Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional impact of ZEB1 mutations associated with posterior polymorphous and Fuchs' endothelial corneal dystrophies.

PURPOSE To assess the impact of zinc finger E-box binding homeobox 1 (ZEB1) gene mutations associated with posterior polymorphous corneal dystrophy 3 (PPCD3) and Fuchs' endothelial corneal dystrophy (FECD). METHODS Thirteen of the 27 previously reported ZEB1 truncating mutations associated with PPCD3 and the six previously reported ZEB1 missense mutations associated with FECD were generated and transiently transfected into a corneal endothelial cell line. Protein abundance was determined by immunoblotting, while intracellular localization was determined by fluorescence confocal microscopy. RESULTS Three of the 13 ZEB1 truncated mutants, and none of the missense mutants, showed significant decrease in mutant ZEB1 protein levels. Predominant nuclear localization was observed for truncated ZEB1 mutant proteins with a predicted molecular weight of less than 92 kilodaltons. The two largest mutant proteins that lacked a putative nuclear localization signal (NLS), p.(Ser638Cysfs*5) and p.(Gln884Argfs*37), primarily localized to the cytoplasm, while the NLS-containing mutant proteins, p.(Glu997Alafs*7) and p.(Glu1039Glyfs*6), primarily localized to the nucleus. All the missense ZEB1 mutant proteins were exclusively present in the nucleus. CONCLUSIONS ZEB1 truncating mutations result in a significant decrease and/or impaired nuclear localization of the encoded protein, indicating that ZEB1 haploinsufficiency in PPCD3 may result from decreased protein production and/or impaired cellular localization. Conversely, as the reported ZEB1 missense mutations do not significantly impact protein abundance or nuclear localization, the effect of these mutations on ZEB1 function and their relationship to FECD, if any, remain to be elucidated.
Novel Demodulation Method for Fiber-Optic Interferometers Based on $\pi/2$ Phase Modulation

This letter proposes a novel demodulation method for fiber-optic interferometer sensors. A fast square wave is added to the reference arm of the interferometer sensor in the form of phase modulation. Starting from this, we successfully developed a simple demodulation method that can greatly improve the conversion efficiency and overcome the unbalanced influences. Our experiment results show that a very small phase shift of about 6.3 × 10-5 rad can be detected, which proves high signal-to-noise ratio demodulated signal and low distortion in our demodulation method. The linearity between demodulated signal and test signal is shown to be over 99%.
Penetration of moxifloxacin into bone in patients undergoing total knee arthroplasty.

OBJECTIVES To investigate plasma and bone moxifloxacin concentrations following oral administration of a single or double dose of the drug, in order to consider its potential role in the treatment of osteomyelitis. PATIENTS AND METHODS Thirty consecutive patients undergoing total knee arthroplasty were recruited. Three groups, of ten patients each, were formed: group A received moxifloxacin 400 mg orally 2 h (range 1.5-2.5) preoperatively, group B received moxifloxacin 400 mg orally 4 h (range 3.5-4.5) preoperatively and group C received moxifloxacin 400 mg orally 14 h preoperatively, followed by a second dose 2 h (range 1.5-2.5) preoperatively. During surgery, at the time of bone removal, a blood sample and aliquots of cortical and cancellous bone were collected and moxifloxacin concentrations were measured by HPLC. RESULTS Mean plasma, cancellous bone and cortical bone concentrations were, respectively: 3.45, 1.89 and 1.43 mg/L for group A; 3.73, 1.81 and 1.56 mg/L for group B; and 6.26, 2.97 and 2.54 mg/L for group C. CONCLUSIONS These data show a good penetration of moxifloxacin into both cancellous and cortical bone, with concentrations, after double dosing, exceeding the MIC90 for most pathogens involved in osteomyelitis and the clinic susceptibility breakpoint for Mycobacterium tuberculosis.
A selective impairment in extracting fearful information from another's eyes in Autism

