cssi/SciSciGPT-SciSciNet huggingface dataset:
Loss of the p12 subunit of DNA polymerase delta leads to a defect in HR and sensitization to PARP inhibitors

Abstract Human DNA polymerase δ is normally present in unstressed, non-dividing cells as a heterotetramer (Pol δ4). Its smallest subunit, p12, is transiently degraded in response to UV damage, as well as during the entry into S-phase, resulting in the conversion of Pol δ4 to a trimer (Pol δ3). In order to further understand the specific cellular roles of these two forms of Pol δ, the gene (POLD4) encoding p12 was disrupted by CRISPR/Cas9 to produce p12 knockout (p12KO) cells. Thus, Pol δ4 is absent in p12KO cells, leaving Pol δ3 as the sole source of Pol δ activity. GFP reporter assays revealed that the p12KO cells exhibited a defect in homologous recombination (HR) repair, indicating that Pol δ4, but not Pol δ3, is required for HR. Expression of Flag-tagged p12 in p12KO cells to restore Pol δ4 alleviated the HR defect. These results establish a specific requirement for Pol δ4 in HR repair. This leads to the prediction that p12KO cells should be more sensitive to chemotherapeutic agents, and should exhibit synthetic lethal killing by PARP inhibitors. These predictions were confirmed by clonogenic cell survival assays of p12KO cells treated with cisplatin and mitomycin C, and with the PARP inhibitors Olaparib, Talazoparib, Rucaparib, and Niraparib. The sensitivity to PARP inhibitors in H1299-p12KO cells was alleviated by expression of Flag-p12. These findings have clinical significance, as the expression levels of p12 could be a predictive biomarker of tumor response to PARP inhibitors. In addition, small cell lung cancers (SCLC) are known to exhibit a defect in p12 expression. Analysis of several SCLC cell lines showed that they exhibit hypersensitivity to PARP inhibitors, providing evidence that loss of p12 expression could represent a novel molecular basis for HR deficiency.
Theorizing Islam: Disciplinary Deconstruction and Reconstruction

The scholarly study of Islam has become ever more insular and apologetic. Academic Islamic Studies has tried to maintain a focus on truth, authenticity, experience and meaning and has effectively avoided discussion of larger social, cultural and ideological issues. Many scholars of Islam have presented themselves to their colleagues, the media and the public as the interpreters of Islam and have done so with an interpretation which tends, almost universally, to the liberal and egalitarian. The ignorance and hostility which the Islamic faith has faced since 9/11 has partly necessitated the taking of such a position. But, as Theorizing Islam argues, the issue remains that only one interpretation of Islam is generally being presented and, as with any interpretation, this has its own assumptions. The aim of Theorizing Islam is to explore the potential for a fuller, more honest and more sophisticated approach to both theory and methodology in the academic study of Islam.
Fractional Calculus with its Applications in Engineering and Technology

This book aims to provide the basic theory of fractional calculus and its applications based on practical schemes and approaches, illustrated with applicable engineering and technical examples, especially focusing on the fractional-order controller design. In the development of this book, the essential theorems and facts in the first two chapters are proven with rigorous mathematical analyses. In addition, the commonly used definitions of Grunwald-Letnikov, Riemann-Liouville, Caputo, and Miller-Ross fractional derivatives are introduced with their properties proved and linked to fractional-order controller design. The last chapter presents several enlightening scenarios of fractional-order control designs, for example, the suppression of machining chatter, the nonlinear motion control of a multilink robot, the simultaneous tracking and stabilization control of a rotary inverted pendulum, and the idle speed control of an internal combustion engine (ICE).
Integration of Large Scale Production and Purification of Biomolecules

Despite the many dramatic advances in biotechnology over the past few years, little attempt has been made to analyze large scale manufacturing schemes for biomolecules. In particular, the production and purification operations have not been studied in an integrated fashion. In many instances, the isolation and purification of the biomolecule could be as extensive and expensive as the synthesis itself. In this paper, the question is addressed from a commercial standpoint.
Teaching NeuroImages: Medically intractable epilepsy and ictal asystole treated with cardiac pacing.

A 43-year-old man with bihemispheric periventricular nodular heterotopia had medically intractable multifocal epilepsy and seizure-related falls. Video-EEG recorded a seizure with ictal asystole, EEG attenuation, and loss of postural tone, reflective of cerebral hypoperfusion (figure 1). After pacemaker implantation, EEG recorded a seizure with ictal cardiac pacing, without EEG attenuation (figure 2). His falls resolved. Antiseizure medications and epilepsy surgery can control seizures and ictal asystole.1 For individuals with intractable epilepsy and ictal asystole who are poor surgical candidates, pacemaker implantation is indicated to prevent injury and any potential contribution of ictal asystole in sudden unexpected death in epilepsy.1,2
Internalization theory for the digital economy

