Miracle-dz/UniFAR-FTUs huggingface dataset:
"BM180": a novel basement membrane protein with a role in stimulus-secretion coupling by lacrimal acinar cells.

Regulated secretion requires the developmental coupling of neuronal or hormonal stimuli to an exocytotic response, a multistep pathway whose appearance may be linked with cellular adhesion to the newly formed exocrine cell basement membrane. We screened for adhesion-associated coupling activity using lacrimal acinar cells and have identified "BM180", a novel basement membrane protein enriched in guanidine HCl extracts of lacrimal and parotid exocrine secretory glands. BM180 resides primarily in a previously inexamined lower molecular-mass basement membrane peak (peak 2) that contains cell adhesion activity inhibitable with the anti-BM180 monoclonal antibody 3E12. Removal of peak 2 by gel filtration or preincubation of basement membrane with 3E12 decreased regulated peroxidase secretion by one-half without affecting constitutive secretion or the amount of cellular peroxidase available for release. Adding back peak 2 restored regulated secretion in a dose-dependent and 3E12-inhibitable manner and suggested a synergistic relationship between BM180 and laminin 1. BM180 has a mobility of 180 and 60 kDa in the absence or presence of dithiothreitol, respectively, and shows no immunological identity by competitive enzyme-linked immunosorbent assay with laminin 1, collagen IV, entactin, fibronectin, BM-40, perlecan, or vitronectin. We propose that BM180 is an important resident of certain glandular basement membranes where it interacts with the cell surface, thereby possibly signaling the appearance of a transducing element in the stimulus-secretion coupling pathway.
The Evolution Of Tactical Tendering In The Netherlands

The reform of public transport introduced in the Netherlands in 2001 is showing its first interesting results as about two third of the country (excluding the four largest agglomerations) has now been submitted to competitive tendering. Differently from many competitive regimes introduced in other parts of Europe, the Dutch regime aims at stimulating innovation in public transport. To this effect, a new passenger transport legislation allows the transport authorities to give operators the possibility to re-design the transport services (routes, timetables, fares, vehicles, etc.) during competitive tendering and/or during the contract period. As presented in earlier papers (van de Velde and Leijenaar, 2001; van de Velde and Pruijmboom, 2005), these legislator’s aims are not necessarily easy to fulfil as various factual, informational or behavioural barriers can stand in the way of such arrangements.
FIGARO: An efficient and objective tool for optimizing microbiome rRNA gene trimming parameters

Summary Microbiome studies continue to provide tremendous insight into the importance of microorganism populations to the macroscopic world. High-throughput DNA sequencing technology (i.e., Next-generation Sequencing) has enabled the cost-effective, rapid assessment of microbial populations when combined with bioinformatic tools capable of identifying microbial taxa and calculating the diversity and composition of biological and environmental samples. Ribosomal RNA gene sequencing, where 16S and 18S rRNA gene sequences are used to identify prokaryotic and eukaryotic species, respectively, is one of the most widely-used techniques currently employed in microbiome analysis. Prior to bioinformatic analysis of these sequences, trimming parameters must be set so that post-trimming sequence information is maximized while expected errors in the sequences themselves are minimized. In this application note, we present FIGARO: a Python–based application designed to maximize read retention after trimming and filtering for quality. FIGARO was designed specifically to increase reproducibility and minimize trial-and-error in trimming parameter selection for a DADA2–based pipeline and will likely be useful for optimizing trimming parameters and minimizing sequence errors in other pipelines as well where paired-end overlap is required. Availability and implementation The FIGARO application is freely available as source code at https://github.com/Zymo-Research/figaro.
Recombinant protein therapeutics from CHO cells : 20 years and counting

