Miracle-dz/UniFAR-FTUs huggingface dataset:
Behavioural effects of single-cell stimulation in Barrel cortex

markdownabstractRodents rely mostly on their whiskers to explore their environment and a large part of their primary somatosensory cortex, called barrel cortex, is dedicated to whisker perception. Several different cell types in barrel cortex were stimulated to explore its effect on perception of a simple whisker movement. For long, it was suspected that interneurons have an inhibitory effect on behaviour and perception. Our results show that stimulation of a single fast-spiking putative interneuron or a highly sensitive whisker responsive cell can actually enhance perception of a simple whisker movement. When stimulating a single non-responsive pyramidal cell, no perceptual bias was detected. These results suggest that animals decode neural activity in a detection task using a selective subset of neurons in the barrel cortex. Secondly, because it is known that stimulation of multiple cells in barrel cortex can lead to whisker movement, we wanted to determine which cell types play a role in this process. Several different cell types in layer 5 of barrel cortex were stimulated one at a time, but we had to conclude that single-cell stimulation in barrel cortex is not sufficient to elicit whisker movements.
Cognitive outcomes following contemporary treatment without cranial irradiation for childhood acute lymphoblastic leukemia.

BACKGROUND Treatment of acute lymphoblastic leukemia (ALL) has included the use of prophylactic cranial irradiation in up to 20% of children with high-risk disease despite known cognitive risks of this treatment modality. METHODS Patients enrolled on the St Jude ALL Total Therapy Study XV, which omitted prophylactic cranial irradiation in all patients, were assessed 120 weeks after completion of consolidation therapy (n = 243) using a comprehensive cognitive battery. χ(2) analysis was used to compare the percentage of below-average performers among the entire ALL patient group to the expected rate based on the normative sample. Univariate logistic regression was used to estimate the effect of intensity of chemotherapy (treatment arm), age at diagnosis, and sex on the probability of below-average performance. All statistical tests were two-sided. RESULTS Overall, the ALL group had a statistically significantly higher risk for below-average performance on a measure of sustained attention (67.31% more than 1 SD below the normative mean for omission errors, P < .001) but not on measures of intellectual functioning, academic skills, or memory. Patients given higher intensity chemotherapy were at greater risk for below-average performance compared with those given lower intensity therapy on measures of processing speed (27.14% vs 6.25%, P = .009) and academic abilities (Math Reasoning: 18.60% vs 3.90%, P = .008; Word Reading: 20.00% vs 2.60%, P = .007; Spelling: 27.91% vs 3.90%, P = .001) and had higher parent-reported hyperactivity (23.00% vs 9.84%, P = .018) and learning problems (35.00% vs 16.39%, P = .005). Neither age at diagnosis nor sex was associated with risk for below-average cognitive performance. CONCLUSIONS Omitting cranial irradiation may help preserve global cognitive abilities, but treatment with chemotherapy alone is not without risks. Caregiver education and development of interventions should address both early attention deficits and cognitive late effects.
EuroPhenome: a repository for high-throughput mouse phenotyping data

The broad aim of biomedical science in the postgenomic era is to link genomic and phenotype information to allow deeper understanding of the processes leading from genomic changes to altered phenotype and disease. The EuroPhenome project (http://www.EuroPhenome.org) is a comprehensive resource for raw and annotated high-throughput phenotyping data arising from projects such as EUMODIC. EUMODIC is gathering data from the EMPReSSslim pipeline (http://www.empress.har.mrc.ac.uk/) which is performed on inbred mouse strains and knock-out lines arising from the EUCOMM project. The EuroPhenome interface allows the user to access the data via the phenotype or genotype. It also allows the user to access the data in a variety of ways, including graphical display, statistical analysis and access to the raw data via web services. The raw phenotyping data captured in EuroPhenome is annotated by an annotation pipeline which automatically identifies statistically different mutants from the appropriate baseline and assigns ontology terms for that specific test. Mutant phenotypes can be quickly identified using two EuroPhenome tools: PhenoMap, a graphical representation of statistically relevant phenotypes, and mining for a mutant using ontology terms. To assist with data definition and cross-database comparisons, phenotype data is annotated using combinations of terms from biological ontologies.
Mechanism of ubiquitin ligation and lysine prioritization by a HECT E3

