Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonhuman primate models for the evaluation of HIV-1 preventive vaccine strategies: model parameter considerations and consequences

Purpose of reviewNonhuman primate (NHP) models of AIDS are powerful systems for evaluating HIV vaccine approaches in vivo. Authentic features of HIV-1 transmission, dissemination, target cell tropism, and pathogenesis, and aspects of anti-HIV-1 immune responses, can be recapitulated in NHPs provided the appropriate, specific model parameters are considered. Here, we discuss key model parameter options and their implications for HIV-1 vaccine evaluation. Recent findingsWith the availability of several different NHP host species/subspecies, different challenge viruses and challenge stock production methods, and various challenge routes and schemata, multiple NHP models of AIDS exist for HIV vaccine evaluation. The recent development of multiple new challenge viruses, including chimeric simian-human immunodeficiency viruses and simian immunodeficiency virus clones, improved characterization of challenge stocks and production methods, and increased insight into specific challenge parameters have resulted in an increase in the number of available models and a better understanding of the implications of specific study design choices. SummaryRecent progress and technical developments promise new insights into basic disease mechanisms and improved models for better preclinical evaluation of interventions to prevent HIV transmission.
Coronary artery calcification compared with carotid intima-media thickness in the prediction of cardiovascular disease incidence: the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND Coronary artery calcium (CAC) and carotid intima-media thickness (IMT) are noninvasive measures of atherosclerosis that consensus panels have recommended as possible additions to risk factor assessment for predicting the probability of cardiovascular disease (CVD) occurrence. Our objective was to assess whether maximum carotid IMT or CAC (Agatston score) is the better predictor of incident CVD. METHODS A prospective cohort study of subjects aged 45 to 84 years in 4 ethnic groups, who were initially free of CVD (n = 6698) was performed, with standardized carotid IMT and CAC measures at baseline, in 6 field centers of the Multi-Ethnic Study of Atherosclerosis (MESA). The main outcome measure was the risk of incident CVD events (coronary heart disease, stroke, and fatal CVD) over a maximum of 5.3 years of follow-up. RESULTS There were 222 CVD events during follow-up. Coronary artery calcium was associated more strongly than carotid IMT with the risk of incident CVD. After adjustment for each other (CAC score and IMT) and age, race, and sex [corrected], the hazard ratio of CVD increased 2.1-fold (95% confidence interval [CI], 1.8-2.5) for each 1-standard deviation (SD) increment of log-transformed CAC score, vs 1.3-fold (95% CI, 1.1-1.4) for each 1-SD increment of the maximum IMT. For coronary heart disease, the hazard ratios per 1-SD increment increased 2.5-fold (95% CI, 2.1-3.1) for CAC score and 1.2-fold (95% CI, 1.0-1.4) for IMT. A receiver operating characteristic curve analysis also suggested that CAC score was a better predictor of incident CVD than was IMT, with areas under the curve of 0.81 vs 0.78, respectively. CONCLUSION Although whether and how to clinically use bioimaging tests of subclinical atherosclerosis remains a topic of debate, this study found that CAC score is a better predictor of subsequent CVD events than carotid IMT.
Reducing HPV-Associated Cancer Globally

Human papillomavirus (HPV)-related cancers are a major worldwide public health concern. Virtually all cervical cancer is HPV related, with 70% caused by HPV16 and -18. Variable proportions of certain noncervical cancers (e.g., anal, vulvar, and oropharyngeal) are HPV related; more than 90% of the HPV-related ones are caused by HPV16, -18. The HPV-related cancers are dominated by cervical cancer in the developing world, where cervical cancer screening is limited. In this setting, widespread uptake of current HPV vaccines by adolescent girls could reduce this cancer's incidence and mortality by approximately two-thirds, with cost-effective screening programs of adult women having the potential to reduce mortality more rapidly. In the industrialized world, some noncervical HPV-related cancers, especially oropharyngeal, are rapidly increasing, and now rival the incidence of cervical cancer, whose rates continue to decline thanks to established cervical screening programs. Therefore, reducing HPV-associated noncervical cancers with HPV vaccination has greater importance in the industrialized world, especially because there are no approved screening programs for these cancers. Preventing the substantial number of noncervical HPV cancers in men will require either “herd” immunity through high-vaccination rates in females or male vaccination. Current HPV vaccination can complement cervical screening in protecting against cervical cancer and may permit the safe reduction of screening intensity in industrialized countries. Second-generation HPV vaccines (active against a broader array of cervical cancer–related HPV types) could prevent an even higher proportion of cervical precancer and cancer and might permit further reductions in screening intensity. Cancer Prev Res; 5(1); 18–23. ©2012 AACR.
Regulation, Integrase-Dependent Excision, and Horizontal Transfer of Genomic Islands in Legionella pneumophila

