Miracle-dz/UniFAR-FTUs huggingface dataset:
Stable, online learning using CMACs for neuroadaptive tracking control of flexible-joint manipulators

An artificial neural network is proposed for the precision control of flexible-joint robots. The training method uses backstepping in an online, direct neuroadaptive scheme in order to guarantee stability. The online weight updates include a learning term that improves performance while maintaining stability. Albus's cerebellar model arithmetic computer algorithm is modified to work for flexible robots by utilizing radial basis functions to deal with the elasticity. The resulting hybrid network is referred to as CMAC-RBF associative memory or CRAM network. Many of the properties of the CMAC for rigid robot control are kept by using CRAM for flexible-joint robots.
HER-2/neu and hTERT Cryptic Epitopes as Novel Targets for Broad Spectrum Tumor Immunotherapy1

Tolerance to tumor-nonmutated self proteins represents a major obstacle for successful cancer immunotherapy. Since this tolerance primarily concerns dominant epitopes, we hypothesized that targeting cryptic epitopes that have a low affinity for HLA could be an efficient strategy to breach the tolerance to tumor Ags. Using the P1Y heteroclitic peptide approach, we identified low affinity cryptic HLA-A*0201-restricted epitopes derived from two widely expressed tumor Ags, HER-2/neu and hTERT. The P1Y variants of four HER-2/neu (neu391, neu402, neu466, neu650)- and two hTERT (hTERT572 and hTERT988)-derived low affinity peptides exhibited strong affinity for HLA-A*0201 and stimulated specific CTL from healthy donor PBMCs. These CTL specifically recognized HER-2/neu- and hTERT-expressing tumor cells of various histological origins. In vivo studies showed that HLA-A*0201 transgenic HHD mice vaccinated with the P1Y variant peptides generated CTL that specifically lysed Ag-expressing tumor cells, thus recognizing the cognate endogenous Ags. These results suggest that heteroclitic variants of low affinity, cryptic epitopes of widely expressed tumor Ags may serve as valid tools for tumor immunotherapy.
The Optimum Time to Initiate Habitual Xylitol Gum-chewing for Obtaining Long-term Caries Prevention

Habitual xylitol gum-chewing may have a long-term preventive effect by reducing the caries risk for several years after the habitual chewing has ended. The goal of this report was (1) to determine if sorbitol and sorbitol/xylitol mixtures provide a long-term benefit, and (2) to determine which teeth benefit most from two-year habitual gum-chewing-those erupting before, during, or after habitual gum-chewing. Children, on average 6 years old, chewed gums sweetened with xylitol, sorbitol, or xylitol/sorbitol mixtures. There was a "no-gum" control group. Five years after the two-year program of habitual gum-chewing ended, 288 children were re-examined. Compared with the no-gum group, sorbitol gums had no significant long-term effect (relative risk [RR], 0.65; 95% confidence interval [c.i.], 0.39 to 1.07; p < 0.18). Xylitol gum and, to a lesser extent, xylitol/sorbitol gum had a long-term preventive effect. During the 5 years after habitual gum-chewing ended, xylitol gums reduced the caries risk 59% (RR, 0.41; 95% c.i., 0.23 to 0.75; p < 0.0034). Xylitol-sorbitol gums reduced the caries risk 44% (RR, 0.56; 95% c.i., 0.36 to 0.89; p < 0.02). The long-term caries risk reduction associated with xylitol strongly depended on when teeth erupted (p < 0.02). Teeth that erupted after 1 year of gum-chewing or after the two-year habitual gum use ended had long-term caries risk reductions of 93% (p < 0.0054) and 88% (p < 0.0004), respectively. Teeth that erupted before the gum-chewing started had no significant long-term prevention (p < 0.30). We concluded that for long-term caries-preventive effects to be maximized, habitual xylitol gum-chewing should be started at least one year before permanent teeth erupt.
Genetic relations of yolk proportion and chick weight with production traits in a White Leghorn line

