cssi/SciSciGPT-SciSciNet huggingface dataset:
Nutlin-3a sensitizes a p53-null neuroblastoma cell line to doxorubicin: Potential roles for p73 and E2F1

3002 Neuroblastoma (NB) is a childhood solid tumor of the sympathetic nervous system arising from neural crest progenitor cells, and children with advanced Stage 3 and 4 cancers are particularly at risk for relapse and chemoresistant disease. Alterations in p53 expression from the wild-type phenotype are rare in NB at diagnosis. However, inactivation or elimination of p53 are common in relapsed NB, one likely mechanism of resistance to therapy. Recently, a selective small-molecule antagonist of Mdm2, Nutlin-3 (N-3), was developed; this binds the p53 pocket of Mdm2, releasing p53 from negative control. Doxorubicin (dox), a genotoxic agent commonly used in NB therapy, induces pleiotropic effects not well understood, but tumor suppressors are known to be upregulated. In this study, we investigated the ability of N-3 to induce apoptosis in a p53-null and dox-resistant NB cell line, LA155N, a cell line containing a homologue of p53 which occurs in multiple isoforms. The full-length, tumor-suppressive form (TAp73alpha) may functionally substitute for p53. Using WST-1 assays, we demonstrated that N-3 sensitizes LA155N cells to dox treatments in a synergistic manner, although cells were relatively resistant to N-3 as a single agent. Immunoblot analysis of N-3 single treatments indicated increases in TAp73alpha levels as well as the transcription factor E2F1, which also binds to Mdm2 and is known to enhance apoptosis in some systems. Although there were no changes in the levels of Bax or pro-caspase-3 following N-3 treatment, combination treatments resulted in increases in Bax and Puma. By cell cycle analysis, we found that N-3 has no effect on subG1-G1 levels, but induces significant cell cycle blocking in combination with dox treatment. Using IP, we showed that p73 binds to Mdm2, and that N-3 prevents this binding. Thus, we used siRNA to knock down p73 expression to reverse the sensitization to the combination treatment. Using three siRNA primer sets, we achieved an almost complete reduction of TAp73alpha with one set, and incremental decreases with two sets, at both protein and mRNA levels. WST-1 assays indicated a reduction of sensitization corresponding to the siRNA used. Strikingly, we found a significant increase in proliferation with N-3 treatment alone following complete TAp73alpha knockdown, and this corresponded to decreased levels of E2F1 seen on immunoblots. Unlike the interaction of p53 with Mdm2, TAp73alpha is protected from proteosomal degradation by its binding to Mdm2. Thus, we conjecture that TAp73alpha interacts with E2F1 to induce apoptosis, that E2F1 and TAp73alpha are stabilized by their association, and that knockdown of TAp73alpha results in E2F1 instability and loss. siRNA knockdown of E2F1 should help to answer these questions. This study begins to address p53-independent mechanisms of Nutlin-3 action in NB, especially in combination with other chemotherapeutics.
Welfare-Improving Cascades and the Effect of Noisy Reviews

We study a setting in which firms produce items whose quality is ex-ante unobservable, but learned by customers over time. Firms take customer learning into account when making production decisions. We focus on the effect that the review process has on product quality. Specifically, we compare equilibrium quality levels in the setting described above to the quality that would be produced if customers could observe item quality directly. We find that in many cases, customers are better off when relying on reviews, i.e. better off in the world where they have less information. The idea behind our result is that the risk of losing future profits due to bad initial reviews may drive firms to produce an exceptional product. This intuitive insight contrasts sharply with much of the previous academic literature on the subject.
1897-P: Vertical Sleeve Gastrectomy Corrects the Metabolic Dysregulation Induced by Hepatocyte-Specific Ablation of p53 in Mice

p53 has been implicated in the pathogenesis of obesity and diabetes, in part, by regulating whole body energy homeostasis. Conflicting evidence from mice with global alterations in p53 expression suggests the effects of p53 on metabolism are tissue-specific. Despite the critical metabolic role of the hepatocyte, the role of hepatocyte p53 is undefined. Bariatric surgery, such as vertical sleeve gastrectomy (VSG), causes high rates of type 2 diabetes remission and improves energy homeostasis at the cellular level. To define the role of hepatocyte p53 in metabolic regulation and the impact of VSG in this context, we performed VSG or sham (S) surgery in high fat diet-fed male hepatocyte-specific p53 knockout (KO) and wild type (WT) mice (n=9-12). Sham-operated mice were fed ad libitum (S-AL) or food restricted to match their body weight to VSG-operated mice (S-WM). Body weight, food intake, adiposity, energy expenditure, and oral glucose tolerance were measured. Hepatocyte p53 ablation increased body weight which was corrected by food restriction and VSG (final weight (g): S-AL-WT=33±1, S-WM-WT=27±1, VSG-WT=29±1, S-AL-KO=38±1, S-WM-KO=28±1, VSG-KO=28±1, P Disclosure M.M. Holter: None. D. Garibay: None. A.K. McGavigan: None. L. Nguyen: None. E. Moore: None. E. Daugherity: None. P. Cohen: None. K.M. Kelly: None. R. Weiss: None. B. Cummings: None. Funding Cornell University; National Cancer Institute (R21CA195002)
Nutritional Support in Postcardiotomy Shock Extracorporeal Membrane Oxygenation Patients: A Prospective, Observational Study.

