Miracle-dz/UniFAR-FTUs huggingface dataset:
Telomere length is greater in ALS than in controls: a whole genome sequencing study

Abstract Background: Amyotrophic lateral sclerosis is a neurodegenerative disease of motor neurons resulting in progressive paralysis and death, typically within 3–5 years. Although the heritability of ALS is about 60%, only about 11% is explained by common gene variants, suggesting that other forms of genetic variation are important. Telomeres maintain DNA integrity during cellular replication and shorten naturally with age. Gender and age are risk factors for ALS and also associated with telomere length. We therefore investigated telomere length in ALS. Methods: We estimated telomere length by applying a bioinformatics analysis to whole genome sequence data of leukocyte-derived DNA from people with ALS and age and gender-matched matched controls in a UK population. We tested the association of telomere length with ALS and ALS survival. Results: There were 1241 people with ALS and 335 controls. The median age for ALS was 62.5 years and for controls, 60.1 years, with a male–female ratio of 62:38. Accounting for age and sex, there was a 9% increase of telomere length in ALS compared to matched controls. Those with longer telomeres had a 16% increase in median survival. Of nine SNPs associated with telomere length, two were also associated with ALS: rs8105767 near the ZNF208 gene (p = 1.29 × 10−4) and rs6772228 (p = 0.001), which is in an intron for the PXK gene. Conclusions: Longer telomeres in leukocyte-derived DNA are associated with ALS, and with increased survival in those with ALS.
Lateral Sclerosis Degeneration Telomere length is greater in ALS than in controls: a whole genome sequencing study

Background: Amyotrophic lateral sclerosis is a neurodegenerative disease of motor neurons resulting in progressive paraly- sis and death, typically within 3 – 5 years. Although the heritability of ALS is about 60%, only about 11% is explained by common gene variants, suggesting that other forms of genetic variation are important. Telomeres maintain DNA integ- rity during cellular replication and shorten naturally with age. Gender and age are risk factors for ALS and also associated with telomere length. We therefore investigated telomere length in ALS. Methods: We estimated telomere length by applying a bioinformatics analysis to whole genome sequence data of leukocyte-derived DNA from people with ALS and age and gender-matched matched controls in a UK population. We tested the association of telomere length with ALS and ALS survival. Results: There were 1241 people with ALS and 335 controls. The median age for ALS was 62.5 years and for controls, 60.1 years, with a male – female ratio of 62:38. Accounting for age and sex, there was a 9% increase of telomere length in ALS compared to matched controls. Those with longer telomeres had a 16% increase in median survival. Of nine SNPs associated with telomere length, two were also associated with ALS: rs8105767 near the ZNF208 gene ( p ¼ 1.29 (cid:3) 10 (cid:4) 4 ) and rs6772228 ( p = 0.001), which is in an intron for the PXK gene. Conclusions: Longer telomeres in leukocyte-derived DNA are associated with ALS, and with increased survival in those with ALS.
Blended psychosocial support for partners of patients with ALS and PMA: results of a randomized controlled trial

Objective: To evaluate whether a blended (face-to-face and online) psychosocial support program for caregivers of patients with Amyotrophic Lateral Sclerosis (ALS) and Progressive Muscular Atrophy (PMA), aimed at enhancing feeling of control over caregiving, reduces psychological distress. Methods: A randomized controlled trial using a wait-list control design was conducted. Caregiver-patient dyads were randomly assigned to either the support program ( n ¼ 74) or to a wait-list control group ( n ¼ 74). The support program, based on Acceptance and Commitment Therapy, consists of 1 face-to-face contact, 6 online guided modules and 1 telephone contact. Participants filled in questionnaires at base- line, 3 and 6 months. Caregivers ’ feeling of control over caregiving was assessed using two self-efficacy measures. Primary outcome was caregivers ’ psychological distress. Secondary outcomes included caregiver burden, caregiver quality of life and patients ’ quality of life and psychological distress. Intention-to-treat and per-protocol analyses were performed using linear mixed models. Results: The support program had no effect on the primary or secondary outcomes, despite a significant positive effect on the intervening variable self-efficacy with regard to control over thoughts. Almost half of the caregivers did not complete the intervention with the most frequently reported reason being lack of time. Caregivers who completed the intervention evaluated the support program positively. Conclusions: The support program did not reduce distress of partners of patients with ALS/PMA but may be beneficial by increasing feeling of control over the caregiving situation. The high level of intervention drop outs may have limited the ability to detect an intervention effect. Trial registration:
Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

