cssi/SciSciGPT-SciSciNet huggingface dataset:
Readers of DNA methylation, the MBD family as potential therapeutic targets

DNA methylation represents a fundamental epigenetic modification that regulates chromatin architecture and gene transcription. Many diseases, including cancer, show aberrant methylation patterns that contribute to the disease phenotype. DNA methylation inhibitors have been used to block methylation dependent gene silencing to treat hematopoietic neoplasms and to restore expression of developmentally silenced genes. However, these inhibitors disrupt methylation globally and show significant off-target toxicities. As an alternative approach, we have been studying readers of DNA methylation, the 5-methylcytosine binding domain family of proteins, as potential therapeutic targets to restore expression of aberrantly and developmentally methylated and silenced genes. In this review, we discuss the role of DNA methylation in gene regulation and cancer development, the structure and function of the 5-methylcytosine binding domain family of proteins, and the possibility of targeting the complexes these proteins form to treat human disease.
Managing an integrated production and inventory system selling to a dual market: Long-term and walk-in

Abstract We consider a manufacturer selling a product through two markets: long-term and walk-in. The walk-in demand is dynamically priced in response to market conditions while the long-term demand is priced ahead of time according to contractual agreements. Demand for the product fluctuates due to varying state-of-the-world conditions evolving according to a finite-state Markov chain. Units are produced ahead of demand, with exponentially distributed production times. If orders cannot be fulfilled immediately, they are either backordered, in the case of the long-term demand, or lost, in the case of the walk-in demand. The objective of the manufacturer is to coordinate pricing, production scheduling and inventory allocation, in order to maximize the expected profit. Due to the different characteristics of the two markets, the long-term market is quoted a single price while the walk-in market is dynamically priced. We formulate the problem as a Markov decision process and characterize the structure of the optimal policy. We show that the optimal policy, in addition to specifying the optimal walk-in market sales price, is characterized by two state-dependent thresholds: one specifies how to allocate inventory among the two markets and the second specifies how to schedule production. We also study the special cases of static and state-of-the-world dependent walk-in market pricing strategies as well as the case of a spot market where the price is exogenously set. Finally, we conduct numerical experiments to show how the optimal policy is affected by system parameter changes.
Slicing the Pie: Asset Allocation in Divestiture

One of the key activities during a separation or divestiture is the assignment of assets between the entities being separated. This involves allocating the ownership of the physical assets and then creating pro forma balance sheets (projected future-state balance sheets of both companies post-separation) based on the asset allocation. In most separations and divestitures, the allocation of shared assets can be a tricky and contentious process.
Role of the TAR Element in Regulating HIV Gene Expression

The human immunodeficiency virus long terminal repeat (HIV LTR) is regulated by multiple cis-acting regulatory sequences.1 Cellular factors which bind to the enhancer, SP1, TATA, and TAR regions are involved in the transcriptional regulation of HIV.2 In addition to cellular proteins, the viral protein, tat, has been shown to greatly stimulate HIV gene expression from the HIV LTR.3, 4
Multiple changes in oncogenes and tumor suppressor genes in human retinoblastoma.

Abstract PURPOSE: To present data to support the hypothesis that human retinoblastoma tumors form by a multistep process. METHODS: Survey of the karyotype of 90 human retinoblastomas, with emphasis on changes in chromosomal regions known to contain oncogenes and tumor suppressor genes. CONCLUSION: The data support the hypothesis that retinoblastoma occurs after multiple and often varied steps, similar to other human malignancies.
Tool Point Dynamics Prediction

Chapter 7 applies receptance coupling to predict the tool point frequency response function (displacement-to-force receptance), which is a required input for the process models detailed in prior chapters. A brief review of Euler-Bernoulli beam theory is provided and closed form solutions for the direct and cross receptances of individual components under free-free and clamped-free boundary conditions are derived. It is demonstrated how these component receptances may be coupled using rigid or flexible-damped connections. The discussion culminates in the approach for modeling the desired tool-holder-spindle-machine assembly receptances. Finally, a receptance coupling method for compensating the effects of accelerometer-cable mass on measured FRFs is reviewed and the receptance coupling technique is applied to model variations in thin rib dynamics during machining.
SEDIMENT INTRODUCTION AND DEPOSITION IN A COASTAL LAGOON, CAPE MAY, NEW JERSEY

Abstract Mud rich sediment exists in northeastern Delaware Bay and crops out along the shoreface and on the inner continental shelf of southern New Jersey. Reworking of this sediment by tidal currents and storm waves generates most of the suspended sediment off Cape May Peninsula. The dispersed inorganic fraction of suspended sediment possesses a primary mode finer than 0.5μm and a secondary mode at 4μm. The mineralogy of the clay fraction is dominated by illite, chlorite, and montmorillonite; the silt fraction contains an abundance of feldspar. A high degree of particle agglomeration is seen in Scanning Electron Microscope (SEM) photographs of suspended sediment collected on filters. Differential screening of seston in situ suggests that most composite particles present in the water column are 5μm and smaller. This offshore reservoir of very fine grained suspended sediment results from the deposition of all coarser components behind barrier islands on flood tides. As inner shelf suspended sediment is drawn through tidal inlets, waning tidal currents first permit deposition of discrete sand grains and large composite particles followed by progressively smaller composite particles moving in a landward direction.
Cash flow risk and capital structure decisions