ABSTRACT Legionella pneumophila is a Gram-negative freshwater agent which multiplies in specialized nutrient-rich vacuoles of amoebae. When replicating in human alveolar macrophages, Legionella can cause Legionnaires' disease. Recently, we identified a new type of conjugation/type IVA secretion system (T4ASS) in L. pneumophila Corby (named trb-tra). Analogous versions of trb-tra are localized on the genomic islands Trb-1 and Trb-2. Both can exist as an episomal circular form, and Trb-1 can be transferred horizontally to other Legionella strains by conjugation. In our current work, we discovered the importance of a site-specific integrase (Int-1, lpc2818) for the excision and conjugation process of Trb-1. Furthermore, we identified the genes lvrRABC (lpc2813 to lpc2816) to be involved in the regulation of Trb-1 excision. In addition, we demonstrated for the first time that a Legionella genomic island (LGI) of L. pneumophila Corby (LpcGI-2) encodes a functional type IV secretion system. The island can be transferred horizontally by conjugation and is integrated site specifically into the genome of the transconjugants. LpcGI-2 generates three different episomal forms. The predominant episomal form, form A, is generated integrase dependently (Lpc1833) and transferred by conjugation in a pilT-dependent manner. Therefore, the genomic islands Trb-1 and LpcGI-2 should be classified as integrative and conjugative elements (ICEs). Coculture studies of L. pneumophila wild-type and mutant strains revealed that the int-1 and lvrRABC genes (located on Trb-1) as well as lpc1833 and pilT (located on LpcGI-2) do not influence the in vivo fitness of L. pneumophila in Acanthamoeba castellanii.
Hybrid pooled–unpooled design for cost‐efficient measurement of biomarkers

Evaluating biomarkers in epidemiological studies can be expensive and time consuming. Many investigators use techniques such as random sampling or pooling biospecimens in order to cut costs and save time on experiments. Commonly, analyses based on pooled data are strongly restricted by distributional assumptions that are challenging to validate because of the pooled biospecimens. Random sampling provides data that can be easily analyzed. However, random sampling methods are not optimal cost‐efficient designs for estimating means. We propose and examine a cost‐efficient hybrid design that involves taking a sample of both pooled and unpooled data in an optimal proportion in order to efficiently estimate the unknown parameters of the biomarker distribution. In addition, we find that this design can be used to estimate and account for different types of measurement and pooling error, without the need to collect validation data or repeated measurements. We show an example where application of the hybrid design leads to minimization of a given loss function based on variances of the estimators of the unknown parameters. Monte Carlo simulation and biomarker data from a study on coronary heart disease are used to demonstrate the proposed methodology. Published in 2010 by John Wiley & Sons, Ltd.
Caught in self-interaction: evolutionary and functional mechanisms of protein homooligomerization

Many soluble and membrane proteins form homooligomeric complexes in a cell which are responsible for the diversity and specificity of many pathways, may mediate and regulate gene expression, activity of enzymes, ion channels, receptors, and cell adhesion processes. The evolutionary and physical mechanisms of oligomerization are very diverse and its general principles have not yet been formulated. Homooligomeric states may be conserved within certain protein subfamilies and might be important in providing specificity to certain substrates while minimizing interactions with other unwanted partners. Moreover, recent studies have led to a greater awareness that transitions between different oligomeric states may regulate protein activity and provide the switch between different pathways. In this paper we summarize the biological importance of homooligomeric assemblies, physico-chemical properties of their interfaces, experimental and computational methods for their identification and prediction. We particularly focus on homooligomer evolution and describe the mechanisms to develop new specificities through the formation of different homooligomeric complexes. Finally, we discuss the possible role of oligomeric transitions in the regulation of protein activity and compile a set of experimental examples with such regulatory mechanisms.
Secure full-duplex relay network using cooperative jamming

In this work, we propose a full-duplex relay (FDR) network for secure communication in the presence of an eavesdropper. We consider both the destination and the amplify-and-forward relay has a full-duplex capability for a higher rate and/or a stronger secrecy performance. In particular, the destination transmits a cooperative jamming signal while receiving the relayed signal. To get analytic understanding, we derive a closed-form expression for the secrecy rate of the proposed FDR network. Numerical evaluations are also conducted to verify the analytic results.
Short Intracortical and Surround Inhibition Are Selectively Reduced during Movement Initiation in Focal Hand Dystonia

