Miracle-dz/UniFAR-FTUs huggingface dataset:
10 Lessons from 10 Years of Measuring and Modeling the Internet's Autonomous Systems

Formally, the Internet inter-domain routing system is a collection of networks, their policies, peering relationships and organizational affiliations, and the addresses they advertize. It also includes components like Internet exchange points. By its very definition, each and every aspect of this system is impacted by BGP, the de-facto standard inter-domain routing protocol. The element of this inter-domain routing system that has attracted the single-most attention within the research community has been the "inter-domain topology". Unfortunately, almost from the get go, the vast majority of studies of this topology, from definition, to measurement, to modeling and analysis, have ignored the central role of BGP in this problem. The legacy is a set of specious findings, unsubstantiated claims, and ill-conceived ideas about the Internet as a whole. By presenting a BGP-focused state-of-the-art treatment of the aspects that are critical for a rigorous study of this inter-domain topology, we demystify in this paper many "controversial" observations reported in the existing literature. At the same time, we illustrate the benefits and richness of new scientific approaches to measuring, modeling, and analyzing the inter-domain topology that are faithful to the BGP-specific nature of this problem domain.
A mixed method for axisymmetric div-curl systems

We present a mixed method for a three-dimensional axisymmetric div-curl system reduced to a two-dimensional computational domain via cylindrical coordinates. We show that when the meridian axisymmetric Maxwell problem is approximated by a mixed method using the lowest order Nedelec elements (for the vector variable) and linear elements (for the Lagrange multiplier), one obtains optimal error estimates in certain weighted Sobolev norms. The main ingredient of the analysis is a sequence of projectors in the weighted norms satisfying some commutativity properties.
The cholesterol‐binding motif of the HIV‐1 glycoprotein gp41 regulates lateral sorting and oligomerization

Enveloped viruses often use membrane lipid rafts to assemble and bud, augment infection and spread efficiently. However, the molecular bases and functional consequences of the partitioning of viral glycoproteins into microdomains remain intriguing questions in virus biology. Here, we measured Foerster resonance energy transfer by fluorescence lifetime imaging microscopy (FLIM‐FRET) to study the role of distinct membrane proximal regions of the human immunodeficiency virus glycoprotein gp41 for lipid raft partitioning in living Chinese hamster ovary cells (CHO‐K1). Gp41 was labelled with a fluorescent protein at the exoplasmic face of the membrane, preventing any interference of the fluorophore with the proposed role of the transmembrane and cytoplasmic domains in lateral organization of gp41. Raft localization was deduced from interaction with an established raft marker, a fluorescently tagged glycophosphatidylinositol anchor and the cholesterol recognition amino acid consensus (CRAC) was identified as the crucial lateral sorting determinant in CHO‐K1 cells. Interestingly, the raft association of gp41 indicates a substantial cell‐to‐cell heterogeneity of the plasma membrane microdomains. In complementary fluorescence polarization microscopy, a distinct CRAC requirement was found for the oligomerization of the gp41 variants. Our data provide further insight into the molecular basis and biological implications of the cholesterol dependent lateral sorting of viral glycoproteins for virus assembly at cellular membranes.
Delayed procedural learning in α7‐nicotinic acetylcholine receptor knockout mice

The α7‐nicotinic acetylcholine receptor (nAChR) has long been a procognitive therapeutic target to treat schizophrenia. Evidence on the role of this receptor in cognition has been lacking, however, in part due to the limited availability of suitable ligands. The behavior of α7‐nAChR knockout (KO) mice has been examined previously, but cognitive assessments using tests with cross‐species translatability have been limited to date. Here, we assessed the cognitive performance of α7‐nAChR KO and wild‐type (WT) littermate mice in the attentional set‐shifting task of executive functioning, the radial arm maze test of spatial working memory span capacity and the novel object recognition test of short‐term memory. The reward motivation of these mutants was assessed using the progressive ratio breakpoint test. In addition, we assessed the exploratory behavior and sensorimotor gating using the behavioral pattern monitor and prepulse inhibition, respectively. α7‐nAChR KO mice exhibited normal set‐shifting, but impaired procedural learning (rule acquisition) in multiple paradigms. Spatial span capacity, short‐term memory, motivation for food, exploration and sensorimotor gating were all comparable to WT littermates. The data presented here support the notion that this receptor is important for such procedural learning, when patterns in the environment become clear and a rule is learned. In combination with the impaired attention observed previously in these mice, this finding suggests that agonist treatments should be examined in clinical studies of attention and procedural learning, perhaps in combination with cognitive behavioral therapy.
Passage Retrieval and Evaluation

