Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Regulation of Transcription Factors by Location-Specific EGF Receptor Signaling via a Spatio-Temporal Interplay of ERK Activation

It is well established that EGFR signals from both the plasma membrane (PM) and endosome (EN). However, very little is known about whether and how the EGFR signals at the PM and EN to differentially regulate various signaling pathways and the physiological outcomes. In this communication, we established a system that allowed the specific activations of EGFR at different cell locations: PM and EN. PM activation of EGFR is achieved by activation of endocytosis-deficient mutant EGFR1010LL/AA stably expressed in CHO cells (CHO-LL/AA cell). EN activation of EGFR is achieved by activating the wild type EGFR stably expressed in CHO cells (CHO-EGFR cell) after its internalization into EN with a previously reported protocol. We showed that both EGFR activations at PM and EN activated ERK to a similar level, but differentially stimulated transcriptional factors c-jun and c-fos. We further showed that EGFR activations at PM and EN resulted in differential spatio-temporal dynamics of phosphorylated ERK which caused the differential activation of two downstream substrates ELK1 and RSK. Finally we showed that EGFR signaling from PM and EN led to different physiological outcomes. CHO-LL/AA cells that only generate PM EGFR signals have a larger cell size and slower proliferation rate than CHO-EGFR cells. We conclude that location-specific EGFR activation differentially regulates cell functions through a spatio-temporal interplay of ERK activation.
Exploring Narrative Gestures on Digital Surfaces

A significant amount of research on digital tables has traditionally investigated the use of hands and fingers to control 2D and 3D artifacts, has even investigated people's expectations when interacting with these devices. However, people often use their hands and body to communicate and express ideas to others. In this work, we explore narrative gestures on a digital table for the purpose of telling stories. We present the results of an observational study of people illustrating stories on a digital table with virtual figurines, and in both a physical sandbox and water with physical figurines. Our results show that the narrative gestures people use to tell stories with objects are highly varied and, in some cases, fundamentally different from the gestures designers and researchers have suggested for controlling digital con-tent. In contrast to smooth, predetermined drags for movement and rotation, people use jiggling, repeated lifting, and bimanual actions to express rich, simultaneous, and independent actions by multiple characters in a story. Based on these results, we suggest that future storytelling designs consider the importance of touch actions for narra-tion, in-place manipulations, the (possibly non-linear) path of a drag, allowing expression through manipulations, and two-handed simultaneous manipulation of multiple objects.
Dnmt1-dependent Chk1 pathway suppression is protective against neuron division

Neuronal differentiation and cell-cycle exit are tightly coordinated, even in pathological situations. When pathological neurons re-enter the cell cycle and progress through the S phase, they undergo cell death instead of division. However, the mechanisms underlying mitotic resistance are mostly unknown. Here, we have found that acute inactivation of retinoblastoma (Rb) family proteins (Rb, p107 and p130) in mouse postmitotic neurons leads to cell death after S-phase progression. Checkpoint kinase 1 (Chk1) pathway activation during the S phase prevented the cell death, and allowed the division of cortical neurons that had undergone acute Rb family inactivation, oxygen-glucose deprivation (OGD) or in vivo hypoxia-ischemia. During neurogenesis, cortical neurons became protected from S-phase Chk1 pathway activation by the DNA methyltransferase Dnmt1, and underwent cell death after S-phase progression. Our results indicate that Chk1 pathway activation overrides mitotic safeguards and uncouples neuronal differentiation from mitotic resistance. Summary: Using a Rb triple knockout mouse model, Chk1 pathway activation during S phase is shown to prevent cell death and override the mitotic resistance of pathological hypoxic and differentiating neurons.
Severity of childhood asthma by socioeconomic status.