Abstract We identify a link between cash flow risk, capital structure decisions and operating cash flows. Firms with higher cash flow volatility have higher debt levels and this positive link is only for firms with the weakest financial performance as measured by operating cash flow. When firms are ranked based on operating cash flows, those in the bottom half increase their use of leverage in the face of increasing cash flow risk. For firms with operating cash flows that are in the upper half, the link between cash flow risk faced by the firm and its use of leverage is not statistically significant.
Structure Dependent Phase Stability and Thermal Expansion of Ruddlesden–Popper Strontium Titanates

Ruddlesden–Popper strontium titanates with composition Srn+1TinO3n+1, RP-n-STO, n = 1, 2, ..., ∞, are prototypical layered perovskites from which many crystal-chemistry principles can be assessed. In addition, their phase stabilities and lattice thermal expansions are essential factors for their usage in realistic devices. In this work, we use first-principles electronic structure methods to determine the n-layer dependent phase stabilities, including thermodynamic energies and pressure–critical temperature (P–Tc) phase diagrams and coefficients of thermal expansion. We correlate these properties with the perovskite (SrTiO3)n·SrO block thickness, n, to show that a change in materials behavior occurs at a critical thickness nc = 3, which we ascribe to the presence (absence) of octahedral layers exhibiting antiferrodistortions at n ≥ 3 (n < 3). Last, we attribute the absence of quasi-two-dimensional lattice anharmonicity in the layered RP titanates to the stiff (SrTiO3)n intrablock Ti–O bonds and strong int...
Indirect effects of bark beetle-generated dead wood on biogeochemical and decomposition processes in a pine forest.

Bark beetle outbreaks are increasing in frequency and intensity, generating massive inventories of dead trees globally. During attacks, trees are pre-inoculated with ophiostomatoid fungi via bark beetles, which has been shown to increase termite presence and feeding. These events may, in turn, alter biogeochemical cycles during decomposition. We examined these relationships by experimentally inoculating dead wood with bluestain fungi in a temperate pine forest. Across ten replicate plots, eight 0.5 m-long logs were inoculated with Ophiostoma minus and eight with distilled water. Half of the logs from each inoculation treatment were covered from above with a mesh cage barrier to exclude aboveground beetles while permitting access by belowground decomposers. After 1 year, significant increases in mass (34%) and decreases in moisture content (− 17%) were observed across all treatments, but no consistent changes in density were evident. C concentrations were 12% greater in bark when barriers were present and 17% greater in sapwood when barriers and inoculation fungi were absent. N concentrations were 16% greater in bark for fungal-inoculated logs and 27% greater when barriers were present. C:N ratios in A horizon soils under fungal-inoculated logs were 12% greater. Furthermore, termites were present fourfold more in fungal-inoculated logs than controls and the presence of termites was associated with 6% less C in sapwood and 11% more N in both sapwood and heartwood. Together these results suggest dead wood generated via bark beetle attacks has different biogeochemical responses during initial decomposition phases, which could have implications for the C status in forests following bark beetle outbreaks.
Pacaca: Mining Object Correlations and Parallelism for Enhancing User Experience with Cloud Storage

Object-based cloud storage presents an unconventional storage model. Exploiting its unique characteristics, such as the strong semantic correlations among objects and the high I/O parallelism potential, can greatly enhance user experience. Unfortunately, current storage optimization techniques, such as the caching and prefetching schemes, are designed for conventional storage and thus are sub-optimal for cloud storage services. In this paper, we propose a client-side cache management framework, called Pacaca, which integrates object clustering, parallelized prefetching, and cost-aware caching to exploit I/O parallelism and object correlations on cloud storage. We first develop an efficient mining scheme, called Frequent Cluster Mining (FCM), to discover object correlations from the access sequence, and then build a prefetching scheme to fetch the correlated objects in parallel. These two schemes are closely coordinated for achieving high prefetching accuracy, proper control on parallelism degree, and effective mis-prefetching detection and handling. After studying the impact of parallelized prefetching on cache management, we further present a cost-aware caching scheme to differentiate low-cost and high-cost objects for efficient caching by leveraging the awareness of parallelism and object correlations. Our experimental results show that our optimization schemes can effectively reduce the access latency, outperforming traditional schemes by up to 58%.
Chlorophyll nitrogen isotope values track shifts between cyanobacteria and eukaryotic algae in a natural phytoplankton community in Lake Erie

