Miracle-dz/UniFAR-FTUs huggingface dataset:
Cue Integration in Spatial Search for Jointly Learned Landmarks but Not for Separately Learned Landmarks

The authors investigated how humans use multiple landmarks to locate a goal. Participants searched for a hidden goal location along a line between 2 distinct landmarks on a computer screen. On baseline trials, the location of the landmarks and goal varied, but the distance between each of the landmarks and the goal was held constant, with 1 landmark always closer to the goal. In Experiment 1, some baseline trials provided both landmarks, and some provided only 1 landmark. On probe trials, both landmarks were shifted apart relative to the previously learned goal location. Participants searched between the locations specified by the 2 landmarks and their search locations were shifted more toward the nearer landmark, suggesting a weighted integration of the conflicting landmarks. Moreover, the observed variance in search responses when both cues were presented in their normal locations was reduced compared to the variance on tests with single landmarks. However, the variance reduction and the weightings of the landmarks did not always show Bayesian optimality. In Experiment 2, some participants were trained only with each of the single landmarks. On subsequent tests with the 2 cues in conflict, searching did not shift toward the nearer landmark and the variance of search responses of these single-cue trained participants was larger than their variance on single-landmark tests, and even larger than the variance predicted by using the 2 landmarks alternatively on different trials. Taken together, these results indicate that cue combination occurs only when the landmarks are presented together during the initial learning experience.
Utility of dexrazoxane for the reduction of anthracycline-induced cardiotoxicity

Dexrazoxane is a derivative of the powerful metal-chelating agent ethyl enediamine tetra acetic acid. Its cardioprotective effect is thought to be due to its ability to chelate iron and reduce the number of metal ions complexed with anthracycline and, consequently, decrease the formation of superoxide radicals. Preclinical studies have confirmed that dexrazoxane has significant activity as a cardioprotective agent against anthracycline-induced cardiotoxicity. Dexrazoxane is well-tolerated, with myelosuppression being the dose-limiting toxicity in Phase I trials. The cardioprotective utility of dexrazoxane has been further illustrated in a number of randomized trials. In addition no significant difference in survival has been observed between the dexrazoxane and control arms of these trials but, in one, a significantly lower response rate was observed in the dexrazoxane compared to placebo arm. Further trials are required to evaluate the efficacy of dexrazoxane in hematological malignancies as well as the adjuvant treatment of breast cancer. Its use in the paediatric setting and in the management of elderly patients with cardiac comorbidity also requires investigation. Recently, interest has focused on the use of dexrazoxane as an antidote for anthracycline extravasation. In addition the general cytoprotective activity of this drug requires further assessment, as well as selectivity in this context.
Introduction of an single nucleodite polymorphism‐based “Major Y‐chromosome haplogroup typing kit” suitable for predicting the geographical origin of male lineages

The European Consortium “High‐throughput analysis of single nucleotide polymorphisms for the forensic identification of persons – SNPforID”, has performed a selection of candidate Y‐chromosome single nucleotide polymorphisms (SNPs) for making inferences on the geographic origin of an unknown sample. From more than 200 SNPs compiled in the phylogenetic tree published by the Y‐Chromosome Consortium, and looking at the population studies previously published, a package of 29 SNPs has been selected for the identification of major population haplogroups. A “Major Y‐chromosome haplogroup typing kit” has been developed, which allows the multiplex amplification of all 29 SNPs in a single reaction. Allele genotyping was performed with a single base extension reaction (minisequencing) detected by CE. The validation of the multiplex was performed in a total of 1126 unrelated males distributed among 12 worldwide populations. The approach takes advantage of the specific geographic distribution of the Y‐chromosome haplogroups and demonstrates the utility of binary polymorphisms to infer the origin of a male lineage.
Role of the immune modulator programmed cell death-1 during development and apoptosis of mouse retinal ganglion cells.