Recombinant protein therapeutics have changed the face of modern medicine in the past decade, and they continue to provide innovative and effective therapies for numerous previously refractory illnesses. Today, they are used in the treatment of a variety of human diseases, ranging from cancers to infertility. These proteins are generally synthesized by large-scale cultivation of genetically engineered “host” cells, which harbor artificially transfected genes encoding for the proteins of interest. For protein therapeutics to be effective, they must be synthesized in biologically active forms, requiring proper folding and post-translational modifications. In many cases, this includes glycosylation, a type of modification where certain carbohydrate moieties are added to specific amino acid residues of the protein. Glycoproteins, as these are usually called, are generally synthesized in mammalian cells, because common microbial hosts like Escherichia coli lack the requisite machinery to synthesize appropriate glycoforms. Several rodentor human-derived cells like 3T3, CHO, BHK, HeLa and HepG2 are frequently used in biomedical research for heterologous protein expression. Despite the availability of a plenitude of cell lines, nearly 70% of all recombinant protein therapeutics produced today are made in Chinese Hamster Ovary (CHO) cells. The current annual sales for biologics produced using CHO cells alone exceed US$30 billion worldwide. The first recombinant therapeutic protein produced in mammalian cells, tissue plasminogen activator (r-tPA, Activase) synthesized using CHO cells, was approved for clinical use in 1987. This marked the beginning of an array of highly successful CHO-based therapeutics (Table), which continue to revolutionize the field of medicine to this day. The knowledge and expertise amassed over the past two decades will most certainly ensure that CHO cells continue to remain the industry's premier workhorse for therapeutic protein production, at least in the near future. In this article, we revisit the evolution of CHO cells, tracing from their origins to the development of current production cell lines, and discuss some important aspects that make them robust and versatile protein expression hosts. Unlike some of its rodent relatives (mouse and rat), the generation of genomic resources for Chinese hamster has been quite limited. Genomic and proteomic tools using these resources can potentially aid in understanding and improving recombinant protein production processes leading to a significant enhancement in the speed with which these therapeutics transition from laboratory molecules to life-saving medicines. We, therefore, devote special attention to the value and need for such information in meeting the challenges of future research and manufacturing processes.
The Fitness Consequences of Aneuploidy Are Driven by Condition-Dependent Gene Effects

Aneuploidy is a hallmark of tumor cells, and yet the precise relationship between aneuploidy and a cell’s proliferative ability, or cellular fitness, has remained elusive. In this study, we have combined a detailed analysis of aneuploid clones isolated from laboratory-evolved populations of Saccharomyces cerevisiae with a systematic, genome-wide screen for the fitness effects of telomeric amplifications to address the relationship between aneuploidy and cellular fitness. We found that aneuploid clones rise to high population frequencies in nutrient-limited evolution experiments and show increased fitness relative to wild type. Direct competition experiments confirmed that three out of four aneuploid events isolated from evolved populations were themselves sufficient to improve fitness. To expand the scope beyond this small number of exemplars, we created a genome-wide collection of >1,800 diploid yeast strains, each containing a different telomeric amplicon (Tamp), ranging in size from 0.4 to 1,000 kb. Using pooled competition experiments in nutrient-limited chemostats followed by high-throughput sequencing of strain-identifying barcodes, we determined the fitness effects of these >1,800 Tamps under three different conditions. Our data revealed that the fitness landscape explored by telomeric amplifications is much broader than that explored by single-gene amplifications. As also observed in the evolved clones, we found the fitness effects of most Tamps to be condition specific, with a minority showing common effects in all three conditions. By integrating our data with previous work that examined the fitness effects of single-gene amplifications genome-wide, we found that a small number of genes within each Tamp are centrally responsible for each Tamp’s fitness effects. Our genome-wide Tamp screen confirmed that telomeric amplifications identified in laboratory-evolved populations generally increased fitness. Our results show that Tamps are mutations that produce large, typically condition-dependent changes in fitness that are important drivers of increased fitness in asexually evolving populations.
Novel Lower Bound on the Performance of a Partial Zero Forcing Receiver in a Mimo Cellular Network