We study the internationalization of digital service multinational enterprises (SMNCs), focusing on how digitalization alters internalization theory’s assumptions about the nature of firm-specific assets (FSAs) and the theory’s predictions about governance choices in cross-border transactions. We invoke Simon’s (Proc Am Philos Soc 106(6):467–482, 1962) near-decomposability concept to explain how digitalization enables two distinct types of FSAs – technology and human capital. Applying the ideas of modularity and skill complexity, we further distinguish between core versus peripheral technology FSAs and between generic versus advanced human capital FSAs. Building on the transferability and appropriability of these strategic assets, we theorize on the FSAs’ internalization propensity in the digital age. We propose that with rising digitalization, the network plays a dual role – as a governance mode and as a strategic resource. Integrating insights from network economics, particularly increasing returns to scale, we propose that network advantages (On) emerge as a distinct strategic resource that merits separate investigation from the traditional asset-based (Oa) and transaction-based (Ot) advantages.
A clinical study to determine the threshold of bronchodilator response for diagnosing asthma in Chinese children

There is few objective, clinically feasible and inexpensive test for diagnosing childhood asthma. We want to find an ideal way to solve it. The control group was 301 non-asthmatic children, and the asthma group was 286 asthmatic children. The asthmatic children were divided into three groups according to the severity of their disease. Pre- and post-bronchodilator spirometer tests were performed, and the main spirometer parameters were compared. The bronchodilator response (BDR) [BDR is used to determine the reversibility of airway obstruction by measuring the changes of forced expiratory volume in the first second (FEV1) before and after inhalation of bronchodilators] was then determined, and the optimal threshold of BDR for diagnosing childhood asthma was found. 301 non-asthmatic children and 286 asthmatic children participated in the study, the demographics were similar. FEV1 for pre-bronchodilator of asthmatic children was significantly lower than that of non-asthmatic children (P ≤ 0.01). BDR of non-asthmatic children was 3.30 ± 3.85%. BDR of asthmatic children was 9.45 ± 9.15%. There was no significant difference in BDR for patients with different severities of asthma within the group. BDR had no statistical correlation with gender, age, height, weight in neither non-asthmatic children nor asthmatic children. On the receiver-operating characteristic curve, a BDR threshold of ≥ 7.5% offered an optimal balance in asthma diagnosis with a sensitivity rate of 50.7% and specificity rate of 87.7%. Meanwhile, with a BDR threshold of ≥ 12%, the sensitivity rate was 28.7% and the specificity rate was 96.3%. A BDR threshold of ≥ 7.5% has more value in childhood asthma diagnosis as compared to ≥ 12%.
Automatic Clinical Procedure Detection for Emergency Services

Understanding a patient’s state is critical to providing optimal care. However, information loss occurs during patient hand-offs (e.g., emergency services (EMS) transferring patient care to a receiving hospital), which hinders care quality. Augmenting the information flow from an EMS vehicle to a receiving hospital may reduce information loss and improve patient outcomes. Such augmentation requires a noninvasive system that can automatically recognize clinical procedures being performed and send near real-time information to a receiving hospital. An automatic clinical procedure detection system that uses wearable sensors, video, and machine-learning to recognize clinical procedures within a controlled environment is presented. The system demonstrated how contextual information and a majority vote method can substantially improve procedure recognition accuracy. Future work concerning computer vision techniques and deep learning are discussed.
Public Address Scholarship and the Effects of Rhetoric

In this essay, I argue that public address scholars should reengage with the effects of rhetoric through attention to reception and circulation/re-circulation. Doing so will deepen our understandin...
Plasma etching of wide bandgap and ultrawide bandgap semiconductors

The precise patterning of front-side mesas, backside vias, and selective removal of ternary alloys are all needed for power device fabrication in the various wide bandgap (AlGaN/GaN, SiC) and ultrawide bandgap (high Al-content alloys, boron nitride, Ga2O3, diamond) semiconductor technologies. The plasma etching conditions used are generally ion-assisted because of the strong bond strengths in these materials, and this creates challenges for the choice of masks in order to have sufficient selectivity over the semiconductor and to avoid mask erosion and micromasking issues. It can also be challenging to achieve practical etch rates without creating excessive damage in the patterned surface. The authors review the optimum choices for plasma chemistries for each of the semiconductors and acknowledge the pioneering work of John Coburn, who first delineated the ion-assisted etch mechanism.The precise patterning of front-side mesas, backside vias, and selective removal of ternary alloys are all needed for power device fabrication in the various wide bandgap (AlGaN/GaN, SiC) and ultrawide bandgap (high Al-content alloys, boron nitride, Ga2O3, diamond) semiconductor technologies. The plasma etching conditions used are generally ion-assisted because of the strong bond strengths in these materials, and this creates challenges for the choice of masks in order to have sufficient selectivity over the semiconductor and to avoid mask erosion and micromasking issues. It can also be challenging to achieve practical etch rates without creating excessive damage in the patterned surface. The authors review the optimum choices for plasma chemistries for each of the semiconductors and acknowledge the pioneering work of John Coburn, who first delineated the ion-assisted etch mechanism.
Investigating resilience in emergency management: An integrative review of literature

