Miracle-dz/UniFAR-FTUs huggingface dataset:
Behavioural and physiological limits to vision in mammals

Human vision is exquisitely sensitive—a dark-adapted observer is capable of reliably detecting the absorption of a few quanta of light. Such sensitivity requires that the sensory receptors of the retina, rod photoreceptors, generate a reliable signal when single photons are absorbed. In addition, the retina must be able to extract this information and relay it to higher visual centres under conditions where very few rods signal single-photon responses while the majority generate only noise. Critical to signal transmission are mechanistic optimizations within rods and their dedicated retinal circuits that enhance the discriminability of single-photon responses by mitigating photoreceptor and synaptic noise. We describe behavioural experiments over the past century that have led to the appreciation of high sensitivity near absolute visual threshold. We further consider mechanisms within rod photoreceptors and dedicated rod circuits that act to extract single-photon responses from cellular noise. We highlight how these studies have shaped our understanding of brain function and point out several unresolved questions in the processing of light near the visual threshold. This article is part of the themed issue ‘Vision in dim light’.
Co-Expression of HER Family Members in Patients with Dukes’ C and D Colon Cancer and Their Impacts on Patient Prognosis and Survival

The human epidermal growth factor receptor (EGFR) is an important therapeutic target in patients with metastatic colorectal cancer and anti-EGFR antibodies cetuximab and panitumumab have been approved for the treatment of such patients. Despite these advances, the duration of response in some patients can be limited. Since, EGFR is capable of forming heterodimers with the other members of the HER (Human epidermal receptor) family, it is important to investigate the co-expression and prognostic significance of all members of the HER family in colorectal cancer patients. The expression of the HER family members were determined in tumour specimens from 86 patients with Dukes’ C and D (metastatic) colon cancer using immunohistochemistry. Sections were scored by the percentage of positive tumour cells and intensity of staining. Their associations with clinicopathological parameters, and overall survival and disease free survival were evaluated using univariate and multivariate analysis. Overall, 43%, 77%, 52% and 92% of the cases were EGFR, HER-2, HER-3 and HER-4 positive respectively. Interestingly, 35%, 24%, 43%, and 18% of the cases had co-expression of EGFR/HER-2, EGFR/HER-3, EGFR/HER-4 and all four members of the HER family respectively. Of these, only the expression of EGFR and co-expression of EGFR/HER-4 were associated with poorer disease-free survival in both univariate and multivariate analysis. Co-expression of all members of the HER family in colon cancer supports the need for further investigations on their predictive value for response to therapy with anti-EGFR mAbs and whether such sub-population of patients may benefit from therapy with the new generation of pan-HER inhibitors.
Oral epithelial cells orchestrate innate type 17 responses to Candida albicans through the virulence factor candidalysin