In patients with focal hand dystonia (FHD), pathological overflow activation occurs in muscles not involved in the movement. Surround inhibition is a neural mechanism that can sharpen desired movement by inhibiting unwanted movement in adjacent muscles. To further establish the phenomenon of surround inhibition and to determine whether short intracortical inhibition (SICI) reflecting inhibition from the local interneurons in primary motor cortex (M1), might play a role in its genesis, single- and paired-pulse transcranial magnetic stimulation (TMS), and Hoffmann reflex testing were applied to evaluate the excitability of the relaxed abductor pollicis brevis muscle (APB) at various intervals during a movement of the index finger in 16 patients with FHD and 20 controls. Whereas controls showed inhibition of APB motor-evoked potential (MEP) size during movement initiation and facilitation of APB MEP size during the maintenance phase, FHD patients did not modulate APB MEP size. In contrast, SICI remained constant in controls, but FHD patients showed reduced SICI during movement initiation. The Hmax/Mmax ratio in control subjects increased during movement initiation. The results provide additional evidence for the presence of surround inhibition in M1, where it occurs only during movement initiation, indicating that different mechanisms underlie movement initiation and maintenance. Thus, surround inhibition is sculpted both in time and space and may be an important neural mechanism during movement initiation to counteract increased spinal excitability. SICI may contribute to its generation, because in patients with FHD, the lack of depression of APB MEP size is accompanied by a reduction in SICI.
Random access technique for millimeter-wave cellular communications

The random access (RA) technique is a key procedure in cellular networks but the overall duration of this technique in millimeter-wave (mm-wave) cellular systems with directional beams is very long because RA preambles (RAPs) should be transmitted in all directions of Tx and Rx beams. In this paper, two different types of preambles (RAP-1 and RAP-2) are proposed to reduce the processing time in the RA stage. In simulation, it is shown that the RAP-2 is suitable for RA in mm-wave cellular systems with directional beams because of the smaller processing time and high detection probability in multi-user environments.
An Analysis of Automated Visual Analysis Classification: Interactive Visualization Task Inference of Cancer Genomics Domain Experts

We show how mouse interaction log classification can help visualization toolsmiths understand how their tools are used “in the wild” through an evaluation of MAGI - a cancer genomics visualization tool. Our primary contribution is an evaluation of twelve visual analysis task classifiers, which compares predictions to task inferences made by pairs of genomics and visualization experts. Our evaluation uses common classifiers that are accessible to most visualization evaluators: <inline-formula><tex-math notation="LaTeX">$k$</tex-math><alternatives> <inline-graphic xlink:href="gramazio-ieq1-2734659.gif"/></alternatives></inline-formula>-nearest neighbors, linear support vector machines, and random forests. By comparing classifier predictions to visual analysis task inferences made by experts, we show that simple automated task classification can have up to 73 percent accuracy and can separate meaningful logs from “junk” logs with up to 91 percent accuracy. Our second contribution is an exploration of common MAGI interaction trends using classification predictions, which expands current knowledge about ecological cancer genomics visualization tasks. Our third contribution is a discussion of how automated task classification can inform iterative tool design. These contributions suggest that mouse interaction log analysis is a viable method for (1) evaluating task requirements of client-side-focused tools, (2) allowing researchers to study experts on larger scales than is typically possible with in-lab observation, and (3) highlighting potential tool evaluation bias.
Characterizing Synaptic Vesicle Proteins Using Synaptosomal Fractions and Cultured Hippocampal Neurons

Cloning and characterization of synaptic vesicle proteins and their binding counterparts on the presynaptic plasma membrane have greatly advanced our understanding of the molecular mechanisms involved in the synaptic vesicle cycle and neurotransmitter release. This unit discusses multidisciplinary approaches to characterize proteins from synaptosome‐enriched subcellular fractions and localize them within cultured neurons. The first approach regroups methods used to isolate synaptic vesicles from rat brain synaptosomal preparations, allowing for specific biochemical investigation of synaptic vesicle proteins. The second is a detailed procedure for pre‐embedding immunogold staining and electron microscopic observation, which permits the morphological identification of proteins in individual vesicles at intact synapses. Additionally, this chapter proposes methods for light microscopic examination of hippocampal neurons. It includes procedures for embryonic and postnatal hippocampal neuron culture and describes an immunocytochemical staining protocol used to investigate synaptic vesicle protein localization with respect to other proteins or subcellular structures. Curr. Protoc. Neurosci. 59:2.7. 1‐2.7. 22. © 2012 by John Wiley & Sons, Inc.
Homogeneity of intracellular electrophysiological properties in different neuronal subtypes in medial preoptic slices containing the sexually dimorphic nucleus of the rat

