cssi/SciSciGPT-SciSciNet huggingface dataset:
Discovery of Novel Proline-Based Neuropeptide FF Receptor Antagonists

The neuropeptide FF (NPFF) system has been implicated in a number of physiological processes including modulating the pharmacological activity of opioid analgesics and several other classes of drugs of abuse. In this study, we report the discovery of a novel proline scaffold with antagonistic activity at the NPFF receptors through a high throughput screening campaign using a functional calcium mobilization assay. Focused structure–activity relationship studies on the initial hit 1 have resulted in several analogs with calcium mobilization potencies in the submicromolar range and modest selectivity for the NPFF1 receptor. Affinities and potencies of these compounds were confirmed in radioligand binding and functional cAMP assays. Two compounds, 16 and 33, had good solubility and blood–brain barrier permeability that fall within the range of CNS permeant candidates without the liability of being a P-glycoprotein substrate. Finally, both compounds reversed fentanyl-induced hyperalgesia in rats when administe...
BEEF CATTLE RETAINED OWNERSHIP AND PROFITABILITY IN TENNESSEE

The effect of animal characteristics and placement decisions on retained ownership profitability of Tennessee cattle from 2005 to 2015 was determined using a mixed model regression. Ex post simulation analysis examined retained ownership profitability by placement season under different animal characteristic and corn price scenarios. Regression results indicate that placement weight, placement season, days on feed, animal health, and animal sex affect retained ownership profitability. Simulation results indicate that winter placement of cattle in feedlots had the highest expected retained ownership profits. Results provide risk-averse producers information regarding the profitability of retained ownership.
The effectiveness of an obstructive sleep apnea screening and treatment program in patients with type 2 diabetes.

Abstract Aims As recommended by current guidelines, we tested the acceptability and impact of screening patients with type 2 diabetes for obstructive sleep apnea (OSA). Methods In a large urban primary care practice, we instituted a telephone-based OSA screening program using a validated tool (STOP-BANG) in patients with type 2 diabetes. Patients identified as high risk were referred for diagnostic sleep testing, and those diagnosed with OSA were offered positive airway pressure (PAP) therapy. We evaluated the impact of PAP on sleep-related symptoms, glycemic control, and hospitalization rates. Results We identified 738 of 818 (90.1%) patients with type 2 diabetes as high risk for OSA. Only 29.2% (n = 213) of high risk patients were willing to undergo diagnostic sleep testing. The prevalence of OSA was 90.6% in this group, but only 66.0% of those with OSA initiated PAP. Patients with higher burden of sleep symptoms were more likely to pursue testing and initiate therapy. PAP use was associated with reduced sleep-related symptoms (mean Epworth sleepiness scale score declined from 8.8 to 7.3, p Conclusions Despite a high prevalence of OSA, willingness to pursue diagnostic testing and treatment was low in an unselected type 2 diabetes population. Furthermore, glycemic control did not improve. Future screening programs should focus on patients with substantial sleep related symptoms as this group is most likely to derive benefit from treatment.
History of Central Asia, Vol. 3. The Age of Islam and the Mongols

Christoph Baumer’s third volume of an intended four-volume series is on par with the previous two volumes. He writes a clear and engaging narrative of the history of Central Asia (and beyond), acco...
Peering Into the Future of CAD Genomics

About 10 years ago, the promise of genome-wide association studies (GWASs) for reducing the burden of coronary artery disease (CAD) was in crisis. GWASs had not enabled the genetic prediction of CAD in populations. Nor had they revealed novel pathobiology. Even GWASs including up to 2000 cases of CAD, an ambitious proposition at the time, found only a single common association at chromosomal position 9p21 that surpassed the stringent significance threshold required for common variants on a genome-wide basis (ie, P <5×10−8).1–4 Although this signal was robust, it only minimally accounted for the family-based heritability and thus risk of CAD,5 and its biological mechanism of action could not be discerned because it mapped to an extended intergenic region. Subsequent GWAS over the following few years incrementally identified more CAD loci but still failed to account appreciably for CAD heritability. Article, see p 433 What was wrong? Did family-based heritability overestimate the role of genetics in populations? Did the heritability reside in rare instead of common genetic variants?6 Was there a need to consider gene-by-environment interactions? Certainly, all of these explanations contribute to a complete picture of CAD genetics. However, since the initial CAD GWASs, it has also been recognized that the heritability of CAD, like other complex traits, is substantially composed of many more variants than had been anticipated, each with a small effect. Such a genetic architecture, consisting of hundreds or even thousands of small genetic influences, can only be dissected with large samples; and the carefully nurtured cohort studies that have been highly effective for conventional CAD epidemiology are typically not large enough. In other words, as …
Variations in the long-term uplift rate due to the Altiplano-Puna magma body observed with Sentinel-1 interferometry

Abstract We present new Interferometric Synthetic Aperture Radar (InSAR) observations of surface deformation in the Altiplano–Puna region (South America) where previous studies documented a broad uplift at an average rate of ∼10 mm/yr. We use data from the Sentinel-1 satellite mission to produce high-resolution velocity maps and time series of surface displacements between years 2014–2017. The data reveal that the uplift has slowed down substantially compared to the 1992–2010 epoch and is characterized by short-term fluctuations on time scales of months to years. The observed variations in uplift rate may indicate a non-steady supply of melt and/or volatiles from the partially molten Altiplano–Puna Magma Body (APMB) into an incipient diapir forming in the roof of the APMB.
The Buddhist Unconscious (Alaya-vijnana) and Jung’s Collective Unconscious: What Does It Mean to Be Liberated from the Self?

