Miracle-dz/UniFAR-FTUs huggingface dataset:
Specificity of Cerebellar Vermian Abnormalities in Autism: A Quantitative Magnetic Resonance Imaging Study

To gain insight into the specificity of cerebellar vermian abnormalities reported in autism, we conducted a magnetic resonance imaging (MRI) study of boys with either of two conditions associated with autism, Down syndrome and fragile X syndrome, compared with boys with idiopathic autism and controls. The subjects, ranging in age from 3 to 9 years, included 16 boys with Down syndrome + autism and 11 boys with Down syndrome only; 13 boys with fragile X syndrome + autism and 9 boys with fragile X syndrome only; 10 boys with idiopathic autism; and 22 controls. Diagnosis of autism was based on DSM-IV criteria, confirmed primarily by the Autism Diagnostic Interview. T1-weighted midsagittal MRIs were used to measure midline structures. Intracranial area, reflecting brain size, was significantly smaller in subjects with Down syndrome. Therefore, all vermian measures were expressed as ratios to intracranial area. Analysis of covariance (covarying for age and IQ) demonstrated that posterior vermi (lobules VI—VII and VIII—X) were markedly smaller in both Down syndrome groups and those with fragile X syndrome only, whereas only lobules VI—VII were reduced in idiopathic autism. Factorial analyses of variance tested interactions between autism factor and the diagnosis of Down syndrome or fragile X syndrome. The size of lobules VI—VII/intracranial area was dependent on autism status only in fragile X syndrome, with ratios significantly larger in fragile X syndrome with autism with respect to fragile X syndrome only. We conclude that selective posterior vermis hypoplasia is seen not only in idiopathic autism but also in Down syndrome and some individuals with fragile X syndrome. However, reductions in vermian lobules VI and VII appear to be specific to idiopathic autism, whereas increased size of lobules VI and VII is associated with autism in fragile X syndrome. The latter results are consistent with MRI studies showing lobules VI—VII hyperplasia in a subset of subjects with idiopathic autism and cerebral and hippocampal enlargements in fragile X syndrome. (J Child Neurol 2003;18:463—470).
Mechanism of gene expression by the glucocorticoid receptor: Role of protein‐protein interactions

The glucocorticoid receptor belongs to an important class of transcription factors that alter the expression of target genes in response to a specific hormone signal. The glucocorticoid receptor can function at least at three levels: (1) recruitment of the general transcription machinery; (2) modulation of transcription factor action, independent of DNA binding, through direct protein‐protein interactions; and (3) modulation of chromatin structure to allow the assembly of other gene regulatory proteins and/or the general transcription machinery on the DNA. This review will focus on the multifaceted nature of protein‐protein interactions involving the glucocorticoid receptor and basal transcription factors, coactivators and other transcription factors, occurring at these different levels of regulation.
Launching Integrative Experiences through Linked Courses: The Future Educators Learning Community (FELC)

This article describes the first implementation of the Future Educators Learning Community, and particularly, the impact of three linked courses and instructor collaboration. With supporting literature and the context and background of this learning community as the foundation, our experiences are structured into three distinct categories: preparing, implementing, and reflecting upon our journey. Pertinent logistics are discussed as well as the importance of ongoing communication and collaboration in response to real-time feedback from students. Throughout this initial implementation, recurring themes emerged that extended meaning for both students and instructors. The article concludes with important lessons learned, as well a poetic representation of the initial Future Educator Learning Community.
Why Permit Telework? Exploring the Determinants of California City Governments’ Decisions to Permit Telework

This study examines what factors influence a local government’s decision to permit its employees to telework. Drawing on insights from contingency theory, this study investigates how external forces influence California local governments’ decisions regarding whether or not to permit telework for their employees. To examine this question, this article uses the 2010 International City/County Management Association survey data and the 2009 American Communities Survey by the U.S. Census Bureau as its primary data sources. The findings show that various contextual factors such as municipal climate protection efforts, citizen participation, population diversity, political institutions, and support from state legislators play a significant role in a city government’s decision to permit telework for city employees.
More Donors, More Democracy

