, counting, and tabulation, election management bodies, and dispute-settlement authorities. This paper reviews critically the constitutional provisions on elections and the Electoral Act 2006 in the context of the challenges of achieving credible elections in Nigeria.
“Pharm‐Ecology” of Diet Shifting: Biotransformation of Plant Secondary Compounds in Creosote (Larrea tridentata) by a Woodrat Herbivore, Neotoma lepida

Diet switching in mammalian herbivores may necessitate a change in the biotransformation enzymes used to process plant secondary compounds (PSCs). We investigated differences in the biotransformation system in the mammalian herbivore, Neotoma lepida, after a radical shift in diet and secondary compound composition. Populations of N. lepida in the Mojave Desert have evolved over the past 10,000 years to feed on creosote (Larrea tridentata) from an ancestral state of consuming juniper (Juniperus osteosperma). This dietary shift represents a marked change in the dietary composition of PSCs in that creosote leaves are coated with phenolic resin, whereas juniper is high in terpenes but lacks phenolic resin. We quantified the enzyme activity of five major groups of biotransformation enzymes (cytochrome P450s, NAD(P)H:quinone oxidoreductase, glutathione conjugation, sulfation, and glucuronidation) recognized for their importance to mammalian biotransformation for the elimination of foreign compounds. Enzyme activities were compared between populations of Mojave and Great Basin woodrats fed control and creosote diets. In response to creosote, the Mojave population had greater levels of cytochrome P450s (CYP2B, CYP1A) and glutathione conjugation liver enzymes compared with the Great Basin population. Our results suggest that elevated levels of cytochrome P450s and glutathione conjugation enzymes in the Mojave population may be the underlying biotransformation mechanisms that facilitate feeding on creosote.
The Real Exchange Rate and Foreign Direct Investment in the United States: Relative Wealth vs. Relative Wage Effects

There has been a significant correlation between United States inward foreign direct investment and the United States real exchange rate since the 1970s. Two alternative reasons for this relationship are that the real exchange rate affects the relative cost of labor and that the real exchange rate alters relative wealth across countries. In this paper we explore these alternatives by examining the determinants of four measures of inward foreign direct investment to the United States from seven industrial countries over the period 1979 to 1991. We find strong evidence that relative wealth significantly affects U.S. inward foreign direct investment. We find no evidence that relative wages have a significant impact on the determination of U.S. foreign direct investment. These results are robust to the choice of countries in our sample and when controlling for changes in tax codes.
Differentiation of Murine Pulmonary Neuroendocrine Cells Human Neuroendocrine Lung Carcinomas and Mediates the Growth Factor Independence-1 Is Expressed in Primary

Human small cell lung cancers might be derived from pulmonary cells with a neuroendocrine phenotype. They are driven to proliferate by autocrine and paracrine neuropeptide growth factor stimulation. The molecular basis of the neuroendocrine phenotype of lung carcinomas is relatively unknown. The Achaete-Scute Homologue-1 (ASH1) transcription factor is critically required for the formation of pulmonary neuroendocrine cells and is a marker for human small cell lung cancers. The Drosophila orthologues of ASH1 (Achaete and Scute) and the growth factor independence-1 (GFI1) oncoprotein (Senseless) genetically interact to inhibit Notch signaling and specify fly sensory organ development. Here, we show that GFI1, as with ASH1, is expressed in neuroendocrine lung cancer cell lines and that GFI1 in lung cancer cell lines functions as a DNA-binding transcriptional repressor protein. Forced expression of GFI1 potentiates tumor formation of small-cell lung carcinoma cells. In primary human lung cancer specimens, GFI1 expression strongly correlates with expression of ASH1, the neuroendocrine growth factor gastrinreleasing peptide, and neuroendocrine markers synaptophysin and chromogranin A (P < 0.0000001). GFI1 colocalizes with chromogranin A and calcitonin-gene–related peptide in embryonic and adult murine pulmonary neuroendocrine cells. In addition, mice with a mutation in GFI1 display abnormal development of pulmonary neuroendocrine cells, indicating that GFI1 is important for neuroendocrine differentiation.
Acyl peptide hydrolase, a serine proteinase isolated from conditioned medium of neuroblastoma cells, degrades the amyloid‐β peptide

Considerable evidence indicates that the amyloid‐β (Aβ) peptide, a proteolytic fragment of the amyloid precursor protein, is the pathogenic agent in Alzheimer's disease (AD). A number of proteases have been reported as capable of degrading Aβ, among them: neprilysin, insulin‐degrading enzyme, endothelin‐converting enzyme‐1 and ‐2, angiotensin‐converting enzyme and plasmin. These proteases, originating from a variety of cell types, degrade Aβ of various conformational states and in different cellular locations. We report here the isolation of a serine protease from serum‐free conditioned medium of human neuroblastoma cells. Tandem mass spectrometry (MS/MS)‐based sequencing of the isolated protein identified acyl peptide hydrolase (APH; EC3.4.19.1) as the active peptidase. APH is one of four members of the prolyl oligopeptidase family of serine proteases expressed in a variety of cells and tissues, including erythrocytes, liver and brain, but its precise biological activity is unknown. Here, we describe the identification of APH as an Aβ‐degrading enzyme, and we show that the degradation of Aβ by APH isolated from transfected cells is inhibited by APH‐specific inhibitors, as well as by synthetic Aβ peptide. In addition, we cloned APH from human brain and from neuroblastoma cells. Most importantly, our results indicate that APH expression in AD brain is lower than in age‐matched controls.
Cross-Layer Design in Wireless Mesh Networks

The conventional layered-protocol architecture does not provide optimal performance for wireless mesh networks (WMNs). The method of optimization decomposition of the protocol stack can achieve optimal network performance. This method usually results in a clean-slate protocol architecture that is different from the protocol architecture of WMNs. Such a difference actually demonstrates the need for a cross-layer design. Specific features pertaining to WMNs also show the need for cross-layer optimization across different protocol layers. In this paper, motivations for cross-layer design in WMNs are stated first. Moreover, cross-layer optimization schemes and algorithms between different protocol layers are investigated with an objective of shedding light on open research problems and new approaches. Guidelines for carrying out cross-layer design in WMNs are also provided in this paper.