1. The main purpose of this study was to estimate genetic correlations between yolk proportion, chick weight and production traits using an animal model. 2. Direct-direct genetic correlations were estimated between yolk proportion and age at first egg (−0·34), body weight at 20 (0·10), 40 (0·58) and 60 (0·52) weeks of age, egg number (0·56), egg mass (0·59), feed intake (0·64) and feed conversion (−0·25). 3. Maternal-direct genetic correlations were estimated between chick weight and age at first egg (0·40), body weight at 20 (0·57), 40 (0·66) and 60 (0·56) weeks of age, egg number (−0·50), egg mass (0·21), feed intake (0·45) and feed conversion (0·17), respectively. 4. In conclusion, the results suggest that selection on a higher yolk proportion would not have any unfavourable effects on egg production. Maternal-direct genetic correlations between chick weight and production traits resembled direct-direct genetic correlations between egg weight and production traits found in other studies.
Comparative Analysis of Disease Activity Measures, Use of Biologic Agents, Body Mass Index, Radiographic Features, and Bone Density in Psoriatic Arthritis and Rheumatoid Arthritis Patients Followed in a Large U.S. Disease Registry

Objective. To compare disease activity, radiographic features, and bone density in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) matched cohorts. Methods. Disease activity and radiographic data in the Consortium of Rheumatology Researchers of North America database from 2001 to 2008 were compared for 2481 patients with PsA and 17,107 patients with RA subsequently matched for age, gender, and disease duration. Radiographic outcomes included presence of erosions, and joint deformity. In addition, bone mineral density (BMD) scores for lumbar spine (L-spine) and femoral neck were compared using the same matching criteria plus weight and smoking status. Results. Tender (4.5 vs 3.4, p < 0.001) and swollen (4.4 vs 2.9, p < 0.012) joint counts, and modified Health Assessment Questionnaire scores were significantly higher (0.4 vs 0.3, p < 0.001) in patients with RA compared with patients with PsA. Patient general health and pain scores were also higher in patients with RA vs patients with PsA. Joint erosions (47.4% vs 37.6%, p = 0.020) and deformity (25.2% vs 21.6%, p = 0.021) were more prevalent in RA than PsA. In multivariate analysis, a reduced prevalence of erosions in PsA vs RA was noted (OR 0.609, p < 0.001). After matching, T-scores for L-spine (−0.54 vs −0.36, p = 0.077) and femoral neck (−0.88 vs −0.93, p = 0.643) were similar in patients with RA and patients with PsA, although body weight was a major confounder. Conclusion. The level of disease activity and radiographic damage was significantly higher for RA vs PsA subjects, although the magnitude of differences was relatively small. BMD levels were comparable between cohorts. Outcomes in patients with PsA and patients with RA may be more similar than previously reported.
Incipient fault online estimation based on Kullback-Leibler Divergence and fast moving window PCA

The realization of early detection of incipient faults makes great sense for the guarantee of system performance and security operation. Therefore, It is necessary to estimate the fault amplitude especially when the system security assessment is the main goal. Regarding the incipient fault with low Fault-Noise-ratio (FNR), in this paper, a practical online fault estimation method is presented for multivariate processes. Statistics based on Kullback-Leibler Divergence (KLD), that is characterized with a high sensitivity to incipient fault, are utilized for the realization of small deviation estimation. Based on the Gaussian assumption, KLDs of different principal components, that characterizes the difference between free-fault and fault case, are computed online through updating the mean and variance of scores. The simulation confirms the feasibility and effectiveness of the proposed incipient fault diagnosis method.
Dietary exposure of BDE‐47 and BDE‐99 and effects on behavior, bioenergetics, and thyroid function in juvenile red‐eared sliders (Trachemys scripta elegans) and common snapping turtles (Chelydra serpentina)

Juvenile red‐eared sliders (Trachemys scripta elegans) and snapping turtles (Chelydra serpentina) were fed food dosed with brominated diphenyl ether‐47 (BDE‐47) or BDE‐99 for 6 mo beginning approximately 9 mo posthatch. During the exposure period, measurements of growth, bioenergetics, and behavior were made; thyroid function and accumulation were quantified postexposure. Whole‐body concentrations of both congeners were lower in red‐eared sliders compared with snapping turtles after 6 mo of exposure. Snapping turtles receiving BDE‐47 had significantly elevated standard metabolic rates after 3 mo and 4 mo of exposure (p = 0.014 and p = 0.019, respectively). When exposed to BDE‐99, red‐eared sliders were slower to right themselves after having been inverted (p < 0.0001). Total glandular thyroxine concentrations were significantly reduced in red‐eared sliders exposed to BDE‐47 (mean control, 8080 ng/g; mean BDE‐47, 5126 ng/g; p = 0.034). These results demonstrate that dietary exposure to BDE‐47 and BDE‐99 can elicit a suite of responses in 2 species of turtles, but that the red‐eared slider appears to be a more sensitive species to the measured end points. Environ Toxicol Chem 2014;33:2810–2817. © 2014 SETAC
Structure and Conformation of Tetra-meso-, Octa-β-, and Dodecasubstituted 22,24-Dihydroporphyrins (Porphyrin Dications)

