cssi/SciSciGPT-SciSciNet huggingface dataset:
Gene-level analysis of rare variants in 363,977 whole exome sequences reveals an association of GIGYF1 loss of function with diabetes

Abstract Sequencing of large cohorts offers an unprecedented opportunity to identify rare genetic variants and to find novel contributors to human disease. We used gene-based collapsing tests to identify genes associated with glucose, HbA1c and type 2 diabetes (T2D) diagnosis in 363,977 exome-sequenced participants in the UK Biobank. We identified associations for variants in GCK, HNF1A and PDX1, which are known to be involved in Mendelian forms of diabetes. Notably, we uncovered novel associations for GIGYF1, a gene not previously implicated by human genetics, in diabetes. GIGYF1 predicted loss of function (pLOF) variants associated with increased levels of glucose (0.77 mmol/L increase, p = 4.42 × 10-12) and HbA1c (4.33 mmol/mol, p = 1.28 × 10-14) as well as T2D diagnosis (OR = 4.15, p= 6.14 ×10-11). Multiple rare variants contributed to these associations, including singleton variants. GIGYF1 pLOF also associated with decreased cholesterol levels as well as an increased risk of hypothyroidism. The association of GIGYF1 pLOF with T2D diagnosis replicated in an independent cohort from the Geisinger Health System. In addition, a common variant association for glucose and T2D was identified at the GIGYF1 locus. Our results highlight the role of GIGYF1 in regulating insulin signaling and protecting from diabetes. Author Summary Genetic studies focused on high impact variants in protein-coding regions of the genome can provide valuable insight into the biology of human disease. As these variants tend to be rare, studying them requires large cohort sizes and methods to aggregate variants that are likely to have a similar biological impact. We studied how rare genetic variants contribute to type 2 diabetes (T2D) using sequencing data from 363,977 participants in the UK Biobank, employing methods to aggregate variants at the level of individual genes. As well as identifying genes known to be involved in inherited forms of diabetes, we uncovered a novel association for GIGYF1. GIGYF1 loss of function associated with increased risk of T2D and increased levels of the diabetes biomarkers glucose and HbA1c. This association was also seen in an independent dataset. GIGYF1 encodes a protein that binds a negative regulator of the insulin receptor that has not been well-characterized in the literature. By highlighting the importance of GIGYF1 in modulating insulin signaling these results may lead to new therapeutic approaches for diabetes as well as a new appreciation for GIGYF1 loss of function as a genetic risk factor for T2D.
Management of the Patients with Negative Radioiodine Scan and Elevated Serum Thyroglobulin

This chapter addresses the dilemma facing the clinician when serum thyroglobulin (Tg) is clearly measurable post-thyroidectomy and radioiodine ablation, thereby indicating evidence of residual thyroid cancer, but traditional isotopic scans with iodine-123 or iodine-131 are negative and hence the source of the thyroglobulin cannot be localizable. Causes for a Tg-positive/scan-negative situation are described as is the approach to management of such patients by methods of alternative imaging modalities or by empiric radioiodine treatment. The opposite clinical picture of the patient with an undetectable serum Tg but a positive isotope scan is also discussed briefly.
Teleworkers and Their Use of an Enterprise Social Networking Platform

This study surveyed teleworker usage of a social networking platform within an enterprise. Compared to on-campus employees, teleworkers exhibited earlier adoption, higher percentage of contributions, more variance in work hours, and lower membership in socially-oriented groups (versus work focused groups). The last result seems counterintuitive, and we propose two possible reasons for this phenomenon: the perceived need to cultivate an external perception of productivity, and lack of access to social events tied to specific geographic office locations. In addition, we provide insights, gleaned from interviews, into teleworker use of collaboration tools.
Tetra-ethyl-ammonium (2,2'-bipyridine)tetra-cyanidocobaltate(III) sesquihydrate acetonitrile solvate.

The title complex, (C8H20N)[Co(CN)4(C10H8N2)]·CH3CN·1.5H2O, consists of tetra­ethyl ammonium cations, mononuclear [CoIIIbpy(CN)4]− anions and uncoordinated water and acetonitrile mol­ecules. The CoIII atom is six-coordinated by two 2,2′-bipyridine (bpy) N atoms and four cyanide C atoms in a distorted octa­hedral geometry. The acute bite angle of the chelating bpy [82.28 (8)°] is the main factor accounting for this distortion. In addition, the tetra­ethyl­ammonium cation is significantly disordered [occupancy ratio 0.611 (3):0.389 (3)]. The presence of water mol­ecules, one of which is disordered over two positions about an inversion center, results in the formation of a network of O—H⋯N hydrogen bonds involving the cyanide N atoms.
Photographic Color Display Technology