There is a growing need for resilience in dealing with unexpected events during disasters. The purpose of this review was to summarize and synthesize the literature that examined resilience in the context of emergency management (EM). Four groups of findings were synthesized: definitions, key dimensions, technical tools, and research settings employed in the research. First, definitions of resilience, improvisation, and adaptation were summarized and critically evaluated. Second, four key dimensions of EM resilience were identified: collective sensemaking, team decision making, harmonizing work-as-imagined and work-as-done, and interaction and coordination. Third, this review identified five prevalent technical tools used to enhance resilience in EM: mapmaking, event history logging, mobile communication applications, integrated information management system, and decision support tools. Fourth, two major design features of emergency simulations, incident scenarios and participant roles, are evaluated. For each finding, directions for future research efforts to improve resilience in EM are proposed.
A 96-well high-throughput, rapid-screening platform of extracellular electron transfer in microbial fuel cells.

Abstract Microbial extracellular electron transfer (EET) stimulates a plethora of intellectual concepts leading to potential applications that offer environmentally sustainable advances in the fields of biofuels, wastewater treatment, bioremediation, desalination, and biosensing. Despite its vast potential and remarkable research efforts to date, bacterial electrogenicity is arguably the most underdeveloped technology used to confront the aforementioned challenges. Severe limitations are placed in the intrinsic energy and electron transfer processes of naturally occurring microorganisms. Significant boosts in this technology can be achieved with the growth of synthetic biology tools that manipulate microbial electron transfer pathways and improve their electrogenic potential. In particular, electrogenic Pseudomonas aeruginosa has been studied with the utility of its complete genome being sequenced coupled with well-established techniques for genetic manipulation. To optimize power density production, a high-throughput, rapid and highly sensitive test array for measuring the electrogenicity of hundreds of genetically engineered P. aeruginosa mutants is needed. This task is not trivial, as the accurate and parallel quantitative measurements of bacterial electrogenicity require long measurement times (~tens of days), continuous introduction of organic fuels (~tends of milliliters), architecturally complex and often inefficient devices, and labor-intensive operation. The overall objective of this work was to enable rapid ( 100-fold improvement), and high-throughput (>96 wells) characterization of bacterial electrogenicity from a single 5 μL culture suspension. This project used paper as a substratum that inherently produces favorable conditions for easy, rapid, and sensitive control of an electrogenic microbial suspension. From 95 isogenic P. aeruginosa mutant, an hmgA mutant generated the highest power density (39 μW/cm2), which is higher than that of wild-type P. aeruginosa and even the strongly electrogenic organism, Shewanella oneidensis (25 μW/cm2). In summary, this work will serve as a springboard for the development of novel paradigms for genetic networks that will help develop mutations or over-expression and synthetic biology constructs to identify genes in P. aeruginosa and other organisms that enhance electrogenic performance in microbial fuel cells (MFCs).
Deep Learned Multi-Modal Traffic Agent Predictions for Truck Platooning Cut-Ins

Recent advances in Driver-Assisted Truck Platooning (DATP) have shown success in linking multiple trucks in leader-follower platoons using Cooperative Adaptive Cruise Control (CACC). Such set ups allow for closer spacing between trucks which leads to fuel savings. Given that frontal collisions are the most common type of highway accident for heavy trucks, one key issue to truck platooning is handling situations in which vehicles cut-in between platooning trucks. Having more accurate and quicker predictions would improve the safety and efficiency of truck platooning by allowing the control system to react to the intruder sooner and allow for proper spacing before the cutin occurs. Moreover, reduction in false-positives could prevent the CACC from reacting to cut-in vehicles too early, leading to increased benefit from DATP. In this paper, we implement a deep neural network that generates multimodal predictions of traffic agents around a truck platoon. The method uses Long Short-Term Memory networks in an ensemble architecture to predict possible future positions with attached probabilities of vehicles passing by a truck platoon for 5 second horizons. The network performance is compared to a baseline of common state-based predictors including the Constant Velocity Predictor, the Constant Acceleration Predictor, and the Constant Steer Predictor.
Making an Impact: An Initial Review of U.S. Sport League Corporate Social Responsibility Responses During COVID-19

COVID-19 has brought about an unprecedented time where a majority of major American sporting organizations have ceased competition Corporate social responsibility (CSR) actions, historically an avenue for sport organizations to positively impact society, provide a compelling avenue of study during this time While researchers have observed the role of CSR and crisis communication when the crisis arises from within the organization, there is a need to understand CSR shifts and responses when the crisis is on a societal level This commentary examines efforts of major U S sport league CSR programs (National Basketball Association/Women's National Basketball Association, National Football League, Major League Baseball, Major League Soccer, and National Hockey League), starting in mid-March when the majority of organizations ceased competition Data were gathered using a mixed-methods approach of qualitative interviews, secondary research, and social media sentiment analysis Key findings included the emergence of two different approaches to CSR communication strategies among U S sport leagues as well as three clear themes of COVID-19- related communication: educate, assist, and inspire In addition, this commentary provides an initial glance at consumer response to CSR programs, showing both positive and negative sentiment trends
College Football Referee Bias and Sports Betting Impact

