cssi/SciSciGPT-SciSciNet huggingface dataset:
Bexarotene normalizes chemotherapy-induced myelin decompaction and reverses cognitive and sensorimotor deficits in mice

Frequently reported neurotoxic sequelae of cancer treatment include cognitive deficits and sensorimotor abnormalities that have long-lasting negative effects on the quality of life of an increasing number of cancer survivors. The underlying mechanisms are not fully understood and there is no effective treatment. We show here that cisplatin treatment of mice not only caused cognitive dysfunction but also impaired sensorimotor function. These functional deficits are associated with reduced myelin density and complexity in the cingulate and sensorimotor cortex. At the ultrastructural level, myelin abnormalities were characterized by decompaction. We used this model to examine the effect of bexarotene, an agonist of the RXR-family of nuclear receptors. Administration of only five daily doses of bexarotene after completion of cisplatin treatment was sufficient to normalize myelin density and fiber coherency and to restore myelin compaction in cingulate and sensorimotor cortex. Functionally, bexarotene normalized performance of cisplatin-treated mice in tests for cognitive and sensorimotor function. RNAseq analysis identified the TR/RXR pathway as one of the top canonical pathways activated by administration of bexarotene to cisplatin-treated mice. Bexarotene also activated neuregulin and netrin pathways that are implicated in myelin formation/maintenance, synaptic function and axonal guidance. In conclusion, short term treatment with bexarotene is sufficient to reverse the adverse effects of cisplatin on white matter structure, cognitive function, and sensorimotor performance. These encouraging findings warrant further studies into potential clinical translation and the underlying mechanisms of bexarotene for chemobrain.
Quantification of Metastatic Prostate Cancer Whole-Body Tumor Burden with 18F-FDG PET Parameters and Associations with Overall Survival After First-Line Abiraterone or Enzalutamide: A Single-Center Retrospective Cohort Study.

RATIONALE: New biomarkers for metastatic prostate cancer are needed. The aim of this study was to evaluate the prognostic value of FDG-PET whole body tumor burden parameters in patients with metastatic prostate cancer who received first line abiraterone or enzalutamide therapy. METHODS: Retrospective study of patients with metastatic castration-sensitive (mCSPC, n = 25) and metastatic castration-resistant prostate cancer (mCRPC, n = 71) who underwent 18F-FDG-PET/CT within 90 days before first-line treatment with abiraterone or enzalutamide at a tertiary care academic cancer center. Whole-body tumor burden on PET/CT was quantified as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) and correlated with overall survival (OS) probabilities using Kaplan-Meier curves and Cox models. RESULTS: The median follow-up in survivors was 56.3 months (IQR: 37.7, 66.8); the median OS for patients with mCRPC and mCSPC was 27.8 and 76.1 months (p<.001). On univariate analysis, the OS probability of mCRPC patients was significantly associated with plasma levels of alkaline phosphatase (HR: 1.90, p<.001) and lactate dehydrogenase (HR: 1.01, p<.001), hemoglobin levels (HR: 0.80, P = .013), whole body SUVmax (HR: 1.14, p<0.001), the number of FDG-avid metastases (HR: 1.08, p<0.001), whole body MTV (HR: 1.86, p<.001) and TLG (HR: 1.84, p<.001). In multivariable analysis with stepwise variable selection, hemoglobin levels (HR: 0.81, P = 0.013) and whole-body TLG (HR: 1.88, p<.001) were independently associated with OS. In mCSPC patients, no significant association was observed between these variables and OS. CONCLUSION: In patients with mCRPC receiving first-line treatment with abiraterone or enzalutamide, FDG PET WB TLG is independently associated with OS and might be used as quantitative prognostic imaging biomarker.
Targeting an anchored phosphatase-deacetylase unit restores renal ciliary homeostasis

Abstract Pathophysiological defects in water homeostasis can lead to renal failure. Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder associated with abnormal cytoskeletal dynamics in the kidney collecting ducts and perturbed calcium and cAMP signaling in the ciliary compartment. We show that collecting ducts in mice lacking the A-Kinase anchoring protein AKAP220 exhibit enhanced development of primary cilia. Mechanistic studies reveal that AKAP220-associated protein phosphatase 1 (PP1) mediates this phenotype by promoting changes in the stability of histone deacetylase 6 (HDAC6) with concomitant defects in actin dynamics. This proceeds through a previously unrecognized adaptor function for PP1 as all ciliogenesis and cytoskeletal phenotypes are recapitulated in mIMCD3 knock-in cells expressing a phosphatase-targeting defective AKAP220-ΔPP1 mutant. Pharmacological blocking of local HDAC6 activity alters cilia development and reduces cystogenesis in kidney-on-chip and organoid models of ADPKD. These findings identify the AKAP220-PPI-HDAC6 pathway as a key effector in primary cilia development.
Percutaneous Mitral Valve Repair in Cardiac Amyloidosis and Severe Mitral Regurgitation.

