Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanistic Differences between Nucleic Acid Chaperone Activities of the Gag Proteins of Rous Sarcoma Virus and Human Immunodeficiency Virus Type 1 Are Attributed to the MA Domain

ABSTRACT Host cell tRNAs are recruited for use as primers to initiate reverse transcription in retroviruses. Human immunodeficiency virus type 1 (HIV-1) uses tRNALys3 as the replication primer, whereas Rous sarcoma virus (RSV) uses tRNATrp. The nucleic acid (NA) chaperone function of the nucleocapsid (NC) domain of HIV-1 Gag is responsible for annealing tRNALys3 to the genomic RNA (gRNA) primer binding site (PBS). Compared to HIV-1, little is known about the chaperone activity of RSV Gag. In this work, using purified RSV Gag containing an N-terminal His tag and a deletion of the majority of the protease domain (H6.Gag.3h), gel shift assays were used to monitor the annealing of tRNATrp to a PBS-containing RSV RNA. Here, we show that similar to HIV-1 Gag lacking the p6 domain (GagΔp6), RSV H6.Gag. 3h is a more efficient chaperone on a molar basis than NC; however, in contrast to the HIV-1 system, both RSV H6.Gag. 3h and NC have comparable annealing rates at protein saturation. The NC domain of RSV H6.Gag. 3h is required for annealing, whereas deletion of the matrix (MA) domain, which stimulates the rate of HIV-1 GagΔp6 annealing, has little effect on RSV H6.Gag. 3h chaperone function. Competition assays confirmed that RSV MA binds inositol phosphates (IPs), but in contrast to HIV-1 GagΔp6, IPs do not stimulate RSV H6.Gag. 3h chaperone activity unless the MA domain is replaced with HIV-1 MA. We conclude that differences in the MA domains are primarily responsible for mechanistic differences in RSV and HIV-1 Gag NA chaperone function. IMPORTANCE Mounting evidence suggests that the Gag polyprotein is responsible for annealing primer tRNAs to the PBS to initiate reverse transcription in retroviruses, but only HIV-1 Gag chaperone activity has been demonstrated in vitro. Understanding RSV Gag's NA chaperone function will allow us to determine whether there is a common mechanism among retroviruses. This report shows for the first time that full-length RSV Gag lacking the protease domain is a highly efficient NA chaperone in vitro, and NC is required for this activity. In contrast to results obtained for HIV-1 Gag, due to the weak nucleic acid binding affinity of the RSV MA domain, inositol phosphates do not regulate RSV Gag-facilitated tRNA annealing despite the fact that they bind to MA. These studies provide insight into the viral regulation of tRNA primer annealing, which is a potential target for antiretroviral therapy.
Chemical Evolution of the Galaxy

Standard models for the chemical evolution of the Galaxy are reviewed with particular emphasis on the history of the abundance gradients in the disk. The effects on the disk structure and metallicity of gas accretion are discussed, showing that a significant fraction of the current disk mass has been accreted in the last Gyrs and that the chemical abundances of the infalling gas can be non primordial but should not exceed ∼0.3 Z⊙. The distributions with time and with galactocentric distance of chemical elements are discussed, comparing the observational data with the corresponding theoretical predictions by standard models, which reproduce very well the ISM abundances at various epochs, but not equally well all the features derived from observations of old stellar objects.
Shungite as the natural pantry of nanoscale reduced graphene oxide

Shungite is presented as a natural carbon allotrope of a multilevel fractal structure that is formed by a successive aggregation of ~1 nm reduced graphene oxide nanosheets. Turbostratic stacks of the sheets of ~1.5 nm in thickness and globular composition of the stacks of ~6 nm in size determine the secondary and tertiary levels of the structure. Aggregates of globules of tens of nanometers complete the structure. Molecular theory of graphene oxide, supported by large experience gained by the modern graphene science, has led to the foundation of the suggested presentation. The microscopic view has found a definite confirmation when analyzing the available empirical appearance of shungite. To our knowledge, this is the first time a geological process is described at quantum level.
Throughput Optimal Decentralized Scheduling of Multi-Hop Networks with End-to-End Deadline Constraints: II Wireless Networks with Interference

