Miracle-dz/UniFAR-FTUs huggingface dataset:
Linking Taiwan's subcritical Hsuehshan Range topography and foreland basin architecture

The contemporary presence of the Puli Topographic Embayment within the Taiwanese thrust belt provides insight into processes that initiate and maintain a subcritical state in a thin‐skinned compressive wedge. Orogen‐scale analyses of Taiwan have succeeded in describing the processes and interactions that affect overall development of the thrust belt; however, relatively little is known about which processes or boundary conditions control first‐order organization of strain at intermediate scales within the orogenic wedge. We investigate spatial and temporal scales of variation in the overall topographic and structural architecture of a critical wedge and explore the boundary conditions that affect very rapid shortening and erosion at intermediate scales on the order of 101 kilometers and 104–105 years. Causal links between the structural and synorogenic stratigraphic architecture of the foreland basin and coincidence of the Puli Topographic Embayment provide a valuable case study of the effects of changing boundary conditions (e.g., variable erodibility or strength of rocks along strike) controlling the evolution of critically tapered thin‐skinned orogens. Deeper incision of river networks into a thicker sequence of unconsolidated synorogenic sediments in the central western foreland may affect the onset of a topographically subcritical state.
NONSUPINE POSITIONING IN MACULAR HOLE SURGERY: A Noninferiority Randomized Clinical Trial

Purpose: To determine whether nonsupine positioning (NSP) is noninferior to face-down positioning (FDP) in full-thickness macular hole (FTMH) surgery. Methods: This is a single-center, open-label, randomized controlled trial. Between October 2013 and October 2014, pseudophakic participants underwent pars plana vitrectomy, internal limiting membrane peeling, and perfluoropropane gas tamponade and were randomly allocated to either FDP or NSP. The primary (noninferior) outcome was FTMH closure. The sample size was based on an estimated 95% closure rate and a −15% noninferiority margin for the NSP group. The secondary outcome was Early Treatment Diabetic Retinopathy Study visual acuity at 3 months. Additionally, intraocular gas fill on postoperative Day 4 was measured. Results: Eighty-one participants were enrolled. Final analysis of 68 participants demonstrated equal closure rates in both positioning groups: 33/34 (97.1%; 95% confidence interval: 84.7–99.9). Closure rates in the ≥400-&mgr;m FTMH subgroup were similar, 93.8% and 100.0% in the FDP and NSP groups, respectively (P = 0.43). Final visual acuity did not differ significantly between the groups (P = 0.60). Median gas fill was 78% (range: 57–86) in the FDP group and 76% (range: 56–85) in the NSP group (P = 0.51). Gas fill in closed FTMHs was significantly higher than in unclosed FTMHs (P = 0.02). Conclusion: Nonsupine positioning is noninferior to FDP in FTMH surgery. Furthermore, results suggest that the degree of gas fill affects FTMH closure.
A Simulation Study Comparing Multiple Imputation Methods for Incomplete Longitudinal Ordinal Data

Multiple imputation (MI) is now a reference solution for handling missing data. The default method for MI is the Multivariate Normal Imputation (MNI) algorithm that is based on the multivariate normal distribution. In the presence of longitudinal ordinal missing data, where the Gaussian assumption is no longer valid, application of the MNI method is questionable. This simulation study compares the performance of the MNI and ordinal imputation regression model for incomplete longitudinal ordinal data for situations covering various numbers of categories of the ordinal outcome, time occasions, sample sizes, rates of missingness, well-balanced, and skewed data.
Exercise--it's never too late: the strong-for-life program.

