cssi/SciSciGPT-SciSciNet huggingface dataset:
Identification of Raloxifene as a Novel CB2 Inverse Agonist

The purpose of the current study was to apply a high throughput assay to systematically screen a library of food and drug administration (FDA)-approved drugs as potential ligands for the cannabinoid receptor 2 (CB2). A cell-based, homogenous time resolved fluorescence (HTRF) method for measuring changes in intracellular cAMP levels was validated and found to be suitable for testing ligands that may act on CB2. Among the 640 FDA-approved drugs screened, raloxifene, a drug used to treat/prevent post-menopausal osteoporosis, was identified for the first time to be a novel CB2 inverse agonist. Our results demonstrated that by acting on CB2, raloxifene enhances forskolin-stimulated cAMP accumulation in a concentration-dependant manner. Furthermore, our data showed that raloxifene competes concentration-dependently for specific [(3)H]CP-55,940 binding to CB2. In addition, raloxifene pretreatment caused a rightward shift of the concentration-response curves of the cannabinoid agonists CP-55,940, HU-210, and WIN55,212-2. Raloxifene antagonism is most likely competitive in nature, as these rightward shifts were parallel and were not associated with any changes in the efficacy of cannabinoid agonists on CB2. Our discovery that raloxfiene is an inverse agonist for CB2 suggests that it might be possible to repurpose this FDA-approved drug for novel therapeutic indications for which CB2 is a target. Furthermore, identifying raloxifene as a CB2 inverse agonist also provides important novel mechanisms of actions to explain the known therapeutic effects of raloxifene.
Suppressing N-Myc downstream regulated gene 1 reactivates senescence signaling and inhibits tumor growth in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most lethal malignancy worldwide with no curative therapies. To discover potentially novel therapeutic targets for HCC, we previously studied the gene expression profiles of HCC patients and identified that significant upregulation of N-Myc downstream regulated gene 1 (NDRG1) is associated with more aggressive phenotypes and poorer overall survival of HCC patients. In this study, we further used a loss-of-function approach (RNA interference) to understand the role of NDRG1 in hepatocarcinogenesis. We found that suppression of NDRG1 significantly impaired HCC cell growth through inducing extensive cellular senescence of HCC cells both in vitro and in vivo, accompanied by cell cycle arrest at the G1 phase. The observed antitumor effects of NDRG1 suppression were correlated with activation of major senescence-associated signaling pathways, such as upregulation of tumor suppressors p53, p21 and p16, and decreased phosphorylated Rb. To obtain further insights into the clinical significance of NDRG1-modulated senescence in HCC patients, immunohistochemistry staining of 92 cases of HCC patients was done. We found that high NDRG1 expression (n = 66) is associated with low p21 (n = 82; P < 0.001) and low p16 (n = 86; P < 0.001) levels. In conclusion, this study demonstrated that NDRG1 is a potential therapeutic target for HCC because its suppression triggers senescence of HCC cells through activating glycogen synthase kinase-3β–p53 pathway, thereby inhibiting tumor progression.
24-Hour ICH Score Is a Better Predictor of Outcome than Admission ICH Score

Background. The ICH score is a validated tool for predicting 30-day morbidity and mortality in patients with intracerebral hemorrhage. Aims and/or Hypothesis. The aim of this study is to determine if the ICH score calculated 24 hours after admission is a better predictor of mortality than the ICH score calculated on admission. Methods. Patients presenting to our center with ICH from 7/08–12/10 were retrospectively identified from our prospective stroke registry. ICH scores were calculated based on initial Glasgow coma scale (GCS) and emergent head computed tomography (CT) on initial presentation and were recalculated after 24 hours. Results. A total of 91 patients out of 121 had complete data for admission and 24-hour ICH score. The ICH score changed in 38% from baseline to 24 hours. After adjusting for age, NIHSS on admission, and glucose, ICH score at 24 hours was a significant, independent predictor of mortality (OR = 2.71, 95% CI 1–19–6.20, and ), but ICH score on admission was not (OR = 2.14, 95% CI 0.88–5.24, and ). Conclusion. Early determination of the ICH score may incorrectly estimate the severity and expected outcome after ICH. Calculations of the ICH score 24 hours after admission will better predict early outcomes.
The Meaning of the U.S. Preventive Services Task Force Grade I Recommendation: Screening for Hepatitis C Virus Infection

The U.S. Preventive Services Task Force (USPSTF) formulates evidence-based recommendations for clinical preventive services. These recommendations are communicated by letter grades that reflect the quality of evidence and the magnitude of net health benefit expected from delivering the preventive service. When the USPSTF finds insufficient evidence to determine the balance of health benefits or harms of delivering a preventive service, because of a lack of studies, poor-quality studies, or good-quality studies with conflicting results, the USPSTF assigns the service an I letter grade. The USPSTF found insufficient evidence to recommend for or against screening for hepatitis C virus infection in high-risk individuals (I letter grade). This recommendation reflects the need for further research that would provide adequate evidence to assess the net health benefit for persons screened for hepatitis C virus infection.
The Birth of Heresy: A Millennial Phenomenon