At the interface of Buddhist psychology and Jungian psychology, there has been a lot of confusion about whether Jung’s archetype of Self is the same as or different from the Buddha’s teachings on No-Self. In this essay, I argue that the archetype of Self arises from the collective unconscious which is analogous to the alaya-vijnana (“storehouse consciousness” or “substrate consciousness”) and is not the same phenomenon as No-Self. I will draw on the scholarship just now emerging in Buddhist studies that analyzes the development of the Buddhist “unconscious” through the evolution of Abhidharma psychology into Yogacara psychology in third- to fifth-century India. My interest is the phenomenology of experience both in Yogacara and in Jungian psychology. By clarifying the Self from this perspective, we can clarify the functioning of the collective unconscious as it arises in dreams, culture, language, and individuals. We also, then, clarify the possibilities of becoming free or liberated from the collective or consensual world in our everyday reality. I will focus especially on the nature of consciousness/unconsciousness, unconscious complexes, subjectivity, intersubjectivity, and human suffering.
State and Local Party Organizations in the 21st Century

This paper presents results of a 2010 survey of 1,215 local party chairs in 49 states. The data focus on local party structure and activity, state-local party integration and party organizational culture. The analysis suggests local parties are organizationally mature, though most have not become permanent work organizations. The activities of local parties have undergone an important shift away from activities related to campaign money and fundraising and toward activities requiring volunteers and labor. At the same time, there has been notable disintegration in state-local cooperation. Party organizational cultures are generally effective, but there are systematic differences between the Democratic and Republican parties. Moreover, the data suggest cultural styles reflect various features of the political environment, including mass ideology, interparty competition and legislative professionalism.
The Future of EUS

EUS has evolved from diagnostic imaging to tissue sampling, and most recently to therapy. This chapter provides thoughts about where the field of EUS may be headed over the next 5–10 years in terms of echoendoscope and accessory development, disease management, and training. The future of EUS is bright, and we should expect a number of creative new EUS therapies in the near future.
Differential assessment and management of asthma vs chronic obstructive pulmonary disease.

Context Asthma and chronic obstructive pulmonary disease (COPD) are prevalent respiratory conditions with overlapping disease characteristics. Differentiation between asthma and COPD is important because several aspects of the guideline-recommended management strategies differ for these conditions. This review identifies the epidemiologic, etiologic, and clinical distinctions of these diseases to assist physicians and other clinicians in differentiating between asthma and COPD. Key components of the guideline-recommended management approaches for these conditions are also reviewed.
Specialized Plastids Trigger Tissue-Specific Signaling for Systemic Stress Response in Plants

Plastids comprise a complex set of organelles in plants that can undergo distinctive patterns of differentiation and redifferentiation during their lifespan. Plastids localized to the epidermis and vascular parenchyma are distinctive in size, structural features, and functions. These plastids are termed “sensory” plastids, and here we show their proteome to be distinct from chloroplasts, with specialized stress-associated features. The distinctive sensory plastid proteome in Arabidopsis (Arabidopsis thaliana) derives from spatiotemporal regulation of nuclear genes encoding plastid-targeted proteins. Perturbation caused by depletion of the sensory plastid-specific protein MutS HOMOLOG1 conditioned local, programmed changes in gene networks controlling chromatin, stress-related phytohormone, and circadian clock behavior and producing a global, systemic stress response in the plant. We posit that the sensory plastid participates in sensing environmental stress, integrating this sensory function with epigenetic and gene expression circuitry to condition heritable stress memory.
Topkapi: parallel and fast sketches for finding top-K frequent elements

Identifying the top-K frequent items is one of the most common and important operations in large data processing systems. As a result, several solutions have been proposed to solve this problem approximately. In this paper, we identify that in modern distributed settings with both multi-node as well as multi-core parallelism, existing algorithms, although theoretically sound, are suboptimal from the performance perspective. In particular, for identifying top-K frequent items, Count-Min Sketch (CMS) has fantastic update time but lack the important property of reducibility which is needed for exploiting available massive data parallelism. On the other end, popular Frequent algorithm (FA) leads to reducible summaries but the update costs are significant. In this paper, we present Topkapi, a fast and parallel algorithm for finding top-K frequent items, which gives the best of both worlds, i.e., it is reducible as well as efficient update time similar to CMS. Topkapi possesses strong theoretical guarantees and leads to significant performance gains due to increased parallelism, relative to past work.
Revolutionary anti-authoritarian movements and anarchist studies

The three works under review here problematize standard narratives about anarchist movements and the ways in which people attempt to exist without hierarchical authority. Modern anarchism has persi...
Work-Family Issues Among Self-Employed Married Women

