cssi/SciSciGPT-SciSciNet huggingface dataset:
A Cell Cycle-Regulated Toxoplasma Deubiquitinase, TgOTUD3A, Targets Polyubiquitins with Specific Lysine Linkages.

ABSTRACT The contribution of ubiquitin-mediated mechanisms in the regulation of the Toxoplasma gondii cell cycle has remained largely unexplored. Here, we describe the functional characterization of a T. gondii deubiquitinase (TGGT1_258780) of the ovarian-tumor domain-containing (OTU) family, which, based on its structural homology to the human OTUD3 clade, has been designated TgOTUD3A. The TgOTUD3A protein is expressed in a cell cycle-dependent manner mimicking its mRNA expression, indicating that it is regulated primarily at the transcriptional level. TgOTUD3A, which was found in the cytoplasm at low levels in G1 parasites, increased in abundance with the progression of the cell cycle and exhibited partial localization to the developing daughter scaffolds during cytokinesis. Recombinant TgOTUD3A but not a catalytic-site mutant TgOTUD3A (C229A) exhibited activity against poly- but not monoubiquitinated targets. This activity was selective for polyubiquitin chains with preference for specific lysine linkages (K48 > K11 > K63). All three of these polyubiquitin linkage modifications were found to be present in Toxoplasma, where they exhibited differential levels and localization patterns in a cell cycle-dependent manner. TgOTUD3A removed ubiquitin from the K48- but not the K63-linked ubiquitinated T. gondii proteins independently of the modified target protein, thereby exhibiting the characteristics of an exodeubiquitinase. In addition to cell cycle association, the demonstration of multiple ubiquitin linkages together with the selective deubiquitinase activity of TgOTUD3A reveals an unappreciated level of complexity in the T. gondii “ubiquitin code.” IMPORTANCE The role of ubiquitin-mediated processes in the regulation of the apicomplexan cell cycle is beginning to be elucidated. The recent analysis of the Toxoplasma “ubiquitome” highlights the importance of ubiquitination in the parasite cell cycle. The machinery regulating the ubiquitin dynamics in T. gondii has remained understudied. Here, we provide a biochemical characterization of an OTU (ovarian tumor) family deubiquitinase, TgOTUD3A, defining its localization and dynamic expression pattern at various stages of the cell cycle. We further establish that TgOTUD3A has activity preference for polyubiquitin chains with certain lysine linkages—such unique activity has not been previously reported in any apicomplexan. This is particularly important given the finding in this study that Toxoplasma gondii proteins are modified by diverse lysine-linked polyubiquitin chains and that these modifications are very dynamic across the cell cycle, pointing toward the sophistication of the “ubiquitin code” as a potential mechanism to regulate parasite biology.
Defending the Principle of Legality in Afghanistan: Toward a Unified Interpretation of Article 130 to the Afghan Constitution

The 2004 Constitution of Afghanistan is one of the main sources of criminal law, not because it defines crimes and punishments, but because it establishes the fundamental, individual rights and liberties that impact criminal law and procedure. Among these is the principle of legality, as expressed in Article 27. This is the doctrine that no person shall be held criminally liable for any conduct unless a statute criminalizing that conduct precedes it. This doctrine is based on the idea that it would be unjust to announce that an act is illegal, or increase punishment for a crime, after that act has been committed. In the context of Afghanistan, however, this doctrine is complicated by Article 130 to the Afghan Constitution, in which courts are directed to use Hanafi Fiqh (jurisprudence) to fill in the gaps when no provision in the Constitution or other Afghan statutes offers a path to justice. This article explains that based on Article 130, many criminal courts have used Hanafi jurisprudence to justify convicting individuals for crimes or subjecting individuals to punishments that exist under certain interpretations of Hanafi jurisprudence, but the crimes and punishments are not codified in the Afghan Criminal Code. This article argues that these interpretations of Article 130 not only violate the principle of legality set forth in Article 27 of the Afghan Constitution, but also contradict international law. In addition, this article asserts that differences in judicial training are at the root of why some jurists interpret Article 130 to allow for this level discretion and some do not. Finally, the article suggests that this problem might be helped by (1) using a similar approach as was used in Iran and Egypt, amending the Penal Code to include all legally recognized Tazir crimes; and (2) developing a system of secondary sources, like annotated codes, legal encyclopedias, and treatises, to help to shape future practice and bring more stability and consistency to judicial interpretation and rule of law.
Association of Sleep Duration, Symptoms, and Disorders with Mortality in Adults with Chronic Kidney Disease.

