Miracle-dz/UniFAR-FTUs huggingface dataset:
A combinatorial library for the binuclear metal center of bacterial phosphotriesterase

Phosphotriesterase (PTE) is a zinc metalloenzyme that catalyzes the hydrolysis of an extensive array of organophosphate pesticides and mammalian acetylcholinesterase nerve agents. Although the three‐dimensional crystal structure of PTE has been solved (M. M. Benning et al., Biochemistry 34:7973–7978, 1995), the precise functions of the individual amino acid residues that interact directly with the substrate at the active site are largely unknown. To construct mutants of PTE with altered specificities for particular target substrates, a simple methodology for generating a library of mutants at specific sites was developed. In this investigation, four of the six protein ligands to the binuclear metal site (His‐55, His‐57, His‐201, and His‐230) were targeted for further characterization and investigation. Using the polymerase chain reaction (PCR) protocols, a library of modified PTE genes was generated by simultaneously creating random combinations of histidine and cysteine codons at these four positions. The 16 possible DNA sequences were isolated and confirmed by dideoxy‐DNA sequencing. The 16 mutant proteins were expressed in Escherichia coli and grown with the presence or absence of 1 mM CoCl2, ZnSO4, or CdSO4in the growth medium. When grown in the presence of CoCl2, the H57C protein cell lysate showed greater activity for the hydrolysis of paraoxon than the wild type PTE cell lysate. H201C and H230C exhibited up to 15% of the wild‐type activity, while H55C, a green protein, was inactive under all assay conditions. All other mutants had <10−5 of wild‐type activity. None of the purified mutants that exhibited catalytic activity had a significantly altered Km for paraoxon. Proteins 29:553–561, 1997. © 1997 Wiley‐Liss, Inc.
The relationship between light, dopamine release and horizontal cell coupling in the mudpuppy retina.

1. The effect of different experimental conditions on electrical coupling between horizontal cells in the mudpuppy retina was studied by comparing the changes in responses to illumination of the central and peripheral portions of the receptive field, using centred spot and annulus stimuli. An increase in the amplitude of the response to a centred spot stimulus and a decrease in the amplitude of the response to a concentric annulus indicated a decrease in coupling, and vice versa. 2. Dopamine (10‐250 microM) caused a decrease in coupling between horizontal cells. The uncoupling effect of dopamine was much greater in dark‐adapted than in light‐adapted retinas. The effect of the D1‐receptor agonist SKF38393 was similar to that of dopamine. The effect of the D2‐receptor agonist LY171555 on coupling was opposite to that of dopamine; this was attributed to a reduction in endogenous dopamine release. 3. The D1 antagonist SCH23390 (15 microM) caused an increase in coupling between horizontal cells. This effect was much greater in light‐adapted than in dark‐adapted retinas. 4. The glutamate analogue 2‐amino‐4‐phosphonobutyrate (APB), which hyperpolarizes on‐centre bipolar cells and blocks their responses to light, caused an increase in coupling between horizontal cells. This effect of APB was greater in light‐adapted retinas than in dark‐adapted retinas. The effect of APB on coupling could be reversed by the addition of dopamine, but the effect of dopamine on coupling could not be reversed by the addition of APB. These results suggest that APB increases horizontal cell coupling by causing a decrease in dopamine release. 5. In dark‐adapted retinas, 2.5 min exposure to an adapting light caused a decrease in coupling between horizontal cells; the uncoupling effect of the adapting light was blocked in the presence of either SCH23390 or APB. 6. The results suggest that coupling between horizontal cells in the mudpuppy retina is decreased by dopamine acting at D1 receptors, that the release of dopamine affecting horizontal cells is greater under light‐adapted conditions, and that the pathway by which exposure to light increases this dopamine release is mainly via on‐centre bipolar cells.
Nonlinear Perturbations and Conservation Laws on Curved Backgrounds in GR and Other Metric Theories

