Miracle-dz/UniFAR-FTUs huggingface dataset:
Subthalamic Nucleus Lesions Enhance the Psychomotor-Activating, Incentive Motivational, and Neurobiological Effects of Cocaine

The subthalamic nucleus (STN) is traditionally thought to be involved in motor control, and dysfunction of the STN is thought to contribute to movement disorders. Here, we show that the STN also plays an important role in motivational processes and the response to drugs of abuse. Specifically, bilateral STN lesions produced a dose-dependent increase in the psychomotor-activating effects of cocaine, the rate at which animals acquired cocaine self-administration, and the motivation for cocaine assessed using a progressive ratio schedule. Furthermore, bilateral STN lesions enhanced the ability of cocaine to induce gene expression in the nucleus accumbens and caudate–putamen, two structures known to be involved in mediating the psychomotor-activating and incentive motivational effects of drugs of abuse. These findings suggest that engagement of the STN serves to dampen the psychomotor-activating and incentive motivational effects of drugs of abuse. Thus, the STN may serve as a novel target for therapeutic interventions aimed at treating drug dependence.
Positive deviance study to inform a Chagas disease control program in southern Ecuador

Chagas disease is caused by Trypanosoma cruzi, which is mainly transmitted by the faeces of triatomine insects that find favourable environments in poorly constructed houses. Previous studies have documented persistent triatomine infestation in houses in the province of Loja in southern Ecuador despite repeated insecticide and educational interventions. We aim to develop a sustainable strategy for the interruption of Chagas disease transmission by promoting living environments that are designed to prevent colonisation of rural houses by triatomines. This study used positive deviance to inform the design of an anti-triatomine prototype house by identifying knowledge, attitudes and practices used by families that have remained triatomine-free (2010-2012). Positive deviants reported practices that included maintenance of structural elements of the house, fumigation of dwellings and animal shelters, sweeping with "insect repellent" plants and relocation of domestic animals away from the house, among others. Participants favoured construction materials that do not drastically differ from those currently used (adobe walls and tile roofs). They also expressed their belief in a clear connection between a clean house and health. The family's economic dynamics affect space use and must be considered in the prototype's design. Overall, the results indicate a positive climate for the introduction of housing improvements as a protective measure against Chagas disease in this region.
Wage Rigidities in an Estimated DSGE Model of the UK Labour Market

We estimate a New Keynesian model with matching frictions and nominal wage rigidities on UK data. We are able to identify important structural parameters, recover the unobservable shocks that have affected the UK economy since 1971 and study the transmission mechanism. With matching frictions, wage rigidities have limited effect on inflation dynamics, despite improving the empirical performance of the model. The reason is that with matching frictions, marginal costs depend on unit labour costs and on an additional component related to search costs. Wage rigidities affect both components in opposite ways leaving marginal costs and inflation virtually unaffected.
Structural Bioinformatics a Machine Learning Approach to Predicting Protein–ligand Binding Affinity with Applications to Molecular Docking

Motivation: Accurately predicting the binding affinities of large sets of diverse protein–ligand complexes is an extremely challenging task. The scoring functions that attempt such computational prediction are essential for analysing the outputs of molecular docking, which in turn is an important technique for drug discovery, chemical biology and structural biology. Each scoring function assumes a predetermined theory-inspired functional form for the relationship between the variables that characterize the complex, which also include parameters fitted to experimental or simulation data and its predicted binding affinity. The inherent problem of this rigid approach is that it leads to poor predictivity for those complexes that do not conform to the modelling assumptions. Moreover, resampling strategies, such as cross-validation or bootstrapping, are still not systematically used to guard against the overfitting of calibration data in parameter estimation for scoring functions. Results: We propose a novel scoring function (RF-Score) that circumvents the need for problematic modelling assumptions via non-parametric machine learning. In particular, Random Forest was used to implicitly capture binding effects that are hard to model explicitly. RF-Score is compared with the state of the art on the demanding PDBbind benchmark. Results show that RF-Score is a very competitive scoring function. Importantly, RF-Score's performance was shown to improve dramatically with training set size and hence the future availability of more high-quality structural and interaction data is expected to lead to improved versions of RF-Score.
The Poverty of Political Culture