Information retrieval researchers have studied passage retrieval extensively, yet there is no consensus within the community about how to evaluate the results of passage retrieval experiments. This paper describes five character-level passage evaluation measures and tasks for which they may be appropriate. In the second half of the paper we compare several passage retrieval models, including a new generative mixture model that outperforms strong baselines on many of the evaluation measures discussed in part one.
Chapter 26: The Cultural Politics of Schools: Implications for Leadership

There is an increasing interest among educational researchers in the ways resistance occurs in schools and how schools systematically silence the voices of students, teachers, and disenfranchised communi­ ties. The literature on institutional resistance and silencing is part of a broader literature that addresses the cultural politics of schools (Kan­ pol, 1992; Quantz, Rogers, and Dantley, 1991). 'Cultural politics' refers to the ways schools (a.) silence 'disruptive' voices, (b.) serve as sites in which student identities are negotiated within contexts that reflect the complex and interactive dynamics of class, race, gender, dis­ ability, and sexual orientation, and (c.) embed power relations in the structures, practices, curriculum, and everyday life of schools (Cherry­ holmes, 1988) 1. In this chapter I will, first, discuss why the dominant paradigm in the field of educational administration has ignored and/or been unable to meaningfully incorporate the research on cultural politics, including a discussion of how notions of 'culture' and 'politics' have been con­ structed within the field. Second, I will briefly review the literature on school cultural politics and discuss how it might inform current work in the area of school leadership, concentrating specifically on the cul­ tural politics associated with inequality, control, resistance, and iden­ tity. Finally, I will argue that the question of who school administrators ultimately work for has not been seriously theorized in the field of edu­ cational politics. In spite of a thick cloud of empowerment rhetoric, the present commitment of most appears to be to the legitimation of a non­ democratic and unequal status quo, rather than to the creation of demo­ cratic school cultures in which multiple voices and ways of being in schools and society are legitimated.
Patrones espaciales de la diáspora china en el mundo, España y Madrid

La dimension espacial es clave para entender las migraciones internacionales. En la diaspora china contemporanea esta afirmacion es aun mas pertinente dado que estamos ante un fenomeno global con varias escalas espaciales de analisis implicadas. Ademas, se trata de un proceso con un alto grado de selectividad espacial, lo que implica que solo cristalice en espacios urbanos muy dinamicos. En este sentido, Espana se ha convertido en los ultimos anos en destino preferente de la ancestral diaspora china, lo que nos permite presenciar el alumbramiento y desarrollo de enclaves etnicos en forma de chinatowns en las principales ciudades espanolas; con Madrid como referencia clave en este proceso. En este articulo, tras la exposicion de las interpretaciones teoricas que enmarcan el posterior analisis empirico, se estudiara este fenomeno a escala global, europea, nacional y local, gracias a la precision que ofrecen los Sistemas de Informacion Geografica para la identificacion de patrones espaciales. Palabras clave: Enclave etnico, Chinatown, diaspora china, logicas espaciales, migraciones internacionales, inmigracion china. __________________________ The spatial dimension is key to understanding international migrations. In the case of contemporary Chinese diaspora such statement is even more relevant given its condition of global phenomenon involving various spatial scales of analysis. Furthermore, its high degree of spatial selectivity implies that it only crystallizes within very dynamic urban spaces. In this sense, in last years Spain has become a preferred destination of ancient Chinese diaspora, allowing us to witness the birth and development of ethnic enclaves as Chinatowns in major Spanish cities. Madrid is a key reference in this process. After a revision of the theoretical interpretations given, the paper deals with the study of the phenomenon on a global, European and national scales, as well as in local levels, using capable GIS tools to identify spatial patterns. Keywords: Ethnic enclave, Chinatown, Chinese diaspora, spatial logic, international migration, immigration, China.
Lactococcin G Is a Potassium Ion-Conducting, Two-Component Bacteriocin