Purpose: This study examined work-family, work domain, and satisfaction differences between self-employed married women (N=206) who were independently self-employed (ISE) and those who owned a business with employees (Owners). Design/Methodology/Approach: ANOVAs and multiple regressions were used to identify differences on the study variables between ISEs and Owners. Findings: ISEs were significantly more likely to report higher flexibility in managing work and family, that their schedule met their needs, and have higher job satisfaction. Owners reported significantly higher work interfering with family (WIF), work hours, and were more likely to attend to work demands over family demands. Regression analysis revealed differential predictors of WIF for ISEs and Owners. Schedule fit, work hours, and depression were significant for ISEs. Life satisfaction was significant for Owners. Research Limitations: The identification of self-employed individuals as well as those who were ISEs or Owners was based on single questions. How individuals became self-employed cannot be addressed. The smaller sample size for Owners is a concern but it reflects the reality that ISE is a more accessible to many women. Originality/Value: The findings indicate that work-family issues and other variables are related to the type of small business for married women. There are similarities and differences between these two groups of married women.
Solving the army's cyber workforce planning problem using stochastic optimization and discrete-event simulation modeling

The U.S. Army Cyber Proponent (Office Chief of Cyber) within the Army’s Cyber Center of Excellence is responsible for making many personnel decisions impacting officers in the Army Cyber Branch (ACB). Some of the key leader decisions include how many new cyber officers to hire and/or branch transfer into the ACB each year, and how many cyber officers to promote to the next higher rank (grade) each year. We refer to this decision problem as the Army’s Cyber Workforce Planning Problem. We develop and employ a discrete-event simulation model to validate the number of accessions, branch transfers, and promotions (by grade and cyber specialty) prescribed by the optimal solution to a corresponding stochastic goal program that is formulated to meet the demands of the current force structure under conditions of uncertainty in officer retention. In doing so, this research provides effective decision-support to senior cyber leaders and force management technicians.
Substantial Preoperative Work Is Unaccounted for in Total Hip and Knee Arthroplasty.

Abstract Background The Centers for Medicare and Medicaid Services has recently designated the codes for total hip and knee arthroplasty as misvalued and has asked the Relative Value Scale Update Committee (RUC) to review the work required to perform these procedures. Although other studies have reported time spent on perioperative and postoperative care, time spent on coordinating and performing preoperative care is not included in current RUC methodology and has yet to be addressed in literature. Methods We prospectively tracked a consecutive series of 438 primary total hip arthroplasty and total knee arthroplasty patients by one of the 5 surgeons over a 3-month period. Each clinical staff member tracked the amount of time to perform each preoperative care task from the last clinic visit until day of surgery. Data were analyzed separately between providers and ancillary medical staff. Results Although the current RUC review includes 40 minutes of preservice time on the day of surgery, surgeons spent an average of an additional 43.2 minutes while physician assistants and nurse practitioners spent an additional 97.9 minutes per patient on preoperative care prior to that time. Ancillary medical staff spent a mean of 110.2 minutes per patient. The most common tasks include preoperative phone calls, templating and surgical planning, and preoperative patient education classes. Conclusion Surgeons and advanced practice providers spend nearly 2 hours per arthroplasty patient on preoperative care not accounted for in current RUC methodology. As readmissions, hospital stay, and complication rates continue to decline, Centers for Medicare and Medicaid Services should consider the substantial work required during the preoperative phase to allow for these improved outcomes.
Behavioral Pharmacology of Opiates

The purpose of this chapter is to describe and discuss what is currently known about the behavioral pharmacology of opioids in infra-humans and humans. This is a daunting task, given the breadth and depth of research that has been conducted during the past 50 years. Several reviews on the behavioral pharmacology of opioids cover certain areas in much greater detail than what can be covered here; the reader is encouraged to refer to these reviews, some of which appear yearly as an “update” (see Appendix for review bibliography).*
Modeling Probability Density Functions as Data Objects

Abstract Recent developments in the probabilistic and statistical analysis of probability density functions are reviewed. Density functions are treated as data objects for which suitable notions of the center of distribution and variability are discussed. Special attention is given to nonlinear methods that respect the constraints density functions must obey. Regression, time series and spatial models are discussed. The exposition is illustrated with data examples. A supplementary vignette contains expanded versions of data analyses with accompanying codes.
A new short-faced archosauriform from the Upper Triassic Placerias/Downs' quarry complex, Arizona, USA, expands the morphological diversity of the Triassic archosauriform radiation