A country’s democracy improves when it receives democracy aid from more donor countries. This finding appears surprising from a development perspective, as the presence of a large number of donors, or more generally “fragmented aid,” has been shown to negatively affect the recipient country. But fragmented aid can be beneficial: diversity among donors provides choice to the local actors involved in the process of democratization. It thus creates a “marketplace for idea support,” which increases the viability of the resulting institutions. In contrast, a highly concentrated donor community can lead to the imposition of an institutional blueprint, designed in advance and not adapted to the needs of the recipient society. An instrumental variable analysis with panel data for 130 countries from 1994 to 2013, explicit tests of the causal mechanism, and anecdotal evidence from Ghana provide strong support for the benefits of diverse democracy aid.
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency.

BACKGROUND Somatic mutations have the potential to encode "non-self" immunogenic antigens. We hypothesized that tumors with a large number of somatic mutations due to mismatch-repair defects may be susceptible to immune checkpoint blockade. METHODS We conducted a phase 2 study to evaluate the clinical activity of pembrolizumab, an anti-programmed death 1 immune checkpoint inhibitor, in 41 patients with progressive metastatic carcinoma with or without mismatch-repair deficiency. Pembrolizumab was administered intravenously at a dose of 10 mg per kilogram of body weight every 14 days in patients with mismatch repair-deficient colorectal cancers, patients with mismatch repair-proficient colorectal cancers, and patients with mismatch repair-deficient cancers that were not colorectal. The coprimary end points were the immune-related objective response rate and the 20-week immune-related progression-free survival rate. RESULTS The immune-related objective response rate and immune-related progression-free survival rate were 40% (4 of 10 patients) and 78% (7 of 9 patients), respectively, for mismatch repair-deficient colorectal cancers and 0% (0 of 18 patients) and 11% (2 of 18 patients) for mismatch repair-proficient colorectal cancers. The median progression-free survival and overall survival were not reached in the cohort with mismatch repair-deficient colorectal cancer but were 2.2 and 5.0 months, respectively, in the cohort with mismatch repair-proficient colorectal cancer (hazard ratio for disease progression or death, 0.10 [P<0.001], and hazard ratio for death, 0.22 [P=0.05]). Patients with mismatch repair-deficient noncolorectal cancer had responses similar to those of patients with mismatch repair-deficient colorectal cancer (immune-related objective response rate, 71% [5 of 7 patients]; immune-related progression-free survival rate, 67% [4 of 6 patients]). Whole-exome sequencing revealed a mean of 1782 somatic mutations per tumor in mismatch repair-deficient tumors, as compared with 73 in mismatch repair-proficient tumors (P=0.007), and high somatic mutation loads were associated with prolonged progression-free survival (P=0.02). CONCLUSIONS This study showed that mismatch-repair status predicted clinical benefit of immune checkpoint blockade with pembrolizumab. (Funded by Johns Hopkins University and others; ClinicalTrials.gov number, NCT01876511.).
Evidence for Presynaptic Adenosine A2a Receptors Associated with Norepinephrine Release and Their Desensitization in the Rat Nucleus Tractus Solitarius

