Miracle-dz/UniFAR-FTUs huggingface dataset:
NMR chemical shift and relaxation measurements provide evidence for the coupled folding and binding of the p53 transactivation domain

The interaction between the acidic transactivation domain of the human tumor suppressor protein p53 (p53TAD) and the 70 kDa subunit of human replication protein A (hRPA70) was investigated using heteronuclear magnetic resonance spectroscopy. A 1H–15N heteronuclear single quantum coherence (HSQC) titration experiment was performed on a 15N-labeled fragment of hRPA70, containing the N-terminal 168 residues (hRPA701–168) and p53TAD. HRPA701–168 residues important for binding were identified and found to be localized to a prominent basic cleft. This binding site overlapped with a previously identified single-stranded DNA-binding site, suggesting that a competitive binding mechanism may regulate the formation of p53TAD–hRPA70 complex. The amide 1H and 15N chemical shifts of an uniformly 15N-labeled sample of p53TAD were also monitored before and after the addition of unlabeled hRPA701–168. In the presence of unlabeled hRPA701–168, resonance lineshapes increased and corresponding intensity reductions were observed for specific p53TAD residues. The largest intensity reductions were observed for p53TAD residues 42–56. Minimal binding was observed between p53TAD and a mutant form of hRPA701–168, where the basic cleft residue R41 was changed to a glutamic acid (R41E), demonstrating that ionic interactions play an important role in specifying the binding interface. The region of p53TAD most affected by binding hRPA701–168 was found to have some residual alpha helical and beta strand structure; however, this structure was not stabilized by binding hRPA701–168. 15N relaxation experiments were performed to monitor changes in backbone dynamics of p53TAD when bound to hRPA701–168. Large changes in both the transverse (R2) and rotating frame (R1ρ) relaxation rates were observed for a subset of the p53TAD residues that had 1H–15N HSQC resonance intensity reductions during the complex formation. The folding of p53TAD upon complex formation is suggested by the pattern of changes observed for both R2 and R1ρ. A model that couples the formation of a weak encounter complex between p53TAD and hRPA701–168 to the folding of p53TAD is discussed in the context of a functional role for the p53–hRPA70 complex in DNA repair.
Finite size errors in quantum many-body simulations of extended systems

Further developments are introduced in the theory of finite-size errors in quantum many-body simulations of extended systems using periodic boundary conditions. We show that our recently introduced model periodic Coulomb interaction @A. J. Williamson et al., Phys. Rev. B 55, R4851 ~1997! # can be applied consistently to all Coulomb interactions in the system. The model periodic Coulomb interaction greatly reduces the finite-size errors in quantum many-body simulations. We illustrate the practical application of our techniques with Hartree-Fock and variational and diffusion quantum Monte Carlo calculations for ground- and excited-state calculations. We demonstrate that the finite-size effects in electron promotion and electron addition/subtraction excitation energy calculations are very similar. @S0163-1829~99! 07303-8#
Multimarket Contact in the Hospital Industry

Hospitals in the United States increasingly belong to multihospital systems that operate in numerous geographic markets. A large literature in management and economics suggests that competition between firms may be softened as a result of multimarket contact—i.e., firms competing with one another in multiple markets simultaneously. Exploiting plausibly exogenous variation in multimarket contact generated by out-of-market consolidation, I find that increases in multimarket contact over the 2000–2010 period led to higher hospital prices. These results suggest that continued hospital consolidation may produce higher prices even if that consolidation only minimally affects within-market concentration. (JEL G34, G38, I11, I18, K21, L41)
Guaranteeing input tracking for constrained systems: Theory and application to demand response

A method for certifying exact input trackability for constrained discrete time linear systems is introduced in this paper. A signal is assumed to be drawn from a reference set and the system must track this signal with a linear combination of its inputs. Using methods inspired from robust model predictive control, the proposed approach certifies the ability of a system to track any reference drawn from a polytopic set on a finite time horizon by solving a linear program. Optimization over a parameterization of the set of reference signals is discussed, and particular instances of parameterization of this set that result in a convex program are identified, allowing one to find the largest set of trackable signals of some class. Infinite horizon feasibility of the methods proposed is obtained through use of invariant sets, and an implicit description of such an invariant set is proposed. These results are tailored for the application of power consumption tracking for loads, where the operator of the load needs to certify in advance his ability to fulfill some requirement set by the network operator. An example of a building heating system illustrates the results.
PD-L 1 Expression in the Merkel Cell Carcinoma Microenvironment : Association with In fl ammation , Merkel Cell Polyomavirus , and Overall Survival