Candidalysin, a hypha-associated fungal peptide, drives interleukin-17 responses to Candida albicans. Calibrating antifungal responses Immune responses to fungal infections are complicated by the fact that fungi can exist in multiple forms depending on environmental cues. Here, Verma et al. have evaluated innate immune responses to Candida albicans, a fungus that transitions from yeast to filamentous hyphae as infection progresses. They find that candidalysin, a hypha-associated protein and virulence factor, serves as a danger signal that potentiates the immune response to C. albicans. Candidalysin-deficient strains of C. albicans caused minimal epithelial damage and elicited a blunted type 17 immune response. The authors propose that the innate antifungal responses to C. albicans are driven by a synergy between cellular damage triggered by candidalysin that is further amplified by interleukin-17 driven inflammation. Candida albicans is a dimorphic commensal fungus that causes severe oral infections in immunodeficient patients. Invasion of C. albicans hyphae into oral epithelium is an essential virulence trait. Interleukin-17 (IL-17) signaling is required for both innate and adaptive immunity to C. albicans. During the innate response, IL-17 is produced by γδ T cells and a poorly understood population of innate-acting CD4+ αβ T cell receptor (TCRαβ)+ cells, but only the TCRαβ+ cells expand during acute infection. Confirming the innate nature of these cells, the TCR was not detectably activated during the primary response, as evidenced by Nur77eGFP mice that report antigen-specific signaling through the TCR. Rather, the expansion of innate TCRαβ+ cells was driven by both intrinsic and extrinsic IL-1R signaling. Unexpectedly, there was no requirement for CCR6/CCL20-dependent recruitment or prototypical fungal pattern recognition receptors. However, C. albicans mutants that cannot switch from yeast to hyphae showed impaired TCRαβ+ cell proliferation and Il17a expression. This prompted us to assess the role of candidalysin, a hyphal-associated peptide that damages oral epithelial cells and triggers production of inflammatory cytokines including IL-1. Candidalysin-deficient strains failed to up-regulate Il17a or drive the proliferation of innate TCRαβ+ cells. Moreover, candidalysin signaled synergistically with IL-17, which further augmented the expression of IL-1α/β and other cytokines. Thus, IL-17 and C. albicans, via secreted candidalysin, amplify inflammation in a self-reinforcing feed-forward loop. These findings challenge the paradigm that hyphal formation per se is required for the oral innate response and demonstrate that establishment of IL-1– and IL-17–dependent innate immunity is induced by tissue-damaging hyphae.
Embroidered archimedean spiral electrodes for contactless prosthetic control

With continuous advancements on active prosthetics the detection of the user's intention becomes the new technological bottleneck. While electromyography (EMG) is widely used to detect individual muscular contributions, sweat and relative sensor movements degrade the quality of the signal over time. In this paper, we bypass the problems created with the skin contact analyzing the muscular activation with Archimedean Spiral (AS) electrodes. We compare traditional EMG electrodes with AS electrodes, stacked up in textile embroidered layers to improve their functionality, and eventually adding a layer of cloth/silicon between the electrodes and the human skin to ascertain the feasibility of the method. We use n=9 volunteers to perform a loaded wrist extension and record signals from the extensor digitorum muscle group. We evaluate the amplitude and noise from all results and conclude that the AS electrode is capable of detecting muscular activation without touching the skin. As part of a low-cost prosthetic initiative, this EMG alternative can be potentially embedded to the prosthetic socket to improve usage and reduce adaptation problems.
ECAS A-B-C: alternate forms of the Edinburgh Cognitive and Behavioural ALS Screen

Abstract Background: The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) is a short assessment by which neuropsychological symptoms can be detected and quantified in people with ALS. To avoid potential practice effects with repeated administration, here we present alternative versions of the ECAS suitable for measuring change over time. Objective: To develop two alternate versions of the ECAS: ECAS-B and ECAS-C. Method: One hundred and forty-nine healthy adult participants were recruited. Thirty participants completed a pilot study in developing the alternate versions. Two groups of 40 participants were administered the ECAS-B or ECAS-C and compared to published data of the original ECAS (ECAS-A) to determine equivalence. An additional 39 participants were administered the ECAS consecutively, either repeating the original version (ECAS-A-A-A) serially or the different versions (ECAS-A-B-C) to determine potential practice effects. Recordings of assessments were scored by a second researcher to determine inter-rater reliability. Results: No significant differences were found between versions (A, B, C) of the composite performance measures of ALS Specific, ALS Non-Specific, and ECAS Total scores. Repeated serial administration of ECAS-A (A-A-A) produced some practice effects for composite scores, whereas no such effects were found when alternate versions were administered serially (A-B-C). Exceptionally high intra-class correlations were found for all three versions of the ECAS suggesting a high degree of rater agreement. Conclusion: The newly developed alternate forms of the ECAS are both highly equitable to the original ECAS-A and enable avoidance of practice effects, thus supporting their use in measuring cognition and behaviour over time.
Influence of passive ultrasonic irrigation on the efficiency of various irrigation solutions in removing smear layer: a scanning electron microscope study