This article reviews color photographic output technology based on silver halide materials. The largest product market in this category is reflection print material, such as that used in color photographic paper. Color paper is used primarily for making prints from photographic negatives and recently, as a high quality output medium for digital images. A number of other types of products employ very similar emulsion technology. In addition to reflection display materials, several types of transmissive color photographic display materials use this technology. The film that is used for projecting motion pictures (motion picture “print” film) is based on this technology. Large color photographic display materials, used primarily for advertising, are available on either clear or translucent plastic supports. These materials also use nearly identical emulsion technology to that used in photographic paper and motion picture print film. Because photographic emulsion technology is the basis for, and common among all of these different types of color photographic display products, photographic emulsion technology for display materials is the focus of this review. There is relatively little information published in journal articles or product information on the technologies described in this report. For this reason, this article relies heavily on information published in the patent literature. Although the patent literature gives a good indication of the type of technologies available and areas of research and intellectual property interest, it does not specifically show which technologies are actually used, or in which products. As such, this article focuses on the technologies available in color photographic display materials and should not be taken to indicate or imply which technologies, compounds, or materials are used in any particular product. Keywords: structure; photography; paper base; coatings; emulsion characteristics; iodide source; sensitization; digital images; dye bleach; ILFochrome
Development of a Mechatronics-Based Citizen Science Platform for Aquatic Environmental Monitoring

In this paper, we present the design and proof of concept of a low-cost, self-sustained mobile surface vehicle for environmental monitoring. The vehicle is equipped with water quality sensors and cameras for image acquisition and two thrusters allowing it to maneuver. The device is part of a citizen science system wherein volunteers help in the environmental recovery of polluted bodies of water by performing online research and classification tasks. While aiding in environmental recovery, the users become more proficient in wildlife classification and water quality assessment. Telemetry collected by the vehicle is wirelessly uploaded to a web-based interface allowing volunteers to access images, positioning information, and water quality sensor data. The citizen science system allows for the study of social networking and human–computer interaction based on user activity. Specifically, the platform can be utilized to experiment with different interfaces and social interactions in hypothesis-driven research on human–computer interactions.
Defending the American Dream: Coverage of the Jonathan Pollard Spy Case

This article contemplates the journalistic coverage of American espionage as an attempt to maintain consonance with broader cultural discourses about what it means to be an American. Tracking the American press coverage of the Jonathan Pollard spy case, the article demonstrates that the press turns espionage into a phenomenon upholding fundamental American beliefs in openness, sincerity, and straightforwardness. It shows that, rather than represent espionage as a phenomenon embodying deceit, secrecy, and immoral action, the press turns espionage into a phenomenon that communicates that one is what one says one is and that one's self presentation reflects one's insides. Ultimately, however, this representation of espionage undermines a full understanding of how—and why—spying works in culture.
Design, Analysis, and Reporting of Crossover Trials for Inclusion in a Meta-Analysis

Randomized crossover trials are clinical experiments in which participants are assigned randomly to a sequence of treatments and each participant serves as his/her own control in estimating treatment effect. We need a better understanding of the validity of their results to enable recommendations as to which crossover trials can be included in meta-analysis and for development of reporting guidelines. Objective To evaluate the characteristics of the design, analysis, and reporting of crossover trials for inclusion in a meta-analysis of treatment for primary open-angle glaucoma and to provide empirical evidence to inform the development of tools to assess the validity of the results from crossover trials and reporting guidelines.
Controlled processing during sequencing.

Longstanding evidence has identified a role for the frontal cortex in sequencing within both linguistic and non-linguistic domains. More recently, neuropsychological studies have suggested a specific role for the left premotor-prefrontal junction (BA 44/6) in selection between competing alternatives during sequencing. In this study, we used neuroimaging with healthy adults to confirm and extend knowledge about the neural correlates of sequencing. Participants reproduced visually presented sequences of syllables and words using manual button presses. Items in the sequence were presented either consecutively or concurrently. Concurrent presentation is known to trigger the planning of multiple responses, which might compete with one another. Therefore, we hypothesized that regions involved in controlled processing would show greater recruitment during the concurrent than the consecutive condition. Whole-brain analysis showed concurrent > consecutive activation in sensory, motor and somatosensory cortices and notably also in rostral-dorsal anterior cingulate cortex (ACC). Region of interest analyses showed increased activation within left BA 44/6 and correlation between this region’s activation and behavioral response times. Functional connectivity analysis revealed increased connectivity between left BA 44/6 and the posterior lobe of the cerebellum during the concurrent than the consecutive condition. These results corroborate recent evidence and demonstrate the involvement of BA 44/6 and other control regions when ordering co-activated representations.
Characteristics of lipids and their feeding value in swine diets

In livestock diets, energy is one of the most expensive nutritional components of feed formulation. Because lipids are a concentrated energy source, inclusion of lipids are known to affect growth rate and feed efficiency, but are also known to affect diet palatability, feed dustiness, and pellet quality. In reviewing the literature, the majority of research studies conducted on the subject of lipids have focused mainly on the effects of feeding presumably high quality lipids on growth performance, digestion, and metabolism in young animals. There is, however, the wide array of composition and quality differences among lipid sources available to the animal industry making it essential to understand differences in lipid composition and quality factors affecting their digestion and metabolism more fully. In addition there is often confusion in lipid nomenclature, measuring lipid content and composition, and evaluating quality factors necessary to understand the true feeding value to animals. Lastly, advances in understanding lipid digestion, post-absorption metabolism, and physiological processes (e.g., cell division and differentiation, immune function and inflammation); and in metabolic oxidative stress in the animal and lipid peroxidation, necessitates a more compressive assessment of factors affecting the value of lipid supplementation to livestock diets. The following review provides insight into lipid classification, digestion and absorption, lipid peroxidation indices, lipid quality and nutritional value, and antioxidants in growing pigs.
Computer-assisted densitometric image analysis in periodontal radiography. A methodological study