An atypical pattern of facial expression processing in children with autism spectrum disorder (ASD) has been discussed in previous studies. In this study, we systematically examined the hypothesis of selective abnormality of gaze pattern of in children with ASD using three emotion judgment “bubble” tasks. In this study, we used a data‐driven driven technique, referred to as “Bubbles” to examine the hypothesis that ASD children will not show a general but rather a selective abnormality in extracting eyes information expressed by different emotions. Results indicated that similar to non‐ASD individuals, ASD individuals used information from other people's eyes to judge happiness and anger. In contrast, ASD individuals showed a remarkable reduction in processing the eye region in fearful face, together with enhanced processing of the mouth, compared with the control group. The results suggest that a selective abnormality in extracting eyes information of fearful face without abnormality in processing eyes area of other basic facial emotions is a key and characteristic feature of autistic facial cognition. To our knowledge, this finding regarding the selective abnormality in extracting fearful information from another's eyes in ASDs has never been reported in previous studies and the information gathered as a part of this pilot research project has important clinical implications for social information processing training. For example, as children with ASD are more vulnerable to fear processing, training related to fear should be stressed. Autism Res 2016, 9: 1002–1011. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
A relaxed LMI approach to actuator fault detection and isolation

This paper presents an intuitive Fault Detection and Isolation (FDI) synthesis method for linear time invariant systems subject to faults. The proposed method uses the notion of ultimate boundedness to relax certain feasibility conditions, meaning that the resulting problem can be posed in a similar manner to an intuitive ℌ∞ minimization problem. It is then possible to show, using a quadratic Lyapunov function, that the error states are bounded - rather than they converge asymptotically to zero - and that minimizing a certain design parameter can enhance detectability properties. In this way, it is possible to pose the FDI problem as the solution to a set of linear matrix inequalities which do not restrict the value of the performance variable as strictly as in some other approaches. In addition, it is possible to intuitively off-set detectability/isolation properties and robustness to signal uncertainty. The paper demonstrates the effectiveness of the proposed synthesis technique through a simulation example.
An ionospheric clutter recognition method based on machine learning

Ionospheric clutter is the primary factor that affecting High Frequency Surface Wave Radar (HFSWR) detection performance. In order to draw up an adaptive detection strategy suitable in various environment, a novel algorithm is proposed in this paper to recognize ionospheric clutter. The algorithm firstly extracts a series of features, after that, it takes advantage of Genetic Algorithm (GA) to select effective features. Finally, Support Vector Machine (SVM) is applied to acquire a global ionospheric clutter recognition result. Experiments constructed on the real data show that the proposed method can achieve a better performance with the average recognition accuracy up to 86%.
The relationship between gastrointestinal symptom attribution, bothersomeness, and antiretroviral adherence among adults with HIV

ABSTRACT Patients who attribute their symptoms to HIV medications, rather than disease, may be prone to switching antiretrovirals (ARVs) and experience poor retention/adherence to care. Gastrointestinal (GI) symptoms (e.g., nausea/vomiting) are often experienced as a side effect of ARVs, but little is known about the relationship of symptom attribution and bothersomeness to adherence. We hypothesized that attribution of a GI symptom to ARVs is associated with a reduction in adherence, and that this relationship is moderated by the bothersomeness of the symptom. Data for our analysis come from the pre-randomization enrollment period of a larger study testing an adherence improvement intervention. Analyses revealed that patients with diarrhea who attributed the symptom to ARVs (compared to those who did not) had significantly worse adherence. We did not find a significant moderating effect of bothersomeness on this relationship. Incorporating patient beliefs about causes of symptoms into clinical care may contribute to improved symptom and medication management, and better adherence.
Biomechanical examination of the ‘plateau phenomenon’ in ActiGraph vertical activity counts