The field-theoretical approach is reviewed. Perturbations in general relativity as well as in an arbitrary $D$-dimensional metric theory are studied on a background, which is a solution (arbitrary) of the theory. Lagrangian for perturbations is defined, and field equations for perturbations are derived from the variational principle. These equations are exact and equivalent to the equations in the standard formulation, but can be approximate also. The field-theoretical description is invariant under gauge (inner) transformations, which can be presented both in exact and approximate forms. Following the usual field-theoretical prescription, conserved quantities for perturbations are constructed. Conserved currents are expressed through divergences of superpotentials -- antisymmetric tensor densities. This form allows to relate a necessity to consider local properties of perturbations with a theoretical representation of the quasi-local nature of conserved quantities in metric theories. Applications of the formalism in general relativity are discussed. Generalized formulae for an arbitrary metric $D$-dimensional theory are tested in the Einstein-Gauss-Bonnet gravity.
Book Review: Franklin E. Zimring The Great American Crime Decline New York, NY: Oxford University Press, 2007. 258 pp. US$ 29.95 (hbk). ISBN 978—0-19—518115—9

The Great American Crime Decline is another worthy contribution to the field of criminology from Franklin Zimring. The book addresses the allimportant topic of the significant crime decline which occurred in the United States during the 1990s. It is divided into three parts, each made up of two chapters. Four appendices provide further data and methodological details. Part I paints the landscape of the crime decline in the United States (Chapter 1) and of the reaction to it from various constituencies (Chapter 2). For the purpose at hand, Zimring focuses on the following seven FBI Uniform Crime Report index offences: homicide; rape; aggravated assault; robbery; burglary; auto theft; larceny. By almost all accounts, the United States has experienced a substantial decline in crime rates throughout the 1990s. The decline has not yet ended (Clark, 2007). With the exception of Canada, this crime decline has seen no parallel in any other western hemisphere country. In a great lesson in criminological humility, Zimring exposes the pessimism which characterized the talk emanating from many of the prominent voices in the field just prior to the decline, and even while it was in full swing—in short, the ‘great American crime decline’ came as a complete surprise to all. This only goes to show what sort of a mind-set develops in a discipline which emerged approximately 175 years ago because of, and overall tended to react to, negative situations; its capacity to see, react to and explain good news is grossly atrophied. In Part II, Zimring evaluates the research on the three most commonly tested hypotheses to explain the crime decline: imprisonment, demography and the economy (Chapter 3). Then (Chapter 4), Zimring examines three new hypotheses considered to have had an impact on crime in the 1990s: (1) increased levels of policing, on the one hand, and the sharper management of policing, on the other; (2) the subsidence of the crack cocaine epidemic; and (3) the increased Theoretical Criminology © 2008 SAGE Publications Los Angeles, London, New Delhi, Singapore and Washington DC www.sagepublications. com Vol. 12(4): 545–563; 1362–4806 DOI: 10.1177/1362480608097155
How Many Protein-Protein Interactions Types Exist in Nature?

“Protein quaternary structure universe” refers to the ensemble of all protein-protein complexes across all organisms in nature. The number of quaternary folds thus corresponds to the number of ways proteins physically interact with other proteins. This study focuses on answering two basic questions: Whether the number of protein-protein interactions is limited and, if yes, how many different quaternary folds exist in nature. By all-to-all sequence and structure comparisons, we grouped the protein complexes in the protein data bank (PDB) into 3,629 families and 1,761 folds. A statistical model was introduced to obtain the quantitative relation between the numbers of quaternary families and quaternary folds in nature. The total number of possible protein-protein interactions was estimated around 4,000, which indicates that the current protein repository contains only 42% of quaternary folds in nature and a full coverage needs approximately a quarter century of experimental effort. The results have important implications to the protein complex structural modeling and the structure genomics of protein-protein interactions.
P21-activated kinase 1 (PAK1) as a therapeutic target in BRAF wild-type melanoma.