A comparative crystallographic analysis of the conformation of porphyrin diacids with various substituent types reveals considerable differences in the degree of nonplanarity and distortion modes. Diacids of 5,10,15,20-tetraarylporphyrins generally exhibit typical saddledistorted macrocycles with displacements of the Cb positions in the range of 0.7-1.0 Å. Adding peripheral substituents, i.e., using dodecasubstituted porphyrins for the diacid formation yields similar distortion types albeit with larger out-of-plane displacements. As a result of the combined effect of both peripheral (interaction between the Cb and Cm substituents) and core (interaction between the four inner hydrogen atoms) steric strain the maximum Cb displacements reach 1.3-1.5 Å. Quite a different situation is observed for the diacids of 2,3,7,8,12,13,17,18-octaalkylporphyrins. Here, macrocycles with pair-wise displacement of neighboring pyrrole rings and significant NH pyramidalization and those with classic saddle distortion are found. Generally, octa- β-substituted porphyrin diacids show smaller degrees of nonplanarity; Cb displacements ranged from 0.06 to 0.72 Å. On the basis of the overall degree of conformational distortion (⊿24 = average deviation of the 24 macrocycles atoms from the mean plane), the three different types of porphyrin macrocycles studied differ considerably in their degree of conformational flexibility. For several porphyrin crystal structures with different counterions and/or solvate molecules were obtained. Taking into account results from the literature 2,3,7,8,12,13,17,18-octaethyl-22,24-dihydro-5,10,15. ,20-tetraphenylporphyrin (13) shows the smallest degree of flexibility (⊿24 = 0.61-0.63 Å; four different X-ray structures), while 22,24-dihydro-5,10,15,20-tetraphenylporphyrin (1) is more flexible (Z⊿24 = 0.42-0.52 Å; four structures). The largest flexibility is observed for 2,3,7,8,12,13,18-octaethyl- 22,24-dihydroporphyrin (7) (⊿24 = 0.02-0.33 Å; four structures).
Endometriosi: impatto sulla fertilità

328 L’endometriosi è una patologia ginecologica caratterizzata dalla presenza di tessuto endometriale all’esterno della cavità uterina. Sebbene l’esatta prevalenza dell’endometriosi nella popolazione generale non sia conosciuta, essa rappresenta una patologia frequente tra le donne in età riproduttiva (1), venendo infatti riscontrata in una percentuale variabile dal 20 al 90% delle donne con dolore pelvico e/o infertilità (2, 3). È una delle patologie ginecologiche più controverse: infatti, nonostante il particolare interesse riservatole negli ultimi decenni dall’intera comunità scientifica e la notevole esperienza clinica acquisita in materia, resta un enigma da risolvere per le peculiari implicazioni fisiopatologiche. In particolare, complessa e fortemente dibattuta risulta la pur inequivocabile relazione esistente fra endometriosi ed infertilità (4). Se infatti è plausibile che nelle forme moderate/severe di endometriosi (stadio III e IV) la sterilità sia primariamente dovuta ad un fattore meccanico, ovvero alla sovversione della normale anatomia pelvica (es. alterazioni del rapporto tubo-ovarico, distorsione/ostruzione tubarica), non è ancora ben chiarita la ragione dell’incidenza di infertilità/subinfertilità nelle donne affette da endometriosi minima/lieve (stadio I e II), ovvero in assenza di aderenze e di lesioni endometriosiche gravi. Ad oggi, sembra che nessuno dei meccanismi ipotizzati, possa, da solo, spiegare in maniera esaustiva la sterilità nell’endometriosi e che, invece, essa riconosca un’etiologia multifattoriale. Ci siamo proposti pertanto, attraverso un’attenta rivisitazione della letteratura internazionale, di analizzare i principali fattori eziologici che sembrerebbero maggiormente implicati nel determinismo dell’infertilità nella patologia endometriosica.
Functional properties and Ca2-dependent feedback modulation of voltage-gated Ca2 channels in glutamatergic nerve terminals of the mammalian auditory brainstem.