BACKGROUND A review of studies on the association between childhood asthma and socioeconomic status (SES) in industrialized countries leads to the conclusion that there does not seem to be a clear association. A study from Aberdeen published 25 years ago, however, shows that among children with asthma, severe asthma is most prevalent in the lower social class, but this distinction between grades of asthma severity has been largely ignored since. METHODS We screened all fourth grade schoolchildren of German nationality in Munich (4434 children, response rate 87 percent), distinguishing three severity grades in the same way as the study in Aberdeen. RESULTS Prevalences of childhood asthma are reported by severity grade and SES. Prevalence of severe asthma was found to be significantly higher in the low as compared with the high socioeconomic group (Odds ratio = 2.37; 95 percent confidence interval: 1.28-4.41). This association could not be explained by established risk factors. CONCLUSIONS More attention should be paid to the association between severe asthma and SES, with measures such as targeting early diagnosis and treatment towards low socioeconomic groups.
A $di/dt$ Compensation Technique in Delay Testing by Disconnecting Power Pins

Scan-based delay testing increases power consumption, particularly peak power, due to excessive simultaneous signal switching. The instantaneous current changes increase the ground level during signal switching, slowing down the operational speed. When the switching activity increases during test operations, it is necessary to pay special attention to determine whether the speed failures are due to extra switching, since the blind application of delay testing can greatly affect the yield of a device. This paper demonstrates that cycle time adjustment is best suited to compensate for the timing issues resulting from the higher switching activity in delay testing. In the proposed method, the power pins are disconnected in an increasing number to find a proper level of cycle period adjustment. The power pins of a chip are experimentally disconnected to observe the ground bounce behavior, which is also demonstrated in simulations. The experimental results also demonstrate that the proposed method can avoid the problem of abandoning good devices by cycle adjustment.
The impacts of inbreeding, drift and selection on genetic diversity in captive breeding populations

The goal of captive breeding programmes is often to maintain genetic diversity until re‐introductions can occur. However, due in part to changes that occur in captive populations, approximately one‐third of re‐introductions fail. We evaluated genetic changes in captive populations using microsatellites and mtDNA. We analysed six populations of white‐footed mice that were propagated for 20 generations using two replicates of three protocols: random mating (RAN), minimizing mean kinship (MK) and selection for docility (DOC). We found that MK resulted in the slowest loss of microsatellite genetic diversity compared to RAN and DOC. However, the loss of mtDNA haplotypes was not consistent among replicate lines. We compared our empirical data to simulated data and found no evidence of selection. Our results suggest that although the effects of drift may not be fully mitigated, MK reduces the loss of alleles due to inbreeding more effectively than random mating or docility selection. Therefore, MK should be preferred for captive breeding. Furthermore, our simulations show that incorporating microsatellite data into the MK framework reduced the magnitude of drift, which may have applications in long‐term or extremely genetically depauperate captive populations.
NADPH oxidase inhibitor diphenyliodonium abolishes lipopolysaccharide‐induced down‐regulation of transferrin receptor expression in N2a and BV‐2 cells

The activation of cellular inflammatory response is tightly linked to induced production of reactive oxygen species (ROS) and nitric oxide (NO), which in turn have been identified as important regulators of cellular iron metabolism. In the present study, we have used the microglia cell line BV‐2 and the neuroblastoma cell line N2a to study the regulatory effects of the microbial agent lipopolysaccharide (LPS) on the expression of the transferrin receptor (TfR) and ferritin in cell lines with different characteristics. The receptor mainly responsible for LPS recognition is the Toll‐like receptor 4 (TLR4) that triggers a variety of intracellular signalling cascades leading to the induction of transcription of target genes involved in the innate immune response. Among the pathways to be activated is the MAPK cascade leading to the activation of nuclear factor‐κB that induces transcription of a variety of genes, e.g., inducible nitric oxide synthase (iNOS). The TLR4‐mediated LPS response also induces the production of ROS through a mechanism(s) suggested to involve the activation of NADPH oxidase(s). This study shows that exposure of BV‐2 and N2a cells to LPS results in decreased TfR protein levels and increased H‐ferritin mRNA levels. The LPS down‐regulatory effect on TfR protein expression is abolished by the NADPH oxidase inhibitor diphenyliodonium (DPI) but is not affected by the free radical scavenger N‐acetyl‐L‐cysteine (NAC) or the iNOS inhibitor aminoguanidine (AG). The increased H‐ferritin mRNA levels in response to LPS are not affected by DPI, NAC, or AG. © 2006 Wiley‐Liss, Inc.
Effect of additive particles on mechanical, thermal, and cell functioning properties of poly(methyl methacrylate) cement