PURPOSE Mammalian programmed cell death (PD)-1 is a membrane-associated receptor regulating the balance between T-cell activation, tolerance, and immunopathology; however, its role in neurons has not yet been defined. The hypothesis that PD-1 signaling actively promotes retinal ganglion cell (RGC) death within the developing mouse retina was investigated. METHODS Mature retinal cell types expressing PD-1 were identified by immunofluorescence staining of vertical retina sections; developmental expression was localized by immunostaining and quantified by Western blot analysis. PD-1 involvement in developmental RGC survival was assessed in vitro using retinal explants and in vivo using PD-1 knockout mice. PD-1 ligand gene expression was detected by RT-PCR. RESULTS PD-1 is expressed in most adult RGCs and undergoes dynamic upregulation during the early postnatal window of retinal cell maturation and physiological programmed cell death (PCD). In vitro blockade of PD-1 signaling during this time selectively increases the survival of RGCs. Furthermore, PD-1-deficient mice show a selective increase in RGC number in the neonatal retina at the peak of developmental RGC death. Lastly, gene expression of the immune PD-1 ligand genes Pdcd1lg1 and Pdcd1lg2 was found throughout postnatal retina maturation. CONCLUSIONS These findings collectively support a novel role for a PD-1-mediated signaling pathway in developmental PCD during postnatal RGC maturation.
Legal considerations surrounding surrogacy in Ukraine.

OBJECTIVE The aim of the study is to analyze the legal framework regulating surrogacy relations in Ukraine, its main loopholes and collisions, and provide suggestions to improve the Ukrainian legislation on surrogacy. PATIENTS AND METHODS Materials and methods: The methodological framework of the research consists of general methods of analysis and synthesis, formal logical method and formal legal method. CONCLUSION Conclusions: The procedure for the implementation of surrogacy in Ukraine is enshrined in several regulatory acts. Ukrainian legislation has some loopholes and collisions, representing the challenges that have to be addressed in the nearest future. It is necessary to reconsider the existing legal acts to strengthen state control and supervision in this area for proper protection of the rights and responsibilities of subjects entering surrogate agreements.
Balanced Versus Single-Ended Detection of DPSK: Degraded Advantage Due to Fiber Nonlinearities

We study the effect of nonlinear transmission on the receiver sensitivity advantage of differential-phase-shift-keying systems using balanced detection. We show how the accumulation of nonlinear phase noise owing to the Gordon-Mollenauer effect reduces the advantage of balanced detection, until it is completely eliminated in highly nonlinear scenarios. The results of our analysis are consistent with existing experimental observations
Effects of a modified-live virus vaccine against porcine reproductive and respiratory syndrome in boars.

OBJECTIVES To determine whether vaccine virus is found in serum and semen of vaccinated boars, whether vaccination prevents subsequent shedding of wild-type virus after challenge exposure, and whether semen and blood variables are altered after vaccination or challenge exposure with wild-type virus, or both. DESIGN Throughout the 50-day postvaccination period, serum and semen from exposed boars were evaluated for the presence of porcine reproductive and respiratory syndrome virus (PRRSV). All boars were then challenge-exposed with PRRSV isolate VR-2332 and evaluated for an additional 27 days. Semen quality variables, serostatus, and blood variables were monitored. ANIMALS 7 PRRSV-seronegative adult boars. PROCEDURE Semen was collected 3 times weekly and evaluated by use of a nested reverse-transcriptase polymerase chain reaction for detection of PRRSV RNA. Serum was obtained weekly and evaluated by nested reverse-transcriptase polymerase chain reaction, virus isolation, and PRRSV ELISA. Semen quality variables were evaluated 3 times weekly, and CBC was performed weekly. RESULTS Vaccine virus was shed in the semen of all vaccinated boars, but shedding was of shorter duration in 4 of 5 vaccinated boars than that generally observed after exposure to wild-type virus. After challenge exposure, shedding of wild-type virus in semen was shortened or eliminated in 4 of 5 vaccinated boars. Percentage of forward movement and normal spermatozoal morphology and motility were significantly reduced in vaccinated boars after challenge exposure. CONCLUSIONS Vaccine virus was shed in semen of vaccinated boars, but vaccination generally reduced or eliminated shedding of wild-type PRRSV after challenge exposure. Semen quality appeared to be less than optimal, particularly after vaccination and subsequent challenge exposure with wild-type virus. CLINICAL RELEVANCE Extra-label use of the PRRSV vaccine in boars remains controversial because some boars may still shed wild-type virus in semen after challenge exposure at postvaccination day 50. Semen quality also appeared to be altered after vaccination and subsequent challenge exposure.
Reflection on modern methods: trial emulation in the presence of immortal-time bias. Assessing the benefit of major surgery for elderly lung cancer patients using observational data