The analyses reported by Granato, Inglehart, and Leblang (1996; hereafter GIL) are a major improvement over the studies that we examined in our paper. Especially notable is their explicit evaluation of the cultural explanation against a major rival, as represented by endogenous growth models of scholars like Barro (1991), Levine and Renelt (1992), and Helliwell (1994). These models regress economic growth rates over a given period on a set of initial economic, human capital, and other variables. It is in the context of such models that GIL report a significant, independent effect of culture on growth. GIL's attention to the robustness of their estimates contrasts sharply with the studies evaluated in Jackman and Miller (1996). Their analysis departs from recent treatments in another way. In contrast to Inglehart (1990), for example, who examines the seven different components of culture that we discuss, GIL restrict their attention to just two: postmaterialism and achievement motivation. They find that only achievement motivation affects growth, which serves as the basis for their conclusion about the importance of culture. In this sense, their work stands as a key amendment to recent studies with their emphasis on norms of trust, satisfaction, participation, and the like and signals a return to earlier work, exemplified most notably by McClelland's studies of need for achievement (1961; 1963; McClelland and Winter 1969). Given the exclusion of the former norms from GIL's analysis, along with their reported nonresults for postmaterialism, we take it that they regard achievement motivation as the only "cultural" value affecting economic growth. This narrows the field a good deal. ' While there is thus much to recommend their paper over previous work, GIL's conclusion is ultimately unconvincing, on both theoretical and empirical grounds. We address these areas in turn.
Ironic effects of compulsive perseveration

Individuals with obsessive-compulsive disorder (OCD) exhibit perseverative behaviours, like checking, to reduce uncertainty, but perseveration paradoxically enhances uncertainty. It is unclear what mechanism might be responsible. We hypothesised that perseverative OC-like behaviour produces “semantic satiation” and interferes with the accessibility of meaning. Healthy participants repeated 20 types of OC-like checking behaviour nonperseveratively (2 times) or perseveratively (20 times). Afterwards, they decided as quickly as possible whether a picture was semantically related to the checked object. The nonperseverative condition showed spreading of activation: Judgements were faster for related than for unrelated objects and pictures. The effect was blocked in the perseverative condition, where reaction times for related and unrelated items were similar. The results suggest that the ironic effects of compulsive perseveration are due to interference with spreading of activation.
Time Course of Antibiotic and Antifungal Concentrations in Corneal Organ Culture

Purpose: Contamination with bacteria and/or fungi is a serious complication in organ-cultured corneas. Hence, antibiotic and antifungal agents are added to the culture medium. The concentration of different antimicrobial and antifungal additives to the media over time has so far not been investigated in detail and is the aim of this study. Methods: Nine human fresh corneoscleral discs were stored in corneal culture medium consisting of 2% fetal bovine serum and minimal essential medium. In addition, the culture medium contained 1200 &mgr;g/mL penicillin G, 25 &mgr;g/mL amphotericin B, 120 &mgr;g/mL streptomycin, and 100 &mgr;g/mL voriconazole. The concentration of amphotericin B used was 10 times higher than in clinical routine to facilitate its detection. The cultures were kept at 37°C for 28 days. At days 0, 7, 14, 21, and 28, samples of the culture medium were harvested for analysis of antimicrobial concentrations by liquid chromatography and electrospray ionization tandem mass spectrometry. Results: During corneal storage, the concentration of all antibiotics and antifungal agents declined significantly. By day 28, penicillin G was reduced to 14% of the original concentration. Amphotericin B and streptomycin retained approximately 60% of the original concentration to the end of the experiment and voriconazole maintained stable concentrations after an initial decline to approximately 80% at 7 days. Conclusions: Throughout the entire storage period, the concentrations of penicillin G, streptomycin, and voriconazole exceeded the minimum inhibitory concentrations of all common contaminants, obviating the need for a change of the medium for antimicrobial reasons. Based on the minimum inhibitory concentrations and our findings, the initial concentration of amphotericin B should be raised to 5 &mgr;g/mL.
The small molecule ISRIB rescues the stability and activity of Vanishing White Matter Disease eIF2B mutant complexes