This article provides a critical response to R. I. Moore's keynote paper for the millennial special issue of the Journal of Religious History. Moore dismisses any connection between the reports of popular heresies in the early eleventh century and millennial concerns, either chronological or prophetic, and argues that the documents tell us almost nothing reliable about popular religiosity at this time. This response suggests that there are many good reasons for interpreting the evidence from a millennial perspective. The religious activity of the period (relic cults, pilgrimage, peace assemblies, penitential processions, apostolic movements, «heresy» and its persecution, anti-Jewish violence) should be viewed as part of a larger interrelated whole, rather than as discrete, unrelated phenomena. The article then focuses on Rodulfus Glaber's famous treatment of the peasant heretic Leutard in 1000 as a case study in such an approach. It reads Glaber not as a confused and incomprehensible historian, but a subtle and complex one who believed that the chronological millennium of 1000 marked an apocalyptic turning point, and whose narratives were crafted to convey as much about this transformation as possible.
Implementation of on-line zone control strategies for optimal ramp metering in the Minneapolis Ring Road

This paper presents the results from field implementation of gain scheduling in a feedforward/feedback zonal control system, in which sets of ramps along a freeway zone or section are controlled in a coordinated manner. An optimization algorithm determines the zone-optimal gains based on feedback from the performance of the closed-loop freeway system. Because the parameters, i.e., ramp rates adapt to traffic conditions in a closed loop, the new system is one step closer to being adaptive. The system is a practical alternative to advanced theoretical concepts of freeway corridor control, and can be integrated with gain scheduling currently available at traffic management centers.
Foreseeable Effects of CO 2 -induced Climatic Change: Freshwater Concerns

Freshwater environments are expected to be particularly responsive to temperature rises and changed precipitation regimes that are anticipated to result from progressive increases in atmospheric carbon dioxide from fossil-fuel combustion. Recognition of potential impacts on aquatic systems should strengthen research and management planning for the future, and provide more confident estimates of the risks from CO 2 elevation than those at present available. This report briefly evaluates those aquatic impacts that are believed to be important and worthy of investigation and quantitative forecasting. Priorities for additional research have been suggested for the issues discussed herein. These priorities vary according to the use of pertinent data, the credibility of presumed risk (which may change as, for example, climatic models are better refined), the timing in relation to prerequisite information, current efforts already under way, and the feasibility of obtaining the desired data. The ranking remains subjective, however, and debatable.
Experimental investigation of large-signal traveling-wave magnetron theory

Experiments conducted on a beam-type backward-wave amplifier which closely approximates the theoretical thin-beam model used in the large-signal analysis of Sedin have resulted in gain and phase shift characteristics which are in good quantitative agreement with the adiabatic portion of both the Sedin and Gandhi-Rowe theories. Efficiencies approaching the theoretically-predicted maximum have been observed. By driving the amplifier to very large signal levels a conversion efficiency for power available from the initial potential energy of the beam of 63 per cent was obtained with a corresponding value of 45 per cent for the total electronic efficiency. An important feature of this experimental amplifier is the electron gun design which is based on a theory by Kino. That this gun is capable of producing a well-confined, rectilinear-flow thin beam is demonstrated by visual observations of the beam thickness which indicate that \omega_{c}/\omega_{p} is as low as 1.17, a value close to that for a laminar-flow Brillouin beam ( \omega_{c} = \omega_{p} ).
Indications for and limitations of treatment of poliomyelitis

Summary Poliomyelitis is self-limited and if deformities are prevented the end result is determined largely by the damage done to the motor cells during the acute febrile stage. Many patients recover completely without treatment and others remain extensively paralyzed in spite of the best treatment. No known treatment affects the degree or extent of the initial paralysis, but we are able to ameliorate the effects of the disease. In the acute febrile stage the treatment is general medical care plus protection of the patient from irritation. If the respiratory function is affected, efforts must be made to save the patient's life. In the subacute stage rest and immobilization dominate the treatment. We relieve the patient's pain, protect paralyzed muscles from stretching, prevent early deformities due to the contracture of painful muscles, and give the injured nerve cells the best possible chance to recover. In the convalescent stage we protect and restore the maximum of power to the weakened muscles, stretch the contracted muscles and restore normal movement to the parts, and train the patient to use his weak extremities. In the chronic stage we prevent or minimize late deformities and increase function by braces and surgery.
Subepithelial space in otitis media.