Abstract: Rat medullary brain segments containing primarily nucleus tractus solitarius (NTS) were used for superfusion studies of evoked transmitter release and for isotherm receptor binding assays. Isotherm binding assays with [3H]CGS‐21680 on membranes prepared from NTS tissue blocks indicated a single high‐affinity binding site with a KD of 5.1 ± 1.4 nM and a Bmax of 20.6 ± 2.4 fmol/mg of protein. The binding density for [3H]CGS‐21680 on NTS membranes was 23 times less than comparable binding on membranes from striatal tissue. Electrically stimulated (1 min at 25 mA, 2 ms, 3 Hz) release of [3H]norepinephrine ([3H]NE) from 400‐µm‐thick NTS tissue slices resulted in an S2/S1 ratio of 0.96 ± 0.02. Superfusion of single tissue slices with 0.1–100 nM CGS‐21680, a selective adenosine A2a receptor agonist, for 5 min before the S2 stimulus produced a significant concentration‐dependent increase in the S2/S1 fractional release ratio that was maximal (31.3% increase) at 1.0 nM. However, superfusion of tissue slices with CGS‐21680 over the same concentration range for 20 min before the S2 stimulus did not alter the S2/S1 ratio significantly from control release ratios. The augmented release of [3H]NE mediated by 1.0 nM CGS‐21680 with a 5‐min tissue exposure was abolished by 1.0 and 10 nM CGS‐15943 as well as by 100 nM 8‐(3‐chlorostyryl)caffeine, both A2a receptor antagonists, but not by 1.0 nM 8‐cyclopentyl‐1,3‐dipropylxanthine, the A1 receptor antagonist. Taken together, these results suggest that CGS‐21680 augmented the evoked release of [3H]NE in the NTS via activation of presynaptic A2a receptors within the same concentration range as the binding affinity observed for [3H]CGS‐21680. It was also apparent that this population of presynaptic adenosine A2a receptors in the NTS desensitized within 20 min because the augmenting action of CGS‐21680 on evoked transmitter release was not evident at the longer interval.
A method of vessel tracking for vessel diameter measurement on retinal images

A method of vessel tracking has been developed for quantification of vessel diameters of retinal images. This method utilises twin Gaussian functions to model the distribution of grey level over a vessel cross section. The diameter of the vessel at the cross section can then be calculated using the functions. The variation of vessel diameter in the direction of vessel longitude axis has been described by a tracking technique based on parameters of modelled intensity distribution curves over every cross section. This enables us to obtain an average diameter over any length of a vessel and to develop more parameters for diagnosis and study of vascular diseases.
Inhibition of soluble epoxide hydrolase activity by compounds isolated from the aerial parts of Glycosmis stenocarpa

Abstract The aim of this study is to search for soluble epoxide hydrolase (sEH) inhibitors from natural plants, bioassay-guided fractionation of lipophilic n-hexane and chloroform layers of an extract of the aerial parts of Glycosmis stenocarpa led to the isolation of 12 compounds (1–12) including murrayafoline-A (1), isomahanine (2), bisisomahanine (3), saropeptate (4), (24 S)-ergost-4-en-3,6-dione (5), stigmasta-4-en-3,6-dion (6), stigmast-4-en-3-one (7), β-sitosterol (8), 24-methylpollinastanol (9), trans-phytol (10), neosarmentol III (11) and (+)-epiloliolide (12). Their structures were elucidated on the basis of spectroscopic data. Among them, neosarmentol III (11) was isolated from nature for the first time. All the isolated compounds were evaluated for their inhibitory activity against sEH. Among isolated carbazole-type compounds, isomahanine (2) and bisisomahanine (3) were identified as a potent inhibitor of sEH, with IC50 values of 22.5 ± 1.7 and 7.7 ± 1.2 µM, respectively. Moreover, the inhibitory action of 2 and 3 represented mixed-type enzyme inhibition.
Responses of Action Potential and K+ Currents to Temperature Acclimation in Fish Hearts: Phylogeny or Thermal Preferences?

Electrical activity of the heart is assumed to be one of the key factors that set thermal tolerance limits for ectothermic vertebrates. Therefore, we hypothesized that in thermal acclimation—the duration of cardiac action potential and the repolarizing K+ currents that regulate action potential duration (APD)—the rapid component of the delayed rectifier K+ current (IKr) and the inward rectifier K+ current (IK1) are more plastic in eurythermal than in stenothermal fish species. The hypothesis was tested in six freshwater teleosts representing four different fish orders (Cadiformes, Cypriniformes, Perciformes, Salmoniformes) acclimated at +4°C (cold acclimation) or +18°C (warm acclimation). In cold acclimation, a compensatory shortening of APD occurred in all species regardless of thermal tolerances, life styles, or phylogenies of the fish, suggesting that this response is a common characteristic of the teleost heart. The strength of the response did not, however, obey simple eurythermy‐stenothermy gradation but differed among the phylogenetic groups. Salmoniformes fish showed the greatest acclimation capacity of cardiac electrical activity, whereas the weakest response appeared in the perch (Perciformes) heart. The underlying ionic mechanisms were also partly phylogeny dependent. Modification of the IKr current was almost ubiquitously involved in acclimation response of fish cardiac myocytes to temperature, while the ability to change the IK1 current under chronic thermal stress was absent or showed inverse compensation in Salmoniformes species. Thus, in Salmoniformes fish, the thermal plasticity of APD is strongly based on IKr, while other fish groups rely on both IKr and IK1.
The opportunity costs of commuting: the value of a commuting satellite account framework with an example from Lisbon Metropolitan Area*