The most common bone cement material used clinically today for orthopedic surgery is poly(methyl methacrylate) (PMMA). Conventional PMMA bone cement has several mechanical, thermal, and biological disadvantages. To overcome these problems, researchers have investigated combinations of PMMA bone cement and several bioactive particles (micrometers to nanometers in size), such as magnesium oxide, hydroxyapatite, chitosan, barium sulfate, and silica. A study comparing the effect of these individual additives on the mechanical, thermal, and cell functional properties of PMMA would be important to enable selection of suitable additives and design improved PMMA cement for orthopedic applications. Therefore, the goal of this study was to determine the effect of inclusion of magnesium oxide, hydroxyapatite, chitosan, barium sulfate, and silica additives in PMMA on the mechanical, thermal, and cell functional performance of PMMA. American Society for Testing and Materials standard three-point bend flexural and fracture tests were conducted to determine the flexural strength, flexural modulus, and fracture toughness of the different PMMA samples. A custom-made temperature measurement system was used to determine maximum curing temperature and the time needed for each PMMA sample to reach its maximum curing temperature. Osteoblast adhesion and proliferation experiments were performed to determine cell viability using the different PMMA cements. We found that flexural strength and fracture toughness were significantly greater for PMMA specimens that incorporated silica than for the other specimens. All additives prolonged the time taken to reach maximum curing temperature and significantly improved cell adhesion of the PMMA samples. The results of this study could be useful for improving the union of implant-PMMA or bone-PMMA interfaces by incorporating nanoparticles into PMMA cement for orthopedic and orthodontic applications.
Reappraisal of the Optic Nerve Hypoplasia Syndrome

Background Optic nerve hypoplasia (ONH) has been described as an increasingly prevalent cause of congenital blindness. Its association with hypopituitarism and absent septum pellucidum has been recognized for more than 40 years as “septo-optic dysplasia” or “de Morsier syndrome. ” More recent studies have suggested that these associations are independent of one another. This review was designed to assess the historical and recent evidence for associations of neuroradiologic, endocrinologic, and developmental problems in patients with ONH. Evidence acquisition Historical and contemporary literature review. Results The medical literature does not support the notion that Georges de Morsier ever described a case of ONH or recognized its association with hypopituitarism or missing septum pellucidum. Recognition of the critical association of ONH with hypopituitarism should be attributed to William Hoyt. Hypopituitarism and other more recently identified associations with ONH, such as developmental delay, hypothalamic dysfunction, and autism, are independent of septum pellucidum development. Other common neuroradiographic associations, such as corpus callosum hypoplasia, gyrus dysplasia, and cortical heterotopia, may have prognostic significance. Conclusions Children with ONH need to be monitored for many systemic, developmental, and even life-threatening problems independent of the status of the septum pellucidum. “Septo-optic dysplasia” and “de Morsier syndrome” are historically inaccurate and clinically misleading terms that should be abandoned.
Evaluation of manual wheelchairs by individuals with spinal cord injuries