The role of the subepithelial space (SES) has not received sufficient attention in assessing pathogenesis, pathology, and, therefore, clinical diagnosis and treatment of the various forms of otitis media (OM). Temporal bones from patients with OM were classified as cases of acute purulent (POM), serous (SOM), mucoid or secretory (MOM), or chronic otitis media (COM). Controlled morphometric studies were made of cellular components of the SES, along with studies of the epithelium and middle car space. Corollary studies of biochemistry, cellular components, and prostaglandins (PGs) were done on fluid from the human middle ear. Middle ear effusions (MEE) from animal models of SOM, MOM, and POM were analyzed biochemically. Findings are surprising in that the SES was more actively involved in all forms of OM than had been thought, especially in MOM and COM. Implications are discussed.
Ablation Predictions for Carbonaceous Materials Using Two Databases for Species Thermodynamics

During previous work at NASA Ames Research Center, most ablation predictions were obtained using a species thermodynamics database derived primarily from the JANAF thermochemical tables. However, the chemical equilibrium with applications thermodynamics database, also used by NASA, is considered more up to date. In this work, ablation analyses were performed for carbon and carbon phenolic materials using both sets of species thermodynamics. The ablation predictions are comparable at low and moderate heat fluxes, where the dominant mechanism is carbon oxidation. For high heat fluxes where sublimation is important, the predictions differ, with the chemical equilibrium with applications model predicting a lower ablation rate. The disagreement is greater for carbon phenolic than for carbon, and this difference is attributed to hydrocarbon species that may contribute to the ablation rate. Sample calculations for representative Orion and Stardust environments show significant differences only in the sublimation...
Ovarian cortical transplantation

Evaluation of: Kiran G, Kiran H, Coban YK, Guven AM: Ovarian cortical transplantation may be an alternative to hormone therapy in patients with early climacterium. Fertil. Steril. 84, 1509 (2005) [1] . Describes a report of a 46-year-old woman who had a total abdominal hysterectomy and bilateral salpingo-oophorectomy. After surgery, the patient underwent ovarian cortical transplantation of fresh autologous ovarian cortical strips to her lower abdomen. Follicle-stimulating hormone, luteinizing hormone and estradiol were measured at 3-month intervals. This paper describes the last year of her sampling, ending at 18 months postsurgery. The patient had no menopausal symptoms. Hormonal secretion was at times at postmenopausal levels and at times at premenopausal levels. There was evidence of folliculogenesis and ovulation.
The impact of external factors on productivity in an engineering support organization

The authors explore the degree to which software engineering is actually practiced in a large computational support organization. The results reveal that practitioners generally have not adopted these techniques. This failure can be attributed primarily to the environmental conditions under which software is being developed and, in particular, to the external constraints placed on the organization. Problems created by the environment are discussed in relation to the major phases of the software life-cycle model, the sources of such problems are identified, and solutions to the problems are presented. The environmental factors impacting productivity are categorized and the findings extended to engineering support organizations in general. >
On IIR echo cancellation

Least mean square (LMS) algorithms using output error criteria suffer from stability and convergence problems when applied to infinite impulse response (IIR) structures. These problems have been overcome to a certain extent using the equation error method. However, the method results in biased estimates in the presence of measurement noise. To obtain consistent estimates other methods like the Steiglitz-McBride method (SMM) and the instrumental variable method (IVM) are used. An echo canceller is implemented on TMS320C25 digital signal processor using a variant of the SMM method. >
A streaming framework for seamless building reconstruction from large-scale aerial LiDAR data

We present a streaming framework for seamless building reconstruction from huge aerial LiDAR point sets. By storing data as stream files on hard disk and using main memory as only a temporary storage for ongoing computation, we achieve efficient out-of-core data management. This gives us the ability to handle data sets with hundreds of millions of points in a uniform manner. By adapting a building modeling pipeline into our streaming framework, we create the whole urban model of Atlanta from 17.7 GB LiDAR data with 683 M points in under 25 hours using less than 1 GB memory. To integrate this complex modeling pipeline with our streaming framework, we develop a state propagation mechanism, and extend current reconstruction algorithms to handle the large scale of data.
Just-in-Time Purification: An Effective Solution for Cherry-Picking and Purifying Active Compounds from Large Legacy Libraries

Many companies possess a compound collection consisting of purified compounds and of unpurified products from combinatorial libraries. Using commercial and proprietary compounds as examples, this report provides clear examples of the significant impact purification can have on the activity observed for a compound and highlights the need to retest the purified compounds prior to creating structure-activity relationships. Crude mixtures made with commercial compounds led to an increase in the number of false positives in the SXR-GAL4 assay as compared with their pure and purified counterparts. An examination of proprietary compounds in an HIV assay resulted in the purification of 61 active crude synthetic mixtures. Of these 61 compounds, 32 were 5-fold less active and 2 were 5-fold more active after purification. This report details a semiautomated process developed and implemented for cherry-picking, tracking, and selectively purifying compounds found active in high-throughput screening campaigns.
Seeing like the BIS on Capital Rules: Institutionalising Self-regulation in Global Finance