Lactococcin G is a novel lactococcal bacteriocin whose activity depends on the complementary action of two peptides, termed (cid:97) and (cid:98) . Peptide synthesis of the (cid:97) and (cid:98) peptides yielded biologically active lactococcin G, which was used in mode-of-action studies on sensitive cells of Lactococcus lactis . Approximately equivalent amounts of both peptides were required for optimal bactericidal effect. No effect was observed with either the (cid:97) or (cid:98) peptide in the absence of the complementary peptide. The combination of (cid:97) and (cid:98) peptides (lactococcin G) dissipates the membrane potential ( (cid:68)(cid:99) ), and as a consequence cells release (cid:97) -aminoisobutyrate, a non-metabolizable alanine analog that is accumulated through a proton motive-force dependent mechanism. In addition, the cellular ATP level is dramatically reduced, which results in a drastic decrease of the ATP-driven glutamate uptake. Lactococcin G does not form a proton-conducting pore, as it has no effect on
Correlation between 1,5-anhydroglucitol and glycemic excursions in type 2 diabetic patients.

BACKGROUND The accurate and comprehensive assessment of glycemic control in patients with diabetes is important for optimizing glycemic management and for formulating personalized diabetic treatment schemes. This study aimed to analyze the correlation between 1,5-anhydroglucitol (1,5-AG) and glycemic excursions in type 2 diabetic patients. METHODS Seventy-one outpatients with type 2 diabetes mellitus were randomly recruited from Chinese People's Liberation Army General Hospital. Using a continuous glucose monitoring system (CGMS), these patients' blood glucose levels were monitored for three consecutive days to obtain mean blood glucose (MBG) data. Intraday glycemic excursions were evaluated using the mean amplitude of glycemic excursions (MAGE), the largest amplitude of glycemic excursions (LAGE), standard deviation of blood glucose (SDBG) and the M-value. Interday glycemic excursion was assessed by absolute mean of daily difference (MODD). Postprandial glycemic fluctuations were evaluated using postprandial glucose excursions (PPGE) and postprandial incremental area under the curve (iAUC). Fasting venous blood samples were collected to measure serum 1,5-AG, whole-blood hemoglobin A1c (HbA1c) and serum glycated albumin (GA). Clinical markers of glycemia and parameters of glycemic excursions from CGMS were analyzed using the Pearson correlation coefficient and multivariate stepwise regression. RESULTS Pearson correlation analysis revealed that 1,5-AG was significantly correlated with MAGE, SDBG, M-value, LAGE, PPGE and iAUC (r values were -0.509, -0.430, -0.530, -0.462, -0.416 and -0.435, respectively, P < 0.01), especially in moderately and well-controlled patients, based on defined HbA1c levels. Multivariate stepwise regression analysis revealed a negative correlation between 1,5-AG and the above parameters, but not HbA1c and GA. Finally, HbA1c and GA were positively correlated with MBG and fasting blood glucose (FBG). CONCLUSIONS 1,5-AG was much better than HbA1c and GA as a marker of glycemic excursions in type 2 diabetic patients. Based on these results 1,5-AG is the best metric for assessing postprandial glucose levels in moderately and well-controlled patients, while HbA1c and GA were superior to 1,5-AG for monitoring MBG and FBG.
High Throughput Screen Identifies Small Molecule Inhibitors Specific for Mycobacterium tuberculosis Phosphoserine Phosphatase*