The Placerias/Downs’ Quarry complex in eastern Arizona, USA, is the most diverse Upper Triassic vertebrate locality known. We report a new short-faced archosauriform, Syntomiprosopus sucherorum gen. et sp. nov., represented by four incomplete mandibles, that expands that diversity with a morphology unique among Late Triassic archosauriforms. The most distinctive feature of Syntomiprosopus gen. nov. is its anteroposteriorly short, robust mandible with 3–4 anterior, a larger caniniform, and 1–3 “postcanine” alveoli. The size and shape of the alveoli and the preserved tips of replacement teeth preclude assignment to any taxon known only from teeth. Additional autapomorphies of S. sucherorum gen. et sp. nov. include a large fossa associated with the mandibular fenestra, an interdigitating suture of the surangular with the dentary, fine texture ornamenting the medial surface of the splenial, and a surangular ridge that completes a 90° arc. The external surfaces of the mandibles bear shallow, densely packed, irregular, fine pits and narrow, arcuate grooves. This combination of character states allows an archosauriform assignment; however, an associated and similarly sized braincase indicates that Syntomiprosopus n. gen. may represent previously unsampled disparity in early-diverging crocodylomorphs. The Placerias Quarry is Adamanian (Norian, maximum depositional age ~219 Ma), and this specimen appears to be an early example of shortening of the skull, which occurs later in diverse archosaur lineages, including the Late Cretaceous crocodyliform Simosuchus. This is another case where Triassic archosauriforms occupied morphospace converged upon by other archosaurs later in the Mesozoic and further demonstrates that even well-sampled localities can yield new taxa.
SCISSOR™: a single-cell inferred site-specific omics resource for tumor microenvironment association study

Tumor tissues are heterogeneous with different cell types in tumor microenvironment, which play an important role in tumorigenesis and tumor progression. Several computational algorithms and tools have been developed to infer the cell composition from bulk transcriptome profiles. However, they ignore the tissue specificity and thus a new resource for tissue-specific cell transcriptomic reference is needed for inferring cell composition in tumor microenvironment and exploring their association with clinical outcomes and tumor omics. In this study, we developed SCISSOR™ (https://thecailab.com/scissor/), an online open resource to fulfill that demand by integrating five orthogonal omics data of >6031 large-scale bulk samples, patient clinical outcomes and 451 917 high-granularity tissue-specific single-cell transcriptomic profiles of 16 cancer types. SCISSOR™ provides five major analysis modules that enable flexible modeling with adjustable parameters and dynamic visualization approaches. SCISSOR™ is valuable as a new resource for promoting tumor heterogeneity and tumor-tumor microenvironment cell interaction research, by delineating cells in the tissue-specific tumor microenvironment and characterizing their associations with tumor omics and clinical outcomes.
Re: "Psychiatric Medication Users by Age and Sex".

To the Editor: In “Psychiatric Medication Users by Age and Sex,” the author found that the reported use of psychiatric medications increased from 1999 to 2018.[1][1] There were no comments regarding the effectiveness or benefits of this change, but the study evidenced the burden of mental health
Regulation, Economic Theory of

Abstract Regulation takes many forms in practice, including price, quality, disclosure, privacy, and externality regulation. Popular methods for regulating the prices charged by public utilities include rate of return regulation, price cap regulation, and yardstick regulation. The optimal design of regulatory policy varies with industry structure and institutions, with regulatory objectives and policy instruments, and with the prevailing information structure.
On-line NMR detection in capillary electrophoresis using an RF microcoil

The goal of this research is the development of a capillary electrophoresis nuclear magnetic resonance (CENMR) detector. Using an RF microcoil, this technique has a detection limit of the order of nanograms.
The Causal Poset Is Directed but Not Lattice Ordered

In the causal set approach to discrete quantum gravity the universe grows one element at a time in discrete steps. At each step the process has the form of a causal set (causet) and the "completed" universe is given by a path through a discretely growing chain of causets. The collection of causets forms a partially ordered set (poset) in a natural way. We first show that this poset is directed. We then give a counterexample which shows it is not lattice ordered.
Forensic Techniques for Image Source Classification: A Comparative Study

Digital images can be captured or generated by a variety of sources including digital cameras, scanners and computer graphics softwares. In many cases it is important to be able to determine the source of a digital image such as for criminal and forensic investigation. Based on their originating mechanism digital images can be classified into three classes: digital camera images, scanner generated images and computer-graphics generated images. Image source classification is helpful as a first step for identifying the unique device or system which produced the image. This paper presents a survey of different methods for solving image source classification problem, some improvements over them and compares their performance in a common framework. As expected with the advances in computer graphics techniques, artificial images are becoming closer and closer to the natural ones and harder to distinguish by human visual system. Hence, the methods based on characteristics of image generating process are more successful than those based on image content.
Kidney and Bone: Physiological and Pathophysiological Relationships