How does the Bank for International Settlements (BIS) ‘see’ global financial supervision? This article finds that the BIS's approach to bank supervision relies on private banks to be self-regulating entities and favours the interests of the largest global banks and financial centres. The BIS's private, club-like design and culture insulate private-sector participation in global financial policy-making from governmental control and oversight, blur the line between the public and private spheres of policy-making and allow private norms to shape public norms in global financial governance. Moreover, the BIS's normative framework concerning financial-market governance, in general, and bank supervision, in particular, is shaped by the bank's long-standing belief that state intervention into financial markets in the form of regulations and controls produces suboptimal economic outcomes. Rather than resulting from external factors such as great power dominance, regulatory capture or the search for ‘best practice...
Effect of snack food by-product inclusion on production of laying hens

The increased interest in becoming green for consumers and companies is driving groups to de- velop innovative ways to become more efficient and reduce their waste. Foods past their expiration dates are large sources of waste and are causing food-manu- facturing companies to develop waste disposal strate- gies. Integrating by-products from these companies into animal diets, specifically that of laying hens, could be significantly more cost effective for both the human food manufacturers and the agricultural producers. The study's objective is to evaluate laying hen diets con- taining snack food by-product, consisting mostly of ex- pired potato chips, and the effect on hen performance. In total, 192 White Leghorn laying hens (45 wk old) were selected from the Michigan State University Poul- try Farm. Hens were housed in conventional cages (3 birds/cage) and received 1 of 4 diets for 5 wk: 1) indus- try control corn-soybean meal, 2) control with 3% by- product, 3) control with 6% by-product, and 4) control with 9% by-product. Diets were formulated to be iso- caloric, isonitrogenous, and balanced for sodium. Feed intake was measured for 3 consecutive days each week, and no overall differences between treatments were ob- served. However, during the first week, feed intake was significantly higher in birds fed the 6% and 9% diets compared with those fed control (P < 0.05). Birds fed the 6% had a higher feed intake than that of the control again during the fourth week (P < 0.01). Egg produc- tion, egg weight, and specific gravity were measured weekly. Hen BW was measured on d 1, 14, 28, and 35. Egg production, egg weight, specific gravity, and BW were not significantly affected by the addition of snack food by-products to the diet. In conclusion, the addi- tion of expired snack food by-product into poultry diets does not significantly affect laying hen egg production and has the potential to be used as an alternative feed stuff in the future.
Ten Works That Mattered Most

For the 10th Anniversary Issue of this journal, I was asked to discuss the ten books or articles that have most influenced my academic work. Since academics like the mix of intellectual and personal gossip such ventures provide, I am posting my selections and discussions. Other contributors to this project include Justice Stephen Breyer, Catherine MacKinnon, Philip Bobbitt, Jeremy Waldron, Seyla Benhabib, Sam Issacharoff, Martin Shapiro, and Michel Rosenfeld.
MOLT-MIGRATION IN WESTERN TANAGERS (PIRANGA LUDOVICIANA): AGE EFFECTS, AERODYNAMICS, AND CONSERVATION IMPLICATIONS

Abstract We describe timing and location of the prebasic molt in Western Tanagers (Piranga ludoviciana), focusing on age class differences in premolt movements. Most adults migrate south to the American Southwest where they stop to molt before moving on to their wintering grounds. Molting adults are found in southern mountain regions (Sierra Madres and southern Rockies) and in the Mexican monsoon region, where late summer rains cause a substantial increase in productivity. In contrast, juvenile Western Tanagers move to nearby montane habitats to molt before migrating, a previously undocumented strategy in western passerines that show molt-related movements. By molting in nearby montane habitats, juveniles avoid the aerodynamic cost of migrating in their “fluffy”, aerodynamically inefficient juvenal plumage. Western Tanagers are the fifth species known to use the Mexican monsoon region during the prebasic molt, further affirming the importance of that area to the conservation of Neotropical migrants that b...
Reply: Hypochloremia in Acute Decompensated Heart Failure.

We appreciate the comments from Dr. Lim regarding our analysis investigating the prognostic role of serum chloride levels in acute decompensated heart failure (ADHF). As discussed, chloride levels can be affected by a diversity of mechanisms in ADHF. Indeed, hypochloremia and hyponatremia can
Statistical Evidence for Common Ancestry: Testing for Signal in Silent Sites