A videobased computer assisted densitometric image analysis (CADIA) system to quantify alveolar bone density changes on standardized dental radiographs was tested. An algorithm was used for grey level correction of a subsequent image to the baseline image. Quantitative information regarding positive and/or negative grey level changes were obtained automatically. Comparison of the ability of CADIA to detect surgically induced bone loss with interpretation of digital subtraction images and conventional radiographic interpretation revealed that CADIA was the most sensitive of the 3 methods, followed by interpretation of digital subtraction images which was considerably more sensitive than conventional radiographic interpretation. CADIA was capable of assessing differences in alveolar bone changes due to periodontal surgery between sites exposed to ostectomy/osteoplasty and control sites and sites exposed to periodontal surgery without ostectomy/osteoplasty. Finally, CADIA was capable of assessing differences in remodeling activity over 4-6 weeks after periodontal surgery between 45 surgical sites and 45 control sites. The system offers an objective method to quantitatively follow alveolar bone density changes over time and appears to be the most sensitive of previously described radiographic interpretation techniques.
In Brief: Atlantic seasonal hurricane forecast

Two hurricane forecasters are predicting that 2008 will be an above-average Atlantic basin tropical cyclone season with an above-average probability of a major hurricane making landfall in the United States. During 2008, there could be about seven hurricanes (the annual average is 5.9) and 13 named storms (the average is 9.6), according to a 7 December report by Philip Klotzbach, research scientist at Colorado State University in Fort Collins, and William Gray, university professor emeritus of atmospheric sciences. The forecasters indicate that they believe the Atlantic basin is in an active hurricane cycle that is associated with a strong thermohaline circulation and an active phase of the Atlantic Multidecadal Oscillation. The report notes that, “real-time operational early December forecasts have not shown forecast skill over climatology during this 16-year period [1992–2007]. This has occurred despite the fact that the skill over the hindcast period…showed appreciable skill.” For more information, visit the Web site: http://hurricane.atmos.colostate.edu/Forecasts/2007/dec2007/dec2007.pdf.
Comparison of the claim percent gross margin earned by Texas community independent pharmacies for dual-eligible beneficiary claims before and after Medicare Part D

Abstract Objectives To describe dual eligibles’ claims before and after Medicare Part D and to evaluate the effect that Medicare Part D has had on the claim percent gross margin (CPGM) earned by Texas community independent pharmacies. Design Nonexperimental time series study. Setting Texas, October 2005 through September 2006. Participants 313 community independent pharmacies. Intervention Review of more than 150,000 Medicaid and 300,000 Medicare Part D claims acquired from a drug claims processor. Main outcome measures CPGM per prescription claim before and after the implementation of Medicare Part D, controlling for generic/brand drug status. Results The mean CPGM for prescriptions dispensed before Part D (Medicaid claims) was 26.7%. The mean CPGM for claims dispensed after Part D (Medicare claims) was 17.0% (using ingredient costs in 2006 dollars) or 20.4% (using ingredient costs adjusted to 2005 dollars), a reduction of 36.3% and 23.6%, respectively. Under both Medicaid and Part D, pharmacies earned higher margins for generic drugs (39.9% and 29.5%, respectively) than for brand-name drugs (8.7% and 8.3%, respectively). Conclusion These results support community pharmacy assertions of lower reimbursements from Part D payers compared with Medicaid payers. Based on these results, pharmacies can respond to this evolving environment by carefully reviewing their Part D plans’ impact on CPGM and taking available steps to increase the proportion of generic drugs dispensed to Medicare beneficiaries.
Some of my favorite results with Endre Csáki and Pál Révész - A survey

Some topics of our twenty some years of joint work is discussed. Just to name a few; joint behavior of the maximum of the Wiener process and its location, global and local almost sure limit theorems, strong approximation of the planar local time difference, a general Strassen type theorem, maximal local time on subsets.
Evaluation of chest seal performance in a swine model: comparison of Asherman vs. Bolin seal.

