Miracle-dz/UniFAR-FTUs huggingface dataset:
Slow Conduction in the Border Zones of Patchy Fibrosis Stabilizes the Drivers for Atrial Fibrillation: Insights from Multi-Scale Human Atrial Modeling

Introduction: The genesis of atrial fibrillation (AF) and success of AF ablation therapy have been strongly linked with atrial fibrosis. Increasing evidence suggests that patient-specific distributions of fibrosis may determine the locations of electrical drivers (rotors) sustaining AF, but the underlying mechanisms are incompletely understood. This study aims to elucidate a missing mechanistic link between patient-specific fibrosis distributions and AF drivers. Methods: 3D atrial models integrated human atrial geometry, rule-based fiber orientation, region-specific electrophysiology, and AF-induced ionic remodeling. A novel detailed model for an atrial fibroblast was developed, and effects of myocyte-fibroblast (M-F) coupling were explored at single-cell, 1D tissue and 3D atria levels. Left atrial LGE MRI datasets from 3 chronic AF patients were segmented to provide the patient-specific distributions of fibrosis. The data was non-linearly registered and mapped to the 3D atria model. Six distinctive fibrosis levels (0–healthy tissue, 5–dense fibrosis) were identified based on LGE MRI intensity and modeled as progressively increasing M-F coupling and decreasing atrial tissue coupling. Uniform 3D atrial model with diffuse (level 2) fibrosis was considered for comparison. Results: In single cells and tissue, the largest effect of atrial M-F coupling was on the myocyte resting membrane potential, leading to partial inactivation of sodium current and reduction of conduction velocity (CV). In the 3D atria, further to the M-F coupling, effects of fibrosis on tissue coupling greatly reduce atrial CV. AF was initiated by fast pacing in each 3D model with either uniform or patient-specific fibrosis. High variation in fibrosis distributions between the models resulted in varying complexity of AF, with several drivers emerging. In the diffuse fibrosis models, waves randomly meandered through the atria, whereas in each the patient-specific models, rotors stabilized in fibrotic regions. The rotors propagated slowly around the border zones of patchy fibrosis (levels 3–4), failing to spread into inner areas of dense fibrosis. Conclusion: Rotors stabilize in the border zones of patchy fibrosis in 3D atria, where slow conduction enable the development of circuits within relatively small regions. Our results can provide a mechanistic explanation for the clinical efficacy of ablation around fibrotic regions.
A founder MLH1 mutation in families from the districts of Modena and Reggio-Emilia in northern Italy with hereditary non-polyposis colorectal cancer associated with protein elongation and instability

Hereditary non-polyposis colorectal cancer (HNPCC), or Lynch syndrome, is an autosomal dominant condition predisposing to tumours of the large bowel and other sites. In HNPCC, cancer predisposition is usually inherited as a highly penetrant trait, with a tendency to the development of multiple tumours. Clinical diagnosis of HNPCC is based on the so-called modified “Amsterdam criteria”,1 which include: ( a ) the presence of at least three family members—one of whom must be a first degree relative to two other members—affected with carcinoma of the colon, rectum, endometrium, small bowel, or urothelium; ( b ) a direct transmission of the disease from parent to child; ( c ) the occurrence of at least one tumour before the patient reaches 50 years of age; and ( d ) the exclusion of a diagnosis of familial adenomatous polyposis. The genetic defects underlying most HNPCC cases are represented by constitutional point mutations of one of several genes encoding for proteins of the DNA mismatch repair complex. The vast majority of mutations are located in the major mismatch repair genes MSH2 and MLH1 (International Collaborative Group on HNPCC Mutation Database). The constitutional defects most commonly identified are nonsense, splice-site, or frameshift alterations, which all predict the synthesis of shorter, non-functional proteins. Tumours arising in carriers of mismatch repair gene mutations are characterised by a high frequency of insertion or deletion type somatic mutations within microsatellite repeats.2 These are the expression of mismatch repair deficiency, which arises when a second somatic mutation affecting the wild-type allele fully inactivates the gene locus already altered in the germline.3 Inactivation of a specific mismatch repair locus in a HNPCC tumour is often revealed by immunohistochemical methods, which show absence of nuclear staining following incubation with antibodies against the mismatch repair protein encoded by the mutant gene.4 In addition to genetic heterogeneity, HNPCC …
Nicotine Self-Administration Impairs Hippocampal Plasticity