OBJECTIVES This investigation determined whether an in-home resistance training program achieved health benefits in older adults with disabilities. METHODS A randomized controlled trial compared the effects of assigning 215 older persons to either a home-based resistance exercise training group or a waiting list control group. Assessments were conducted at baseline and at 3 and 6 months following randomization. The program consisted of videotaped exercise routines performed with elastic bands of varying thickness. RESULTS High rates of exercise adherence were achieved, with 89% of the recommended exercise sessions performed over 6 months. Relative to controls, subjects who participated in the program achieved statistically significant lower extremity strength improvements of 6% to 12%, a 20% improvement in tandem gait, and a 15% to 18% reduction in physical and overall disability at the 6-month follow-up. No adverse health effects were encountered. CONCLUSIONS These findings provide important evidence that home-based resistance exercise programs designed for older persons with disabilities hold promise as an effective public health strategy.
Action in context - context in action : towards a grounded theory of software design

This thesis develops a model and a theory of software design. Thirty-two transcripts of interviews with software designers were analysed using the Grounded Theory method. The first set of sixteen interviews drawn from the field of Digital Interactive Multimedia (Data-set A) was used to develop the model and theory, the second set of sixteen interviews drawn from one source of technical literature (Data-set B) was used to test and enhance the initial outcomes. Final outcomes are then grounded in the general literature on problem solving and design. The model is concerned to capture a rich, holistic picture of software design. It is descriptive rather than prescriptive, concerned to capture how software design is done rather than advocate how it ought to be done. The theory is a development of the model and is presented initially as a theoretical framework and then as a series of propositions. The theoretical framework is a function of the juxtaposition of specific properties or attributes of the "core category", which uniquely explains the phenomenon. Its outcome is four design scenarios. Each scenario is of interest as an explanation of software design practice but two scenarios wherein such practice does not "fit" the design context are of most interest. It is argued that these scenarios can be used to identify and explain design breakdowns. Finally, the thesis purports to explicate the "Meta-process" - the process through which the inductive model and theory was developed. This is an unusual objective for a piece of IS research but valid nonetheless and significant, given the complexity of the research method used and the dearth of good process accounts in the IS literature and elsewhere.
Therapeutics , Targets , and Chemical Biology MDM 2 Small-Molecule Antagonist RG 7112 Activates p 53 Signaling and Regresses Human Tumors in Preclinical Cancer Models

MDM2 negatively regulates p53 stability and many human tumors overproduce MDM2 as a mechanism to restrict p53 function. Thus, inhibitors of p53-MDM2 binding that can reactivate p53 in cancer cells may offer an effective approach for cancer therapy. RG7112 is a potent and selective member of the nutlin family of MDM2 antagonists currently in phase I clinical studies. RG7112 binds MDM2 with high affinity (KD 11 nmol/L), blocking its interactions with p53 in vitro. A crystal structure of the RG7112–MDM2 complex revealed that the small molecule binds in the p53 pocket of MDM2, mimicking the interactions of critical p53 amino acid residues. Treatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis. RG7112 showed potent antitumor activity against a panel of solid tumor cell lines. However, its apoptotic activity varied widely with the best response observed in osteosarcoma cells with MDM2 gene amplification. Interestingly, inhibition of caspase activity did not change the kinetics of p53-induced cell death. Oral administration of RG7112 to human xenograft-bearing mice at nontoxic concentrations caused dosedependent changes in proliferation/apoptosis biomarkers as well as tumor inhibition and regression. Notably, RG7112 was highly synergistic with androgen deprivation in LNCaP xenograft tumors. Our findings offer a preclinical proof-of-concept that RG7112 is effective in treatment of solid tumors expressing wild-type p53. Cancer Res; 73(8); 1–11. 2013 AACR.
Effects of GSM-Modulated Radiofrequency Electromagnetic Fields on Mouse Bone Marrow Cells