Summary Introduction Chest seals are externally applied devices used to treat an open pneumothorax. There is concern that chest seals used for treatment of an open pneumothorax can fail due to coagulation or malfunction of the external vent and poor skin adherence. Chest seal failure may lead to respiratory compromise or the development of a tension pneumothorax. The objective of this project was to compare the efficacy and adhesive capacity of two chest seals: Asherman and Bolin. Methods An open pneumothorax model in the swine (30 kg) was developed to test the performance of Asherman (n = 8) and Bolin (n = 8) seals based on haemodynamic and ultrasonographic changes following intrathoracic air and blood infusion. Seal adherence measured on a scale from 0 (poor) to 3 (good) was tested on dry skin and skin soiled with blood. Results After standardised perforation of the chest cavity and aperture blocking, an air infusion of 372 (S.D. 214 ml) was sufficient to reduce mean arterial pressure (MAP) by 20%. Both chest seals prevented a significant fall in MAP after infusion of 1500 ml air into the chest cavity, and had similar adherence scores (2.6 (S.D. 0.8) and 2.8 (S.D. 0.6)) on dry skin. However, on blood soiled skin the Bolin seal had a higher score (2.7 (S.D. 0.6) vs. 0.4 (S.D. 0.7); p Conclusions The Bolin and Asherman chest seals were equivalent in preventing the development of a tension pneumothorax in this open pneumothorax model. However, the Bolin chest seal demonstrated stronger adherence in blood soiled conditions.
Sussman and zahler: Throwing the baby out with the bath water

Sussman and Zahler have delivered a damaging blow to the use of catastrophe theory in the behavioral sciences. this article points out that most of the behavioral scientist's tools, such as regression analysis, are subject to the same criticisms, and to reject them is in effect to throw the baby out with the bath water.
RESEARCH ARTICLE: Institutional Change and Sustainable Forestry: The Development and Struggles of Forest Certification in Finland

Forest certification has quickly emerged as a prominent non-governmental policy approach to forest management, where market and civic stakeholders play increasingly important roles in new institutional development. In Finland, this development has been characterized by an adversarial and politicized environment between entrenched interest groups competing for decision-making authority in forestry governance. In this article, we discuss key distinctions between the two rival certification schemes, Forest Stewardship Council (FSC) and Finnish Forest Certification System (FFCS), and explain the factors in the development process that led to the domination of the forest landowner- and forest industry-led FFCS. A central finding is that, although an alternative to traditional governmental approaches to forest management, the dominant FFCS adopted and modified traditional rulemaking processes and institutionalized the status quo of rulemaking and rule makers that existed prior to the development of forest certification. This resulted in the elimination of new perspectives in FFCS certification development. An absence of incentives and facilitating mechanisms to build trust between old and new policy participants fostered the collapse of a new integrated policy network in Finland.Environmental Practice 10:4–12 (2008)
A prospective, multicenter, randomized trial of the Onyx liquid embolic system and N-butyl cyanoacrylate embolization of cerebral arteriovenous malformations: Clinical article

Object The Onyx liquid embolic system (Onyx) was approved in the European Union in 1999 for embolization of lesions in the intracranial and peripheral vasculature, including brain arteriovenous malformations (AVMs) and hypervascular tumors. In 2001 a prospective, equivalence, multicenter, randomized controlled trial was initiated to support a submission for FDA approval. The objective of this study was to verify the safety and efficacy of Onyx compared with N-butyl cyanoacrylate (NBCA) for the presurgical treatment of brain AVMs. Methods One hundred seventeen patients with brain AVMs were treated with either Onyx (54 patients) or NBCA (63 patients) for presurgical endovascular embolization between May 2001 and April 2003. The primary end point was technical success in achieving ≥ 50% reduction in AVM volume. Secondary end points were operative blood loss and resection time. All adverse events (AEs) were reported and assigned a relationship to the Onyx or NBCA system, treatment, disease, surgery, or other/...
On the intrinsic nature of states of consciousness: O'Shaughnessy and the mythology of the attention

What are the states of consciousness in themselves, those pulses of mentality that follow one upon another in tight succession and constitute the stream of consciousness? William James conceives of each of them as being, typically, a complex unitary awareness that instantiates many features and takes a multiplicity of objects. In contrast, Brian O’Shaughnessy claims that the basic durational component of the stream of consciousness is the attention, which he understands to be something like a psychic space that is simultaneously occupied by several experiences. Whereas, according to the first conception, emotion is a feature of a temporal segment of the stream of consciousness and colors through and through each consciousness state that instantiates it, the second conception considers an emotion to be a distinct one of a system of simultaneous experiences that interact with each other, for example, limiting each other’s number and intensity. Among other matters discussed is the two theorists’ mutually contrasting conception of how the non-inferential awareness which we have of our states of consciousness is accomplished.
The Sensualization of Flânerie

Flânerie changed over the nineteenth century. The distant, detached flâneur came alive to sensuality. The sensual flâneur explored street flowers and foods in a Paris altered by urbanization. In Le Ventre de Paris Zola fixes on les Halles to study the sensualization of the city. The painter Claude Lantier is a flâneur who cannot resist the offerings to the senses, especially the ‘lower’ senses of smell, touch, and taste. Entrapped in his sensual flâneries, Claude is unable to complete his painting of les Halles. Zola succeeds. The writer-flâneur uses sensuality rather than being used by it, keeping his distance even as he plunges his readers into the city of sensualized flânerie.
Thermodynamic Analysis of Receptors Based on Guanidinium/Boronic Acid Groups for the Complexation of Carboxylates, α-Hydroxycarboxylates, and Diols: Driving Force for Binding and Cooperativity

