Miracle-dz/UniFAR-FTUs huggingface dataset:
The COUP-TFII/Neuropilin-2 is a molecular switch steering diencephalon-derived GABAergic neurons in the developing mouse brain

Significance Recently the preoptic area (POa) has been shown to be a source of GABAergic neurons in the medial amygdala and cerebral cortex, where they are thought to play a pivotal role in emotions and intelligence, respectively. However, it is unknown how the POa-derived neurons migrate and selectively segregate into either the amygdala or cortex. By using focal in utero labeling of the POa, we show that switching on/off the transcription factor COUP-TFII (Chicken ovalbumin upstream promoter transcription factor II) and the receptor Neuropilin-2 (Nrp2) directs the POa-derived neurons toward either the amygdala or cortex. Our study revealed an essential role of COUP-TFII/Nrp2 expression dynamics in the development of the amygdala and cortex. The preoptic area (POa) of the rostral diencephalon supplies the neocortex and the amygdala with GABAergic neurons in the developing mouse brain. However, the molecular mechanisms that determine the pathway and destinations of POa-derived neurons have not yet been identified. Here we show that Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII)–induced expression of Neuropilin-2 (Nrp2) and its down-regulation control the destination of POa-derived GABAergic neurons. Initially, a majority of the POa-derived migrating neurons express COUP-TFII and form a caudal migratory stream toward the caudal subpallium. When a subpopulation of cells steers toward the neocortex, they exhibit decreased expression of COUP-TFII and Nrp2. The present findings show that suppression of COUP-TFII/Nrp2 changed the destination of the cells into the neocortex, whereas overexpression of COUP-TFII/Nrp2 caused cells to end up in the medial part of the amygdala. Taken together, these results reveal that COUP-TFII/Nrp2 is a molecular switch determining the pathway and destination of migrating GABAergic neurons born in the POa.
Rhizobium Attachment to Clover Roots

SUMMARY The adhesion of rhizobia to surfaces of clover roots was examined by an indirect plate-counting assay and phase-contrast microscopy. The number of Rhizobium trifolii cells attached to clover root segments increased in approximately linear fashion during the first hour of incubation, but did not change appreciably thereafter. The addition of 30 mm-2-deoxy-d-glucose, which effectively inhibits binding of clover root lectin, did not promote the release of previously attached bacteria nor inhibit subsequent attachment to either root segments or root hairs. Rhizobia of several heterologous species attached to clover roots in numbers comparable to those of strains of R. trifolii, the homologous species. These results indicate that rhizobia have effective mechanisms of adhesion to non-host roots and that clover lectin contributed little or nothing to attachment under the conditions examined.
Pharmacogenomic assessment of cisplatin-based chemotherapy outcomes in ovarian cancer.

AIM Cisplatin and its analogs are potent antitumor agents. However, their use is restricted by significant variability in tumor response and toxicity. There is a great need to identify genetic markers to predict the most important adverse events and patient outcomes. MATERIALS & METHODS We have evaluated the association between polymorphisms in 106 genes involved mainly in xenobiotic metabolism, DNA repair, the cell cycle and apoptosis, and outcomes in 104 ovarian cancer patients receiving cisplatin-cyclophosphamide chemotherapy. Arrayed primer extension technology was used to genotype 228 SNPs. RESULTS Ten SNPs in nine genes were found to be associated with one or more of the assessed clinical end points. SNPs in TPMT and NQO1 were significantly associated with progression-free survival. Polymorphisms in ERCC5, RAD52, MUTYH and LIG3 correlated with the occurrence of severe neutropenia. SNPs in NAT2 and EPHX1 were associated with anemia and nephrotoxicity, respectively. A SNP in ADH1C was correlated with complete tumor response. CONCLUSION The results obtained suggest that SNPs in different genes involved in drug metabolism can be important in identifying patients at risk for nonresponse to or toxicity from cisplatin-based treatment.
The Effects of Gasdynamics, Cooling, Star Formation, and Numerical Resolution in Simulations of Cluster Formation