Introduction In general populations, short and long sleep duration, poor sleep quality, and sleep disorders have been associated with increased risk of death. We evaluated these associations in individuals with CKD. Methods This was a prospective cohort study of 1452 NHANES 2005 to 2008 participants with CKD. CKD was defined by estimated glomerular filtration rate 2 or urine albumin-to-creatinine ratio ≥30 mg/g. Sleep duration, sleep symptoms (difficulty falling asleep, difficulty staying asleep, daytime sleepiness, and nonrestorative sleep), and sleep disorders (restless legs syndrome and sleep apnea) were self-reported. Vital status was determined using NHANES mortality linkage through December 31, 2011. Results In this cohort, the mean age was 61 years, 58% were women, and 75% non-Hispanic white. During 4.4 years of median follow-up, we observed 234 deaths, of which 75 were due to cardiovascular causes. In multivariable analyses, compared with individuals who reported 7 to 8 hours of sleep, HR (95% CI) for all-cause mortality for sleep duration 8 hours were 1.50 (1.08–2.10) and 1.36 (0.89–2.08), respectively. The corresponding HR (95% CI) for cardiovascular mortality were 1.56 (0.72–3.37) and 1.56 (0.66–3.65). Nonrestorative sleep and restless legs syndrome were associated with increased risk for all-cause mortality (HR, 1.63 [95% CI, 1.13–2.35], and HR, 1.69 [95% CI, 1.04–275], respectively). Discussion In adults with CKD, short sleep duration, nonrestorative sleep, and restless legs syndrome are associated with increased risk of death. These findings underscore the importance of promoting adequate sleep in patients with CKD, and the need for future studies evaluating the impact of sleep interventions in this population.
Lipoprotein Heterogeneity Early in Pregnancy and Preterm Birth

Background The concentration and size of lipoprotein particles are associated with race, inflammation, and disease. When triglycerides are high, as in pregnancy, lipoprotein particle size may have physiologic importance beyond conventional lipid measurements. We considered that lipoprotein particles may be related to preterm birth (PTB) and explored race differences. Materials and Methods Samples were collected at 9 weeks' gestation (22 PTB [ Results Women with PTB had lower VLDL-P (− 10.66 nmol/L, p = 0.03) and higher systemic inflammation (+ 19.2 µmol/L, p = 0.02) compared with women with term births, independent of race, pre-pregnancy body mass index, and smoking. Black versus white women had lower VLDL-P and higher HDL cholesterol (both p Conclusion Women with PTB had lower VLDL-P early in pregnancy, which may represent impaired lipid response. Black–white differences in the lipoprotein profile are similar to nonpregnant adults, but race-specific lipoprotein and inflammation associations with PTB warrant further study.
Evaluating Workplace Constructs Using Computerized Techniques of Space Syntax

Previous literature on space syntax showed how workspace layout generated boundaries that created relationships of accessibility and visibility (Rashid et al. 2005). These measures in turn regulated occupants’ behavior and activities. Previous research also measured the impact of spatial layouts and various organizational constructs such as employees’ performance, satisfaction, and face-to-face communication levels. However, there is little research that documents whether these techniques are implemented in professional practice. Within this chapter, the author discusses and compares the visual properties of six different semi-government and private offices in Dubai regarding their terms of intelligibility and their expected level of face-to-face communication among employees. The author provides a comparison between these offices and mainstream workplace concepts using space syntax techniques. The goal of using these techniques is to establish a systematic and an objective way in describing the relationship between organizational constructs and office layouts.
With Malice Towards All? Moral Authority, Violence, and the (Affective) Discipline of Basketball (Bodies):

This article examines National Basketball Association Commissioner David Stern’s press conference on November 21, 2004, in response to the brawl between the Detroit Pistons and Indiana Pacers 2 day...
Ferroelectricity in Polar Polymer-Based FETs: A Hysteresis Analysis

There is an increasing number of reports on polar polymer-based Ferroelectric Field Effect Transistors (FeFETs), where the hysteresis of the drain current - gate voltage (Id-Vg) curve is investigated as the result of the ferroelectric polarization effect. However, separating ferroelectric effect from many of the factors (such as charge injection/trapping and the presence of mobile ions in the polymer) that confound interpretation is still confusing and controversial. This work presents a methodology to reliably identify the confounding factors which obscure the polarization effect in FeFETs. Careful observation of the Id-Vg curves, as well as monitoring the Id-Vg hysteresis and flat band voltage shift as a function of temperature and sweep frequency identifies the dominant mechanism. This methodology is demonstrated using 15-nm thick high glass transition temperature polar polymer-based FeFETs. In these devices, room temperature hysteresis is largely a consequence of charge trapping and mobile ions, while ferroelectric polarization is observed at elevated temperatures. This methodology can be used to unambiguously prove the effect of ferroelectric polarization in FeFETs.
The ATLAS Detector at the LHC

In order to learn more about fundamental interactions, particle physics offers three directions: increasing the energy, increasing the intensity or increasing the precision. The Large Hadron Collider (LHC) clearly pushes the energy frontier by achieving unprecedented collision energies. But it also provides very large datasets to test very weak interactions and the excellent performance of its experiments allows to improve the precision of measurements on some parameters and properties significantly. Being a hadron collider, the momentum transfer in the collisions is not fixed to one exact energy (as opposed to electron-positron colliders) and it is an excellent machine for discovering new particles.
1810. Therapeutic Drug Monitoring of Azole Antifungals at an Academic Medical Center: Opportunities and Lessons Learned