Abstract Prisco, M. G. , Nasta, F. , Rosado, M. M. , Lovisolo, G. A. , Marino, C. and Pioli, C. Effects of GSM-Modulated Radiofrequency Electromagnetic Fields on Mouse Bone Marrow Cells. Radiat. Res. 170, 803–810 (2008). We examined the effects of in vivo exposure to a GSM-modulated 900 MHz RF field on the ability of bone marrow cells to differentiate, colonize lymphatic organs, and rescue lethally X-irradiated mice from death. X-irradiated mice were injected with medium alone or containing bone marrow cells from either RF-field-exposed (SAR 2 W/kg, 2 h/day, 5 days/ week, 4 weeks) or sham-exposed or cage control donor mice. Whereas all mice injected with medium alone died, mice that received bone marrow cells survived. Three and 6 weeks after bone marrow cell transplantation, no differences in thymus cellularity and in the frequencies of differentiating cell subpopulations (identified by CD4/CD8 expression) were observed among the three transplanted groups. Mitogen-induced thymocyte proliferation yielded comparable levels in all transplanted groups. As to the spleen, no effects of the RF-field exposure on cell number, percentages of B and T (CD4 and CD8) cells, B- and T-cell proliferation, and IFN-γ production were found in transplanted mice. In conclusion, our results show no effect of in vivo exposure to GSM-modulated RF fields on the ability of bone marrow precursor cells to home and colonize lymphoid organs and differentiate in phenotypically and functionally mature T and B lymphocytes.
External validation of the paracetamol-aminotransferase multiplication product to predict hepatotoxicity from paracetamol overdose

Abstract Context. Risk prediction in paracetamol (acetaminophen, or APAP) poisoning treated with acetylcysteine helps guide initial patient management and disposition. The paracetamol-aminotransferase multiplication product may be a useful and less time-sensitive risk predictor. Objective. The aim of this study was to validate this multiplication product in an independent cohort of patients with paracetamol overdose. Materials and methods. Using an existing toxicology dataset of poisoned patients from two large inner-city United Kingdom teaching hospitals, we retrospectively identified by electronic search all paracetamol overdoses from February 2005 to March 2013. We assessed the diagnostic accuracy of the multiplication product (serum APAP concentration × alanine transaminase [ALT] activity), especially at the pre-specified cut-off points of 1 500 mg/L × IU/L (10 000 micromol/L × IU/L) and 10 000 mg/L × IU/L (66 000 micromol/L × IU/L). The primary outcome was hepatotoxicity defined by a peak ALT > 1000 IU/L. Results. Of 3823 total paracetamol overdose presentations, there were 2743 acute single, 452 delayed single (> 24 h post overdose), 426 staggered (ingestion over > 1 h), and 202 supratherapeutic ingestions. Altogether, 34 patients developed hepatotoxicity. Among the acute single-ingestion patients, a multiplication product > 10 000 mg/L × IU/L had a sensitivity of 80% (95% confidence interval [CI]: 44%, 96%) and specificity of 99.6% [99.3%, 99.8%], while a product > 1 500 mg/L × IU/L had a sensitivity of 100% [66%, 100%] and specificity of 92% [91%, 93%]. Overall, 16 patients with a multiplication product > 10 000 mg/L × IU/L developed hepatotoxicity (likelihood ratio: 250, 95% CI: 130, 480), and 4 patients with a multiplication product between 1 500 and 10 000 (likelihood ratio: 2.5, 95% CI: 1.0, 6.0). No patient with a product < 1 500 mg/L × IU/L who received acetylcysteine developed hepatotoxicity. Conclusions. Regardless of ingestion type, a product > 10 000 mg/L × IU/L was associated with a very high likelihood, and < 1 500 mg/L × IU/L with a very low likelihood, of developing hepatotoxicity in patients treated with acetylcysteine.
Protein extraction from secondary sludge of paper mill wastewater and its utilization as a wood adhesive

In this study, secondary sludge (SS) from a kraft paper mill was used as a source of biomass to recover protein and investigate its potential use as a wood adhesive. The process of protein recovery involved disruption of the floc structure in alkaline medium to disintegrate and release intercellular contents into the aqueous phase followed by separation of soluble protein. Finally, the soluble protein was subjected to low pH precipitation and the pelletized sludge protein, referred to as recovered sludge protein (RSP) was tested for crude protein, moisture, and other contents. A significant process yield of 90% in terms of precipitation of soluble protein from disintegrated sludge was estimated through calorimetric studies, whereas an overall material balance confirmed a RSP yield of up to 23% based on total suspended solids of raw sludge. The RSP containing 30% crude protein was used as a wood adhesive and its adhesion performance was compared with soy protein isolate (SPI) and phenol formaldehyde (PF) resin. The testing of plywood lap joints has shown up to 41% shear strength level of RSP adhesive compared to PF. This work demonstrates the technical feasibility and potential of SS as a biomass resource to develop eco-friendly adhesives for wood composite applications.
Effects of medium composition on penicillin-induced hydrolysis and loss of RNA and culture turbidity in group A streptococci