Background: Phosphoserine phosphatase (PSP) is an essential enzyme involved in l-serine biosynthesis. Results: High throughput screen was performed to identify specific PSP inhibitors with activity against intracellular bacteria. Conclusion: Validation of PSP as a drug target would lead to identification of scaffolds with a novel mechanism. Significance: This is the first report demonstrating selective inhibition of M. tuberculosis PSP enzyme. The emergence of drug-resistant strains of Mycobacterium tuberculosis makes identification and validation of newer drug targets a global priority. Phosphoserine phosphatase (PSP), a key essential metabolic enzyme involved in conversion of O-phospho-l-serine to l-serine, was characterized in this study. The M. tuberculosis genome harbors all enzymes involved in l-serine biosynthesis including two PSP homologs: Rv0505c (SerB1) and Rv3042c (SerB2). In the present study, we have biochemically characterized SerB2 enzyme and developed malachite green-based high throughput assay system to identify SerB2 inhibitors. We have identified 10 compounds that were structurally different from known PSP inhibitors, and few of these scaffolds were highly specific in their ability to inhibit SerB2 enzyme, were noncytotoxic against mammalian cell lines, and inhibited M. tuberculosis growth in vitro. Surface plasmon resonance experiments demonstrated the relative binding for these inhibitors. The two best hits identified in our screen, clorobiocin and rosaniline, were bactericidal in activity and killed intracellular bacteria in a dose-dependent manner. We have also identified amino acid residues critical for these SerB2-small molecule interactions. This is the first study where we validate that M. tuberculosis SerB2 is a druggable and suitable target to pursue for further high throughput assay system screening.
From GWAS to function: lessons from blood cells

Haematopoiesis, or the process of formation of mature blood cells from committed progenitors, represents an accessible and well‐studied paradigm of cell differentiation and lineage specification. Genetic association studies provide a powerful approach to discover new genes, biological pathways and mechanisms underlying haematopoietic development. Here, we highlight recent findings of genomewide association studies (GWAS) linking 145 genomic loci to traits affecting the formation of red and white cells and platelets in European and other ancestries. We present strategies to address the main challenges in GWAS discoveries, particularly to find functional and regulatory effects of genetic variants, and to identify genes through which these genetic variants affect haematological phenotypes. We argue that studies of haematological trait variation provide an ideal paradigm for understanding the function of GWAS‐associated variants owing to the accessible nature of cells, simple cellular phenotype and focused efforts to characterize the genetic and epigenetic factors influencing the regulatory landscape in highly pure mature cell populations.
Association of chronic insomnia symptoms and recurrent extreme sleep duration over 10 years with well-being in older adults: a cohort study

Objectives The extent to which aspects of sleep affect well-being in the long-term remains unclear. This longitudinal study examines the association between chronic insomnia symptoms, recurrent sleep duration and well-being at older ages. Setting A prospective cohort of UK civil servants (the Whitehall II study). Participants 4491 women and men (25.2% women) with sleep measured 3 times over 10 years and well-being once at age 55–79 years. Insomnia symptoms and sleep duration were assessed through self-reports in 1997–1999, 2003–2004 and 2007–2009. Primary outcome measures Indicators of well-being, measured in 2007–2009, were the Control, Autonomy, Self-realisation and Pleasure measure (CASP-19) of overall well-being (range 0–57) and the physical and mental well-being component scores (range 0–100) of the Short Form Health Survey (SF-36). Results In maximally adjusted analyses, chronic insomnia symptoms were associated with poorer overall well-being (difference between insomnia at 3 assessments vs none −7.0 (SE=0.4) p<0.001), mental well-being (difference −6.9 (SE=0.4), p<0.001) and physical well-being (difference −2.8 (SE=0.4), p<0.001) independently of the other sleep measures. There was a suggestion of a dose–response pattern in these associations. In addition, recurrent short sleep (difference between ≤5 h sleep reported at 3 assessments vs none −1.7 (SE=0.7), p<0.05) and recurrent long sleep (difference between >9 h reported at 2 or 3 assessments vs none −3.5 (SE=0.9), p<0.001) were associated with poorer physical well-being. Conclusions We conclude that in older people, chronic insomnia symptoms are negatively associated with all aspects of well-being, whereas recurrent long and short sleep is only associated with reduced physical well-being.
Bi-directional route optimization in mobile IP over wireless LAN