Conferences entrust college football referees to impartially officiate games. However, a growing body of research documents officiating biases in sports. We focus on bias among major college football referees. Following a natural experiment approach, we contrast in-conference games with a quasi-control group consisting of games involving teams from different conferences. Specifically, we find significant relationships between the betting line variables—expected game closeness and clear game favorite—and penalties among ACC and former Big East officials that suggests bias toward the underdog team during in-conference games. Additionally, we find home field bias in the ACC and Big XII and bias of game pace in the Big XII and former Big East. We also do a preliminary examination of the biases’ roots. Some biases we pinpoint are, counterintuitively, revenue-inhibiting for certain conferences. Our results show the potential impact on-field referees have on games and the underlying revenue streams for the conferences. They also highlight oft-discussed, but rarely researched, officiating biases at the intersection of game integrity and the commercial goals of the competing programs and the conferences they represent. To lessen such friction, we advocate for centralization of the management and oversight of college football referees. We conclude by explaining how such biases could impact expanded legalized sports betting after the US Supreme Court removed restrictions on state-by-state regulation in 2018.
Analysis of hydrocarbon under-filled and water-filled Miocene deepwater reservoirs, eastern Mexico offshore

Abstract Hydrocarbon exploration in the deepwater portion of the southwestern Gulf of Mexico commenced a decade ago, but discoveries have not been able to meet the optimistic expectations based on historical success in the northern Gulf of Mexico. Despite the existence of organic-rich source rocks and high-quality Miocene reservoir rocks, there is a concern that the lack of significant hydrocarbon accumulations in some prominent traps in the northern Catemaco fold belt (Veracruz Trough) resulted from an ineffective sealing and/or trapping mechanism. By integrating drill core, 3D seismic, and well data provided by the Mexican National Hydrocarbon Commission (CNH), this paper attempts to evaluate the cause of hydrocarbon under-filled or water-filled Miocene traps within the Veracruz Trough, using the prominent structural closures drilled by Pemex-operated Kunah-1 and Yoka-1 deepwater wells as case studies. Three hypotheses are considered and analyzed for these two large traps: top seal leakage, existence of unmapped shallow spill points, and late trap formation relative to timing of hydrocarbon generation and migration. Seal rock leakage analyses, which involves downhole pressure data analysis and mercury injection capillary pressure laboratory measurements on cuttings, suggest that many of the evaluated intra reservoir and top seal rocks could have held significantly taller hydrocarbon columns than encountered by the wells. In addition, 3D seismic structural interpretation around the Yoka trap indicates that all mapped spill points are much deeper than the observed fluid contacts. However, the trap formation timing assessment shows that by the time the traps began to develop, the main oil generation phases had largely concluded, and gas generation was at a very late stage for the most prominent source rocks. Consequently, a more robust explanation for the Kunah and Yoka under-filled and water-filled structures is due to a timing mismatch, with late trap formation relative to an earlier hydrocarbon charge.
Genetic variation in catechol-O-methyltransferase is associated with individual differences in conditioned pain modulation in healthy subjects.

BACKGROUND Genetic variation in the catechol-O-methyltransferase (COMT) gene is associated with sensitivity to both acute experimental pain and chronic pain conditions. Four single nucleotide polymorphisms (SNPs) have traditionally been used to infer three common haplotypes designated as low, average and high pain sensitivity and are reported to affect both COMT enzymatic activity and pain sensitivity. One mechanism that may partly explain individual differences in sensitivity to pain is conditioned pain modulation (CPM). We hypothesized that variation in CPM may have a genetic basis. METHODS We evaluated CPM in 77 healthy pain-free Caucasian subjects by applying repeated mechanical stimuli to the dominant forearm using 26-g von Frey filament as the test stimulus with immersion of the non-dominant hand in hot water as the conditioning stimulus. We assayed COMT SNP genotypes by the TaqMan method using DNA extracted from saliva. RESULTS SNP rs4680 (val158 met) was not associated with individual differences in CPM. However, CPM was associated with COMT low pain sensitivity haplotypes under an additive model (p = 0.004) and the effect was independent of gender. CONCLUSIONS We show that, although four SNPs are used to infer COMT haplotypes, the low pain sensitivity haplotype is determined by SNP rs6269 (located in the 5' regulatory region of COMT), suggesting that inherited variation in gene expression may underlie individual differences in pain modulation. Analysis of 13 global populations revealed that the COMT low pain sensitivity haplotype varies in frequency from 13% to 44% and showed that two SNPs are sufficient to distinguish all COMT haplotypes in most populations.
Applications of Optically Controlled Gold Nanostructures in Biomedical Engineering

Since their inception, optical tweezers have proven to be a useful tool for improving human understanding of the microscopic world with wide-ranging applications across science. In recent years, they have found many particularly appealing applications in the field of biomedical engineering which harnesses the knowledge and skills in engineering to tackle problems in biology and medicine. Notably, metallic nanostructures like gold nanoparticles have proven to be an excellent tool for OT-based micromanipulation due to their large polarizability and relatively low cytotoxicity. In this article, we review the progress made in the application of optically trapped gold nanomaterials to problems in bioengineering. After an introduction to the basic methods of optical trapping, we give an overview of potential applications to bioengineering specifically: nano/biomaterials, microfluidics, drug delivery, biosensing, biophotonics and imaging, and mechanobiology/single-molecule biophysics. We highlight the recent research progress, discuss challenges, and provide possible future directions in this field.
Other Surgical Treatment