This paper determines if the leveling off (‘plateau/inverted-U’ phenomenon) of vertical ActiGraph activity counts during running at higher speeds is attributable to the monitor's signal filtering and acceleration detection characteristics. Ten endurance-trained male participants (mean (SD) age = 28.2 (4.7) years) walked at 3, 5 and 7 km h−1, and ran at 8, 10, 12, 14, 16, 18 and 20 km h−1 on a force treadmill while wearing an ActiGraph GT3X monitor at the waist. Triaxial accelerations of the body's center of mass (CoM) and frequency content of these accelerations were computed from the force treadmill data. GT3X vertical activity counts demonstrated the expected ‘plateau/inverted-U’ phenomenon. In contrast, vertical CoM accelerations increased with increasing speed (1.32 ± 0.26 g at 10 km h−1 and 1.68 ± 0.24 g at 20 km h−1). The dominant frequency in the CoM acceleration signals increased with running speed (14.8 ± 3.2 Hz at 10 km h−1 and 24.8 ± 3.2 Hz at 20 km h−1) and lay beyond the ActiGraph band-pass filter (0.25 to 2.5 Hz) limits. In conclusion, CoM acceleration magnitudes during walking and running lie within the ActiGraph monitor's dynamic acceleration detecting capability. Acceleration signals of higher frequencies that are eliminated by the ActiGraph band-pass filter may be necessary to distinguish among exercise intensity at higher running speeds.
Phosphoenolpyruvate-dependent fructose phosphotransferase system of Rhodopseudomonas sphaeroides: purification and physicochemical and immunochemical characterization of a membrane-associated enzyme I.

The phosphotransferase system (PTS) of the phototrophic bacterium Rhodopseudomonas sphaeroides consists of a component located in the cytoplasmic membrane and a membrane-associated enzyme called "soluble factor" (SF) [Saier, M. H. , Feucht, B. U. , & Roseman, S. (1971) J. Biol. Chem. 246, 7819--7821]. SF has been partially purified by a combination of hydrophobic interaction and ion-exchange and gel-permeation chromatography. SF is similar to Escherichia coli enzyme I in its molecular characteristics and enzymatic properties. It has a molecular weight of 85 000 and readily dimerizes. Phosphoenolpyruvate and Mg2+ stabilize the dimer. The enzyme catalyzes the conversion of phosphoenolpyruvate into pyruvate and becomes phosphorylated in the process. The phosphoryl group is subsequently transferred to fructose in the presence of R. sphaeroides membranes. SF substitutes for E. coli enzyme I in fructose or glucose phosphorylation with E. coli enzyme II and HPr. The activities of SF with the R. sphaeroides PTS and the E. coli PTS reside on structurally distinct molecules as shown by their response to limited proteolytic digestion and by immunochemical studies. The activity of SF with the E. coli PTS arises during the isolation procedure and is most likely due to the removal of HPr-like protein from SF.
Tyrosine kinase activation in breast carcinoma with correlation to HER-2/neu gene amplification and receptor overexpression.

The HER-2/neu oncogene encodes a transmembrane receptor with intrinsic tyrosine kinase activity. A pilot study was performed to investigate downstream effects of HER-2/neu (or related growth factor receptor) activation by identifying phosphorylated tyrosine. Fifty-four breast carcinomas were evaluated for HER-2/neu overexpression by the HercepTest (Dako, Carpinteria, CA) and the monoclonal CB11 antibody (Ventana, Tucson, AZ). Phosphotyrosine (an indication of tyrosine kinase activity) was detected by an antiphosphotyrosine mouse monoclonal antibody (Upstate Biotechnology, Lake Placid, NY). The gene amplification status was evaluated in 50 of the 54 cases by fluorescence in situ hybridization (FISH) using the Ventana gene probe. The HER-2/neu oncogene amplification was detected in 28% (14 of 50) of cases. Of the 14 cases showing oncogene amplification, tyrosine kinase activity was detected in 9 (64.2%) cases. There was moderate agreement between HER-2/neu gene amplification and tyrosine kinase activity (kappa = 0.43). Immunohistochemical staining of 3+ (with both HercepTest and CB11) showed better agreement with HER-2/neu oncogene amplification and increased tyrosine kinase activity than 2+ immunohistochemical staining. Overall, oncogene amplification and overexpression correlated with increased tyrosine kinase activity, supporting the mechanism of tyrosine kinase activation by HER-2/neu amplification and overexpression. However, 7 cases showing increased tyrosine kinase activity did not show gene amplification or 3+ receptor expression (by either HercepTest or CB11), raising the possibility of other growth factor receptors operating via the tyrosine kinase pathway. There was no apparent correlation between tyrosine kinase activity and hormone receptor status (estrogen or progesterone). Increased tyrosine kinase activity is more commonly associated with higher-grade tumors and thus may correlate with aggressive biologic behavior in breast carcinoma. The results of this pilot study suggest that a larger-scale investigation into downstream activation of tyrosine kinase and correlation to clinical outcome or response to Herceptin therapy may identify subsets of patients whose clinical response or outcome may be predicted by tyrosine kinase activation.
Transitions across various continuing care settings.