The thermodynamics of guanidinium and boronic acid interactions with carboxylates, alpha-hydroxycarboxylates, and diols were studied by determination of the binding constants of a variety of different guests to four different hosts (7-10). Each host contains a different combination of guanidinium groups and boronic acids. The guests included molecules with carboxylate and/or diol moieties, such as citrate, tartrate, and fructose, among others. The Gibbs free energies of binding were determined by UV/Vis absorption spectroscopy, by use of indicator displacement assays. The receptor based on three guanidinium groups (7) was selective for the tricarboxylate guest. The receptors that incorporated boronic acids (8-10) had higher affinities for guests that included alpha-hydroxycarboxylate and catechol moieties over guests containing only carboxylates or alkanediols. Isothermal titration calorimetry revealed the enthalpic and entropic contributions to the Gibbs free energies of binding. The binding of citrate and tartrate was investigated with hosts 7-10, for which all the binding events were exothermic, with positive entropy. Because of the selectivity of hosts 8-10, a simple boronic acid (14) was also investigated and determined to be selective for alpha-hydroxycarboxylates and catechols over amino acids and alkanediols. Further, the cooperativity of 8 and 9 in binding tartrate was also investigated, revealing little or no cooperativity with 8, but negative cooperativity with 9. A linear entropy/enthalpy compensation relationship for all the hosts 7-10, 14, and the carboxylate-/diol-containing guests was also obtained. This relationship indicates that increasing enthalpy of binding is offset by similar losses in entropy for molecular recognition involving guanidinium and boronic acid groups.
Generalization of Conditions due to Domb for Reducing the Number of Unknown Terms in the Ising Fugacity Expansion

The derivation of low-temperature series for the Ising model is simplified by a high-temperature symmetry condition, a general proof of which does not exist in the open literature. The magnetic linked-cluster expansion provides an elementary and general proof.
Storm event exports of dissolved organic nitrogen (DON) across multiple catchments in a glaciated forested watershed

[1] Storm event patterns of dissolved organic nitrogen (DON) were studied for multiple events across four catchments (1.6–696 ha) in a forested, glaciated watershed in western New York State. Highest concentrations of DON in the watershed were recorded for litter leachate followed by throughfall. Storm event concentrations of DON consistently peaked at or before peak discharge while dissolved organic carbon (DOC) concentrations peaked on the hydrograph recession limbs. Concentrations of DON in stream water were derived from throughfall and litter layer while the DOC expression was attributed to throughfall, litter, and the flushing of the mineral soil by a rising water table. Temporal patterns of ammonium (NH4+) concentrations during events consistently matched those of DON indicating similar sources and flow paths. A previously validated end-member mixing analysis (EMMA) for NO3− failed to predict the DON concentrations observed in streamflow. DON concentrations and DON as % of total dissolved nitrogen (TDN) differed considerably between baseflow (% DON: 6 to 19%) and storm events (% DON: 6 to 64%). DON concentrations and % DON of TDN increased with catchment size and amount of saturated/wetland areas. A wetland catchment that consistently yielded high storm-event DOC concentrations produced variable amounts of DON, indicating a decoupling of DOC and DON dynamics in the wetland. Our study suggests that storm events and watershed characteristics, especially the proportion of saturated and wetland areas, may have a greater influence on DON exports than atmospheric N deposition.
Specific binding sites in the rabbit kidney for prostaglandin A.

Abstract Competitive binding studies of various prostaglandins with homogenates of rabbit renal cortex, outer medulla and papilla demonstrate higher specificity for prostaglandin A. There is high affinity for PGA binding to the extracts which is saturable and time and temperature dependent. The results suggest the presence of specific binding sites in the rabbit kidney for PGA.
T1-relaxation kinetics of extracellular, intracellular and intravascular MR contrast agents in normal and acutely reperfused infarcted myocardium using echo-planar MR imaging.

The objective of this study was to determine and compare if MR contrast agents distributed into various compartments can provide estimation of fractional distribution volume (FDV) in normal and infarcted myocardium using inversion recovery echo-planar MR imaging (IR EPI). Three different types of MR agents were investigated: (a) an extracellular agent, GdDTPA-BMA (0.1 mmol/kg); (b) an intravascular agent, GdDTPA-albumin (0.025 mmol/kg); and (c) an intracellular agent, manganese chloride (0.025 mmol/kg). The null point was determined from a series of IR EPI images in which TI was varied. Temporal changes in ΔR1 (ΔR1 = 1/T1post-1/T1pre) were measured during the initial 29–59 min after administration. Rats (n = 24) were subjected to 1-h coronary artery occlusion/reperfusion. Histochemical staining confirmed the presence and location of infarction. GdDTPA-BMA caused increase in ΔR1 of infarction < blood < < normal myocardium. ΔR1 ratios were 1.55 ± 0.08 for infarction and 0.33 ± 0.03 for normal myocardium, consistent with FDV of 0.82 ± 0.04 and 0.18 ± 0.01. The fractional distribution of this agent in normal myocardium approximated the extracellular space of myocardium. GdDTPA-albumin caused increase in ΔR1 of blood < < infarction < < normal myocardium. ΔR1 ratio in normal, but not infarcted, myocardium was constant at 0.10 ± 0.02 and approximated fractional blood volume. MnCl2 caused equivalent increase in ΔR1 of normal and infarcted myocardium. ΔR1 of normal myocardium did not change overtime, whereas ΔR1 of blood rapidly decreased, leading to overestimation of FDV in normal and infarcted myocardium. In conclusion, extracellular, intravascular and intracellular MR contrast agents exhibited different T1-relaxation kinetics in both normal and infarcted myocardium. Constant ΔR1 ratio (myocardium/blood) after administration of MR contrast agent is a prerequisite for estimation of FDV of MR contrast agent in myocardium.
War in Pre‐Colonial Eastern Africa: The Patterns and Meanings of State‐level Conflict in the Nineteenth Century – By Richard Reid

