Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-term nutritional and neurodevelopmental outcome of liver transplantation in infants aged less than 12 months.

BACKGROUND Liver transplantation is established treatment for children with end-stage liver disease and has a 5-year survival rate of 80% to 85%, even in infants under 12 months. Long-term outcome in nutritional rehabilitation and normal development is unknown. This study aimed to prospectively evaluate growth and psychoneurologic performance of children who undergo liver transplantation in infancy. METHODS Twenty-five infants (18 girls, 7 boys) who underwent liver transplantation at less than 12 months of age (median age, 9 months) were evaluated for 4 years. Growth measurements were expressed as standard deviation scores (SDSs; mean +/- SEM), and psychoneurologic performance was assessed with the unrevised Griffiths Mental Ability Scales (normal range, 80-120). RESULTS Four children died during the study (4-year survival, 84%). The children were malnourished before transplantation (SDSs: weight, -1.9 +/- 0.2; midarm muscle area, -0.93 +/- 0.3; midarm fat area, -1.52 +/- 0.3; and height, -0.95 +/- 0.3). Nutritional rehabilitation for all parameters occurred within 12 to 24 months after transplantation, which was most significant for weight (-1.1 +/- 0.2, P = 0.001), midarm muscle area (0.74 +/- 0.3, P = 0.001), and midarm fat area (-0.44 +/- 0.3, P = 0.01). There was some improvement in height (-0.72 +/- 0.3, P = 0.14), which was not significant, although infants who were severely stunted before transplantation (mean height standard deviation score [SDS] -2.46) showed significant catch-up at 1 year after transplantation (mean height SDS -1.2, P = 0.003). Psychoneurologic scores were within normal limits before transplantation and were maintained for the 4-year follow-up period, although individual scores varied during this period. Improved nutritional status was associated with increased muscle bulk and subsequent improvement in motor scores from 90.6 at initial assessment to 97.3 at 4 years (P = 0.28). There was a temporary reduction in social skills and eye-hand coordination in the first year, which may have been an effect of the hospital environment or cyclosporine immunosuppression. Language abilities also regressed during the first year, possibly related to the effect of nasogastric tube feeding in delaying normal speech development. CONCLUSIONS Liver transplantation in infancy has not only a successful outcome but is also associated with long-term catch-up growth and nutrition and maintenance of normal development.
Agonistic Human Antibodies Binding to Lecithin-Cholesterol Acyltransferase Modulate High Density Lipoprotein Metabolism*

Drug discovery opportunities where loss-of-function alleles of a target gene link to a disease-relevant phenotype often require an agonism approach to up-regulate or re-establish the activity of the target gene. Antibody therapy is increasingly recognized as a favored drug modality due to multiple desirable pharmacological properties. However, agonistic antibodies that enhance the activities of the target enzymes are rarely developed because the discovery of agonistic antibodies remains elusive. Here we report an innovative scheme of discovery and characterization of human antibodies capable of binding to and agonizing a circulating enzyme lecithin cholesterol acyltransferase (LCAT). Utilizing a modified human LCAT protein with enhanced enzymatic activity as an immunogen, we generated fully human monoclonal antibodies using the XenoMouseTM platform. One of the resultant agonistic antibodies, 27C3, binds to and substantially enhances the activity of LCAT from humans and cynomolgus macaques. X-ray crystallographic analysis of the 2.45 Å LCAT-27C3 complex shows that 27C3 binding does not induce notable structural changes in LCAT. A single administration of 27C3 to cynomolgus monkeys led to a rapid increase of plasma LCAT enzymatic activity and a 35% increase of the high density lipoprotein cholesterol that was observed up to 32 days after 27C3 administration. Thus, this novel scheme of immunization in conjunction with high throughput screening may represent an effective strategy for discovering agonistic antibodies against other enzyme targets. 27C3 and other agonistic human anti-human LCAT monoclonal antibodies described herein hold potential for therapeutic development for the treatment of dyslipidemia and cardiovascular disease.
Helium behavior at fcc-bcc semicoherent interfaces: trapping, clustering, nucleation, and growth of cavities

