cssi/SciSciGPT-SciSciNet huggingface dataset:
Immunotherapeutic Approaches to Sarcoma

Current therapies in advanced sarcomas are primarily based on cytotoxic chemotherapy and have modest efficacy coupled with significant toxicity. Little progress has been made in the field since imatinib was approved for the treatment of gastrointestinal stromal tumor (GIST) in 2002 despite the recent FDA approval of the multi-tyrosine kinase inhibitor pazopanib. Novel therapies are clearly needed. Immunotherapy utilizing checkpoint inhibitors has yielded significant clinical benefit in multiple solid tumors manifesting as durable responses in melanoma, kidney, lung, and bladder cancers, as well as hematologic malignancies. Given the success in several “non-immunogenic” tumors and recent preclinical data, there is sufficient evidence to support the use of immunotherapy in sarcoma. Cytokine-based therapies have shown no benefit in the advanced setting. Two large randomized trials of muramyl tripeptide or of interferon maintenance in resected osteosarcoma patients did not provide unequivocal statistically significant benefit. More promising results have been reported in small studies evaluating vaccines and adoptive T cell therapy in specific subtypes of sarcoma such as synovial sarcoma, which widely expresses the immunogenic cancer testis antigen NY-ESO-1. Emerging approaches with chimeric antigen receptor (CAR)-engineered T cells are hypothesis-generating and thought-provoking. However, the unprecedented clinical activity and excellent safety profile of checkpoint inhibitors targeting programmed death-1 receptor and its ligand (PD-1/PD-L1) have galvanized the field and generated much enthusiasm to harness the power of immunotherapy in pursuit of cures in patients with advanced sarcomas. An ongoing phase II study (SARC028) will hopefully usher an era of investigation of this exciting approach in sarcoma. However, it is unlikely that one agent will carry a universal cure and future approaches need to focus on patient selection as well as on identifying the optimal combination of checkpoint inhibitors with targeted therapy, chemotherapy, or radiation therapy.
Activating newborn neurons suppresses depression and anxiety-like behaviors

The etiology of major depressive disorder (MDD), the leading cause of worldwide disability, is unknown. The neurogenic hypothesis proposes that MDD is linked to impairments of adult neurogenesis in the hippocampal dentate gyrus (DG), while the effects of antidepressants are mediated by increased neurogenesis. However, alterations in neurogenesis and endophenotypes are not always causally linked, and the relationship between increased neurogenesis and altered behavior is controversial. To address causality, we used chemogenetics in transgenic mice to selectively manipulate activity of newborn DG neurons. Suppressing excitability of newborn neurons without altering neurogenesis abolish the antidepressant effects of fluoxetine. Remarkably, activating these neurons is sufficient to alleviate depression-like behavior and reverse the adverse effects of unpredictable chronic mild stress. Our results demonstrate a direct causal relationship between newborn neuronal activity and affective behavior. Thus, strategies that target not only neurogenesis but also activity of newborn neurons may lead to more effective antidepressants. It is unclear if there is a causal link between increased neurogenesis and altered affective behaviors in major depressive disorders. Here, the authors show that selectively suppressing the excitability of newborn neurons, without altering neurogenesis, abolishes the antidepressant effects of fluoxetine.
Algarve, the Mediterranean, and the Atlantic

EnglishJoaquim Romero Magalhaes was to begin with a regional historian rooted in the French Annales tradition of social and economic history. His regional history of the Algarve in the sixteenth to eighteenth centuries overflows into the much wider and evolving complexes within which the Portuguese region was framed—the ageing Mediterranean and the growing Atlantic, and their shifting balance in the weaving of a new world economy. It is in the regional origins of Romero Magalhaes’s trajectory that we find many of the topics and problems that he developed in his historical travels across the empire. portuguesJoaquim Romero Magalhaes foi, antes de mais, um historiador regional enraizado na tradicao da historia economica e social dos Annales. A sua historia regional do Algarve entre os seculos XVI e XVIII transborda para os complexos muito mais amplos e em transformacao que enquadravam a regiao portuguesa—o Mediterrâneo em envelhecimento e o Atlântico em crescimento, e o seu equilibrio em mutacao no tecer de uma economia mundial nascente. E nas origens regionais da trajetoria de Romero Magalhaes que encontramos muitos dos topicos e dos problemas que ele desenvolveu nas suas viagens historicas pelo imperio.
Computerized Advisory Decision Support for Cardiovascular Diseases in Primary Care: A Cluster Randomized Trial.