Despite recent interest in cognitive changes in patients with amyotrophic lateral sclerosis (ALS), investigations of language function looking at the level of word, sentence and discourse processing are relatively scarce. Data were obtained from 26 patients with sporadic ALS and 26 healthy controls matched for age, education, gender, anxiety, depression and executive function performance. Standardized language tasks included confrontation naming, semantic access
Derivation of norms for the Dutch version of the Edinburgh cognitive and behavioral ALS screen

Background: The Edinburgh cognitive and behavioral ALS screen (ECAS) was developed specifically to detect cognitive and behavioral changes in patients with amyotrophic lateral sclerosis (ALS). Differences with regard to normative data of different (language) versions of neuropsychological tests such as the ECAS exist. Objective: To derive norms for the Dutch version of the ECAS. Methods: Normative data were derived from a large sample of 690 control subjects and cog- nitive profiles were compared between a matched sample of 428 patients with ALS and 428 control subjects. Results: Age, level of education, and sex were significantly associated with performance on the ECAS in the normative sample. ECAS data were not normally distributed and therefore normative data were expressed as percentile ranks. The comparison of ECAS scores between patients and control subjects demonstrated that patients obtained significantly lower scores for language, executive function, verbal fluency, and memory, which is in line with the established cognitive profile of ALS. Conclusion: For an accurate interpretation of ECAS results, it is important to derive normative data in large samples with nonparametric methods. The present normative data provide healthcare professionals with an accurate estimate of how common or uncommon patients ’ ECAS scores are and provide a useful supplement to existing cut-off scores.
Application of Ground Penetrating Radar to Identification of Thickness and Structure of Sediments in Postglacial Lakes, Illustrated with an Example of the Mały Staw Lake (The Karkonosze Mountains)

This paper has been aimed at demonstrating the applicability of the ground penetrating radar to acquiring basic information on lake sediments and geomorphological conditions of their deposition in the basin of Mały Staw lake. The lake area is one of the most comprehensively studied part of the Polish part of the Karkonosze Mountains. The application of radar soundings enabled a fast and environmentally friendly verification as well as updating the results of previous research on the thickness and structure of the sediments of this glacial lake. Mały Staw lake is formed at the postglacial depression in the granite bedrock. The bottom of the lake is composed of limnic deposits of the maximum thickness reaching up to 15 m. The postglacial formations occurring below them probably contain a buried moraine of the youngest recessional phase. Solid rock is located about 25 meters beneath the current bottom of the lake.
Lactoferrin: Balancing Ups and Downs of Inflammation Due to Microbial Infections

Lactoferrin (Lf) is a glycoprotein of the primary innate immune-defense system of mammals present in milk and other mucosal secretions. This protein of the transferrin family has broad antimicrobial properties by depriving pathogens from iron, or disrupting their plasma membranes through its highly cationic charge. Noteworthy, Lf also exhibits immunomodulatory activities performing up- and down-regulation of innate and adaptive immune cells, contributing to the homeostasis in mucosal surfaces exposed to myriad of microbial agents, such as the gastrointestinal and respiratory tracts. Although the inflammatory process is essential for the control of invasive infectious agents, the development of an exacerbated or chronic inflammation results in tissue damage with life-threatening consequences. In this review, we highlight recent findings in in vitro and in vivo models of the gut, lung, oral cavity, mammary gland, and liver infections that provide experimental evidence supporting the therapeutic role of human and bovine Lf in promoting some parameters of inflammation and protecting against the deleterious effects of bacterial, viral, fungal and protozoan-associated inflammation. Thus, this new knowledge of Lf immunomodulation paves the way to more effective design of treatments that include native or synthetic Lf derivatives, which may be useful to reduce immune-mediated tissue damage in infectious diseases.
Does Downward Nominal Wage Rigidity Dampen Wage Increases ? An Analysis of German Micro Data 1975-2007

