Miracle-dz/UniFAR-FTUs huggingface dataset:
Pyridines and Pyrimidines Mediating Activity against an Efflux-Negative Strain of Candida albicans through Putative Inhibition of Lanosterol Demethylase

ABSTRACT The first step in ergosterol biosynthesis in Saccharomyces cerevisiae consists of the condensation of two acetyl coenzyme A (acetyl-CoA) moieties by acetoacetyl-CoA thiolase, encoded by ERG10. The inhibition of the sterol pathway results in feedback activation of ERG10 transcription. A cell-based reporter assay, in which increased ERG10 transcription results in elevated specific β-galactosidase activity, was used to find novel inhibitors of ergosterol biosynthesis that could serve as chemical starting points for the development of novel antifungal agents. A class of pyridines and pyrimidines identified in this way had no detectable activity against the major fungal pathogen Candida albicans (MICs > 64 μg · ml−1). However, a strain of C. albicans lacking the Cdr1p and Cdr2p efflux pumps was sensitive to the compounds (with MICs ranging from 2 to 64 μg · ml−1), suggesting that they are efficiently removed from wild-type cells. Quantitative analysis of sterol intermediates that accumulated during growth inhibition revealed the accumulation of lanosterol at the expense of ergosterol. Furthermore, a clear correlation was found between the 50% inhibitory concentration at which the sterol profile was altered and the antifungal activity, measured as the MIC. This finding strongly suggests that the inhibition of growth was caused by a reduction in ergosterol synthesis. The compounds described here are a novel class of antifungal pyridines and pyrimidines and the first pyri(mi)dines to be shown to putatively mediate their antifungal activity against C. albicans via lanosterol demethylase.
The impact of low-frequency stimulation of the pedunculopontine nucleus region on reaction time in parkinsonism

Objectives Attentional augmentation and enhanced motor function are potential mechanisms by which stimulation of the region of the pedunculopontine nucleus (PPN) may improve gait in parkinsonism. Here, the authors assess the impact of stimulation of this region on attentional and motor aspects of reaction task performance in patients with parkinsonism. Methods Eleven patients implanted with PPN stimulators underwent computerised assessment of simple, choice and digit vigilance reaction tasks. Patients were assessed ‘off medication’ during stimulation at different frequencies (0 Hz, 5 Hz, 10 Hz and ‘therapeutic’ 20–35 Hz). There were two primary endpoints: ‘Speed of Reaction’ (sum of the mean task reaction times) and ‘Accuracy of Reaction’ (reflecting omissions and percentage of correct responses). Baseline performance was compared with age- and sex-matched healthy controls. Clinical effects of stimulation were assessed using the Unified Parkinson's Disease Rating Scale and a falls frequency scale. Results Compared with healthy controls, subjects had significant deficits in ‘Speed of Reaction’ and in all mean task reaction times. ‘Accuracy of Reaction’ was not different from healthy controls and did not improve with stimulation. ‘Speed of Reaction’ significantly improved with stimulation at therapeutic frequencies (20–35 Hz). Of the individual tasks, only simple reaction time improved significantly. Simple reaction time distribution analysis revealed a general speeding of responses rather than a selective reduction in outliers. Acute PPN stimulation improved gait and balance but not akinesia scores. Chronic PPN stimulation significantly improved falls frequency. Falls score improvement significantly correlated with changes to simple reaction time with therapeutic stimulation. Conclusion The pattern of reaction time improvement with stimulation of the PPN area suggests a benefit on motor performance, rather than augmentation of attention.
Information and the Skewness of Music Sales

This paper studies the role of product discovery in the demand for recorded music. We show that releasing a new album causes a substantial and permanent increase in sales of the artist's old albums—especially if the new release is a hit. Patterns in these “backward spillovers” suggest that they result from consumers discovering the artist upon hearing the new release. To explore the implications of consumers’ incomplete information, we estimate a simple, learning‐based model of market demand. Our results imply that the distribution of sales is substantially more skewed than it would be if consumers were more fully informed.
A Multi-Center Study to Evaluate the Performance of Phage Amplified Biologically Assay for Detecting TB in Sputum in the Pulmonary TB Patients