The sexually dimorphic nucleus of the preoptic area (SDN‐POA) is larger in male than in female rats, the male phenotype requiring the presence of circulating androgens perinatally. These experiments investigated the intracellular electrophysiology and morphology of SDN‐POA neurons and compared these properties with those of other medial preoptic area (MPOA) neurons. Biocytin‐injected cells in the SDN‐POA either had one or two primary dendrites, or they had multipolar dendritic arrays; dendrites were aspiny or sparsely spiny and displayed limited branching. Neurons in other parts of the MPOA were similar morphologically. Regardless of morphology, neurons situated in either the SDN‐POA or surrounding MPOA had low‐threshold potentials and linear or nearly linear current‐voltage relations. In most (73%) cells, stimulation of the dorsal preoptic region evoked a fast excitatory postsynaptic potential followed by a fast inhibitory postsynaptic potential (IPSP). Bicuculline blocked the fast IPSPs, which reversed near the Cl2 equilibrium potential (‐71 ± 5mV), indicating their mediation by gamma‐aminobutyric acid (GABA)A receptors.
Consistency of cooperative caching in mobile peer-to-peer systems over MANET

Caching consistency is an important issue for cooperative caching in mobile environments but has not been adequately addressed for mobile ad hoc networks (MANETs). In this paper, we proposed a novel approach, called RPCC (relay peer-based caching consistency), to addressing the caching consistency issues in a MANET. With the help of relay peers between the source host and cache hosts, both push-based and pull-based strategies can be employed, which helps to reduce the communication overhead and query latency. The source host pushes the data to relay peers and cache hosts pull the data from relay peers. These operations can be performed asynchronously and simultaneously. Moreover, the proposed RPCC approach is flexible in that it can deal with different consistency requirements adaptively. Simulation results demonstrated that RPCC outperforms the traditional push and pull based strategies by taking their advantages while at the same time avoiding their weakness.
Voltammetric optimisation of TEMPO-mediated oxidations at cellulose fabric

N-Oxyl mediated oxidations are becoming widely applied to the selective oxidation of a range of substrates bearing primary alcohol groups, including renewable biopolymers such as cellulose, but screening of mediators and oxidation conditions can be a laborious process, potentially limiting discovery of new mediators and/or optimised conditions for reaction. We describe a simple method for rapid voltammetric screening of mediators and reaction conditions that requires only small quantities of mediator (so is suitable for screening new synthetic or natural mediators) and yet yields information about relative efficiency of mediator, optimum pH, and preferred buffer identity. Such methodology may be used to speed mediator screening and selection of optimal and greenest reaction conditions prior to preparation, or isolation, of large quantities of mediators.
Population genomics of the inbred Scandinavian wolf

The Scandinavian wolf population represents one of the genetically most well‐characterized examples of a severely bottlenecked natural population (with only two founders), and of how the addition of new genetic material (one immigrant) can at least temporarily provide a ‘genetic rescue’. However, inbreeding depression has been observed in this population and in the absence of additional immigrants, its long‐term viability is questioned. To study the effects of inbreeding and selection on genomic diversity, we performed a genomic scan with approximately 250 microsatellite markers distributed across all autosomes and the X chromosome. We found linkage disequilibrium (LD) that extended up to distances of 50 Mb, exceeding that of most outbreeding species studied thus far. LD was particularly pronounced on the X chromosome. Overall levels of observed genomic heterozygosity did not deviate significantly from simulations based on known population history, giving no support for a general selection for heterozygotes. However, we found evidence supporting balancing selection at a number of loci and also evidence suggesting directional selection at other loci. For markers on chromosome 23, the signal of selection was particularly strong, indicating that purifying selection against deleterious alleles may have occurred even in this very small population. These data suggest that population genomics allows the exploration of the effects of neutral and non‐neutral evolution on a finer scale than what has previously been possible.
The changes in access to higher education in China

Access to higher education in China has changed since the 1990s.Data from the urban and rural statistics shows that,if the tiers of higher education are not distinguished,the equality of access opportunities,either in urban or rural areas,have been improved greatly;using meta analysis method to the available relevant empirical research,if the tiers of higher education are distinguished,the children with better social-economical status are more likely to get access to elite universities.
A Dynamic Approach to the Empirical Study on EFL Peer-group Prior Evaluation: From a Sociocultural Perspective

Based on the Dynamic Systems Theory,the present research,an experiment on 98 Chinese non-English majors,aims to see the effects of peer-group prior evaluation on L2 writing from a sociocultural perspective.It is found that peer-group evaluation prior to teacher feedback has significant influence on L2 writing.However at the beginning of the experiment,the L2 writing level of students fell instead of rising.At the end of the experiment,the level raised up significantly,and the dialogic nature of interaction and the Dynamic Systems Theory account for this characteristic.
Initial testing (stage 1) of a monoclonal antibody (SCH 717454) against the IGF‐1 receptor by the pediatric preclinical testing program

SCH 717454 (19D12) is a fully human antibody directed against the insulin‐like growth factor 1 receptor (IGF‐1R), which is implicated in the growth and metastatic phenotype of a broad range of malignancies. The activity of SCH 717454 was evaluated against the in vitro and in vivo panels of the Pediatric Preclinical Testing Program (PPTP).