Abstract Amyloidosis is an infiltrative disease with severe impact on the cardiac anatomy resulting in structural changes 1 . Mitral valve insult from the infiltrative process, although rare, has been known to cause severe mitral regurgitation 4 . Due to underlying comorbidities these patients may not be surgical candidates. 17 , 18 , 19 , 20 The role of percutaneous mitral valve repair in cardiac amyloidosis has been described in a few prior cases. 4 , 15 We review the epidemiology, diagnosis, and treatment of cardiac amyloidosis. We also highlight prior cases described in the literature of cardiac amyloidosis and severe mitral regurgitation, while discussing the role of percutaneous mitral valve repair in these patients.
Prostate Cancer Immunotherapy-Finally in From the Cold?

Purpose of review Despite significant progress, patients with metastatic prostate cancer continue to have poor prognosis. Immunotherapy has revolutionized cancer care for many tumor types but has a limited role in the treatment of prostate cancer. This review discusses the promise of immunotherapy in prostate cancer treatment with an emphasis on emerging therapeutic targets. Recent findings Most prostate tumors have low tumor mutational burden and lack immunogenicity, representing significant hurdles to induction of anti-tumor immunity. However, recent research centered on deciphering key mechanisms of immune resistance in the prostate tumor microenvironment has led to the discovery of a range of new treatment targets. These discoveries are currently being translated into innovative immunotherapy clinical trials for patients with prostate cancer. Recent progress includes early evidence of activity for these novel approaches and the identification of potential predictive biomarkers of response. Novel treatment strategies using new antigen-directed therapies, drugs targeting the immunosuppressive tumor microenvironment, and combination immunotherapy therapies show great potential and are currently in clinical development. In addition, a deeper understanding of predictors of response and resistance to immunotherapy in prostate cancer is allowing for a more personalized approach to therapy.
The Effect of Cultural Trust on Cooperation in Two Behavioral Experiments

Trust is an important factor for cooperation in social dilemmas because of uncertainty and free-riding fears. Many contemporary social problems are characterized by uncertainty because they depend ...
Macroscopic to Microscopic - A Case of Crohn's Disease Progressing to Collagenous Colitis.

The association between microscopic colitis (MC) and inflammatory bowel disease (IBD) is uncertain and infrequently reported. Rare cases in the literature consist of simultaneous MC and IBD, or progression of one condition to the other. We present a unique case of clinically and endoscopically diagnosed and successfully treated IBD that revealed MC on histology months later due to reappearance of diarrhea. Common pathophysiologic mechanisms, such as tumor necrosis factor α and T helper type 1 cells, may explain the MC and IBD relationship. During endoscopy, a prompt biopsy should be taken if suspicious for MC, thus decreasing the duration of patient's symptoms and saving healthcare costs.
Comprehensive Review of the Literature to Teach Campus Navigation to Young Adults with Intellectual and Developmental Disabilities

Young adults with intellectual and developmental disabilities (I/DD) experience unique challenges as they transition to living and learning on a college campus, including independent campus navigation. The purpose of this study was to present the results of a comprehensive literature review of interventions designed to improve campus navigation among young adults with I/DD. A second purpose of this review is to present the practical considerations of the interventions to support informed instructional decisions among practitioners.
Structural Results for POMDPs

Partially observable Markov decision processes (POMDP) are used to describe stochastic systems with incomplete information about the state of the system. Owing to the complexity of POMDP analysis, a primary goal is to identify conditions under which the optimal policy has a structure that is simple to implement. A priori knowledge of policy structure makes its computation, communication, and implementation fast and effective. This article discusses the optimal policy structures for the general POMDP model and provides examples of such structures in the context of maintenance optimization. A brief overview of the research results concerning policy structures in different application areas is provided. Keywords: Markov decision process; control limit policy; reduction; POMDP; maintenance optimization
Schelling Formalized: Strategic Choices of Non-Rational Personas

We introduce a framework that explains non-rationality in non-repeated games. In our framework a player i adopts a binding "persona" - a temporary utility function --- that they honestly signal before play. By adopting a "non-rational" persona, i may cause changes in their opponents' behavior that increases $i$'s true utility. We use this framework to explain experimental data in the Traveler's Dilemma and to show how cooperation can arise in the Prisoner's Dilemma (PD). We then predict a crowding out phenomenon in the PD. We also predict a tradeoff between the robustness and the benefit of cooperation in the PD.
A necessary and sufficient condition for lifting the hyperelliptic involution

Let X denote a Riemann surface which possesses a fixed point free group of automorphisms with a hyperelliptic orbit space. A criterion is proved which determines whether the hyperelliptic involution lifts to an automorphism of X. Necessary and sufficient conditions are stated which determine when a lift of the hyperelliptic involution is fixed point free. A complete determination is made of the abelian groups which may arise as automorphism groups of surfaces which possess a fixed point free lift. Hyperelliptic Riemann surfaces are natural objects of interest and have been studied quite extensively. They have simple defining equations and, since they admit an involution, they constitute a family of Riemann surfaces whose members admit a nontrivial automorphism. Covering surfaces of hyperelliptic surfaces have also been closely examined. The question of when a hyperelliptic surface can have a hyperelliptic cover was investigated in [2], [5], [8], and [10]. It was shown in [6] that if a Riemann surface X admits an abelian, fixed point free automorphism group H, then the hyperelliptic involution lifts to X. In addition, in [6] it was stated that if H is cyclic of prime order, then the lift of the hyperelliptic involution is never fixed point free. Further results concerning when the hyperelliptic involution lifts to a covering surface are contained in [1]. Let X be a compact Riemann surface which admits a fixed point free automorphism group H < Aut(X) with a hyperelliptic orbit space. In this paper we give necessary and sufficient conditions which determine when the hyperelliptic involution lifts to X. In addition, we give necessary and sufficient conditions which determine when such a lift is fixed point free. A complete determination is made of the abelian groups which may arise as automorphism groups of surfaces which possess a fixed point free lift. These results are combined with results in [12] to yield specific examples of automorphism groups yielding a hyperelliptic orbit space.
α,β-Methylene-adenosine 5′-Triphosphate: A COMPETITIVE INHIBITOR OF ADENYLATE CYCLASE IN FAT AND LIVER CELL MEMBRANES