Merkel cell carcinoma (MCC) is a lethal, virus-associated cancer that lacks effective therapies for advanced disease. Agents blocking the PD-1/PD-L1 pathway have shown objective, durable tumor regressions in patients with advanced solid malignancies and efficacy has been linked to PD-L1 expression in the tumor microenvironment. To investigate whether MCC might be a target for PD-1/PD-L1 blockade, we examined MCC PD-L1 expression, its association with tumor-infiltrating lymphocytes (TIL), Merkel cell polyomavirus (MCPyV), and overall survival. Sixty-seven MCC specimens from 49 patients were assessed with immunohistochemistry for PD-L1 expression by tumor cells and TILs, and immune infiltrates were characterized phenotypically. Tumor cell and TIL PD-L1 expression were observed in 49% and 55% of patients, respectively. In specimens with PD-L1 (þ) tumor cells, 97% (28/29) showed a geographic association with immune infiltrates. Among specimens with moderate-severe TIL intensities, 100% (29/29) showed PD-L1 expression by tumor cells. Significant associations were also observed between the presence of MCPyV DNA, a brisk inflammatory response, and tumor cell PD-L1 expression: MCPyV(-) tumor cells were uniformly PD-L1(-). Taken together, these findings suggest that a local tumor-specific and potentially MCPyV-specific immune response drives tumor PD-L1 expression, similar to previous observations in melanoma and head and neck squamous cell carcinomas. In multivariate analyses, PD-L1(-)MCCswere independently associatedwithworse overall survival [HR 3.12; 95% confidence interval, 1.28– 7.61; P 1⁄4 0.012]. These findings suggest that an endogenous immune response promotes PD-L1 expression in theMCCmicroenvironment whenMCPyV is present, and provide a rationale for investigating therapies blocking PD-1/PD-L1 for patients with MCC. Cancer Immunol Res; 1(2); 1–10. 2013 AACR.
Psychophysiological Measures of Drowsiness as Estimators of Mental Fatigue and Performance Degradation during Sleep Deprivation

Abstract : This paper describes a methodology developed to measure 'drowsiness' electrophysiologically as an index of chronic fatigue experienced during periods of sleep loss. Nine volunteers performed continuous cognitive workload schedule with 15 min breaks occurring every 2 hrs throughout a 64 hr sleep deprivation experiment. To measure fatigue a 4 min eyes closed relaxation period was embedded one every hour within a battery of cognitive tasks. The subjects were instructed to relax with their eyes closed but remain awake and alert. At the end of this 4 min period, a bell sounded which cued the subjects to open their eyes and indicate their subjective level of drowsiness. EEG signals collected during these periods were both visually scored and computer quantified. Two raters visually scored the signals for: (1) time of first stage 1 sleep onset, (2) number of stage 1 sleep onsets, (3) shortest and longest time in stage 1 and (4) total amount of stage 1 sleep (or deeper). Period analysis was performed on the digitized data and a drowsiness scale was developed by subtracting the amount of theta and delta from alpha while controlling for individual differences by dividing the result by alpha minus theta minus delta activity present during baselines. (js)
A syntactic rule-based method for automatic pathway information extraction from biomédical literature

Automatically extracting protein pathway information from the vast amount of published literature helps us understand diseases and discover new drug targets. In this paper, we propose a syntactic rule-based method for extracting pathway relation information from Medline abstracts. This method takes into account comprehensive dependency types and negative connectives when extracting relations from syntactic analysis results. The benchmarking results demonstrate the effectiveness of our method.
Did sugarcane expansion lead to GDP growth in São Paulo state ? An analysis at municipal level using propensity score-based estimators *

Previous studies suggest that sugarcane expansion in Brazil is linked with economic growth. This study tests these findings in sugarcane-expanding municipalities in São Paulo state. In particular, I examine whether municipalities that have increased their sugarcane production have as a result experienced higher GDP per capita growth. Whereas previous studies only demonstrated associations between sugarcane expansion and economic growth, this study establishes a causal link. Using estimators based on the propensity score, I compare GDP per capita growth in sugarcane-expanding municipalities with suitable controls. The results indicate that there is no statistically significant impact of sugarcane expansion on GDP per capita growth in municipalities in São Paulo state. JEL classification: C14, C21, O13, R13
Brownian Motion of a Massive Binary

The dynamical friction and diffusion coefficients are derived for a massive binary that moves against a uniform background of stars. The random impulses exerted on the binary's center of mass by the field stars are greater than those exerted on a point particle due to inelastic scattering. The frictional force acting on the binary is less than that acting on a point particle due to randomization of the trajectories of field stars that pass near the binary. Both effects tend to increase the random motion of a binary compared with that of a point mass. If the maximum effective impact parameter for gravitational encounters is comparable to the radius of gravitational influence of the binary, its Brownian velocity can be increased by a modest factor (≲2) compared with that of a single particle. This condition is probably fulfilled in the case of binary supermassive black holes in galactic nuclei.
An exploration of social desirability within the white Afrikaans–speaking group