The sections in this article are: 1 Chemical and Cellular Composition of Bone 1.1 Extracellular Constituents of Bone 1.2 Bone Cells 2 Development and Structure of Bone 2.1 Endochondral Ossification 2.2 Intramembranous Ossification 3 Skeletal Growth and Modeling 3.1 Principles of Skeletal Growth 3.2 Skeletal Modeling 3.3 Epiphyseal Closure 3.4 Bone Cell Function and Skeletal Growth and Modeling 4 Bone Turnover and the Remodeling Cycle 4.1 Skeletal Remodeling 4.2 Cellular Control of Bone Remodeling 5 Fracture Healing 6 Bone Cell Function and Fracture Repair 7 Interrelationships of Kidney and Bone in Normal Physiology 7.1 General Considerations 7.2 Overall Calcium Balance 7.3 Hormonal Control of Mineral Ion Homeostasis 7.4 Role of the Parathyroid Glands in the Calcium Homeostatic System 7.5 Bone Cell Function and Ionic Homeostasis 7.6 Aspects of Renal Function Essential for Normal Skeletal Structure and Function and Ionic Homeostasis 8 Metabolic Bone Disease 8.1 Osteitis Fibrosa 8.2 Osteomalacia 8.3 Osteoporosis 9 Laboratory Evaluation of Metabolic Bone Disease 9.1 Direct Assays of Calcium-Regulating Hormones in Blood 9.2 Clinical Assessment of the Function of Target Organs for Calcium-Regulating Hormones 10 Abnormalities in Renal Function Leading to Skeletal Disease 10.1 Abnormalities in Renal Calcium Handling 10.2 Abnormalities in Renal Phosphate Handling 10.3 Hypo- and Hypermagnesemia Due to Renal Causes 10.4 Renal Tubular Acidosis 10.5 Primary Abnormalities in Vitamin D Metabolism 10.6 Renal Resistance to PTH: Pseudohypoparathyroidism 10.7 Chronic Renal Insufficiency 10.8 Pathophysiology of Renal Osteodystrophy 11 Disorders Affecting the Homeostatic Mechanisms Linking Kidney and Bone 11.1 Primary Hyperparathyroidism 11.2 Humoral Hypercalcemia of Malignancy 11.3 Hypoparathyroidism 11.4 Deficient Quantities and Action of Vitamin D 11.5 Hypervitaminosis D 11.6 Sarcoidosis and Other Granulomatous Diseases 12 Other Hormonal Abnormalities and Drugs Affecting Both Bone and Kidney 12.1 Calcitonin 12.2 Growth Hormone 12.3 Estrogen 12.4 Glucocorticoids 12.5 Insulin 12.6 Thyroid Hormones 13 Miscellaneous Associations Between Bone and Kidney 13.1 Disorders Affecting Both Kidney and Bone 13.2 Pharmacological Agents Affecting Both Kidney and Bone 14 Effects of Bone Disease on the Kidney
WE HAVEN'T TALKED IN 30 YEARS!: Relationship reconnection and internet use at midlife

The phenomenon of reconnection of dormant ties using internet communication technologies has been identified as having salience in the use of social media forms by midlife and older adults. Dormant ties, as distinguished from those that are merely inactive, are those that were once operational, but which have lapsed under the stressors of time, distance and circumstance, such as relationships between former college friends, neighbors or work colleagues. Reconnection is the process by which these dormant ties become active again, and is an activity which is supported in unique ways by internet communication technologies. This study presents findings from interviews with midlife adults on how the use of email, social network sites and search engines is leveraged to enhance and support the reconnection of dormant relationships and maintain weak ties. Grounded in a life course perspective, it examines how the experiences of longevity and the life course alter perceptions of the attributes and drawbacks that t...
Tobacco dependence treatment: Influence of training experiences on clinical activities among otolaryngologists

Objectives/Hypothesis Although one in five U.S. adults continue to smoke, healthcare providers often fail to provide basic, effective interventions. This is particularly true for physician specialists. This study sought to investigate perceived role, self-efficacy, practice behaviors, and attitudes among otolaryngologists as they relate to the delivery of tobacco treatment services. Study Design This study involved a single administration of a survey questionnaire to current members of the American Academy of Otolaryngology Head and Neck Surgery (AAO-HNS). Methods A questionnaire was mailed up to three times to active members. Results Survey response rate was 39% (N = 2127). Based on an evaluation of treatment factors categorized according to the National Cancer Institute's 5A's approach, trained providers generally rated themselves consistently higher than untrained providers across areas of clinical activity. Minimal differences were noted for Ask and Advise, moderate for Assess, and the greatest for Assist and Arrange. Trained providers also indicated more positive attitudes towards treatment. Conclusions While the level of performance was reasonable for otolaryngologists relative to other specialists in the published literature, overall tobacco treatment activity remains unacceptably low. This study suggests the positive impact of training and the potential value of making such experiences widely available. Laryngoscope, 123:3005–3009, 2013
A NEW SYNTHETIC ROUTE TO PROSTAGLANDINS

Abstract A short synthetic route to prostaglandins is described which depends on oxime-based methodology and which involves the joining of intermediates 9 , 11 , and 12 in a one-flask operation.
Effect of conflict between the body parts on perceptual adaptation

Two groups of subjects adapted to prismatic displacement. One adapted in a visual target condition, in which they pointed to an external visual target with their right index fingers. The other adapted in a body target condition, in which they pointed to their left index fingers with their right index fingers. The visual target group showed more adaptation of the right hand and less adaptation of the left hand than did the body target group. These results are consistent with an assimilation tendency within the proprioceptive modality, namely that body parts that are in contact tend to be perceived as occupying the same spatial position.
Proteasome gene upregulation: a possible mechanism for intestinal adaptation.