We derive and study a novel lower bound on the performance of a partial zero forcing (PZF) receiver in the uplink of a cellular network, where the mobile locations are modeled as a homogeneous Poisson Point Process (HPPP). The PZF is a suboptimal receiver. Yet, it is easy to analyze and in many cases is close to optimal. Furthermore, the analysis of the PZF gives more insight on the behavior of the network than the optimal MMSE receiver (for example, we study the optimal distance within which interference should be suppressed). Unlike the existing analysis for the optimal MMSE receiver, our novel bound holds also in the presence of thermal noise and for finite number of antennas. This bound is easy to evaluate and proved to be asymptotically tight. Comparing to the asymptotic result for MMSE, we also give the exact SINR loss of PZF compared to MMSE.
A novel decision-making unit for automated maneuver of articulated vehicles in real traffic situations

In this paper, a new decision-making algorithm for double lane change maneuver of an articulated vehicle in real dynamic circumstances is studied. A novel method for determining the decision conditions is used based on the articulated vehicle kinematics and dynamics. Through this method, several points of the articulated vehicle are considered in various situations when conducting double lane change maneuver, and the critical points are determined. A new realistic dynamic method is used based on a 16-degrees of freedom dynamic model of the articulated vehicle. The sliding mode control method is utilized to increase the method efficiency. Therefore, the least safe time to perform the double lane change maneuver is extracted based on the sliding mode control method as tracking control. A new Articulated Vehicle Least safe time formulation is determined for dynamic circumstances. Based on the results of simulated test, the acceptable time range is also established for conducting the lane change maneuver. The lane change maneuver is generalized to the double lane change maneuver. Decision-making algorithm is introduced based on real traffic situations. The dynamic approach and the decision-making algorithm are verified. Results show the validity of the reflected method meaning that the decision-making algorithm is acceptable.
ÉPOCA DE MATURACÃO DOS FRUTOS, BENEFICIAMENTO E GERMINAÇÃO DE SEMENTES DE ESPÉCIES LENHOSAS DO CERRADO

A obtencao de sementes e mudas e um dos principais obstaculos a restauracao da vegetacao do Bioma Cerrado. Pouco se conhece da biologia reprodutiva, da fenologia, das tecnicas de beneficiamento e da germinacao das sementes para a maioria das especies. O objetivo desta pesquisa foi conhecer alguns aspectos relativos a fenologia e a germinacao de sementes de 39 especies arbustivas ou arboreas do Cerrado, visando a facilitar a producao de mudas para a restauracao desse ecossistema. Das especies testadas, seis apresentaram germinacao nula e as demais, diferentes padroes em tempo e em taxa de germinacao. De modo geral, a germinacao foi demorada e as taxas de germinacao, baixas. As maiores porcentagens obtidas foram 78% e 76%, para Cybistax antisyphilitica e Eriotheca gracilipes, respectivamente. Na analise da epoca de maturacao dos frutos, verificou-se que ha um padrao muito bem definido no qual as especies zoocoricas tem os frutos maduros nos meses chuvosos, e aquelas especies com dispersao independente da fauna, as anemocoricas e as barocoricas, a maturacao ocorre nos meses secos. Termos para indexacao : cerrado, sementes, germinacao, dispersao. FRUIT RIPENING, HARDLING PROCEDURES AND SEED GERMINATION OF SOME CERRADO WOODY SPECIES Abstract - One of the main obstacles to restore Cerrado vegetation is the lack of knowledge on seeds and seedlings production. There is no information about reproductive biology, phenology, seeds technology and germination for most Cerrado species. The aim of this research was to obtain some of this information, concerning to 39 Cerrado wood species, to help in the restoration of cerrado vegetation. Among the species tested, six did not germinate and the others showed different patterns of germination timing and rate. In general, germination was low and slow. The highest germination rates were 78 and 76%, for Cybistax antisyphilitica and Eriotheca gracilipes, respectivelly. There is a well defined pattern relative to dispersal syndrome and season of fruiting, with zoocory being concentrated in rainy months and other syndromes (anemocory and barocory) concentrated in dry months. Index terms : cerrado, seeds, germination, dispersion.
Learning Perceptual Organization in Infancy