ABSTRACT Commuting affects regional and urban economies. It shapes urban areas, defines their relationships with neighboring regions, intensifies economic flows and exacerbates energy consumption and greenhouse gas emissions. This paper sets out a proposal for an innovative commuting satellite account (CSA), integrated in a multi-regional input–output model. This framework combines commuting activities with regional distribution of income, distinct household consumption structures, real estate renting activities and the energy consumption and environmental flows incorporated in the different industries. To assess the opportunity costs of commuting, the CSA framework is applied to the Lisbon Metropolitan Area. The socio-economic-environmental impacts of a scenario in which commuters become non-commuters by moving their residence to the municipality in which they work are estimated. The analysis indicates that: commuting, in general, induces significant economic and environmental opportunity costs. Finally, the adoption of policy-oriented recommendations contributing to limit sprawling in metropolitan regions is discussed.
Phenotypic repertoire of the FNR regulatory network in Escherichia coli

The FNR protein in Escherichia coli is an O2 sensor that modifies global gene expression to adapt the cell to anaerobic growth. Regulation of FNR involves continuous cycling of the protein between its active and inactive states under aerobic conditions without apparent function. This raises the question of what benefit to the overall life cycle might compensate for the cost of cycling and reveals that the role of this process is poorly understood. To address this problem, we introduce the concept of a ‘system design space’, which provides a rigorous definition of phenotype at the molecular level and a means of visualizing the phenotypic repertoire of the system. Our analysis reveals undesirable and desirable phenotypes with an optimal constellation of parameter values for the system. To facilitate a more concrete understanding of what the design space represents, we analyse mutations that alter the apparent dimerization rate constant of FNR. We show that our estimated wild‐type value of this rate constant, which is difficult to measure in situ, is located within this constellation and that the behaviour of the system is compromised in mutants if the value of the apparent dimerization rate constant lies beyond the bounds of this optimal constellation.
Population pharmacokinetics of steady‐state carbamazepine in Egyptian epilepsy patients

What is Known and Objective: Individualization of carbamazepine (CBZ) dosage regimen in patients with epilepsy based on based on therapeutic drug monitoring (TDM) followed by estimation of pharmacokinetic (PK) parameters can help in better control of epilepsy. Our objective was to establish a population (POP) PK model of CBZ for Egyptian adult and pediatric patients with epilepsy.
Cytogenetics of the true bug infraorder Cimicomorpha (Hemiptera, Heteroptera): a review

Abstract The Cimicomorpha is one of the largest and highly diversified infraorders of the Heteroptera. This group is also highly diversified cytogenetically and demonstrates a number of unusual cytogenetic characters such as holokinetic chromosomes; m-chromosomes; multiple sex chromosome systems; post-reduction of sex chromosomes in meiosis; variation in the presence/absence of chiasmata in spermatogenesis; different types of achiasmate meiosis. We present here a review of essential cytogenetic characters of the Cimicomorpha and outline the chief objectives and goals of future investigations in the field.
Genome Sequence of Saccharomyces carlsbergensis, the World’s First Pure Culture Lager Yeast