eIF2B is a dedicated guanine nucleotide exchange factor for eIF2, the GTPase that is essential to initiate mRNA translation. The integrated stress response (ISR) signaling pathway inhibits eIF2B activity, attenuates global protein synthesis and upregulates a set of stress-response proteins. Partial loss-of-function mutations in eIF2B cause a neurodegenerative disorder called Vanishing White Matter Disease (VWMD). Previously, we showed that the small molecule ISRIB is a specific activator of eIF2B (Sidrauski et al., 2015). Here, we report that various VWMD mutations destabilize the decameric eIF2B holoenzyme and impair its enzymatic activity. ISRIB stabilizes VWMD mutant eIF2B in the decameric form and restores the residual catalytic activity to wild-type levels. Moreover, ISRIB blocks activation of the ISR in cells carrying these mutations. As such, ISRIB promises to be an invaluable tool in proof-of-concept studies aiming to ameliorate defects resulting from inappropriate or pathological activation of the ISR.
Automatic Technology Mapping for Generalized Fundamental-Mode Asynchronous Designs

We address the problem of technology mapping for generalized fundamental-mode asynchronous designs. In this design style we can separate the combinational portions of the design from the sequential portions, similar to synchronous design styles. We examine each step of algorithmic technology mapping for its influence on the hazard behavior of the modified network. We then present modifications to an existing synchronous technology mapper to work for this asynchronous design style. We present efficient algorithms for hazard analysis that are used during the mapping process. These algorithms have been implemented and incorporated into the program CERES to produce a technology mapper suitable for asynchronous designs.
Prediction of pKa values using the PM6 semiempirical method

The PM6 semiempirical method and the dispersion and hydrogen bond-corrected PM6-D3H+ method are used together with the SMD and COSMO continuum solvation models to predict pKa values of pyridines, alcohols, phenols, benzoic acids, carboxylic acids, and phenols using isodesmic reactions and compared to published ab initio results. The pKa values of pyridines, alcohols, phenols, and benzoic acids considered in this study can generally be predicted with PM6 and ab initio methods to within the same overall accuracy, with average mean absolute differences (MADs) of 0.6–0.7 pH units. For carboxylic acids, the accuracy (0.7–1.0 pH units) is also comparable to ab initio results if a single outlier is removed. For primary, secondary, and tertiary amines the accuracy is, respectively, similar (0.5–0.6), slightly worse (0.5–1.0), and worse (1.0–2.5), provided that di- and tri-ethylamine are used as reference molecules for secondary and tertiary amines. When applied to a drug-like molecule where an empirical pKa predictor exhibits a large (4.9 pH unit) error, we find that the errors for PM6-based predictions are roughly the same in magnitude but opposite in sign. As a result, most of the PM6-based methods predict the correct protonation state at physiological pH, while the empirical predictor does not. The computational cost is around 2–5 min per conformer per core processor, making PM6-based pKa prediction computationally efficient enough to be used for high-throughput screening using on the order of 100 core processors.
DNA Amplifications and Aneuploidy, High Proliferative Activity and Impaired Cell Cycle Control Characterize Breast Carcinomas with Poor Prognosis

