Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Mismatched Nucleotides in Activating the hMSH2-hMSH6 Molecular Switch*

We have previously shown that hMSH2-hMSH6 contains an intrinsic ATPase which is activated by mismatch-provoked ADP→ATP exchange that coordinately induces the formation of a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone (1, 2). These studies suggested that mismatch repair could be propagated by a signaling event transduced via diffusion of ATP-bound hMSH2-hMSH6 molecular switches to the DNA repair machinery. The Molecular Switch model (Fishel, R. (1998) Genes Dev. 12, 2096–2101) is considerably different than the Hydrolysis-Driven Translocation model (Blackwell, L. J., Martik, D., Bjornson, K. P., Bjornson, E. S., and Modrich, P. (1998) J. Biol. Chem. 273, 32055–32062) and makes additional testable predictions beyond the demonstration of hydrolysis-independent diffusion (Gradia, S., Subramanian, D., Wilson, T., Acharya, S., Makhov, A., Griffith, J., and Fishel, R. (1999) Mol. Cell3, 255–261): (i) individual mismatch-provoked ADP→ATP exchange should be unique and rate-limiting, and (ii) thek cat·DNA for the DNA-stimulated ATPase activity should decrease with increasing chain length. Here we have examined hMSH2-hMSH6 affinity and ATPase stimulatory activity for several DNA substrates containing mispaired nucleotides as well as the chain length dependence of a defined mismatch under physiological conditions. We find that the results are most consistent with the predictions of the Molecular Switch model.
Comparing the awareness of and beliefs in sexually transmitted infections among university students in Madagascar and the United States of America

Young adults have a higher risk of contracting sexually transmitted infections (STIs) than other age groups. This risk may be mediated by their social and cultural setting which can impact young adults’ awareness of, beliefs in, and risk of contracting STIs (including HIV/AIDS). In order to understand how these factors vary among young adults of different cultures, it is important to study these issues on a cross-cultural scale. This study aimed to increase understanding of the relationship between the culture of a place of study and: (1) STI awareness; (2) belief in STIs; and (3) self-reported STI prevalence in the study population. Survey data were collected from university students in Madagascar (n = 242 surveys in 2013) and the United States of America (n = 199 surveys in 2015). Compared to students at the American university, students at the Malagasy university: (1) did not appear to have a conclusively lower awareness of STIs; (2) did not differ in rates of belief in the existence of gonorrhea and syphilis, but had higher rates of disbelief in HIV/AIDS; and (3) were more likely to report having been infected with syphilis and gonorrhea, but not with HIV/AIDS. Students at the Malagasy university also listed different reasons than the students at the American university for why they believed in the existence of STIs. These findings highlight the need for further cross-cultural research to better adapt intervention strategies to different cultural settings.
What side effects are problematic for patients prescribed antipsychotic medication? The Maudsley Side Effects (MSE) measure for antipsychotic medication

Background Capturing service users’ perspectives can highlight additional and different concerns to those of clinicians, but there are no up to date, self-report psychometrically sound measures of side effects of antipsychotic medications. Aim To develop a psychometrically sound measure to identify antipsychotic side effects important to service users, the Maudsley Side Effects (MSE) measure. Method An initial item bank was subjected to a Delphi exercise (n = 9) with psychiatrists and pharmacists, followed by service user focus groups and expert panels (n = 15) to determine item relevance and language. Feasibility and comprehensive psychometric properties were established in two samples (N43 and N50). We investigated whether we could predict the three most important side effects for individuals from their frequency, severity and life impact. Results MSE is a 53-item measure with good reliability and validity. Poorer mental and physical health, but not psychotic symptoms, was related to side-effect burden. Seventy-nine percent of items were chosen as one of the three most important effects. Severity, impact and distress only predicted ‘putting on weight’ which was more distressing, more severe and had more life impact in those for whom it was most important. Conclusions MSE is a self-report questionnaire that identifies reliably the side-effect burden as experienced by patients. Identifying key side effects important to patients can act as a starting point for joint decision making on the type and the dose of medication.
Prevalence of Congenital Heart Disease among Infants from 2012 to 2014 in Langfang, China