Plenty of studies document the existence of downward nominal wage rigidity (DNWR). Elsby (2009) argues that the macroeconomic effects of DNWR may be weak, because DNWR leads to a compression of wage increases. Using micro-data from the US and UK, he finds evidence for a compression of wage increases when DNWR binds. Our analyses try to determine whether the predictions of Elsby’s (2009) model and his findings apply to Germany too. In addition to OLS regressions suggested by Elsby we apply Seemingly Unrelated Regressions and Quantile Regressions. We find that higher percentiles of the unconditional and conditional distribution of real wage growth are compressed when DNWR binds. The impact of DNWR on the percentiles of the unconditional distribution of wage changes is comparable to those in UK. For Germany the effect on the distributions is mainly due to the development of wages for blue-collar workers.
Innate lymphoid cells: a new key player in atopic dermatitis

Atopic dermatitis (AD) is a common allergic inflammatory skin condition mainly caused by gene variants, immune disorders, and environmental risk factors. The T helper (Th) 2 immune response mediated by interleukin (IL)-4/13 is generally believed to be central in the pathogenesis of AD. It has been shown that innate lymphoid cells (ILCs) play a major effector cell role in the immune response in tissue homeostasis and inflammation and fascinating details about the interaction between innate and adaptive immunity. Changes in ILCs may contribute to the onset and progression of AD, and ILC2s especially have gained much attention. However, the role of ILCs in AD still needs to be further elucidated. This review summarizes the role of ILCs in skin homeostasis and highlights the signaling pathways in which ILCs may be involved in AD, thus providing valuable insights into the behavior of ILCs in skin homeostasis and inflammation, as well as new approaches to treating AD.
Innate lymphoid cells : sparking inflammatory rheumatic disease ?

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/art.40068 © 2017 American College of Rheumatology Received: Sep 29, 2016; Revised: Jan 24, 2017; Accepted: Feb 07, 2017
Modulation of Implicit Sensory and Sensorimotor Learning: An Investigation Within and Across Sensory Modalities

Implicit forms of learning are what govern many aspects of human perception, cognition, and actions. This dissertation describes three studies, each of which investigated a different type of implicit learning. The first study examined visual perceptual learning. Findings from the first study suggested that, with training, people learned to detect subtle differences between rhythmic visual sequences, but their improvement depended on which sensory modalities were engaged during training. Namely, visual rhythm perception was only improved when the auditory modality was engaged during training. The second study examined whether passive exposure to sequences in multiple sensory modalities would facilitate subsequent performance in a visuomotor sequence task. However, the results failed to reveal a significant benefit of passive sequence exposure to visuomotor performance. Finally, the third study examined the effect of statistical learning on internal stimulus representations. The results indicated that when stimuli were repeatedly presented in predictable sequences, the perceptual saliency of some of the stimuli was enhanced relative to others, depending on their degree of predictability within the sequences. Each of these studies has the potential to make a significant contribution to the research literature and, more generally, to expand our understanding of basic mechanisms of human learning.
Lithospheric Thinning by Mantle Plumes

