Miracle-dz/UniFAR-FTUs huggingface dataset:
Electrically Evoked Release of [3H]Noradrenaline from Mouse Cultured Sympathetic Neurons

Abstract: Cultured neurons from the thoracolumbar sympathetic chain of newborn mice are known to possess release‐inhibiting α2‐autoreceptors. The present study was carried out in a search for release‐modulating heteroreceptors on these neurons. Primary cultures were preincubated with [3H]noradrenaline and then superfused and stimulated by single pulses, trains of 8 pulses at 100 Hz, or trains of 36 pulses at 3 Hz. The cholinergic agonist carbachol reduced the evoked overflow of tritium. Experiments with antagonists indicated that the inhibition was mediated by M2 muscarinic receptors. The cannabinoid agonist WIN 55,212‐2 reduced the evoked overflow of tritium through CB1 receptors. Prostaglandin E2, sulprostone, and somatostatin also caused presynaptic inhibition. The inhibitory effects of carbachol, WIN 55,212‐2, prostaglandin E2, and somatostatin were abolished (at the highest concentration of WIN 55,212‐2 almost abolished) by pretreatment of the cultures with pertussis toxin (250 ng/ml). Several drugs, including the β2‐adrenoceptor agonist salbutamol, opioid receptor agonists, neuropeptide Y, angiotensin II, and bradykinin, failed to change the evoked overflow of tritium. These results demonstrate a distinct pattern of presynaptic inhibitory heteroreceptors, all coupled to pertussis toxin‐sensitive G proteins. The lack of operation of several presynaptic receptors known to exist in adult mice in situ may be due to the age of the (newborn) donor animals or to the culture conditions.
Measurements of Energetic Particle Radiation in Transit to Mars on the Mars Science Laboratory

Going to Mars The Mars Science Laboratory spacecraft containing the Curiosity rover, was launched from Earth in November 2011 and arrived at Gale crater on Mars in August 2012. Zeitlin et al. (p. 1080) report measurements of the energetic particle radiation environment inside the spacecraft during its cruise to Mars, confirming the hazard likely to be posed by this radiation to astronauts on a future potential trip to Mars. Williams et al. (p. 1068, see the Perspective by Jerolmack) report the detection of sedimentary conglomerates (pebbles mixed with sand and turned to rock) at Gale crater. The rounding of the rocks suggests abrasion of the pebbles as they were transported by flowing water several kilometers or more from their source. The radiation dose on a round-trip to Mars could represent a large fraction of the accepted lifetime limit for astronauts. The Mars Science Laboratory spacecraft, containing the Curiosity rover, was launched to Mars on 26 November 2011, and for most of the 253-day, 560-million-kilometer cruise to Mars, the Radiation Assessment Detector made detailed measurements of the energetic particle radiation environment inside the spacecraft. These data provide insights into the radiation hazards that would be associated with a human mission to Mars. We report measurements of the radiation dose, dose equivalent, and linear energy transfer spectra. The dose equivalent for even the shortest round-trip with current propulsion systems and comparable shielding is found to be 0.66 ± 0.12 sievert.
Mini-Arthrotomy for Lateral Discoid Menisci in Children

Background: Long-term results after partial, extended, or complete resection of lateral discoid meniscus in children revealed knee arthritis. The purpose of this study was to evaluate whether the operative approach, arthrotomy or arthroscopy, has an impact on the outcome and the development of arthritis. Methods: A retrospective comparison of 2 well matching groups totaling 40 children with symptomatic lateral discoid meniscus (48 knees, mean age 8.9 years, 13 male and 27 female patients). Meniscus resection was performed via mini-arthrotomy in group 1 (n = 17 patients, 20 knees) and arthroscopically in group 2 (n = 23 patients, 28 knees). Results: In the follow-up (mean 57 months in group 1, 62 months in group 2), functional results indicated a trend to better results in the International Knee Documentation Committee score (P = 0.12) and in the Lysholm score for group 1 (P = 0.13) but not in the Ikeuchi score (P = 0.48). The comparison of the radiographic arthritis grading in the follow-up showed no significant arthritis in either group (P = 0.22). The overall complication rate was similar in both groups (2/20, 10% in group 1; 3/28, 12% in group 2). Conclusions: Most likely because of the appropriate visualization of the children's joint and the easier instrumentation, the mini-arthrotomy led to slightly superior results compared with those after arthroscopic resection regarding functional outcome and 5 years after surgery. We can recommend the mini-arthrotomy for the resection of lateral discoid meniscus particularly in young children with narrow joint spaces and for surgeons that are not familiar with arthroscopies of small joints. Level of Evidence: III (therapeutic study, case series with control group).
Differential C Isotope Discrimination by Fungi during Decomposition of C3- and C4-Derived Sucrose