Orientation: South Africa’s society can be seen as highly diversified, with linguistic and cultural differences. This diversity has long been a challenge for psychologists using personality measures. Furthermore, social desirability affects the truthfulness of personality measures, as people may present themselves in a more positive light to gain social approval. Research purpose: The purpose of the study is to explore social desirability within the white Afrikaans group (WAG). Motivation for the study: To gain better understanding of how social desirability is understood in the WAG. The South African Personality Inventory project will incorporate the findings (together with other language and cultural social desirability studies), to develop a unified South African social desirability instrument. Research design, approach and method: A qualitative design from a phenomenological approach was used to collect data from the WAG (N = 60). A combined convenience and quota non-probability sampling method was used to study adult white Afrikaans-speaking people. Semi-structured interviews were conducted and content analysis was utilised to evaluate the data. Main findings: Six main themes were identified, which the white Afrikaans-speaking group perceive as socially desirable and undesirable, and feature they will exhibit in order to make a positive impression on others. The six main themes are facilitating, gender-based, intellectopenness, interpersonal relatedness, intrapersonal relatedness and value-based themes. Practical/Managerial implications: From the accumulated data the assumption that can be made is that people, in reasonable terms, demonstrate a need to make a favourable impression on others. If meeting someone for the first time, the need to leave a favourable impression on the person will be intrinsically driven by one’s need for social acceptance. Contribution/Value add: Broad understanding of how social desirability is perceived by the white Afrikaans-speaking group, as well as what impression management tactics they will exhibit when seeking to make a favourable impression.
Detecting Implicit Expressions of Sentiment in Text Based on Commonsense Knowledge

Sentiment analysis is one of the recent, highly dynamic fields in Natural Language Processing. Most existing approaches are based on word-level analysis of texts and are able to detect only explicit expressions of sentiment. In this paper, we present an approach towards automatically detecting emotions (as underlying components of sentiment) from contexts in which no clues of sentiment appear, based on commonsense knowledge. The resource we built towards this aim -- EmotiNet - is a knowledge base of concepts with associated affective value. Preliminary evaluations show that this approach is appropriate for the task of implicit emotion detection, thus improving the performance of sentiment detection and classification in text.
Dialogue in the Lecture Hall: Teacher–Student Communication and Students’ Perceptions of Their Learning

Dialogue is often advocated as a way to engage students in active learning. Yet, most studies of dialogic teaching focus on small classes where discussion is relatively easy to encourage. Additionally, very little is known about students’ perceptions of dialogue and its relationship to their learning. This essay draws from Martin Buber's philosophy to describe dialogue as a way of communicating that involves presence, openness, mutuality, emergence, and voice. The case study investigates one instructor's efforts to teach dialogically in an introductory lecture course and her students’ characterizations of the aspects of teacher–student communication that help them learn. Analysis shows that students’ descriptions were consistent with dialogic elements of presence and voice, but not otherness or mutuality. Implications for dialogic teaching and scholarship are discussed.
Direct Estimation of Non-Rigid Registrations with Image-Based Self-Occlusion Reasoning

The registration problem for images of a deforming surface has been well studied. External occlusions are usually well-handled. In 2D image-based registration, self- occlusions are more challenging. Consequently, the surface is usually assumed to be only slightly self-occluding. This paper is about image-based non-rigid registration with self-occlusion reasoning. A specific framework explicitly modeling self-occlusions is proposed. It is combined with an intensity-based, i.e. direct, data term for registration. Self-occlusions are detected as shrinking areas in the 2D warp. Experimental results on several challenging datasets show that our approach successfully registers images with self-occlusions while effectively detecting the occluded regions.
Cas-OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA-guided endonucleases

Summary: The Type II clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system is an adaptive immune response in prokaryotes, protecting host cells against invading phages or plasmids by cleaving these foreign DNA species in a targeted manner. CRISPR/Cas-derived RNA-guided engineered nucleases (RGENs) enable genome editing in cultured cells, animals and plants, but are limited by off-target mutations. Here, we present a novel algorithm termed Cas-OFFinder that searches for potential off-target sites in a given genome or user-defined sequences. Unlike other algorithms currently available for identification of RGEN off-target sites, Cas-OFFinder is not limited by the number of mismatches and allows variations in protospacer-adjacent motif sequences recognized by Cas9, the essential protein component in RGENs. Cas-OFFinder is available as a command-line program or accessible via our website. Availability and implementation: Cas-OFFinder free access at http://www.rgenome. net/cas-offinder. Contact: baesau@snu.ac. kr or jskim01@snu.ac. kr
REIHE INFORMATIK 14 / 2002 A Reactive Location Service for Mobile Ad Hoc Networks