Abstract Background/Purpose The mechanisms that control intestinal adaptation remain unknown. To better understand the adaptive process, microarray technology was used to analyze gene expression in a rat model of intestinal adaptation. Methods Adult male Sprague-Dawley rats underwent either a massive small bowel resection (70%) with anastomosis or a sham operation with small bowel transection and reanastomosis. After 21 days, ileal mucosa RNA was extracted. Individual RNA samples (n = 5 per group) were labeled and hybridized to 10 separate RAE 230A rat GeneChips. The signal values were calculated and the 2 groups were compared using a t test with the multiple testing correction of Benjamini and Hochberg (false discovery rate of 10%). Probe sets were analyzed for overrepresented physiologic pathways using Expression Analysis Systematic Explorer (EASE). Results Of the 15,866 probe sets on the RAE 230A GeneChip, 5437 probe sets were unexpressed and excluded. Of the remaining 10,429 probe sets, several overrepresented pathways (EASE score Conclusions Proteasomes may play a critical role in regulating the proliferation of intestinal mucosa during intestinal adaptation.
The Effect of Novel Promoter Variants in MATE1 and MATE2 on the Pharmacokinetics and Pharmacodynamics of Metformin

Interindividual variation in response to metformin, first-line therapy for type 2 diabetes, is substantial. Given that transporters are determinants of metformin pharmacokinetics, we examined the effects of promoter variants in both multidrug and toxin extrusion protein 1 (MATE1) (g.-66T → C, rs2252281) and MATE2 (g.-130G → A, rs12943590) on variation in metformin disposition and response. The pharmacokinetics and glucose-lowering effects of metformin were assessed in healthy volunteers (n = 57) receiving metformin. The renal and secretory clearances of metformin were higher (22% and 26%, respectively) in carriers of variant MATE2 who were also MATE1 reference (P < 0.05). Both MATE genotypes were associated with altered post-metformin glucose tolerance, with variant carriers of MATE1 and MATE2 having an enhanced (P < 0.01) and reduced (P < 0.05) response, respectively. Consistent with these results, patients with diabetes (n = 145) carrying the MATE1 variant showed enhanced metformin response. These findings suggest that promoter variants of MATE1 and MATE2 are important determinants of metformin disposition and response in healthy volunteers and diabetic patients.
One-zero sampling in the study of primate behavior

One-zero (Hansen) frequency, the proportion of time samples during which a certain behavior occurs, measures a linear combination of prevalence (the proportion of time an animal spends in a behavior) and of incidence (the number of bouts of a behavior per hour) with a non-negligible perturbation due to the clustering characteristics of behavior relative to the time interval length. The exact relationship is derived theoretically and demonstrated empirically usingLeger's data base of chimpanzee behavior. It is recommended that, whenever possible, time sampling methods other than One-zero Sampling be used in the study of behavior.
Sensible rules for remembering duals—the S-O-B method

We present a natural motivation and simple mnemonic for creating the dual LP of any linear program- ming problem.
Roles of the Sea in Medieval England

Roles of the Sea in Medieval England by Richard Gorski (ed.) The Boydell Press, Woodbridge, 2012, £50 (hb) 194 pages, with 2 maps, index ISBN 978-1-84383-701-5 Most of the eight essays in this volu...
Inhibition of HIV-1 integrase by flavones, caffeic acid phenethyl ester (CAPE) and related compounds

The inhibition of HIV-1 integrase by flavones and related compounds was investigated biochemically and by means of structure-activity relationships. Purified enzyme and synthetic oligonucleotides were used to assay for three reactions catalysed by integrase: (1) processing of 3' termini by cleavage of the terminal dinucleotide; (2) strand transfer, which models the integration step; and (3) "disintegration," which models the reversal of the strand transfer reaction. Inhibitions of all three reactions by flavones generally occurred in parallel, but caffeic acid phenethyl ester (CAPE) appeared to inhibit reaction 2 selectively. CAPE, however, inhibited reactions 1 and 3 effectively when preincubated with the enzyme, suggesting that this compound differs from the flavones primarily in requiring more time to block the enzyme. The core integrase fragment consisting of amino acids 50-212 retained the ability to catalyse reaction 3, and flavones and CAPE retained the ability to inhibit. Hence, the putative zinc-finger region that is deleted in this fragment is probably not the target of inhibition. Inhibition by flavones usually required the presence of at least one ortho pair of phenolic hydroxyl groups and at least one or two additional hydroxyl groups. Potency was enhanced by the presence of additional hydroxyl groups, especially when present in ortho pairs or in adjacent groups of three. Inhibitory activity was reduced or eliminated by methoxy or glycosidic substitutions or by saturation of the 2,3 double bond. These structure-activity findings for flavones were generally concordant with those previously reported for reverse transcriptase and topoisomerase II. These findings are discussed in the context of a review of the effects of flavones on various enzymes, the possible mechanisms of inhibition, and the potential for building upon a general pharmacophore to generate target specificity.
Adenosine-to-inosine RNA editing and human disease