We present the analysis of a suite of simulations of a Virgo-mass galaxy cluster. Undertaken within the framework of standard cold dark matter cosmology, these simulations were performed at differing resolutions and with increasingly complex physical processes, with the goal of identifying the effects of each on the evolution of the cluster. We focus on the cluster at the present epoch and examine properties including the radial distributions of density, temperature, entropy, and velocity. We also map "observable" projected properties such as the surface mass density, X-ray surface brightness, and Sunyaev-Zeldovich signature. We identify significant differences between the simulations, which highlights the need for caution when comparing numerical simulations to observations of galaxy clusters. While resolution affects the inner density profile in dark matter simulations, the addition of a gaseous component, especially one that cools and forms stars, affects the entire cluster. For example, in simulations with gasdynamics but no cooling, improving the gravitational force resolution from 200 to 14 kpc increases the X-ray luminosity and emission-weighted temperature by factors of 2.9 and 1.6, respectively, and it changes the form of the X-ray surface brightness and temperature profiles. At the higher resolution, a simulation that includes cooling and star formation converts 30% of the cluster baryons into stars and produces a massive central galaxy that substantially alters the cluster potential well. This cluster has 20% higher X-ray luminosity and 30% higher emission-weighted temperature than the corresponding cluster in the no-cooling simulation. Its properties are reasonably close to those of observed X-ray dominant (XD) clusters, with conversion of cooled gas into stars greatly reducing the observational conflicts found by Suginohara & Ostriker in simulations with cooling but no star formation. We conclude that both resolution and included physical processes play important roles in simulating the formation and evolution of galaxy clusters. Therefore, physical inferences drawn from simulations that do not include gaseous components that can cool and form stars present a poor representation of reality.
Redoubtable Sensor Networks

We give, for the first time, a precise mathematical analysis of the connectivity and security properties of sensor networks that make use of the random predistribution of keys. We also show how to set the parameters---pool and key ring size---in such a way that the network is not only connected with high probability via secure links but also provably resilient, in the following sense: We formally show that any adversary that captures sensors at random with the aim of compromising a constant fraction of the secure links must capture at least a constant fraction of the nodes of the network. In the context of wireless sensor networks where random predistribution of keys is employed, we are the first to provide a mathematically precise proof, with a clear indication of parameter choice, that two crucial properties---connectivity via secure links and resilience against malicious attacks---can be obtained simultaneously. We also show in a mathematically rigorous way that the network enjoys another strong security property. The adversary cannot partition the network into two linear size components, compromising all the links between them, unless it captures linearly many nodes. This implies that the network is also fault tolerant with respect to node failures. Our theoretical results are complemented by extensive simulations that reinforce our main conclusions.
Open junctions in the endothelium of the postcapillary venules of the diaphragm

We have previously established that approximately 30% of the endothelial junctions in the pericytic venules of the mouse diaphragm are open to a gap of approximately 30--60 A, and are fully permeated by hemeundecapeptide (H11P) (mol diam approximately 20 A). To estimate the size limit for molecules that can permeate these junctions, we have administered graded tracers intravenously and studied their behavior at the level of pericytic venules in bipolar microvascular fields (BMFs) in the mouse diaphragm. Horseradish peroxidase (HRP) (mol diam approximately 50 A) permeated only approximately 50% of the open junctions of the venular endothelium. Outflow through venular junctions appeared to be modest since the tracer remained restricted to the perivenular spaces. Hemoglobin (Hb, mol diam 64 x 55 x 50 A) permeated only a few (less than 5%), and ferritin (mol diam 110 A), practically none, of the endothelial junctions of the pericytic venules. The findings suggest that under normal conditions the size limit for permeant molecules for open venular junctions is approximately 60 A. Replicas of freeze-fracture preparations from appropriate regions in BMF showed that the intercellular junctions of the venular endothelium have the same organization as previously described for the corresponding segments of the microvasculature in the omentum and mesentery: discontinuous creases or grooves either free of or marked by few intramembrane particles only. Administration of histamine (topically or systemically) and 5-hydroxytryptamine (5-HT) (topically) resulted in typical focal separations of the endothelial junctions and intramural deposits of large tracer particles (carbon black) in the postcapillary venules.
A Scalable Multimedia Multicast Protocol for Emergency Systems