Exposure to penicillin G of exponentially growing cultures of group A streptococci growing in chemically defined medium (CDM) can lead to extensive loss of culture turbidity. Significant reductions in culture turbidity did not accompany comparable treatments of group A streptococci growing in Todd-Hewitt broth (THB). Studies with THB and a high-molecular-weight (greater than 12,000) fraction of THB demonstrated that components in this complex medium inhibited the efflux of RNA hydrolysis products from otherwise intact cells. Hydrolysis products accumulated intracellularly and inhibited the extensive hydrolysis of RNA and consequently the loss of culture turbidity. Results of survival studies with cultures of group A streptococci exposed to penicillin G in THB demonstrated that this treatment protocol produces conditions of phenotypic tolerance relative to exposure in CDM. In combination, these findings provide further support for the hypothesis of RNA hydrolysis as the bactericidal mechanism of penicillin G action in this nonlytic death phenotype.
Human Epidermal Growth Factor Receptor (EGFR) Aligned on the Plasma Membrane Adopts Key Features of Drosophila EGFR Asymmetry

ABSTRACT The ability of epidermal growth factor receptor (EGFR) to control cell fate is defined by its affinity for ligand. Current models suggest that ligand-binding heterogeneity arises from negative cooperativity in signaling receptor dimers, for which the asymmetry of the extracellular region of the Drosophila EGFR has recently provided a structural basis. However, no asymmetry is apparent in the isolated extracellular region of the human EGFR. Human EGFR also differs from the Drosophila EGFR in that negative cooperativity is found only in full-length receptors in cells. To gain structural insights into the human EGFR in situ, we developed an approach based on quantitative Förster resonance energy transfer (FRET) imaging, combined with Monte Carlo and molecular dynamics simulations, to probe receptor conformation in epithelial cells. We experimentally demonstrate a high-affinity ligand-binding human EGFR conformation consistent with the extracellular region aligned flat on the plasma membrane. We explored the relevance of this conformation to ligand-binding heterogeneity and found that the asymmetry of this structure shares key features with that of the Drosophila EGFR, suggesting that the structural basis for negative cooperativity is conserved from invertebrates to humans but that in human EGFR the extracellular region asymmetry requires interactions with the plasma membrane.
Microstructure of Concrete with Aggregates from Construction and Demolition Waste Recycling Plants

Abstract This paper intends to analyze the microstructure of concrete with recycled aggregates (RA) from construction and demolition waste from various Portuguese recycling plants. To that effect, several scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) analyses were performed. Various concrete mixes were evaluated in order to analyze the influence of the RA’s collection point and consequently of their composition on the mixes’ characteristics. Afterward all the mixes were subjected to the capillary water absorption test in order to quantitatively evaluate their porosity. Results from the SEM/EDS analysis were compared with those from capillary water absorption test. The SEM/EDS analysis showed that the bond capacity of aggregates to the new cement paste is greatly influenced by the RA’s nature. On the other hand, there was an increase in porosity with the incorporation of RA.
Immune response to influenza vaccine and pneumococcal polysaccharide vaccine under IL-6 signal inhibition therapy with tocilizumab