ABSTRACT Stable isotope analysis is a major tool used in ecosystem studies to establish pathways and rates of C exchange between various ecosystem components. Little is known about isotopic effects of many such components, especially microbes. Here we report on the discovery of an unexpected pattern of C isotopic discrimination by basidiomycete fungi with far-reaching consequences for our understanding of isotopic processing in ecosystems where these microbes mediate material transfers across trophic levels. We measured fractionation effects on three ecologically relevant basidiomycete species under controlled laboratory conditions. Sucrose derived from C3 and C4 plants is fractionated differentially by these microbes in a taxon-specific manner. The differentiation between mycorrhizal and saprotrophic fungi observed in the field by others is not explained by intrinsic discrimination patterns. Fractionation occurs during sugar uptake and is sensitive to the nonrandom distribution of stable isotopes in the sucrose molecule. The balance between respiratory physiology and fermentative physiology modulates the degree of fractionation. These discoveries disprove the assumption that fungal C processing does not significantly alter the distribution of stable C isotopes and provide the basis for a reevaluation of ecosystem models based on isotopic evidence that involve C transfer across microbial interfaces. We provide a mechanism to account for the observed differential discrimination effects.
MODELLING RAPID COASTAL CATCH-UP AFTER DEFENCE REMOVAL ALONG THE SOFT CLIFF COAST OF HAPPISBURGH, UK

There are currently no well-established methods of predicting coastal catch-up, i.e. the response of shores to the removal of existing coast protection. Such estimates are vital to inform decisions around the renewal of such structures. At a deeper level, the lack of predictive methods undermines progress towards more sustainable approaches to coastal management, and the implementation of policies of managed realignment. Some progress has been made in recent years using the SCAPE numerical modelling tool (e.g. Walkden et al, 2015). That study demonstrated coastal response that included retreat beyond the position the shore would have been expected to reach in the absence of coast protection (i.e. coast protection apparently causing a net loss of land). That study raised important questions, but was limited in the respect that it represented the coast in two-dimensions (i.e. without alongshore interactions). In this work we illustrate how the novel Coastal Modelling Environment (CoastalME, Payo et al. 2017) is able to reproduce coastal catch-up at Happisburgh at the East coast of UK, and to do so with more physical realism than was possible with the SCAPE model, including accounting for alongshore variations).
Cowpea bruchid Callosobruchus maculatus uses a three‐component strategy to overcome a plant defensive cysteine protease inhibitor

The soybean cysteine protease inhibitor, soyacystatin N (scN), negatively impacts growth and development of the cowpea bruchid, Callosobruchus maculatus[Koiwa et al. (1998) Plant J 14: 371–379]. However, the developmental delay and feeding inhibition caused by dietary scN occurred only during the early developmental stages (the 1st, 2nd and 3rd instars) of the cowpea bruchid. The 4th instar larvae reared on scN diet (adapted) exhibited rates of feeding and development which were comparable to those feeding on an scN‐free diet (unadapted) prior to pupation. Total gut proteolytic capacity at this larval stage significantly increased in the scN‐adapted insects. The elevated enzymatic activity was attributed to a differential expression of insect gut cysteine proteases (representing the major digestive enzymes), and of aspartic proteases. scN degradation by the gut extract was observed only in adapted bruchids, and this activity appeared to be a combined effect of scN‐induced cysteine and aspartic proteases. Thirty cDNAs encoding cathepsin L‐like cysteine proteases were isolated from insect guts, and they were differentially regulated by dietary scN. Our results suggest that the cowpea bruchid adapts to the challenge of scN by qualitative and quantitative remodelling of its digestive protease complement, and by activating scN‐degrading protease activity.
A BIOCHEMICAL FRAMEWORK FOR MODELING THE FUNCTIONAL METABOLISM OF THE HUMAN BRAIN