To evaluate the influence of passive ultrasonic irrigation (PUI) to remove the smear layer with different irrigation solutions. Seventy‐eight single rooted mandibular premolars were used. The working lengths were measured and the root canals were prepared by using nickel titanium rotary files. The specimens were subjected to six different irrigation regimens: sodium hypochloride (NaOCl) with classic irrigation (CI); NaOCl with PUI; EDTA with CI; EDTA with PUI; QMix with CI; and QMix with PUI. The specimens were split longitudinally. Scanning electron microscopy images were taken to evaluate the amount of residual smear layer and scored. Statistical analysis was performed with the Kruskal–Wallis test. The Dunn's test was used for post hoc testing after the Kruskal–Wallis test. The smear layer scores of apical thirds were significantly higher than coronal and middle thirds except for NaOCl + CI group (p < 0.001). The irrigation with PUI improved the efficacy of all irrigation solutions on removal of smear layer in both coronal and middle thirds (p < 0.001). The PUI activation increased the activity of NaOCl, EDTA, and QMix, respectively without any significance. All irrigation regimens were significantly more effective in coronal and middle thirds compared to apical third. PUI significantly increased the efficacy of smear layer removal regardless of irrigation solution.
Quantifying Damage Due to Aggregate Expansion in Cement Matrix

Synopsis: Concrete is a composite of aggregates in a cement paste matrix. Dissimilar volume changes in these constituent materials may result in localized stress development. This is particularly problematic when the aggregate expands more than the surrounding paste. This expansion results in tensile stress development in the cement paste matrix which can lead to micro-cracking in the cement paste matrix. These micro-cracks can eventually coalesce and localize in visible cracking. Quantifying this type of damage can be difficult. This paper describes a conceptual model and physical simulation of this damage considering the expansion of polymeric inclusions (i.e., aggregates) in cement paste matrix subjected to temperature changes. Thermal loading (i.e., temperature change) was selected since it provides a method to control the expansion. Physical experiments were performed where continuous length change measurement and acoustic emission measurements were carried out. These experimental methods are used to better understand the mechanics of the damage. The experimental results indicate that a deviation from classical composite behavior occurs when damage develops which can be seen in the length change measurements. This deviation can be used to quantify the extent of damage. A numerical model is used to interpret the experimental results. An Eshelby misfit approach was used to determine the pressure created by the expanding aggregate. This enables the stresses that develop in a composite material to be determined. A linear fracture mechanics failure criterion is used to calculate the onset of damage formation. Results are in agreement with length change measurements and acoustic emission measurements. A composite damage model for direct calculation of the extent of damage from length change measurements is proposed.
Impact of high-intensity endurance exercise on regional left and right ventricular myocardial mechanics

Aims Strenuous endurance exercise acutely increases myocardial wall stress and evokes transient functional cardiac perturbations. However, it is unclear whether exercise-induced functional cardiac disturbances are ubiquitous throughout the myocardium or are segment specific. The aim of this study was to examine the influence of high-intensity endurance exercise on global and segmental left (LV) and right (RV) ventricular tissue deformation (strain). Methods and results Echocardiography was used to measure strain in 23 active men (age: 28 ± 2 years; VO2 peak: 4.5 ± 0.7 L min−1) at rest and during a standardized low-intensity exercise challenge, before and after a 90-min high-intensity endurance cycling intervention. Following the cycling intervention, LV and RV global strain decreased at rest (LV: −18.4 ± 0.4% vs. −17.7 ± 0.4%, P < 0.05; RV: −27.6 ± 0.7% vs. −26.4 ± 0.6%, P < 0.05) and by a greater extent during the low-intensity exercise challenge (LV: −21.3 ± 0.4% vs. −19.2 ± 0.5%, P < 0.01; RV: −28.4 ± 0.8% vs. −23.5 ± 0.9%, P < 0.01). Reductions in LV strain were unique to regions of RV attachment (e.g. LV septum: −24.4 ± 0.5% vs. −21.4 ± 0.6%, P < 0.01) with lateral (−18.9 ± 0.4% vs. −18.4 ± 0.5%) and posterior segments (−19.5 ± 0.4% vs. −18.8 ± 0.7%) unaffected. Similarly, augmentation of strain from rest to exercise was abolished in the RV free wall (−1.1 ± 1.0% vs. 2.9 ± 1.2%, P < 0.01), reduced in the septum (−4.6 ± 0.4% vs. −2.4 ± 0.5%, P < 0.01), and unchanged in the lateral (−1.2 ± 0.6% vs. −0.9 ± 0.6%) and posterior walls (−1.7 ± 0.6% vs. −1.3 ± 0.7%). Conclusion Changes in ventricular strain following high-intensity exercise are more profound in the right ventricle than in the left ventricle. Reductions in LV strain were unique to the septal myocardium and may reflect ventricular interactions secondary to exercise-induced RV dysfunction.
Detection of essential hypertension with physiological signals from wearable devices