Abstract Chlorophylls are produced by all photosynthetic organisms and are ideal targets for compound-specific isotopic studies of phytoplankton. In laboratory cultures, the difference between the nitrogen (N) isotope ratio (δ15N value) of chlorophyll and the δ15N value of biomass, known as epor, varies taxonomically, yielding potential applications for studying productivity in modern and ancient environments. Here we take advantage of the annual cyanobacterial bloom in Lake Erie, USA, to demonstrate epor patterns in a natural community. The resulting time series shows that environmental observations are similar to laboratory cultures: predicted epor endmember values range from 4.6‰ to 7.4‰ for eukaryotic algae, and −18‰ to −21‰ for cyanobacteria. Because the range and sensitivity of epor is similar between laboratory and natural settings, the data support the use of epor as a reliable tracer of the relative contributions of cyanobacteria and eukaryotic algae to nutrient utilization and primary production in lacustrine environments.
Introduction to the Special Issue on Theory in Nonverbal Communication

To a striking degree, the study of nonverbal behavior and nonverbal communication has benefited from thoughtful attention to sophisticated theory. The Special Issue on Theoretical Approaches to Nonverbal Communication presents several core contemporary theoretical approaches. This introduction places these approaches to emotion, communication, and social influence into a general context in this field.
Dual-Function Intravascular Catheter for Atherosclerosis Diagnostics

We herein present a novel intravascular catheter, with dual-functions of electrical impedance spectroscopy (EIS) and flow fraction reserve (FFR), validated in live pig animal for atherosclerosis/plaques diagnostics. FFR has been the standard tool in determining plaque vulnerability yet could produce false negative results when stenosis is relatively small. Meanwhile, EIS has been demonstrated to specifically distinguish the lipid-rich pool, the signifying feature of rupture-prone plaques. The synergetic performance of these two functionalities can significantly enhance state-of-art diagnostics accuracy for atherosclerosis.
Social Trust and Reciprocity Among Adolescent Girls Exposed to Interpersonal Violence.

Trauma research has traditionally focused on altered emotion regulation and its role in psychopathology, whereas mechanisms of social behavior remain comparatively unexplored, particularly among ad...
Effects of multi-stage milling method on the energy consumption of comminuting forest residuals

Abstract This study has evaluated the comminution energy reduction efficiency of a multi-stage milling method and established a mathematical model for estimating the specific energy consumption as a function of moisture content and particle size change. A Bliss hammer mill was employed to grind the feedstock targeting at two final screen sizes of 0.84 and 0.69 mm. For the target screen size of 0.84 mm, the single-stage, two-stage, and three-stage milling process were employed. Whereas, the single-stage, two-stage, and four-stage milling process were employed for the 0.69-mm target screen size. Four moisture content levels were employed, i.e. 6 %, 12 %, 18 %, and 28 %. While the final particle sizes and distributions were similar independent of the intermediate stages, the results showed that the single-stage milling consumed 43 % more energy than the three-stage grinding process. Also, multi-stage milling runs more stable in grinding high-moisture content materials. In addition, a mathematical model based on Bond’s comminution law was established to predict the specific energy consumption with the moisture content and the particle sizes before and after grinding.
Analysis of quantitative [I-123] mIBG SPECT/CT in a phantom and in patients with neuroblastoma.

To determine the accuracy of quantitative SPECT, intersystem and interpatient standardized uptake value (SUV) calculation consistency for a manufacturer-independent quantitative SPECT/CT reconstruction algorithm, and the range of SUVs of normal and neoplastic tissue. A NEMA body phantom with 6 spheres (ranging 10–37 mm) was filled with a known activity-to-volume ratio and used to determine the contrast recovery coefficient (CRC) for each visible sphere, and the measured SUV accuracy of those spheres and background water solution. One hundred eleven 123I-metaiodobenzylguanidine ([I-123] mIBG) SPECT/CT examinations from 43 patients were reconstructed using SUV SPECT® (HERMES Medical Solutions Inc.); 42 examinations were acquired using a GE Infinia Hawkeye 4 SPECT/CT, and 69 were acquired on a Siemens Symbia Intevo SPECT/CT. Inter scanner SUV analysis of 9 regions of normal [I-123] mIBG tissue uptake was conducted. Intrapatient mean SUV variability was calculated by measuring normal liver uptake within patients scanned on both cameras. The intensity of uptake by neoplastic tissue in the images was quantified using maximum SUV and, if present, compared over time. The phantom results of the visible spheres and background resulted in accuracy calculations better than 5–10% with CRC correction. Interscanner SUV variability showed no statistical difference (average p value 0.559; range 0.066–1.0) among the 9 normal tissues analyzed. Intrapatient liver mean SUV varied ≤ 16% as calculated for 28 patients (87 examinations) studied on both scanners. In one patient, a thoracic tumor evaluated over 10 time points (18 months) underwent a 74% (3.1/12.0) reduction in maximum SUV with treatment. The results demonstrate quantitative accuracy to better than 10%, and both consistent SUV calculation between 2 different SPECT/CT scanners for 9 tissues, and low intrapatient measurement variability for quantitative SPECT/CT analysis in a pediatric population with neuroblastoma. Quantitative SPECT/CT offers the opportunity for objective analysis of tumor response using [I-123] mIBG by normalizing the uptake to injected dose and patient weight, as is done for PET.
Relationships between ethylene biosynthetic pathway metabolites during banana fruit ripening