Ubiquitination by HECT E3 enzymes regulates myriad processes, including tumor suppression, transcription, protein trafficking, and degradation. HECT E3s use a two-step mechanism to ligate ubiquitin to target proteins. The first step is guided by interactions between the catalytic HECT domain and the E2∼ubiquitin intermediate, which promote formation of a transient, thioester-bonded HECT∼ubiquitin intermediate. Here we report that the second step of ligation is mediated by a distinct catalytic architecture established by both the HECT E3 and its covalently linked ubiquitin. The structure of a chemically trapped proxy for an E3∼ubiquitin-substrate intermediate reveals three-way interactions between ubiquitin and the bilobal HECT domain orienting the E3∼ubiquitin thioester bond for ligation, and restricting the location of the substrate-binding domain to prioritize target lysines for ubiquitination. The data allow visualization of an E2-to-E3-to-substrate ubiquitin transfer cascade, and show how HECT-specific ubiquitin interactions driving multiple reactions are repurposed by a major E3 conformational change to promote ligation. DOI: http://dx.doi. org/10.7554/eLife.00828. 001
COMMENTARY Rewarding and Punishing Properties of Deep Brain Stimulation: The Most Promising Entry Points for Constitutive Studies of Affective Experiences in Other Animal s... With Profound Psychiatric Implications for Human Consciousness and Psychiatric Therapeutics

Neither experimental psychology nor neuroscience has made much progress in understanding the constitution (the hard-problem) of consciousness, although affective issues are finally being intensively considered. Miskovic and colleagues provide a penetrating essay into the problem and the conceptual advances being made, without sufficient consideration of the critical role of animal brain research in such enterprises. I will argue that the task will be much easier when we integrate human and animal findings, especially because animal brain research—particularly with regard to the identification of rewarding and punishing brain systems (namely, the affective neuroscience strategy)—will be very useful in informing how primal affective states in humans are created from brain dynamics.
Comparison of the effects of cationic porphyrins on DNA properties: Influence of GC content of native and synthetic polymers

Interactions of meso‐tetra(4‐N‐methylpyridyl)porphyrin [TMpyP(4)], meso‐tetra(2‐N‐methylpyridyl)porphyrin [TMpyP(2)], and meso‐tetra(para‐N‐trimethylanilinium)porphyrin (TMAP) with several native and synthetic DNAs were studied by a variety of physical techniques: nmr (31P and 1H), absorption spectroscopy, viscosity, and flow dichroism (FD). Of the three porphyrins studied, only the interaction of TMpyP(4) with poly [d(G‐C)2] was fully consistent with intercalation. In particular, a large increase in viscosity, a downfield 31P‐nmr signal (ca. ‐1 ppm), and upfield imino proton signals (11 to 12 ppm range) were observed. Comparison of the effects of TMpyP(4) on DNAs of different GC contents revealed larger changes in solution viscosity with increased GC content. However, the characteristic changes in 31P‐ and 1H‐nmr spectra were not observed. The viscosity increases observed in studies with poly[d(A‐C)(G‐T)] and C. Perf. DNA were much lower than with poly[d(G‐C)2], M. Lys. DNA, and calf thymus DNA. Thus, GC sequence and content are clearly important. The principal change in the 31P‐nmr signal of native DNA is the appearance of a very broad shoulder centered at ca. ‐2.0 ppm, which is larger in M. Lys. DNA than in C. Perf. DNA. FD studies indicate highly ordered TMpyP(4) cations arranged perpendicular to the DNA axis of calf thymus DNA. Together, these results suggest the major effects of TMpyP(4) on DNA properties are due to strong GC‐binding interactions that influence DNA structure. The data are consistent with combined intercalative and outside binding interactions of TMpyP(4) with GC regions of DNA. In contrast, similar studies with TMAP suggest that it influences AT regions of DNA by an outside binding mode. On the other hand, TMpyP(2) effects on DNA properties are consistent with nonselective outside binding.
Jacobi Elliptic Cliffordian Functions