1. The common ancestry of life is supported by an enormous body of evidence and is universally accepted within the scientific community. However, some potential sources of data that can be used to test the thesis of common ancestry have not yet been formally analyzed. 2. We developed a new test of common ancestry based on nucleotide sequences at amino acid invariant sites in aligned homologous protein coding genes. We reasoned that since nucleotide variation at amino acid invariant sites is selectively neutral and, thus, unlikely to be due to convergent evolution, the observation that an amino acid is consistently encoded by the same codon sequence in different species could provide strong evidence of their common ancestry. Our method uses the observed variation in codon sequences at amino acid invariant sites as a test statistic, and compares such variation to that which is expected under three different models of codon frequency under the alternative hypothesis of separate ancestry. We also examine hierarchical structure in the nucleotide sequences at amino acid invariant sites and quantified agreement between trees generated from amino acid sequence and those inferred from the nucleotide sequences at amino acid invariant sites. 3. When these tests are applied to the primate families as a test case, we find that observed nucleotide variation at amino acid invariant sites is considerably lower than nucleotide variation predicted by any model of codon frequency under separate ancestry. Phylogenetic trees generated from amino-acid invariant site nucleotide data agree with those generated from protein-coding data, and there is far more hierarchical structure in amino-acid invariant site data than would be expected under separate ancestry. 4. We definitively reject the separate ancestry of the primate families, and demonstrate that our tests can be applied to any group of interest to test common ancestry.
Treatment of sustained monomorphic narrow‐complex ventricular tachycardia in a 16‐year‐old Arab mare with a constant rate of infusion of lidocaine and oral propranolol

Summary A 16-year-old Arab mare was referred for treatment of a tachydysrhythmia detected on electrocardiogram by the referring veterinarian. Monomorphic, narrow-complex ventricular tachycardia (VT) was confirmed by electro-cardiogram in a normal base-apex configuration. Subsequent diagnostic testing, including echocardiography and measurement of plasma cardiac troponin concentration, did not reveal a definitive cause for the dysrhythmia. Conversion of VT to ventricular bigeminy occurred following treatment with magnesium sulfate and lidocaine hydrochloride, administered intravenously. Treatment with orally administered propranolol subsequently led to conversion to sinus rhythm with intermittent ventricular premature complexes (VPCs). Oral prednisolone treatment was also initiated to address the possibility that VT resulted from underlying myocarditis. The mare was discharged with oral propranolol, a tapering course of prednisolone, and exercise restriction. Follow-up cardiac examination 6 weeks later revealed persistent, intermittent VPCs and reversion to VT occurred during exercise. Sinus rhythm with intermittent VPCs was re-established following the administration of lidocaine. The mare was again discharged with oral propranolol therapy, which was subsequently replaced with oral sotalol. Sudden death occurred 4 weeks later but a post mortem examination was not performed.
Unsteady acoustic wave propagation in a transonic compressor cascade

The need for improved performance and reduced noise levels has motivated engineers to assess the effects of flow unsteadiness on the aeroacoustic phenomena present in axial-flow turbomachines. A primary source of adverse aeroacoustic effects (noise) and performance degradation is the aerodynamic interaction between adjacent blade rows. One type of aerodynamic interaction is referred to as potential-flow interaction. Potentialflow interactions result from the variations in the velocity potential or pressure fields associated with the blades of a neighboring row, and their effects uopn the blades of a given row moving at a different rotational speed. This type of interaction is of serious concern when the axial spacing between adjacent blade rows is small or the Mach number is high. In the current investigation, unsteady acoustic excitations are introduced upstream and downstream of a transonic compressor cascade. The predicted results indicate that the unsteadiness associated with downstream-propagating acoustic excitations is nearly linear, while the unsteadiness introduced by the upstream-propagating acoustic disturbances is strongly nonlinear. In addition, upstreampropagating acoustic waves can alter the time-averaged location of the shock, reduce the time-averaged mass flow, and increase the time-averaged flow turning.
Sex offender registration and notification laws: thoughts from registered sex offenders in three states

Purpose – In the USA, sex offender policy research has focussed on demographic characteristics of registrants, recidivism rates of registrants, accuracy and completeness of listed information, and the collateral consequences experienced by registrants. This growing body of research demonstrates the need to explore offender perceptions of sex offender registration and notification (SORN) laws. The purpose of this paper is to assess whether registration related variables influenced sex offenders’ opinions about the registry, compliance with the registry, self-worth, and deterrence perceptions. Design/methodology/approach – This paper utilized a sample of 286 male registered sex offenders (RSO) in Pennsylvania, Texas, and Wisconsin. Four multivariate regression models were run to examine registration related variables impact on sex offender opinions of the registry, registry compliance, feelings of self-worth, and perceptions of deterrence. Findings – The multivariate regression results suggest registration ...
The Effect of Supervised Exercise Training on Symptoms of Chemotherapy- Induced Peripheral Neuropathy