Abstract Background Despite the 6000 patients treated with extracorporeal membrane oxygenation (ECMO) annually, there is a paucity of data regarding the nutritional management of these patients. Materials and methods We performed a prospective, observational study of nutrition in postcardiotomy shock patients at our institution. Over a 3.5-year study period, we identified 50 ECMO patients and 225 non-ECMO patients. We identified type, amount, duration, and disruption of nutritional delivery by cohort. The primary outcome was percent of caloric goal met, and secondary outcome was gastrointestinal complications. Results ECMO patients met less of their caloric (29% versus 40%, P = 0.017) and protein goals (34% versus 55%, P Conclusions –ECMO patients received significantly less nutrition support compared with a non-ECMO population. Tube feed hold deficits could potentially be avoided by utilizing postpyloric tubes to feed through procedures, by eliminating holds for vasopressors/inotropes in hemodynamically stable patients, or by establishing volume-based feeding protocols. Further clinical studies are needed to establish efficacy of these interventions and to understand the impact of nutrition on outcomes in ECMO patients.
The effects of a positional feedback device on rollator walker use: a validation study.

Background: According to clinical guidelines, rolling walker users should walk with their feet between the posterior wheels of the walker; however approximately 50% of users do not. Objective: To d...
Reconstruction of External Forces Beyond Measured Points Using a Modal Filtering Decomposition Approach

A methodology for the reconstruction of dynamic loads from vibration response data is developed which employs a well-correlated finite element model to permit load identification at locations where no response measurements are available; this is extended from a force reconstruction approach based upon modal filtering. Force reconstruction is approached from a modal perspective, where modal responses are estimated from physical response data, followed by independent reconstruction of modal forces for each modal oscillator. Modal force estimates are analyzed in aggregate via singular value decomposition to permit identification of input locations which are compatible with the estimated modal force patterns. Modal forces are then returned to the physical domain via transformation by modal matrices. Experimental validation is performed with a free-free beam subject to multiple impact.
Will Russia's Pivot to Asia Last?

Abstract Will the Russian Federation's current “turn to the East” have lasting significance? After the annexation of Crimea and the escalated confrontation with the West, Vladimir Putin's government declared it was turning to the East by cultivating ties both with the People's Republic of China and other governments. Russia has “turned to the East” repeatedly throughout its history, from the tsarist era to the present day. In the past, geopolitical and economic factors have hindered Russia's Asian Pivots and caused the Kremlin to turn back toward Europe.
The Impact of Interprofessional Education on Healthcare Team Performance: A Theoretical Model and Recommendations

In this chapter, a model suggesting that interprofessional education (IPE) enhances both attitudes towards other professions and knowledge of other professions’ expertise and roles (i.e., transactive memory systems) is proposed. Together, these lead to improved team processes (e.g., strategy formulation, coordination, communication, monitoring and backup behavior), and ultimately, more effective team performance for interprofessional teams. However, in order for IPE to elicit these outcomes, a needs analysis should be conducted to develop learning objectives, and training content, structure, and instructional methods must be tailored to the specific learners and available resources.
Radiology Mentoring Program for Early Career Faculty-Implementation and Outcomes

Abstract Objective To implement a mentoring program for early career faculty in an academic radiology department and to assess its impact on career development. Methods A formal departmental mentoring program for early career faculty (instructors) who were paired with senior radiologists outside of their division was implemented. The program provided structured one-on-one mentoring, creation of a mentoring network, and opportunities for peer mentoring. A survey was conducted before and 1 year after initiation of the program. Historical data on promotion over 5 years before the implementation of the program was used to determine the impact on the rate of promotion. The study was exempt from institutional review board approval. Results Before and 1 year after implementation of the mentoring program, 57% versus 86% of instructors were satisfied with their mentor (P = .04); 43% versus 90% felt that by encouraging mentorship, the department valued their professional development (P = .001); 38% versus 86% felt that the department created an environment that promoted feedback and sharing of information (P = .002); and 43% versus 76% felt that faculty strove to support each other (P = .03). Since implementation of the program, 43% of instructors received grant funding, 50% received other awards, and 10 instructors were promoted to assistant professor, compared with an average of 4.2/y over the past 5 years. Of those, three were underrepresented minorities in medicine versus none in the previous 5 years. Conclusions A mentoring program helped to advance the careers of early career and minority radiology faculty and helped create an atmosphere of more openness and support in the department.
A patient-specific model combining antimüllerian hormone and body mass index as a predictor of polycystic ovary syndrome and other oligo-anovulation disorders.