Abstract The ATP analog, α,β-methylene-adenosine 5'-triphosphate (Ap(CH2)pp), competitively inhibits the basal as well as the glucagon- and NaF-stimulated activity of adenylate cyclase in isolated liver membrane preparations. The dissociation constant (Ki) of the inhibitor, 0.5 mm, is independent of the concentration of glucagon or NaF and is somewhat lower than the apparent Km for ATP. The phosphonic acid analog of ATP also inhibits competitively (Ki, 1.2 mm) the epinephrine-stimulated adenylate cyclase activity of membranes prepared from homogenates of isolated fat cells. The enzyme activity stimulated by NaF in these membranes is also inhibited by Ap(CH2)pp. The ADP analog, α,β-methylene-adenosine 5'-diphosphate does not significantly inhibit the activity of adenylate cyclase of liver cell membranes.
Central nervous system receptors involved in mediating the inhibitory action of neuropeptide Y on luteinizing hormone secretion in the male rhesus monkey (Macaca mulatta).

An earlier finding that gonadotropin-releasing hormone (GnRH) secretion may be triggered prematurely in the juvenile male monkey by central administration of 1229U91, a Y1 receptor antagonist, contributed to our current hypothesis that neuropeptide Y (NPY) is a major component of the brake that holds pulsatile GnRH release in check during prepubertal development in primates. However, 1229U91 is also a Y4 receptor agonist, and the present study was conducted to further examine the role of the Y1 receptor in mediating the putative inhibitory action of NPY on GnRH release. Agonadal juvenile and postpubertal male monkeys were implanted with i.v. and i.c.v. cannulae to gain continuous access to the venous and cerebroventricular circulations without sedation. Luteinizing hormone (LH) secretion was measured to provide an indirect index of GnRH release. The specific Y1 antagonists, VD-11 (476 microg; n = 4) and isopropyl 3-chloro-5-[1-((6-[2-(5-ethyl-4-methyl-1,3-thiazol-2-yl)ethyl]-4-morpholin-4-ylpyridin-2-yl)amino)ethyl]phenylcarbamate (Compound A, 300 microg; n = 4), did not mimic the stimulatory action of 1229U91 on GnRH secretion in the juvenile male monkey. Additionally, neither NPY (200 microg; n = 2), a general Y receptor agonist, nor rPP (100 microg; n = 4), a Y4 agonist, mimicked the action of 1229U91 in stimulating GnRH release. Moreover, previous exposure of the hypothalamus of juvenile monkeys (n = 5) to NPY (660 microg) failed to block 1229U91-induced (200 microg) GnRH release. However, the action of NPY (364 microg) in inhibiting GnRH release postpubertally was attenuated by 1229U91 (300 microg). We conclude that, although the action of exogenous NPY to suppress GnRH release from the postpubertal hypothalamus appears to be mediated, at least in part, by the Y1 receptor, the existence of a Y1 receptor pathway inhibitory to GnRH release in the prepubertal hypothalamus remains to be substantiated.
Formalization of RBAC policy with object class hierarchy

Formal methods and reasoning techniques can be useful tools for the representation and analysis of security policies and access control procedures. This paper presents a logical approach to representing and evaluating role-based access control (RBAC) policies, using description logics and a proof method, called tableaux. We propose a new variation of the RBAC model with a classification mechanism for objects. The key feature supported is the ability to model object classes, and class hierarchies used to restrict the validity and to control the propagation of authorization rules. We also demonstrate how access control decisions are made by tableaux, considering role and class hierarchies.
A VLSI circuit of lamprey unit pattern generator

The purpose of this research is to develop an analog VLSI electronic circuit that mimics the behavior of the biological lamprey spinal cord. The lamprey is an eel-like lower vertebrate with a relatively simple nervous system. The pattern generator for locomotion is distributed along the 100 spinal segments of the lamprey spinal cord and can be treated as a chain of coupled unit pattern generators (uPG) with oscillatory properties. In this work we consider a 4 neuron uPG model. Bifurcation analysis of this model indicates a wide range of behaviors. In addition, a CMOS analog integrated circuit has been designed, fabricated and tested which models the biological lamprey unit pattern generator. Measurement results show that the electronic circuit behavior is qualitatively similar to that of the numerical model.
The delivery of critical care services in US trauma centers: is the standard being met?