This report describes a method for extraction, separation, and quantification of 1-aminocyclopropane-l-carboxylic acid (ACC) by reverse-phase, high-performance liquid chromatography (HPLC). A 20 to 21 minute run time (ACC at 19.65 min) in a linear gradient mode yielded a baseline separation of ACC from other «-amino acids. The rates of ethylene (C2H4) production and respiration showed two bursts during fruit ripening. The first burst in C2H4 production preceded the respiratory climacteric peak, whereas the second burst in C2H4 production occurred concurrently with the second burst in respiration. The increase as well as the decrease in C2H4 production was related to ACC content, but an unknown mechanism might have also been involved. The content of l-(malonylamino)cyclopropane-l-carboxylic acid (MACC) fluctuated during all phases of banana ripening, MACC content was not related to the rate of C2H4 production or respiration.
Gender, Race, and Intersectionality in Campaign Finance

Campaign finance research has given greater attention to race and gender, but, due to data limitations, only separately. Using new data on the ethnoracial and gender backgrounds of contributors, we provide the first estimates of the ethnorace-gender distribution of campaign contributions. We find that women of color are more underrepresented in campaign finance than predicted by existing analyses of race or gender alone. We also use within-district variation to compare how candidate race, gender, and their interaction affect the race and gender distributions of campaign contributions. We find that the effect of shared ethnorace is many times larger than that of shared gender or their interaction. Gender effects are heterogeneous by ethnorace and party; shared gender is most predictive for contributions from white and black Democratic women. The findings suggest a need for greater attention to intersectionality in research on political participation.
Influence of Aliphatic and Aromatic Fluorine Groups on Gas Permeability and Morphology of Fluorinated Polyimide Films

Partially fluorinated polymers often exhibit exceptional membrane-based separation performance for a variety of gas pairs. While many gas transport studies focus on the incorporation of aliphatic f...
Drift and Erosion in Software Architecture: Summary and Prevention Strategies

Disciplined practice of software architecture, and the broader encompassing discipline of software design, is fundamental to a project's success in every stage of the software life cycle. Choosing and implementing an appropriate architecture maximizes team velocity by structuring a project to meet business needs and adhere to quality standards. One enemy of good architecture is architecture drift, where software systems implement an architecture that is not specified. Even worse, architecture erosion threatens projects in the form of design decisions that violate prescriptive architecture as well as quality attributes. In this paper, we will discuss the importance of a reliable architecture, the symptoms of architecture drift and erosion, and some of the existing tools and methods used to combat them.
Relations between b → cτν decay modes in scalar models

As a consequence of the Ward identity for hadronic matrix elements, we find relations between the differential decay rates of semileptonic decay modes with the underlying quark-level transition b → cτν, which are valid in scalar models. The decay-mode dependent scalar form factor is the only necessary theoretical ingredient for the relations. Otherwise, they combine measurable decay rates as a function of the invariant mass-squared of the lepton pair q2 in such a way that a universal decay-mode independent function is found for decays to vector and pseudoscalar mesons, respectively. This can be applied to the decays $$ B\to {D}^{\ast}\tau v,{B}_s\to {D}_s^{\ast}\tau v,{B}_c\to J/\psi \tau v $$ and B → Dτv, Bs → Dsτv, Bc → ηcτv, with implications for R(D(*)), $$ R\left({D}_s^{\left(\ast \right)}\right) $$ , R(J/ψ), R(ηc), and ℬ(Bc → τv). The slope and curvature of the characteristic q2-dependence is proportional to scalar new physics parameters, facilitating their straight forward extraction, complementary to global fits.
Engineered mutant α-ENaC subunit mRNA delivered by lipid nanoparticles reduces amiloride currents in cystic fibrosis-based cell and mice models

Cystic fibrosis (CF) results from mutations in the chloride-conducting CF transmembrane conductance regulator (CFTR) gene. Airway dehydration and impaired mucociliary clearance in CF is proposed to result in tonic epithelial sodium channel (ENaC) activity, which drives amiloride-sensitive electrogenic sodium absorption. Decreasing sodium absorption by inhibiting ENaC can reverse airway surface liquid dehydration. Here, we inhibit endogenous heterotrimeric ENaC channels by introducing inactivating mutant ENaC α mRNA (αmutENaC). Lipid nanoparticles carrying αmutENaC were transfected in CF-based airway cells in vitro and in vivo. We observed a significant decrease in macroscopic as well as amiloride-sensitive ENaC currents and an increase in airway surface liquid height in CF airway cells. Similarly, intranasal transfection of αmutENaC mRNA decreased amiloride-sensitive nasal potential difference in CFTRKO mice. These data suggest that mRNA-based ENaC inhibition is a powerful strategy for reducing mucus dehydration and has therapeutic potential for treating CF in all patients, independent of genotype.
Reflections on Security, Race, and Rights Twenty Years After 9/11