PURPOSE to compare cross-nationally the sources and rates of admission and discharge in nursing homes. METHODS data on admission were used from the Minimum Data Set of the Resident Assessment Instrument as collected in a multi-nation database at the University of Michigan. Additional data containing longitudinal episodes were used from databases in the Netherlands, Switzerland and the USA. RESULTS the sources and rates of admission and discharge in nursing homes vary widely between countries. In Japan 47.5% of the sample was admitted from another long-term care setting, in Italy and the USA 36% and 42% respectively were admitted directly from hospital, while in Denmark and Iceland more than 60% came from home. The longitudinal data show that in the Netherlands, residents' return to home was much more likely than in Geneva or the USA (27% vs 5% vs 10%) and that in the USA a relatively large number of nursing home residents (>45%) was discharged (intermittently) to a hospital within 180 days after first admission as compared to the Netherlands (10%). CONCLUSIONS there are large differences between countries in admission and discharge to and from nursing homes. Various policies, payment schemes, care patterns and routine referrals influence this and can be studied with cross-national data now available.
Remittances, International Reserves, and Exchange Rate Regimes

International reserves are experiencing a significant increase, in part as a result of specific policies but also from the development of external factors, like remittances. This paper examines the role that remittances play in the accumulation of reserves, and uses a dynamic panel model for a group of 9 Latin American countries in the period 1997-2010 to uncover its influence. Our results show that international reserves are influenced positively by higher trade surpluses, exchange rate depreciations, interest rate differentials, rises in commodity prices and higher inflows of remittances. In fact, the influence that remittances exert on reserves is the strongest and most consistent amongst our determinants. Not surprisingly, we uncover a differential impact of remittances emanating from specific characteristics, like location of the receiving country, relative importance of remittances in terms of GDP, and the exchange rate regime in place, with countries operating under more rigid exchange rate regimes experience the expected magnified effect on reserves.
Work in progress - a case study of transformation in Higher Education

Universities in Spain have launched one of the most ambitious and significant changes in their history through the adoption of the so-called Bologna process. The European Higher Education Area (EHEA) to be established by this effort aims at promoting mobility and internationally comparable degree programs within European Union (EU). This paper presents an implementation experience at Carlos III University, with a focus on their Engineering School. The objectives of this study are two-fold: (i) to share the implementation experience so that other Spanish universities may be able to adopt any success factors from the case study, and (ii) to inform other higher educational institutes around the world about significant changes taking place in their counterparts in Spain. In addition, a data collection system is being developed so that the effectiveness of the new system can objectively be measured and analyzed. Experiences with EC2000 changes initiated by Accreditation Board for Engineering and Technology (ABET) in USA will also be compared with the Spanish experience.
Nurse-Led Medicines' Monitoring for Patients with Dementia in Care Homes: A Pragmatic Cohort Stepped Wedge Cluster Randomised Trial