Abstract Objectives. To evaluate humoral immune response to influenza vaccine and polysaccharide pneumococcal vaccine in patients with rheumatoid arthritis (RA) or Castleman's disease (CD) during tocilizumab therapy. Methods. Thirty-eight patients (28 RA and 10 CD) receiving tocilizumab and 39 RA patients receiving TNF inhibitors and/or synthetic DMARDs subcutaneously received a single dose of a split-virion inactivated influenza vaccine containing A(New Caledonia (NC):H1N1), A(Hiroshima (HIR):H3N2) and B(Malaysia (MAL)) strains. Twenty-one RA patients using tocilizumab also received 23-valent polysaccharide pneumococcal vaccine. Antibody titers were measured every 4 weeks for a total of 12 weeks after vaccination. Results. In the tocilizumab group, seroprotective titers (40-fold or more) were obtained in 36/38(95%) for A(NC), 35/38(92%) for A(HIR) and 32/38(84%) for B(MAL). In the patients with baseline antibody titer < 40-fold, 11/11(100%), 7/8(88%) and 18/20(90%) patients showed four-fold or more increase in the titer from baseline to A(NC), A(HIR) and B(MAL), respectively. Patients using TNF inhibitors and/or DMARDs showed similar responses. Pneumococcal antibody titers increased at least two-fold in more than 9 of 12 serotypes, which continued for longer than 12 weeks in all the patients. Conclusion. Interleukin-6 (IL-6) blocking therapy with tocilizumab did not affect the humoral immune response to both influenza and pneumococcal vaccines.
Sleep disturbance and deficits of sustained attention following stroke

ABSTRACT Objective: To simultaneously investigate the prevalence of and impact that the poststroke complications of daytime sleepiness, poor sleep quality, depression, and fatigue may be having upon deficits of sustained attention, as assessed using the Psychomotor Vigilance Task (PVT). Method: Twenty-two patients with stroke (mean age: 68.23 ± 12.17 years) and 20 healthy control participants (mean age: 68.1 ± 9.5 years) completed subjective measures of daytime sleepiness, sleep quality, fatigue, and depression and an objective measure of sustained attention as assessed using the PVT. Results: Patients with stroke compared to controls showed heightened levels of fatigue (p = .001, η2 = .29) and depression (p = .002, η2 = .23), plus greater deficits of sustained attention as reflected by poorer performance across all PVT outcome measures including: slower mean reaction times (p = .002, η2 = .22); increased number of lapses (p = .002, η2 = .24); and greater variability in reaction time (RT) responses (p = .016, η2 = .15). Reaction time distribution analysis suggested that daytime sleepiness and sleep quality had little influence across PVT performance; however, depressive symptomology was associated with longer RT responses, indicative of inattention, and fatigue impacted upon the entire distribution of PVT responses. Conclusions: PVT performance illustrated significant deficits across the domain of sustained attention for patients with stroke in comparison to healthy controls, in terms of inattention as well as slower sensory–motor speed. The common poststroke complications of depressive symptomology and fatigue appear to be associated with these deficits in sustained attention, warranting further investigation.
Functional hemispheric asymmetries during the planning and manual control of virtual avatar movements

Both hemispheres contribute to motor control beyond the innervation of the contralateral alpha motoneurons. The left hemisphere has been associated with higher-order aspects of motor control like sequencing and temporal processing, the right hemisphere with the transformation of visual information to guide movements in space. In the visuomotor context, empirical evidence regarding the latter has been limited though the right hemisphere’s specialization for visuospatial processing is well-documented in perceptual tasks. This study operationalized temporal and spatial processing demands during visuomotor processing and investigated hemispheric asymmetries in neural activation during the unimanual control of a visual cursor by grip force. Functional asymmetries were investigated separately for visuomotor planning and online control during functional magnetic resonance imaging in 19 young, healthy, right-handed participants. The expected cursor movement was coded with different visual trajectories. During planning when spatial processing demands predominated, activity was right-lateralized in a hand-independent manner in the inferior temporal lobe, occipito-parietal border, and ventral premotor cortex. When temporal processing demands overweighed spatial demands, BOLD responses during planning were left-lateralized in the temporo-parietal junction. During online control of the cursor, right lateralization was not observed. Instead, left lateralization occurred in the intraparietal sulcus. Our results identify movement phase and spatiotemporal demands as important determinants of dynamic hemispheric asymmetries during visuomotor processing. We suggest that, within a bilateral visuomotor network, the right hemisphere exhibits a processing preference for planning global spatial movement features whereas the left hemisphere preferentially times local features of visual movement trajectories and adjusts movement online.