Thermo-mechanical thinning of the lithosphere by mantle plumes is essential for intra-plate volcanism, the initiation of rifting, the evolution of Earth’s lower continental crust and the genesis of metals, diamonds and hydrocarbons. To develop a new understanding of how a mantle plume thins the overlying lithosphere beneath moving plates, we use 2-D and 3-D numerical models based on a finite-element discretization on anisotropic adaptive meshes. Our models include Earth-like material properties for the upper mantle (e.g. temperature and viscosity contrasts, non-Newtonian rheology) discretised at a local mesh resolution that has previously been considered intractable. In our simulations, a plume is injected at the base of the model (670 km depth) with a prescribed mass flux that is consistent with surface observations of topographic swells: from 0.5 (e.g. Louisville, Bermuda, Darfur) to 7 Mg/s (Hawaii). We undertake a systematic numerical study, across a wide parameter space, to investigate the effect of plume buoyancy flux, plate velocity, rheology law and Rayleigh number on processes leading to a reduction of the depth of the Lithosphere Asthenosphere boundary (LAB), such as small-scale convection (SSC) (‘dripping’), or delamination of the lower lithosphere.
The Importance of Historical Linkages in Shaping Population Density across Space

This study aims to investigate the extent to which history matters in shaping population distribution across space. In the wake of the current literature, the idea is to model individual location preferences by focusing on selected local determinants (neighborhood, education, income, amenities and distance from the CBD), while also taking into account temporal and spatial dependence in location choices. Our preliminary results revel the importance of segregation factors in shaping recent population density distribution.
Strong Balmer Lines in Old Stellar Populations: No Need for Young Ages in Ellipticals?

Comparing models of Simple Stellar Populations (SSPs) with observed line strengths generally provides a tool for breaking the age-metallicity degeneracy in elliptical galaxies. Because of the wide range of Balmer line strengths observed, ellipticals have been interpreted as exhibiting an appreciable scatter in age. In this paper, we analyze Composite Stellar Population models with a simple mix of an old metal-rich and an old metal-poor component. We show that these models simultaneously produce strong Balmer lines and strong metallic lines without invoking a young population. The key to this result is that our models are based on SSPs that better match the steep increase of Hβ in metal-poor globular clusters than models in the literature. Hence, the scatter of Hβ observed in cluster and luminous field elliptical galaxies can be explained by a spread in the metallicity of old stellar populations. We check our model with respect to the so-called G-dwarf problem in ellipticals. For a galaxy subsample covering a large range in 1500-V colors, we demonstrate that the addition of an old metal-poor subcomponent does not invalidate other observational constraints like colors and the flux in the mid-UV.
Relevance of Pipe Period on Kelvin-Voigt Viscoelastic Parameters: 1D and 2D Inverse Transient Analysis

AbstractThis paper presents the results of the calibration by means of a microgenetic algorithm, using Kelvin-Voigt viscoelastic parameters, to reproduce experimental unsteady flow tests in a polymeric pipe. During the tests, different pipe lengths—which give rise to different periods of the pressure oscillations—and initial discharges have been considered. The mechanical parameters of the viscoelastic models are estimated using both one-dimensional (1D) and quasi two-dimensional (2D) models. The calibration of Kelvin-Voigt models with 2, 3, 5, and 7 parameters, respectively, proves the substantial independence of the elastic modulus and the dependence of the retardation time on the pipe period (i.e., the pipe length). Moreover, in most cases, the increase in the number of mechanical parameters allows a better simulation of a single transient. However, the larger the number of parameters, the greater the risk of overfitting, and the more difficult the search for general laws of dependence of the parameter.
On the Heat Capacity, Entropy, and “Glass Transition” of Vitreous Ice