The most commonly performed surgical procedures for IIH are venous sinus stenting and cerebrospinal fluid shunting. However, many patients with IIH have other issues and may benefit from other types of surgeries. These include treatments for jugular vein narrowing, cerebrospinal fluid leak repairs, fusion operations for abnormal head movement on the spine, and others. This last chapter will briefly discuss other surgical procedures that may be recommended, why they are done, and what to expect before and after treatment.
The Association of Psychological Well-Being With Sensory and Cognitive Function and Neuronal Health in Aging Adults.

ObjectivesPsychological well-being (PWB) may be a potential modifiable risk factor of age-related diseases. We aimed to determine associations of PWB with sensorineural and cognitive function and n...
Regulation of α-Amylase Synthesis in Bacillus Subtilis

In batch culture, the end of exponential growth triggers many microorganisms to synthesize a variety of compounds not produced (or produced at low level) during growth. Among the compounds produced at the end of growth are antibiotics and extracellular enzymes, some of which are of industrial importance. The molecular mechanisms regulating the timing of the synthesis of these compounds is not known but their production appears to be in response to nutrient starvation. In addition the synthesis of many of these compounds is repressed by the availability of readily metabolized nutrients such as glucose.
A knowledge-based approach to multiple query processing in distributed database system

The collective processing of multiple queries in a database system has recently received renewed attention due to its capability of improving the overall performance of a database system and its applicability to the design of knowledge-based expert systems and extensible database systems. A new multiple query processing strategy is presented which utilizes semantic knowledge on data integrity and information on predicate conditions of the access paths (plans) of queries. The processing of multiple queries is accomplished by the utilization of subset relationships between intermediate results of query executions, which is inferred employing both semantic knowledge and logical information. Given a set of fixed order access plans, the A* algorithm is used to find the set of reformulated access plans which is optimal for a given collection of semantic knowledge.
Overexpression of Bcl-2 or Bcl-xL Inhibits Ara-C-induced CPP32/Yama Protease Activity and Apoptosis of Human Acute Myelogenous Leukemia HL-60 Cells

Abstract Ara-C has been shown to induce apoptosis of human acute myelogenous leukemia HL-60 cells. The DNA repair enzyme poly(ADP-ribose) polymerase (PARP) is known to be degraded during apoptosis. PARP as a substrate is cleaved by the Yama protease, encoded by the CPP32β/Yama gene. Yama belongs to the interleukin 1β converting enzyme/ced-3 family of cysteine proteases that are activated as a cascade, producing proteolytic cleavage of specific substrates that results in the morphological and biochemical features of apoptosis. In the present studies, we determined the effect of high intracellular levels of the antiapoptosis Bcl-2 or Bcl-xL protein on Yama protease activation and PARP degradation during Ara-C-induced apoptosis. For this, we utilized HL-60/Bcl-2, HL-60/Bcl-xL, or control HL-60/neo cells, which were created by transfection of the cDNA of the bcl-2, bcl-xL, or the neomycin-resistant genes, respectively. As compared to HL-60/neo, HL-60/Bcl-2 and HL-60/Bcl-xL cells have 5-fold greater expression of Bcl-2 and Bcl-xL, respectively. However, these cell lines have similar levels of p32Yama and PARP. Treatment with 10 or 100 µm Ara-C for 4 h produced DNA fragmentation and morphological features of apoptosis in HL-60/neo cells. This was associated with the cleavage and activation of p32Yama and PARP degradation but not with the induction of Yama mRNA. In contrast, in HL-60/Bcl-2 and HL-60/Bcl-xL cells, Ara-C-induced p32Yama activation by its cleavage, PARP degradation and apoptosis were significantly inhibited. High Bcl-2 and Bcl-xL levels in these cells also inhibited Yama protease activity, PARP degradation, and apoptosis due to clinically relevant concentrations of etoposide and mitoxantrone. These results suggest that the activation of the Yama protease and PARP degradation are involved in Ara-C-, etoposide-, or mitoxantrone-induced apoptosis. In addition, they suggest that Bcl-2 and Bcl-xL antagonize drug-induced apoptosis by a mechanism that interferes in the activity of a key cysteine protease that is involved in the execution of apoptosis.
Efficient Type Inference and Coercion in Computer Algebra

Computer algebra systems of the new generation, like Scratchpad, are characterized by a very rich type concept, which models the relationship between mathematical domains of computation. To use these systems interactively, however, the user should be freed of type information. A type inference mechanism determines the appropriate function to call. All known models which allow to define a semantics for type inference cannot express the rich “mathematical” type structure, so presently type inference is done heuristically. The following paper defines a semantics for a subproblem therof, namely coercion, which is based on rewrite rules. From this definition, an efficient coercion algorithm for Scratchpad is constructed using graph techniques.
Zinc: Fluorescent Sensors