Background: Congenital heart disease (CHD) is the most common congenital malformations with high mortality and morbidity. The prevalence of CHD reported previously ranged from 4 per 1000 live births to 50 per 1000 live births. In this cross-sectional study, we aimed to document the prevalence of CHD in Langfang district of Hebei Province, China by analyzing data collected by hospitals located in 11 the counties of the district, as supported by a public health campaign. Methods: A total of 67,718 consecutive 3-month-old infants were included from July 19, 2012 to July 18, 2014. Structural abnormalities were diagnosed based on echocardiography findings, including two-dimensional and color Doppler echocardiography results. Results: Of the 67,718 infants, 1554 were found to have cardiac structural abnormalities. The total prevalence of CHD was 22.9 per 1000 live births, a value significantly higher than the previously reported prevalence of 8 cases per 1000 live births. The top five most common cardiac abnormalities were as follows: atrial septal defect (ASD, 605 cases, 8.93‰); ventricular septal defect (550 cases, 8.12‰); patent ductus arteriosus (228 cases, 3.37‰); pulmonary stenosis (66 cases, 0.97‰); and tetralogy of Fallot (32 cases, 0.47‰). The CHD prevalence differed by gender in this study (&khgr;2 = 23.498, P < 0.001), and the majority of ASD cases were females. Regional differences in prevalence were also found (&khgr;2 = 24.602, P < 0.001); a higher prevalence was found in urban areas (32.2 cases per 1000 live births) than in rural areas (21.1 cases per 1000 live births). There was a significant difference in the prevalence of CHD in preterm versus full-term infants (&khgr;2 = 133.443, P < 0.001). Prevalence of CHD in infants of maternal aged 35 years or over was significantly higher (&khgr;2 = 86.917, P < 0.001). Conclusions: The prevalence of CHD in Langfang district was within the range reported using echocardiography. Echocardiography can be used to early diagnose the CHD.
Dementia and motor vehicle crash hospitalizations

Objective To determine the effect of physician reporting laws and state licensing requirements on crash hospitalizations among drivers with dementia. Methods A study of drivers hospitalized because of vehicle crashes, identified from the State Inpatient Databases of the Agency for Healthcare Research and Quality. Multivariable logistic regression was used to examine the effect of mandatory physician reporting of at-risk drivers and state licensing requirement on the prevalence of dementia among hospitalized drivers. Results Physician reporting laws, mandated or legally protected, were not associated with a lower likelihood of dementia among crash hospitalized drivers. Hospitalized drivers aged 60 to 69 years in states with in-person renewal laws were 37% to 38% less likely to have dementia than drivers in other states and 23% to 28% less likely in states with vision testing at in-person renewal. Road testing was associated with lower dementia prevalence among hospitalized drivers aged 80 years and older. Conclusion Vision testing at in-person renewal and in-person renewal requirements were significantly related with a lower prevalence of dementia in hospitalized older adults among drivers aged 60 to 69 years. Road testing was significantly associated with a lower proportion of dementia among hospitalized drivers aged 80 years and older. Mandatory physician driver reporting laws lacked any independent association with prevalence of dementia among hospitalized drivers.
Worst-Case Crosstalk Measurements of Cables—The Multinetwork Analyzer Method

Alien crosstalk (AXT) between Ethernet cables produces interference and poses a potential threat to system security. AXT is challenging to measure in pre-existing installations because of the need for instrumentation at both the near- and far ends. Although commercially available portable equipment for this purpose exists, baluns must be used to excite the balanced modes on Ethernet cables, which restricts the bandwidth and includes the unwanted response of the baluns. Here, a novel measurement system is proposed that does not use baluns. The proposed system uses unbalanced network analyzers that are placed at both ends of the cable run. The analyzers are synchronized and phase locked, and the resulting unbalanced crosstalk measurements are then mathematically converted to balanced and common modes. A new calibration method for multiple network analyzers is presented and validated. Worst-case alien crosstalk measurements of Category 6 unshielded twisted pairs using the proposed system are then presented.
The Relationship Between the Use of a Worksite Medical Home and ED Visits or Hospitalizations