Background Although there is substantial evidence supporting the benefits of an intensivist model of critical care delivery, the extent to which this model has been adopted by trauma centers across the United States is unknown. We set out to evaluate how critical care is delivered in Level I and II trauma centers and the extent to which these centers implement evidence-based patient care practices known to improve outcome. Methods All Level I and Level II trauma centers in the United States were surveyed using a previously validated questionnaire pertaining to the organizational characteristics of critical care units. Questions identifying the impediments to the implementation of an intensivist model of critical care delivery were added to the original survey. An intensivist model intensive care unit (ICU) was defined as one meeting all of the following criteria: a) the physician director was board certified in critical care; b) >50% of physicians responsible for care were board certified in critical care; c) an intensivist made daily rounds on the patients; and d) an intensive care team had the authority to write orders on the patients. The survey respondents were also queried regarding the extent to which they complied with evidence-based guidelines for care in the ICU. Results The overall response rate was 65% (295 centers). Only 61% of Level I centers and 22% of Level II centers provided an intensivist model of critical care delivery. Sixty-nine percent of centers had a form of collaborative care with an intensivist, but few centers had dedicated intensivists without responsibilities outside the ICU. The most common reason cited for not involving an intensivist in the delivery of critical care services was a concern regarding a loss of continuity of care. There was limited implementation of evidence-based practices in the ICU; the model of critical care delivery had no effect on rates of implementation of these practices. Conclusion The process of trauma center verification and designation should assure a high quality of trauma care. In keeping with these expectations of quality, the delivery of critical care services in trauma centers should evolve to a model that both includes the trauma surgeon in the care of the injured and allows for collaboration with a dedicated intensivist, who may or may not be a surgeon. The benefits of an intensivist model might be distinct from the utilization of evidence-based practices, suggesting that there might be incremental benefit in using these practices as markers of quality.
Estimation of the log-normal mean

The most commonly used estimator for a log-normal mean is the sample mean. In this paper, we show that this estimator can have a large mean square error, even for large samples. Then, we study three main alternative estimators: (i) a uniformly minimum variance unbiased (UMVU) estimator; (ii) a maximum likelihood (ML) estimator; (iii) a conditionally minimal mean square error (MSE) estimator. We find that the conditionally minimal MSE estimator has the smallest mean square error among the four estimators considered here, regardless of the sample size and the skewness of the log-normal population. However, for large samples (n > or = 200), the UMVU estimator, the ML estimator, and the conditionally minimal MSE estimators have very similar mean square errors. Since the ML estimator is the easiest to compute among these three estimators, for large samples we recommend the use of the ML estimator. For small to moderate samples, we recommend the use of the conditionally minimal MSE estimator.
Link prediction of multimedia social network via unsupervised face recognition

We propose a new challenge for predicting links of social networks by unsupervised face recognition on photo albums. We solve the task by formulating it into Kernel Set Discovery problem. We enhance Affinity Propagation algorithm to tackle the problem with more constraints. More specifically, the face cannot appear more than once in the same photo and we impose constraints such that detected face images in the same photograph are never clustered into the same person. We construct a synthetic dataset based on AT\&T image benchmark for empirical validation. Moreover, we validate our algorithms by a real world application which contains a real friend relation on the Web 2.0 social network system. Results indicate our Constraint Affinity Propagation method is suitable to unsupervisedly predict links of social network.
Theory for the Solubility of Gases in Polymers: Application to Monatomic Solutes

The polymer reference interaction site model (PRISM theory) is applied to the problem of calculating the solubility of monatomic gases in amorphous polyethylene. One can consider this system as an ...
Localization in the core- and 4d-electrons of niobium metal

Abstract The first direct observation of the localization of a fraction of the 4d-electron in Nb as well as some pronounced core deformation is reported. The theoretical predictions of Harmon and Ho [1] and of Morruzi et al. [2] are used to extract the corresponding information from the data. A Nb spherical crystal of 0.2 cm radius has been measured on the γ-ray single crystal diffractometer of the Missouri University Research reactor. This instrument uses the 153 Sm wavelength at 0.1202 A. The sample was at room temperature. It is shown that the spherically symmetric 4d-electron localization occurs between 0.51 and 0.67 A away from the nucleus positions and that the “core effect” is seen between 0.32 and 0.37 A.
Uterine receptor-estradiol complexes and their interaction with nuclear binding sites.

Abstract Extensive analysis of nuclear bound estrogen receptor complexes (RnE) demonstrated the presence of two high affinity binding sites: K d , 0.10–0.20 nM and 2–4 nM, respectively. The high affinity complex constitutes about 30% of the total quantity of nuclear bound complexes. In addition two types of binding sites for RnE complexes were demonstrated by the resistance of RnE complexes to salt extraction by 0.4 M KCl. Immature rats were injected with estradiol and at various times after the injection the uteri were removed, homogenized and fractionated. The quantities of estrogen-receptor complexes in the cytosol (Re), in 0.4 M KCl-extracts of the nuclear pellets (Rn-extractable) and in the nuclear pellet after KCl-extraction (Rn-resistant) were determined. Rc rapidly declined during the first 30 min and then increased slowly over the next two h. Rn-extractable increased rapidly during the first 20 min after injection and then dropped to control levels over the following 160min. Rn-resistant increased slowly reaching a maximum after 60 min and then declining slowly during the subsequent 120 min. When uterine nuclear fractions from rats treated with 2.5μg of estradiol l h prior to sacrifice, were assayed for the quantity of receptor-steroid complexes, it was found that they contained about 5-6 times the amount found in the corresponding fraction from rats treated with 0.1 μg. About 80% of the receptor-hormone complexes found in the nucleus after injection of the high dose of estrogen was extractable by 0.4 M KCl, whereas the corresponding figure after the low dose treatment was approx. 50%. These results show the presence of two classes of receptor-estradiol complexes with different affinities for the hormone. Both classes of complexes exist in the nucleus partly as KCl-extractable and partly as KCl-resistant. The shift from Rn-extractable to Rn-resistant form might reflect changes in the conformation of the RnE complexes upon association with specific acceptor sites.
The Developmental History of the Motor Neuron