Chemotherapy-Induced Peripheral Neuropathy is a common, dose-limiting effect of chemotherapy treatment. Pharmacological therapies are largely uneffective, making the investigation of other interventions warranted. Homebased exercise programs have produced promising improvements in quality of life and pain symptoms, yet compliance to programs is low. Thus, the purpose of this investigation was to examine the outcomes of a structured, supervised exercise program in reducing symptoms of CIPN and improving physical fitness and overall QOL. A total of 38 individuals actively in chemotherapy treatment participated in this investigation. The McGill QOL and Leeds Assessment of Neuropathic Symptoms and Signs questionnaires, followed by a comprehensive fitness evaluation was administered both before and after the 12-week supervised exercise program. Results revealed that 12-weeks of supervised exercise training helped attenuate symptoms of CIPN. Overall QOL was significantly improved, and troublesome symptoms related to CIPN significantly decreased (p<0.05). Thus, we assert that exercise is an effective tool in managing symptoms of CIPN.
Large size and high light do not lower the cost of reproduction for the Neotropical herb Goeppertia marantifolia

UNLABELLED • PREMISE OF THE STUDY Sexual reproduction is often associated with a cost in terms of reduced survival, growth, or future reproduction. It has been proposed that plant size and the environment (availability of key resources) can sometimes lower or even nullify the cost of reproduction.• METHODS We address this issue experimentally with the Neotropical herb Goeppertia marantifolia, by manipulating sexual reproductive effort and measuring the demographic performance of plants and of their clonal offspring, in the context of natural variation in light availability.• KEY RESULTS Plants in the high-reproductive-effort treatment grew less between seasons but did not differ in their probability of flowering the second season or in inflorescence size compared with plants in the low-effort treatment. Reproductive effort of parent plants influenced the leaf area of their clonal offspring. Plants that invested less in sexual reproduction produced clonal offspring that were initially larger than those produced by plants that invested more in reproduction. The magnitude of this effect was greater in parent plants that received two seasons of the manipulated reproductive effort than in those that received a single season. The trade-off between reproductive modes dampened with time, leading to smaller differences in clonal offspring leaf area between treatments over time.• CONCLUSIONS We found evidence of a cost of reproduction and trade-offs between reproductive modes, although the magnitude of these costs was small. However, we found no evidence of lower costs of reproduction for larger plants or for plants in higher-light environments over our 2-yr study period.
Impact of Atrazine Prohibition on the Sustainability of Weed Management in Wisconsin Maize Production.

Background Controversy has surrounded atrazine owing to its susceptibility to leaching and run-off, with regular calls for a ban or restrictions on its use. In the context of a decreasing trend in the percentage of US maize using no-till since 2008, coinciding with the trend of glyphosate-resistant weeds becoming problematic in the Midwestern United States, we empirically examine how atrazine use restrictions have impacted the diversity of weed management practices used by Wisconsin maize farmers. Results Using survey data from farms inside and outside atrazine prohibition areas, we found that prohibiting atrazine did not directly impact tillage practices, but rather it increased the adoption of herbicide-resistant seed, which then increased adoption of conservation tillage systems. We also found that prohibiting atrazine and using herbicide-resistant seed reduced the number of herbicide sites of action used. Conclusions The results indicate that prohibiting atrazine reduced the diversity of weed management practices, which increased the risk of herbicide resistance. Our concern is that a regulatory policy to address one issue (atrazine in groundwater) has induced farmer responses that increase problems with another issue (herbicide-resistant weeds) that longer term will contribute to water quality problems from increased soil erosion and offset the initial benefits. © 2016 Society of Chemical Industry.
Easing into your new practice after residency: tips for success.

A successful transition from training to practice hinges on prudent personal and professional development.
Interaction of PIP2 with the XIP region of the cardiac Na/Ca exchanger

The sarcolemmal Na/Ca exchanger undergoes an inactivation process in which exchange activity decays over several seconds following activation by the application of Na to the intracellular surface o...
Yttrium-90 Radioembolization as a Salvage Treatment following Chemoembolization for Hepatocellular Carcinoma.

Abstract Purpose To determine safety and efficacy of yttrium-90 ( 90 Y) transarterial radioembolization (TARE) in patients who have undergone chemoembolization for hepatocellular carcinoma. Materials and Methods A retrospective study identified 40 patients (median age 61 y; range, 44–84 y) who underwent 90 Y mapping angiography and had undergone ≥ one prior chemoembolizations. There were 4 (10%) patients in Barcelona Clinic Liver Cancer stage A, 7 (17.5%) in stage B, and 29 (72.5%) in stage C; 28 (70%) were Child-Pugh class A and 12 (30%) were class B. Median tumor diameter was 4.2 cm (range, 1–11.6 cm). The most common indications for changing to TARE were tumor progression (35/40; 86%) and development of portal vein thrombus (15/40; 37.5%). Results Of 40 patients, 29 (72.5%) underwent TARE; the most common reasons for not undergoing TARE were attenuated hepatic arteries (5/11), high pulmonary shunt (4/11), and poor arterial flow (2/11). Patients who underwent ≤ 4 chemoembolizations to the TARE target tended to be more likely to undergo TARE after mapping than patients who had > 4 chemoembolizations ( P = .056). Most common grade ≥ 3 toxicities were fatigue (9/29; 31%) and biochemical alterations (bilirubin [3/29; 10.3%], albumin [4/29; 13.8%], aspartate aminotransferase [5/29; 17.2%]). Of 27 patients treated with TARE with follow-up, responses were 11 (41%) complete response, 5 (19%) partial response, 2 (7%) stable disease, and 9 (33%) progressive disease. Median progression-free survival and overall survival were 90 days and 257 days. Conclusions TARE is safe and effective salvage therapy in patients after chemoembolization. In patients who have undergone > 4 chemoembolizations to the 90 Y target, feasibility of TARE tends to be decreased.
Medial Temporal Lobe Activation in Learning