The most distinctive feature of counterterrorism is its preventive enforcement paradigm. In contrast to traditional crime wherein law enforcement usually become involved after the crime has occurred, terrorism crimes pose such a high risk of human death and massive property destruction that government agents engage in predictive policing as a matter of policy. On its face, preventing terrorism appears to be a sound security measure, but in practice it has proven to be susceptible to racial politics and anti-Muslim stereotypes. FBI agents, immigration officials, and local police treat religious and dissident Muslims as presumptively suspect. These biases infect how investigative authority and prosecutorial discretion has been exercised since the 9/11 terrorist attacks. The racial politics of counterterrorism, thus, defines success more by the number of Muslim men the government can put in jail or deport (regardless how inept, young, mentally ill, or otherwise incompetent they may be) than preventing real terrorist plots. Within the context of systemic racism in the criminal justice system that has been incarcerating black and brown people for generations, this outcome should come as no surprise. Indeed, counterterrorism is implemented by the same law enforcement agencies who criminalize Black men as presumptively dangerous and violent. While the scope of national security laws deployed to (over) police Muslim American communities is too far-reaching to exhume here, this essay expounds on three counterterrorism practices that have been most harmful to their civil and dignitary rights: 1) FBI “voluntary” interviews, 2) physical and electronic surveillance, and 3) predatory sting operations led by dubious informants and overzealous undercover agents. All three have been wildly successful in chilling religious freedom, censuring political dissent, and making Muslim-Americans feel like second-class citizens. My critiques center on both law and selective enforcement because the two cannot be disconnected, whether in national security targeting Muslims or criminal justice targeting African Americans. Law alone cannot solve racialized counterterrorism because it is in essence a cultural problem. Regardless how neutral laws may be on their face, their enforcement will continue to be racist (among other disparate outcomes) so long as racism permeates American society. Hence the motto of the twenty-first century civil rights movement is “Black Lives Matter.” Until that declaration is taken as true by police officers, prosecutors, judges, and the general public, no amount of legal reforms can protect African American communities from the ravages of a facially neutral but anti-Black racist criminal justice system. The same applies to Muslims and Arabs in the national security context. Until FBI agents, the intelligence community, diplomats, prosecutors, immigration officers, and judges understand that terrorism by Muslims arises from individual and localized socio-political causes, the national security apparatus will continue to primarily target Muslims.
Hydrophilic packaging of iron oxide nanoclusters for highly sensitive imaging.

Superparamagnetic iron oxide nanoparticles (SPIONs) are used as imaging probes to provide contrast in magnetic resonance images. Successful use of SPIONs in targeted applications greatly depends on their ability to generate contrast, even at low levels of accumulation, in the tissue of interest. In the present study, we report that SPION nanoclusters packaged to a controlled size by a hyperbranched polyglycerol (HPG) can target tissue defects and have a high relaxivity of 719 mM(-1) s(-1), which was close to their theoretical maximal limit. The resulting nanoclusters were able to identify regions of defective vasculature in an ischemic murine hindlimb using MRI with iron doses that were 5-10 fold lower than those typically used in preclinical studies. Such high relaxivity was attributed to the molecular architecture of HPG, which mimics that of the water retentive polysaccharide, glycogen. The results of this study will be broadly useful in sensitive imaging applications.
Growth cone "collapse" in vivo: are inhibitory interactions mediated by gap junctions?

In the leech embryo, oppositely directed axons of homologous anterior pagoda (AP) neurons overlap with each other extensively within the nerves that link adjacent ganglia, and inhibit each other9s further growth (Gao and Macagno, 1987b). During this 5–8 d period of inhibition, the axons begin to grow thin, and eventually they retract completely. However, deletion of one overlapping AP cell results in the renewed growth of the remaining AP cell9s axon, which then innervates territory vacated by the killed cell. Thus, each neuron can detect the presence of the other, and adjust its branching pattern accordingly. To begin to explore how these neurons detect and inhibit each other, we tested for direct communication between them. Dye fills with fluorescent chromophores suggested direct contact between their axons at the light level, and this was confirmed by serial-section electron microscopic analysis. Morphological features resembling aspects of gap junctions were observed where the projections were closely apposed, and subsequent electrophysiological recordings demonstrated electrical coupling between the mutually inhibited axons. Confirmation that these projections communicate via gap junctions was obtained using intracellular injection of 5-HT as a tracer, followed by anti-5-HT immunohistochemistry. The tracer passed selectively between AP neurons. We propose that the gap junctions formed between the transient projections of the developing AP neurons may mediate the exchange of the signals that permit homologs to recognize each other and to inhibit the further forward progress of these projections.
Culture and Psychiatric Diagnosis

Since the publication of DSM-IV in 1994, neurobiologists and anthropologists have criticized the rigidity of its diagnostic criteria that appear to exclude whole classes of alternate illness presentations, as well as the lack of attention in contemporary psychiatric nosology to the role of contextual factors in the emergence and characteristics of psychopathology. Experts in culture and mental health have responded to these criticisms by revising the very process of diagnosis for DSM-5. Specifically, the DSM-5 Cultural Issues Subgroup has recommended that concepts of culture be included more prominently in several areas: an introductory chapter on Cultural Aspects of Psychiatric Diagnosis - composed of a conceptual introduction, a revised Outline for Cultural Formulation, a Cultural Formulation Interview that operationalizes this Outline, and a glossary on cultural concepts of distress - as well as material directly related to culture that is incorporated into the description of each disorder. This chapter surveys these recommendations to demonstrate how culture and context interact with psychiatric diagnosis at multiple levels. A greater appreciation of the interplay between culture, context, and biology can help clinicians improve diagnostic and treatment planning.
Do We Have Any Justified Moral Beliefs