In recent years, the study of warfare in Africa was subordinated to urgent interests in understanding the violence that graphically illustrated global humanitarian emergencies. Richard Reid returns...
An 86% Efficiency 12 µW Self-Sustaining PV Energy Harvesting System With Hysteresis Regulation and Time-Domain MPPT for IOT Smart Nodes

This paper presents a fully-integrated µW-level photovoltaic (PV) self-sustaining energy harvesting system proposed for smart nodes of Internet of Things (IOT) networks. A hysteresis regulation is designed to provide a constant 3.3 V output voltage for a host of applications, including powering sensors, signal processors, and wireless transmitters. Due to the stringent power budget in IOT scenarios, the power consumption of the harvesting system is optimized by multiple system and circuit level techniques. Firstly, the hill-climbing MPPT mechanism reuses and processes the information of the hysteresis controller in the time-domain and is free of power hungry analog circuits. Secondly, the typical power-performance tradeoff of the hysteresis controller is solved by a self-triggered one-shot mechanism. Thus, the output regulation achieves high-performance and yet low-power operations. Thirdly, to execute the impedance tuning of MPPT, the capacitor value modulation (CVM) scheme is proposed instead of the conventional frequency modulation scheme, avoiding quiescent power consumption. Utilizing a commercial PV cell of 2.5 cm 2 , the proposed system provides 0–21 µW output power to the IOT smart nodes. Measured results showed that the PV harvesting system achieved both ultra-low power operation capability at 12 µW and a peak self-sustaining efficiency of 86%.
Relation of perfusion defects observed with myocardial contrast echocardiography to the severity of coronary stenosis: Correlation with thallium-201 single-photon emission tomography☆

It has been previously shown that myocardial contrast echocardiography is a valuable technique for delineating regions of myocardial underperfusion secondary to coronary occlusion and to critical coronary stenoses in the presence of hyperemic stimulation. The aim of this study was to determine whether myocardial contrast echocardiography performed with a stable solution of sonicated albumin could detect regions of myocardial underperfusion resulting from various degrees of coronary stenosis. The perfusion defect produced in 16 open chest dogs was compared with the anatomic area at risk measured by the postmortem dual-perfusion technique and with thallium-201 single-photon emission tomography (SPECT). During a transient (20-s) coronary occlusion, a perfusion defect was observed with contrast echocardiography in 14 of the 15 dogs in which the occlusion was produced. The perfusion defect correlated significantly with the anatomic area at risk (r = 0.74; p less than 0.002). During dipyridamole-induced hyperemia, 12 of the 16 dogs with a partial coronary stenosis had a visible area of hypoperfusion by contrast echocardiography. The four dogs without a perfusion defect had a stenosis that resulted in a mild (0% to 50%) reduction in dipyridamole-induced hyperemia. The size of the perfusion defect during stenosis correlated significantly with the anatomic area at risk (r = 0.61; p = 0.02). Thallium-201 SPECT demonstrated a perfusion defect in all 14 dogs analyzed during dipyridamole-induced hyperemia; the size of the perfusion defect correlated with the anatomic area at risk (r = 0.58; p less than 0.03) and with the perfusion defect by contrast echocardiography (r = 0.58; p less than 0.03). Thus, myocardial contrast echocardiography can be used to visualize and quantitate the amount of jeopardized myocardium during moderate to severe degrees of coronary stenosis. The results obtained show a correlation with the anatomic area at risk similar to that obtained with thallium-201 SPECT.
Analysis of Lignite-Derived Gases by Automated Gas Chromatography

Automation of the selection of the sample stream (or the standard gas mixture for frequent calibration) and the automation of the sample-gas purging prior to sample injection are highly desirable for analysis of gases derived from coal and lignite. The automated gas-chromatographic system is comprised of an isothermal-multicolumn gas chromatograph and an integrator capable of performing the data analysis and controlling the GC operation. The gaseous sample injected into the GC is separated using the five columns in the system; the switching valves control the choice and time of the sequential use of different columns. The selection of streams to be sampled can be programmed and switching executed by using external relays. The automated system can also transmit the data to a computer for direct processing for plant control. The gas analyzer offers short analysis times as well as a simple operational procedure for everyday use. Because the GC system is a delicate apparatus, manual operation by inexperienced personnel may result in equipment failure and faulty analysis. However, after the system is totally automated and well-written programs are used, the GC system works well, day and night, for months without any problems.
Mxi1-Srα: a novel Mxi1 isoform with enhanced transcriptional repression potential