ABSTRACT Purpose To evaluate the impact of an outpatient computerized advisory clinical decision support system (CDSS) on adherence to guideline-recommended treatment for heart failure, atrial fibrillation, and hyperlipidemia. Methods Twenty care teams (109 clinicians) in a primary care practice were cluster-randomized to either access or no access to an advisory CDSS integrated into the electronic medical record. For patients with an outpatient visit the CDSS determined if they had heart failure with reduced ejection fraction, hyperlipidemia, and/or atrial fibrillation; and if so, was the patient receiving guideline-recommended treatment. In the intervention group, an alert was visible in the medical record if there was a discrepancy between current and guideline-recommended treatment. Clicking the alert displayed the treatment discrepancy and recommended treatment. Outcomes included prescribing patterns, self-reported use of decision aids and self-reported efficiency. The trial was conducted between May 1 and November 15, 2016 and incorporated 16,310 patient visits. Results The advisory CDSS increased adherence to guideline-recommended treatment for heart failure (odds ratio 7.6 [95% confidence interval, 1.2, 47.5]), but had no impact in atrial fibrillation (OR 0.94 [0.15, 5.94]) or hyperlipidemia (OR 1.1 [0.6, 1.8]). Clinicians with access to the CDSS self-reported greater use of risk assessment tools for heart failure (3.6 [1.1] vs 2.7 [1.0], mean [SD] on a 5-point scale) but not for atrial fibrillation or hyperlipidemia. The CDSS did not impact self-assessed efficiency. The overall usage of the CDSS was low (19%). Conclusions A computerized advisory CDSS improved adherence to guideline-recommended treatment for heart failure but not for atrial fibrillation or hyperlipidemia.
Presidential Transitions: The Shaping and Reshaping of the Federal Regulatory Agenda

The federal administrative state does more lawmaking, by some measures, than Congress. In 2001, Congress passed 21 major statutes (Barshay 2001) and 115 other public laws (Final Resume 2003). In contrast, in that year, cabinet departments, the Executive Office of the President, and independent agencies promulgated 70 significant rules and 3,369 other rules (GAO 2005). (The law defines significant, or major, rules as those that have at least a $100 million, or otherwise significant, effect on the economy.) This research project examines changes in federal agency rulemaking between 1983 and 2002, using a large dataset from the Unified Agenda of Federal Regulatory and Deregulatory Actions. Do shifts in the quantity of rulemaking-related activities depend on changes in the White House or on the independence of agencies? What role do Congress and the courts play? What are the implications of patterns of regulatory activity for agency legitimacy, judicial deference to agency decisions, and desired agency activities during Presidential transitions? This paper presents some preliminary results.
Solid Pancreatic Masses

There is a wide variety of solid neoplasms that affect the pancreas. The vast majority of them will be ductal adenocarcinoma and neuroendocrine tumors. MSCT has significantly increased both the detection and improved preoperative staging of pancreatic adenocarcinoma. Volume acquisitions facilitate the creation of high-quality 3D images that provide superior depiction of peripancreatic extension of disease allowing appropriate therapeutic decision making; however pancreas specific multiphase MSCT protocols are required to achieve these results. Additionally, multiphase MSCT has increased the detection of small neuroendocrine tumors. Finally, although there are several much more unusual pancreatic tumors, both primary and secondary that may be infrequently encountered in clinical practice, a more detailed discussion of metastases to the pancreas and non-neoplastic focal pancreatic masses is offered.
Multispecific drugs herald a new era of biopharmaceutical innovation

The modern biopharmaceutical industry traces its roots to the dawn of the twentieth century, coincident with marketing of aspirin—a signature event in the history of modern drug development. Although the archetypal discovery process did not change markedly in the first seven decades of the industry, the past fifty years have seen two successive waves of transformative innovation in the development of drug molecules: the rise of ‘rational drug discovery’ methodology in the 1970s, followed by the invention of recombinant protein-based therapeutic agents in the 1980s. An incipient fourth wave is the advent of multispecific drugs. The successful development of prospectively designed multispecific drugs has the potential to reconfigure our ideas of how target-based therapeutic molecules can work, and what it is possible to achieve with them. Here I review the two major classes of multispecific drugs: those that enrich a therapeutic agent at a particular site of action and those that link a therapeutic target to a biological effector. The latter class—being freed from the constraint of having to directly modulate the target upon binding—may enable access to components of the proteome that currently cannot be targeted by drugs. The development and future prospects of prospectively designed multispecific drugs, which have the potential to transform the biopharmaceutical industry by enabling the targeting of currently inaccessible components of the proteome, are reviewed.
Six shocks without premonitory symptoms

A 62-year-old man with ischemic cardiomyopathy (NYHA Class II, left-ventricular ejection fraction 29%) underwent implantation of a prophylactic dual-chamber ICD (Atlas DR V-242) 2 years ago. During a febrile illness, he received six shocks without premonitory symptoms. Diagnosis and management are discussed.
PubMed 2.0

After years of strategic planning, the National Library of Medicine has introduced an updated and redesigned version of its PubMed health sciences research website. The new website features a more modern and responsive interface, especially on mobile devices. Tools and features have been relocated to make them more intuitive for new users. While not without some turbulence and slight discomfort for long-time users adjusting to the modernized interface and search engine, the new version of the PubMed website introduced in 2020 succeeds in the website's time-honored task of collecting and making freely accessible high-quality health sciences information and resources.
Xinjie Hu, Aekyung Jung, and Gengsheng Qin (2020), “Interval Estimation for the Correlation Coefficient,” The American Statistician, 74:1, 29–36: Comment by Krishnamoorthy and Xia