Objective To determine whether a patient-specific predictive model combining antimullerian hormone (AMH) levels and body mass index (BMI) can aid in the diagnosis of polycystic ovary syndrome (PCOS) and other ovulatory dysfunction disorders (OVDYS) among infertile women. Design Retrospective cohort study. Setting Academic fertility center. Patient(s) One thousand and ten infertile women undergoing 3,160 intrauterine insemination (IUI) cycles, stratified by diagnosis in three groups: PCOS, OVDYS, and other etiologies. Intervention(s) Ovulation induction followed by IUI or ultrasound-monitored natural cycles. Main Outcome Measure(s) The probability of either PCOS or OVDYS diagnosis based on AMH levels alone and a patient-specific predictive model that combines serum AMH and patient’s BMI. Result(s) Median and interquartile range (IQR) for the serum AMH levels (ng/mL) were the highest in women with PCOS, and lowest in those with other infertility causes. Overall, for every 1 ng/mL increase in AMH, the odds of PCOS and OVDYS versus other causes increased by 55% and 24%, respectively. Postestimation from multivariate logistic regression models showed that PCOS diagnosis can be predicted with lower AMH values in women with a higher BMI compared with the AMH values predicting PCOS in normal-weight or underweight patients. The receiver operating characteristic curves reinforced these findings, and the best cutoffs for PCOS diagnosis were 7.5, 4.4, and 4.1 ng/mL for women belonging to the BMI groups 18.5–24.9, 25.0–29.9, and ≥30.0 kg/m2, respectively. Conclusion(s) Taking into account AMH and BMI, we developed a model that predicts the probability of an oligo-anovulation diagnosis, thus facilitating patient-specific counseling in the infertility setting.
The ultra-high efficiency gas turbine engine, UHEGT, Part II: A numerical study on reducing the stator blade surface temperature by indexing fuel injectors and using film cooling:

In the Ultra-High Efficiency Gas Turbine Engine, UHEGT (introduced in our previous studies) the combustion process is no longer contained in isolation between the compressor and turbine, rather dis...
Reconstructing the Corporation: From Shareholder Primacy to Shared Governance

Modern corporations contribute to a wide range of contemporary problems, including income inequality, global warming, and the influence of money in politics. Their relentless pursuit of profits, though, is the natural outcome of the doctrine of shareholder primacy. As the consensus around this doctrine crumbles, it has become increasingly clear that the prerogatives of corporate governance have been improperly limited to shareholders. It is time to examine shareholder primacy and its attendant governance features anew, and reorient the literature around the basic purpose of corporations. This book critically examines the current state of corporate governance law and provides decisive rebuttals to longstanding arguments for the exclusive shareholder franchise. Reconstructing the Corporation presents a new model of corporate governance - one that builds on the theory of the firm as well as a novel theory of democratic participation - to support the extension of the corporate franchise to employees.
‘It was made to appear to them so’: the crucifixion, Jews and Sasanian war propaganda in the Qur’ān

The quranic sūra The Women 4:157-58 says that Jews claimed to have killed and crucified Christ but denies that they did so. Rather, the verse says, ‘it was made to appear to them so.’ For centuries...
Dupilumab Induced Limbal Stem Cell Deficiency

Dupilumab is a monoclonal antibody that is used for the treatment of atopic dermatitis (AD) in adults. However, increasing reports of ocular complications including conjunctivitis and dry eye disease have been documented. In this report, we describe a case of a patient who developed limbal stem cell deficiency (LSCD) after prolonged Dupilumab use. A 56-year-old Caucasian male with a history of AD presented with gradual onset cloudy vision and extensive diffuse symblepharon resulting from Dupilumab treatment. He was diagnosed with cicatrizing blepharoconjunctivitis and secondary LSCD after slit lamp examination. In conclusion, LSCD secondary to cicatricial disease is a severe adverse ocular complication caused from long-term Dupilumab treatment.
Captives or prisoners: society and obligation in Medieval Iberia

Resumen en: There are important differences between the medieval captive and the modern prisoner of war. While, in each instance, their societies desire their libera...
Perspectives and Future Directions

This chapter contains sections titled: Current Developments Online Dynamic Contingency Screening Further Improvements Phasor Measurement Unit (PMU)-Assisted Online ATC Determination Emerging Applications Concluding Remarks
Role of reactive oxygen species in vascular remodeling associated with pulmonary hypertension.

Several manifestations of neonatal pulmonary hypertension are associated with vascular remodeling, resulting in increased muscularity of the small pulmonary arteries. Abnormal structural development of the pulmonary vasculature has been implicated in persistent pulmonary hypertension of the newborn (PPHN). Increased plasma levels of the vasoconstrictor endothelin-1 (ET-1) have been demonstrated in patients with PPHN, which is likely to contribute to hypertension. In addition, several studies have identified a role for ET-1 in the proliferation of vascular smooth muscle cells (SMCs), suggesting that ET-1 may also be involved in the vascular remodeling characteristic of this disease. However, the mechanisms of ET-1-induced SMC proliferation are unclear and appear to differ between cells from different origins within the vasculature. In SMCs isolated from fetal pulmonary arterial cells, ET-1 stimulated proliferation via an induction of reactive species (ROS). Furthermore, other lines of evidence have demonst...
Also seeking common ground in conservation.