Abstract An analysis of the thermal properties of vitreous ice shows that both its heat capacity Cp and its entropy above 100 K are partly configurational in origin. The configurational contribution increases with temperature, and the excess Cp and entropy near the solid-liquid transformation temperature are 36.7 and 2.1 J K-1 mo1-1, respectively. The increase is interpreted as indicating the onset of molecular mobility in vitreous ice. The configurational Cp , of the melt of vitreous ice at 133.6 K, of ≈ 36.7 J K-1 mo1-1, is the same as the configurational Cp , of water at 273 K. Thus, the short-range order in the melt differs little from that in water at 273 K. The maximum calorimetric residual entropy of vitreous ice is 13.4 J K-1 mol-1, which is in fair agreement with the maximum value of 9.2 J K-1 mol-1 anticipated for a tetrahedral random-network model with fully disordered positions of H atoms. Thermodynamic consideration of a glass transition in supercooled liquid water indicates that there is no continuity of state between supercooled water and vitreous ice and, therefore, the structure and thermodynamic properties of a possible glassy state of water should be different from that of vapour-deposited vitreous ice. This paper is published in full in Philosophical Magazine, Eighth Ser. , Vol. 35, No. 4, 1977, p. 1077-90.
Stock-Recruit Analyses of Fraser River Sockeye Salmon

Three types of stock-recruit models (log-log, Ricker, Beverton-Holt) were applied to 57 years of adult returns (R) and eff ective female spawners (E) data from 17 biologically-based Conservation Units (CUs) of sockeye salmon from the Fraser River in British Columbia, Canada (hereafter “Fraser sockeye”). Log-log regressions of R on E showed little evidence of eff ects of density (within CUs) on survival, implying that habitat capacity does not presently limit Fraser sockeye abundance. Shared survival among CUs, the fi rst principal component of log(R/E), accounted for 46% of the variance, remarkable given the wide variety of freshwater and marine habitats experienced by the CUs. Six low-survival events in six decades accounted for much of the shared survival pattern. The r2 values for Ricker models were low, indicating that attempts to manage and/or assess Fraser sockeye using Ricker curves fi t to individual CUs will, in general, face low explanatory power. A suite of increasingly complicated Bayesian regressions, based on the Beverton-Holt model, quantifi ed the precision of capacity estimates, but these were always imprecise and the Widely Applicable Information Criterion (WAIC) indicated overfi tting in all but the simplest models. A variance factor for the relative precision of estimates of R, based on the proportion of spawners from each CU in groups of co-migrating CUs (i.e., runs), was eff ective only in models in which WAIC indicated over-fi tting. Improving the precision of capacity estimates for Fraser sockeye salmon, using similar models, will require mobilizing biological knowledge (i.e., historical metadata) about each CU, including estimates of abundance with identifi ed precision and indicators of habitat capacity at multiple life-history stages including the abundance of potential competitors in marine habitats. Researchers analyzing stock recruitment data for salmon populations and other species are strongly encouraged to pay attention to factors aff ecting the various categories of data in their models, i.e., to examine the associated metadata.
The acquisition of inductive constraints

Human learners routinely make inductive inferences, or inferences that go beyond the data they have observed. Inferences like these must be supported by constraints, some of which are innate, although others are almost certainly learned. This thesis presents a hierarchical Bayesian framework that helps to explain the nature, use and acquisition of inductive constraints. Hierarchical Bayesian models include multiple levels of abstraction, and the representations at the upper levels place constraints on the representations at the lower levels. The probabilistic nature of these models allows them to make statistical inferences at multiple levels of abstraction. In particular, they show how knowledge can be acquired at levels quite remote from the data of experience—levels where the representations learned are naturally described as inductive constraints. Hierarchical Bayesian models can address inductive problems from many domains but this thesis focuses on models that address three aspects of high-level cognition. The first model is sensitive to patterns of feature variability, and acquires constraints similar to the shape bias in word learning. The second model acquires causal schemata—systems of abstract causal knowledge that allow learners to discover causal relationships given very sparse data. The final model discovers the structural form of a domain—for instance, it discovers whether the relationships between a set of entities are best described by a tree, a chain, a ring, or some other kind of representation. The hierarchical Bayesian approach captures several principles that go beyond traditional formulations of learning theory. It supports learning at multiple levels of abstraction, it handles structured representations, and it helps to explain how learning can succeed given sparse and noisy data. Principles like these are needed to explain how humans acquire rich systems of knowledge, and hierarchical Bayesian models point the way towards a modern learning theory that is better able to capture the sophistication of human learning. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253-1690.)