Nicotine, the neuroactive compound responsible for tobacco addiction, is primarily believed to have beneficial effects on the adult brain. However, in heavy smokers, abstinence from nicotine is accompanied by cognitive impairments that suggest adverse effects of nicotine on brain plasticity. For this reason, we studied changes in plasticity-related processes in the dentate gyrus (DG) of the hippocampal formation of animals trained to self-administer nicotine. The DG was chosen because it undergoes profound plastic rearrangements, many of which have been related to memory and learning performances. In this region, we examined the expression of the polysialylated (PSA) forms of neural cell adhesion molecule (NCAM), PSA-NCAM, neurogenesis, and cell death by measuring the number of pyknotic cells. It was found that nicotine self-administration profoundly decreased, in a dose-dependent manner, the expression of PSA-NCAM in the DG; a significant effect was observed at all the doses tested (0.02, 0.04, and 0.08 mg/kg per infusion). Neurogenesis was also decreased in the DG, but a significant effect was observed only for the two highest doses of nicotine. Finally, the same doses that decreased neurogenesis also increased cell death. These results raise an important additional concern for the health consequences of nicotine abuse and open new insight on the possible neural mechanisms of tobacco addiction.
Transcription factor NFE2L2/NRF2 is a regulator of macroautophagy genes

ABSTRACT Autophagy is a highly coordinated process that is controlled at several levels including transcriptional regulation. Here, we identify the transcription factor NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2) as a regulator of autophagy gene expression and its relevance in a mouse model of Alzheimer disease (AD) that reproduces impaired APP (amyloid β precursor protein) and human (Hs)MAPT/TAU processing, clearance and aggregation. We screened the chromatin immunoprecipitation database ENCODE for 2 proteins, MAFK and BACH1, that bind the NFE2L2-regulated enhancer antioxidant response element (ARE). Using a script generated from the JASPAR's consensus ARE sequence, we identified 27 putative AREs in 16 autophagy-related genes. Twelve of these sequences were validated as NFE2L2 regulated AREs in 9 autophagy genes by additional ChIP assays and quantitative RT-PCR on human and mouse cells after NFE2L2 activation with sulforaphane. Mouse embryo fibroblasts of nfe2l2-knockout mice exhibited reduced expression of autophagy genes, which was rescued by an NFE2L2 expressing lentivirus, and impaired autophagy flux when exposed to hydrogen peroxide. NFE2L2-deficient mice co-expressing HsAPPV717I and HsMAPTP301L, exhibited more intracellular aggregates of these proteins and reduced neuronal levels of SQSTM1/p62, CALCOCO2/NDP52, ULK1, ATG5 and GABARAPL1. Also, colocalization of HsAPPV717I and HsMAPTP301L with the NFE2L2-regulated autophagy marker SQSTM1/p62 was reduced in the absence of NFE2L2. In AD patients, neurons expressing high levels of APP or MAPT also expressed SQSTM1/p62 and nuclear NFE2L2, suggesting their attempt to degrade intraneuronal aggregates through autophagy. This study shows that NFE2L2 modulates autophagy gene expression and suggests a new strategy to combat proteinopathies.
Large-signal analysis of MOS varactors in CMOS -Gm LC VCOs

MOS varactors are used extensively as tunable elements in the tank circuits of RF voltage-controlled oscillators (VCOs) based on submicrometer CMOS technologies. MOS varactor topologies include conventional D = S = B connected, inversion-mode (I-MOS), and accumulation-mode (A-MOS) structures. When incorporated into the VCO tank circuit, the large-signal swing of the VCO output oscillation modulates the varactor capacitance in time, resulting in a VCO tuning curve that deviates from the dc tuning curve of the particular varactor structure. This paper presents a detailed analysis of this large-signal effect. Simulated results are compared to measurements for an example 2.5-GHz complementary -G/sub m/ LC VCO using I-MOS varactors implemented in 0.35-/spl mu/m CMOS technology.
Honeybee Blue- and Ultraviolet-Sensitive Opsins: Cloning, Heterologous Expression in Drosophila, and Physiological Characterization