Emergency system and public safety have been of major concern to authorities of all countries in the world for the last decade. It is usually the case that multi- disciplinary rescuers may need to join hands in achieving a common goal; which implies a large number of people to be coordinated. However, the deployment of a multi-disciplinary emergency system and/or the deployment of a public safety system might involve a large number of nodes in ad hoc networks. On one side, scalability of ad hoc networks has always been a challenge mainly because of limited bandwidth and limited resources of the participating nodes. While on the other side, ensuring public safety and the solicitation of quick emergency responses are always desirable but remain challenging. This paper presents a scalable multimedia multicast protocol for emergency system (SCAMMES), based on the affinity of nodes' movement in a group and the localisation of emergency operations, to distribute multimedia efficiently in Large Ad hoc Networks for Emergency System (LANES).
Evaluation of 8q24 and 17q Risk Loci and Prostate Cancer Mortality

Purpose: Variants at chromosomal loci 8q24 and 17q are established risk factors for prostate cancer. Many studies have confirmed the findings for risk, but few have examined aggressiveness and other clinical variables in detail. Additionally, Gleason score is typically used as a surrogate for the primary end point of prostate cancer mortality. We investigated whether the 8q24 and 17q risk variants are associated with clinical variables as well as prostate cancer mortality. Experimental Design: In the Physicians' Health Study (1,347 cases and 1,462 controls), the Dana-Farber Harvard Cancer Center Specialized Program of Research Excellence (Gelb Center; 3,714 cases), and the Fred Hutchinson Cancer Research Center King County Case-Control Studies (1,308 cases and 1,266 controls), we examined eight previously identified 8q24 and 17q risk variants for association with prostate cancer mortality in men of European ancestry. We considered associations with other surrogate markers of prostate cancer aggressiveness, such as Gleason score, pathologic stage, prostate-specific antigen at diagnosis, and age at diagnosis. Results: Six of the eight variants were confirmed as prostate cancer risk factors. Several variants were nominally associated with age at diagnosis; when totaling all alleles for single nucleotide polymorphisms significantly associated with risk, each additional allele decreased age at diagnosis by an average of 6 months in the Physicians' Health Study (P = 0.0005) and 4 months in the Dana-Farber Harvard Cancer Center Specialized Program of Research Excellence (Gelb Center) cohort (P = 0.0016). However, there were no statistically significant associations with prostate cancer mortality. Conclusions: Our results suggest that the 8q24 and 17q prostate cancer risk variants may influence age at diagnosis but not disease aggressiveness.
Reconstruction of protein form with X-ray solution scattering and a genetic algorithm.

We have reconstructed, from experimental approximately 2 nm resolution X-ray solution scattering profiles, the corresponding shapes and sizes of myoglobin, troponin C, spermadhesin PSP-I/PSP-II, chymotrypsinogen A, superoxide dismutase, ovalbumin, tubulin, nitrite reductase, catalase, the structural change of troponin C upon dissociation of the two high affinity Ca(2+), and the solution model structure of a tandem pair of fibronectin type III cytoplasmic domains of integrin alpha6beta4 before determination of its crystal structure. To this purpose we have designed a new genetic algorithm which gradually explores a discrete search space and evolves convergent models made of several hundred beads (down to 0.3 nm radius) best fitting the scattering profile upon Debye calculation, without geometrical constraints or penalty for loose beads. This is a procedure of effective numerical transformation of the one-dimensional scattering profiles into three-dimensional model structures. The number of beads in models is correlated with the protein molecular mass (with one exception). The shape and approximate dimensions of each protein have been retrieved by a set of ten solution models, essentially superimposable with the available crystal structures.
Gabapentin for chronic neuropathic pain and fibromyalgia in adults.