Background Therapeutic drug monitoring (TDM) is a valuable tool for certain antifungals as it may increase the probability of a successful outcome, minimize drug-related toxicity and interactions, and potentially prevent emergent resistance. With an increasing emphasis on the need for antifungal and laboratory stewardship, we sought to review azole antifungal TDM practices at our institution.
Rainfall thresholds for flow generation in desert ephemeral streams

Rainfall thresholds for streamflow generation are commonly mentioned in the literature, but studies rarely include methods for quantifying and comparing thresholds. This paper quantifies thresholds in ephemeral streams and evaluates how they are affected by rainfall and watershed properties. The study sites are in southern Arizona, USA; one is hyperarid and the other is semiarid. At both sites rainfall and streamflow were monitored in watersheds ranging from 10−3 to 102 km2. Streams flowed an average of 0–5 times per year in hyperarid watersheds and 3–11 times per year in semiarid watersheds. Although hyperarid sites had fewer flow events, their flow frequency (fraction of rain events causing flow) was higher than in semiarid sites for small (
A Comparison of Diurnal Resting Sites Used by Sylvilagus audubonii and Lepus californicus in the Chihuahuan Desert

Sylvilagus audubonii (desert cottontail) and Lepus californicus (black-tailed jackrabbit) occur in sympatry in the southwestern United States and northern Mexico. During the daytime, both species occupy shallow excavations under shrubs known as forms. Comparisons of form and shrub characteristics between the 2 species can provide insights into connections between body size, physiology, and behavior. I examined forms of the 2 species in the Chihuahuan Desert in southern New Mexico, USA, from 2014 to 2016. In response to temperature, S. audubonii varied the structure of its forms and dug burrows, whereas L. californicus did not. Sylvilagus audubonii forms were most commonly located in the centers of patches of shrubs, whereas L. californicus forms were most commonly on the edges of patches. Overhead canopy depth and exposure to direct sunlight were not different between the 2 species, but canopy heights were less at S. audubonii forms than at L. californicus forms. Sylvilagus audubonii individuals were less visible to predators than L. californicus individuals at predator eye level in all directions, and the horizontal extent of canopies was greater at S. audubonii forms than at L. californicus forms in all directions except to the left side. An asymmetry was evident in the exposure of S. audubonii to predators, which may be the result of brain lateralization. Although distance to nearest neighbor shrubs was not different between the 2 species, open space around L. californicus forms was greater than around S. audubonii forms. Lepus californicus forms were located under Larrea tridentata in proportion to its availability and more often than forms of S. audubonii, which were located under L. tridentata less often than it was available. These observations are consistent with concordant ensembles of adaptations in which S. audubonii is smaller, more sensitive to heat, and more inclined to hide rather than run from predators in comparison with L. californicus.
Artificial Neural Network Approach to Determine Elastic Modulus of Carbon Fiber-Reinforced Laminates

Recognized as a prominent material for engineering applications, carbon fiber-reinforced laminated composites require significant effort to characterize due to their anisotropic structure and viscoelastic nature. Dynamic mechanical analysis has been used to accelerate the testing process by transforming the measured viscoelastic properties to elastic modulus. To expand the transformation to anisotropic materials, artificial neural network approach is used to build the master relationship of the storage modulus in three in-plane directions. Using rotation transformation, the stiffness tensor can be calculated to extrapolate the frequency domain viscoelastic properties in any orientation with respect to the fiber direction. The viscoelastic properties are transformed to time domain relaxation function using the linear relationship of viscoelasticity. Stress response with a certain strain history is predicted and the elastic modulus is extracted. Compared to the experimental flexural test results, the artificial neural network-based method achieved an error of less than 7.3%. The results show that the transformation can predict the anisotropic material behavior at a wide range of temperatures and strain rates.
Flood evacuation and rescue: the identification of critical road segments using whole-landscape features

Abstract When studying real-world infrastructure systems as networks, one common avenue of analysis is the identification of critical network elements. These features are often defined as the nodes or edges in a given network that play an outsized role in the structure and functionality of the system. When network systems are under duress, particularly during (or just after) large-scale natural disasters, the continuity of networks is heavily dependent on these critical elements. If the critical features are vulnerable to disruption, the robustness of the network is compromised. The purpose of this paper is to introduce a novel geocomputational method for detecting critical road segments in a post-disaster landscape, with an eye toward human mobility and emergency response. This method accounts for the impacts of non-road landscape features on the overall traversability of an area and is contrasted with traditional critical feature analysis. The developed method provides several advantages, including the ability to produce higher-resolution, higher-fidelity criticality metrics for individual road segments. The paper concludes with a discussion on potential benefits to strategic urban planning, evacuation, and rescue planning during extreme events.
Risk Factors and Outcomes of Intracardiac Thrombosis During Orthotopic Liver Transplantation.