The existence of complex control mechanisms in the catabolism of molecules utilized for energy production forms the basis of the relationship between function and metabolic regulation. This is especially important in the brain, where numerous in vitro and in vivo experiments have lend support to the theory of the coupling between neuronal activity and energy metabolism, a view enlightened several decades ago and now consolidated. Notwithstanding, many details remained unresolved about the fate of nutrients within the brain parenchyma and the consequent exchanges of substances, particularly between neurons and astrocytes, whose involvement in the neurometabolic coupling is well established. Unfortunately, due to limited spatial and temporal resolution, the currently available experimental techniques do not allow specific measurements of cerebral metabolites in different cell types in situ. Therefore, the analysis of the incomplete experimental data requires the formulation and application of mathematical models. In this paper, we explore these theoretical accounts in the construction of a unified biochemical framework of supply and demand in the context of compartmentalized brain energy metabolism. The model successfully predicts the time-course of observable variables, while providing information about a number of processes underlying neural activity. Future work is expected to gain insights by testing the model with respect to different hypotheses about transport and metabolic cell specialization, as well as about the degree of activation of neurons and astrocytes following brain stimulation.
Why do smallholder farmers insist on living in flood prone areas? Understanding self-perceived vulnerability and dynamics of local adaptation in Malawi

v LAY ABSTRACT . vii TABLE OF CONTENTS . ix LIST OF TABLES . xiii LIST OF FIGURES . xv LIST OF MAPS . xvii ACKNOWLEDGEMENTS . xix DEDICATION . xxi ACRONYMS . xxiii CHAPTER ONE: INTRODUCTION . 1 1.1 Motivation of the Research . 1 1.2 Personal Experience and Interest . 3 1.3 Vulnerability and Adaptation to Climate Change Variability . 4 1.4 Research Context . 6 1.5 Research Objective . 11 1.6 Research Questions . 12 1.7 Theoretical Framework . 12 1.8 Methodology . 14 1.9 Thesis Layout . 15 CHAPTER TWO: LITERATURE REVIEW . 21 2.
A magnetic resonance imaging-based articulatory and acoustic study of "retroflex" and "bunched" American English /r/.

Speakers of rhotic dialects of North American English show a range of different tongue configurations for /r/. These variants produce acoustic profiles that are indistinguishable for the first three formants [Delattre, P., and Freeman, D. C. , (1968). "A dialect study of American English r's by x-ray motion picture," Linguistics 44, 28-69; Westbury, J. R. et al. (1998), "Differences among speakers in lingual articulation for American English /r/," Speech Commun. 26, 203-206]. It is puzzling why this should be so, given the very different vocal tract configurations involved. In this paper, two subjects whose productions of "retroflex" /r/ and "bunched" /r/ show similar patterns of F1-F3 but very different spacing between F4 and F5 are contrasted. Using finite element analysis and area functions based on magnetic resonance images of the vocal tract for sustained productions, the results of computer vocal tract models are compared to actual speech recordings. In particular, formant-cavity affiliations are explored using formant sensitivity functions and vocal tract simple-tube models. The difference in F4/F5 patterns between the subjects is confirmed for several additional subjects with retroflex and bunched vocal tract configurations. The results suggest that the F4/F5 differences between the variants can be largely explained by differences in whether the long cavity behind the palatal constriction acts as a half- or a quarter-wavelength resonator.
Dual‐affinity avidin molecules