The functional properties of mammalian presynaptic nerve endings remain elusive since most terminals of the central nervous system are not accessible to direct electrophysiological recordings. In the present study, functional properties and Ca2+-dependent feedback modulation of presynaptic voltage-gated Ca2+ channels were studied by direct recordings from two types of large glutamatergic nerve terminals of the mammalian auditory brainstem endbulbs of Held and calyces of Held. Endbulb of Held terminals were identified by their high input resistance and small capacitance. Presynaptic VGCCs in endbulbs were predominantly of the P/Q type and expressed at a high density with an estimated average number of 6400 channels per terminal. Presynaptic Ca2+ currents activated and deactivated rapidly. Simulations of action potential (AP)-driven gating of VGCCs suggests that endbulb APs trigger brief Ca2+ influx with a mean half-width of 240 µs and a peak amplitude of 0.45 nA which results from the opening of approximately 2600 channels. Endbulb terminals are endowed with a large readily releasable vesicle pool (1064 vesicles) of which only a small fraction is consumed during a single AP-like stimulus. Unlike Ca2+ currents at the calyx of Held, ICa(V) of endbulb terminals showed no inactivation during trains of AP-like presynaptic depolarizations. Because of their larger size, calyx of Held terminals can be easily visualized. Presynaptic P/Q-type channels expressed in calyx terminals show two types of Ca2+-dependent feedback regulation inactivation (CDI) and facilitation (CDF). We studied the mechanisms and intracellular Ca2+ requirements for CDI and CDF. ICa(V) in calyx terminals inactivated with a biphasic time course. The fast component of inactivation was Ca2+-dependent. CDI during sustained depolarizations was relatively insensitive to Ca2+ chelators. The contribution to ICa(V) inactivation of Ca2+ depletion from the synaptic cleft or that of metabotropic feedback mechanisms was negligible. Recovery of ICa(V) from inactivation was slow and followed a biexponential time course with average time constants of ~320 ms and ~7.2 s. In contrast, ICa(V) facilitation decayed very fast with an average time constant of ~30 ms. Intracellular Ca2+ requirement for CDI and CDF were probed by Ca2+ uncaging via flash photolysis. [Ca2+]i elevations in the micromolar range were sufficient to induce CDI and CDF. Half maximum concentrations were ~6 µM and ~2 µM for CDI and CDF, respectively. During repetitive AP firing, the global [Ca2+]i can easily reach levels of a few micromoles in unperturbed calyx terminals suggesting that CDF and CDI can be induced during normal physiological presynaptic AP firing. Because of the divergent onset and recovery kinetics of CDI and CDF, facilitation of VGCCs is expected to occur during high-frequency AP bursts. In contrast, low-frequency firing will lead to cumulative inactivation of presynaptic VGCCs.
eneration and characterization of a tomato DCL 3-silencing mutant

DICER-like 3 (DCL3) is a major player in heterochromatic 24-nucleotide (nt) small RNA (sRNA) and long microRNA (lmiRNA) biogenesis, and higher plant DCL3 mutants have been characterized from Arabidopsis thaliana and rice. Here, a tomato DCL3 (SlDCL3) mutant was generated through the use of trans-activated artificial miRNA and characterized. Constitutive trans-activation knocked down SlDCL3 levels by ∼64%, resulting in dramatically decreased 24-nt sRNA levels and a significant increase in 21and 22-nt sRNAs. The latter was correlated with specific upregulation of SlDCL4 and SlDCL2b, which function in the biogenesis of 21and 22-nt sRNAs, respectively. Moreover, at the majority of sRNA-generating genomic loci, an almost complete overlap between small RNA signatures of control and silenced seedlings was observed, suggesting that the reductions in 24-nt sRNAs at these loci were compensated for by biogenesis of 21-
Matrix metalloproteinase-13 and membrane type-1 matrix metalloproteinase in peritoneal fluid of women with endometriosis

Objective. It is becoming more and more evident that different types of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in the pathogenesis of endometriosis. The aim of the present study was to measure levels of the active forms of MMP-13 and membrane type-1 matrix metalloproteinase (MT1-MMP)/MMP-14 as well as TIMP-2 in the peritoneal fluid of women with endometriosis. Study design. We determined the levels of the active forms MMP-13 and MT1-MMP/MMP-14 as well as TIMP-2 in the peritoneal fluid of 20 women with endometriosis and 18 controls by different types of enzyme-linked immunosorbent assay. Results. We found that the concentrations (mean ± standard deviation) of total active MMP-13 and endogenous active MT1-MMP/MMP-14 in the peritoneal fluid of patients with endometriosis were 1.69 ± 0.67 and 3.12 ± 1.07 ng/ml, respectively. In control women the corresponding values were 3.02 ± 0.43 and 4.45 ± 1.03 ng/ml. The differences were statistically significant (p < 0.0001 and p < 0.0004 for MMP-13 and MMP-14, respectively). Levels of TIMP-2 did not differ significantly. Conclusions. Decreased concentrations of active MMP-13 and MT1-MMP/MMP-14 may imply that the proteolytic activity of the peritoneal milieu of women with endometriosis is disturbed, which may have implications in the pathogenesis of the disease.
SU-F-J-96: Comparison of Frame-Based and Mutual Information Registration Techniques for CT and MR Image Sets.