It has been demonstrated that older infants (6- to 7-month-olds), but not younger infants (3- to 4-month-olds), use form similarity to organize stimuli consisting of X and O elements. We investigated whether utilization of form similarity is governed by maturation or experience by contrasting how infants perform when familiarized with a single exemplar versus multiple exemplars depicting a particular organization. In Experiment 1, 3- to 4-month-olds failed to organize alternating columns or rows of squares and diamonds or Hs and Is, respectively. In Experiment 2, same-aged infants familiarized with all three patterns (X-O, square-diamond, H-I) displayed evidence of organization. The results suggest that 3- to 4-month-olds can use form similarity to organize visual patterns in a concept-formation task. The findings imply that perceptual organization based on form similarity is learned through experience with multiple patterns depicting a common arrangement, rather than immediately apprehended in an individual pattern.
Responsiveness on the Interactive Grid

The Grid vision promises the secure and dynamic sharing of heterogeneous resources across the Internet. To date the emphasis has been on supercomputing scenarios where a relatively long running job is submitted to the Grid, requiring little interaction with the end user. More recently, with the emerging aspirations of Grid aficionados to use it for a much wider range of purposes - e-commerce and inter-enterprise computing for example - the issue of using the Grid for distributed, highly interactive applications has been raised. In our case this has emerged within a project seeking to build a European Learning Grid Infrastructure (ELeGI). Distributed learning environments need to be engaging and responsive, and as such it is important that, in addition to the dynamic resource sharing, service-oriented model offered by the Grid, that it can also meet the responsiveness needs of end users. In this paper we extend earlier work on analysing delay in distributed interactive applications to investigate the performance of the foremost Grid toolkit, Globus, in the context of distributed learning.
Who seeks genetic susceptibility testing for Alzheimer’s disease? Findings from a multisite, randomized clinical trial

Purpose: Alzheimer’s disease, for which one form of the apolipoprotein E (APOE) genotype is a risk factor, provides a paradigm in which to examine response to susceptibility testing for common, complex diseases. This study’s main purposes were to estimate interest in such testing and to examine demographic predictors of study participation.Methods: In this 3-site, randomized clinical trial (RCT), the intervention was a risk assessment program wherein genetic counselors educated adult children of AD patients about lifetime risk of disease based on their gender, family history, and APOE genotype. Two groups of participants were followed from initial contact to RCT enrollment: those who were systematically contacted through research registries, and those who were self-referred.Results: Of 196 systematically contacted participants, 47, or 24%, progressed from initial contact to RCT enrollment. These participants were more likely to be below age 60 (adjusted OR = 3.83, P < 0.01) and college educated (adjusted OR = 3.48, P < 0.01). Of 179 self-referred participants, 115, or 64%, progressed from initial contact to RCT enrollment. Most self-referred participants had a college education and were female (79%). Conclusions: In the first RCT to examine genetic susceptibility testing for AD, uptake rates were sufficiently high to merit concern that future test demand may strain available education and counseling resources. Findings suggest that susceptibility testing for AD may be of particular interest to women, college educated persons, and persons below age 60.
Enhanced expression and activity of DNA polymerase beta in chronic myelogenous leukemia.