Let X1,…,Xn be a sample from a bivariate normal distribution with mean vector μ and the covariance matrix Σ , N2(μ,Σ) . Define X¯=1n∑i=1nXi and S=∑i=1n(Xi−X¯)(Xi−X¯)′. Hu, Jung, and Qin (2020) have...
Mother’s Milk Messaging™ (MMM): Mothers Favor Daily Texting and Reliability of App Content in Qualitative Evaluation

Background: Although the benefits and advantages of breastfeeding (BF) are known, disparities exist in BF practices from different ethnic/racial groups. We developed and evaluated an app (MMM) in English and Spanish to help mothers from late trimester through 2 months postpartum meet their BF goals. MMM includes theoretical-based text messaging with social support features, videos and evidence-based written content to encourage BF exclusivity and duration among first time mothers. Objective: To understand the perspectives of first-time …
Status Positivus, ‘Status Impositivus’: Breves Reflexiones Sobre La Protección De Hecho De Los Derechos Fundamentales a Través Del Derecho Tributario (Status Positivus, 'Status Impositivus': Brief Thoughts About The De Facto Protection of Constitutional Rights Through Tax Law)

Spanish Abstract: Proteger los derechos humanos y los derechos fundamentales cuesta dinero. El Estado, en su doble rol de recaudador y protector de los contribuyentes, debe formular de manera justa y equitativa las bases juridicas para exigir el pago de impuestos a los contribuyentes de la manera mas eficiente posible, y distribuir dichos recursos honestamente para asegurar el funcionamiento de las instituciones sociales y estatales que dan cumplimiento efectivo a los derechos fundamentales. El presente trabajo pretende brindar sucintas consideraciones sobre la finalidad factica de las finanzas publicas y la tributacion: la proteccion efectiva de los derechos fundamentales en el territorio de la Republica como condicion sine qua non para el fortalecimiento del Estado social de derecho en el Paraguay. La primera parte es introductoria a las formas de actuacion del Estado y su estrecha relacion con la ciencia tributaria. El segundo apartado analiza la situacion actual de la cobertura de los derechos fundamentales con los recursos tributarios del Estado, y brinda algunas consideraciones para reformas fiscales a posteriori. La tercera parte concluye. English Abstract: The protection of human rights and constitutional rights costs money. The State, acting simultaneously as tax collector and protector of the taxpayers, is obliged to just and fairly formulate the legal basis for collecting taxes in the most efficient way possible. Furthermore, the distribution of said resources shall be made in an honest and transparent fashion, in order to ensure proper functioning of social and state institutions which ultimately are responsible for guaranteeing the constitutional rights of the taxpayers. This essay briefly examines considerations about the factual purpose of public finances and tax law: the effective protection of the constitutional rights in the Republic of Paraguay as sine qua non condition for strengthening the social rule of law (welfare state). The first section introduces some functions of state intervention and its close relationship with tax law. The second section analyzes the coverage of constitutional rights in Paraguay with tax resources, and provides basic considerations for future tax reforms. The third section concludes the essay.
Dante ‘davanti a la ruina’ (Inferno v, 34): Minos, the Ruins of Hell, and the Book of Nahum

After discussing why Minos and the domain he overlooks seem similarly compounded from rational and unintelligible elements, I argue that the ‘ruina’ before which the lustful curse in Canto v of Inf...
The impacts of model structure, parameter uncertainty and experimental design on Earth system model simulations of litter bag decomposition experiments

Abstract. Accurate Earth system model simulations of the terrestrial carbon cycle and its feedbacks to climate critically depend on algorithms representing the decomposition of litter and soil organic matter. Litter bag studies, in which specific types of plant litter are subject to varying environmental conditions in the field and decomposition is measured, serve as valuable benchmarks for model performance. Here we test the Energy Exascale Earth System land model (ELM), which has two different structural representations of decomposition, using observations from the Long-term Intersite Decomposition Experiment (LIDET) over six different biomes and six different leaf litter types. We find that seasonal patterns in soil conditions and nutrient availability have large effects on decomposition rates, and that it is critical to include this in the simulation design. Despite widely differing base decomposition rates between the two different model structures, the models produce similar temporal patterns of decomposition when nitrogen is limiting. Both models overpredict the fraction of original nitrogen present as a function of carbon remaining when using default parameterizations. A parameter sensitivity analysis indicates strong dependence of model outputs on nitrogen limitation, carbon use efficiency and decomposition rates. A large spread in model predictions when considering an ensemble of possible parameter combinations strongly suggests parameter uncertainty may be more influential than model structural uncertainty, and that new measurement and modelling approaches may be necessary to constrain these uncertainties.
Pacemaker lead related myocardial perforation.