Abstract Acquiring real-world evidence is crucial to support health policy, but observational studies are prone to serious biases. An approach was recently proposed to overcome confounding and immortal-time biases within the emulated trial framework. This tutorial provides a step-by-step description of the design and analysis of emulated trials, as well as R and Stata code, to facilitate its use in practice. The steps consist in: (i) specifying the target trial and inclusion criteria; (ii) cloning patients; (iii) defining censoring and survival times; (iv) estimating the weights to account for informative censoring introduced by design; and (v) analysing these data. These steps are illustrated with observational data to assess the benefit of surgery among 70–89-year-old patients diagnosed with early-stage lung cancer. Because of the severe unbalance of the patient characteristics between treatment arms (surgery yes/no), a naïve Kaplan-Meier survival analysis of the initial cohort severely overestimated the benefit of surgery on 1-year survival (22% difference), as did a survival analysis of the cloned dataset when informative censoring was ignored (17% difference). By contrast, the estimated weights adequately removed the covariate imbalance. The weighted analysis still showed evidence of a benefit, though smaller (11% difference), of surgery among older lung cancer patients on 1-year survival. Complementing the CERBOT tool, this tutorial explains how to proceed to conduct emulated trials using observational data in the presence of immortal-time bias. The strength of this approach is its transparency and its principles that are easily understandable by non-specialists.
Activation of putative transposition intermediate formation in tumor cells.

The transcription levels of two families of mouse repetitive elements namely intracisternal A particle (IAP) genes, and B2 sequences were analyzed in different tumor cells and normal tissues. These sequences belong to two major classes of mobile elements present in the mouse genome. The Northern blots containing poly(A) + RNAs from tumor cells and normal tissues were hybridized to the cloned IAP gene and B2 sequence. The content of IAP gene transcripts in tumor cells is much higher than in normal cells. A 10‐ to 100‐fold difference was found. The predominant IAP‐gene specific RNAs in all investigated tumor cells were 9.5, 6.8 and 5.3 kb long. Additional RNA species were found in some of the tumors. The active synthesis of small cytoplasmic B2 RNA transcribed by RNA polymerase III was also detected in most tumor cells tested. Usually it was higher than in normal cells. Free closed circular DNAs hybridizing to IAP gene probes were cloned from Ehrlich ascites carcinoma cells. We speculate that the data obtained indicate the enhanced transposition of mobile elements in tumor cells which may be an important factor of tumor progression.
Kinins Promote B2 Receptor Endocytosis and Delay Constitutive B1 Receptor Endocytosis