The well-known Jacobi elliptic functions sn(z), cn(z), dn(z) are defined in higher dimensional spaces by the following method. Consider the Clifford algebra of the antieuclidean vector space of dimension 2m + 1. Let x be the identity mapping on the space of scalars + vectors. The holomorphic Cliffordian functions may be viewed roughly as generated by the powers of x, namely xn , their derivatives, their sums, their limits (cf: zn for classical holomorphic functions). In that context it is possible to define the same type of functions as Jacobi's.
New Insights in to the Intrinsic and Acquired Drug Resistance Mechanisms in Mycobacteria

Infectious diseases caused by clinically important Mycobacteria continue to be an important public health problem worldwide primarily due to emergence of drug resistance crisis. In recent years, the control of tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (MTB), is hampered by the emergence of multidrug resistance (MDR), defined as resistance to at least isoniazid (INH) and rifampicin (RIF), two key drugs in the treatment of the disease. Despite the availability of curative anti-TB therapy, inappropriate and inadequate treatment has allowed MTB to acquire resistance to the most important anti-TB drugs. Likewise, for most mycobacteria other than MTB, the outcome of drug treatment is poor and is likely related to the high levels of antibiotic resistance. Thus, a better knowledge of the underlying mechanisms of drug resistance in mycobacteria could aid not only to select the best therapeutic options but also to develop novel drugs that can overwhelm the existing resistance mechanisms. In this article, we review the distinctive mechanisms of antibiotic resistance in mycobacteria.
Molekulare Variabilität der monogenen peripheren Neuropathien

Zusammenfassung Die Charcot-Marie-Tooth-(CMT-)Erkrankungen, synonym zu den hereditären motorischen und sensiblen Neuropathien (HMSN), umfassen eine klinisch und genetisch heterogene Gruppe von Erkrankungen des peripheren Nervensystems. Traditionell wird zwischen demyelinisierender (CMT1, Dejerine-Sottas-Syndrom [DSS] und CMT4) sowie axonaler Form (CMT2) unterschieden. Bei etwa 70% der Patienten mit demyelinisierender Form liegt eine 1,4 Mb große Tandem-Duplikation im Chromosom 17p11.2-12 (CMT Typ 1A) vor. Die reziproke Deletion ist die häufigste Ursache der familiären rekurrierenden Neuropathie (HNPP, auch tomakulöse Neuropathie genannt). Die beiden Erkrankungen werden auf einen jeweils entgegengesetzten Gendosiseffekt des peripheren Myelinprotein-22-Gens (PMP22) zurückgeführt. Die intensive Forschung der vergangenen 11 Jahre hat zur Kenntnis von etwa 10 ursächlichen Genen und über 30 assoziierten Genorten geführt. Die Kenntnisse über die vielfältigen ursächlichen Gene haben auch zu einem differenzierteren Verständnis der häufig gemischt axonaldemyelinisierenden Phänotypen geführt. Die Analyse dieser Gene und Proteine wird zu weiteren Einsichten in die molekulare und zelluläre Basis des neuronalen Metabolismus und damit der peripheren Neuropathien führen.
On infinite-horizon probabilistic properties and stochastic bisimulation functions

This work investigates infinite-horizon properties over discrete-time stochastic models with continuous state spaces. The focus is on understanding how the structural features of a model (e.g., the presence of absorbing sets) affect the values of these properties and relate to their uniqueness. Furthermore, we argue that the investigation of these features can lead to approximation bounds for the value of such properties, as well as to improvements on their computation. The article employs the presented results to find a stochastic bisimulation function of two processes.
Dynamic Stereotypes about Women and Men in Latin America and the United States

To test the hypothesis that a group undergoing social change is believed to adopt traits associated with its new roles, this study examined perceptions of women and men of the past, present, and future in Brazil, Chile, and the United States. These dynamic stereotypes, which are present-day beliefs about a group as changing its characteristics, followed the specific profile of role change in each nation. The perception of men as increasing in masculine characteristics, which was found only in Chile and Brazil, cohered with changes in their roles following industrialization and democratization. The perception of women as increasing in masculine characteristics, which was found in all three nations, cohered with their increasing participation in public roles.
On speech quality assessment of artificial bandwidth extension