Objective To evaluate the performance of phage amplified biologically assay (PhaB) for detecting tuberculosis (TB) in sputum in the pulmonary tuberculosis (PTB) patients. Methods Shanghai Tuberculosis Key Laboratory of Shanghai Pulmonary Hospital participated in the project in collaboration with the laboratories of six hospitals and a total of 1660 eligible participants (1351 PTB patients and 309 non-TB patients) were included in the study. The sputum samples from the participants were detected by smear microscopy, PhaB, and Löwenstein-Jensen (L-J) culture method, respectively. Results The overall sensitivity of PhaB were higher than that of L-J culture and smear microscopy (p<0.05). The sensitivity of PhaB for detecting smear-negative specimens was obviously higher than that of L-J culture (p<0.05). Compared with L-J culture, the overall sensitivity, specificity, PPV, NPV, ACC and Kappa value of PhaB were 98.4 (95% Cl: 96.9–99.3), 71.6 (95% Cl: 68.4–74.6), 67.7, 98.7, 81.7% and 0.643, respectively. The detection median time of PhaB only needed 48 hours, which was significantly less than that (31 days) of L-J culture method. Conclusion PhaB method is a rapid and sensitive method for detecting TB in sputum in PTB patients; especially for the diagnosis of smear-negative PTB, PhaB method is obviously more sensitive than L-J culture method.
Curcumin Improves Palmitate-Induced Insulin Resistance in Human Umbilical Vein Endothelial Cells by Maintaining Proteostasis in Endoplasmic Reticulum

Dysfunction of proteasome and autophagy will result in disturbance of endoplasmic reticulum (ER) proteostasis, and thus lead to long-term and chronic ER stress and subsequent unfolded protein response (UPR), which is implicated in the occurrence and development of insulin resistance. Curcumin exerts beneficial metabolic effects in in vitro cells and in vivo animal models of diabetes and diabetic complications including cardiovascular diseases, due to its powerful anti-oxidative and anti-inflammatory properties. However, its impacts on insulin resistance of endothelial cells and its underlying mechanism(s) remain ill-defined. Herein, we tested the hypothesis that curcumin action in ER protein quality control was related to improvement of insulin resistance in human umbilical vein endothelial cells (HUVECs) cultured with saturated fatty acid palmitate. We found that palmitate treatment induced insulin resistance of HUVECs and activated both the ubiquitin-proteasome system (UPS) and autophagy. Palmitate-stimulated activation of the UPS and autophagy was attenuated by pharmacological inhibition of ER stress. In addition, curcumin supplementation mitigated palmitate-induced insulin resistance, inhibited the UPS, and activated autophagy. Furthermore, curcumin administration suppressed palmitate-induced protein aggregation and ER stress. Genetic inhibition of autophagy by silencing autophagy protein 5 (Atg5) completely restored total protein ubiquitination and protein aggregation in HUVECs treated with combined curcumin and palmitate. Atg5-knockdown also abolished the beneficial effects of curcumin on palmitate-induced ER stress, JNK/IRS-1 pathway as well as insulin signaling. Our results reveal that curcumin-activated autophagy could maintain proteostasis in ER leading to attenuation of ER stress and subsequent inhibition of JNK/IRS-1 pathway and improvement of insulin resistance.
SECOND SEASON QUIET OBSERVATIONS: MEASUREMENTS OF THE COSMIC MICROWAVE BACKGROUND POLARIZATION POWER SPECTRUM AT 95 GHz