Upon sustained insult, kinins are released and many kinin responses, such as inflammatory pain, adapt from a B2 receptor (B2R) type in the acute phase to a B1 receptor (B1R) type in the chronic phase. In this study, we show that kinins modulate receptor endocytosis to rapidly decrease B2R and increase B1R on the cell surface. B2Rs, which require agonist for activity, are stable plasma membrane components without agonist but recruit β-arrestin 2, internalize in a clathrin-dependent manner, and recycle rapidly upon agonist treatment. In contrast, B1Rs, which are inducible and constitutively active, constitutively internalize without agonist via a clathrin-dependent pathway, do not recruit β-arrestin 2, bind G protein-coupled receptor sorting protein, and target lysosomes for degradation. Agonist delays B1R endocytosis, thus transiently stabilizing the receptor. Most of the receptor trafficking phenotypes are transplantable from one receptor to the other through exchange of the C-terminal receptor tails, indicating that the tails contain epitopes that are important for the binding of protein partners that participate in the endocytic and postendocytic receptor choices. It is noteworthy that the agonist delay of B1R endocytosis is not transplanted to the B2R via the B1R tail, suggesting that this property of the B1R requires another domain. These events provide a rapid kinin-dependent mechanism for 1) regulating the constitutive B1R activity and 2) shifting the balance of accessible receptors in favor of B1R.
Organophosphate pesticides induce morphological abnormalities and decrease locomotor activity and heart rate in Danio rerio and Xenopus laevis

Organophosphate pesticides (OPs), a class of acetylcholinesterase inhibitors, are used widely in agriculture to reduce insect populations. Because of the conservation of acetylcholinesterase between invertebrates and vertebrates, OPs also can adversely affect nontarget species, such as aquatic and terrestrial animals. This study used uniform conditions to analyze the morphological and physiological effects caused by developmental exposure to 3 commonly used OPs—chlorpyrifos, dichlorvos, and diazinon—on 2 aquatic vertebrate species, Danio rerio (zebrafish) and Xenopus laevis. Survival, locomotor activity, heart rate, and gross anatomical abnormalities, including kyphosis and edema, were observed over a 5‐d period in response to OP concentrations ranging from 0 µM to 1000 µM. Both zebrafish and Xenopus showed decreased survival for all 3 OPs at higher concentrations. However, Xenopus showed higher mortality than zebrafish at lower chlorpyrifos and dichlorvos concentrations. Both models showed a dose‐dependent decrease in heart rate and free‐swimming larval activity in response to chlorpyrifos and dichlorvos. In addition, kyphosis and decreased spine length were prominent in Xenopus in response to 10 µM of chlorpyrifos and 0.1 µM dichlorvos. Although diazinon induced no effects on skeletal and cardiac motor activity in either species, it did induce cardiac edemas in zebrafish. Differences in the biological actions of OPs and their differential effects in these 2 vertebrate models demonstrate the importance of using common protocols and multiple models to evaluate the ecotoxicology of OPs. Environ Toxicol Chem 2014;33:1337–1345. © 2014 SETAC
The RHCE allele ceRT: D epitope 6 expression does not require D‐specific amino acids

BACKGROUND: False‐positive D typing in patients may lead to anti‐D immunization caused by D+ transfusions or by omission of anti‐D prophylaxis. Known causes of such errors are RhCE variants carrying RhD‐specific amino acids and cold agglutinin activity of some frequently used monoclonal anti‐D.
Reconstruction of the spatio-temporal diversification and ecological niche evolution of Helianthemum (Cistaceae) in the Canary Islands using Genotyping-by-Sequencing data.

BACKGROUND AND AIMS Several biogeographic models have been proposed to explain the colonization and diversification patterns of Macaronesian lineages. In this study, we calculated the diversification rates and explored what model better explains the current distribution of the 15 endemic species to the Canary Islands belonging to Helianthemum sect. Helianthemum (Cistaceae). METHODS We performed robust phylogenetic reconstructions based on genotyping-by-sequencing (GBS) data and analysed the timing, the biogeographical history and the ecological niche conservatism of this endemic Canarian clade. KEY RESULTS Our phylogenetic analyses provide strong support for the monophyly of this clade, and retrieved five lineages not currently restricted to a single island. The pristine colonization event took place in the Pleistocene (c. 1.82 Ma) via dispersal to Tenerife by a Mediterranean ancestor. CONCLUSIONS The rapid and abundant diversification (0.75-1.85 spp. Ma-1) undergone by this Canarian clade seems the result of complex inter-island dispersal events followed by allopatric speciation driven mostly by niche conservatism, i.e. inter-island dispersal towards niches featuring similar environmental conditions. Nevertheless, significant instances of ecological niche shifts have also been observed in some lineages, remarkably contributing to the overall diversification history of this clade.
Fold prediction by a hierarchy of sequence, threading, and modeling methods