Consider a multihop wireless network serving multiple flows in which wireless link interference constraints are described by a link interference graph. For such a network, we design routing-scheduling policies that maximize the end-to-end timely throughput of the network. Timely throughput of a flow $f$ is defined as the average rate at which packets of flow $f$ reach their destination node $d_f$ within their deadline. Our policy has several surprising characteristics. Firstly, we show that the optimal routing-scheduling decision for an individual packet that is present at a wireless node $i\in V$ is solely a function of its location, and "age". Thus, a wireless node $i$ does not require the knowledge of the "global" network state in order to maximize the timely throughput. We notice that in comparison, under the backpressure routing policy, a node $i$ requires only the knowledge of its neighbours queue lengths in order to guarantee maximal stability, and hence is decentralized. The key difference arises due to the fact that in our set-up the packets loose their utility once their "age" has crossed their deadline, thus making the task of optimizing timely throughput much more challenging than that of ensuring network stability. Of course, due to this key difference, the decision process involved in maximizing the timely throughput is also much more complex than that involved in ensuring network-wide queue stabilization. In view of this, our results are somewhat surprising.
A NLG-based Application for Walking Directions

This work describes an online application that uses Natural Language Generation (NLG) methods to generate walking directions in combination with dynamic 2D visualisation. We make use of third party resources, which provide for a given query (geographic) routes and landmarks along the way. We present a statistical model that can be used for generating natural language directions. This model is trained on a corpus of walking directions annotated with POS, grammatical information, frame-semantics and markup for temporal structure.
Target validation and structure–activity analysis of a series of novel PCNA inhibitors

Proliferating cell nuclear antigen (PCNA) plays an essential role in DNA replication and repair. Tumor cells express high levels of PCNA, identifying it as a potentially ideal target for cancer therapy. Previously, we identified nine compounds termed PCNA inhibitors (PCNA‐Is) that bind directly to PCNA, stabilize PCNA trimer structure, reduce chromatin‐associated PCNA, and selectively inhibit tumor cell growth. Of these compounds, PCNA‐I1 was most potent. The purpose of this study is to further establish targeting of PCNA by PCNA‐I1 and to identify PCNA‐I1 analogs with superior potencies. We found that PCNA‐I1 does not affect the level of chromatin‐associated PCNA harboring point mutations at the predicted binding site of PCNA‐I1. Forty‐six PCNA‐I1 analogs with structures of 1‐hydrazonomethyl‐2‐hydroxy (scaffold A), 2‐hydrazonomethyl‐1‐hydroxy (scaffold B), 2‐hydrazonomethyl‐3‐hydroxy (scaffold C), and 4‐pyridyl hydrazine (scaffold D) were analyzed for their effects on cell growth in four tumor cell lines and PCNA trimer stabilization. Compounds in scaffold group A and group B showed the highest trimer stabilization and the most potent cell growth inhibitory activities with a significant potency advantage observed in the Z isomers of scaffold A. The absence of trimer stabilization and growth inhibitory effects in compounds of scaffold group D confirms the essentiality of the hydroxynaphthyl substructure. Compounds structure–activity relationship (SAR)‐6 and SAR‐24 were analyzed for their effects on and found to reduce chromatin‐associated PCNA in tumor cells. This study led to the identification of SAR‐24, a compound with superior potencies and potentially improved solubility, which will be used for future development of PCNA‐targeting cancer therapies.
Personality and Social Psychology Review Xx(x) 1 –21 Sensory Processing Sensitivity: a Review in the Light of the Evolution of Biological Responsivity