In his response to my recent editorial (Soule 2013), Kareiva (2014) seeks to “correct some misimpressions” while seeking common ground. I am grateful for Kareiva’s collegial response and his agreement that nature (biodiversity) must be protected and conserved for its own sake as well as for utilitarian reasons.1 Kareiva celebrates the achievements of his employer, The Nature Conservancy (TNC), globally the most influential conservation NGO. TNC has been a powerful actor and an effective implementer of habitat protection as well as a key voice for educating the public about the threats to nature. Its scientists, staff, and donors deserve our gratitude. If TNC did not exist, conservationists would need to invent such an organization. Not only do I harbor no hostility to the hundreds of dedicated staff of TNC, I salute their manifold contributions to conservation. Another point of agreement is that protected areas, by themselves, are too limited in size. Combined they constitute only about 13% of Earth (Le Saout et al. 2013), considered far too little to achieve comprehensive biodiversity protection (Noss et al. 2012). The solution is to create more protected areas and to improve their management when possible. We agree, as well, that lands subject to resource extraction, agriculture, grazing, and logging must be managed in ways that minimize damage to biodiversity, in part because diverse ecosystems are more stable and resilient (Tilman 2012). But wishing does not make it so. Not nearly enough sensitively managed wildlife habitat is effectively protected in the Unites States or elsewhere to arrest the extinction crisis. In addition, ecological degradation is exacerbated by some government agencies such as the U.S. Department of Agriculture’s Wildlife Services antipredator program and The U.S. Bureau of Land Management’s aggressive leasing of public lands for fossil fuel exploration and extraction in Wyoming and other states (Beckman et al. 2012).
Bookmark hierarchies and collaborative recommendation

GiveALink.org is a social bookmarking site where users may donate and view their personal bookmark files online securely. The bookmarks are analyzed to build a new generation of intelligent information retrieval techniques to recommend, search, and personalize the Web. GiveALink does not use tags, content, or links in the submitted Web pages. Instead we present a semantic similarity measure for URLs that takes advantage both of the hierarchical structure in the bookmark files of individual users, and of collaborative filtering across users. In addition, we build a recommendation and search engine from ranking algorithms based on popularity and novelty measures extracted from the similarity-induced network. Search results can be personalized using the bookmarks submitted by a user. We evaluate a subset of the proposed ranking measures by conducting a study with human subjects.
Patterns of Weakness, Classification of Motor Neuron Disease, and Clinical Diagnosis of Sporadic Amyotrophic Lateral Sclerosis

Abstract When approaching a patient with suspected motor neuron disease (MND), the pattern of weakness on examination helps distinguish MND from other diseases of peripheral nerves, the neuromuscular junction, or muscle. MND is a clinical diagnosis supported by findings on electrodiagnostic testing. MNDs exist on a spectrum, from a pure lower motor neuron to mixed upper and lower motor neuron to a pure upper motor neuron variant. Amyotrophic lateral sclerosis (ALS) is a progressive mixed upper and lower motor neuron disorder, most commonly sporadic, which is invariably fatal. This article describes a pattern approach to identifying MND and clinical features of sporadic ALS.
“I am hoping you can point me in the right direction regarding playground accessibility”: a case study of a community which lacked social policy toward playground accessibility

Social policy is a step to improving living conditions, enhancing society or preventing social injustices. The playground is a safe place for children and families to develop relationships, experience happiness and enjoy community. While there have been a few case studies examining playground accessibility, a more comprehensive assessment and evaluation of playground accessibility across the leisure profession has not yet been completed. The purpose of this paper is to present a descriptive case study regarding playground accessibility through assessment of accessible design features of playgrounds in two neighbouring communities in the United States. The collective findings of this study raise several issues and ask the question: “Are community park and recreation leaders aware of the lack of inclusive and accessible playground spaces?” Findings from this study can be used to develop social policies that facilitate enable inclusive playgrounds.
Decreased formation of inositol trisphosphate in Madin-Darby canine kidney cells under conditions of β-glucosidase inhibition☆

Abstract Recent work has demonstrated the enhancement of hormone-stimulated inositol trisphosphate formation in renal epithelial cells under conditions of glucosylceramide depletion. The role of glucosylceramide metabolism was explored further by exposing Madin-Darby canine kidney (MDCK) cells to the β-glucosidase inhibitor conduritol B epoxide, which produced time-dependent and concentration-dependent increases in glucosylceramide levels and decreased bradykinin-stimulated inositol trisphosphate formation from isolated MDCK cell membranes. These data provide further support for an association between glucosylceramide levels and hormone-stimulated inositol trisphosphate formation.
A Color Metric from Opponent-Color Visual Channels†

A Euclidean metric for colorimetric evaluations based on an opponent-color system was described by Ingling and Tsou. The metric was shown to work well for predicting the results of the standard color-discrimination experiment. The metric is applied to the surface-color data of the Munsell collection, the Morley, Munn, and Billmeyer data, and the data from the ISCC Committee on Color Difference Problems.
The influence of task and location on solvent exposures in a printing plant.