Early detection of essential hypertension can support the prevention of cardiovascular disease, a leading cause of death. The traditional method of identification of hypertension involves periodic blood pressure measurement using brachial cuff-based measurement devices. While these devices are non-invasive, they require manual setup for each measurement and they are not suitable for continuous monitoring. Research has shown that physiological signals such as Heart Rate Variability, which is a measure of the cardiac autonomic activity, is correlated with blood pressure. Wearable devices capable of measuring physiological signals such as Heart Rate, Galvanic Skin Response, Skin Temperature have recently become ubiquitous. However, these signals are not accurate and are prone to noise due to different artifacts. In this paper a) we present a data collection protocol for continuous non-invasive monitoring of physiological signals from wearable devices; b) we implement signal processing techniques for signal estimation; c) we explore how the continuous monitoring of these physiological signals can be used to identify hypertensive patients; d) We conduct a pilot study with a group of normotensive and hypertensive patients to test our techniques. We show that physiological signals extracted from wearable devices can distinguish between these two groups with high accuracy.
MotAB-like machinery drives the movement of MreB filaments during bacterial gliding motility

Significance MreB is a bacterial actin that supports cell wall synthesis and rod-like morphology in many bacteria. In the bacterium Myxococcus xanthus, MreB is also required for gliding motility. In this work, we studied the movement of MreB particles during M. xanthus gliding motility at high spatial and temporal resolution. We found that MreB provides a scaffold for the gliding motors while the gliding machinery drives the movement of MreB filaments. The interplay between MreB and the gliding machineries is analogous to the interdependent movements of myosin motors and actin in eukaryotic cells. Since their discovery, actin-like homologs have been implicated in many spatially organized cellular processes in bacteria. This study expands our knowledge of MreB function in bacterial gliding motility. MreB is a bacterial actin that is important for cell shape and cell wall biosynthesis in many bacterial species. MreB also plays crucial roles in Myxococcus xanthus gliding motility, but the underlying mechanism remains unknown. Here we tracked the dynamics of single MreB particles in M. xanthus using single-particle tracking photoactivated localization microscopy. We found that a subpopulation of MreB particles moves rapidly along helical trajectories, similar to the movements of the MotAB-like gliding motors. The rapid MreB motion was stalled in the mutants that carried truncated gliding motors. Remarkably, M. xanthus MreB moves one to two orders of magnitude faster than its homologs that move along with the cell wall synthesis machinery in Bacillus subtilis and Escherichia coli, and this rapid movement was not affected by the inhibitors of cell wall biosynthesis. Our results show that in M. xanthus, MreB provides a scaffold for the gliding motors while the gliding machinery drives the movement of MreB filaments, analogous to the interdependent movements of myosin motors and actin in eukaryotic cells.
Nonactivated Protein C in the Treatment of Neonatal Sepsis: A Retrospective Analysis of Outcome