The Q/U Imaging ExperimenT (QUIET) has observed the cosmic microwave background (CMB) at 43 and 95 GHz. The 43 GHz results have been published in a previous paper, and here we report the measurement of CMB polarization power spectra using the 95 GHz data. This data set comprises 5337 hr of observations recorded by an array of 84 polarized coherent receivers with a total array sensitivity of 87 μK. Four low-foreground fields were observed, covering a total of ∼1000 deg2 with an effective angular resolution of 12. ′8, allowing for constraints on primordial gravitational waves and high signal-to-noise measurements of the E-modes across three acoustic peaks. The data reduction was performed using two independent analysis pipelines, one based on a pseudo-Cℓ (PCL) cross-correlation approach, and the other on a maximum-likelihood (ML) approach. All data selection criteria and filters were modified until a predefined set of null tests had been satisfied before inspecting any non-null power spectrum. The results derived by the two pipelines are in good agreement. We characterize the EE, EB, and BB power spectra between ℓ = 25 and 975 and find that the EE spectrum is consistent with ΛCDM, while the BB power spectrum is consistent with zero. Based on these measurements, we constrain the tensor-to-scalar ratio to r = 1.1+0.9 − 0.8 (r < 2.8 at 95% C.L.) as derived by the ML pipeline, and r = 1.2+0.9 − 0.8 (r < 2.7 at 95% C.L.) as derived by the PCL pipeline. In one of the fields, we find a correlation with the dust component of the Planck Sky Model, though the corresponding excess power is small compared to statistical errors. Finally, we derive limits on all known systematic errors, and demonstrate that these correspond to a tensor-to-scalar ratio smaller than r = 0.01, the lowest level yet reported in the literature.
Special Education and the New Mental Health: A Response to New Direction of CCBD?

■ The emphasis or focus of a professional association often shifts imperceptibly over time in ways that neither its membership nor its leadership seems able to recognize until pivotal events compel it to do so. The historical shift from psychodynamic to behavioral approaches in special education for children with emotional or behavioral disorders began just about a half century ago and largely coincided with the formation of its primary professional association, the Council for Children with Behavioral Disor ders (CCBD), a subdivision of the Council for Exceptional Children (CEC). That CCBD's 50th Anniversary also seems to coincide with the fact that its recent loss of membership has now slipped to a level below 50% is unfortunate. The coincidence of these two pivotal events, however, is fortuitous. CCBD leader
Prevalence of Helicobacter pylori in children in eastern Turkey and molecular typing of isolates

The objectives of the present study were to determine Helicobacter pylori via culture, polymerase chain reaction and histopathological diagnosis in 101 children ranging in age from 4 to 18 years, to identify the association among restriction fragment length polymorphism types and clinical disease and to investigate the relationships among different isolates of H. pylori in different age groups. We observed a high prevalence of H. pylori infections in children between the ages of 13 and 18 (75.8%), while children aged 4 to 6 years had the lowest prevalence of infection (40%). H. pylori was detected in 30.7% (31 of 101), 66.3% (67 of 101) and 63.2% (60 of 95) of children as determined by culture methods, PCR and histological examination, respectively. H. pylori isolates with RFLP types I and III were the most common among children with antral nodularity, whereas RFLP types II and IV were the least detected types. Interestingly, all isolates from peptic ulcer patients were type III. Although our results show a high prevalence of H. pylori infections in the pediatric population in eastern Turkey, no association was identified between H. pylori infection with antral nodularity and recurring abdominal pain. In addition, we found low genetic variation among H. pylori isolates from children and no association between RFLP types and antral nodularity (p > 0.05). Additionally, we found that H. pylori isolates with specific RFLP types were predominant in different age groups.
Unifying Visual-Semantic Embeddings with Multimodal Neural Language Models

Inspired by recent advances in multimodal learning and machine translation, we introduce an encoder-decoder pipeline that learns (a): a multimodal joint embedding space with images and text and (b): a novel language model for decoding distributed representations from our space. Our pipeline effectively unifies joint image-text embedding models with multimodal neural language models. We introduce the structure-content neural language model that disentangles the structure of a sentence to its content, conditioned on representations produced by the encoder. The encoder allows one to rank images and sentences while the decoder can generate novel descriptions from scratch. Using LSTM to encode sentences, we match the state-of-the-art performance on Flickr8K and Flickr30K without using object detections. We also set new best results when using the 19-layer Oxford convolutional network. Furthermore we show that with linear encoders, the learned embedding space captures multimodal regularities in terms of vector space arithmetic e.g. *image of a blue car* - "blue" + "red" is near images of red cars. Sample captions generated for 800 images are made available for comparison.
Dealing with large bananas