A work measurement technique was used to monitor the activities of seven printing press operators. Repeated observations were made to learn workers' tasks and workers' locations in the plant, and a photoionization detector was used to measure the instantaneous solvent concentration in each worker's breathing zone. Location data, analyzed using a computer aided design system, did not show any indication that there were high or low exposure areas. Regression, however, showed that a significant amount of variability in a worker's exposures was accounted for by the number of times the worker performed a certain “hazardous task” (r2=0.57). The results indicate that it may be possible to simplify industrial hygiene sampling strategies by using work measurement data, such as time study or work sampling, to identify maximum risk employees.
Organogels with Fe(III) complexes of phosphorus-containing amphiphiles as two-component isothermal gelators.

The properties of thermally reversible organogels in which the gelators consist of a phosphonic acid monoester, phosphonic acid, or phosphoric acid monoester and a ferric salt are probed by IR and ...
Isomorphism: Setting the record straight

This paper attempts to set forth and correct recent misinterpretations of the Gestalt concept of isomorphism. It distinguishes the new “isomorphisms” currently being proposed from the original conception of Gestalt psychology. Finally, it reviews the implications of isomorphism tested experimentally by Kohler and his collaborators, through the demonstrations of steady cortical currents during perception. Experimental attempts to discredit the theory of cortical currents are evaluated.
The mother of all endocytosis

Massive endocytosis is initiated by a series of steps that involve a sudden influx of calcium ions, changes in mitochondria, and modification of surface proteins by lipids. A better understanding of this process could lead to new approaches to reducing the tissue damage that is caused by heart attacks.
Scalability of silicon photonic enabled optically connected memory

We investigate the performance of a high-speed optical switch for optically connected memory and study free-carrier absorption losses as the switch scales. The bit-rate dependent optical power budget is also analyzed for optically connected memory.
Effect of adrenocorticotropin injection and stress on milk cortisol content.

Abstract The purpose of this study was to determine whether cortisol content of milk might objectively measure stress in lactating dairy cows. A procedure has been developed for measuring cortisol in milk samples by a combination of solvent extraction, chromatography, and competitive protein-binding procedures. cortisol is normally in cow's milk, and injection of 200 IU adrenocorticotropin into five cows caused an increase in concentration of cortisol in milk from 2.5 ng/ml to 8.7 ng/ml. The stress of shipping 39 cows by truck from one dairy to another also increased the concentration of cortisol in milk and decreased milk production. We correlated the concentration of cortisol in milk with the average concentration in blood during the interval of milk secretion. Under control conditions and after injection of adrenocorticotropin to increase circulating cortisol, the regression equations describing the transport of cortisol from blood to milk are nearly identical. These results are interpreted to indicate that the mammary gland is integrating the circulating concentration of cortisol, and, therefore, the cortisol concentration in milk reflects the average concentration in blood during the interval of milk synthesis. Because the secretion of cortisol into milk is one example of a more general phenomenon, a model is presented to describe the diffusion of materials across the mammary secretory cell and into milk.
Development of streptavidin-based nanocomplex for siRNA delivery

In our previous study, we have identified a PCBP2 siRNA that exhibits antifibrotic activity in rat hepatic stellate cells (HSCs) by inhibition of αCP2, a protein responsible for stabilization of the collagen α1 (I) mRNA in alcoholic liver fibrosis. This study aims to develop a streptavidin-based nanocomplex that can efficiently deliver the PCBP2 siRNA to HSCs. Biotin–siRNA and biotin–cholesterol were mixed with streptavidin to form the streptavidin–biotin complex, which was further condensed electrostatically with positively charged protamine to form the final multicomponent siRNA nanocomplex in the size range of 150–250 nm. The siRNA nanocomplex does not induce cytotoxicity in rat HSCs as compared to commercially available transfection agents. The cellular uptake efficiency of the siRNA nanocomplex is higher in rat HSCs than other cell lines, such as Caco-2 and PC-3, indicating that receptor-mediated endocytosis mainly contributes to the cellular uptake of the siRNA nanocomplex. The siRNA nanocomplex exh...
Metformin targets ovarian cancer stem cells in vitro and in vivo

Purpose Studies in non-gynecologic tumors indicate that metformin inhibits growth of cancer stem cells (CSC). Diabetic patients with ovarian cancer who are taking metformin have better outcomes than those not taking metformin. The purpose of this study was to directly address the impact of metformin on ovarian CSC.
Do modern humans and Neandertals have different patterns of cranial integration

Abstract Studies of cranial differences between modern humans and Neandertals have identified several characteristics for which the two groups differ in their mean values, the proportional relationships with other traits, or both. However, the limited number of fairly complete Neandertals has hindered investigations into patterns of integration – covariance and correlation among traits – in this fossil group. Here, we use multiple approaches specifically designed to deal with fragmentary fossils to test if metric cranial traits in Neandertals fit modern human patterns of integration. Based on 37 traits collected from a sample of 2524 modern humans from Howells’ data set and 20 Neandertals, we show that overall patterns of cranial integration are significantly different between Neandertals and modern humans. However, at the same time, Neandertals are consistent with a modern human pattern of integration for more than three-quarters of the traits. Additionally, the differences between the predicted and actual values for the deviating traits are rather small, indicating that the differences in integration are subtle. Traits for which Neandertals deviate from modern human integration patterns tend to be found in regions where Neandertals and modern humans are known to also differ in their mean values. We conclude that the evolution of patterns of cranial integration is a cause for caution but also presents an opportunity for understanding cranial differences between modern humans and Neandertals.
The sequences of the S2 genome segments of reovirus serotype 3 and of the dsRNA-negative mutant ts447