Background: Previously, we found that plasma protein C (PC) activity ⩽10% significantly increased the probability of the occurrence of death during neonatal sepsis. Accordingly, if the activity of plasma PC declined during the course of sepsis to ⩽10%, we administered a nonactivated PC zymogen to increase a PC activity. The aim of that retrospective analysis was to explore treatment effects of PC zymogen supplementation in septic infants, with plasma PC activity ⩽10%. Methods: A database was used to locate 85 newborns treated with PC from among 458 analyzed infants with confirmed sepsis. Results: The median birth weight and gestational age of treated infants were, respectively, 1010.0 g and 29 weeks. In 47 infants, early-onset sepsis developed, whereas in 38 neonates, late-onset sepsis was recognized. PC was given as a single dose of 200 IU/kg. Among 458 septic patients, death occurred in 19 newborns (4.2%), exclusively in infants with plasma PC activity ⩽10%. In 15 infants, death occurred in the course of early-onset sepsis and 4 newborns died of late-onset sepsis (early-onset sepsis vs. late-onset sepsis; P = 0.036; &khgr;2 with the Yates correction). Conclusions: An increased risk of death in septic neonates with plasma PC activity ⩽10% suggests the necessity for its evaluation and possibility of supplementation of PC zymogen.
Effects of low power microwave radiation on biological activity of Collagenase enzyme and growth rate of S. Cerevisiae yeast

Recently, microwave radiation, a type/subset of non-ionizing electromagnetic radiation (EMR) has been widely used in industry, medicine, as well as food technology and mobile communication. Use of mobile phones is rapidly growing. Four years from now, 5.1 billion people will be mobile phone users around the globe - almost 1 billion more mobile users than the 4.3 billion people worldwide using them now. Consequently, exposure to weak radiofrequency/microwave radiation generated by these devices is markedly increasing. Accordingly, public concern about potential hazards on human health is mounting [1]. Thermal effects of radiofrequency/microwave radiation are very well-known and extensively studied. Of particular interest are non-thermal effects of microwave exposures on biological systems. Nonthermal effects are described as changes in cellular metabolism caused by both resonance absorption and induced EMR and are often accompanied by a specific biological response. Non-thermal biological effects are measurable changes in biological systems that may or may not be associated with adverse health effects. In this study we studied non-thermal effects of low power microwave exposures on kinetics of L-lactate dehydrogenase enzyme and growth rate of yeast Saccharomyces Cerevisiae strains type II. The selected model systems were continuously exposed to microwave radiation at the frequency of 968MHz and power of 10dBm using the designed and constructed (custom made) Transverse Electro-Magnetic (TEM) cell [2]. The findings reveal that microwave radiation at 968MHz and power of 10dBm inhibits L-lactate dehydrogenase enzyme activity by 26% and increases significantly (15%) the proliferation rate of yeast cells.
Outbreak of Klebsiella pneumoniae Carbapenemase–Producing Citrobacter freundii at a Tertiary Acute Care Facility in Miami, Florida

OBJECTIVE To describe the investigation and control of a rare cluster of Klebsiella pneumoniae carbapenemase–producing Citrobacter freundii in a hospital in southern Florida. METHODS An epidemiologic investigation, review of infection prevention procedures, and molecular studies including whole genome sequencing were conducted. RESULTS An outbreak of K. pneumoniae carbapenemase–3-producing C. freundii was identified at a tertiary hospital in Florida in 2014. Of the 6 cases identified, 3 occurred in the same intensive care unit and were caused by the same clone. For 2 of the 3 remaining cases, the isolates had low carbapenem minimum inhibitory concentrations and were unrelated by whole genome sequencing. As a response to the outbreak, supplementary environmental cleaning was implemented, including closure and terminal cleaning of the unit where the 3 cases clustered, in addition to the infection control bundle already in place at the time. No further cases were identified after these additional interventions. CONCLUSIONS Although C. freundii is not a species that commonly demonstrates carbapenem resistance, our findings suggest that carbapenemase-producing C. freundii may be underdetected even when active surveillance is in place and has a potential to cause hospital outbreak. Infect Control Hosp Epidemiol 2017;38:320–326