Worksite medical homes may be a good model for improving employee health. The aim of this study was to compare the likelihood of being seen in the emergency department (ED) or being hospitalized by level of use (no use, occasional use, or primary care) of a worksite medical home, overall and by type of user (employee, adult dependent, or pediatric dependent). This was a retrospective analysis of claims data, using covariate-adjusted logistic regression models for ED visits and inpatient hospitalizations. Secondary data for the years 2006 to 2008 from a company that offers an on-site health care center (HCC) were used. Analyses were based on a data set that combines health plan claims and human resources demographic data. Overall, people who did not use the HCC were more likely to be seen in the ED (adjusted odds ratio [OR] = 1.20, 95% confidence interval or CI [1.06, 1.37], P = .005) or to be hospitalized (adjusted OR = 1.58; 95% CI [1.34, 1.86]; P < .0001) compared with those who used the HCC for primary care. Both ED visits and hospitalizations for employees and dependents in this study were lower among those who used the worksite medical home for primary care. Worksite medical homes can improve chronic disease management and thus reduce ED visits and hospitalizations. These findings contribute to growing evidence that worksite medical homes are potentially cost-effective.
Loss of SLC25A46 causes neurodegeneration by affecting mitochondrial dynamics and energy production in mice

Recently, we identified biallelic mutations of SLC25A46 in patients with multiple neuropathies. Functional studies revealed that SLC25A46 may play an important role in mitochondrial dynamics by mediating mitochondrial fission. However, the cellular basis and pathogenic mechanism of the SLC25A46-related neuropathies are not fully understood. Thus, we generated a Slc25a46 knock-out mouse model. Mice lacking SLC25A46 displayed severe ataxia, mainly caused by degeneration of Purkinje cells. Increased numbers of small, unmyelinated and degenerated optic nerves as well as loss of retinal ganglion cells indicated optic atrophy. Compound muscle action potentials in peripheral nerves showed peripheral neuropathy associated with degeneration and demyelination in axons. Mutant cerebellar neurons have large mitochondria, which exhibit abnormal distribution and transport. Biochemically mutant mice showed impaired electron transport chain activity and accumulated autophagy markers. Our results suggest that loss of SLC25A46 causes degeneration in neurons by affecting mitochondrial dynamics and energy production.
Optimization of a multi-target voltages switched capacitor converter

In this paper, an efficient voltage scalable switched capacitor converter (SCC) for 1.1V battery-powered system is presented. The SCC employs a binary resolution technique to step-down the input voltage to a range of voltages, while keeping the efficiency high. An optimization strategy for designing multi-topology SCC is presented to improve the effectiveness of the circuit and to preserve efficiency over large load voltages.
Towards a Socially Optimal Multi-Modal Routing Platform

The increasing rate of urbanization has added pressure on the already constrained transportation networks in our communities. Ride-sharing platforms such as Uber and Lyft are becoming a more commonplace, particularly in urban environments. While such services may be deemed more convenient than riding public transit due to their on-demand nature, reports show that they do not necessarily decrease the congestion in major cities. One of the key problems is that typically mobility decision support systems focus on individual utility and react only after congestion appears. In this paper, we propose socially considerate multi-modal routing algorithms that are proactive and consider, via predictions, the shared effect of riders on the overall efficacy of mobility services. We have adapted the MATSim simulator framework to incorporate the proposed algorithms present a simulation analysis of a case study in Nashville, Tennessee that assesses the effects of our routing models on the traffic congestion for different levels of penetration and adoption of socially considerate routes. Our results indicate that even at a low penetration (social ratio), we are able to achieve an improvement in system-level performance.
Human Papillomavirus 16 Infection Induces VAP-Dependent Endosomal Tubulation