Abstract The most temperature-sensitive dsRNA-negative mutant of reovirus serotype 3 is ts447; the amount of dsRNA formed in cells infected with it at 39° is less than 0.1% of that formed in cells with wt virus at 37°. The genome segment in which this mutation is located is S2. We compare here the sequence of the S2 genome segment of wt reovirus serotype 3 with that of mutant ts447. The two sequences differ in three locations, at two of which there are C to U transitions, while at the third there is an A to G transition. All cause amino acid changes (Ala to Val, Ala to Val, and Asn to Asp, respectively). One mutation (at nucleotide position 581, which causes an Ala to Val change) causes the length of an α-helix to be significantly reduced and may be that which is responsible for the is phenotype.
Evaluation of cost of dynamic controllability and optimal surge capacity without dynamic models

It is well-known that the most economical design from a steady-state economics perspective does not necessarily need to be easily controllable and might, in some extreme cases, even be uncontrollable. It is important to evaluate and quantify the dynamic controllability of a process at the design stage. Zheng and Mahajanam (Ind. Eng. Chem. Res. 1999, 38, 999−1006) introduced a simple controllability index (ν) to quantify dynamic controllability in terms of economics. The dynamic controllability index is defined as the smallest additional surge capacity required to meet all of the control objectives and constraints dynamically for all of the expected disturbances. The index depends quantitatively on the process design and the control system alternative for each design. It has been found useful to compare plantwide control alternatives quantitatively (AIChE J. 1999, 45, 1255−1265). The main difficulty in applying the above method at the design stage is the need for a rigorous dynamic model, which is rarely a...
Teaching neuroimages: susceptibility-weighted MRI: first clue to DAVF complicating sinovenous thrombosis.

A 61-year-old man with factor V Leiden thrombophilia presented with hemorrhage and transverse sinus thrombosis (figure, A). Four years later, he developed worsening aphasia, new hemorrhage, and hemispheric edema (figure, B). Susceptibility-weighted imaging (SWI) showed bright signal in the straight sinus (figure, C). A dural arteriovenous fistula (DAVF) was diagnosed (figure, D). The brain edema improved (figure, E) and SWI sinus hyperintensity resolved after endovascular disconnection of the fistula (figure, F). The authors thank the members of the Yale–New Haven Hospital Neurovascular & Stroke Programs for discussions and critical review of the manuscript.
DOES DEFENSE SPENDING REALLY PROMOTE AGGREGATE OUTPUT IN THE UNITED STATES

Many studies have examined the relationship between defense spending and growth in real aggregate output with mixed results. Most recently, Atesoglu (2002) finds a positive relationship between defense spending and output. Capturing the error correction term as the long run adjustment parameter and including the long run adjustment in the relationship, we do not find evidence that defense spending promotes growth in real output. Instead, defense spending responds to aggregate income shocks. We re‐estimated the relationship and dummied all US military conflicts with similar results concerning military spending's effect on output. Interestingly, we find trade‐offs between defense and non‐defense government spending during war time. ∗ The views expressed in this paper are those of the authors and do not necessarily reflect the official policy or position of the US Air Force, the Department of Defense, or the US Government. The authors would like to express their thanks for the comments from Craig Stone and t...
Measuring regular equivalence in symmetric structures

Abstract A method for computing the extent to which all pairs of points is a symmetric graph are regularly equivalent is proposed. By considering the relative centralities of points connected by an edge, the symmetric graph is decomposed into two asymmetric graphs. These asymmetric graphs provide the input for the regular equivalence algorithm, REGE, of White and Reitz (1983).
Prognostic importance of weight loss in patients with coronary heart disease regardless of initial body mass index.

BackgroundRecently, mild elevations in body mass index (BMI) have been related to better outcomes in patients with coronary heart disease. Our aim was to determine whether patients with coronary heart disease who are participating in cardiac rehabilitation would have improved outcomes if they lost weight and whether this would depend on initial BMI.MethodsThis is a prospective cohort study of 377 consecutive patients enrolled at a cardiac rehabilitation program, aged 30–85 years with a mean follow-up of 6.4 ± 1.8 years. We measured total mortality, acute cardiovascular events (fatal and nonfatal myocardial infarction, fatal and nonfatal stroke, emergent revascularization in the setting of unstable angina, and hospitalization for congestive heart failure) and a composite outcome (mortality + acute cardiovascular events). Statistical testing used Cox Proportional Hazards Regression.ResultsOn average, the weight loss group (n = 220) lost 3.6 ± 4.1 kg, and the nonweight loss group (n = 157) gained 1.5 ± 1.4 k...
Concentration-dependent conditioned place preference to inhaled toluene vapors in rats.