The honeybee (Apis mellifera) visual system contains three classes of retinal photoreceptor cells that are maximally sensitive to light at 440 nm (blue), 350 nm (ultraviolet), and 540 nm (green). We performed a PCR-based screen to identify the genes encoding the Apis blue- and ultraviolet (UV)-sensitive opsins. We obtained cDNAs that encode proteins having a high degree of sequence and structural similarity to other invertebrate and vertebrate visual pigments. The Apis blue opsin cDNA encodes a protein of 377 amino acids that is most closely related to other invertebrate visual pigments that are thought to be blue-sensitive. The UV opsin cDNA encodes a protein of 371 amino acids that is most closely related to the UV-sensitive Drosophila Rh3 and Rh4 opsins. To test whether these novel Apis opsin genes encode functional visual pigments and to determine their spectral properties, we expressed them in the R1–6 photoreceptor cells of blindninaE mutant Drosophila, which lack the major opsin of the fly compound eye. We found that the expression of either the Apis blue- or UV-sensitive opsin in transgenic flies rescued the visual defect of ninaEmutants, indicating that both genes encode functional visual pigments. Spectral sensitivity measurements of these flies demonstrated that the blue and UV visual pigments are maximally sensitive to light at 439 and 353 nm, respectively. These maxima are in excellent agreement with those determined previously by single-cell recordings fromApis photoreceptor cells and provide definitive evidence that the genes described here encode visual pigments having blue and UV sensitivity.
Analysis of parallel implementations of the ant colony optimization applied to the minimum weight vertex cover problem

In this paper we analyze various parallel implementations of the Ant Colony Optimization (ACO) applied to the Minimum Weight Vertex Cover Problem (MWVCP). We investigated the ACO algorithms applied to the MWCVP before. Here, we observe the behavior of different parallel topologies and corresponding algorithms like fully connected, replace worst, ring and independent parallel runs. We also present a variation of the algorithm corresponding to the ring topology that maintains the diversity of the search, but still moves to areas with better solutions.
Mechanical Properties and Eco-Efficiency of Steel Fiber Reinforced Alkali-Activated Slag Concrete

Conventional concrete production that uses ordinary Portland cement (OPC) as a binder seems unsustainable due to its high energy consumption, natural resource exhaustion and huge carbon dioxide (CO2) emissions. To transform the conventional process of concrete production to a more sustainable process, the replacement of high energy-consumptive PC with new binders such as fly ash and alkali-activated slag (AAS) from available industrial by-products has been recognized as an alternative. This paper investigates the effect of curing conditions and steel fiber inclusion on the compressive and flexural performance of AAS concrete with a specified compressive strength of 40 MPa to evaluate the feasibility of AAS concrete as an alternative to normal concrete for CO2 emission reduction in the concrete industry. Their performances are compared with reference concrete produced using OPC. The eco-efficiency of AAS use for concrete production was also evaluated by binder intensity and CO2 intensity based on the test results and literature data. Test results show that it is possible to produce AAS concrete with compressive and flexural performances comparable to conventional concrete. Wet-curing and steel fiber inclusion improve the mechanical performance of AAS concrete. Also, the utilization of AAS as a sustainable binder can lead to significant CO2 emissions reduction and resources and energy conservation in the concrete industry.
A Performance and Area Efficient Architecture for Intrusion Detection Systems