The F.O. Schmitt Lecture and Prize in Neuroscience was established by the Associates of the Neurosciences Research Program in 1973 to mark the seventieth birthday of Francis O. Schmitt, founder of the organization. The purpose of the award is to recognize, encourage, and advance the achievement of excellence in neuroscience.
Synthesis of ribosomal RNA on a protein-DNA complex isolated from bacteria: A comparison of ribosomal RNA synthesis in vitro and in vivo

Abstract RNA was synthesized without added RNA polymerase on protein-DNA complexes isolated from Escherichia coli and Bacillus megaterium. The RNA product had a higher average guanosine/uridine ratio than RNA synthesized from the purified DNA with purified RNA polymerase. A portion of the RNA having a high G U ratio hybridized efficiently to DNA, but only at small RNA/DNA inputs. This hybridization was competed by purified ribosomal RNA and the amount of rRNA required to give maximum competition was the amount required to saturate the rRNA-complementary DNA. In control experiments there was no detectable competition by rRNA with RNA synthesized from purified DNA. It is concluded that a significant fraction of the RNA synthesized in vitro from the protein-DNA complex is rRNA. The actual value of this fraction (45 ± 5% under the growth conditions used) was determined in competition hybridization experiments in which labeled rRNA was included to define hybridization efficiencies. The same value for this rRNA fraction was found in pulse-labeled RNA synthesized in vivo, suggesting that the distribution of RNA polymerase molecules on the DNA of the complex was similar to that in the cell. Results given here and previously reported indicate that synthesis on the complex was primarily a result of chain extension, and that little or no initiation of RNA chains occurs. The amount of rRNA synthesized at the time the reaction terminated was equivalent to about 480 molecules each of 23 s and 16 s size per DNA molecule of 3 × 109 daltons. These two observations together indicated that there were about a hundred RNA polymerase molecules bound to each rRNA (23 s) cistron in the protein-DNA complex. The initial rate of total RNA synthesis on the complex per unit amount of DNA was estimated to be about 20% of the rate occurring in vivo.
Reversal in enantioselectivity of tert-butyl versus phenyl-substituted bis(oxazoline) copper(II) catalyzed hetero Diels-Alder and ene reactions. Crystallographic and mechanistic studies

Abstract X-Ray crystal structures of the Cu[(S,S)-tert-Bu-bis(oxazoline)](H2O)2(SbF6)2 (6), Cu[(S,S)-Ph-bis(oxazoline)](H2O)2(SbF6)2 (7), and Cu[(S,S)-iso-Pr-bis(oxazoline)](H2O)2(SbF6)2 (8) complexes are presented. Implications of the structural details are considered in the context of the opposite enantiofacial biases conferred by complexes Cu[(S,S)-tert-Bu-bis(oxazoline)](X)2 (1, X = OTf or SbF6) and Cu[(S,S)-Ph-bis(oxazoline)](X)2 (2) in hetero Diels-Alder and glyoxylate ene reactions. Structural and mechanistic studies suggest that a change in geometry at the metal center is not necessarily responsible for the reversal in enantioselectivity.
Congenital calcinosis cutis of the ear

Congenital calcinosis cutis is a relatively rare event. Herein we report 3 cases of congenital calcinosis cutis that all appeared in the exact same location on the ear. A possible mechanism of pathogenesis is discussed.
Chemical reactivities of hafnium and its derived boride, carbide and nitride compounds at relatively mild temperature

MB 2 /SiC composites are materials of choice for ultra-high-temperature structural applications, primarily in the aerospace arena. These composites are processed in a hot-press operation at a temperature range of 1900 to 2200°C. This article assesses potential mild-temperature (below 1500°C) chemical reactions that may lead to structures and coatings made of HfB 2 /SiC under pressureless or mild-pressure conditions. The reactions are anticipated to be involved in reactive and shape-forming processes, where ceramic precursors and/or reactive powders are incorporated. This article pays special attention to exothermic reactions as well as to formers of a liquid phase; both can aid the desired phase formation, microstructure development, and sintering of the composite under milder conditions than currently practiced. Reactions between loosely mixed powders with melting points significantly above 1500°C were detected by X-ray diffraction (XRD) analyses. Significant solid-phase reactions of the loose powder mixtures were observed at this mild temperature in powder form. Preliminary microstructural studies using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X-ray Spectroscopy (EDX) techniques have confirmed the presence of unique reaction mechanisms between the loosely connected particles. Good examples are the reactions between Hf powder and powders of BN or B 4 C, all having melting points above 2200°C, which form at 1500°C, or below HfB 2 /HfN and HfB 2 /HfC crystalline domains, respectively. These reactions are less intuitive than the reaction with B 2 O 3 , which forms HfB 2 /HfO 2 , potentially via molten or gaseous phases of boron oxide.
Chlorpromazine inhibits loss of contractile function, compliance and ATP in ischemic rabbit heart.