Many problems call for a mixture of generic and speci(cid:12)c programming techniques. We propose a polytypic programming approach based on generalised (monadic) folds where a separation is made between basic fold algebras that model generic behaviour and updates on these algebras that model speci(cid:12)c behaviour. We identify particular basic algebras as well as some algebra combinators, and we show how these facilitate structured programming with updatable fold algebras. This blend of genericity and speci(cid:12)city allows programming with folds to scale up to applications involving large systems of mutually recursive datatypes. Finally, we address the possibility of providing generic de(cid:12)nitions for the functions, algebras, and combinators that we propose.
Comparison of isoflurane and sevoflurane in anaesthesia for day care surgeries using classical laryngeal mask airway

Background: In the present study, we compared isoflurane with sevoflurane in day care surgeries in order to determine the suitability of each agent for anaesthesia with Classical laryngeal mask airway (LMA). Aims: The aim of this study has been to compare isoflurane and sevoflurane as maintenance anaesthetic agents in day care surgeries with respect to intraoperative haemodynamics, recovery profile, time of first postoperative analgesia and pain score, adverse effects when used with classical LMA. Settings and Design: This open - level, prospective randomized study was carried out on 60 patients who were admitted on a day care basis for elective short surgical procedures. Methods: The patients were randomly assigned to one of the two study groups of 30 patients each. First group was maintained on isoflurane and second on sevoflurane as inhalational agent. Statistical Analysis: The observations obtained in both the groups were recorded and tabulated. Statistical analysis was carried out using the Student t test, Chi-square test, Mann-Whitney test. Results: Emergence from Sevoflurane was significantly quicker as compared to isoflurane. Sevoflurane group also showed earlier discharge time from the post anaesthesia care unit (PACU)-1 as compared to isoflurane group, but discharge time was same from the PACU-1. Isoflurane has more incidences of mild airway hyper reactivity when compared to sevoflurane. Conclusions: It can be concluded that both isoflurane and sevoflurane are suitable for day care anaesthesia. Sevoflurane has little advantages of less airway hyper reactivity and quicker emergence and discharge from PACU-1.
Integration of Structural and Semantic Models for Multimedia Metadata Management

The management and exchange of multimedia data is challenging due to the variety of formats, standards and intended applications. In addition, production of multimedia data is rapidly increasing due to the availability of off-the-shelf, modern digital devices that can be used by even inexperienced users. It is likely that this volume of information will only increase in the future. A key goal of the MUSCLE (Multimedia Understanding through Semantics, Computation and Learning) network is to develop tools, technologies and standards to facilitate the interoperability of multimedia content and support the exchange of such data. One approach for achieving this was the creation of a specific "E-Team", composed of the authors, to discuss core questions and practical issues based on the participant's individual work. In this paper, we present the relevant points of view with regards to sharing experiences and to extracting and integrating multimedia data and metadata from different modes (text, images, video).
High Prevalence of Echocardiographic Abnormalities in Diabetic Youths

M-mode echocardiography was performed on 107 young insulin-dependent diabetic subjects aged 2 – 24 yr (± SE: 13.8 ± 0.4 yr) and 636 age-group-matched controls. All patients were normotensive and free of cardiorespiratory symptoms. Diabetic patients showed a high prevalence of echocardiographic abnormalities that increased with age. Mean dimensions of the left atrium, right ventricle, and left ventricle (systolic and diastolic) were increased significantly in diabetic individuals (P < 0.01). Hypertrophy of the interventricular septum was present in some patients older than 12 yr of age. Mean interventricular septum excursion was markedly decreased in diabetic individuals compared with controls (3.9 ± 0.1 mm versus 5.6 ± 0.2 mm, respectively; P < 0.01). Fifteen percent of the diabetic patients but none of the controls had septal excursions less than 3 mm (2 SD below mean). Patients with decreased septal excursions showed a higher prevalence of other echocardiographic abnormalities than patients with normal septal excursions. Echocardiographic abnormalities did not correlate with either duration of diabetes or glucose control as assessed by hemoglobin Alc and plasma glucose concentrations at the time of echocardiographic testing. The results show a high prevalence of echocardiographic abnormalities in young diabetic subjects that may represent preclinical cardiomyopathy.
Can ‘eye’ tell if you are paying attention? The use of mobile eye-trackers to measure academic engagement in the primary-school classroom.