In order to explore whether specific cytogenetic abnormalities can be used to stratify tumors with a distinctly different clinical course, we performed comparative genomic hybridization (CGH) of tumors from patients who were diagnosed with metastatic disease after an interval of less than 2 years or who remained free from distant metastases for more than 10 years. All patients presented with distant metastases after mastectomy indicating that none of the patients in this study was cured and free of remaining tumor cells. Tumors in the group of short‐term survivors showed a higher average number of chromosomal copy alterations compared to the long‐term survivors. Of note, the number of sub‐chromosomal high‐level copy number increases (amplifications) was significantly increased in the group of short‐term survivors. In both short‐ and long‐term survivors recurrent chromosomal gains were mapped to chromosomes 1q, 4q, 8q, and 5p. Copy number changes that were more frequent in the group of short‐term survivors included gains of chromosome 3q, 9p, 11p and 11q and loss of 17p. Our results indicate that low‐ and high grade malignant breast adenocarcinomas are characterized by a specific pattern of chromosomal copy number changes. Furthermore, immunohistochemical evaluation of the expression levels of Ki‐67, p27KIP1, p21WAF1, p53, cyclin A and cyclin E revealed a correlation between increased proliferative activity and poor outcome.
Locked Plating of Periprosthetic Femur Fractures Above Total Knee Arthroplasty

Background: Fractures of the femur above a total knee arthroplasty (TKA) are becoming increasingly common in the osteoporotic, aging populations of developed countries. Treatment of these fractures is complicated by the presence of a knee prosthesis, frequently limiting the bone available for distal fracture fixation. The recent application of minimally invasive surgical techniques and locked plate technology to this problem offers the promise of stable, fixed-angle fixation of small distal fracture fragments with limited surgical exposure. The purpose of this study is to report the clinical and radiographic outcomes of fracture fixation using this technique in patients with periprosthetic femur fractures above TKA. Methods: Fifty-three patients presenting with periprosthetic femur fractures above a TKA were treated with osteosynthesis. One patient was lost to follow-up resulting in 52 patients with complete data. Thirty-four patients were treated with plate fixation and 18 patients underwent retrograde intramedullary nail fixation (RIMN). Using a comprehensive electronic medical record, we recorded data regarding patient-related demographics, nature of the fractures, the operative treatment, and clinical and radiographic outcomes for all patients treated with osteosynthesis. Results: Successful fracture healing occurred in 75% of patients (39 of 52). Mean operating time was 91.6 ± 6.8 minutes in the RIMN group and 87.4 ± 6.4 minutes in the locked plating (LP) group (P = 0.46). Mean intraoperative blood loss was 182 ± 31.6 mL in the RIMN group and 177.5 ± 23.4 mL in the LP group (P = 0.91). The mean time to bone union was 3.7 ± 0.30 months in the RIMN group and 4.0 ± 0.27 months in the LP group (P = 0.95). The most common cause of treatment failure was patient death within 6 months (9 patients [17%]); three of 18 were treated with a nail and 6 of 34 with a plate (P = 1.0). In the LP group, three (9%) sustained fracture nonunions, three (9%) sustained fracture malunions, and two (6%) sustained surgical site infections. In the RIMN group, one (6%) failed to unite as a result of infection and two (11%) developed fracture malunions. There were no significant differences between patients treated with LP and those treated with RIMN. Conclusions: Despite significant advances in surgical technique and implant design, the treatment of periprosthetic femur fractures above a TKA remains a challenge. LP using an indirect reduction technique is applicable to most patients and prosthetic designs and can provide similar favorable results as compared with treatment with a RIMN in periprosthetic femoral fractures. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
In vitro and in vivo antibiofilm activity of a coral associated actinomycete against drug resistant Staphylococcus aureus biofilms

Staphylococcus aureus is now amongst the most important pathogenic bacteria responsible for bloodstream nosocomial infections and for biofilm formation on indwelling medical devices. Its increasing resistance to common antibiotics, partly attributed to its ability to form biofilms, is a challenge for the development of new antimicrobial agents. Accordingly, the goal of this study was to evaluate the effect of a coral associated actinomycete (CAA) - 3 on S. aureus biofilms both in vitro and in vivo. Methanolic extracts of CAA-3 showed a reduction in in vitro biofilm formation by S. aureus ATCC 11632, methicillin resistant S. aureus ATCC 33591 and clinical isolates of S. aureus at the biofilm inhibitory concentration (BIC) of 0.1 mg ml−1. Furthermore, confocal laser scanning microscope (CLSM) studies provide evidence of CAA-3 inhibiting intestinal colonisation of S. aureus in the nematode Caenorhabditis elegans. To conclude, this study for the first time, reports CAA as a promising source of anti-biofilm compounds, for developing novel drugs against highly resistant staphylococcal biofilms.
The eroded genome of a Psychotria leaf symbiont: hypotheses about lifestyle and interactions with its plant host.