Abstract Objectives Toluene is present in many commercial products and is subject to abuse by inhalation. The goal of this study was to extend previous reports indicating that rats will exhibit a positive conditioned place preference to inhaled toluene vapors and to determine the dose–response relationship for inhaled toluene in terms of exposure concentration and number of exposures. For the conditioned place preference experiments rats were exposed to toluene vapors at concentrations of 800, 2000, 3000 or 5000 ppm in one compartment of a three-compartment box. Results Following six conditioning sessions with toluene, a significant place preference was obtained at 2000 and 3000 ppm, but not at 800 or 5000 ppm. Extending the number of toluene pairings at the 2000 and 3000 ppm concentration to 12 significantly enhanced the place preference compared to that at six pairings. Conclusions These experiments extend our previous finding that rats will show a conditioned place preference to inhaled toluene, and indicate that a reinforcing “dose” of toluene depends on both the concentration and number of pairings.
Absence of HER2 overexpression in metastatic malignant melanoma.

Background and Objectives Currently available systemic therapies for malignant melanoma produce low response rates in patients, and more effective treatment modalities are clearly needed. Trastuzumab (Herceptin®), the antibody to the HER2 oncoprotein, has had a significant impact on therapy for patients with HER2-overexpressing metastatic breast cancer. This study examined the incidences of HER2 protein overexpression and HER2 gene amplification in metastatic malignant melanoma, which remain unclear in the literature. Methods The study evaluated patients with stage III and stage IV malignant melanoma who were treated between 1983 and 1999. Tissue blocks were retrieved and reviewed to confirm the diagnosis. From the 101 cases identified, 49 (31 stage III and 18 stage IV) had sufficient residual tumor sample to enable an assay to be performed. The blocks were tested for HER2 overexpression using the DAKO HercepTest™ immunohistochemical (IHC) assay. Any sample that tested 1+ or greater for HER2 expression on IHC and a randomly selected subset of HER2-negative samples were tested for the presence of HER2 gene amplification using the Vysis PathVysion™ fluorescence in situ hybridization (FISH) assay. Results The median age of the 49 selected patients was 52.2 years, and the male-to-female ratio was 1.23:1 (27 men to 22 women). All of the 49 cases of malignant melanoma were negative for HER2 overexpression by IHC. However, two samples (3%) were found to have a weak level of HER2 expression (1+ level of staining). Subsequent FISH results on the samples that were 1+ on IHC were negative for HER2 gene amplification. FISH results on 21 other randomly selected IHC-negative samples were also negative for HER2 amplification. Flow cytometry failed to show HER2 overexpression in two melanoma cell lines, and treatment of these cells with trastuzumab did not affect their proliferation rate. Conclusions We found a low incidence of HER2 expression and no evidence of HER2 protein overexpression or HER2 gene amplification in metastatic malignant melanoma tissues. Therefore, routine testing for HER2 overexpression or HER2 amplification would not be of benefit in this patient population. These results also imply that anti-HER2 therapy with trastuzumab is highly unlikely to provide benefit for patients with metastatic melanoma. J. Surg. Oncol. 2003;84:82–88. © 2003 Wiley-Liss, Inc.
Targeted Therapy in Ovarian Cancer

Ovarian cancer is the most common cause of mortality of tumors from gynecologic origin and is often diagnosed after patients have already progressed to advanced disease stage. The current standard of care for treatment of ovarian cancer includes cytoreductive surgery followed by adjuvant chemotherapy. Unfortunately, many patients will recur and ultimately die from their disease. Targeted therapies have been evaluated in ovarian cancer as a method to overcome resistant disease. Angiogenesis inhibitors have shown success in many tumor types and have also demonstrated promise in trials involving patients with ovarian cancer. PARP inhibitors may be potentially active agents in patients with BRCA-associated ovarian cancer. Trials that have evaluated combinations of targeted agents have often revealed untoward toxicities, thus tempering enthusiasm for this approach.
The Perinucleolar Compartment and Transcription

The perinucleolar compartment (PNC) is a unique nuclear structure localized at the periphery of the nucleolus. Several small RNAs transcribed by RNA polymerase III and two hnRNP proteins have been localized in the PNC (Ghetti, A., S. Pinol-Roma, W.M. Michael, C. Morandi, and G. Dreyfuss. 1992. Nucleic Acids Res. 20:3671-3678; Matera, A.G., M.R. Frey, K. Margelot, and S.L. Wolin. 1995. J. Cell Biol. 129:1181- 1193; Timchenko, L.T., J.W. Miller, N.A. Timchenko, D.R. DeVore, K.V. Datar, L. Lin, R. Roberts, C.T. Caskey, and M.S. Swanson. 1996. Nucleic Acids Res. 24: 4407-4414; Huang, S., T. Deerinck, M.H. Ellisman, and D.L. Spector. 1997. J. Cell Biol. 137:965-974). In this report, we show that the PNC incorporates Br-UTP and FITC-conjugated CTP within 5 min of pulse labeling. Selective inhibition of RNA polymerase I does not appreciably affect the nucleotide incorporation in the PNC. Inhibition of all RNA polymerases by actinomycin D blocks the incorporation completely, suggesting that Br-UTP incorporation in the PNC is due to transcription by RNA polymerases II and/or III. Treatment of cells with an RNA polymerase II and III inhibitor induces a significant reorganization of the PNC. In addition, double labeling experiments showed that poly(A) RNA and some of the factors required for pre-mRNA processing were localized in the PNC in addition to being distributed in their previously characterized nucleoplasmic domains. Fluorescence recovery after photobleaching (FRAP) analysis revealed a rapid turnover of polypyrimidine tract binding protein within the PNC, demonstrating the dynamic nature of the structure. Together, these findings suggest that the PNC is a functional compartment involved in RNA metabolism in the cell nucleus.
Diagnosis and management of late onset osteoradionecrosis of the mandible