BACKGROUND This review updates parts of two earlier Cochrane reviews investigating effects of gabapentin in chronic neuropathic pain (pain due to nerve damage). Antiepileptic drugs are used to manage pain, predominantly for chronic neuropathic pain, especially when the pain is lancinating or burning. OBJECTIVES To evaluate the analgesic effectiveness and adverse effects of gabapentin for chronic neuropathic pain management. SEARCH STRATEGY We identified randomised trials of gabapentin in acute, chronic or cancer pain from MEDLINE, EMBASE, and CENTRAL. We obtained clinical trial reports and synopses of published and unpublished studies from Internet sources. The date of the most recent search was January 2011. SELECTION CRITERIA Randomised, double-blind studies reporting the analgesic and adverse effects of gabapentin in neuropathic pain with assessment of pain intensity and/or pain relief, using validated scales. Participants were adults aged 18 and over. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data. We calculated numbers needed to treat to benefit (NNTs), concentrating on IMMPACT (Initiative on Methods, Measurement and Pain Assessment in Clinical Trials) definitions of at least moderate and substantial benefit, and to harm (NNH) for adverse effects and withdrawal. Meta-analysis was undertaken using a fixed-effect model. MAIN RESULTS Twenty-nine studies (3571 participants), studied gabapentin at daily doses of 1200 mg or more in 12 chronic pain conditions; 78% of participants were in studies of postherpetic neuralgia, painful diabetic neuropathy or mixed neuropathic pain. Using the IMMPACT definition of at least moderate benefit, gabapentin was superior to placebo in 14 studies with 2831 participants, 43% improving with gabapentin and 26% with placebo; the NNT was 5.8 (4.8 to 7.2). Using the IMMPACT definition of substantial benefit, gabapentin was superior to placebo in 13 studies with 2627 participants, 31% improving with gabapentin and 17% with placebo; the NNT was 6.8 (5.6 to 8.7). These estimates of efficacy are more conservative than those reported in a previous review. Data from few studies and participants were available for other painful conditions.Adverse events occurred significantly more often with gabapentin. Persons taking gabapentin can expect to have at least one adverse event (66%), withdraw because of an adverse event (12%), suffer dizziness (21%), somnolence (16%), peripheral oedema (8%), and gait disturbance (9%). Serious adverse events (4%) were no more common than with placebo.There were insufficient data for comparisons with other active treatments. AUTHORS' CONCLUSIONS Gabapentin provides pain relief of a high level in about a third of people who take if for painful neuropathic pain. Adverse events are frequent, but mostly tolerable. More conservative estimates of efficacy resulted from using better definitions of efficacy outcome at higher, clinically important, levels, combined with a considerable increase in the numbers of studies and participants available for analysis.
Towards Automated Binding Affinity Prediction Using an Iterative Linear Interaction Energy Approach

Binding affinity prediction of potential drugs to target and off-target proteins is an essential asset in drug development. These predictions require the calculation of binding free energies. In such calculations, it is a major challenge to properly account for both the dynamic nature of the protein and the possible variety of ligand-binding orientations, while keeping computational costs tractable. Recently, an iterative Linear Interaction Energy (LIE) approach was introduced, in which results from multiple simulations of a protein-ligand complex are combined into a single binding free energy using a Boltzmann weighting-based scheme. This method was shown to reach experimental accuracy for flexible proteins while retaining the computational efficiency of the general LIE approach. Here, we show that the iterative LIE approach can be used to predict binding affinities in an automated way. A workflow was designed using preselected protein conformations, automated ligand docking and clustering, and a (semi-)automated molecular dynamics simulation setup. We show that using this workflow, binding affinities of aryloxypropanolamines to the malleable Cytochrome P450 2D6 enzyme can be predicted without a priori knowledge of dominant protein-ligand conformations. In addition, we provide an outlook for an approach to assess the quality of the LIE predictions, based on simulation outcomes only.
Hunting for valuables from landfills and assessing their market opportunities A case study with Kudjape landfill in Estonia