Permanent pacemaker (PPM) insertion is widely used to treat cardiac rhythm disorders; approximately 600,000 pacemakers are implanted annually in the US (Wood and Ellenbogen, 2002). Almost 9% of patients who receive a permanent pacemaker, however, experience a variety of medical complications such as infections, battery problems, programming issues, lead migration, or lead fracture (Greenspon et al., 2012). Moreover 1-2% of these patients will encounter severe lead-related problems within 30 days of their pacemaker insertion (Kirkfeldt et al., 2014; Kiviniemi et al., 1999). In this report, we focus on an uncommon but serious complication of PPM insertion: right ventricular lead perforation leading to a pericardial effusion. Although lead perforation is a relatively rare occurrence, this event can be life-threatening, and should be considered in the differential diagnosis when patients present to the emergency department (ED) with relevant symptoms and recent PPM insertion. Specifically, patients who experience complications from pacemaker insertion may present to the ED with a variety of symptoms such as chest pain, syncope, dyspnea, or even dizziness (Squire and Niemann, 2006). Pacemaker complications include pneumothorax, pleural and/or pericardial effusions, and infection, placing the patient at serious risk for significant harm (Squire and Niemann, 2006; Shingaki et al., 2015). The evaluation of a lead-related issue typically involves chest radiography to visualize abnormal lead placement and check for a pneumothorax or pleural effusion, and a 12‑lead electrocardiogram (ECG) to detect pacing errors. We present the case of a patient who presented to the ED three days after his pacemaker insertion with chest pain and dyspnea; he was subsequently diagnosed with a lead perforation into the pericardial space resulting in a pericardial effusion.
Adverse childhood experiences exacerbate the association between day-to-day discrimination and mental health symptomatology in undergraduate students.

Abstract Background Adverse childhood experiences (ACEs) and day-to-day discrimination (hereafter, “discrimination”) both contribute to mental health symptomatology in young adulthood, but how these constructs interact and whether they are associated with mental health remains unclear. This study evaluated whether the relation between discrimination in young adulthood and mental health symptomatology varied as a function of ACEs exposure. Methods Undergraduates (n = 251) completed self-report measures related to ACEs, discrimination, and mental health symptomatology (i.e., depression, anxiety, somatization, and psychological distress). Linear and logistic regression models were implemented to test for potential exacerbation effects of ACEs on the relation between discrimination and mental health symptomatology. Results Participants with greater discrimination exposure and ACEs reported significantly more depression, anxiety, and somatic symptoms, along with more psychological distress, relative to those with less discrimination exposure and few or no ACEs. Limitations Data were cross-sectional, thus, causality cannot be inferred. ACEs and discrimination measures examined ACE counts and general discrimination, respectively, which did not allow for examination of possible differences across specific ACEs (e.g., childhood sexual abuse vs. neglect) or specific types of discrimination (e.g., sexual-orientation-based discrimination vs. race-based discrimination). Conclusions These results are among the first to inform the conceptualization of ACEs and discrimination in etiological models of young adults’ mental health. Both ACEs and discrimination, rather than exposure to only one of these stressors, may be synergistically associated with young adults’ mental health symptomatology. Clinicians could address stress-sensitive mental health issues by assessing for both ACEs and discrimination exposure.
What's New in Kinesiology

(1972). What's New in Kinesiology. Journal of Health, Physical Education, Recreation: Vol. 43, Including Leisure Today, pp. 83-84.
Signal Transduction and Cross Regulation in the Escherichia coli Phosphate Regulon by PhoR, CreC, and Acetyl Phosphate

This chapter focuses on the control of the Pho regulon by the signal transduction pathways involving the Pi sensor PhoR, the catabolite regulatory sensor CreC, and acetyl phosphate. It is also poorly understood whether cross regulation by CreC or by acetyl phosphate has a bonafide role in Pho regulon control under certain conditions in normal cells. Therefore, some speculations are provided about the nature of the Pi signal transduction pathway and about the roles of CreC and acetyl phosphate in Pho regulon control. The chapter discusses signal transduction pathways of the Pho regulon. A Pi repression complex may contain all components of the Pst system, PhoU, and PhoR, because all these are required for Pi repression. By testing effects due to ackA and pta mutations, it was shown that activation of the Pho regulon in the absence of both PhoR and CreC requires acetyl phosphate synthesis. Evolutionarily related proteins share sequence similarities at the protein level with other members of the same family. Therefore, sensors are probably structurally and functionally similar to other sensors, and response regulators are probably structurally and functionally similar to other response regulators. The primary control of the Pho regulon involves a signal transduction pathway responsive to the extracellular Pi level.
Creating an Intraoperative MRI Suite for the Musculoskeletal Tumor Center.

Background Altered anatomy in a previously irradiated surgical bed can make accurate localization of anatomic landmarks and local recurrence nearly impossible. The use of intraoperative MRI (iMRI) has been described in neurosurgical settings, but to our knowledge, no such description has been made regarding its utility for local recurrence localization in sarcoma surgery.
The monoamine oxidase catalyzed degradation of phenelzine-l-14C, an irreversible inhibitor of monoamine oxidase--I. Studies in vitro.