Osteoradionecrosis (ORN) is frequently encountered in clinical dental practice. The identification and management of such a lesion is often challenging. This clinical report is based on a patient who had radiation therapy to the head and neck region for a salivary gland malignancy. The patient developed ORN of the mandible 12 years later. This demonstrates the need to understand the pathophysiology of this condition better than we currently know.
Origin of the 0.97 eV luminescence in irradiated silicon

Abstract Optical detection of magnetic resonance studies are described for the well-studied optical center with zero phonon line at 0.97 eV in irradiated silicon. Analysis of the S=1 ODMR spin Hamiltonian reveals a low symmetry (C lh ) center and a resolved 29 Si hyperfine interaction with a single silicon atom. In a specially enriched 13 C doped sample we find additional hf interactions with two equivalent carbon atoms. At elevated temperatures, the defect reorients easily from one C lh distortion to another around a common 〈111t> axis; during this reorientation the spin density remains located on the same silicon atom and the same carbon pair. From these results we construct a model comprising two adjacent (substitutional) carbon atoms and an interstitial silicon atom which has distorted out from a bond-centered position. We conclude that the same defect gives rise to the Si-G11 EPR spectrum when positively charged.
Empathy-induced altruism in a prisoner's dilemma II: what if the target of empathy has defected?

What if participants in a one-trial prisoner's dilemma know before making their decision that the other person has already defected? From the perspective of classic game theory, a dilemma no longer exists. It is clearly in their best interest to defect too. The empathy-altruism hypothesis predicts, however, that if they feel empathy for the other, then a dilemma remains: self-interest counsels defection; empathy-induced altruism counsels not. This motivational conflict should lead at least some empathically aroused individuals not to defect. To test this prediction, we placed 60 undergraduate women in a one-trial prisoner's dilemma in which they knew the other had already defected. Among those not induced to feel empathy, very few (0.05) did not defect in return. Among those induced to feel empathy for the other, almost half (0.45) did not defect. These results underscore the power of empathy-induced altruism to affect responses in a prisoner's dilemma. Copyright © 2001 John Wiley & Sons, Ltd.
The presence of P700 in chloroplast fragments prepared by short time incubation with Triton X-100.

Abstract A procedure was recently described by R. Malkin ( Biochim. Biophys. Acta , 253 (1971) 421) by which fragments having Photosystem II activity could be derived from chloroplasts. These fragments could photoreduce NADP + but were completely devoid of P700, thus giving considerable support to the new “Three-Light-Reaction” scheme in green plant photosynthesis. The results presented here show that the Triton chloroplast fragments still contain approximately 30 to 40% initial P700 as assayed by EPR and difference spectroscopy. The failure to detect P700 in the earlier publication, either by chemical or photochemical assay, was because of the lack of plastocyanin in the reaction medium. This electron carrier is necessary for the reduction of P700 by ascorbate in the Triton fragments. The photoreduction of methyl viologen or NADP + by these fragments with ascorbate as electron donor in the presence of plastocyanin is shown to be a Photosystem I reaction. The maximal Photosystem I activity is about 35% of that of the starting material. The fragments exhibit an increased EPR Signal II.
Medicaid status is associated with higher complication rates after spine surgery.

Study Design. Multivariate analysis of prospectively collected registry data. Objective. To determine the effect of payor status on complication rates after spine surgery. Summary of Background Data. Understanding the risk of perioperative complications is an essential aspect in improving patient outcomes. Previous studies have looked at complication rates after spine surgery and factors related to increased perioperative complications. In other areas of medicine, there has been a growing body of evidence gathered to evaluate the role of payor status on outcomes and complications. Several studies have found increased complication rates and inferior outcomes in the uninsured and Medicaid insured. Methods. The Spine End Results Registry (2003–2004) is a collection of prospectively collected data on all patients who underwent spine surgery at our 2 institutions. Extensive demographic data, including payor status, and medical information were prospectively recorded as described previously by Mirza et al.16 Medical complications were defined in detail a priori and were prospectively recorded for at least 2 years after surgery. Using univariate and multivariate analysis, we determined risk of postoperative medical complications dependent on payor status. Results. A total of 1591 patients underwent spine surgery in 2003 and 2004 that met our criteria and were included in our analysis. With the multivariate analysis and by controlling for age, patients whose insurer was Medicaid had a 1.68 odds ratio (95% confidence interval: 1.23–2.29; P = 0.001) of having any adverse event when compared with the privately insured. Conclusion. After univariate and multivariate analyses, Medicaid insurance status was found to be a risk factor for postoperative complications. This corresponds to an ever-growing body of medical literature that has shown similar trends and raises the concern of underinsurance. Conclusion. Level of Evidence: 2