We present and analyze a reactive location service (RLS) for mobile ad hoc networks. RLS provides a mobile node in a wireless ad-hoc network with the means to inquire the current geographical position of another node on-demand and can be used as a building block for location-based routing. We provide a comparison of RLS to an ideal omniscient location service as well as to the complex Grid Location Service (GLS). In addition, we compare the performance of greedy location-based routing in combination with RLS to the performance of a non-location-based ad hoc routing approach, namely Dynamic Source Routing (DSR). DSR was chosen for the comparison since RLS can be considered an adaptation of DSR’s route discovery mechanisms to the location-based domain. We also introduce and study possible optimizations for RLS, in particular caching, random re-broadcast jitter, and re-broadcast suppression. The quantitative results of our NS-2 simulation study show a very good performance of RLS combined with greedy routing, outperforming GLS and DSR for scenarios with high mobility and high node density.
Prospective Evaluation of a Cluster Pr o gramme for Finnish Forestry and Forest Industries

In this paper, we report a prospective evaluation process for a major research program for the Finnish forestry and forest industries. To a significant extent, this process was based on fifteen participatory workshops where tools of operational research F most notably multi-criteria methods embedded in a group support system F were deployed to help representatives from industry, the research community, and public administration in the assessment of socio-economic impacts and the identification of further research topics. Drawing upon this case study, we also analyze the preconditions, advantages, and limitations of similar kinds of participatory processes in the implementation of formative and summative evaluations.
Applicable Analysis and Discrete Mathematics

We present a linear time algorithm that computes the number of eigenvalues of a unicyclic graph in a given real interval. It operates directly on the graph, so that the matrix is not needed explicitly. The algorithm is applied to study the multiplicities of eigenvalues of closed caterpillars, obtain the spectrum of balanced closed caterpillars and give sufficient conditions for these graphs to be non-integral. We also use our method to study the distribution of eigenvalues of unicyclic graphs formed by adding a fixed number of copies of a path to each node in a cycle. We show that they are not integral graphs.
Effective certificate revocation scheme based on weighted voting game approach

Mobile ad hoc networks (MANETs) are wireless networks that have a wide range of applications because of their dynamic topologies and ease of deployment. Owing to the independent and dynamic nature of mobile nodes, the topology of a MANET often changes and is prone to various attacks. Therefore, substantial research in the area of security is required. Certificate revocation is an effective mechanism for providing network security services. However, the existing schemes are not well suited to MANETs because of their considerable overhead or low accuracy with respect to certificate revocation. In this study, the authors investigate a distributed certificate revocation protocol. On the basis of the game-theoretic model, they design a new voting-based security scheme. Their game-based security paradigm can provide the ability to practically respond to the current system conditions and is suitable for real MANET operations. Simulation results demonstrate the effectiveness and the efficiency of their scheme with respect to certificate revocation. Finally, they discuss the results of an evaluation provide an outlook on the future work in this field.
Web services and data integration

The developments of XML [4] and Web services [3] arechanging radically the art of data integration. We brieflydescribe Web services and consider some of their impacton data integration. We argue that XML and Web servicesprovide the proper infrastructure for data integration at theWeb scale. This is illustrated by some work going on atINRIA on Active XML, that is XML extended by allowingthe embedding of calls to Web services.
Inhibition of Langerhans Cell Maturation by Human Papillomavirus Type 16: A Novel Role for the Annexin A2 Heterotetramer in Immune Suppression

High-risk human papillomaviruses (HPVs) are sexually transmitted viruses causally associated with several cancers. During its natural life cycle, HPV16, the most common high-risk genotype, infects the epithelial basal cells in a process facilitated through a recently identified receptor, the annexin A2 heterotetramer (A2t). During infection, HPV16 also interacts with Langerhans cells (LC), the APC of the epithelium, inducing immune suppression, which is mediated by the HPV16 L2 minor capsid protein. Despite the importance of these virus-immune cell interactions, the specific mechanisms of HPV16 entry into LC and HPV16-induced immune suppression remain undefined. An N-terminal peptide of HPV16 L2 (aa 108–126) has been shown to specifically interact with A2t. In this study, we show that incubation of human LC with this peptide blocks binding of HPV16. Inhibiting this interaction with an A2t ligand or by small interfering RNA downregulation of A2t significantly decreases HPV16 internalization into LC in an L2-dependent manner. A2t is associated with suppression of LC maturation as demonstrated through attenuated secretion of Th1-associated cytokines and decreased surface expression of MHC class II on LC exposed to A2t. Conversely, small molecule inhibition of A2t prevents HPV16-induced suppression of LC immune function as indicated by significantly increased secretion of inflammatory cytokines and surface expression of CD86 in HPV16 treated LC pre-exposed to A2t inhibitors. These results demonstrate that HPV16 suppresses LC maturation through an interaction with A2t, revealing a novel role for this protein.