Landfill mining is an alternative technology that merges the ideas of material recycling and sustainable waste management. This paper reports a case study to estimate the value of landfilled materials and their respective market opportunities, based on a full-scale landfill mining project in Estonia. During the project, a dump site (Kudjape, Estonia) was excavated with the main objectives of extracting soil-like final cover material with the function of methane degradation. In total, about 57,777 m3 of waste was processed, particularly the uppermost 10-year layer of waste. Manual sorting was performed in four test pits to determine the detailed composition of wastes. 11,610 kg of waste was screened on site, resulting in fine (<40 mm) and coarse (>40 mm) fractions with the share of 54% and 46%, respectively. Some portion of the fine fraction was sieved further to obtain a very fine grained fraction of <10 mm and analyzed for its potential for metals recovery. The average chemical composition of the <10 mm soil-like fraction suggests that it offers opportunities for metal (Cr, Cu, Ni, Pb, and Zn) extraction and recovery. The findings from this study highlight the importance of implementing best available site-specific technologies for on-site separation up to 10 mm grain size, and the importance of developing and implementing innovative extraction methods for materials recovery from soil-like fractions.
Connectionist Rules of Language

A modular connectionist network is described that learns the German verb paradigm. The architecture of the network is in accordance with the rule{associative memory hypothesis proposed by Pinker (1991): it is composed of a connectionist short-term memory enabling it to process symbolic rules and an associative memory acting as a lexicon. The network successfully learns the German verb paradigm and generalizes to novel verbs in ways that correspond to empirical data. Lesioning the model gives further evidence for the rule{ associative memory hypothesis: When the lexicon is cut oo, the network strongly overgeneralizes the regular participle , indicating that regular forms are produced with the short-term memory but irregular forms rely on the lexicon. However, in contrast to the rule{association theory, the two paths are not strongly dissociated, but both the short-term memory and the lexicon work together in producing many participles. The success of the network model is seen as evidence that emergent linguistic rules need not be implemented as rules in the brain.
The Determinants of Traditional Medicine Use in Northern Tanzania: A Mixed-Methods Study

Introduction Traditional medicines are an important part of healthcare in sub-Saharan Africa, and building successful disease treatment programs that are sensitive to traditional medicine practices will require an understanding of their current use and roles, including from a biomedical perspective. Therefore, we conducted a mixed-method study in Northern Tanzania in order to characterize the extent of and reasons for the use of traditional medicines among the general population so that we can better inform public health efforts in the region. Methods Between December 2013 and June 2014 in Kilimanjaro, Tanzania, we conducted 5 focus group discussions and 27 in-depth interviews of key informants. The data from these sessions were analyzed using an inductive framework method with cultural insider-outsider coding. From these results, we developed a structured survey designed to test different aspects of traditional medicine use and administered it to a random sample of 655 adults from the community. The results were triangulated to explore converging and diverging themes. Results Most structured survey participants (68%) reported knowing someone who frequently used traditional medicines, and the majority (56%) reported using them themselves in the previous year. The most common uses were for symptomatic ailments (42%), chronic diseases (15%), reproductive problems (11%), and malaria/febrile illnesses (11%). We identified five major determinants for traditional medicine use in Northern Tanzania: biomedical healthcare delivery, credibility of traditional practices, strong cultural identities, individual health status, and disease understanding. Conclusions In order to better formulate effective local disease management programs that are sensitive to TM practices, we described the determinants of TM use. Additionally, we found TM use to be high in Northern Tanzania and that its use is not limited to lower-income areas or rural settings. After symptomatic ailments, chronic diseases were reported as the most common reason for TM use which may be particularly important in Northern Tanzania where non-communicable diseases are a rapidly growing burden.