Fluorescent sensors for visualizing Zn(II) in living cells permit researchers to quantify the amount of Zn(II), define where Zn(II) is located at the subcellular level, and track dynamics of Zn(II) in response to cellular stimuli. Sensors have been developed in all three major classes: small-molecule indicators, genetically encoded sensors composed of fluorescent proteins, and hybrid probes that contain a genetically encoded element combined with an exogenous cofactor. Probes have been targeted to mitochondria, endoplasmic reticulum (ER), Golgi, nucleus, plasma membrane, vesicles, and cytosol in order to monitor Zn(II) in these locales. This article summarizes the overall design, biophysical, and photophysical properties of the major Zn(II) sensors. Keywords: zinc; sensor; probe; indicator; genetically encoded sensor; fluorescent; FRET; imaging
Health Maintenance Organization (HMO)

A health maintenance organization (HMO) is a type of managed care health insurance plan. HMOs operate similarly to other types of health insurance plans in several ways. In exchange for a monthly health insurance premium payment, the HMO provides customers with health insurance that pays for approved health care services. Similar to traditional health insurance, the price customers pay for their monthly premium is adjusted based on the health risk of the particular patient. An HMO is also different from traditional health insurance in several ways. Unlike traditional plans that generally allow customers to seek care from any licensed provider of their choice, an HMO uses a predetermined network of approved physicians and health care providers. Customers have the option of using physicians and health care providers outside of this network; however the HMO is not responsible for the cost of these services. All customers of an HMO are required to designate a primary care physician (PCP) that acts as their “gatekeeper.” In the HMO model, all visits to specialists and access to medical services must be approved by this PCP, otherwise the HMO is not responsible for paying for the health care services. Keywords: health; health administration; health care
We were not Orphans Stories from the Waco State Home

Sherry Matthews began collecting histories of former Waco State Home residents after attending a reunion with her older brother, one of three who had been sent to the Home when Sherry was three yea...
Incomplete Organizations: Legal Entities and Asset Partitioning in Roman Commerce

In this chapter we analyze ancient Rome’s law of business entities from the perspective of asset partitioning, by which we mean the delimiting of creditor collection rights based on the distinction between business assets and personal assets. Asset partitioning, which is an essential legal attribute of modern business forms such as the partnership and the business corporation, reduces borrowing costs by simplifying credit-risk assessment and expediting insolvency proceedings. We find that ancient Roman business arrangements, such as the societas (very loosely, “partnership”) and the slave-run business endowed by the slaveowner with a peculium (a sum of capital), did not give business creditors the first claim to business assets, making these forms of organization non-entities according to the criterion of asset partitioning. It appears that the only true legal entity used to form profit-seeking firms was the societas publicanorum, which roughly resembled the modern limited partnership. But use of that form was generally limited to firms providing services contracted out by the state. Moreover, the societas publicanorum was largely a creature of the Republic, and was largely abandoned during the Empire. Although Rome had a complex economy and sophisticated commercial law, and was familiar with most of the types of asset partitioning we see in modern legal systems, it ultimately failed to develop legal entities for general use in commerce. Apparent reasons include the Roman aristocracy’s disparagement of commerce, the emperors’ wariness of strong organizations outside the state, and the society’s continuing reliance on the family -- a durable and complex legal entity in its own right -- to handle many of the needs of commerce.
Food Quality: Safety, Nutrition, and Labeling

This paper discussed food quality issues associated with both food safety and food nutritional content. Policy approaches to satisfying consumer demands for safe, nutritious food are described from administrative as well as economic perspectives. Current priority issues include instituting better ways of reducing risks from microbial pathogens, from agricultural chemical residues, and ? on the nutritional front ? enhancing the nutritional profile of consumers' diets. Nutrition labeling changes have been achieved. Thus, dietary change must be attained primarily through effective means of enhancing nutritional knowledge, changing attitudes and, ultimately, behavior. The paper concludes by considering the development of the next agricultural/food legislation and the chances of integrating food quality issues in the general legislation.
Demyelination with hemophagocytic lymphohistiocytosis of the CNS.

A case of hemophagocytic lymphohistiocytosis with central nervous system involvement in an infant is presented. Marked demyelination of cerebral and cerebellar white matter is associated with an intense histiocytic infiltration and astrogliosis. Histiocytes phagocytic of erythrocytes and lymphocytes are noted in a meningeal, subependymal, and perivascular distribution. Severe depletion of lymphoid tissue, associated with histiocytic infiltration, is also seen in multiple organs. While the etiology of this disease is unknown, alterations in the immune response and possible viral relationships are explored.
Rhabdomyolysis: An unusual complication of cytotoxic chemotherapy