Abstract Background Intracardiac thrombosis incidence during orthotopic liver transplantation is estimated at 0.36% to 6.2% with mortality up to 68%. We aimed to evaluate risk factors and outcomes related to intracardiac thrombosis during orthotopic liver transplantation. Materials and Methods A comprehensive retrospective data review of 388 patients who underwent orthotopic liver transplantation at an urban transplant center from January 2013 to October 2016 was obtained. Results Six patients were found to have documented intracardiac thrombosis; 4 cases were recognized during the reperfusion stage and 1 during pre-anhepatic stage. All allografts were procured from decreased donors with a median donor age of 44 years (interquartile range, 35.25-49.75) and the cause of death was listed as cerebrovascular accident in 5 donors. Preoperative demographic, clinical, laboratory, and historical risk factors did not differ in patients with thrombosis. None had a prior history of trans-jugular intrahepatic portosystemic shunt or gastrointestinal bleeding. Three patients had renal injury, but no intraoperative hemodialysis was performed. Transesophageal echocardiographic findings included elevated pulmonary artery pressure (1/6), right ventricular strain (1/6), and pulmonary artery thrombus (1/6). Three patients died intraoperatively. Tissue plasminogen activator alone was given to 1 patient who did not survive, intravenous heparin only to 1 patient with resolution, and a combination of both was used in 2 patients with clot resolution achieved. Conclusion Cardiac thrombosis should be considered in patients having hemodynamic compromise during liver transplantation. Transesophageal echocardiography is a useful diagnostic tool. Intracardiac thrombosis treatment remains challenging; however, using both thrombolytics and heparin could achieve better results.
Effects of mangrove deforestation on near-shore coral reefs

Mangrove forests are among the world's most vulnerable subtropical and tropical habitats. With global losses already in excess of 50%, mangroves are being lost more rapidly than tropical rainforests. Those losses are critical to society because mangroves filter terrestrial contaminants, protecting coral reefs from eutrophication, sedimentation, and resulting degradation. Utila is a small island northeast of Honduras, well known for its diving opportunities. Anthropogenic development reduces the island's mangrove forests, threatening the health of surrounding coral reefs. We examined the effects of mangrove deforestation on coral reefs using shoreline mangrove density, near-shore nitrate levels, and algal coverage on adjacent reefs. These variables were measured offshore of both developed and undeveloped coasts. Mangrove density was significantly lower along the developed than the undeveloped coast (mean 0.27 stems/m2 vs. 3.01 stems/m2, respectively, p < 0.0001). Nitrate levels were significantly higher along the developed coast than along the undeveloped coast (mean 22.7 mg/L vs. 7.9 mg/L, respectively, p < 0.0001), as was algal cover (mean 48.1% vs. 32.4%, respectively, p < 0.0001). These results support arguments to reduce mangrove deforestation and encourage reforestation, which will protect not only mangroves and corals, but also avoid negative impacts to the local economy, which often is heavily reliant on dive tourism and fisheries.
Immunotherapies for Aging-Related Neurodegenerative Diseases—Emerging Perspectives and New Targets

Neurological disorders such as Alzheimer's disease (AD), Lewy body dementia (LBD), frontotemporal dementia (FTD), and vascular dementia (VCID) have no disease-modifying treatments to date and now constitute a dementia crisis that affects 5 million in the USA and over 50 million worldwide. The most common pathological hallmark of these age-related neurodegenerative diseases is the accumulation of specific proteins, including amyloid beta (Aβ), tau, α-synuclein (α-syn), TAR DNA-binding protein 43 (TDP43), and repeat-associated non-ATG (RAN) peptides, in the intra- and extracellular spaces of selected brain regions. Whereas it remains controversial whether these accumulations are pathogenic or merely a byproduct of disease, the majority of therapeutic research has focused on clearing protein aggregates. Immunotherapies have garnered particular attention for their ability to target specific protein strains and conformations as well as promote clearance. Immunotherapies can also be neuroprotective: by neutralizing extracellular protein aggregates, they reduce spread, synaptic damage, and neuroinflammation. This review will briefly examine the current state of research in immunotherapies against the 3 most commonly targeted proteins for age-related neurodegenerative disease: Aβ, tau, and α-syn. The discussion will then turn to combinatorial strategies that enhance the effects of immunotherapy against aggregating protein, followed by new potential targets of immunotherapy such as aging-related processes.
Family Income and Gang Presence in the Neighborhood: Diminished Returns of Black Families

Background: Based on the Minorities’ Diminished Returns (MDRs) framework, indicators of high socioeconomic status, such as higher family income, show weaker protective effects on various developmental, behavioral, and health outcomes for Black than White families. As a result of these MDRs, Black families who access education and income still report high levels of depression, smoking, obesity, and chronic disease. Limited knowledge exists on MDRs of income on neighborhood quality. Aims: Built on the MDRs framework, this study tested the hypothesis of whether the effect of family income and maternal education at birth on neighborhood gang presence varies between Black and White families. The hypotheses were that: (1) higher income families would report lower gang presence in their neighborhood, and (2) compared to Whites, Blacks would show weaker protective effects of family income on gang presence in their neighborhood. Methods: The Fragile Families and Child Wellbeing Study is a 15-year follow up study of a random sample of births in cities with larger than 200,000 population. Two thousand nine hundred and nineteen White or Black families were included and were followed from birth of their child for 15 years. The predictors were family income and maternal education at birth, treated as categorical variables. The outcome was gang presence in the neighborhood at age 15. Logistic regression was used for data analysis. Results: Higher maternal education at birth was inversely associated with gang presence in the neighborhoods, while family income at birth did not show an effect on reducing gang presence in the neighborhood at age 15. Family income at birth and race interact, suggesting that the association between family income at birth and gang presence in the neighborhood at age 15 was weaker for Black than White families. Our race-stratified models also showed an inverse effect of family income at birth on gang presence in the neighborhood at age 15 in White but not Black families. Conclusions: Diminished returns of family income at birth on neighborhood safety and social disorder may be a mechanism that contributes to racial health disparities in higher socioeconomic status and also poor outcomes for Black families across socioeconomic status (SES) levels. That is, a smaller protective effect of family income on changing the real lives of Black compared to White families may be one of the mechanisms by which health is worse than expected in Black families, across the entire SES spectrum. The health, behavioral, and developmental disparities are not only due to the racial gap in SES but also diminishing returns of socioeconomic status indicators such as family income for racial minorities. Research should study contextual and structural factors that reduce Black families’ ability to mobilize their human capital and secure health outcomes in urban settings.
Exploring gender and sexuality through a Twitter lens: the digital framing effect of the #fertilityday campaign by female users