During the transition to wideband speech telephony, artificial bandwidth extension (ABE) could help to preserve customer satisfaction by enhancing speech quality in case of narrowband (NB) calls. However, the assessment of speech quality for ABE systems is still an open question. In the literature, instrumental measures are often used to judge the quality of ABE solutions. When subjective listening tests are considered, they most often use a comparison category rating (CCR) scale and, more rarely, an absolute category rating (ACR) scale. This paper investigates the relevance of instrumental and subjective assessment methods for ABE systems. An ACR and a CCR test are organized. Their results are compared and discussed. Discrepancies between these two tests open the discussion for the design of a proper subjective listening test for ABE systems. Some instrumental measures are also evaluated. A poor correlation between these measures and the subjective results is observed.
Fair load-side control for frequency regulation in smart grids

Frequency control rebalances supply and demand while maintaining the network state within operational margins. It is implemented using fast ramping reserves that are expensive and non-renewable, and which are expected to grow with the increasing penetration of renewables. The most promising solution to this problem is the use of demand response, i.e. load participation in frequency control. Yet it is still unclear how to efficiently integrate load participation without introducing instabilities and violating operational constraints. In this paper we present a comprehensive load-side frequency control mechanism that can maintain the grid within operational constraints. Our controllers can rebalance supply and demand after disturbances, restore the frequency to its nominal value and preserve inter-area power flows. Furthermore, our controllers are distributed (unlike generation-side), fair among participating loads, and can further maintain line flows within thermal limits. We prove that such a distributed load-side control is globally asymptotically stable and illustrate its convergence with simulation.
Tumor Targeting, Trifunctional Dendritic Wedge

We report in vitro and in vivo evaluation of a newly designed trifunctional theranostic agent for targeting solid tumors. This agent combines a dendritic wedge with high boron content for boron neutron capture therapy or boron MRI, a monomethine cyanine dye for visible-light fluorescent imaging, and an integrin ligand for efficient tumor targeting. We report photophysical properties of the new agent, its cellular uptake and in vitro targeting properties. Using live animal imaging and intravital microscopy (IVM) techniques, we observed a rapid accumulation of the agent and its retention for a prolonged period of time (up to 7 days) in fully established animal models of human melanoma and murine mammary adenocarcinoma. This macromolecular theranostic agent can be used for targeted delivery of high boron load into solid tumors for future applications in boron neutron capture therapy.
Intransigent or ‘Sticky’ Symptoms: Hypnotherapy and the Deconstruction of Ambivalence

Previous work has shown that intransigent symptomatic behaviour can be seen as reflecting the conservation of an ambivalent autonomy in family systems. Such behaviour often implies, expresses, and even recursively conserves certain ambivalent meanings that in time have become central to and entrenched in the system. All members of the system either knowingly or unwittingly contribute to the maintenance of these ideas which then find expression in symptomatic behaviour. If treatment is aimed at the symptomatic behaviour itself it often encourages the conservation of the ambivalent ideas underlying the symptoms and the symptoms then also remain. This is when symptoms do not readily respond to treatment, when they become resistant or ‘sticky’. Seen in this light treatment should rather be aimed at the co-operative deconstruction of the entrenched meanings, helping them to transform into more functional, less ambivalent, understandings and actions. It is the aim in this paper to show by means of a case description how hypnosis and the meanings generally attributed to it can be employed, as part of psychotherapy, for this purpose. This involves the use of hypnosis to gain a co-created understanding or reframing of the ambivalent ideas while simultaneously being respectful of the symptom, followed by suggested actions coherent with this new understanding, leading to ‘spontaneous’ (hypnotic) disappearance of the symptom.
Properties of chloride-stimulated 45Ca flux in skinned muscle fibers