Mxi1 belongs to the Myc/Max/Mad network of proteins that have been implicated in the control of multiple aspects of cellular behavior. Previously, we had reported that the mouse mxi1 gene gives rise to two distinct transcript forms that can encode proteins with dramatically different functional abilities. The Mxi1-SR protein (here termed Mxi1-SRβ) can interact with Sin3/histone deacetylase and function as a potent transcriptional repressor and growth suppressor, while the Mxi1-WR protein lacks these activities. Here, we describe a new mxi1-derived transcript form (termed mxi1-SRα) whose expression is governed by its own promoter, resulting in a spatiotemporally distinct expression profile from that of the highly related mxi1-SRβ form. Moreover, the Mxi1-SRα protein product, with its unique Sin3 interacting domain, has a greater affinity than its Mxi1-SRβ counterpart for the Sin3 adapter proteins as well as an enhanced potential for transcriptional repression in transient reporter assays. Our identification of this novel Mxi1 isoform that results from alternative 5′ exon usage adds an additional layer of complexity to the Mad/Mxi1 family. In addition, our findings warrant re-evaluation of mxi1 expression patterns on the cellular level and its status in human cancer samples, with a renewed focus on the distinct isoforms.
Cyclin D1/PRAD1 as a central target in oncogenesis.

Abstract The role of the PRAD1 gene in human tumorigenesis was demonstrated by its initial cloning from the breakpoint region on chromosome band 11q13 of the inv(11)(pl5ql3) in a subset of parathyroid adenomas and also by the demonstration of its likely role as the elusive and long-sought Bcl-1 oncogene in t(11; 14)-bearing B cell lymphoma. PRAD1 encodes cyclin D1, a member of a family of G1 cyclins, whose cDNA was also cloned by rescue of a defective budding yeast lacking G1 cyclins and through its inducibility by a cytokine. Furthermore, cyclin D1/PRAD1 appears to be a “driver” oncogene on the 11q13 amplicon in a number of primary human tumors. Transformation and transgenic mice studies have demonstrated that PRAD1 is indeed an oncogene, whose tumorigenic potential requires cooperativity with other oncogenic “hits”. It is now established that cancer cells contain multiple genetic changes. There are two categories of cellular genes in which genetic change contributes to development of neoplasia: oncogenes and tumor suppressor genes. Both positive and negative regulatory forces from oncogenes and tumor suppressor genes appear to converge on cyclin D and its associated CDKs. Interestingly, cyclin D1/PRAD1 has been more directly and widely implicated as a key actor in human cancers than have other cyclins and, for that matter, CDKs. Although the functional explanation for this special role of cyclin D1 in oncogenesis remains incomplete, the evidence that cyclin D1/PRAD1 is indeed a central target in oncogenesis is clearcut. An even larger role in cancer can be postulated by more broadly considering other components of the cell cycle regulatory pathway involving cyclin D1, such as CDK4, p16, and pRb, all of which have been directly implicated in human cancer. It is hoped that further studies will lead to an understanding of the precise role of cyclin D1/PRAD1 in cell cycle control and oncogenesis and also to the rational design of new therapeutic strategies.
Mutation in the CYP21B gene (Ile-172----Asn) causes steroid 21-hydroxylase deficiency

Steroid 21-hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia. It results from a deficiency in a specific cytochrome P450, P450c21 (P450XXIA). The gene encoding this protein (CYP21B) and a closely linked pseudogene (CYP21A) are located in the HLA complex on chromosome 6p. Many mutant alleles are associated with deletions of CYP21B; we report the cloning and characterization of a nondeleted mutant CYP21B gene. This mutant gene is expressed on transfection into mouse Y1 adrenal cells, producing mRNA levels similar to those seen after transfection of the normal CYP21B gene. In codon 172 of the mutant gene, the normal codon ATC, encoding isoleucine, has been changed to AAC, encoding asparagine. This mutation is normally present in the CYP21A pseudogene, so that it may have been transferred to the mutant CYP21B gene by gene conversion. Hybridization of oligonucleotide probes corresponding to this and two other mutations normally present in CYP21A demonstrated that 4 out of 20 patients carried the codon 172 mutation; in one of these patients, the mutation was present as part of a larger gene conversion involving at least exons 3-6. Gene conversion may be a frequent cause of 21-hydroxylase deficiency alleles due to the presence of six chi-like sequences (GCTGGGG) in the CYP21 genes and the close proximity of the CYP21A pseudogene, which has several potentially deleterious mutations.
A Selective ε-Protein Kinase C Antagonist Inhibits Protection of Cardiac Myocytes from Hypoxia-induced Cell Death