Psychologists (e.g., Gosling, 2001) have looked at personality differences within animal species to confirm in an independent context some of the personality differences found in humans, finding extraversion and neuroticism particularly easy to observe reliably in mammals and to explain in humans from an evolutionary perspective. This article looks at the reverse by seeking in humans somewhat different basic traits that evolutionary biologists studying animal personality have delineated, as well as applying the thinking of these biologists to the evolution of human personality traits. Specifically, this article reviews the research on the trait of sensory processing sensitivity (SPS; E. Aron & Aron, 1997) in the light of the evidence from evolutionary biology that many personality differences in nonhuman species (e. After briefly defining the SPS trait and model, this article first discusses how biologists studying animal personality have conceptualized this trait of a general sensitivity to the environment; second, reviews research on human personality and temperament differences that, although usually not designed to do so, strongly suggests this general sensitivity; third, reviews support for the SPS model focusing on studies using the scale, all of which bears on the extent to which SPS in humans corresponds to biological responsivity. is proposed to be a genetically determined trait involving a deeper (in the sense of Craik & Lockhart, 1972) cognitive processing of stimuli that is driven by higher emotional reactivity. Direct genetic encoding of depth of processing is not the only possible path to differences in this or any other personality difference. General personality differences can be related to many factors, including of course the physical and social environment, development of specialized skills through experience using them, and as a side effect of other inherited traits such as growth rate in nonhuman animals (Stamps, 2007) and body size and strength in human extraverts (Lukaszewski & Roney, 2011). But from the outset (E. Aron & Aron, 1997) we have seen SPS as the manifestation in our species of one Abstract This article reviews the literature on sensory processing sensitivity (SPS) in light of growing evidence from evolutionary biology that many personality differences in nonhuman species involve being more or less responsive, reactive, flexible, or sensitive to the environment. After briefly defining SPS, it first discusses how biologists studying animal personality have conceptualized this general environmental sensitivity. Second, it reviews relevant previous human personality/temperament work, focusing on crossover interactions (where a trait generates …
Speaker Clustering and Cluster Purification Methods for RT07 and RT09 Evaluation Meeting Data

This paper presents a design strategy for the speaker diarization system in the IIR submissions to the 2007 and 2009 NIST Rich Transcription Meeting Recognition Evaluations (RT07 and RT09) for the multiple distant microphone (MDM) condition. The system features two algorithms supporting two important steps in a diarization process. The first step is Initial Segmentation and Clustering (ISC), and the second one is cluster merging and purification. In the ISC step, we propose a histogram quantization and clustering technique based on time delay of arrival (TDOA) features by analyzing the correlation among the signals across multiple distant microphones. In the cluster merging and purification step, we further merge the speaker clusters using a Bayesian information criterion (BIC) to consolidate the clusters to arrive at one-cluster-per-speaker. The two steps work in tandem to form an integral process. We propose a novel Consensus Based Cluster Purification (CBCP) method that involves a technique to remove impure speaker segments in the speaker clusters before speaker modeling in the cluster purification process. The system reports a state-of-the-art performance of speaker diarization for RT07 and RT09 MDM condition with 7.47% and 8.77% Diarization error rates (DERs), respectively, for both overlapping and non-overlapping speech.
A New Model to Produce Infectious Hepatitis C Virus without the Replication Requirement