Intrusion Detection Systems (IDS) have emerged as one of the most promising ways to secure systems in network. An IDS operates by scanning packet-data for known signatures and accordingly takes requisite action. However, scanning bytes in the packet payload and checking for more than 20,000 signatures becomes a computationally intensive task. Additionally, with signatures doubling almost every 30 months, this complexity will aggravate further. IDS commonly uses the Aho-Corasick state machine based search to scan packets for signatures. However, the huge size of the state machine negatively impacts the performance and area efficiency of the underlying hardware. In this work, we propose novel mechanisms to compactly store the state machine thereby improving the area efficiency. We observe over 2X reduction in area for storing the state machine in comparison to BS-FSM [19]. We investigate various approaches to improve the performance efficiency. We pipeline the processing of consecutive bytes accessing the upper-most level, the frequently accessed level, of the state machine. In order to further enhance the performance efficiency, we use a dedicated hardware unit specifically tuned for traversal using our proposed storage mechanism. We observe that our proposed architecture outperforms BS-FSM based approaches [13, 14, 19].
Mindfulness Interventions for College Students with ADHD: A Multiple Single Case Research Design

ABSTRACT A multiple single case research design (SCRD) was used to examine two mindfulness interventions (MBSR and Vipassana meditation). Impacted symptoms of Attention Deficit Hyperactivity Disorder (ADHD), psychological distress, mindfulness, and treatment satisfaction in college students were examined via single subject and group analyses. Results indicated that 57% of the seven-person sample evidenced decreases in ADHD symptoms, 72% decreased in distress, 72% increased on the trait measure of mindfulness, and treatment satisfaction was high. Clinical implications and future directions are discussed.
Parallel Processing of Nociceptive A-δ Inputs in SII and Midcingulate Cortex in Humans

The cingulate cortex (CC) as a part of the “medial” pain subsystem is generally assumed to be involved in the affective and/or cognitive dimensions of pain processing, which are viewed as relatively slow processes compared with the sensory-discriminative pain coding by the lateral second somatosensory area (SII)–insular cortex. The present study aimed at characterizing the location and timing of the CC evoked responses during the 1 s period after a painful laser stimulus, by exploring the whole rostrocaudal extent of this cortical area using intracortical recordings in humans. Only a restricted area in the median CC region responded to painful stimulation, namely the posterior midcingulate cortex (pMCC), the location of which is consistent with the so-called “motor CC” in monkeys. Cingulate pain responses showed two components, of which the earliest peaked at latencies similar to those obtained in SII. These data provide direct evidence that activations underlying the processing of nociceptive information can occur simultaneously in the “medial” and “lateral” subsystems. The existence of short-latency pMCC responses to pain further indicates that the “medial pain system” is not devoted exclusively to the processing of emotional information, but is also involved in fast attentional orienting and motor withdrawal responses to pain inputs. These functions are, not surprisingly, conducted in parallel with pain intensity coding and stimulus localization specifically subserved by the sensory-discriminative “lateral” pain system.
Vice-Virtue Bundles

We introduce a simple solution to help consumers manage choices between healthy and unhealthy food options: vice-virtue bundles. Vice-virtue bundles are item aggregates with varying proportions of both vice and virtue, holding overall quantity constant. Four studies compare choice and perceptions of differently composed vice-virtue bundles relative to one another and to pure vice and pure virtue options. Although multiple consumer segments can be identified, results suggest that people overall tend to prefer vice-virtue bundles with small 1 4 to medium 1 2 proportions of vice rather than large 3 4 proportions of vice. Moreover, people generally rate vice-virtue bundles with small vice proportions as healthier but similarly tasty as bundles with larger vice proportions. For most individuals, choice patterns are different from those predicted by variety-seeking accounts alone. Instead, these findings provide evidence of asymmetric effectiveness of small vice and virtue proportions at addressing taste and health goals, respectively. Data, as supplemental material, are available at http://dx.doi. org/10.1287/mnsc.2014. 2053 . This paper was accepted by Yuval Rottenstreich, judgment and decision making.
'I live sustainably' : exploring sustainable narratives through the lens of identity expression and motivational drives