Abstract Rats receiving approx. 2.5 mg kg of phenelzine-1-14C by the intraperitoneal route were placed in metabolism cages and their urine collected for 24 hr. Phenylacetic-1-14C acid was recovered as a major metabolite. Pretreatment of the animals with tranylcypromine (10 mg kg ) or pargyline (100 mg kg ) prior to injection of radioactive phenelzine markedly reduced the urinary excretion of phenylacetic-1-14C acid and the excretion of other unidentified metabolites appeared to increase. Inhibition of monoamine oxidase (MAO) with tranylcypromine or pargyline had no effect on the urinary excretion of an equimolar dose of phenylacetic-1-14C acid administered by the same route. Therefore, pretreatment of rats with tranylcypromine or pargyline appears to have decreased the bioconversion of the injected phenelzine to phenylacetic acid. These results provide further evidence that phenelzine, in addition to being an irreversible inhibitor, is also a substrate of MAO in the intact animal.
On The Dynamics Of Perez Lauraudogoitia's Supertask

The supertasks described by Perez Laraudogoitia, involving the dynamics of a system containing an infinite number of particles in a bounded region of space, are characterized by the nonconservation of energy and by the spontaneous motion of particles (“self-excitation”'). We argue that these features arise from the inadequacy of the local, particle-by-particle description used to analyze the supertasks. A global analysis, involving embeddings in Hilbert spaces, clarifies these supertasks and avoids what we regard as their nonphysical features.
Permeability of bacterial spores. III. Permeation relative to germination.

Abstract Black, S. H. (The University of Michigan, Ann Arbor) and Philipp Gerhardt. Permeability of bacterial spores. III. Permeation relative to germination. J. Bacteriol. 83:301–308. 1962.—The passive diffusion of solutes into dormant spores, characterized previously with the test organism Bacillus cereus strain terminalis, has now been examined in relation to germination. Dormant spores did not take up specific germinants differently than they did other compounds, under conditions optimal for germination. Germinated spores, viable but prevented from growing out, displayed some changes in permeability, evidenced by increased total uptake of glucose and water and by observable penetration of a fluorescigenic dye. Heat-killed spores were as permeable to glucose and the dye as germinated ones.
First-Order Probabilistic Models for Coreference Resolution

Traditional noun phrase coreference resolution systems represent features only of pairs of noun phrases. In this paper, we propose a machine learning method that enables features over sets of noun phrases, resulting in a first-order probabilistic model for coreference. We outline a set of approximations that make this approach practical, and apply our method to the ACE coreference dataset, achieving a 45% error reduction over a comparable method that only considers features of pairs of noun phrases. This result demonstrates an example of how a firstorder logic representation can be incorporated into a probabilistic model and scaled efficiently.
Preferences, Information and Settlement Failure

Abstract Asymmetric information on preferences is a potentially important explanation of bargaining failure. Preferences are not directly observable and information about preferences may be difficult to credibly establish to a bargaining partner. Unobserved preferences which may be relevant for pretrial bargaining include the degree of risk aversion, the degree of litigiousness, and a taste for fairness. These contrast with fact based explanations such as asymmetric information on the probability of a finding for the plaintiff at trial or on the extent of the plaintiff’s damages. In this paper, we show that there is an important difference between informational asymmetries which are fact based and those which are preference based. In particular, with a fact based asymmetry, the standard bargaining model predicts trials regardless of whether the uninformed party or the informed party makes the offer. By contrast, under the preference based explanation, disputes are only predicted in the model in which the uninformed party makes the offer. We illustrate this point in a simple model of pretrial bargaining.
Risk-benefit analysis of lumbar puncture to evaluate for nontraumatic subarachnoid hemorrhage in adult ED patients

Abstract Objective The objective of the study is to compare the risks and benefits of lumbar puncture (LP) to evaluate for subarachnoid hemorrhage (SAH) after a normal head computed tomographic (CT) scan. Methods This was an observational study of adult emergency department patients at a single hospital who presented with headache and underwent LP after a normal head CT to evaluate for SAH. Lumbar puncture results classified as indicating a SAH included xanthochromia in cerebrospinal fluid (CSF) or red blood cells in the final tube of CSF with an aneurysm or arteriovenous malformation on cerebral angiography. An LP-related complication was defined as hospitalization or a return visit due to symptoms attributed to the LP. Proportions of the study patients who had SAH diagnosed by LP and who experienced an LP-related complication were compared. Results The study included 302 patients, including 2 (0.66%) who were diagnosed with SAH based on LP (number needed to diagnose, 151); both of these patients had a known intracranial aneurysm. Eighteen (5.96%) patients experienced an LP-related complication (P Conclusion The yield of LP for diagnosing SAH in adults with nontraumatic headache after a normal head CT was very low. The severity of LP-related complications was low, but complications were more common than SAH diagnoses. Lumbar puncture may not be advisable after a normal head CT to evaluate for SAH, particularly in patients with low-risk clinical features for SAH.
Deriving Object Octree from Images

Octrees are used in many 3-D representation problems because they provide a compact data structure, allow rapid access to information, and implement efficient data manipulation algorithms. The initial acquisition of the 3-D information, however, is a common problem. This paper describes an algorithm to construct the octree representation of a 3-D object from silhouette images of the object. The images must be obtained from nine viewing directions corresponding to the three "face-on" and six "edge-on" views of an upright cube. The execution time is found to be linear in the number of nodes in the octree.
PHENYLKETONURIA. A REVIEW OF SOME DEFICITS IN OUR INFORMATION.