A recently reported dual‐chain avidin was modified further to contain two distinct, independent types of ligand‐binding sites within a single polypeptide chain. Chicken avidin is normally a tetrameric glycoprotein that binds water‐soluble d‐biotin with extreme affinity (Kd ≈ 10−15 M). Avidin is utilized in various applications and techniques in the life sciences and in the nanosciences. In a recent study, we described a novel avidin monomer‐fusion chimera that joins two circularly permuted monomers into a single polypeptide chain. Two of these dual‐chain avidins were observed to associate spontaneously to form a dimer equivalent to the wt tetramer. In the present study, we successfully used this scaffold to generate avidins in which the neighboring biotin‐binding sites of dual‐chain avidin exhibit two different affinities for biotin. In these novel avidins, one of the two binding sites in each polypeptide chain, the pseudodimer, is genetically modified to have lower binding affinity for biotin, whereas the remaining binding site still exhibits the high‐affinity characteristic of the wt protein. The pseudotetramer (i.e., a dimer of dual‐chain avidins) has two high and two lower affinity biotin‐binding sites. The usefulness of these novel proteins was demonstrated by immobilizing dual‐affinity avidin with its high‐affinity sites. The sites with lower affinity were then used for affinity purification of a biotinylated enzyme. These “dual‐affinity” avidin molecules open up wholly new possibilities in avidin–biotin technology, where they may have uses as novel bioseparation tools, carrier proteins, or nanoscale adapters. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Y-Chromosome Variation in Altaian Kazakhs Reveals a Common Paternal Gene Pool for Kazakhs and the Influence of Mongolian Expansions

Kazakh populations have traditionally lived as nomadic pastoralists that seasonally migrate across the steppe and surrounding mountain ranges in Kazakhstan and southern Siberia. To clarify their population history from a paternal perspective, we analyzed the non-recombining portion of the Y-chromosome from Kazakh populations living in southern Altai Republic, Russia, using a high-resolution analysis of 60 biallelic markers and 17 STRs. We noted distinct differences in the patterns of genetic variation between maternal and paternal genetic systems in the Altaian Kazakhs. While they possess a variety of East and West Eurasian mtDNA haplogroups, only three East Eurasian paternal haplogroups appear at significant frequencies (C3*, C3c and O3a3c*). In addition, the Y-STR data revealed low genetic diversity within these lineages. Analysis of the combined biallelic and STR data also demonstrated genetic differences among Kazakh populations from across Central Asia. The observed differences between Altaian Kazakhs and indigenous Kazakhs were not the result of admixture between Altaian Kazakhs and indigenous Altaians. Overall, the shared paternal ancestry of Kazakhs differentiates them from other Central Asian populations. In addition, all of them showed evidence of genetic influence by the 13th century CE Mongol Empire. Ultimately, the social and cultural traditions of the Kazakhs shaped their current pattern of genetic variation.
Effects of Short-Term Nutritional Interventions on Right Ventricular Function in Healthy Men

Background A physiological model of increased plasma nonesterified fatty acid (NEFA) levels result in myocardial triglyceride (TG) accumulation, which is related to cardiac dysfunction. A pathophysiological model of increased plasma NEFA levels result in hepatic steatosis, which has been linked to abnormal myocardial energy metabolism. Hepatic steatosis is accompanied by hepatic inflammation, reflected by plasma cholesteryl ester transfer protein (CETP) levels. The current study aimed to investigate effects of these models via different nutritional interventions on right ventricular (RV) function. Methods Fifteen men (age 25.0±6.6 years) were included and underwent magnetic resonance imaging and spectroscopy in this prospective crossover intervention study. RV function, myocardial and hepatic TG content, and CETP levels were assessed on three occasions: after normal diet, very low-calorie diet (VLCD, physiological model) and high-fat high-energy (HFHE, pathophysiological model) diet (all 3-days diets, randomly ordered, washout phase at least 14 days). Results VLCD induced a decrease in mean E deceleration by 27%. Myocardial TG content increased by 55%, whereas hepatic TG content decreased by 32%. Plasma CETP levels decreased by 14% (all P<0.05). HFHE diet induced a decrease in E/A by 19% (P<0.05). Myocardial TG content did not change, whereas hepatic TG content increased by 112% (P<0.01). Plasma CETP levels increased by 14% (P<0.05). Conclusions These findings show that RV diastolic function is impaired after short-term VLCD and HFHE diet in healthy men, respectively a physiological and a pathophysiological model of increased plasma NEFA levels. After short-term VLCD, myocardial lipotoxicity may be of importance in decreased RV diastolic function. RV diastolic dysfunction is accompanied by increased hepatic TG content and plasma CETP levels after short-term HFHE diet, suggesting that systemic inflammation reflecting local macrophage infiltration in the heart may be involved in RV dysfunction.
Enhancing Genetic Algorithms using Multi Mutations