He implanted into metals precipitates into nanoscale bubbles that grow into voids, degrading the properties of engineering alloys in nuclear energy applications. In this thesis, multi-scale modeling techniques and neutron reflectometry measurements are used to study the He trapping, clustering and growth of clusters at fcc-bcc interfaces. Choosing Cu-Nb as a model fcc-bcc interface, a predictive Cu-Nb-He interatomic potential is constructed using density functional theory. These calculations show that two-body radial forces are sufficient to describe interactions of He with fcc Cu and bcc Nb. Atomistic simulations reveal that He is initially trapped in the form of stable, sub-nanometer platelet-shaped clusters and not bubbles at the Cu-Nb interface. This behavior occurs due to the spatial heterogeneity of interface energy: He wets high energy, heliophilic regions while avoiding low energy, heliophobic ones. Using these insights, the maximum He concentration that can be stored without forming bubbles at any interface in terms of its location-dependent energy distribution may be predicted. The modeling predictions are validated by neutron reflectometry measurements, which show that interfacial He bubbles form only above a critical He concentration and provide evidence for the presence of stable He platelets below a critical He concentration. This work paves the way for the design of composite structural materials with increased resistance to He-induced degradation by tailoring the types of interfaces they contain. Thesis Supervisor: Michael J. Demkowicz Title: Assistant Professor of Materials Science and Engineering
Dosimetric comparison of Acuros XB, AAA, and XVMC in stereotactic body radiotherapy for lung cancer.

PURPOSE To compare the dosimetric performance of Acuros XB (AXB), anisotropic analytical algorithm (AAA), and x-ray voxel Monte Carlo (XVMC) in heterogeneous phantoms and lung stereotactic body radiotherapy (SBRT) plans. METHODS Water- and lung-equivalent phantoms were combined to evaluate the percentage depth dose and dose profile. The radiation treatment machine Novalis (BrainLab AG, Feldkirchen, Germany) with an x-ray beam energy of 6 MV was used to calculate the doses in the composite phantom at a source-to-surface distance of 100 cm with a gantry angle of 0°. Subsequently, the clinical lung SBRT plans for the 26 consecutive patients were transferred from the iPlan (ver. 4.1; BrainLab AG) to the Eclipse treatment planning systems (ver. 11.0.3; Varian Medical Systems, Palo Alto, CA). The doses were then recalculated with AXB and AAA while maintaining the XVMC-calculated monitor units and beam arrangement. Then the dose-volumetric data obtained using the three different radiation dose calculation algorithms were compared. RESULTS The results from AXB and XVMC agreed with measurements within ± 3.0% for the lung-equivalent phantom with a 6 × 6 cm(2) field size, whereas AAA values were higher than measurements in the heterogeneous zone and near the boundary, with the greatest difference being 4.1%. AXB and XVMC agreed well with measurements in terms of the profile shape at the boundary of the heterogeneous zone. For the lung SBRT plans, AXB yielded lower values than XVMC in terms of the maximum doses of ITV and PTV; however, the differences were within ± 3.0%. In addition to the dose-volumetric data, the dose distribution analysis showed that AXB yielded dose distribution calculations that were closer to those with XVMC than did AAA. Means ± standard deviation of the computation time was 221.6 ± 53.1 s (range, 124-358 s), 66.1 ± 16.0 s (range, 42-94 s), and 6.7 ± 1.1 s (range, 5-9 s) for XVMC, AXB, and AAA, respectively. CONCLUSIONS In the phantom evaluations, AXB and XVMC agreed better with measurements than did AAA. Calculations differed in the density-changing zones (substance boundaries) between AXB/XVMC and AAA. In the lung SBRT cases, a comparative analysis of dose-volumetric data and dose distributions with XVMC demonstrated that the AXB provided better agreement with XVMC than AAA. The computation time of AXB was faster than that of XVMC; therefore, AXB has better balance in terms of the dosimetric performance and computation speed for clinical use than XVMC.
A Short Note on Constrained Linear Control Systems With Multiplicative Ellipsoidal Uncertainty