Several plant species of the genus Psychotria (Rubiaceae) harbour Burkholderia sp. bacteria within specialized leaf nodules. The bacteria are transmitted vertically between plant generations and have not yet been cultured outside of their host. This symbiosis is also generally described as obligatory because plants devoid of symbionts fail to develop into mature individuals. We sequenced for the first time the genome of the symbiont of Psychotria kirkii in order to shed some light on the nature of their symbiotic relationship. We found that the 4 Mb genome of Candidatus Burkholderia kirkii (B. kirkii) is small for a Burkholderia species and displays features consistent with ongoing genome erosion such as large proportions of pseudogenes and transposable elements. Reductive genome evolution affected a wide array of functional categories that may hinder the ability of the symbiont to be free-living. The genome does not encode functions commonly found in plant symbionts such as nitrogen fixation or plant hormone metabolism. Instead, a collection of genes for secondary metabolites' synthesis is located on the 140 kb plasmid of B. kirkii and suggests that leaf nodule symbiosis benefits the host by providing protection against herbivores or pathogens.
Effectiveness of Mindfulness-Based Cognitive Therapy on Reduction of Depression and Anxiety Symptoms in Mothers of Children With Cancer

Background Findings demonstrated that parents of children with cancer experience elevated levels of distress, depression, anxiety, posttraumatic stress symptoms, and subjective symptoms of stress. In this study, we determined effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) on reduction of depression and anxiety symptoms in mothers of children with cancer. Methods Four mothers whose children had cancer were diagnosed to have depression and anxiety symptoms, using Beck Anxiety Inventory, Beck Depression Inventory II, and Structured Clinical Interview for DSM-IV. They were selected through purposeful sampling to participate in this experimental single-case study. After the baseline was determined, subjects attended an eight-session program of Mindfulness-Based Cognitive Therapy. Results The comparison of baseline and post-test showed that depression and anxiety symptoms decreased through MBCT. Improvement quotient for depression and anxiety of each subject was good. Conclusion Data showed that MBCT reduced depression and anxiety symptoms in mothers of children with cancer.
Wireless Networks Should Spread Spectrum Based on Demands

Today’s local-area, mesh and cellular networks assign a single narrow-band channel to a node, and this assignment remains fixed over long time scales. Using network traces, we show that the load within a network can vary significantly even over short time scales on the order of tens of seconds. Therefore, we make the case for allocating spectrum ondemand to nodes and regions of the network that need it. We present an architecture that shares the entire spectrum on-demand using spread-spectrum codes. If implemented, the system will achieve fine-grained spectrum allocation for bursty traffic without requiring inter-cell coordination. Preliminary experiments suggest a throughput improvement of 75% over commodity 802.11b networks. By eschewing the notion of channelization, and matching demand bursts with spectrum dynamically, better wireless networks that sustain higher throughputs may be designed.
Introducing numerical bounds to improve event-based neural network simulation

Although the spike-trains in neural networks are mainly constrained by the neural dynamics itself, global temporal constraints (refractoriness, time precision, propagation delays, .) are also to be taken into account. These constraints are revisited in this paper in order to use them in event-based simulation paradigms. We first review these constraints, and discuss their consequences at the simulation level, showing how event-based simulation of time-constrained networks can be simplified in this context: the underlying data-structures are strongly simplified, while event-based and clock-based mechanisms can be easily mixed. These ideas are applied to punctual conductance-based generalized integrate-and-fire neural networks simulation, while spike-response model (SRM) simulations are also revisited within this framework. As an outcome, a fast minimal complementary alternative with respect to existing simulation event-based methods, with the possibility to simulate interesting neuron models is implemented and experimented.