Regional cerebral blood flow was examined by PET recordings during multiple-trial learning in healthy volunteers tested at Guy’s and St Thomas’s Hospitals and the MRC Cyclotron Unit, Hammersmith Hospital, London.
Characterization of Host Cell Mutants Significantly Resistant to Cryptosporidium parvum Infection

Cryptosporidium parvum is a parasitic protist and a causative agent of mild to severe diarrheal diseases in humans and animals. Despite its globally recognized importance, knowledge on the mechanism of parasite invasion and molecular interactions between host cells and the parasite is limited. Here we report the establishment of 43 mutant cell lines derived from HCT-8 cells by UV-induced mutagenesis and the characterization of three mutants with significantly reduced susceptibility to cryptosporidial infection. Based on qRT-PCR assay performed at 18 h post-infection time, the parasite loads could be reduced by ~45%, ~35% and ~20% in mutants A05, B08 and B12, respectively (p<0.001 in all three mutants vs. HCT-8 cells). The mutagenesis mainly affected the attachment of parasite in A05 (i.e., ~30% reduction, p<0.001 vs. HCT-8), and intracellular development in B08 and B12. The three cell mutants may serve as valuable reagents to further investigate the mechanism of parasite invasion and intracellular development by identifying the gene mutations associated with the parasite attachment (A05) and intracellular development (B08 and B12). This article is protected by copyright. All rights reserved.
DNA Methylation and Globin Gene Expression.

Understanding how the human γ-globin gene is regulated has important clinical implications because increased levels of fetal hemoglobin (HbF) are beneficial to patients with sickle cell disease and β-thalassemia. DNA methylation is strongly implicated in developmental silencing of the γ-globin gene based on: an inverse correlation between DNA methylation of the γ-globin gene and its expression, the acquisition of CpG residues within the γ-globin 5' region during evolution as the γ-globin gene was recruited to fetal stage expression, and the ability of pharmacological inhibitors of DNA methyltransferase (5-azacytidine; decitabine) to reactivate high-level expression of the γ-globin gene in experimental primates that led to clinical trials demonstrating that decitabine increased HbF to therapeutic levels in patients with sickle cell disease. Decitabine treatment in vivo decreases DNA methylation of the γ-globin gene and increases association of RNA polymerase II, acetyl Histone H3 and H4, and Histone H3 (lys4) trimethyl with the γ-globin gene, strongly suggesting that decitabine increases γ-globin gene transcription. These results are consistent with the hypothesis that γ-globin expression in adults is repressed by the binding of methyl DNA binding proteins to the methylated γ-globin promoter with subsequent recruitment of co-repressor complexes that actively repress γ-globin transcription. The reduction of γ-globin gene DNA methylation induced pharmacologically in adults by decitabine is linked to high level γ-globin expression, as is the complete loss of γ-globin gene methylation attained physiologically during erythroid differentiation of fetal liver hematopoietic progenitor cells. The mechanism of action of the drug has not been definitively established, however, and the role of DNA methylation in regulation of γ-globin gene expression remains an active area of investigation. High level γ-globin expression in baboon erythroid progenitor cell cultures without a reduction of γ-globin gene DNA methylation suggests the existence of alternative mechanisms of activation. In addition to reducing DNA methylation, decitabine activates the p38 MAP kinase pathway, increases p21WAF, and accelerates terminal erythroid differentiation. The role of these effects remains to be investigated. Increased understanding of the role of DNA methylation in γ-globin gene regulation is likely to impact the design of future therapies to increase HbF levels.
Age and Gender Effects in Recent Violence Perpetration.

Although we know much about the effects of violence on victims, we know less about individuals who perpetrate violence. In the present study, we used a large, nationally representative sample of ad...
Frostbite, Injury, and Trauma in the Extremities

The objective of the study is to review the current methods of evaluating and managing both frostbite injury and non-thermal extremity vascular trauma, with an emphasis on endovascular techniques. The traditional management of frostbite has a well-established role for the rapid rewarming of injured tissues. This literature review highlights the evolution of the various management techniques with a specific focus on the more recent role of intra-vascular catheter-directed thrombolytic therapy. Non-thermal extremity trauma with resulting vascular injury requires prompt diagnosis that relies heavily on both the physical examination and the appropriate imaging. Frostbite injury manifests as a progressive insult with distinct pathophysiologic phases during which imaging can guide appropriate care. Traditional medical management, in combination with intra-vascular catheter-directed thrombolytic regimens, can restore blood flow to poorly or non-perfused digits, thereby ultimately reducing the risk of delayed amputation. Non-thermal trauma to the extremities can result in a variety of vascular injuries. Interventional radiology plays a key role in diagnosis and an expanding role using transcatheter therapies in order to provide efficacious and optimal management of patients with vascular injury.
An Approach to Measurement in Quantum Mechanics