This technical note revisits the classical robust control question of how to design linear control laws for uncertain linear dynamic systems. We formulate this robust control design problem from a modern optimal control perspective which allows us to take into account control and state constraints that have to be satisfied by the closed-loop system for all possible uncertainty scenarios. The contribution of this technical note is the derivation of a conservative but computationally tractable robust control design problem formulation for the case that multiplicative uncertainties are present in the linear dynamic systems, which render the robust control problem non-convex in general. Here, our approximation technique relies on propagating ellipsoidal bounds on the reachable states of the closed-loop system. The methods developed in this technical note can also be used as a building block for tube based model predictive control schemes, where robustly designed linear control laws can help to reduce the conservatism of open-loop predictions. We illustrate the proposed techniques with a numerical case study.
Probabilistic noninterference in a concurrent language

The authors previously give a type system that guarantees that well-typed multi-threaded programs are possibilistically noninterfering. If thread scheduling is probabilistic, however, then well-typed programs may have probabilistic timing channels. They describe how they can be eliminated without making the type system more restrictive. They show that well-typed concurrent programs are probabilistically noninterfering if every total command with a high guard executes atomically. The proof uses the concept of a probabilistic state of a computation, following the work of Kozen (1981).
Deactivation of the GATA Transcription Factor ELT-2 Is a Major Driver of Normal Aging in C. elegans

To understand the molecular processes underlying aging, we screened modENCODE ChIP-seq data to identify transcription factors that bind to age-regulated genes in C. elegans. The most significant hit was the GATA transcription factor encoded by elt-2, which is responsible for inducing expression of intestinal genes during embryogenesis. Expression of ELT-2 decreases during aging, beginning in middle age. We identified genes regulated by ELT-2 in the intestine during embryogenesis, and then showed that these developmental genes markedly decrease in expression as worms grow old. Overexpression of elt-2 extends lifespan and slows the rate of gene expression changes that occur during normal aging. Thus, our results identify the developmental regulator ELT-2 as a major driver of normal aging in C. elegans.
Budding process during the organogenesis of the ventral prostatic lobe in mongolian gerbil

The prostate is a mammalian gland that shows a complex process of organogenesis. Here, a morphological study to characterize the organogenesis of the ventral prostate lobe in male gerbils was conducted. The urogenital sinus (UGS) was dissected out and processed for paraffin embedding. Histological sections were subjected to cytochemical, immunofluorescence, immunohistochemical, and three‐dimensional reconstruction techniques. We found that the first ventral buds emerged from the ventral urethral epithelium between the days 20 and 21 of prenatal life, reaching the ventral mesenchymal pad and initiating the branching process on the first day of postnatal life. The buds presented a V‐shaped elongation, suggesting that the smooth muscle layer (SML) plays an important role during budding events. Indeed, whereas the androgen receptor (AR) was preferentially found in the UGS mesenchyme (UGM), estrogen receptor alpha (ERα) was localized in both the UGM and in the emerging buds. This study characterized the morphological aspects of the budding process in a different rodent from rat and mice, serving as a new model for future studies on developmental biology of the prostate. Microsc. Res. Tech. 77:458–466, 2014. © 2014 Wiley Periodicals, Inc.
Acoustic feature analysis in speech emotion primitives estimation

We recently proposed a family of robust linear and nonlinear estimation techniques for recognizing the three emotion primitives‐valence, activation, and dominance‐from speech. These were based on both local and global speech duration, energy, MFCC and pitch features. This paper aims to study the relative importance of these four categories of acoustic features in this emotion estimation context. Three measures are considered: the number of features from each category when all features are used in selection, the mean absolute error (MAE) when each category is used separately, and the MAE when a category is excluded from feature selection. We find that the relative importance is in the order of MFCC > Energy ! Pitch > Duration. Additionally, estimator fusion almost always improves performance, and locally weighted fusion always outperforms average fusion regardless of the number of features used. Index Terms: Emotion estimation, 3D emotion space, speech analysis, estimator fusion, support vector regression, robust regression, locally linear reconstruction, locally weighted fusion
Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells

Invasion and metastasis of aggressive breast cancer cells is the final and fatal step during cancer progression, and is the least understood genetically. Clinically, there are still limited therapeutic interventions for aggressive and metastatic breast cancers available. Clearly, effective and nontoxic therapies are urgently required. Id-1, an inhibitor of basic helix-loop-helix transcription factors, has recently been shown to be a key regulator of the metastatic potential of breast and additional cancers. Using a mouse model, we previously determined that metastatic breast cancer cells became significantly less invasive in vitro and less metastatic in vivo when Id-1 was down-regulated by stable transduction with antisense Id-1. It is not possible at this point, however, to use antisense technology to reduce Id-1 expression in patients with metastatic breast cancer. Here, we report that cannabidiol (CBD), a cannabinoid with a low-toxicity profile, could down-regulate Id-1 expression in aggressive human breast cancer cells. The CBD concentrations effective at inhibiting Id-1 expression correlated with those used to inhibit the proliferative and invasive phenotype of breast cancer cells. CBD was able to inhibit Id-1 expression at the mRNA and protein level in a concentration-dependent fashion. These effects seemed to occur as the result of an inhibition of the Id-1 gene at the promoter level. Importantly, CBD did not inhibit invasiveness in cells that ectopically expressed Id-1. In conclusion, CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells leading to the down-regulation of tumor aggressiveness. [Mol Cancer Ther 2007;6(11):2921–7]
To Resolve or Not To Resolve, that Is the Question: The Dual-Path Model of Incongruity Resolution and Absurd Verbal Humor by fMRI

It is well accepted that the humor comprehension processing involves incongruity detection and resolution and then induces a feeling of amusement. However, this three-stage model of humor processing does not apply to absurd humor (so-called nonsense humor). Absurd humor contains an unresolvable incongruity but can still induce a feeling of mirth. In this study, we used functional magnetic resonance imaging (fMRI) to identify the neural mechanisms of absurd humor. Specifically, we aimed to investigate the neural substrates associated with the complete resolution of incongruity resolution humor and partial resolution of absurd humor. Based on the fMRI data, we propose a dual-path model of incongruity resolution and absurd verbal humor. According to this model, the detection and resolution for the incongruity of incongruity resolution humor activate brain regions involved in the temporo-parietal lobe (TPJ) implicated in the integration of multiple information and precuneus, likely to be involved in the ability of perspective taking. The appreciation of incongruity resolution humor activates regions the posterior cingulate cortex (PCC), implicated in autobiographic or event memory retrieval, and parahippocampal gyrus (PHG), implying the funny feeling. By contrast, the partial resolution of absurd humor elicits greater activation in the fusiform gyrus which have been implicated in word processing, inferior frontal gyrus (IFG) for the process of incongruity resolution and superior temporal gyrus (STG) for the pragmatic awareness.
Social support and quality of life among lung cancer patients: a systematic review

This systematic review analyzed the relationships between social support and quality of life (QOL) indicators among lung cancer patients. In particular, the patterns of relationships between different social support facets and sources (received and perceived support from healthcare professionals, family, and friends) and QOL aspects (emotional, physical symptoms, functional, and social) as well as the global QOL index were investigated.
Towards Incremental Reasoning Through Updates in OWL-DL

In this paper, we investigate incrementally updating classi-ﬁcations of ontologies encoded in the expressive description logic SHOIN ( D ), which also corresponds to the W3C standard Web Ontology Language, OWL-DL. In particular we present various optimizations for incremental classiﬁcation under both axiom addition and removal. Several of the optimizations are independent of the logic and proof theory as long as classiﬁcation can be reduced to satisﬁability testing. Additionally, we provide an empirical analysis of the optimizations through an experimental implementation in the Pellet OWL-DL reasoner.
Condition Monitoring of DC-Link Electrolytic Capacitors in Adjustable-Speed Drives