PURPOSE To compare the accuracy of CT-MR registration using a mutual information method with registration using a frame-based localizer box. METHODS Ten patients having the Leksell head frame and scanned with a modality specific localizer box were imported into the treatment planning system. The fiducial rods of the localizer box were contoured on both the MR and CT scans. The skull was contoured on the CT images. The MR and CT images were registered by two methods. The frame-based method used the transformation that minimized the mean square distance of the centroids of the contours of the fiducial rods from a mathematical model of the localizer. The mutual information method used automated image registration tools in the TPS and was restricted to a volume-of-interest defined by the skull contours with a 5 mm margin. For each case, the two registrations were adjusted by two evaluation teams, each comprised of an experienced radiation oncologist and neurosurgeon, to optimize alignment in the region of the brainstem. The teams were blinded to the registration method. RESULTS The mean adjustment was 0.4 mm (range 0 to 2 mm) and 0.2 mm (range 0 to 1 mm) for the frame and mutual information methods, respectively. The median difference between the frame and mutual information registrations was 0.3 mm, but was not statistically significant using the Wilcoxon signed rank test (p=0.37). CONCLUSION The difference between frame and mutual information registration techniques was neither statistically significant nor, for most applications, clinically important. These results suggest that mutual information is equivalent to frame-based image registration for radiosurgery. Work is ongoing to add additional evaluators and to assess the differences between evaluators.
Vascular viewpoint

Question: Is a history of pre-existing atherothrombotic disease associated with an increased risk of subsequent ischemic events, and is it associated with a reduction in efficacy of clopidogrel? Population: Patients with recent ischemic stroke (IS), myocardial infarction (MI), or established peripheral arterial disease, and a history of pre-existing symptomatic atherothrombotic disease (IS and=or MI) were enrolled in the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial. CAPRIE was a randomized, blinded, clinical trial comparing the efficacy of clopidogrel with aspirin in patients at risk of ischemic events. Design and methods: Retrospective, subgroup analysis of 4496 patients with a prior history of symptomatic atherothrombotic disease from the CAPRIE study. Results: Compared with the overall population of CAPRIE, patients with pre-existing symptomatic atherothrombotic disease have elevated rates of IS, MI, or vascular death. The 3-year rates of IS, MI, or vascular death were 20.4% with clopidogrel and 23.8% with aspirin (absolute risk reduction: 3.4%; 95% CI: -0.2 to 7.0; number needed to treat: 29; relative risk reduction: 14.9% (95% CI: 0.3 to 27.3; p = 0.045)). Conclusion: Patients with a history of previous symptomatic atherothrombotic disease suffer a high rate of subsequent ischemic events. Among these patients, the absolute risk reduction of clopidogrel over aspirin is greater compared with patients without pre-existing atherothrombotic disease.
MEK-Specific Inhibitor U0126 Blocks Spread of Borna Disease Virus in Cultured Cells

ABSTRACT Borna disease virus (BDV) is a highly neurotropic virus that causes Borna disease, a virus-induced immune-mediated encephalomyelitis, in a variety of warm-blooded animals. Recent studies reported that BDV can be detected in patients with psychiatric disorders. BDV is noncytopathic, replicates in the nucleus of infected cells, and spreads intraaxonally in vivo. Upon infection of susceptible cultured cells, virus can be detected in foci. Little is known about the cellular components required for BDV replication. Here, we show that the cellular Raf/MEK/ERK signaling cascade is activated upon infection with BDV. In the presence of the MEK-specific inhibitor U0126, cells get infected with BDV; however, there is a block in virus spread to neighboring cells. The effect of the inhibitor on virus spread was still observed when the compound was added 2 h postinfection but not if treatment was initiated as late as 4 h after infection. Our results provide new insights into the BDV-host cell interaction and show that virus infection can be controlled with drugs interfering with a cellular signaling pathway. Since concentrations of the MEK inhibitor required to block BDV focus formation are not toxic for the host cells, our finding may be important with respect to antiviral drug development.