Digital media have significantly contributed to the articulating and shaping of the contemporary debate about gender and sexuality, often disrupting numerous stereotypes promoted insistently by the...
Efficacy and safety of immune checkpoint blockade in self‐identified Black patients with advanced non–small cell lung cancer

Background To the authors' knowledge, race-based differences in efficacy for the treatment of patients with advanced non-small cell lung cancer (NSCLC) have not been studied to date due to the underrepresentation of patients of minority backgrounds in pivotal trials. In the current study, the authors examined real-world differences in outcome in a diverse patient population. Methods The authors retrospectively analyzed the clinical outcomes of patients with advanced NSCLC who were treated with single-agent immune checkpoint blockade (ICB) between 2013 and July 2018 at Winship Cancer Institute of Emory University in Atlanta, Georgia. Primary efficacy comparison between Black patients and White patients was performed using bivariate and multivariate analyses for overall survival (OS) and progression-free survival (PFS). Results Data from 257 patients were analyzed. The median age of the patients was 69 years; 50.6% of the patients were female, 63.4% were White, 29.5% were Black, and 7.1% of the patients were of "other" race. ICB was the first-line treatment in 51 patients (19.9%), the second-line treatment in 161 patients (62.6%), and the third-line treatment in 33 patients (12.9%). The most commonly used agents were nivolumab (49.0%), pembrolizumab (25.2%), and atezolizumab (21.3%). No differences with regard to OS (P = .839) and PFS (P = .235) were noted between Black and White patients. The sample overall response rate was 20.6% (15.2% in Black patients and 23.1% in White patients). No differences with regard to OS (P = .081) and PFS (P = .176) were observed between female and male patients. The rate of immune-related adverse events was found to be similar in Black and White patients (20.0% vs 29.9%; P = .148). On multivariate analysis, race was not found to be significantly associated with OS or PFS. Conclusions Real-world analysis of the authors' institutional experience demonstrated similar efficacy and tolerability of ICB in Black versus White patients with advanced NSCLC. Larger multi-institutional studies including other US minority populations would make the findings of the current study more generalizable.
The Premise and Development of CHECK IN-Check-In for Exchange of Clinical and Key Information to Enhance Palliative Care Discussions for Patients With Limited English Proficiency.

Communication regarding serious illness is challenging in most circumstances. Patients with Limited English Proficiency (LEP) have unique language and cultural needs that often require collaboratio...
An Exhaustive Survey on P4 Programmable Data Plane Switches: Taxonomy, Applications, Challenges, and Future Trends

Traditionally, the data plane has been designed with fixed functions to forward packets using a small set of protocols. This closed-design paradigm has limited the capability of the switches to proprietary implementations which are hard-coded by vendors, inducing a lengthy, costly, and inflexible process. Recently, data plane programmability has attracted significant attention from both the research community and the industry, permitting operators and programmers in general to run customized packet processing functions. This open-design paradigm is paving the way for an unprecedented wave of innovation and experimentation by reducing the time of designing, testing, and adopting new protocols; enabling a customized, top-down approach to develop network applications; providing granular visibility of packet events defined by the programmer; reducing complexity and enhancing resource utilization of the programmable switches; and drastically improving the performance of applications that are offloaded to the data plane. Despite the impressive advantages of programmable data plane switches and their importance in modern networks, the literature has been missing a comprehensive survey. To this end, this paper provides a background encompassing an overview of the evolution of networks from legacy to programmable, describing the essentials of programmable switches, and summarizing their advantages over Software-defined Networking (SDN) and legacy devices. The paper then presents a unique, comprehensive taxonomy of applications developed with P4 language; surveying, classifying, and analyzing more than 200 articles; discussing challenges and considerations; and presenting future perspectives and open research issues.
Dissecting Monomer-Dimer Equilibrium of an RNase P Protein Provides Insight Into the Synergistic Flexibility of 5' Leader Pre-tRNA Recognition