ABSTRACT Human papillomavirus (HPV) infection involves complex interactions with the endocytic transport machinery, which ultimately facilitates the entry of the incoming viral genomes into the trans-Golgi network (TGN) and their subsequent nuclear entry during mitosis. The endosomal pathway is a highly dynamic intracellular transport system, which consists of vesicular compartments and tubular extensions, although it is currently unclear whether incoming viruses specifically alter the endocytic machinery. In this study, using MICAL-L1 as a marker for tubulating endosomes, we show that incoming HPV-16 virions induce a profound alteration in global levels of endocytic tubulation. In addition, we also show a critical requirement for the endoplasmic reticulum (ER)-anchored protein VAP in this process. VAP plays an essential role in actin nucleation and endosome-to-Golgi transport. Indeed, the loss of VAP results in a dramatic decrease in the level of endosomal tubulation induced by incoming HPV-16 virions. This is also accompanied by a marked reduction in virus infectivity. In VAP knockdown cells, we see that the defect in virus trafficking occurs after capsid disassembly but prior to localization at the trans-Golgi network, with the incoming virion-transduced DNA accumulating in Vps29/TGN46-positive hybrid vesicles. Taken together, these studies demonstrate that infection with HPV-16 virions induces marked alterations of endocytic transport pathways, some of which are VAP dependent and required for the endosome-to-Golgi transport of the incoming viral L2/DNA complex. IMPORTANCE Human papillomavirus infectious entry involves multiple interactions with the endocytic transport machinery. In this study, we show that incoming HPV-16 virions induce a dramatic increase in endocytic tubulation. This tubulation requires ER-associated VAP, which plays a critical role in ensuring the delivery of cargoes from the endocytic compartments to the trans-Golgi network. Indeed, the loss of VAP blocks HPV infectious entry at a step after capsid uncoating but prior to localization at the trans-Golgi network. These results define a critical role for ER-associated VAP in endocytic tubulation and in HPV-16 infectious entry.
Collagen fibril orientation in the human corneal stroma and its implication in keratoconus.

PURPOSE The kind and the degree of preferred collagen fibril orientation in normal human corneal stroma were investigated as important qualities of the cornea with respect to its mechanical properties and, hence, to refractive surgery. To determine whether this information is relevant to corneal disease, the authors investigated collagen fibril orientation in several corneas with keratoconus. METHODS By means of low-angle x-ray scattering, 17 normal human corneas and four corneas of eyes with keratoconus were investigated. RESULTS Collagen fibrils in the normal human corneal stroma showed two preferred orientations orthogonal to each other. These were the horizontal and the vertical directions. The authors defined a degree of orientation gamma, determined to be gamma = 0.49 +/- 0.10 (mean +/- SD). This means that the excess of the preferentially oriented fibrils in relation to the total number of fibrils was approximately 49%. It follows from this value that approximately two thirds of the fibrils (66%) were within in a 45 degrees sector (+/-22.5 degrees) around the horizontal and vertical meridians, whereas approximately one third (34%) is oriented in the oblique sectors in between. No statistically significant variation of gamma within a central 7 mm zone could be detected in normal corneas. The orthogonal arrangement of the collagen fibrils was, however, profoundly altered in keratoconus, in which nonorthogonal orientations were found inside the apical scar. CONCLUSIONS The normal human corneal stroma shows a considerable degree of structural anisotropy. It is characterized by two preferred collagen fibril orientations orthogonal to each other. Alteration of the regular orthogonal arrangement of the fibrils in keratoconus may be related to the biomechanical instability of the tissue.
Spectrum Sensing via Energy Detector in Low SNR

As in IEEE 802.22 proposal, the spectrum sensing technique should be capable enough to sense the primary signal with very low receiver sensitivity such as at -116 dBm. In this paper, the detection performance of an energy detector used for the spectrum sensing in cognitive radio networks is investigated under very low signal-to-noise ratio (SNR) level. The analysis focuses on the derivation of a closed-form expression for the average missed-detection probability over Rayleigh fading and Nakagami-$m$ fading channels. Subsequently, the detection threshold is optimized as minimizing the total error rate. The analysis is validated by numerical and simulation results. The sensing requirements defined in IEEE 802.22 are also discussed with numerical examples.
The network from above and below