Numerous constraints significantly hamper the experimental study of hepatitis C virus (HCV). Robust replication in cell culture occurs with only a few strains, and is invariably accompanied by adaptive mutations that impair in vivo infectivity/replication. This problem complicates the production and study of authentic HCV, including the most prevalent and clinically important genotype 1 (subtypes 1a and 1b). Here we describe a novel cell culture approach to generate infectious HCV virions without the HCV replication requirement and the associated cell-adaptive mutations. The system is based on our finding that the intracellular environment generated by a West-Nile virus (WNV) subgenomic replicon rendered a mammalian cell line permissive for assembly and release of infectious HCV particles, wherein the HCV RNA with correct 5′ and 3′ termini was produced in the cytoplasm by a plasmid-driven dual bacteriophage RNA polymerase-based transcription/amplification system. The released particles preferentially contained the HCV-based RNA compared to the WNV subgenomic RNA. Several variations of this system are described with different HCV-based RNAs: (i) HCV bicistronic particles (HCVbp) containing RNA encoding the HCV structural genes upstream of a cell-adapted subgenomic replicon, (ii) HCV reporter particles (HCVrp) containing RNA encoding the bacteriophage SP6 RNA polymerase in place of HCV nonstructural genes, and (iii) HCV wild-type particles (HCVwt) containing unmodified RNA genomes of diverse genotypes (1a, strain H77; 1b, strain Con1; 2a, strain JFH-1). Infectivity was assessed based on the signals generated by the HCV RNA molecules introduced into the cytoplasm of target cells upon virus entry, i.e. HCV RNA replication and protein production for HCVbp in Huh-7.5 cells as well as for HCVwt in HepG2-CD81 cells and human liver slices, and SP6 RNA polymerase-driven firefly luciferase for HCVrp in target cells displaying candidate HCV surface receptors. HCV infectivity was inhibited by pre-incubation of the particles with anti-HCV antibodies and by a treatment of the target cells with leukocyte interferon plus ribavirin. The production of authentic infectious HCV particles of virtually any genotype without the adaptive mutations associated with in vitro HCV replication represents a new paradigm to decipher the requirements for HCV assembly, release, and entry, amenable to analyses of wild type and genetically modified viruses of the most clinically significant HCV genotypes.
Exosomes Derived from Human Endothelial Progenitor Cells Accelerate Cutaneous Wound Healing by Promoting Angiogenesis Through Erk1/2 Signaling

Chronic skin wounds represent one of the most common and disabling complications of diabetes. Endothelial progenitor cells (EPCs) are precursors of endothelial cells and can enhance diabetic wound repair by facilitating neovascularization. Recent studies indicate that the transplanted cells exert therapeutic effects primarily via a paracrine mechanism and exosomes are an important paracrine factor that can be directly used as therapeutic agents for regenerative medicine. However, application of exosomes in diabetic wound repair has been rarely reported. In this study, we demonstrated that the exosomes derived from human umbilical cord blood-derived EPCs (EPC-Exos) possessed robust pro-angiogenic and wound healing effects in streptozotocin-induced diabetic rats. By using a series of in vitro functional assays, we found that EPC-Exos could be incorporated into endothelial cells and significantly enhance endothelial cells' proliferation, migration, and angiogenic tubule formation. Moreover, microarray analyses indicated that exosomes treatment markedly altered the expression of a class of genes involved in Erk1/2 signaling pathway. It was further confirmed with functional study that this signaling process was the critical mediator during the exosomes-induced angiogenic responses of endothelial cells. Therefore, EPC-Exos are able to stimulate angiogenic activities of endothelial cells by activating Erk1/2 signaling, which finally facilitates cutaneous wound repair and regeneration.
Aerobic capacity in late adolescents infected with HIV and controls

Objectives : The objective of this study was to determine if aerobic capacity was diminished in late adolescents infected with HIV compared to controls matched for age, gender, and physical activity level. Study design : This study was a quasi-experimental cross sectional analysis. Subjects (11 female, four male) were 15 late adolescents with HIV (18 - 0.03 years) (CD4: 499.2 - 37.5 cells/mm 3, viral load: 22043 - 9976.6 copies/ml, haematocrit: 36.4 - 1.2) and 15 age, gender, and activity level matched controls (18 - 0.03) who underwent maximal treadmill exercise testing, while oxygen consumption, carbon dioxide production, ventilation, and ECG data were simultaneously recorded via open circuit spirometry and electrocardiography. Results : Peak oxygen consumption ( p < 0.003), peak treadmill stage ( p < 0.003), treadmill duration ( p < 0.004), and oxygen pulse ( p < 0.009) were lower in those infected with HIV compared to controls. Functional aerobic impairment was observed in the late adolescents infected with HIV, pointing toward pathological limitations of the oxidative metabolic pathway. Conclusion : This study has demonstrated that aerobic capacity was reduced substantially in late adolescents infected with HIV, below that observed in controls. The findings suggest that this decrease in oxidative capacity was due to mechanisms other than physiologic deconditioning.
Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy–causing mutations