Ribonuclease P (RNase P) is a universal RNA-protein endonuclease that catalyzes 5' precursor-tRNA (ptRNA) processing. The RNase P RNA plays the catalytic role in ptRNA processing; however, the RNase P protein is required for catalysis in vivo and interacts with the 5' leader sequence. A single P RNA and a P protein form the functional RNase P holoenzyme yet dimeric forms of bacterial RNase P can interact with non-tRNA substrates and influence bacterial cell growth. Oligomeric forms of the P protein can also occur in vitro and occlude the 5' leader ptRNA binding interface, presenting a challenge in accurately defining the substrate recognition properties. To overcome this, concentration and temperature dependent NMR studies were performed on a thermostable RNase P protein from Thermatoga maritima. NMR relaxation (R1, R2), heteronuclear NOE, and diffusion ordered spectroscopy (DOSY) experiments were analyzed, identifying a monomeric species through the determination of the diffusion coefficients (D) and rotational correlation times (τc). Experimental diffusion coefficients and τc values for the predominant monomer (2.17 ± 0.36 * 10-10 m2/s, τ c = 5.3 ns) or dimer (1.87 ± 0.40* 10-10 m2/s, τ c = 9.7 ns) protein assemblies at 45°C correlate well with calculated diffusion coefficients derived from the crystallographic P protein structure (PDB 1NZ0). The identification of a monomeric P protein conformer from relaxation data and chemical shift information enabled us to gain novel insight into the structure of the P protein, highlighting a lack of structural convergence of the N-terminus (residues 1-14) in solution. We propose that the N-terminus of the bacterial P protein is partially disordered and adopts a stable conformation in the presence of RNA. In addition, we have determined the location of the 5' leader RNA in solution and measured the affinity of the 5' leader RNA-P protein interaction. We show that the monomer P protein interacts with RNA at the 5' leader binding cleft that was previously identified using X-ray crystallography. Data support a model where N-terminal protein flexibility is stabilized by holoenzyme formation and helps to accommodate the 5' leader region of ptRNA. Taken together, local structural changes of the P protein and the 5' leader RNA provide a means to obtain optimal substrate alignment and activation of the RNase P holoenzyme.
Electron capture and positron decay of /sup 206/Fr and /sup 208/Fr and the energy levels of /sup 206/Rn and /sup 208/Rn

The isotopes /sup 206/Fr and /sup 208/Fr were produced by the reactions Ir(/sup 20/Ne,xn)/sup 206,208/Fr and mass separated on-line. The electron-capture and positron decays to /sup 206/Rn and /sup 208/Rn were studied by collecting ..gamma.. ray and internal conversion electron singles spectra as a function of decay time as well as ..gamma..-..gamma.., ..gamma..-e/sup -/, and ..gamma..-x ray coincidence spectra. The energies and many of the spins were determined for 18 excited, even parity states in /sup 208/Rn and for 10 excited, even parity states in /sup 206/Rn. These nuclei appear to be excellent candidates for interpretation in terms of a weak coupling shell model. The energy levels were also compared to the predictions of the interacting boson approximation model.
Grid cell spatial tuning reduced following systemic muscarinic receptor blockade

Grid cells of the medial entorhinal cortex exhibit a periodic and stable pattern of spatial tuning that may reflect the output of a path integration system. This grid pattern has been hypothesized to serve as a spatial coordinate system for navigation and memory function. The mechanisms underlying the generation of this characteristic tuning pattern remain poorly understood. Systemic administration of the muscarinic antagonist scopolamine flattens the typically positive correlation between running speed and entorhinal theta frequency in rats. The loss of this neural correlate of velocity, an important signal for the calculation of path integration, raises the question of what influence scopolamine has on the grid cell tuning as a read out of the path integration system. To test this, the spatial tuning properties of grid cells were compared before and after systemic administration of scopolamine as rats completed laps on a circle track for food rewards. The results show that the spatial tuning of the grid cells was reduced following scopolamine administration. The tuning of head direction cells, in contrast, was not reduced by scopolamine. This is the first report to demonstrate a link between cholinergic function and grid cell tuning. This work suggests that the loss of tuning in the grid cell network may underlie the navigational disorientation observed in Alzheimer's patients and elderly individuals with reduced cholinergic tone.
Organizational Citizenship Behavior, Organizational Communication, and Burnout: The Buffering Role of Perceived Organizational Support and Psychological Contracts

This study investigated the communicative role of perceived organizational support and psychological contracts in fulfilling exchange relationships and buffering burnout in employees contributing extra role time organizational citizenship behaviors (ERT-OCB). The lens of social information processing positioned burnout as a job attitude subject to the influence of the organization’s communication environment that informs employees as to the value they and their extra role time contributions hold with the organization. Participants (N = d461), high school teachers coaching debate teams from 46 states, completed questionnaires. Findings showed that both organizational support and psychological contract fulfillment buffered the positive relationship between ERT-OCB and burnout.
Cohomology of Hierarchical Tilings