Abstract Using a modified Langendorf preparation, rabbit hearts were either continuously perfused at 37°C for 150 min, in the presence of O 2 and substrate, or after a 30 min equilibration period exposed to global ischemia followed by 30 min of reperfusion. Ischemia, for 90 min at 27°C or for 60 min at 37°C was compared. Perfusion pressure, heart rate, and ventricular volume were maintained constant. Contractile function and metabolic status were assessed. The effect of chlorpromazine, administered (30 mg/kg IP) 30 min prior to sacrifice, was compared to the untreated animal. 1. (1) Chlorpromazine had little effect on the contractile function or metabolic status of hearts continuously perfused for 150 min in the presence of O 2 and substrate. 2. (2) The chloropromazine-treated hearts maintained contractile function and metabolic status at preischemic levels following exposure to 90 min of global ischemia at 27°C and reperfusion at 37°C. Untreated hearts exhibited a severe deterioration in both contractile and metabolic parameters under the same conditions. Both untreated and chlorpromazine-treated hearts exhibited loss of contractile function after 60 min ischemia at 37°C; untreated hearts had undetectable ATP levels while chlorpromazine-treated hearts exhibited low levels of ATP. 3. (3) Untreated hearts, exposed to 90 min of ischemia at 27°C, exhibited a significant loss in compliance, while the compliance of chlorpromazine-treated hearts was unchanged from pre-ischemic levels. Reperfusion of untreated hearts, after 60 min of ischemia at 37°C, led to further loss of compliance, while chlorpromazine-treated hearts remained at the ischemic level. 4. (4) Thus, chloropromazine confers significant protection against loss of contractility, loss of ATP and decrease in compliance induced by ischemia at 27°C and prevents the further post-ischemic rise in diastolic tension after 60 min of ischemia at 37°C.
Development of spherical gaussian-based point charge models for the evaluation of electrostatic potentials

Abstract A set of charge- and dipole moment-conserving point charge models of the electron density of a spherical Gaussian-based wavefunction is described. A particular model may be chosen to satisfy the computational and/or accuracy requirements of a given application. Criteria for selection of models for the evaluation of electrostatic potentials are detailed and tested in an application to the porphyrin molecule.
Ontogenesis of receptive field characteristics in the dorsal lateral geniculate nucleus of the rabbit

The responses of rabbit dorsal lateral geniculate neurons to light or optic nerve shock were tested for 415 units in 43 rabbit pups 2--20 days of age. Units were driven by optic nerve shock at the youngest ages tested, but could not be driven by light until postnatal day six. Examples of each of the three prominent categories of receptive fields found in the adult were first observed at 8 days of age. Cells with receptive field properties not characteristic of the dorsal lateral geniculate nucleus of the adult were encountered until 17 days of age. The percentage of neurons with uniform and motion sensitive receptive fields approached adult levels soon after eye opening (11--12 days) but the percentage of cells with concentric receptive fields showed a steady increase throughout the neonatal period studied. The relevance of our data to the development of the visual response in the dorsal lateral geniculate nucleus and striate cortex is discussed.
Interactions of Dust Grains with Coronal Mass Ejections and Solar Cycle Variations of the F-Coronal Brightness

The density of interplanetary dust increases sunward to reach its maximum in the F corona, where its scattered white-light emission dominates that of the electron K corona above about 3 Solar Radius. The dust will interact with both the particles and fields of antisunward propagating coronal mass ejections (CMEs). To understand the effects of the CME/dust interactions we consider the dominant forces, with and without CMEs. acting on the dust in the 3-5 Solar Radius region. Dust grain orbits are then computed to compare the drift rates from 5 to 3 Solar Radius. for periods of minimum and maximum solar activity, where a simple CME model is adopted to distinguish between the two periods. The ion-drag force, even in the quiet solar wind, reduces the drift time by a significant factor from its value estimated with the Poynting-Robertson drag force alone. The ion-drag effects of CMEs result in even shorter drift times of the large (greater than or approx. 3 microns) dust grains. hence faster depletion rates and lower dust-pain densities, at solar maxima. If dominated by thermal emission, the near-infrared brightness will thus display solar cycle variations close to the dust plane of symmetry. While trapping the smallest of the grains, the CME magnetic fields also scatter the grains of intermediate size (0.1-3 microns) in latitude. If light scattering by small grains close to the Sun dominates the optical brightness. the scattering by the CME magnetic fields will result in a solar cycle variation of the optical brightness distribution not exceeding 100% at high latitudes, with a higher isotropy reached at solar maxima. A good degree of latitudinal isotropy is already reached at low solar activity since the magnetic fields of the quiet solar wind so close to the Sun are able to scatter the small (less than or approx. 3 microns) grains up to the polar regions in only a few days or less, producing strong perturbations of their trajectories in less than half their orbital periods. Finally, we consider possible observable consequences of individual CME/dust interactions. We show that the dust grains very likely have no observable effect on the dynamics of CMEs. The effect of an individual CME on the dust grains, however, might serve as a forecasting tool for the directions and amplitudes of the magnetic fields within the CME.
High-performance liquid chromatographic assay for the determination of total and free topotecan in the presence and absence of anti-topotecan antibodies in mouse plasma