Isometric force and 45Ca loss from fiber to bath were measured simultaneously in skinned fibers from frog muscle at 19 degrees C. In unstimulated fibers, 45Ca efflux from the sarcoplasmic reticulum (SR) was very slow, with little or no dependence on EGTA (0.1-5 mM) or Mg++ (20 micrometer-1.3 mM). Stimulation by high [Cl] at 0.11 mM Mg++ caused rapid force transients (duration approximately 10 s) and 45Ca release. This response was followed for 55 s, with 5 mM EGTA added to chelate myofilament space (MFS) Ca either (a) after relaxation, (b) near the peak of the force spike, or (c) before or with the stimulus. When EGTA was present during Cl application, stimulation of 45Ca release was undetectable. Analysis of the time-course of tracer loss during the three protocols showed that when EGTA was absent, 16% of the fiber tracer was released from the SR within approximately 3 s, and 70% of the tracer still in the MFS near the peak of the force spike was subsequently reaccumulated. The results suggest that (a) the Cl response is highly Ca-dependent; (b) stimulation increases 45Ca efflux from the SR at least 100-200-fold; and (c) the rate of reaccumulation is much slower than the influx predicted from published data on resting fibers, raising the possibility that depolarization inhibits active Ca transport by the SR.
Evangelising Language Technology: A Practically-Focussed Undergraduate Program

This paper describes an undergraduate program in Language Technology that we have developed at Macquarie University. We question the industrial relevance of much that is taught in NLP courses, and emphasize the need for a practical orientation as a means to growing the size of the field. We argue that a more evangelical approach, both with regard to students and industry, is required. The paper provides an overview of the material we cover, and makes some observations for the future on the basis of our experiences so far.
Discrete Optimization A taxonomy and an empirical analysis of multiple objective ant colony optimization algorithms for the bi-criteria TSP q

The difficulty to solve multiple objective combinatorial optimization problems with traditional techniques has urged researchers to look for alternative, better performing approaches for them. Recently, several algorithms have been proposed which are based on the ant colony optimization metaheuristic. In this contribution, the existing algorithms of this kind are reviewed and a proposal of a taxonomy for them is presented. In addition, an empirical analysis is developed by analyzing their performance on several instances of the bi-criteria traveling salesman problem in comparison with two wellknown multi-objective genetic algorithms. � 2006 Elsevier B.V. All rights reserved.
Genome-Wide Analysis Studies and Chronic Kidney Disease

In recent years, the very high worldwide prevalence of chronic kidney disease (CKD) has led some authors to talk of an “epidemic. ” The progression of CKD varies considerably among individuals despite similar aetiologies, optimal blood pressure, and glycaemic control. Over the last decade, through genome-wide association studies (GWAS), more than 50 genetic loci have been identified in association with CKD. Understanding the genetic basis of CKD could provide a better knowledge of the biology of the involved pathways, thus potentially leading to novel tools for the diagnosis, prevention, and therapy of CKD. In this review, we will analyse the role of GWAS in the study of CKD.
Parasympathetic cerebrovascular innervation: an anterograde tracing from the sphenopalatine ganglion in the rat.

To elucidate parasympathetic cerebrovascular innervation of the rat sphenopalatine ganglion (SPG), we injected wheat germ agglutinin-conjugated horseradish peroxidase into the SPG of one side and traced anterogradely labeled nerve fibers. Three days after the injection, the animals were killed and tissues including the SPG, major cerebral arteries, and ethmoidal arteries were reacted by the tetramethylbenzidine method. A number of cells and nerve fibers labeled with wheat germ agglutinin-conjugated horseradish peroxidase were observed in the SPG. The nasal mucous membrane, the periorbital soft tissue, and the lacrimal gland of the injected side contained numerous labeled nerve fibers. In cerebral vessels, anterogradely labeled nerve fibers were observed around the internal ethmoidal, anterior cerebral, middle cerebral, internal carotid, and posterior cerebral arteries of both sides. A few labeled nerve fibers were seen on the wall of the basilar arteries of the distal portion, and the vertebral arteries contained no labeled nerve fiber. In animals of which the ethmoidal nerve and the external ethmoidal artery were cut together with the surrounding periorbital soft tissues just before entering the ethmoidal foramen, no labeled nerve fiber was identified on the wall of the major cerebral arteries. Although labeled gangliocytes were found in the trigeminal and superior cervical ganglia after the tracer injection to the ipsilateral SPG, the chronic maxillary neurotomy and superior cervical ganglionectomy did not alter the distribution of the labeled nerve fibers on the wall of the cerebral arteries. (ABSTRACT TRUNCATED AT 250 WORDS)