We consider an unconventional approach to the measurement problem in quantum mechanics — we treat the apparatus as a classical system, belonging to the macro-world.
A Delta-V map of the known Main Belt Asteroids

Abstract With the lowered costs of rocket technology and the commercialization of the space industry, asteroid mining is becoming both feasible and potentially profitable. Although the first targets for mining will be the most accessible near Earth objects (NEOs), the Main Belt contains 10 6 times more material by mass. The large scale expansion of this new asteroid mining industry is contingent on being able to rendezvous with Main Belt asteroids (MBAs), and so on the velocity change required of mining spacecraft (delta-v). This paper develops two different flight burn schemes, both starting from Low Earth Orbit (LEO) and ending with a successful MBA rendezvous. These methods are then applied to the ∼ 700,000 asteroids in the Minor Planet Center (MPC) database with well-determined orbits to find low delta-v mining targets among the MBAs. There are 3986 potential MBA targets with a delta-v 8 km s − 1 , but the distribution is steep and reduces to just 4 with delta-v 7 km s-1. The two burn methods are compared and the orbital parameters of low delta-v MBAs are explored.
On Becoming A Psychiatrist

The transition from trainee to practitioner is a relatively neglected “normative crisis” which has been acutely exacerbated in recent years in the field of psychiatry. A weekly seminar for third-year residents, begun as an exploratory venture, was designed to meet phase-specific needs at this crucial turning point. The process that evolved seems best described as a “coping alliance.” A series of seven seminar “structures” is delineated as a way of organizing central issues and illustrating a variety of useful techniques for bringing them into focus. The response of successive groups of participants has thus far been so enthusiastically favorable as to lengthen and widen the scope of the experience. A core bibliography is appended in the hope of aiding others to shape still better instruments for ushering tomorrow’s psychiatrists into a field in crisis.
The difficulty of replacing an inclusive OR-join

Some popular modeling languages for business processes, e.g., BPMN, contain inclusive OR-joins (IOR-joins), but others, e.g., Petri nets, do not. Various scenarios in Business Process Management require, or benefit from, translating a process model from one language to another. This paper studies whether the control flow of a process containing IOR-joins can be translated into a control flow without IOR-joins. First we characterize which IOR-joins can be replaced locally and define a local replacement for each replaceable IOR-join. Then, we present examples that cannot be locally replaced but have a more general translation. We give a non-local replacement technique, together with its condition of applicability, which runs in polynomial time. Finally, we show that there exist simple process models with an IOR-join that cannot be replaced --- in the sense that its synchronization behavior cannot be obtained by any combination of AND and XOR gateways. The proof reveals an intrinsic limitation on the replaceability of IOR-joins and hence the translatability of BPMN-like control flow into Petri nets.
The Impact of Clostridium Histolyticum Collagenase on the Prevalence and Management of Peyronie's Disease in the United States

PURPOSE We evaluated the impact of collagenase clostridium histolyticum (CCH) on rates of diagnosis, treatment, and corporal rupture in Peyronie's disease (PD). We examined the impact of CCH on cost of PD treatment. MATERIALS AND METHODS We extracted data on PD diagnosis (ICD-9 607.95 and ICD-10 N48.6), corporal rupture (ICD-9 959.13 and ICD-10 S39.840A), CCH use (J0775), penile injections (CPT 54200), and corporal rupture repair from 2008 to 2016 in men over 40 years old using the Clinformatics® Data Mart Database (3.7 to 4.9 million males). We analyzed for prevalence of PD, rates of PD treatments, cost associated with treatment, and rates of corporal rupture and repair by year. RESULTS The prevalence of PD was 0.29% in 2013 and did not increase after CCH entered the market in 2014. An average of 2.52% of men with PD received treatment before CCH, compared with 3.75% after (p<0.0001). Penile injection rates increased (1.34% vs. 2.61%, p<0.0001), while rates of surgical treatments decreased between these periods. There was no change in rate of corporal rupture in men with PD before (0.024%) and after (0.024%) CCH. Overall, only 20.0% of corporal ruptures were repaired. After CCH entered practice, a significant increase in cost occurred (p=0.013). CONCLUSIONS The prevalence of men with PD did not change after CCH. However, more men with PD received treatment due to an increase in penile injections. The cost of treating PD increased after CCH became available. The overall prevalence of corporal rupture did not change after CCH entered the market.