The dietary regimen is a difficult one; it must be closely controlled by the physician if complications are to be avoided. Although effective in limiting pathology, if administered early and maintained, evidence is not yet presented as to whether it is fully protective. Estimates of the incidence and prevalence of phenylketonuria are not well established. There are indications that, although rare, the incidence may be considerably higher than the 1 in 20,000 to 25,000 births previously estimated. Discrepancies in the estimates should be explored for possible explanation. These may relate to different population frequencies, definitions of mental retardation, and screening and testing procedures. The degree of variability in the manifestations (or expressivity) of phenylketonuria in mental retardation and other effects has not been adequately examined. Investigation of the factors relating to this variability may provide information regarding the mechanics of pathology and lead to improved screening and therapeutic measures.
Active sleep and its role in the prevention of apoptosis in the developing brain

Abstract The aim of this study is to identify a possible function of Active Sleep (AS), also known as Rapid Eye Movement Sleep (REM) in humans, as a protective state during early Central Nervous System (CNS) development. Previous research suggest pharmacological agents that inhibit high levels of neuronal activity in the CNS (e.g., benzodiazepines, ethanol, and anesthetics) precipitate massive CNS programmed cell death (PCD), in developing mammals. AS is characterized by high levels of CNS activity at levels comparable to waking. AS occupies up to 75% of the circadian cycle in developing mammals (rodents from postnatal days 1–14 days (p1–p14), and humans from prenatal month seven to postnatal year one). Many studies have implicated AS as having an active role in the normal development of the visual system and have documented myriad behavioral anomalies as a result of AS deprivation. Reduced adult brain mass has also been observed after AS deprivation in developing rats during this period, however, no study to date has documented this process as it occurs (i.e., the cellular mechanisms that result in behavioral anomalies or reduced adult brain mass). The purpose of this study is to begin documentation of this process by utilizing histological techniques that identify the PCD process, if it occurs, after acute and prolonged AS deprivation in rats from ages p7 to p14 (a time of active synaptogenesis). Our methodology includes utilization of the α2-adrenergic receptor agonist clonidine, to deprive rat pups of AS at ages varying from p7 to p14. Pilot data from our laboratory has shown that an acute exposure to clonidine significantly reduces time spent in AS. The animals that were AS deprived also showed a statistically significant decrease in brain mass and have stained positively for PCD. If our hypotheses are correct, this research will have major implications with regard to determining the function(s) of REM sleep.
Interrelationships Between Prey Body Size and Growth of Age-0 Yellow Perch

Abstract We conducted laboratory experiments in the summers of 1986 and 1987 to examine the effects of Daphnia pulex body size and ration level on growth of age-0 yellow perch Perca flavescens. Daphnia pulex rations were set at 25 and 40% of yellow perch dry weight. Specific growth rate tended to be higher for smaller fish and decreased with fish size at both ration levels. For the 25% ration, the highest growth rates, 0.023 to 0.024 g/d, were observed when yellow perch were fed meals of D. pulex between 1.4 and 1.8 mm long; growth declined for prey sizes outside this size range. For the 40% ration, no relationship was found between body length of D. pulex and specific growth rate; the mean specific growth rate for the 40% ration was the same as the peak rate for the 25% ration. Multiple-regression analysis was used to examine the dependence of specific growth rate of yellow perch on initial fish length, prey size, and temperature. For the 25% ration, prey size and the square of prey size were the only va...
A method for the study of the incorporation of inorganic radiophosphorus into leukocyte deoxyribonucleic acid.

Abstract A modification of the Schmidt-Thannhauser procedure for isolating DNA coupled with a new method for DNA digestion and an adaptation of the Berenblum and Chain method for phosphorus determination have been shown to be suitable for use in studying the incorporation of inorganic P 32 into leukocyte DNA. With these techniques tracer doses as small as 2 μc/kg are permitted. Peak tagging of rabbit leukocytes was found to occur on the fourth day following injection. Disappearance of the label through the tenth day was virtually exponential.
The Role of Randall’s Plaques in the Pathogenesis of Calcium Stones

Purpose: Knowledge of the inciting lesion in kidney stone formation has remained rudimentary until quite recently. Randall theorized that areas of apatite plaque on the renal papillae would be an ideal site for an overgrowth of calcium oxalate to develop into a calculus. We reviewed in vivo data that have further defined the role of Randall’s plaques in stone disease.Materials and Methods: We examined a set of literature that tested 2 hypotheses, that is 1) Randall’s plaques are a specialized disease that begins as apatite in a unique region of the kidney due to local driving forces and anatomy, and 2) stones that arise from causes different from common calcium oxalate stones do not necessarily arise on plaque.Results: Intraoperative papillary and cortical biopsy specimens obtained during percutaneous nephrolithotomy from the kidneys of 3 types of stone formers (idiopathic calcium stone formers, patients with stones due to bariatric procedures and brushite stone formers) showed unique histopathological fi...
Rotavirus infection of human cholangiocytes parallels the murine model of biliary atresia.