A-to-I RNA editing is a post-transcriptional modification that converts adenosines to inosines in both coding and noncoding RNA transcripts. It is catalyzed by ADAR (adenosine deaminase acting on RNA) enzymes, which exist throughout the body but are most prevalent in the central nervous system. Inosines exhibit properties that are most similar to those of guanosines. As a result, ADAR-mediated editing can post-transcriptionally alter codons, introduce or remove splice sites, or affect the base pairing of the RNA molecule with itself or with other RNAs. A-to-I editing is a mechanism that regulates and diversifies the transcriptome, but the full biological significance of ADARs is not understood. ADARs are highly conserved across vertebrates and are essential for normal development in mammals. Aberrant ADAR activity has been associated with a wide range of human diseases, including cancer, neurological disorders, metabolic diseases, viral infections and autoimmune disorders. ADARs have been shown to contribute to disease pathologies by editing of glutamate receptors, editing of serotonin receptors, mutations in ADAR genes, and by other mechanisms, including recently identified regulatory roles in microRNA processing. Advances in research into many of these diseases may depend on an improved understanding of the biological functions of ADARs. Here, we review recent studies investigating connections between ADAR-mediated RNA editing and human diseases.
EFFECTS OF 5‐HYDROXYTRYPTOPHAN ON SEROTONIN IN NERVE ENDINGS

—Preparations of synaptosomes (P2) from the telencephalon and from the diencephalon plus optic lobes of the pigeon and from the telencephalon of the rat were used to study the effects of 5-hydroxytryptophan (5-HTP) on (a) the levels of serotonin (5-HT) in nerve endings and (b) the release of 5-HT from nerve endings. The levels of 5-HT were significantly higher (3.21 × 0.35 nmol/g original tissue weight) in the P2 fraction isolated from the telencephalon of pigeons given intramuscular injections of 50mg/kg of d,l-5-HTP in comparison to control values (1.42 ± 0.07). A similar twofold increase was observed with the P2 fraction isolated from the diencephalon plus optic lobes. In addition, the levels of 5-HTP and 5-hydroxyindoleacetic acid also increased significantly in these P2 fractions isolated from pigeons given d,l-5-HTP injections in comparison to values obtained for pigeons given saline injections. In vitro studies using preparations of synaptosomes (from both pigeon and rat) labelled with [3H]5-HT indicated that 0.10 mil l-5-HTP increased the release of [3H]5-HT twofold over control values. A concentration as low as 0.001 mm l-5-HTP was tested on the P2 fraction from the telencephalon of the pigeon and was found to significantly increase the release of [3H]5-HT over control values. This effect by l-5-HTP was blocked if a decarboxylase inhibitor was added to the medium. l-5-HTP at a concentration of 1.5 mm had no apparent effect on the release of [3H]norepinephrine or [3H]dopamine from synaptosomes prepared from the telencephalon of the rat or pigeon. The results are discussed in terms of the role of serotonin in producing certain types of behavioral depressions exhibited by pigeons and rats given injections of 5-HTP.
Efficient and robust model fitting with unknown noise scale

This paper addresses the general problem of robust parametric model estimation from data that has both an unknown (and possibly majority) fraction of outliers as well as an unknown scale of measurement noise. We focus on computer vision applications from image correspondences, such as camera resectioning, estimation of the fundamental matrix or relative pose for 3D reconstruction, and estimation of 2D homographies for image registration and motion segmentation, although there are many other applications. In practice, these methods typically rely on a predefined inlier thresholds because automatic scale detection is usually too unreliable or too slow. We propose a new method for robust estimation with automatic scale detection that is faster, more precise and more robust than previous alternatives, and show that it can be practically applied to these problems.
Two-nucleon pick-up from spin-12 targets (I). 57Fe

Abstract We have measured differential cross sections for the (p, t) and (p, τ) reactions on 57Fe at a proton energy of 27 MeV, and for the (d, α) reaction at 16.0 MeV. Several spin-parity assignments for 55Fe and 55Mn are suggested, and comparisons to DWBA calculations allow the identification of those states with a strong two-hole parentage. Attempts to find simple relations between these results and the yields from two-nucleon pick-up reactions on nearby doubly even targets were not successful.
A fractionating column for analysis of nucleic acids

Abstract A readily prepared fractionating column is described that separates several ribonucleic and deoxyribonucleic acids from each other, including the closely similar nucleic acids of T2 and T4 bacteriophages. The column also distinguishes DNA that has been denatured by heat and DNA that has been broken by hydrodynamic shear from the starting material. Some notes are recorded also concerning the preparation of nucleic acids from bacteria and phage by the phenol method.
The effect of uremia on circulating mevalonate metabolism in rats.