Purpose. The aim of this study was to investigate how adults with spinal cord injury assess their satisfaction regarding various aspects and use of their manual wheelchair. Method. The Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST 2.0) together with seven additional questions was sent to 205 adults with SCI. Results. One hundred and twenty-four responses were available. The QUEST 2.0 showed a high level of satisfaction with manual wheelchair properties. However, the respondents were less satisfied with the services offered. Ease of use and comfort were identified as most important. Eighty-nine percent of the respondents rated their level of satisfaction as ‘quite satisfied’ or ‘very satisfied’ in ease of using a manual wheelchair compared with 68% of the respondents that were ‘quite satisfied’ or ‘very satisfied’ with the level of comfort. A greater satisfaction of ease in propulsion indoors compared with sitting comfort in various activities was found. Conclusions. A discrepancy was shown between users not being as satisfied with comfort in sitting in various activities as opposed to satisfaction with propulsion. This indicates the need for increased knowledge and developments concerning individual solutions, incorporating comfort as well as ease of use of a manual wheelchair.
Circulating Microparticles and Coronary Plaque Components Assessed by Virtual Histology Intravascular Ultrasound of the Target Lesion in Patients with Stable Angina

High levels of microparticles (MPs) circulate in the blood of patients with atherosclerotic diseases where they can serve as potential biomarkers of vascular injury and cardiovascular outcome. We used virtual histology intravascular ultrasound (VH-IVUS) to evaluate the relationship between the levels of circulating MPs and the coronary plaque composition in patients with stable angina. We included 35 patients with stable angina (22 men, age 64 ± 9 years) and a de novo target lesion. Preintervention gray-scale and VH-IVUS analysis was performed across the target lesion. Volumetric analysis was performed over a 10-mm-long segment centered at the minimum luminal site. Blood samples were obtained from the femoral artery before coronary angioplasty. MPs were measured using a solid-phase capture assay from a commercial kit. We divided participants into either a low MPs group or high MPs group based on the median value of MPs. There was no significant difference in baseline characteristics between the groups. The plaque burden and remodeling index were similar between the groups. The presence of VH-IVUS-derived thin-cap fibroatheroma was not different between the groups. The percentage of the necrotic core (NC) was significantly higher in the high MPs group than in the low MPs group, both in planar (17.0 ± 8.8% vs. 24.1 ± 6.9%, p = 0.012) and volumetric analyses (17.0 ± 4.8% vs. 22.1 ± 4.3%, p = 0.002). Circulating MPs were positively correlated with the percentage of the NC area at the minimal luminal site (r = 0.491, p = 0.003) and the percentage of the NC volume (r = 0.496, p = 0.002). Elevated levels of circulating MPs were associated with the amount of NC in the target lesion in those with stable angina, suggesting a potential role of circulating MPs as a biomarker for detecting unstable plaque in patients with stable angina.
IFNγ Responses to Pre-erythrocytic and Blood-stage Malaria Antigens Exhibit Differential Associations With Past Exposure and Subsequent Protection.

BACKGROUND The malaria-specific T-cell response is believed to be important for protective immunity. Antimalarial chemoprevention may affect this response by altering exposure to malaria antigens. METHODS We performed interferon γ (IFNγ) ELISpot assays to assess the cellular immune response to blood-stage and pre-erythrocytic antigens longitudinally from 1 to 3 years of age in 196 children enrolled in a randomized trial of antimalarial chemoprevention in Tororo, Uganda, an area of high transmission intensity. RESULTS IFNγ responses to blood-stage antigens, particularly MSP1, were frequently detected, strongly associated with recent malaria exposure, and lower in those adherent to chemoprevention compared to nonadherent children and those randomized to no chemoprevention. IFNγ responses to pre-erythrocytic antigens were infrequent and similar between children randomized to chemoprevention or no chemoprevention. Responses to blood-stage antigens were not associated with subsequent protection from malaria (aHR 0.96, P = .83), but responses to pre-erythrocytic antigens were associated with protection after adjusting for prior malaria exposure (aHR 0.52, P = .009). CONCLUSIONS In this high transmission setting, IFNγ responses to blood-stage antigens were common and associated with recent exposure to malaria but not protection from subsequent malaria. Responses to pre-erythrocytic antigens were uncommon, not associated with exposure but were associated with protection from subsequent malaria.
Pangloss revisited: a critique of the dilution effect and the biodiversity-buffers-disease paradigm