Introduction: Biliary atresia (BA) is the leading indication for liver transplantation in the pediatric population. The murine model of BA supports a viral etiology, because infection of neonatal mice with rhesus rotavirus (RRV) results in biliary obstruction. Viral infection targets the biliary epithelium and development of the model is viral strain dependent. No study has yet determined whether human cholangiocytes are also susceptible to rotaviral infection. We established an in vitro human model using an immortalized human cholangiocyte cell line and primary human cholangiocytes obtained from explanted livers to determine human cholangiocyte susceptibility to rotavirus infection. Methods: Replication and binding assays were performed on immortalized mouse (mCL) and human(H69)cellsusingsixdifferentstrainsofrotavirus.Primaryhumancholangiocyteswere isolated from cadaveric livers, characterized in culture, and infected with RRV, which causes BA in mice, and another simian strain, TUCH, which does not cause BA in mice. Results: Immortalized mouse and human cholangiocytes demonstrated similar patterns of infectivity and binding with different strains of rotavirus. Both cell lines produced a significantly higher viral yield with RRV infection than with the other strains tested. In primary human cholangiocytes, which maintained their epithelial characteristics, as demonstrated by cytokeratin staining, RRV replicated to a yield 1000-fold higher than TUCH. Conclusions: Both immortalized and primary human cholangiocytes are susceptible to RRV infection in a fashion similar to murine cholangiocytes. These novel findings suggest rotavirus infection could have a potential role in the pathogenesis of human BA.
The Draft Genome of Planococcus donghaensis MPA1U2 Reveals Nonsporulation Pathways Controlled by a Conserved Spo0A Regulon

The Planococcaceae are extreme survivors, having been cultured from environments such as deep sea sediments, marine solar salterns, glaciers, permafrost, Antarctic deserts, and sea ice brine. The family contains both sporulating and nonsporulating genera. Here we present the unclosed, draft genome sequence of Planococcus donghaensis strain MPA1U2, a nonsporulating psychrotrophic bacterium isolated from surface coastal water of the Pacific Ocean.
Experimental and Numerical Study of Evaporative Heat Transfer From Ten- Micro Microchannels

Experimental and numerical results are presented for evaporative heat transfer from ten-micron square open-top channels. The radial channels are fabricated in epoxy photoresist on a two micron thick silicon membrane. The working fluid is pumped by capillary forces from a reservoir at the edge of the silicon membrane into the channels where it evaporates. The electrical power dissipated in a thin-film heater in the center of the membrane, the conduction heat transfer rate radially out of the membrane, and the rate of evaporation of the working fluid are measured. A three-dimensional finite difference, time-domain integration is used to predict sensible and latent heat transfer rates. Only 5-10% of the energy dissipated as heat in the thin film heater is carried away as latent heat by the evaporating working fluid. Computed temperatures and heat transfer rates are shown to match the experimental results.Copyright © 2006 by ASME
Susceptibility to Diet-Induced Hepatic Steatosis and Glucocorticoid Resistance in FK506-Binding Protein 52-Deficient Mice

Although FK506-binding protein 52 (FKBP52) is an established positive regulator of glucocorticoid receptor (GR) activity, an in vivo role for FKBP52 in glucocorticoid control of metabolism has not been reported. To address this question, FKBP52+/− mice were placed on a high-fat (HF) diet known to induce obesity, hepatic steatosis, and insulin resistance. Tissue profiling of wild-type mice showed high levels of FKBP52 in the liver but little to no expression in muscle or adipose tissue, predicting a restricted pattern of FKBP52 effects on metabolism. In response to HF, FKBP52+/− mice demonstrated a susceptibility to hyperglycemia and hyperinsulinemia that correlated with reduced insulin clearance and reduced expression of hepatic CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1), a mediator of clearance. Livers of HF-fed mutant mice had high lipid content and elevated expression of lipogenic genes (peroxisome proliferator-activated receptor γ, fatty acid synthase, and sterol regulatory el...
Model-based scheduling for networked control systems

In this paper, we introduce a model-based scheduling strategy to achieve ultimate boundedness stability in the sensor-actuator networked control systems, where the communication network between the sensor and the network controller is subject to time-varying network induced delays and data-packet dropouts. An estimator and a nominal model of the plant are used explicitly at the controller node to generate control action and schedule control action updates. The data transmissions from the sensor to the network controller are “self-triggered” by imposing the scheduling of the data packet transmissions to meet a soft deadline, while the control action updates generated by the network controller are “event-triggered”, with a new measurement of the nominal model's state obtained to update control action whenever a triggering condition is satisfied or whenever the state of the nominal model is reset by the estimator.
Biological applications of colloidal nanocrystals

Due to their interesting properties, research on colloidal nanocrystals has moved in the last few years from fundamental research to first applications in materials science and life sciences. In this review some recent biological applications of colloidal nanocrystals are discussed, without going into biological or chemical details. First, the properties of colloidal nanocrystals and how they can be synthesized are described. Second, the conjugation of nanocrystals with biological molecules is discussed. And third, three different biological applications are introduced: (i) the arrangement of nanocrystal–oligonucleotide conjugates using molecular scaffolds such as single-stranded DNA, (ii) the use of nanocrystal–protein conjugates as fluorescent probes for cellular imaging, and (iii) a motility assay based on the uptake of nanocrystals by living cells.
The psychotherapist's duty to act reasonably to prevent suicide: A proposal to allow rational suicide