Abstract Mevalonate, an essential intermediate in cholesterol synthesis, is metabolized either to sterols or by the shunt pathway to CO 2 . Previous studies have demonstrated that the kidneys are the chief site of circulating mevalonate metabolism by both pathways. Following nephrectomy, as expected, the shunt pathway was reduced by greater than 50%. However, nephrectomy resulted in an enhancement of total body sterologenesis which was due to a marked stimulation of both liver and carcass sterol synthesis. The present study unexpectedly demonstrates that, even in the presence of intact kidneys, uremia induces marked alterations in the metabolism of circulating mevalonate that are similar to those observed following nephrectomy. In rats with normal renal mass the oxidation of mevalonate to CO 2 is reduced by 57% in acutely uremic and by 34% in chronically uremic animals. This reduction in shunt pathway activity directly correlates with the degree of impairment of renal function as measured by plasma BUN and creatinine levels. In contrast to the inhibition of the shunt pathway, acute and chronic uremia is associated with a two- to threefold increase in both hepatic and carcass cholesterol and nonsaponifiable lipid synthesis from circulating mevalonate. In the liver this enhancement of sterologenesis directly correlates with plasma BUN and creatinine concentrations. Renal sterologenesis from circulating mevalonate is not significantly altered by either acute or chronic uremia. This study demonstrates that uremia per se greatly alters circulating mevalonate metabolism resulting in a marked reduction in the shunt pathway and a large stimulation of sterol synthesis in both the liver and carcass.
Alveolar soft part sarcoma following radiotherapy for a spinal hemangioma. A case report.

A case of alveolar soft part sarcoma arising some 20 years later in a site previously irradiated as a treatment for a spinal cord hemangioma is described. This is the first known case of radiation-associated alveolar soft part sarcoma, and it fulfills the criteria for a tumor to be radiation-induced. The coincidental finding of ''viral-like'' particles within some of the tumor cells was noted.
Metamagnetic states in single crystal HoNi2B2C at T ≈ 1.9 K: Torque magnetometry study

Metamagnetic transitions in single-crystal rare-earth nickel borocarbide HoNi2B2C have been studied at T ≈ 1.9 K with a Quantum Design torque magnetometer. With increasing field, transitions to antiferromagnetic, ferrimagnetic, non-collinear, and saturated paramagnetic states take place. The critical fields of the transitions depend crucially on the angle θ between applied field and the easy axis [110]. Measurements of torque along the c axis have been made while changing the angular direction of the magnetic field (parallel to basal tetragonal ab planes) and with changing field at fixed angle over a wide angular range. Two new phase boundaries in the region of the non-collinear phase have been observed, and the direction of the magnetization in this phase has been precisely determined. At low field the antiferromagnetic phase is observed to be multidomain. In the angular range around the hard axis (−6° ≤ ϕ ≤ 6°, where ϕ is the angle between the field and hard axis [100]) the magnetic behavior is found to be “frustrated” with a mixture of phases with different directions of the magnetization.
Ritual and Irony: Observations about the discourse of political change in two Germanies

This essay discusses the communicative background of the political changes in the German Democratic Republic leading up to its first free elections and unification with the Federal Republic of Germany on October 3rd, 1990. I argue that the widening dissonance between the ritualized official political discourse and the citizens’ experience of everyday reality precipitated the dissolution of the socialist experiment in the GDR, particularly by means of the ironization of that discourse. The essay concludes with some observations about the search for a new form of meaningful public discourse necessitated by these events.
Effects of pre-pregnancy body mass index and gestational weight gain on infant anthropometric outcomes.

Objective To determine whether pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) influence infant postnatal growth. Study design Participants were from the Pregnancy, Infection, and Nutrition study, a prospective pregnancy cohort. Term infants with weight or length measurements at approximately 6 months were included (n = 363). Multivariable regression estimated associations for weight-for-age (WAZ), length-for-age (LAZ), and weight-for-length z-scores (WLZ) and rapid infant weight gain with categorical maternal exposures defined with the 2009 Institute of Medicine recommendations. Results Pre-pregnancy overweight and obesity were associated with higher WAZ (linear regression coefficient [β], 0.32; 95% CI, 0.04-0.61) and WLZ (β, 0.39; 95% CI, 0.02-0.76), respectively. Pre-pregnancy BMI was not associated with LAZ. Excessive GWG was associated with higher WAZ (β, 0.39; 95% CI, 0.15-0.62) and LAZ (β, 0.34; 95% CI, 0.12-0.56). Excessive GWG ≥200% of recommended amount was associated with higher WAZ (β, 0.68; 95% CI, 0.28-1.07), LAZ (β, 0.45; 95% CI, 0.06-0.83), and WLZ (β, 0.43; 95% CI, 0.04-0.82). Risk of rapid weight gain increased across maternal exposure categories; however, none of the estimates were significant. Conclusions Pre-pregnancy BMI and GWG are modifiable intrauterine exposures that influence infant postnatal anthropometric outcomes. Further investigation with infant body composition measurements is warranted.
Flow cytofluorometric analysis of the nuclear division cycle of Physarum polycephalum plasmodia

The nuclear cycle kinetics of Physarum polycephalum plasmodia were examined using flow cytofluorometry. The dyes Hoechst 33342 and propidium iodide were used to stain the DNA of isolated nuclei. In asynchronously growing microplasmodia. S phase consists of 13--15% of the nuclear division cycle time. Nuclei isolated from individual macroplasmodia, which have previously been demonstrated to divide in synchrony, were shown to be less synchronized during late S phase than during mitosis. The results obtained demonstrate the feasibility of flow cytometric measurement of the properties of nuclei isolated from a single cell.