In this fine book, Walter Sinnott-Armstrong argues for a "moderate Pyrrhonian" skeptical view about justified moral belief.1 His argument rests on the thesis that the justification of a belief is a relation between that belief and a class of alternatives (83-87). On this thesis, the "contrast-class view," we can assess the justification of a belief relative to various contrast classes. Sinnott-Armstrong argues that there is no showing that any particular class has epistemological priority (97-103; 117-129); because of this we should suspend belief about whether any moral beliefs are justified "without qualification" (130; 251). This is his "Pyrrhonian moral skepticism." Sinnott-Armstrong also argues that moral nihilism cannot be ruled-out (99, 133); given this, no positive moral belief is justified relative to contrast classes that include moral nihilism. Nevertheless, he thinks, some moral beliefs may be justified relative to alternatives that are taken seriously in ordinary deliberation (130-131). This is his "moderate moral skepticism." Sinnott-Armstrong's arguments are rich and subtle. His book includes a sophisticated assessment of debates in epistemology as well as a thorough examination of the epistemological resources of metaethical theories. I cannot do justice to all of this. I will attempt merely to raise problems for the contrast-class view and for Sinnott-Armstrong's position that nihilism cannot be ruled-out.
Instream Flow Methods

Abstract The competing and increasing demands for water pose a formidable challenge for efficient management of instream flows. The offstream demands should in general be satisfied separately. The same instream flow satisfies all the instream flow demands and therefore its determination should be based on the largest of the demands. The demands need not be in the form of flow alone; there may be specific depth and velocity requirements. Methods of estimating minimum instream flow are discussed. They broadly fall into two categories, namely, threshold flow methods to guarantee releases for most of the time; and physically based methods addressing specific aspects of the demands. Keywords: instream flows; hydropower; fish habitat; frequency analysis; flow duration analysis; physical habitat simulation (PHABSIM)
Molecular Cloud Clusters and Chains

We report some preliminary results from the Massachusetts - Stony Brook CO survey of the first galactic quadrant using the 14-meter millimeterwave telescope of the Five College Radio Astronomy Observatory. The survey contains approximately 50 000 observations spaced every 3 arcminutes in 1 and b between longitudes 0° and 90° and latitudes -1° and 1°. We have mapped emission from giant molecular clouds (GMC) which we identified, in earlier more limited strip surveys of the galactic plane (Solomon, Sanders and Scoville 1979; Sanders 1981), on size scales from a few parsecs to hundreds of parsecs, in order to determine the degree of clustering and organization into large-scale features. In addition to the characteristic size of 20 – 60 pc for individual GMC, we find clustering of clouds on a scale of from 100 to 300 pc.
Practical Aspects of Electrochemistry and Applications Towards the Solving of Chemical Problems

Electrochemical techniques such as cyclic voltammetry are now routinely used to probe the chemical reactivity of neutral, oxidized and reduced inorganic, organic and organometallic compounds under a variety of different solution conditions. A number of practical considerations associated with these voltammetric measurements, such as the selection of a given solvent/supporting electrolyte system, are discussed in this paper. Examples are illustrated for the case of Buckminsterfullerene, C60 a compound which undergoes up to five one-electron reductions in nonaqueous media. This compound has only recently become available in relatively large quantities and is an ideal molecule to investigate the effects of media and temperature on multiple redox reactions involving a highly studied and most important species whose electrochemistry is still relatively unknown.
Fluorescent vesicle system. A new technique for measuring blood flow in the retina.

Purpose: To measure blood flow in the retinal circulation and optic nerve head capillaries with an innovative fluorescent vesicle system. Methods: Carboxyfluorescein was encapsulated into liposomes; the vesicles ranged from 0.1 to 2 µm in diameter. After intravenous injection of the liposome suspension, the fundus was viewed using a scanning laser ophthalmoscope. Images of the fundus showing circulating liposomes were stored on videotape. An image analyzing system was used to digitize the captured video frames and transfer them to a computer's hard disk for permanent storage. Software developed in the authors' laboratory allowed them to overlay multiple video frames to create a single image that provided a visible record of the path taken by a particular vesicle in a given time period. The information on this image was used to calculate the velocity of the vesicle, and hence the velocity of the blood flow in the vessel. Results: With this system, individual liposomes as small as 100 nm were visible in all retinal vessels (arteries, capillaries, and veins). Quantitative analysis of vesicle movement in the major retinal vessels of the cynomolgus monkey yielded an average velocity of 9.33 ± 1.67 mm/second in a large vein (diameter, 130 µm) and 16.10 ± 5.7 mm/ second in a large retinal artery (diameter, 64 µm). The average velocity in the macular capillaries was 0.76 mm/second (range, 0.45-1.33 mm/second), whereas the average velocity in the optic nerve head capillaries was 1.39 mm/second (range, 0.96-2.25 mm/ second). Conclusion: The fluorescent vesicle system can be used for simultaneous measurement of blood flow in the retinal arteries, veins, and capillaries of the macula and optic nerve.
Medical student beliefs: spirituality's relationship to health and place in the medical school curriculum