Several fold recognition algorithms are compared to each other in terms of prediction accuracy and significance. It is shown that on standard benchmarks, hybrid methods, which combine scoring based on sequence‐sequence and sequence‐structure matching, surpass both sequence and threading methods in the number of accurate predictions. However, the sequence similarity contributes most to the prediction accuracy. This strongly argues that most examples of apparently nonhomologous proteins with similar folds are actually related by evolution. While disappointing from the perspective of the fundamental understanding of protein folding, this adds a new significance to fold recognition methods as a possible first step in function prediction.
Performance Analysis of `ROCSTAR' Algorithm for CDMA Forward Link Code Detection and Cancellation under Stressing Conditions

In CDMA systems, the mobile on the synchronous forward link has knowledge only of its own spreading code; therefore, blind interference suppression (IS) algorithms are required to cancel the multiple access interference (MAI). A recently developed technique applies auto-regressive spectrum estimation (ARSE) in reduced rank to allow a mobile to estimate the other users' codes by producing a "code spectrum", analogous to the conventional Fourier Transform in frequency analysis. The algorithm, known as ROCSTAR (Reduced Order Code Spectrum Transform using Auto-Regression), enables the mobile to detect the other codes efficiently and with few samples, allowing adaptation to a changing environment. ROCSTAR has been previously shown to provide better probability of detection and lower false alarm rate than full rank ARSE by reducing spurious peaks in the code spectrum with less computational complexity. Code estimation allows interference cancellation (IC) to be done, improving link performance significantly. In this paper, we analyze ROCSTAR's performance under heavy loading, severe multipath spreading, low sample support, and low Eb/N0. ROCSTAR is shown to outperform ARSE, producing high code detection rates (PD) and low code false alarm rates (PFA). Channel estimation using a pilot is performed, and it is shown that performance degradation due to channel estimation errors is less than 3 dB. The dependence on rank is examined and found to be related to the number of multipath components and largely independent of the number of users.
A Signaling Role of Glutamine in Insulin Secretion*

Children with hypoglycemia due to recessive loss of function mutations of the β-cell ATP-sensitive potassium (KATP) channel can develop hypoglycemia in response to protein feeding. We hypothesized that amino acids might stimulate insulin secretion by unknown mechanisms, because the KATP channel-dependent pathway of insulin secretion is defective. We therefore investigated the effects of amino acids on insulin secretion and intracellular calcium in islets from normal and sulfonylurea receptor 1 knockout (SUR1–/–) mice. Even though SUR1–/– mice are euglycemic, their islets are considered a suitable model for studies of the human genetic defect. SUR1–/– islets, but not normal islets, released insulin in response to an amino acid mixture ramp. This response to amino acids was decreased by 60% when glutamine was omitted. Insulin release by SUR1–/– islets was also stimulated by a ramp of glutamine alone. Glutamine was more potent than leucine or dimethyl glutamate. Basal intracellular calcium was elevated in SUR1–/– islets and was increased further by glutamine. In normal islets, methionine sulfoximine, a glutamine synthetase inhibitor, suppressed insulin release in response to a glucose ramp. This inhibition was reversed by glutamine or by 6-diazo-5-oxo-l-norleucine, a non-metabolizable glutamine analogue. High glucose doubled glutamine levels of islets. Methionine sulfoximine inhibition of glucose stimulated insulin secretion was associated with accumulation of glutamate and aspartate. We hypothesize that glutamine plays a critical role as a signaling molecule in amino acid- and glucose-stimulated insulin secretion, and that β-cell depolarization and subsequent intracellular calcium elevation are required for this glutamine effect to occur.