Background People with dementia are susceptible to adverse drug reactions (ADRs). However, they are not always closely monitored for potential problems relating to their medicines: structured nurse-led ADR Profiles have the potential to address this care gap. We aimed to assess the number and nature of clinical problems identified and addressed and changes in prescribing following introduction of nurse-led medicines’ monitoring. Design Pragmatic cohort stepped-wedge cluster Randomised Controlled Trial (RCT) of structured nurse-led medicines’ monitoring versus usual care. Setting Five UK private sector care homes Participants 41 service users, taking at least one antipsychotic, antidepressant or anti-epileptic medicine. Intervention Nurses completed the West Wales ADR (WWADR) Profile for Mental Health Medicines with each participant according to trial step. Outcomes Problems addressed and changes in medicines prescribed. Data Collection and Analysis Information was collected from participants’ notes before randomisation and after each of five monthly trial steps. The impact of the Profile on problems found, actions taken and reduction in mental health medicines was explored in multivariate analyses, accounting for data collection step and site. Results Five of 10 sites and 43 of 49 service users approached participated. Profile administration increased the number of problems addressed from a mean of 6.02 [SD 2.92] to 9.86 [4.48], effect size 3.84, 95% CI 2.57–4.11, P <0.001. For example, pain was more likely to be treated (adjusted Odds Ratio [aOR] 3.84, 1.78–8.30), and more patients attended dentists and opticians (aOR 52.76 [11.80–235.90] and 5.12 [1.45–18.03] respectively). Profile use was associated with reduction in mental health medicines (aOR 4.45, 1.15–17.22). Conclusion The WWADR Profile for Mental Health Medicines can improve the quality and safety of care, and warrants further investigation as a strategy to mitigate the known adverse effects of prescribed medicines. Trial Registration ISRCTN 48133332
5α‐Reductase type 2 gene variant associations with prostate cancer risk, circulating hormone levels and androgenetic alopecia

Controversy exists over the significance of associations between the SRD5A2 (5α‐reductase type 2) polymorphisms, A49T and V89L, and risk of prostate cancer. These potentially functional polymorphisms may alter life‐long exposure to androgens with subsequent effects on male health and aging. The aim of this study was to examine the association of these variants with prostate cancer risk, plasma hormone levels and androgenetic alopecia. Subjects include 827 cases and 736 controls from an Australian population‐based case–control study of prostate cancer. Information on prostate cancer risk factors and patterns of balding were collected. Plasma levels of testosterone, 3α‐diol glucuronide (3α‐diolG), dehydroepiandrosterone sulfate, androstenedione, sex hormone‐binding globulin and estradiol were measured for controls. No associations with the V89L polymorphism were found. Carriers of the rarer A49T A allele were at a 60% higher risk of prostate cancer (OR = 1.60; 95% CI 1.09–2.36; p = 0.02) and 50% lower risk of vertex and frontal balding (p = 0.03) compared with men homozygous for the more common G allele. Although we found little evidence of association between this variant and plasma levels of 5 measured androgens, circulating 3α‐diolG levels were 34% lower in A49T A allele carriers (p < 0.0001). Our study provides evidence that the SRD5A2 A49T A variant is associated with an increased risk of prostate cancer, lower levels of circulating 3α‐diolG and decreased risk of baldness. These findings raise important questions with respect to previous assumptions concerning hormonal influences on prostate cancer risk in ageing males. © 2006 Wiley‐Liss, Inc.
A μ-based approach to small-signal stability analysis of an interconnected distributed energy resource unit and load

The small-signal stability of an interconnected source and load can be analyzed using the frequency-response methods of stability analysis. Existing frequency-response methods of stability analysis introduce artificial conservativeness and do not explicitly address stability robustness against load perturbations, that is, by how much the load can change such that the system will remain stable in the small-signal sense. This paper presents a frequency-response method of stability analysis which provides a less conservative stability condition compared to existing methods, in the sense of having less restriction on the control system; further, the proposed method establishes a robust stability margin in terms of perturbations in load parameters. The proposed method is based on μ analysis, and models the source-load dynamic interaction via a closed-loop system of impedances and admittances. The proposed method is used to examine small-signal stability of an islanded subnetwork extracted from a university campus microgrid, composed of a distributed energy resource (DER) unit feeding a load, providing a study with realistic parameter values. Two case studies are presented to show the features of the proposed method, namely, reduced conservativeness and the establishment of a robust stability margin. Another example is provided to show the application of the proposed stability analysis method in a multi-DER-unit network. The findings of the frequency-domain analysis are illustrated through time-domain simulations around the operating point on the system under study.