It is proposed that society should re-examine its assumptions about suicide. Rational suicide is viewed as an extension of the right to die. After a review of the legal liability of the psychotherapist and psychiatric facility for both inpatient and outpatient suicide, the author presents an analysis of philosophical, ethical, and psychoanalytic arguments for allowing rational suicide. It is argued that emotional pain should be given more legitimacy as a reason for suicide. The decision to live or to die is argued to best rest with the individual. Language: en
Preparation and processing of rare earth chalcogenides

Rare earth chalcogenides are initially prepared by a direct combination of the pure rare earth metal and the pure chalogen element with or without a catalyst. The use of iodine (10 to 100 mg) as a fluxing agent (catalyst), especially to prepare heavy lanthanide chalcogenides, greatly speeds up the formation of the rare earth chalcogenide. The resultant powders are consolidated by melting, pressure assisted sintering (PAS), or pressure assisted reaction sintering (PARS) to obtain near theoretical density solids. Mechanical alloying is a useful technique for preparing ternary alloys. In addition, mechanical alloying and mechanical milling can be used to form metastable allotropic forms of the yttrium and heavy lanthanide sulfides. Chemical analysis techniques are also described because it is strongly recommended that samples prepared by melting should have their chemical compositions verified because of chalogen losses in the melting step.
Oxidation of nuclear-reactor-grade graphite

Abstract An analytical solution is developed for transient, constant-temperature and constant-pressure oxidation of a hollow, porous graphite cylinder by oxygen diffusing from the cylinder surfaces. The following approximations are used: a binary diffusion approximation for all species, a constant value for the product of density and diffusion coefficient, negligibly small mass-average velocity and axial diffusion, a single heterogeneous reaction producing CO 2 , and first-order reaction kinetics with respect to oxygen. The analytical results are in good agreement with data obtained by Klaschka et al for an experimental configuration designed to provide constant-temperature and constantpressure oxidation of a hollow graphite cylinder. Studies of the type presented in this paper are of interest in connection with evaluations of nuclear reactor safety, including possible graphite combustion of the type that may have occurred in connection with the Chernobyl reactor failure.
Outcomes assessment: an examination of the ETS major field test and the comprehensive business exam

This study is the first to examine student performance differences between the major field test in business (MFTB) and the comprehensive business exam (CBE). Results reveal students performed at a statistically significant 50.8 percentile ranking on the CBE compared to a 38.0 percentile ranking on the MFTB. Additionally, this study finds that students transferring business core courses with a grade point average (GPA) of 2.5 or lower perform at a statistically significant lower level on both the MFTB and the CBE than those transferring business core courses with GPAs higher than 2.5. These findings have important implications for assessment of learning purposes.
Topographic electroencephalographic study of transient ischemic attacks

Abstract Twenty-five patients with TIAs in the carotid artery distribution were studied by means of computed mapping of EEG (CME) and conventional EEG. In addition, CT scan and cerebral angiography, and in 10 patients rCBF measurements were performed. The CME provided topographic maps of the average power spectra for each of 6 frequency bands from 2.0 to 29.5 Hz which were displayed two-dimensionally in a color-coded iso-power format. EEG abnormalities were analyzed and the results of the two different methods of EEG interpretation were compared. Sixty-eight percent of the patients showed unilateral abnormalities on CME appropriately lateralized to the clinical symptoms even after these symptoms had cleared completely. Furthermore, 88% of those who were examined within 2 weeks of last TIA showed corresponding CME abnormalities. Only 3 out of 10 TIA patients who had rCBF studies showed reduction of blood flow on the appropriate hemisphere, whereas 7 of the 10 patients had corresponding CME abnormalities. Comparing the results of the CME and of conventional EEG reading revealed the CME to be slightly more sensitive in detecting asymmetrical voltage depression of background activity than the conventional reading of the EEG, while the latter detected low amplitude sporadic activities which were missed by CME. Both methods were equally sensitive in detecting slow wave foci and non-transient symmetrical changes. The two most significant points of this report are the following: first, 68% of the TIA patients studied had residual unilateral abnormalities in CME in their symptom-free period. In the subset of patients subjected to rCBF studies only 30% showed residual flow aberrations, whereas 70% of the same subset demonstrated unilateral abnormalities in CME. Second, though conventional EEG reading by an experienced electroencephalographer can nearly match the performance of CME the CME format makes subtle but useful EEG findings readily available to the uninitiated. The CME also quantifies the data making objective comparisons more amenable to software manipulations for further studies.
Simple spectrophotometric method for determination of zirconium or hafnium in selected molybdenum-base alloys.

A simple analytical procedure is described for accurately and precisely determining the zirconium or hafnium content of molybdenum-base alloys. The procedure is based on the reaction of the reagent Arsenazo III with zirconium or hafnium in strong hydrochloric acid solution. The colored complexes of zirconium or hafnium are formed in the presence of molybdenum. Titanium or rhenium in the alloy have no adverse effect on the zirconium or hafnium complex at the following levels in the selected aliquot: Mo, 10 mg; Re, 10 mg; Ti, 1 mg. The spectrophotometric measurement of the zirconium or hafnium complex is accomplished without prior separation with a relative standard deviation of 1.3 to 2.7 percent.