Acute rhabdomyolysis has rarely been reported after cytotoxic chemotherapy, including cytarabine and 5-azacytidine. We observed a case of acute rhabdomyolysis and renal failure after treatment with mitoxantrone and cyclophosphamide. No other cause of muscle injury could be identified, although biochemical analysis of a muscle biopsy specimen revealed a deficiency of muscle phosphorylase activity. Retreatment with doxorubicin and paclitaxel was not associated with recurrent rhabdomyolysis.
Quarkonium—signal of deconfinement

We discuss quarkonium correlators and spectral functions from a potential model that agrees with the lattice data, and show that screening melts all charmonium states, contrary to previous interpretations.
Molecular weight approximations of ionic polysaccharides by pH determinations

Abstract The molecular weight ( M ) of some ionic polysaccharides was determined by pH measurements inserted in an equation that was derived basically from the dissociation theory of low molecular-weight, weak acids. The equation contained a constant, f , defined as the segment factor, relating each carboxyl group to the repeating monomer. One f was common to the carboxylic acid polysaccharides, and another to the sulfuric acid polysaccharides. The universality of this new equation has not been determined, but M calculated with it gave molecular weights that were mostly in agreement with published M , and with M for pectin, measured by a conventional method (reducing-end-group analysis).
Predictions for surface segregation in intermetallic alloys

Abstract Miedema has proposed an empirical method for predicting surface segregation in intermetallic alloys. We present an overview of his predictions for all transition metal binary combinations. We verify the physical significance of Miedema's parameters and quantify the major factors determining surface segregation phenomena.
Birth order and risk of sudden infant death syndrome: Is the true relationship negative?

The risk of SIDS has been reported consistently as being positively related to parity or birth order. However, the reports in question have failed to take into account the possible confounding effects of sibship size. In the present study it was reasoned that if this were done the relationship would be negative, not positive. In an analysis of births stratified by sibship size positive. In an analysis of births stratified by sibship size occurring in the years 1975-84 in the state of Oregon, it was found that the risk of SIDS in the age range 7-364 days did indeed tend to decrease with increasing birth order when sibship size was held constant. An expected tendency for SIDS rates to increase with increasing sibship size when birth order was held constant was also confirmed. This tendency is probably explained by a negative correlation between family size and socio-economic status. Non-SIDS rates behaved in a similar manner to SIDS rates. The tendency for the risk of SIDS to decrease with increasing birth order was more evident when births following a pregnancy interval of less than 12 months were excluded.
Interferon-gamma-inducible kynurenines/pteridines inflammation cascade: implications for aging and aging-associated psychiatric and medical disorders

This review of literature and our data suggests that up-regulated production of interferon-gamma (IFNG) in periphery and brain triggers a merger of tryptophan (TRY)–kynurenine (KYN) and guanine–tetrahydrobiopterin (BH4) metabolic pathways into inflammation cascade involved in aging and aging-associated medical and psychiatric disorders (AAMPD) (metabolic syndrome, depression, vascular cognitive impairment). IFNG-inducible KYN/pteridines inflammation cascade is characterized by up-regulation of nitric oxide synthase (NOS) activity (induced by KYN) and decreased formation of NOS cofactor, BH4, that results in uncoupling of NOS that shifting arginine from NO to superoxide anion production. Superoxide anion and free radicals among KYN derivatives trigger phospholipase A2-arachidonic acid cascade associated with AAMPD. IFNG-induced up-regulation of indoleamine 2,3-dioxygenase (IDO), rate-limiting enzyme of TRY–KYN pathway, decreases TRY conversion into serotonin (substrate of antidepressant effect) and increases production of KYN associated with diabetes [xanthurenic acid (XA)], anxiety (KYN), psychoses and cognitive impairment (kynurenic acid). IFNG-inducible KYN/pteridines inflammation cascade is impacted by IFNG (+874) T/A genotypes, encoding cytokine production. In addition to literature data on KYN/TRY ratio (IDO activity index), we observe neopterin levels (index of activity of rate-limiting enzyme of guanine–BH4 pathway) to be higher in carriers of high (T) than of low (A) producers alleles; and to correlate with AAMPD markers (e.g., insulin resistance, body mass index, mortality risk), and with IFN-alpha-induced depression in hepatitis C patients. IFNG-inducible cascade is influenced by environmental factors (e.g., vitamin B6 deficiency increases XA formation) and by pharmacological agents; and might offer new approaches for anti-aging and anti-AAMPD interventions.
Neuronal pentraxin with chromo domain (NPCD) is a novel class of protein expressed in multiple neuronal domains