Lager yeast beer production was revolutionized by the introduction of pure culture strains. The first established lager yeast strain is known as the bottom fermenting Saccharomyces carlsbergensis, which was originally termed Unterhefe No. 1 by Emil Chr. Hansen and has been used in production in since 1883. S. carlsbergensis belongs to group I/Saaz-type lager yeast strains and is better adapted to cold growth conditions than group II/Frohberg-type lager yeasts, e.g., the Weihenstephan strain WS34/70. Here, we sequenced S. carlsbergensis using next generation sequencing technologies. Lager yeasts are descendants from hybrids formed between a S. cerevisiae parent and a parent similar to S. eubayanus. Accordingly, the S. carlsbergensis 19.5-Mb genome is substantially larger than the 12-Mb S. cerevisiae genome. Based on the sequence scaffolds, synteny to the S. cerevisae genome, and by using directed polymerase chain reaction for gap closure, we generated a chromosomal map of S. carlsbergensis consisting of 29 unique chromosomes. We present evidence for genome and chromosome evolution within S. carlsbergensis via chromosome loss and loss of heterozygosity specifically of parts derived from the S. cerevisiae parent. Based on our sequence data and via fluorescence-activated cell-sorting analysis, we determined the ploidy of S. carlsbergensis. This inferred that this strain is basically triploid with a diploid S. eubayanus and haploid S. cerevisiae genome content. In contrast the Weihenstephan strain, which we resequenced, is essentially tetraploid composed of two diploid S. cerevisiae and S. eubayanus genomes. Based on conserved translocations between the parental genomes in S. carlsbergensis and the Weihenstephan strain we propose a joint evolutionary ancestry for lager yeast strains.
The ‘normality of unsafety’- foreign solo female travellers in India

ABSTRACT India is generally characterised by a high level of crime against women, particularly domestic and sexual violence. Media, travel-related organisations, and scholarly research have all addressed this issue, especially after a series of rape cases occurred in the country since 2012. Yet, foreign female travellers’ perceptions of safety in India have not been explored in detail by scholars. This is particularly true within the context of solo female travel, which is a growing trend in India. This paper attempts to address this knowledge gap by focusing on foreign solo female travellers’ experiences in India. Based on an analysing of 21 foreign solo female travellers’ online blogs, this paper contends that although tourist spaces and destinations perceived as risky, such as India, may produce high concerns about safety, they only represent one of the several unsafe spaces that women have to navigate through in both their mundane and touristy routines. Importantly, by arguing that solo female travellers have internalised the ‘normality of unsafety’, this paper questions whether solo female travel is a phenomenon that challenges gendered structures of power.
Computer navigation of the acetabular component in total hip arthroplasty: a narrative review

Total hip arthroplasty (THA) is a common procedure for primary osteoarthritis, but increasing numbers are also being performed for other pathologies such as secondary arthritis, inflammatory arthropathies and trauma. Estimates suggest that around 8.5 million people in the UK are affected by joint pain secondary to arthritis and a rising ageing population has resulted in an increase in THA operations of around 4% per year over the last six years. Multiple studies have shown that THA provides improved quality of life scores, but there remains the burden of complications which account for 15% of £1bn NHS liability payouts. DaPalma et al analysed the financial impact of complications following THA and found the additional cost of a dislocation within six weeks of surgery is 342% of the primary cost. Following primary THA, complications may occur as a result of incorrect component positioning of the femoral stem, the acetabular cup or both. It is known that acetabular malposition may lead to increased rates of dislocation, impingement, edge-loading, polyethylene wear, pelvic osteolysis and prosthesis failure. Acetabular component positioning has been described as the single most important factor in dictating risk of dislocation following THA. Furthermore, instability and dislocation after primary THA is the most common single reason for revision surgery accounting for 22.5% of all revisions and 33% of acetabular revisions. We outline the currently available methods of acetabular navigation comparing freehand techniques with computer and robotic-assisted navigation of the acetabular component. Cite this article: Davenport D, Kavarthapu V. Computer navigation of the acetabular component in total hip arthroplasty: a narrative review. EFORT Open Rev 2016;1:279-285. DOI: 10.1302/2058-5241.1. 000050.