Mutation is one of the most important stages of the genetic algorithm because of its impact on the exploration of global optima, and to overcome premature convergence. There are many types of mutation, and the problem lies in selection of the appropriate type, where the decision becomes more difficult and needs more trial and error. This paper investigates the use of more than one mutation operator to enhance the performance of genetic algorithms. Novel mutation operators are proposed, in addition to two selection strategies for the mutation operators, one of which is based on selecting the best mutation operator and the other randomly selects any operator. Several experiments on some Travelling Salesman Problems (TSP) were conducted to evaluate the proposed methods, and these were compared to the well-known exchange mutation and rearrangement mutation. The results show the importance of some of the proposed methods, in addition to the significant enhancement of the genetic algorithm's performance, particularly when using more than one mutation operator.
Ventral tegmental area deep brain stimulation for refractory chronic cluster headache

Objective: To present outcomes in a cohort of medically intractable chronic cluster headache (CCH) patients treated with ventral tegmental area (VTA) deep brain stimulation (DBS). Methods: In an uncontrolled open-label prospective study, 21 patients (17 male; mean age 52 years) with medically refractory CCH were selected for ipsilateral VTA-DBS by a specialist multidisciplinary team including a headache neurologist and functional neurosurgeon. Patients had also failed or were denied access to occipital nerve stimulation within the UK National Health Service. The primary endpoint was improvement in the headache frequency. Secondary outcomes included other headache scores (severity, duration, headache load), medication use, disability and affective scores, quality of life (QoL) measures, and adverse events. Results: Median follow-up was 18 months (range 4–60 months). At the final follow-up point, there was 60% improvement in headache frequency (p = 0.007) and 30% improvement in headache severity (p = 0.001). The headache load (a composite score encompassing frequency, severity, and duration of attacks) improved by 68% (p = 0.002). Total monthly triptan intake of the group dropped by 57% posttreatment. Significant improvement was observed in a number of QoL, disability, and mood scales. Side effects included diplopia, which resolved in 2 patients following stimulation adjustment, and persisted in 1 patient with a history of ipsilateral trochlear nerve palsy. There were no other serious adverse events. Conclusions: This study supports that VTA-DBS may be a safe and effective therapy for refractory CCH patients who failed conventional treatments. Classification of evidence: This study provides Class IV evidence that VTA-DBS decreases headache frequency, severity, and headache load in patients with medically intractable chronic cluster headaches.
Topics in Nonlinear and Robust Estimation Theory

We propose new methods to improve nonlinear filtering and robust estimation algorithms. In the first part of the dissertation, we propose an approach to approximating the ChapmanKolmogorov equation (CKE) for particle-based nonlinear filtering algorithms, using a new proposal distribution and the improved Fast Gauss Transform (IFGT). The new proposal distribution, used to obtain a Monte Carlo (MC) approximation of the CKE, is based on the proposal distribution found in the auxiliary marginal particle filter (AMPF). By using MC integration to approximate the integrals of the AMPF proposal distribution as well as the CKE, we demonstrate significant improvement in terms of both error and computation time. We consider the additive state noise case where the evaluation of the CKE is equivalent to performing kernel density estimation (KDE), thus fast methods such as the IFGT can be used. We also provide much improved performance bounds for the IFGT, and which unlike the previous bound, are consistent with the expectation that the error decreases as the truncation order of the IFGT increases. The experimental results show that we can obtain similar error to the sequential importance sampling (SIS) particle filter, while using fewer particles. In the second part, we consider the problem of estimating a Gaussian random parameter vector that is observed through a linear transformation with added white Gaussian noise when there are both eigenvalue and elementwise uncertainties in the covariance matrix. When the covariance matrix is known then the solution to the problem is given by the minimum mean squared error (MMSE) estimator. Recently a minimax approach in which the estimator is chosen to minimize the worst case of two criteria called the difference regret [28] and the ratio regret [29] in an eigenvalue uncertainty region was proposed. A closed form solution was also presented under the assumption that the Gram matrix of the model matrix weighted by the inverse covariance matrix of the noise vector, and the random parameter’s covariance matrix, are diagonalized by the same unitary matrix (we refer to this as the joint diagonalizability assumption). This assumption significantly limits the applicability of the