BACKGROUND Although remarkable clinical response rates in melanoma have been observed using vemurafenib or dabrafenib in patients with tumors carrying oncogenic mutations in BRAF, a substantial unmet medical need remains for the subset of patients with wild-type BRAF tumors. METHODS To investigate the role of p21-activated kinases (PAKs) in melanoma, we determined PAK1 genomic copy number and protein expression for a panel of human melanoma tissues. PAK1 was inhibited in vitro and in vivo using RNA interference or PF-3758309 inhibitor treatment in a panel of melanoma cell lines with known BRAF and RAS (rat sarcoma) genotype to better understand its role in melanoma cell proliferation and migration. Tumorigenesis was assessed in vivo in female NCR nude mice and analyzed with cubic spline regression and area under the curve analyses. All statistical tests were two-sided. RESULTS Strong cytoplasmic PAK1 protein expression was prevalent in melanomas (27%) and negatively associated with activating mutation of the BRAF oncogene (P < .001). Focal copy number gain of PAK1 at 11q13 was also observed in 9% of melanomas (n = 87; copy number ≥ 2.5) and was mutually exclusive with BRAF mutation (P < .005). Selective PAK1 inhibition attenuated signaling through mitogen-activated protein kinase (MAPK) as well as cytoskeleton-regulating pathways to modulate the proliferation and migration of BRAF wild-type melanoma cells. Treatment of BRAF wild-type melanomas with PF-3758309 PAK inhibitor decreased tumor growth for SK-MEL23 and 537MEL xenografts (91% and 63% inhibition, respectively; P < .001) and MAPK pathway activation in vivo. CONCLUSIONS Taken together, our results provide evidence for a functional role of PAK1 in BRAF wild-type melanoma and therapeutic use of PAK inhibitors in this indication.
Twenty-Five Years after Rodriguez: What Have We Learned?

Twenty-five years ago, the landmark Supreme Court decision in San Antonio Independent School District v. Rodriguez effectively closed the door on educational finance equity litigation in the federal courts. In that case, the high court ruled that despite the glaring disparity in funding between school districts in the San Antonio metropolitan area, the United States Constitution does not require that funding among school districts be equalized. Rodriguez was hardly the last word in school finance litigation, however, as educational finance reform advocates have turned to state courts and constitutions to bring about reform under theories of equity and adequacy in school funding. Using the twenty-fifth anniversary of Rodriguez as a milestone for reflection, this article examines three central assumptions that undergird the Rodriguez decision and fuel the unabated litigation over educational finance schemes: that dollars make a difference in educational outcomes, that courts and policy makers can develop standards for what is an “adequate” education, and that litigation will lead to equity in educational finance.
Security and Privacy Implications of URL Shortening Services

URL shortening services replace long URLs with shorter ones and subsequently redirect all requests for the shortened URL to the original long URL. In this paper we discuss and empirically analyze security and privacy risks caused by the use of URL shortening services. We empirically determine the most popular URL shortening services currently used on Twitter and analyze these with respect to malicious behavior, user tracking, ease of enumeration, and leakage of URLs to search engines. Also, we introduce a new attack scenario to enable SSL-only circumvention using SSLStrip and shortened URLs. Finally, we empirically analyze the use of URL shortening services in more than 7 million spam emails collected over the past seven years and determine the spam detection performance for the most popular services found.
Strong host resistance targeted against a viral suppressor of the plant gene silencing defence mechanism

The 2b protein encoded by cucumber mosaic cucumovirus (Cmv2b) acts as an important virulence determinant by suppressing post‐transcriptional gene silencing (PTGS), a natural plant defence mechanism against viruses. We report here that the tomato aspermy cucumovirus 2b protein (Tav2b), when expressed from the unrelated tobacco mosaic tobamovirus (TMV) RNA genome, activates strong host resistance responses to TMV in tobacco which are typical of the gene‐for‐gene disease resistance mechanism. Domain swapping between Cmv2b, which does not elicit these responses, and Tav2b, revealed functional domains in Tav2b critical for triggering virus resistance and hypersensitive cell death. Furthermore, substitution of two amino acids from Tav2b by those found at the same positions in Cmv2b, Lys21→Val and Arg28→Ser, abolished the ability to induce hypersensitive cell death and virus resistance. However, in Nicotiana benthamiana, a species related to tobacco, Tav2b functions as a virulence determinant and suppresses PTGS. Thus, a viral suppressor of the host gene silencing defence mechanism is the target of another independent host resistance mechanism. Our results provide new insights into the complex molecular strategies employed by viruses and their hosts for defence, counter‐defence and counter counter‐defence.
Incidence and outcome of primary Epstein-Barr virus infection and lymphoproliferative disease in pediatric heart transplant recipients.