Protein kinase C activation is thought to protect cardiac tissue from subsequent ischemic injury by a process termed preconditioning. The protein kinase C isozyme that mediates preconditioning has not yet been identified. Using a cell culture model of hypoxic preconditioning, we found that cardiac myocyte viability after 9 h of hypoxia was increased by more than 50% over control. Preconditioning activated protein kinase C isozymes as evidenced by translocation from one cell compartment to another as follows: there was a 2.1-fold increase in e-protein kinase C activation, a 2.8-fold increase in δ-protein kinase C activation, and no increase in βI-protein kinase C activation. 4β-Phorbol 12-myristate 13-acetate mimicked hypoxic preconditioning, increasing myocyte survival after prolonged hypoxia by 34% compared with control. We previously identified an e-protein kinase C-selective antagonist, eV1-2 peptide, that inhibits e-protein kinase C translocation and function in cardiac myocytes (Johnson, J. A., Gray, M. O., Chen, C.-H., and Mochly-Rosen, D. (1996) J. Biol. Chem. 271, 24962–24966). eV1-2 peptide abolished hypoxic preconditioning and phorbol ester-mediated cardiac protection. Therefore, preconditioning can be induced in this culture model, and activation of e-protein kinase C is critical for cardiac myocyte protection.
Use of a genetically engineered protein for the design of a multivalent MRI contrast agent.

The majority of clinically used contrast agents (CAs) for magnetic resonance imaging have low relaxivities and thus require high concentrations for signal enhancement. Research has turned to multivalent, macromolecular CAs to increase CA efficiency. However, previously developed macromolecular CAs do not provide high relaxivities, have limited biocompatibility, and/or do not have a structure that is readily modifiable to tailor to particular applications. We report a new family of multivalent, biomacromolecular, genetically engineered protein polymer-based CAs; the protein backbone contains evenly spaced lysines that are derivatized with gadolinium (Gd(III)) chelators. The protein’s length and repeating amino acid sequence are genetically specified. We reproducibly obtained conjugates with an average of 8–9 Gd(III) chelators per protein. These multivalent CAs reproducibly provide a high relaxivity of 7.3 mM−1 s−1 per Gd(III) and 62.6 mM−1 s−1 per molecule. Furthermore, they can be incorporated into biomat...
Managing the Computational Cost in a Monte Carlo Simulation by Considering the Value of Information

Monte Carlo simulation is a popular tool for reliability assessment because of its robustness and ease of implementation. However, the computational cost is a major concern. The standard deviation of the estimated failure probability of a system from N replications is proportional to 2 / 1  N . Efforts to reduce computational cost focus on development of intelligent sampling procedures and efficient calculation of the performance function of a system. This paper proposes a new way to manage the computational cost that views design as a decision among alternatives with uncertain reliabilities. Information from a simulation has value only if it enables the designer to make a more informed choice among the alternative designs. Consequently, the value of information from the simulation is equal to the gain from using this information to select the best design.
Compensators via ℋ2-based Model Reduction and Proper Orthogonal Decomposition

Abstract Low order controllers are essential for the design of real time feedback controllers for systems described by partial differential equations (PDEs). We consider a MinMax control design that does not require full state information by using a state estimate in the feedback law. In this study we compare two reduced order modeling approaches to obtain low order state estimators for a system described by a nonlinear PDE. In the first case we investigate an ℋ2-model reduction technique for linear systems. In particular, we implement the iterative rational Krylov algorithm (IRKA) to construct a low dimensional linear state estimator. This method maintains stability properties of the original system and is numerically efficient in that it requires only matrix-vector multiplications and sparse linear solvers. In the second case we construct a nonlinear compensator by including nonlinear terms of the state equation in the differential equation for the compensator. Proper orthogonal decomposition (POD) is then used to determine a reduced order model for the resulting nonlinear equation. We apply these approaches to Burgers equation with periodic boundary conditions.
An effective theory of type refinements

We develop an explicit two level system that allows programmers to reason about the behavior of effectful programs. The first level is an ordinary ML-style type system, which confers standard properties on program behavior. The second level is a conservative extension of the first that uses a logic of type refinements to check more precise properties of program behavior. Our logic is a fragment of intuitionistic linear logic, which gives programmers the ability to reason locally about changes of program state. We provide a generic resource semantics for our logic as well as a sound, decidable, syntactic refinement-checking system. We also prove that refinements give rise to an optimization principle for programs. Finally, we illustrate the power of our system through a number of examples.
Voting and ID Requirements: A Survey of Registered Voters in Three States:

Since the 2000 election, one of the most contentious issues in election administration has been voter identification requirements. This article provides the results of a survey of registered voters...
The effect of radiofrequency hyperthermia on the Ca755 murine adenocarcinoma

Radiofrequency (RF) was used to induce hyperthermia in the Ca755 murine adenocarcinoma. Thermal kinetic studies revealed a selective heating of tumors over normal tissues during RF, which occurred in larger but not smaller tumors. Small tumors required a significantly greater RF output than did larger neoplasms for heating to the tumoricidal range of 42 C. Rates of tumor growth were not changed after single RF treatments at 42 C, but tumors receiving three applications of RF were significantly smaller than a control group at 28 days tumor age. RF may be of value in the treatment of large neoplasms by using multiple applications; however, microscopic mitoses may not be affected directly without simultaneously damaging normal tissues in the RF field.