BACKGROUND Chronic myelogenous leukemia (CML) is characterized by an initial chronic phase that invariably evolves to the more aggressive phase of blast crisis. Although the determinants of this transition are still unknown, it has been shown that the blast crisis is accompanied by genetic instability. MATERIALS AND METHODS The expression and activity of the error-prone DNA polymerase beta (pol beta) were investigated in blood samples from CML patients, by Western blotting and by an in vitro replication assay, respectively. RESULTS Pol beta expression and activity were significantly higher in CML samples compared to those of healthy donors. CONCLUSION Our results suggest that the excess of pol beta in CML could contribute to the genetic instability observed during the evolution of the disease from the chronic phase to blast crisis.
History of the Concept of Disconnectivity in Schizophrenia

AbstractNearly 60 years ago Seymour Kety proposed that research on genetics and brain pathology, but not on neurochemistry, would ultimately lead to an understanding of the pathophysiology of schizophrenia. This article will demonstrate the prescience of Kety’s proposal; advances in our knowledge of brain structure and genetics have shaped our current understanding of the pathophysiology of schizophrenia. Brain-imaging techniques have shown that schizophrenia is associated with cortical atrophy and ventricular enlargement, which progresses for at least a decade after the onset of psychotic symptoms. Cortical atrophy correlates with negative symptoms and cognitive impairment, but not with psychotic symptoms, in schizophrenia. Studies with the Golgi-staining technique that illuminates the entire neuron indicate that cortical atrophy is due to reduced synaptic connectivity on the pyramidal neurons and not due to actual loss of neurons. Results of recent genetic studies indicate that several risk genes for schizophrenia are within two degrees of separation from the N-methy-D-aspartate receptor (NMDAR), a subtype of glutamate receptor that is critical to synapse formation and synaptic plasticity. Inactivation of one of these risk genes that encodes serine racemase, which synthesizes D-serine, an NMDAR co-agonist, reproduces the synaptic pathology of schizophrenia. Thus, widespread loss of cortical synaptic connectivity appears to be the primary pathology in schizophrenia that is driven by multiple risk genes that adversely affect synaptogenesis and synapse maintenance, as hypothesized by Kety.
Improving energy gains of inexact DSP hardware through reciprocative error compensation

We present a zero hardware-overhead design approach called reciprocative error compensation(REC) that significantly enhances the energy-accuracy trade-off gains in inexact signal processing datapaths by using a two-pronged approach: (a) deliberately redesigning the basic arithmetic blocks to effectively compensate for each other's (expected) error through inexact logic minimization, and (b) “reshaping” the response waveforms of the systems being designed to further reduce any residual error. We apply REC to several DSP primitives such as the FFT and FIR filter blocks, and show that this approach delivers 2-3 orders of magnitude lower (expected) error and more than an order of magnitude lesser Signal-to-Noise Ratio (SNR) loss (in dB) over the previously proposed inexact design techniques, while yielding similar energy gains. Post-layout comparisons in the 65nm process technology show that our REC approach achieves upto 73% energy savings (with corresponding delay and area savings of upto 16% and 62% respectively) when compared to an existing exact DSP implementation while trading a relatively small loss in SNR of less than 1.5 dB.
Bayesian Structural Equation Modeling With Cross-Loadings and Residual Covariances

A recent article in the Journal of Management gives a critique of a Bayesian approach to factor analysis proposed in Psychological Methods. This commentary responds to the authors’ critique by clarifying key issues, especially the use of priors for residual covariances. A discussion is also presented of cross-loadings and model selection tools. Simulated data are used to illustrate the ideas. A reanalysis of the example used by the authors reveals a superior model overlooked by the authors.
Uni-directional trusted path: Transaction confirmation on just one device

Commodity computer systems today do not include a full trusted path capability. Consequently, malware can control the user's input and output in order to reveal sensitive information to malicious parties or to generate manipulated transaction requests to service providers. Recent hardware offers compelling features for remote attestation and isolated code execution, however, these mechanisms are not widely used in deployed systems to date. We show how to leverage these mechanisms to establish a “one-way” trusted path allowing service providers to gain assurance that users' transactions were indeed submitted by a human operating the computer, instead of by malware such as transaction generators. We design, implement, and evaluate our solution, and argue that it is practical and offers immediate value in e-commerce, as a replacement for captchas, and in other Internet scenarios.