SUMMARY The twin concepts of zooprophylaxis and the dilution effect originated with vector-borne diseases (malaria), were driven forward by studies on Lyme borreliosis and have now developed into the mantra “biodiversity protects against disease”. The basic idea is that by diluting the assemblage of transmission-competent hosts with non-competent hosts, the probability of vectors feeding on transmission-competent hosts is reduced and so the abundance of infected vectors is lowered. The same principle has recently been applied to other infectious disease systems – tick-borne, insect-borne, indirectly transmitted via intermediate hosts, directly transmitted. It is claimed that the presence of extra species of various sorts, acting through a variety of distinct mechanisms, causes the prevalence of infectious agents to decrease. Examination of the theoretical and empirical evidence for this hypothesis reveals that it applies only in certain circumstances even amongst tick-borne diseases, and even less often if considering the correct metric – abundance rather than prevalence of infected vectors. Whether dilution or amplification occurs depends more on specific community composition than on biodiversity per se. We warn against raising a straw man, an untenable argument easily dismantled and dismissed. The intrinsic value of protecting biodiversity and ecosystem function outweighs this questionable utilitarian justification.
Majority dynamics on trees and the dynamic cavity method

A voter sits on each vertex of an infinite tree of degree $k$, and has to decide between two alternative opinions. At each time step, each voter switches to the opinion of the majority of her neighbors. We analyze this majority process when opinions are initialized to independent and identically distributed random variables. In particular, we bound the threshold value of the initial bias such that the process converges to consensus. In order to prove an upper bound, we characterize the process of a single node in the large $k$-limit. This approach is inspired by the theory of mean field spin-glass and can potentially be generalized to a wider class of models. We also derive a lower bound that is nontrivial for small, odd values of $k$.
The Neural Basis of Implicit

Evidence that human preferences, beliefs, and behavior are influenced by sources that are outside the reach of conscious awareness, control, intention, and self- reflection is incontrovertible. Recent advances in neu- roscience have enabled researchers to investigate the neural basis of these implicit attitudes, particularly atti- tudes involving social groups. From this research, a model with three identified neural components related to the automatic activation and regulation of implicit attitudes is beginning to emerge. The amygdala is implicated in the automatic evaluation of socially relevant stimuli, while the anterior cingulate and dorsolateral prefrontalcortices are involved in the detection and regulation, respectively, of implicit attitudes. Further support for this model comes from the inclusion of these regions in current models con- cerning the cognitive regulation of emotion and the detec- tion of conflict. The identification of a putative neural substrate for implicit attitudes has had a direct impact on psychological research into their nature and operational characteristics.Wediscusshowthisemergingneuralmodel has influenced current research on implicit attitudes and describetheimportanceofsuchmodelsfordirectingfuture research. KEYWORDS—implicit attitude; implicit bias; social cogni- tion; social neuroscience; amygdala
Individual differences in children's understanding of social evaluation concerns

Recent research suggests that children's understanding of self-presentational behaviour-behaviour designed to shape social evaluation-is a function of both cognitive and motivational variables. Furthermore, the motivational factors involved are likely to reflect individual differences in the salience of concerns about social evaluation. The present research represents a first effort to determine whether measures of such differences are indeed associated with the understanding of self-presentational behaviour. In a first experiment, a teacher rating measure of self-monitoring was found to be positively associated with the understanding of self-presentational motives. In a second experiment, a more narrowly specified self-report measure of public self-consciousness was found to have a similar association with the understanding of self-presentation, with no such association found for private self-consciousness. These preliminary results make it clear that our formulations of development in social cognition must indeed include a consideration of individual differences in motivational orientations.