Although much research has examined the construct of academic engagement using behavioural measures such as observations and recording video footage of classrooms, there is little taking advantage of the development of technology enabling researchers to measure possible behavioural indicators of visual attention. The technology in question is a device with the capability to track the eye movements of the wearer whilst in their naturalistic environment. With this in mind, a novel idea was proposed, aiming to establish a link between academic engagement, selective attention and eye-tracking. Therefore, the goal of the present study was to test the feasibility of implementing a mobile eye-tracking device in a primary school classroom as a measure of visual attention, and consequently of academic engagement. One classroom at a local school was used for the study, where the gaze patterns of primary-school aged children were collected during sessions of either literacy or numeracy teaching, with the prediction that the naturally-occurring differences between classroom activities (‘teacher instruction’ and ‘classroom discussion’) would affect where children directed their gaze within their classroom. The main difference found was that children were more likely to fixate onto their close peers or their own work during ‘classroom discussion’, compared to aspects of the environment relating to the teaching of instruction, such as a whiteboard display during ‘teacher instruction’. Additionally, findings suggest that school-children generally remain ‘on-task’ during periods of ‘teacher instruction’ and ‘classroom discussion’, however, they still express some level of distractibility during periods of observation. Understanding how children deploy their attention in an academic context has wide implications, from both a developmental and educational perspective. The feasibility of applying alternative methods such as this research paradigm will be addressed, with suggestions for future adaptations.
The Ghetto Underclass: Social Science Perspectives

The Underclass - William Julius Wilson Issues, Perspectives, and Public Policy The Cost of Racial and Class Exclusion in the Inner City - Lo[um]ic J D Wacquant and William Julius Wilson Urban Industrial Transition and the Underclass - John D Kasarda Absent Fathers in the Inner City - Mercer L Sullivan Sex Codes and Family Life Among Poor Inner-City Youths - Elijah Anderson Employment and Marriage Among Inner-City Fathers - Mark Testa et al Single Mothers, The Underclass, and Social Policy - Sara McLanahan and Irwin Garfinkel Puerto Ricans and the Underclass Debate - Marta Tienda Immigration and the Underclass - Robert D Reischauer The Urban Homeless - Peter H Rossi and James D Wright A Portrait of Urban Dislocation Equal Opportunity and the Estranged Poor - Jennifer L Hochschild The Logic of Workfare - Lawrence M Mead The Underclass and Work Policy Institutional Change and the Challenge of the Underclass - Richard P Nathan
Optimizing the detection of recent tuberculosis infection in children in a high tuberculosis-HIV burden setting.

RATIONALE Children who are young, malnourished, and infected with HIV have significant risk of tuberculosis (TB) morbidity and mortality following TB infection. Treatment of TB infection is hindered by poor detection and limited pediatric data. OBJECTIVES Identify improved testing to detect pediatric TB infection. METHODS This was a prospective community-based study assessing use of the tuberculin skin test and IFN-γ release assays among children (n = 1,343; 6 mo to <15 yr) in TB-HIV high-burden settings; associations with child characteristics were measured. MEASUREMENTS AND MAIN RESULTS Contact tracing detects TB in 8% of child contacts within 3 months of exposure. Among children with no documented contact, tuberculin skin test and QuantiFERON-TB Gold In-Tube positivity was greater than T-SPOT.TB. Nearly 8% of children had IFN-γ release assay positive and skin test negative discordance. In a model accounting for confounders, all tests correlate with TB contact, but IFN-γ release assays correlate better than the tuberculin skin test (P = 0.0011). Indeterminate IFN-γ release assay results were not associated with age. Indeterminate QuantiFERON-TB Gold In-Tube results were more frequent in children infected with HIV (4.7%) than uninfected with HIV (1.9%), whereas T-SPOT.TB indeterminates were rare (0.2%) and not affected by HIV status. Conversion and reversion were not associated with HIV status. Among children infected with HIV, tests correlated less with contact as malnutrition worsened. CONCLUSIONS Where resources allow, use of IFN-γ release assays should be considered in children who are young, recently exposed, and infected with HIV because they may offer advantages compared with the tuberculin skin test for identifying TB infection, and improve targeted, cost-effective delivery of preventive therapy. Affordable tests of infection could dramatically impact global TB control.