Lamin A tail domains are SUMO1 modified at K420 (nuclear localization signal) and K486 (Ig-fold). K486 modification requires Ig-fold surface residues E460 and D461 and is reduced by familial partial lipodystrophy–causing mutations G465D and K486N. These results suggest novel mechanisms of functional control over lamin A in cells.
Some ethical conflicts in emergency care

Background: Decision-making and assessment in emergency situations are complex and result many times in ethical conflicts between different healthcare professionals. Aim: To analyse and describe situations that can generate ethical conflict among nurses working in emergency situations. Methods: Qualitative analysis. A total of 16 emergency nurses took part in interviews and a focus group. Ethical considerations: Organisational approval by the University Hospital, and informed consent and confidentiality were ensured before conducting the research. Result/conclusion: Two categories emerged: one in ‘ethical issues’ and one in ‘emotions and feelings in caring’. The four ethical subcategories are presented: Autonomy, the first sub category: first, the nurse’s ability to practise care on an emergency ward and, second, to support the patient and/or relatives in terms of care and medical treatment. The conflicts arise when the nurse ends up in the middle between the patient and the physician responsible for the diagnosis and treatment from a nature scientific perspective. Reification of injured body: patient was often reified and fragmented, becoming just a leg or arm. Different factors contributed in this perspective. Pain: pain relief was often inadequate but more effectively treated in the emergency medical services than at the emergency department. The nurses highlighted the phenomenon of suffering because they felt that pain was only an object, forgetting the patients’ care need, like separating mind from body. Death: the nurses felt that the emergency services are only prepared to save lives and not to take care of the needs of patients with ‘end-of-life’ care. Another issue was the lack of ethical guidelines during a cardiac arrest. Resuscitation often continues without asking about the patient’s ‘previous wishes’ in terms of resuscitation or not. In these situations, the nurses describe an ethical conflict with the physician in performing their role as the patient’s advocate. The nurses express feelings of distress, suffering, anger and helplessness.
A SEQUENCE OF BINOMIAL COEFFICIENTS RELATED TO LUCAS AND FIBONACCI NUMBERS

Let L(n; k) = n nik i nik k ¢ . We prove that all the zeros of the polynomial Ln(x) = P k‚0 L(n; k)x k are real. The sequence L(n; k) is thus strictly log-concave, and hence unimodal with at most two consecutive maxima. We determine those integers where the maximum is reached. In the last section we prove that L(n; k) satisfles a central limit theorem as well as a local limit theorem.
Midlife Blood Pressure and the Risk of Hippocampal Atrophy: The Honolulu Asia Aging Study

Hippocampal atrophy (HA) is usually attributed to the neurofibrillary tangles and neuritic plaques of Alzheimer disease. However, the hippocampus is vulnerable to global ischemia, which may lead to atrophy. We investigated the association of midlife blood pressure (BP) and late-life HA in a sample of Japanese-American men born between 1900 and 1919. BP was measured on 3 occasions between 1965 and 1971. In 1994 to 1996 a subsample underwent magnetic resonance imaging (MRI) of the brain. Hippocampal volume was estimated by manually drawing regions of interest on relevant scan slices; HA was defined as the lowest quartile of hippocampal volume. Also assessed on the MRI were cortical and subcortical infarcts, lacunes, and white matter hyperintensities. The risk (OR, 95% CI) was estimated for HA associated with systolic (<140 versus ≥140 mm Hg) and diastolic (<90 versus ≥90 mm Hg) BP and with antihypertensive treatment. Analyses were adjusted for sociodemographic factors, other cardiovascular risk factors, apolipoprotein E allele, and correlated brain pathology. Those never treated with antihypertensive medication had a significantly increased risk for HA (OR 1.7; CI=1.12; 2.65). The nontreated subjects with high systolic BP had an increased risk (OR=1.98; CI=0.89; 4.39) for HA. Results were similar for untreated men with high diastolic BP (OR=3.51; CI=1.26; 9.74). In conclusion, treatment with antihypertensive treatment modifies the association of BP and HA, such that high levels of BP adversely affect the hippocampus in persons never treated with antihypertensives.