This thesis explores narratives of individuals who self-identify as living sustainably, with two interlinked aims: (1) to explore how such individuals use sustainable narratives as an expression of their identity, and (2) to explore what motivates them to live sustainably. While novel insights emerge from each of these explorations, findings are also used to shed light on how expressions of identity and motivational drives interplay in sustainable narratives. A brief review of key theories in identity and motivation literatures identifies the Dynamic Model of Identity Development (Hillenbrand & Money, 2015) as well as the Four Drive Theory of Human Motivation (Lawrence & Nohria, 2002) as useful frameworks to guide parts of the empirical research. A more elaborate review and exploration of the existing literature on identity and motivations in relation to sustainability is then provided in the discussion of findings. For the purposes of the empirical research, a total of 35 semi-structured interviews were conducted with individuals self-identifying as living sustainably. While the initial part of the interviews was conducted inductively using a range of projective techniques, the final part of the interviews was guided by the theories described above. The combination of inductive and deductive research enables both theory building and theory testing for the purpose of this study. Drawing on the analysis of participants‘ expressions of identity and motivational drives, as well as the analysis of their interplay, a new typology is developed. This typology classifies individuals as 'Holistically', 'Privately', 'Publicly' or 'Accidentally Sustainable', and offers a representation of associated identity characteristics and motivational drives for each group. Importantly, the findings reveal that individuals in each group differ in terms of key aspects of identity expression. These include whether aspects of personal or social identity are salient, and whether individuals are mostly motivated to live sustainably as a means of acquiring a status and financial benefits, to bond with others, to learn and develop themselves, or to defend their beliefs. While each group emerges with a distinctive portfolio of unique insights, it is the interplay between identity expression and motivational drives that is perhaps most interesting. This culminates with the presentation of a novel typology of identity and motivational elements which can – for the first time – describe, differentiate and explain sustainable narratives of individuals self-identifying as living sustainably.
[The influence of antipsychotic therapy on the cognitive functions of schizophrenic patients].

AIM The aim of the present study was twofold: 1. to compare the efficacy of three antipsychotics (ziprasidone, olanzapine and perazine) in schizophrenia 2. to compare the improvement in cognitive functioning between groups treated with the three different neuroleptics. METHOD A total of 58 Caucasian patients diagnosed with paranoid schizophrenia were recruited into the study group. We used the Polish version of the CIDI (Composite International Diagnostic Interview) to obtain ICD-10 diagnoses. The intensity of psychopathological symptoms was examined using the PANSS. The patients were randomly assigned to treatment with perazine, olanzapine or ziprasidone administered as monotherapy for 3 months. The treatment efficacy was measured as a change in the PANSS (Positive and Negative Syndrome Scale) total score from baseline (T0) to 3 months (T1). The WCST (The Wisconsin Card Sorting Test) was used to measure working memory and executive functions in the evaluated patients. Wilcoxon's and Kruskal-Wallis tests were applied to compare changes in the PANSS scores between the treatment groups. To analyze the cognitive functions, Kruskal-Wallis test for the WCST parameters was used. RESULTS The three antipsychotics similarly reduced the total PANSS score. The WCST parameters in the 3 groups of examined patients using the Kruskal-Wallis test revealed some differences between the three administered antipsychotics. CONCLUSIONS Results suggest that the short-term efficacy of the atypical (olanzapine, ziprasidone) and typical (perazine) antipsychotic drugs did not differ. Based on the analysis, a conclusion can be drawn that the three neuroleptics provided similar improvements in cognitive functioning.
Helium-3 MRI diffusion coefficient: correlation to morphometry in a model of mild emphysema

Hyperpolarised gases have been most recently used in magnetic resonance imaging to demonstrate new image-derived pulmonary function parameters. One of these parameters is the apparent diffusion coefficient, which reflects the sizes of the structures that compartmentalise gas within the lung (i.e. alveolar space). In the present study, noninvasive parameters were compared to microscopic measurements (mean linear intercept and mean alveolar internal area). Nonselective helium‐3 gas density coronal ex vivo images and apparent diffusion maps were acquired in control and elastase-induced panacinar emphysema rats. Total lung capacity was considered the reference for both imaging experiments and lung fixation. A mild degree of emphysema was found based on mean linear intercept (134±25 µm) versus control (85±14 µm). The apparent diffusion coefficients were significantly different between the two groups (0.18±0.02 and 0.15±0.01 cm2·s−1 for elastase and control, respectively). A significant correlation between the apparent diffusion coefficient and corresponding morphometric parameters in mild emphysema was demonstrated for the first time. This study opens the possibility of estimating absolute airspace size using noninvasive techniques.