A rapid and sensitive high-performance liquid chromatographic (HPLC) assay has been developed to allow determination of total (i.e. bound and unbound) and free (i.e. unbound) topotecan (TPT) in mouse plasma in the presence and absence of anti-TPT antibodies. The chromatographic analysis was carried out using reversed-phase isocratic elution with a Nova-Pak C18 column (3.9 mm x 150 mm, 4 microm) protected by a Nova-Pak C18 guard column (3.9 mm x 20 mm, 4 microm), where 10 mM KH(2)PO(4)-methanol-triethylamine (72:26:2 (v/v/v), pH 3.5) was used as the mobile phase. Topotecan was quantified with fluorescence detection using an excitation wavelength of 361 nm and an emission wavelength of 527 nm. The retention time for the internal standard, acridine, and TPT were 7.4 and 9.0 min, respectively. The lower limit of quantitation (LOQ) for TPT was determined as 0.02 ng in mouse plasma and mouse plasma ultrafiltrate, corresponding to a concentration of 1 ng/ml in 20 microl mouse plasma. The assay was shown to be linear over a concentration range of 1-500 ng/ml. The recoveries of free and total TPT from spiked mouse plasma were within 10% of theoretical values (assessed at 1, 20 and 500 ng/ml). The validated HPLC assay was applied to evaluate TPT pharmacokinetics following administration of TPT to Swiss Webster mice and to hyperimmunized and control BALB/c mice. The assay has been shown to be capable for measuring total and free TPT in mouse plasma with high sensitivity and will allow the testing of the effect of anti-TPT antibodies on the disposition of TPT.
Reduction of the Sanders-Koiter equations for fully anisotropic circular cylindrical shells to two coupled equations for a stress and a curvature function

With the aid of the static-geometric duality of Goldenveizer (1961), Cartesian tensor notation, and nondimensionalization, it is shown that the equations of linear shell theory of Sanders (1959) and Koiter (1959), when specialized to a circular cylindrical shell with stress-strain relations exhibiting full anisotropy (21 elastic-geometric constants), can be reduced, with no essential loss of accuracy, to two coupled fourth-order partial differential equations for a stress function F and a curvature function G. Auxiliary formulas for the midsurface displacement components are also given. For isotropic shells with uncoupled stress-strain relations, the equations reduce to a form given by Danielson and Simmonds (1969). The reduction is achieved by adding certain negligibly small terms to the given stress-strain relations. For orthotropic shells of mean radius R and thickness h with uncoupled stress-strain relations, it is shown that the very short decay length of O(√hR) and the very long decay length of O(R√R/h) (associated with separable solutions of the form e -Rz sin n θ ) depend, respectively, to within a relative error of O(h/R ), only on the products of different pairs of the eight possible elastic constants.
Synthesis and Structural Characterization of Several Ruthenium Porphyrin Nitrosyl Complexes

The synthesis, X-ray crystal structures, and some spectroscopic and chemical properties of the nitrosylruthenium(II) porphyrin complexes Ru(TPP)(NO)(ONO), Ru(TPP)(NO)(OH), Ru(OEP)(NO)(ONO), and Ru(OEP)(NO)(OH) (TPP = tetraphenylporphyrinato dianion; OEP = octaethylporphyrinato dianion) derived from the analogous Ru(II) carbonyl complexes are reported. Also described are experiments which quantitatively demonstrate that N2O is formed as a product of the synthesis scheme and that NO serves as the principal oxidant in the transformation of N(II) to N(III). The two TPP complexes are isostructural and consist of columns of molecules stacked along the c axis. The two OEP complexes are also isostructural and can be considered as layers of OEP complexes stacked along the b axis with solvent molecules situated at the cavities between layers. The nitrite ions are coordinated in a unidentate fashion through the oxygen atom. Crystal data for Ru(TPP)(NO)(ONO) (1): M = 789.79, space group I4/m (No. 87), a = 13.6529(6)...
The Federal Offset and the American Death Tax System

I. The State-Federal conflict for possession of sources of revenue, 566.— II. Background of the controversy over the estate tax, 567.— III. Revisions of the Federal levy, 1924–1935, 569.— IV. Effects of these upon State and Federal revenues, 573.— Effects upon the form of State taxes, 575.— Effects upon the rates applied under State laws, 577.— V. Effects of the Act of 1926 upon death duties in Pennsylvania, 581.— VI. Effects upon death duties in Massachusetts, 586.— VII. Effects upon the New York system, 590.— VIII. Conclusions, 596.
Sequence retrieval from genomic databases

This paper describes an algorithm for retrieving sequences from genomic databases. The algorithm presented offers a higher sensitivity by utilizing an absolute metric for scoring the similarity query and the database sequences. Such a metric is an improvement over the existing methodology that utilizes a string-edit or Levenshtein distance. A two-phase sequence retrieval system is built using this methodology and the results presented demonstrate its advantages.
Synthesis and optical characterization of CdTe nanocrystals prepared by ball milling process

Abstract CdTe nanocrystals have been successfully synthesized by mechanical alloying (MA) process. XRD pattern and HRTEM images confirmed the formation of cubic structural CdTe Nan crystals (2–40 nm). The capped CdTe nanocrystals show absorption peaks locating within the visible range of 500–700 nm, when uncapped ones locating within ultraviolet range.
Regulatory watch: Innovation in biologic new molecular entities: 1986-2014.