A new preventive maintenance strategy for the sensorless condition monitoring of inverter dc-link aluminum electrolytic capacitors based on equivalent series resistance (ESR) and capacitance C estimation is proposed. The main concept of the proposed method is to estimate the ESR and C of the capacitor, using the inverter whenever the motor is stopped. The parameters are estimated from the dc-link voltage and stator current measurements available in the inverter with the switched dc-link voltage applied to the motor stator winding. The temperature of the capacitor can also be estimated under thermal equilibrium based on the stator resistance estimate to take the influence of temperature variation into account. An experimental study on a 250-W permanent magnet synchronous motor performed under accelerated capacitor degradation is presented to verify the proposed technique. It is shown that the proposed method provides a reliable and sensitive indication of capacitor aging without additional hardware requirements for reliable, efficient, and safe operation of the inverter and driven process.
Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta‐analysis

New direct oral anticoagulants (NOACs) constitute a novel treatment option for acute venous thromboembolism (VTE), with practical advantages. Individual studies have demonstrated comparable efficacy to that of vitamin K antagonists (VKAs) and have suggested a more favorable safety profile . We performed a meta‐analysis to determine the efficacy and safety of NOACs as compared with those of VKAs in patients with acute VTE.
Induction and mitochondrial localization of cytochrome P450scc system enzymes in normal and transformed ovarian granulosa cells

After ovulation of an oocyte, granulosa cells of the ovarian follicle differentiate into luteal cells and become a major factor dedicated to the synthesis of the steroid hormone progesterone. We recently established granulosa cell lines by cotransfection of granulosa cells with SV-40 and Ha-ras oncogene. In these cells progesterone secretion can be induced by cAMP as in normal rat granulosa cells. The induction of progesterone secretion is observed only after approximately 24 h and closely follows the delayed but quantitatively dramatic induction of the mitochondrial cytochrome P450scc which catalyzes the first step in steroid hormone biosynthesis. The mitochondrial P450 system electron transport proteins, adrenodoxin and adrenodoxin reductase, are also induced but adrenodoxin shows a faster induction. Immunofluorescence studies show that the three enzymes are induced in all cells and incorporated into all mitochondria uniformly. Electron microscopic examination using immunogold technique further confirms this and reveals that adrenodoxin is predominantly located on the matrix side of the inner mitochondrial membrane. Thus, adrenodoxin, which is a small highly charged protein, shows a distribution similar to P450scc which is an integral membrane protein. The uniformity of the response of the cells provides further evidence for the homogeneity of the cell line and makes this new granulosa cell line a highly promising system for the study of the molecular mechanisms involved in changes in gene expression during the process of granulosa cell differentiation.
The Pivotal Role of Airway Smooth Muscle in Asthma Pathophysiology

Asthma is characterized by the association of airway hyperresponsiveness (AHR), inflammation, and remodelling. The aim of the present article is to review the pivotal role of airway smooth muscle (ASM) in the pathophysiology of asthma. ASM is the main effector of AHR. The mechanisms of AHR in asthma may involve a larger release of contractile mediators and/or a lower release of relaxant mediators, an improved ASM cell excitation/contraction coupling, and/or an alteration in the contraction/load coupling. Beyond its contractile function, ASM is also involved in bronchial inflammation and remodelling. Whereas ASM is a target of the inflammatory process, it can also display proinflammatory and immunomodulatory functions, through its synthetic properties and the expression of a wide range of cell surface molecules. ASM remodelling represents a key feature of asthmatic bronchial remodelling. ASM also plays a role in promoting complementary airway structural alterations, in particular by its synthetic function.
An 18‐year follow‐up report on an infant with a duplication of 9q34

An 18-Year Follow-Up Report on an Infant With a Duplication of 9q34 Erin L. Youngs, Timothy McCord, Jessica A. Hellings, Nancy B. Spinner, Adele Schneider, and Merlin G. Butler* Departments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, Kansas Division of Human Genetics, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania Department of Pediatrics, Albert Einstein Medical Center, Philadelphia, Pennsylvania