BACKGROUND The objective of this study was to assess the relationship between Epstein-Barr virus (EBV) infection and posttransplantation lymphoproliferative disease (PTLD) in pediatric heart transplant recipients. EBV is implicated in the development of PTLD. However, the relationship between primary EBV infection and PTLD is not well understood. METHODS Serial EBV titers were determined prospectively in 50 children before and after heart transplantation. Results were correlated with the development of PTLD. The clinical presentation, management, and outcome of PTLD were characterized. RESULTS Before transplantation, EBV titers were positive in 19 and negative in 31 patients. After transplantation, all EBV-positive patients remained positive; 1 developed PTLD. Among EBV-negative patients, 12 of 31 remained negative; none developed PTLD. Nineteen patients demonstrated serologic evidence of primary EBV infection after heart transplantation; 12 developed PTLD. Mean follow-up after heart transplantation was 3.3 years (range 0.4 to 8.4 years). Mean time from heart transplantation to histologic confirmation of PTLD was 29 months (range 3 to 72 months). Survival with PTLD was 92%. CONCLUSIONS Twelve of 13 pediatric heart transplant recipients who developed PTLD had evidence of primary EBV infection. Serial monitoring of EBV titers may lead to earlier identification and improved treatment of PTLD.
Gender diversity in expatriation: evaluating theoretical perspectives

Purpose – The purpose of this paper is to examine the range of theoretical underpinning used to explain women's participation as expatriates with a view to identifying the most promising theoretical lenses for future research.Design/methodology/approach – Drawing upon theoretical explanations in the “women in management” and “women expatriates” literature, four main theoretical domains are identified that are used to understand and explain their continuing low representation as expatriates: women's choices, assignee characteristics, social and societal norms and institutional aspects. Key theories within each domain are evaluated to suggest a future theoretical research framework.Findings – The most promising theoretical explanation of women's low participation as expatriates is identified as being linked to gender stereotyping reinforced within an isomorphic institutional framework.Research limitations/implications – Research into women's inroads into management and into expatriation has generated consid.
Projection and innervation patterns of individual thalamic reticular axons in the thalamus of the adult rat: A three‐dimensional, graphic, and morphometric analysis

The γ‐aminobutyric acid‐ergic thalamic reticular nucleus (Rt), which carries matching topographical maps of both the thalamus and cortex and in which constituent cells can synaptically communicate between each other, is the major extrinsic source of thalamic inhibitions and disinhibitions. Whether all the Rt axonal projections into the thalamus are similarly organized and have common projection and innervation patterns are questions of great interest to further our knowledge of the functioning of the Rt.
LASER PULSE CORRELATION: A METHOD FOR DETECTING SUBTLE TOPOGRAPHIC CHANGE USING LIDAR RETURN WAVEFORMS

We present a technique for using the recorded laser return pulse as a raw observation to detect centimeter-level vertical topographic change from large footprint airborne and spaceborne laser altimetry. We use the correlation of waveforms from coincident footprints as an indication of the similarity in structure of th e waveforms from epoch to epoch, and assume that low correlation is an indicator of vertical structure or elevation change. Thus, using vertically and horizontally geolocated waveforms as raw observables (i.e., waveforms tied to a common reference ellipsoid), we assess whether epoch-to-epoch vertical ground motion results in a decrease in the correlation of coincident waveforms over time, and whether this can be used to quantify the magnitude of the deformation. Results of computer models and an example over an area of eroded beachfront are described.
CONCEPTS OF COLOURS IN CHILDREN WITH CONGENITAL BLINDNESS