The relationship between spirituality and health is receiving increased attention; consequently medical schools have begun asking how and in what manner these issues should be addressed in medical education. Unfortunately, student beliefs concerning spirituality and health have not been adequately assessed. This study examined medical student beliefs regarding the relationship between spirituality and health and the level of instruction spirituality should receive in the curriculum. Questionnaire results from 254 medical students indicated that religiousness and spirituality are important, with spirituality more important than religiousness. Spiritual practices were seen as more helpful for acute and mental health conditions than for chronic or terminal conditions and believed to be more helpful for coping with a health condition than healing tissue. Students believed that patients could benefit from spiritual practices more than they could for their own health conditions. Most students endorsed a lecture...
Schizophrenics’ difficulties in understanding ambiguous sentences

Schizophrenic and control subjects were presented with sentences containing lexical, surface-structure, or underlying-structure ambiguity or no ambiguity and were asked to choose pictures representing the meanings of the sentences. Schizophrenics were significantly impaired in detecting all three types of ambiguity and, in addition, displayed a bias toward the primary meanings of sentences. They were also significantly impaired relative to controls in dealing with unambiguous sentences. However, this was found to be due to excessive response to distractor pictures rather than to lack of understanding of the unambiguous sentences.
Education and Training in Public Administration: Transference of Segmenting Organizational Behavior

Organizations can survive, let alone progress, only if they carry out meaningful transactions with society at large. This process requires they differentiate their “organizational being” to respond to clientele needs and/or user demands. The inherent problem is that these differentiated structures may become segmented into tightly closed systems, being in effect organizations within organization characterized by self-serving vested interests. Expediency becomes the operating rule. Segmentation is common to all societies, but it is especially prevalent in situations of decline. Advanced in this discussion is that the segmentation process may be accelerated and consolidated by in-house training and education, and especially by those of a public management character. A plea is made for universities to become more actively engaged in (a) the preparation and placement of “quality” educated persons and (b) the search/development of new public organization.
Better Verification Through Symmetry

A fundamental difficulty in automatic formal verification of finite-state systems is thestate explosion problem—even relatively simple systems can produce very large state spaces, causing great difficulties for methods that rely on explicit state enumeration. We address the problem by exploiting structuralsymmetries in the description of the system to be verified.
Effects of conformational peptide probe DP4 on bidirectional signaling between DHPR and RyR1 calcium channels in voltage-clamped skeletal muscle fibers.

In skeletal muscle, excitation-contraction coupling involves the activation of dihydropyridine receptors (DHPR) and type-1 ryanodine receptors (RyR1) to produce depolarization-dependent sarcoplasmic reticulum Ca2+ release via orthograde signaling. Another form of DHPR-RyR1 communication is retrograde signaling, in which RyRs modulate the gating of DHPR. DP4 (domain peptide 4), is a peptide corresponding to residues Leu2442-Pro2477 of the central domain of the RyR1 that produces RyR1 channel destabilization. Here we explore the effects of DP4 on orthograde excitation-contraction coupling and retrograde RyR1-DHPR signaling in isolated murine muscle fibers. Intracellular dialysis of DP4 increased the peak amplitude of Ca2+ release during step depolarizations by 64% without affecting its voltage-dependence or kinetics, and also caused a similar increase in Ca2+ release during an action potential waveform. DP4 did not modify either the amplitude or the voltage-dependence of the intramembrane charge movement. However, DP4 augmented DHPR Ca2+ current density without affecting its voltage-dependence. Our results demonstrate that the conformational changes induced by DP4 regulate both orthograde E-C coupling and retrograde RyR1-DHPR signaling.
A study of the effect of optimization function on calculated parameters of wilson equation

Estimated values of Wilson parameters depend upon the objective function which is used in the optimization procedure. The relationships between these estimated parameters seem to be more important than the values themselves, and the desirable paired parameters are confined to a region near ridge lines. This region represents a high level of joint confidence. In this study four different objective functions were used in the investigation of binary and ternary systems. Also, comparisons were made on calculated V/L equilibrium values predicted for ternary systems by using parameters estimated from binary and from the sole use of ternary data. Using the parameters estimated from binary data with a chosen objective function did not produce the best sum of squares of errors in a ternary system for the same objective function. Based on the overall performance, the best objective function to fit parameters in three ternaries is the one to fit the pressure. Les valeurs d'estimation des parametres de Wilson dependent de la fonction objective qu'on emploie dans la methode d'optimisation; les relations entre ces parametres qu'on evalue semblent plus importantes que les valeurs měmes, et les parametres desirables, groupes par deux, sont confines a une region situee pres des lignes de l'arěte, laquelle represente un degre eleve de fiabilite. On a employe, dans le present travail, quatre fonctions objectives differentes pour etudier des systemes binaires et tertiaires. On a aussi fait des comparisons relativement aux valeurs d'equilibre calculees V/L, qu'on avait prevues pour les systemes ternaires au moyen de parametres evalues a partir des donnees sur les systemes binaires et de celles des systemes ternaires seulement. L'emploi des parametres evalues partir des donnees sur les systemes binaires n'a pas produit la meilleure somme de carres d'erreur dans un systeme ternaire pour la měme fonction objective. En se basant sur le rendement global, la meilleure fonction objective qui convient aux parametres dans trois systemes ternaires est celle qui convient a la pression.
Formation properties of solid‐state extruded high density polyethylene fibers