We go over different versions of tiling cohomology (Cech, patternequivariant, PV, quotient) with emphasis on the inverse limit constructions used to compute these cohomologies. We then consider the uses of tiling cohomology to distinguish spaces, to understand deformations, and to help understand maps between tiling spaces. The emphasis of this chapter is on substitution tilings and their generalizations, but the underlying ideas apply equally well to cut-and-project tilings and to tilings defined by local matching rules.
Cool to Critical: Managing Web Services Now

Web services are no longer just hype — they are being sanctioned by the industry on two fronts, standards and products. IBM is investing time, talent, and money on both these fronts, establishing itself as an industry leader. Web services are being developed as the foundation of a new generation of business-to-business and application integration architectures. This places Web services technologies in a business critical role within most enterprises. The corollary to this is that the Web services and the applications that use them must be manageable, from end to end, through the firewalls. The business-to-business Web services applications require management solutions in kind. They must be platform and technology agnostic, available through firewall, internet friendly, and flexible. This presents new challenges and opportunities to management vendors.
The Right to Reparation in International Law for Victims of Armed Conflict

1. Introduction, objectives and method Part I. Responsibility and Legal Standards: 2. State responsibility, the international legal order and development of legal norms for victims 3. Human rights jurisprudence on reparations, international and regional 4. Victims' rights in international criminal law 5. Legal state of play: convergence of international law and reparation as an individual legal right with customary recognition Part II. Transferring Standards into Reality: 6. The role of the UN, promotion of victims' rights and reparations in practice 7. Case study: reparations in Guatemala 8. Case study: reparations in Sierra Leone 9. Case study: reparations in East Timor 10. Case study: reparations in Colombia 11. Reparations in practice: comparative analysis of practice, lessons learnt and future challenges 12. The right to reparation and implementation of the legal norm: emerging convergence of law and practice?
Frequency of unexplained meningeal enhancement in the brain after lumbar puncture.

PURPOSE To examine the hypothesis that lumbar puncture alone may cause meningeal enhancement in the brain. METHODS We prospectively reviewed the brain MR examinations of all patients from a 6-month period who were studied within 1 month after lumbar puncture. We also retrospectively reviewed all cases of dural-arachnoidal enhancement in the brain from the preceding 18-month period. RESULTS In the prospective group, only one case out of 97 enhanced brain MR examinations after lumbar puncture did not have a clear cause for dural-arachnoidal enhancement. In the retrospective group, only one case out of 11 with enhancement was not clearly explained. CONCLUSIONS Dural-arachnoidal enhancement in the brain after lumbar puncture is uncommon, if it occurs at all, and lumbar puncture as a cause of enhancement should be considered a rare diagnosis of exclusion.
Tax Offsets and Netting Operations in Post-Soviet Public Finance

Post-Soviet economies are plagued by a public-sector practice whereby the Ministry of Finance cancels tax liabilities that enterprises owe it in exchange for debts the Ministry owes enterprises. While the practice seems innocuous enough to its practitioners, it has multiple distorting effects. Netting operations distort prices, prevent increased monetization of the economy, and hinder the pace of economic transformation in post-soviet economies. This paper describes the practice of netting operations, draws an analogy with input-output models used in planned economies, and reveals the multiple distorting effects of netting operations.
The Neurospora crassa cyt-20 gene encodes cytosolic and mitochondrial valyl-tRNA synthetases and may have a second function in addition to protein synthesis.

Abstract The cyt-20-1 mutant of Neurospora crassa is a temperature-sensitive, cytochrome b- and aa3-deficient strain that is severely deficient in both mitochondrial and cytosolic protein synthesis (R.A. Collins, H. Bertrand, R.J. LaPolla, and A.M. Lambowitz, Mol. Gen. Genet. 177:73-84, 1979). We cloned the cyt-20+ gene by complementation of the cyt-20-1 mutation and found that it contains a 1,093-amino-acid open reading frame (ORF) that encodes both the cytosolic and mitochondrial valyl-tRNA synthetases (vaIRSs). A second mutation, un-3, which is allelic with cyt-20-1, also results in temperature-sensitive growth, but not in gross deficiencies in cytochromes b and aa3 or protein synthesis. The un-3 mutant had also been reported to have pleiotropic defects in cellular transport process, resulting in resistance to amino acid analogs (M.S. Kappy and R.L. Metzenberg, J. Bacteriol. 94:1629-1637, 1967), but this resistance phenotype is separable from the temperature sensitivity in crosses and may result from a mutation in a different gene. The 1,093-amino-acid ORF encoding vaIRSs is the site of missense mutations resulting in temperature sensitivity in both cyt-20-1 and un-3 and is required for the transformation of both mutants. The opposite strand of the cyt-20 gene encodes an overlapping ORF of 532 amino acids, which may also be functional but is not required for transformation of either mutant. The cyt-20-1 mutation in the vaIRS ORF results in severe deficiencies of both mitochondrial and cytosolic vaIRS activities, whereas the un-3 mutation does not appear to result in a deficiency of these activities or of mitochondrial or cytosolic protein synthesis sufficient to account for its temperature-sensitive growth. The phenotype of the un-3 mutant raises the possibility that the vaIRS ORF has a second function in addition to protein synthesis.
Dosage-dependent modulation of glucose repression by MSN3 (STD1) in Saccharomyces cerevisiae.