We propose to support symmetric bidirectional route optimization in mobile IPv4 considering ingress-filtering routers. We developed subnet-based direct tunneling techniques to improve the routing efficiency for mobile IP and a binding optimization technique to reduce the handoff latency for mobile nodes. An enhanced correspondent agent was introduced to collaborate with the home agent and the foreign agent to support these techniques. Utilizing a tunneling cache, datagrams sent from a mobile node can be directly tunneled to a correspondent agent, including binding update messages. The proposed, approach can maximize the use of a bi-directional tunnel without abandoning the transparency to existing hosts. Learning from our deployment experience, the enhanced mobile IP protocol is suitable for wireless LANs that provide broadband multimedia and location-based services.
Retinoic acid controls body axis extension by directly repressing Fgf8 transcription

Retinoic acid (RA) generated in the mesoderm of vertebrate embryos controls body axis extension by downregulating Fgf8 expression in cells exiting the caudal progenitor zone. RA activates transcription by binding to nuclear RA receptors (RARs) at RA response elements (RAREs), but it is unknown whether RA can directly repress transcription. Here, we analyzed a conserved RARE upstream of Fgf8 that binds RAR isoforms in mouse embryos. Transgenic embryos carrying Fgf8 fused to lacZ exhibited expression similar to caudal Fgf8, but deletion of the RARE resulted in ectopic trunk expression extending into somites and neuroectoderm. Epigenetic analysis using chromatin immunoprecipitation of trunk tissues from E8.25 wild-type and Raldh2−/− embryos lacking RA synthesis revealed RA-dependent recruitment of the repressive histone marker H3K27me3 and polycomb repressive complex 2 (PRC2) near the Fgf8 RARE. The co-regulator RERE, the loss of which results in ectopic Fgf8 expression and somite defects, was recruited near the RARb RARE by RA, but was released from the Fgf8 RARE by RA. Our findings demonstrate that RA directly represses Fgf8 through a RARE-mediated mechanism that promotes repressive chromatin, thus providing valuable insight into the mechanism of RA-FGF antagonism during progenitor cell differentiation.
Socio-Emotional Impacts of Playing Massively Multiplayer Online Role-Playing Games (MMORPGs) on Older Adults

The proportion of people aged 60 and over is growing faster than any other age group. Due to shift from career or family focus, loss of long-term companions and increasing likelihood of chronic and debilitating illness, older adults face some key social and psychological challenges such as loneliness, depression and lack of social support. Gerontology researchers have demonstrated that social interaction is an important component of successful aging. Massively Multiplayer Online Role-Playing Games (MMORPGs) can offer older adults many opportunities to maintain current and develop meaningful and supportive relationships. Drawing on the challenges facing older adults and prior theoretical and empirical studies, this research explored the social and emotional impacts of playing MMORPGs on older adults aged 55 and over, primarily analyzing the relationships between older adults’ social interactions in MMORPGs and six social and emotional factors (i.e., bridging and bonding social capital, loneliness, depression, social support and belongingness). To address this question, four research hypotheses were generated. An online survey was developed and published to eight World of Warcraft (WoW, a popular MMORPG) player forums to gather information about older gamers’ demographic characteristics, play patterns, social interactions in WoW, measurements of six social-emotional dimensions, and challenges facing older adults while playing WoW. Data were collected over a three and half months period (from May 15 to September 1, 2014) from a sample including 222 WoW players aged 55 and older. To answer the research questions and test the four hypotheses, hierarchical multiple regression analysis was applied, and Cohen’s f was computed to compare effect sizes. Similar to their younger counterparts, older adults’ social interactions in MMORPGs can take place on several different levels, and can be casual or intimate, and even romantic. Social interaction in MMORPGs is an important source for older adults’ social learning. The regression analyses revealed that enjoyment of relationships and quality of guild play has deep impacts on older adults’ social and emotional wellbeing.