New therapeutic biologics approved by the US FDA in the past ~30 years have been more innovative on average compared with new small-molecule drugs.
Leading Edge Timing Circuit for Ge-Li Detectors

A circuit for producing a timing signal from the leading edge of slow rising Ge-Li detector output signals is described. In order to preserve the system resolution, the input signal is taken from the output of the charge sensitive preamplifier. An internal discriminator strobes the tunnel diode pick-off to reduce the noise triggering rate. The effects of multiple low-pass time constants on the walk is analyzed and found to be in agreement with the measured results. For input signals having a rise-time of 100 ns, the walk is less than 3 ns and the FWHM time jitter less than 1 ns over the range of l to 10 MeV. A temperature compensated delayed output circuit, adjustable over the range of 50 to 750 ns, is also included for use in conjunction with cross-over timing.
Visualizing 3D objects from 2D cross sectional images displayed in-situ versus ex-situ

The present research investigates how mental visualization of a 3D object from 2D cross sectional images is influenced by displacing the images from the source object, as is customary in medical imaging. Three experiments were conducted to assess people’s ability to integrate spatial information over a series of cross sectional images, in order to visualize an object posed in 3D space. Participants used a hand-held tool to reveal a virtual rod as a sequence of cross-sectional images, which were displayed either directly in the space of exploration (in-situ) or displaced to a remote screen (ex-situ). They manipulated a response stylus to match the virtual rod’s pitch (vertical slant), yaw (horizontal slant), or both. Consistent with the hypothesis that spatial co-location of image and source object facilitates mental visualization, we found that although single dimensions of slant were judged accurately with both displays, judging pitch and yaw simultaneously produced differences in systematic error between in-situ and ex-situ displays. Ex-situ imaging also exhibited errors such that the magnitude of the response was approximately correct but the direction was reversed. Regression analysis indicated that the in-situ judgments were primarily based on spatio-temporal visualization, while the ex-situ judgments relied on an ad hoc, screen-based heuristic. These findings suggest that in-situ displays may be useful in clinical practice by reducing error and facilitating the ability of radiologists to visualize 3D anatomy from cross sectional images.
Alternative Therapies for Curing Cancer: What Do Patients Want? What Do Patients Need?*

Despite her scientific training and experience in medical practice, after being diagnosed with an indolent non-Hodgkin's lymphoma, the author was subjected to intense pressure about alternative therapies from well-meaning friends and relatives. While insulated at first from these forces, disease recurrences and progression increased her vulnerability to the lure of seemingly gentler approaches. A data-driven study of alternative therapeutic methods, however, convinced the author that investigational strategies offered her a better chance of cure or improvement than unproven alternative methods. She offers guidelines for physicians about what patients want, and emphasizes the importance of hope, caring, and information.
The obstetric nightmare of shoulder dystocia: a tale from two perspectives.

Purpose Shoulder dystocia is one of the most terrifying of obstetric emergencies. In this secondary analysis of two qualitative studies, the experiences of shoulder dystocia are compared and contrasted from two perspectives: the mothers and the labor and delivery nurses. Method In the first study mothers' experiences of shoulder dystocia and caring for their children with obstetric brachial plexus injuries were explored. The second study explored secondary traumatic stress in labor and delivery nurses due to exposure to traumatic births. Krippendorff's content analysis technique of clustering was used to identify data that could be grouped together into themes. Results It was striking how similar the perspectives of mothers and their nurses were regarding a shoulder dystocia birth. Four themes emerged from the content analysis of these two data sets: (1) in the midst of the obstetric nightmare; (2) reeling from the trauma that just transpired; (3) enduring heartbreak: the heavy toll on mothers; and (4) haunted by memories: the heavy toll on nurses. Clinical implications Providing emotional support to the mother during shoulder dystocia births and afterward in the postpartum period has been acknowledged. What now needs to be added to best practices for shoulder dystocia are interventions for the nurses themselves. Support for labor and delivery nurses who are involved in this obstetric nightmare is critical.
Endocrine therapy of advanced carcinoma of the prostate

Increasing evidence suggests that growth of the prostatic tissue is regulated by a network of hormones and growth factors, in which androgens play the prominent role. Hormonal manipulation remains the core of treatment for locally advanced and metastatic prostate cancer. Achievement of a complete androgen blockade, by surgical or medical means or a combination of both, offers superior results in palliative management of advanced disease. Management of hormonal refractory cancer, however, remains a challenge to clinicians.