This descriptive qualitative interview study investigates knowledge of colours in students who are congenitally blind. The purpose of this research was to explore how the lack of direct experience with colour, as a result of congenital blindness, affects judgments about semantic concepts. Qualitative methods were used to conduct interviews with 15 students. The results of the study indicate that students know the colours and have a favourite colour. The implications for practice are to pay more attention when we teach students with congenital blindness to associate colours with specific objects. Клучни зборови: боја, дете, визуелно ориентиран вербализам
Clustering Using a Random Walk Based Distance Measure

This work proposes a simple way to improve a clustering algo- rithm. The idea is to exploit a new distance metric called the \Euclidian Commute Time" (ECT) distance, based on a random walk model on a graph derived from the data. Using this distance measure instead of the usual Euclidean distance in a k-means algorithm allows to retrieve well- separated clusters of arbitrary shape, without working hypothesis about their data distribution. Experimental results show that the use of this new distance measure signiflcantly improves the quality of the clustering on the tested data sets.
Shading Contributes to the Reduction of Stem Mechanical Strength by Decreasing Cell Wall Synthesis in Japonica Rice (Oryza sativa L.)

Low solar radiation caused by industrial development and solar dimming has become a limitation in crop production in China. It is widely accepted that low solar radiation influences many aspects of plant development, including slender, weak stems and susceptibility to lodging. However, the underlying mechanisms are not well understood. To clarify how low solar radiation affects stem mechanical strength formation and lodging resistance, the japonica rice cultivars Wuyunjing23 (lodging-resistant) and W3668 (lodging-susceptible) were grown under field conditions with normal light (Control) and shading (the incident light was reduced by 60%) with a black nylon net. The yield and yield components, plant morphological characteristics, the stem mechanical strength, cell wall components, culm microstructure, gene expression correlated with cellulose and lignin biosynthesis were measured. The results showed that shading significantly reduced grain yield attributed to reduction of spikelets per panicles and grain weight. The stem-breaking strength decreased significantly under shading treatment; consequently, resulting in higher lodging index in rice plant in both varieties, as revealed by decreased by culm diameter, culm wall thickness and increased plant height, gravity center height. Compared with control, cell wall components including non-structural carbohydrate, sucrose, cellulose, and lignin reduced quite higher. With histochemical straining, shading largely reduced lignin deposition in the sclerenchyma cells and vascular bundle cells compared with control, and decreased cellulose deposition in the parenchyma cells of culm tissue in both Wuyunjing23 and W3668. And under shading condition, gene expression involved in secondary cell wall synthesis, OsPAL, OsCOMT, OsCCoAOMT, OsCCR, and OsCAD2, and primary cell wall synthesis, OsCesA1, OsCesA3, and OsCesA8 were decreased significantly. These results suggest that gene expression involved in the reduction of lignin and cellulose in both sclerenchyma and parenchyma cells, which attribute to lignin and cellulose in culm tissue and weak mechanical tissue, consequently, result in poor stem strength and higher lodging risks. Highlights: (1) Shading decreases the stem mechanical strength of japonica rice by decreasing non-structural carbohydrate, sucrose, lignin, and cellulose accumulation in culms. (2) The decrease of carbon source under shading condition is the cause for the lower lignin and cellulose accumulation in culm. (3) The expression of genes involved in lignin and primarily cell wall cellulose biosynthesis (OsCesA1, OsCesA3, and OsCesA8) at the stem formation stage are down-regulated under shading condition, inducing defective cell wall development and poor lodging resistance.
Introduction: The Social Context of Living Conditions in Poland

Poles celebrate two anniversaries in 2009: the twentieth anniversary of the transition from communism and the fifth anniversary of admission to the European Union. Changes taking place at present in Polish society are no longer of such a radical nature as the reconstruction of a democratic, free-market system or integration with Europe. They represent first and foremost a gradual improvement of Poland’s socioeconomic system, its adaptation to the conditions and requirements of an integrated Europe, and the acclimation by society to life under new conditions that, while already well established, continue to change constantly. These processes advance not without difficulty and undesirable negative side effects, though their direction is accepted and generally viewed in a positive light by