The receptor tyrosine phosphatase PTPRO is involved in axon guidance, but its intracellular signaling mechanisms are unknown. Signals generated through PTPRO must involve interaction of the intracellular domain with substrates and/or signaling proteins. By screening for proteins interacting with PTPRO's intracellular domain, we have identified a new class of cytoplasmic protein. This novel protein, NPCD (Neuronal Pentraxin with Chromo Domain), has multiple cytoplasmic isoforms generated by alternative splicing that are selectively expressed in neurons. These cytoplasmic NPCD isoforms are composed of a neuronal pentraxin domain (formerly thought exclusively extracellular) linked to a chromo domain (formerly thought exclusively nuclear); this protein motif organization is unprecedented. NPCD isoforms are expressed in numerous regions of the central nervous system, where they are present in distinct subcellular arrangements in different brain regions. NPCD isoforms are mainly associated with the inner side of the plasma membrane in brain neurons and rat PC12 cells in vitro; they are present in cell bodies, processes, and growth cones. The biochemical complexity and neuronal expression pattern of NPCD, together with its interaction with PTPRO, suggests involvement in multiple neuronal processes. J. Comp. Neurol. 481:391–402, 2005. © 2004 Wiley-Liss, Inc.
Another Bridge between Kingdoms: tRNA Splicing in Archaea and Eukaryotes

is the most dangerous question in molecular biology. is much safer. Still, it is difficult to resist asking why so many of the molecular themes that are shared between archaea and eukaryotes appear to involve the Central Dogma—the flow of information from DNA to RNA to protein. Studies of molecular function and the results of genome sequencing projects clearly indicate that the DNA replication and transcription in archaea and eukaryotes have more in common than either kingdom does with the bacteria (Olsen and Woese, 1997 [this issue of Cell]). Now the same seems to be true of the endonuclease components of the tRNA splicing machinery, which are closely allied in archaea and eukaryotes. Translation is more of a patchwork across all three kingdoms (Dennis, 1997 [this issue of Cell]), and the tRNA ligation machinery may well turn out to be another phylogenetic mosaic (Trotta et al. 1997xTrotta, C.R., Miao, F., Arn, E.A., Ho, C.K., Rauhut, R., and Abelson, J.N. Cell. 1997; 89: 849–858Abstract | Full Text | Full Text PDF | PubMedSee all ReferencesTrotta et al. 1997). On the other hand, archaea appear more closely related to bacteria than to eukaryotes from a metabolic standpoint (Olsen and Woese 1997xOlsen, G.J. and Woese, C.R. Cell, this issue. 1997; 89: 991–994See all ReferencesOlsen and Woese 1997). What is going on here? Intermediary metabolism is a delicately balanced network of reactions and one may have to inherit much of the network or suffer the consequences as the delicate balance comes undone. Components of the Central Dogma may also be a package deal. While there are clearly some interchangeable parts, many steps are physically coupled to others, driving selection for integrated pathways. As for the patchwork, perhaps tRNA processing and translation have more interchangeable parts than we imagined.
Remanent moment of high-temperature superconductors: Implications for flux-pinning and glassy models.

Superconducting quantum interference device (SQUID) magnetometer data on a variety of ceramics and crystals of Y-Ba-Cu-O show a remanent moment which accurately equals the difference of the field-cooled and zero-field-cooled moments in the low-field, low-temperature range. This effect is argued to point to a flux pinning rather than a superconductive glass model, particularly for the crystals. This holds true even when the glassy model is extended to include screening effects.
The ecology and status of Swinhoe's egret, with notes on other herons in Southeastern China

Abstract The Chinese or Swinhoe's Egret (Egretta eulophotes) is a species that is threatened with extinction. Very little is known of its habits, and so observations made in Hong Kong, where two or three pairs nested in 1969, are detailed. The species feeds primarily in shallow estuarine water, adopting the parasolling method of active pursuit that is characteristic of the American Snowy Egret. Swinhoe's Egret (and not the Little Egret as many authors have suggested) seems, therefore, to be the ecological equivalent of the New World Snowy Egret. Affinities are discussed, and it is suggested that Swinhoe's Egret has been replaced by the better-adapted Little Egret in inland freshwater areas and by the Reef Egret in marine habitats. In consequence, it now survives only as a relict population inhabiting a specialized niche in localized estuarine and delta areas of the Orient. Swinhoe's Egret appears to be in danger of extinction for biological reasons but Man may have increased the danger. Following the ravages of the plume trade, the Little Egret—by virtue of initially having a larger and more widely dispersed population and therefore a greater potential for population increase —seems to have expanded within the ecological niche that it previously shared with Swinhoe's Egret. Swinhoe's Egret now poses a difficult problem in conservation that is made the more intractable by its virtual restriction to mainland China. There is a need to ensure as much scientific documentation as possible during the next decade, in view of the bird's biological significance in relation to other members of the genus.
Emergence of the Academic Computing Clouds

Computational grids are very large-scale aggregates of communication and computation resources enabling new types of applications and bringing several benefits of economy-of-scale. The first computational grids were established in academic environments during the previous decade, and today are making inroads into the realm of corporate and enterprise computing. Very recently, we observe the emergence of cloud computing as a new potential super structure for corporate, enterprise and academic computing. While cloud computing shares the same original vision of grid computing articulated in the 1990s by Foster, Kesselman and others, there are significant differences. In this paper, we first briefly outline the architecture, technologies and standards of computational grids. We then point at some of notable examples of academic use of grids and sketch the future of research in grids. In the third section, we draw some architectural lines of cloud computing, hint at the design and technology choices and indicate some future challenges. In conclusion, we claim that academic computing clouds might appear soon, supporting the emergence of Science 2.0 activities, some of which we list shortly.