Recently, the HCI community has taken a strong interest in problems associated with networking. Many of those problems have also been the focus of much recent networking research, e.g., traffic identification, network management, access control. In this paper we consider these two quite different viewpoints of the problems specifically associated with home networking. Focusing on traffic identification as a core capability required by much recent HCI work, we explore the mismatch between the approaches the two communities have taken, and suggest some resulting challenges and directions for future work.
Increased skin permeation efficiency of imperatorin via charged ultradeformable lipid vesicles for transdermal delivery

Aim The aim of this work was to develop a novel vesicular carrier, ultradeformable liposomes (UDLs), to expand the applications of the Chinese herbal medicine, imperatorin (IMP), and increase its transdermal delivery. Methods In this study, we prepared IMP-loaded UDLs using the thin-film hydration method and evaluated their encapsulation efficiency, vesicle deformability, skin permeation, and the amounts accumulated in different depths of the skin in vitro. The influence of different charged surfactants on the properties of the UDLs was also investigated. Results The results showed that the UDLs containing cationic surfactants had high entrapment efficiency (60.32%±2.82%), an acceptable particle size (82.4±0.65 nm), high elasticity, and prolonged drug release. The penetration rate of IMP in cationic-UDLs was 3.45-fold greater than that of IMP suspension, which was the highest value among the vesicular carriers. UDLs modified with cationic surfactant also showed higher fluorescence intensity in deeper regions of the epidermis. Conclusion The results of our study suggest that cationic surfactant-modified UDLs could increase the transdermal flux, prolong the release of the drug, and serve as an effective dermal delivery system for IMP.
Towards online trajectory generation considering robot dynamics and torque limits

Generating robot motion trajectories instantaneously in the moment unforeseen sensor events happen is very essential for many real-world robot applications. Using a previous work on online trajectory generation as a basis, this paper proposes an alternative approach that also considers dynamic models. The former class of algorithms does not take into account dynamically changing acceleration capabilities based on maximum actuator forces/torques. This paper extends target velocity-based algorithms of the previous approach by taking into consideration the entire system dynamics when generating trajectories online within one control cycle (typically 1 ms or less). The extension includes the acceleration capabilities of a robot at every discrete time step assuming constant values for the maximum actuator forces/torques, thus allowing the generation of adaptive trajectory profiles during the motion of the robot. Several real-world experimental results using a seven-degree-of-freedom lightweight robot arm underline the relevance of this extension.
Where do bright ideas occur in our brain? Meta-analytic evidence from neuroimaging studies of domain-specific creativity

Many studies have assessed the neural underpinnings of creativity, failing to find a clear anatomical localization. We aimed to provide evidence for a multi-componential neural system for creativity. We applied a general activation likelihood estimation (ALE) meta-analysis to 45 fMRI studies. Three individual ALE analyses were performed to assess creativity in different cognitive domains (Musical, Verbal, and Visuo-spatial). The general ALE revealed that creativity relies on clusters of activations in the bilateral occipital, parietal, frontal, and temporal lobes. The individual ALE revealed different maximal activation in different domains. Musical creativity yields activations in the bilateral medial frontal gyrus, in the left cingulate gyrus, middle frontal gyrus, and inferior parietal lobule and in the right postcentral and fusiform gyri. Verbal creativity yields activations mainly located in the left hemisphere, in the prefrontal cortex, middle and superior temporal gyri, inferior parietal lobule, postcentral and supramarginal gyri, middle occipital gyrus, and insula. The right inferior frontal gyrus and the lingual gyrus were also activated. Visuo-spatial creativity activates the right middle and inferior frontal gyri, the bilateral thalamus and the left precentral gyrus. This evidence suggests that creativity relies on multi-componential neural networks and that different creativity domains depend on different brain regions.