Abstract The SNF1 protein kinase of Saccharomyces cerevisiae is required to relieve glucose repression of transcription. To identify components of the SNF1 pathway, we isolated multicopy suppressors of defects caused by loss of SNF4, an activator of the SNF1 kinase. Increased dosage of the MSN3 gene restored invertase expression in snf4 mutants and also relieved glucose repression in the wild type. Deletion of MSN3 caused no substantial phenotype, and we identified a homolog, MTH1, encoding a protein 61% identical to MSN3. Both are also homologous to chicken fimbrin, human plastin, and yeast SAC6 over a 43-residue region. Deletion of MSN3 and MTH1 together impaired derepression of invertase in response to glucose limitation. Finally, MSN3 physically interacts with the SNF1 protein kinase, as assayed by a two-hybrid system and by in vitro binding studies. MSN3 is the same gene as STD1, a multicopy suppressor of defects caused by overexpression of the C terminus of TATA-binding protein (R. W. Ganster, W. Shen, and M. C. Schmidt, Mol. Cell. Biol. 13:3650-3659, 1993). Taken together, these data suggest that MSN3 modulates the regulatory response to glucose and may couple the SNF1 pathway to transcription.
A role for phospholipids in the binding and metabolism of drugs by hepatic microsomes. Use of the fluorescent hydrophobic probe 1-anilinonaphthalene-8-sulphonate.

1. The pretreatment of rat liver microsomes with phospholipase C or D decreased the N-demethylation of (+)-benzphetamine. The hydroxylation of aniline was essentially unchanged by pretreatment of microsomes with phospholipase C. 2. Some components of the microsomal mixed-function oxidase system were impaired by phospholipases. 3. The fluorescence of 1-anilinonaphthalene-8-sulphonate (ANS) was greatly enhanced by microsomes. Phospholipase C or D markedly decreased ANS–microsome fluorescence. Quantum yield of ANS–microsome fluorescence appeared to be related directly to phospholipid content of microsomes. 4. Most of the drugs studied enhanced ANS–microsome fluorescence. Warfarin, however, displaced ANS fluorescence competitively from microsomes. The latter effect was postulated as being due to warfarin competing with ANS for the cationic site on microsomal phosphatidylcholine. 5. ANS fluorescence was also increased by the presence of phospholipid micelles. The fluorescence of ANS–phosphatidylcholine micelles was modified by warfarin and (+)-benzphetamine in a manner similar to that observed with microsomes. Warfarin decrease of fluorescence was absent when ANS was bound to phosphatidic acid, which lacks a cationic site. 6. Trypsin pretreatment of microsomes did not modify ANS–microsome fluorescence, including drug-induced changes. 7. It was postulated that phospholipids have a permissive role in the metabolism of most drugs by hepatic microsomes and that the ANS probe might reflect interactions of compounds with microsomal membrane phospholipids.
Ocular Manifestations of 22q11.2 Microduplication

Purpose To report a new ocular manifestation of the dup22q11 syndrome and explore involved genes that may offer insight to mechanisms of pathogenesis. Design Case series. Participants Two male patients with this syndrome diagnosed with dup22q11.2. Methods Medical records were reviewed. Duplication was detected in the oligo-single nucleotide polymorphism chromosomal microarray and duplicated genes within the segment where determined by literature and database review. Potential associations between the ophthalmologic manifestations and their physiopathology were investigated. Main Outcome Measures Microarray results and identification of candidate genes within the duplicated segment. Results Our patients demonstrate previously unreported findings of dup22q11.2, including Marcus Gunn jaw winking, Duane's retraction syndrome, and other abnormal eye movements consistent with a congenital cranial dysinnervation disorder (CCDD), retinal vascular tortuosity, and primary infantile glaucoma. The duplicated segment in case 1 includes SNAP29 , which could be linked with the development of retinal vascular tortuosity, and MAPK1 , which seems to play a role in axonal development through the semaphorin pathway, which may serve as a candidate gene for CCDD. In case 2, the CLDN5 gene is within the duplicated segment. CLDN5 could be involved in the pathophysiology of glaucoma. Conclusions Our cases expand the ocular phenotype for duplication of 22q11 and serve to identify potential candidate genes for the development of CCDD, retinal vascular tortuosity, and glaucoma.
Oxidative properties of swollen rat liver mitochondria.

Abstract Rat liver mitochondria undergo extensive swelling when they are incubated in hypotonic sucrose medium containing 5 m m Pi. After 30 min of swelling at 25 °C, a three- to fourfold increase in volume has occurred, accompanied by gross disorganization of the matrix as observed by electron microscopy. Succinate-supported respiration was unchanged, but the respiration of NAD-linked substrates was reduced and there was a complete and irreversible loss of phosphorylation in both cases. β-Hydroxybutyrate-supported respiration was regained completely on addition of NAD to the swollen mitochondria. α-Ketoglutarate- and malate + pyruvate-supported respiration was only partially restored by the addition of NAD. This inhibition of respiration in swollen mitochondria may be due to a disorganization of a putative complex of Krebs cycle enzymes on the inner surface of the inner membrane.