Extrusion rates have been measured for high density polyethylene fibers prepared by solid-state extrusion through a conical die with maximum draw ratio of 52, using constant pressure and temperatures ranging from 0.12 to 0.49 GPa and 60° to 140°C and molecular weights from 5 × 104 to 6 × 106. The processing variables are reported in terms of an apparent elongational viscosity. The logarithm of the extrusion rate was proportional to the applied pressure. Deviation from the Eyring theory of viscosity was found, since lowering of the extrusion temperature to 60°C produced an anomalous decrease in the extrusion rates. The anomaly was explained by the increased friction between die and polymer, the pressure dependence of the yield stress, and by the pressure dependence of the α-relaxation mechanism. Apparent activation energies of 60 and 100 kcal/mole were calculated for the solid-state extrusion in the region 100°–130°C and 80–100°C. Three modes of deformation were observed for each extrusion, consisting of an unsteady state, a second stage of drawing in which the extrusion rate approached a constant value, and a fracture region. The first mode corresponded to orientation and rotation of the crystalline lamellae, as shown by the rapid increase and plateau region of the crystalline and noncrystalline orientation functions. During the second stage of deformation, the apparent elongational viscosity ηE increased linearly with draw ratio, as did the modulus, and this mode was found necessary for the attainment of high modulus fibers. The second mode of deformation was associated with the deformation of the crystalline lamellae and strain hardening in which ηE-approached that for a glass. Strain hardening readily occurred with decreasing temperature, and increasing draw ratio and molecular weight. Continuous extrusion producing uniform modulus fibers was only possible when the maximum draw ratio of the die was less than the fiber draw ratio, where strain hardening occurred. The third mode of deformation limited the maximum modulus obtainable and consisted of fracture or kink planes oblique to the fiber axis. The relations between the processing variables used in the solid-state extrusion and the resulting fiber properties are discussed.
Cell type specific and viral regulation of visna virus gene expression.

Regulation of gene expression of visna virus and other lentiviruses in vivo and in vitro is dependent on both cellular and viral factors. Differentiation and activation of the target cell is essential for transcriptional activation of the viruses. The cellular factors then activate viral transcription and expression of viral genes and viral regulatory proteins further regulate viral gene expression
Radiation exposure: a silent complication of catheter ablation procedures.

o An underappreciated “silent complication” of catheter ablation procedures is radiation exposure. X-ray exposure results in acute complications related to doseand timedependent exposure as well as a cumulative, lifetime risk to not only the patient but also the operator and electrophysiology staff. These risks include acute and subacute dermatologic injury, musculoskeletal injury, cataracts, malignancy, and genetic defects. 3 These risks are heightened for lengthy and multiple ablation procedures (eg, atrial fibrillation) and for vulnerable patients such as pediatric, obese, and pregnant patients. Risk models have been developed to estimate the incremental risk for malignancy attributable to x-ray exposure. Fatal malignancy in pediatric patients (median age 12 years) with relative low-dose fluoroscopy (median exposure of 14 minutes) during a single ablation procedure was associated with a 0.02% excess in lifetime risk. For complex/lengthy electrophysiology procedures, 1 hour of fluoroscopy is associated with an increase in lifetime risk of fatal malignancy of 0.07% for female and 0.1% for male patients. Although the attributable risk seems small, it is important to recall that fluoroscopy exposure is additive, inclusive of exposure related to multiple ablation and device procedures, and is not limited to the electrophysiology laboratory. In many centers, computed tomography imaging and reconstruction of the pulmonary veins is routinely performed before atrial fibrillation ablation. Emphasizing the importance of minimizing radiation exposure during cardiac interventions, the American College of Cardiology has promoted the ALARA principle: Keep fluoroscopic exposure to a level “as low as reasonably achievable.” Advances in the ALARA program are based on advances in technology: removal of secondary radiation grid and programming an ultralow pulsed fluoroscopy rate (two-third reduction in fatal malignancy risk), electroanaomic mapping systems (nearly 50% reduction in fluoros-
Low-field TDDB reliability data to enable accurate lifetime predictions

A 30 month module-based low-field TDDB study of 90nm pitch Back End of the Line (BEOL) interconnect structures and a 9 month study of 80nm pitch BEOL structures have shown that the commonly used root-E extrapolation model is overly conservative at predicting TDDB lifetimes at low applied fields. A less conservative acceleration model is required to make accurate lifetime predictions at low fields.