cssi/SciSciGPT-SciSciNet huggingface dataset:
Eradication of mouse melanoma by combined treatment with recombinant human interleukin 2 and recombinant murine interferon-gamma.

Successful immunotherapy of early s.c. or i.p. (B16) melanoma in syngeneic C57BL/6 (B6) mice was achieved with s.c. peri-lesional injections (for s.c. tumors) or i.p. injections (for i.p. tumors) of recombinant human interleukin 2 (rIL-2) and recombinant murine interferon-gamma (rIFN-gamma). Over a 28-day period, rIL-2 and rIFN-gamma were injected 14 times. Results with this combination were additive with s.c. tumors and synergistic with i.p. tumors. Treatment with 6,250 U-25,000 U of rIL-2 and 2 micrograms of rIFN-gamma began 1-3 days after s.c. inoculation of melanoma. On day 50, 87% (72/83) of mice thus treated were completely free of tumor. None of the 78 control mice (tumor + buffer) survived. Of mice receiving either rIL-2 or rIFN-gamma alone, 59% (47/79) and 53% (44/83), respectively, were tumor-free. I.p. tumors were also eradicated by i.p. injections of rIL-2 (50,000 U) with rIFN-gamma (5, 10, and 15 micrograms) as judged by absence of tumor in 81% (21/26) of mice autopsied between days 45 and 65. No control mice survived, and only 17% (2/12) and 20% (6/30) given either rIL-2 or rIFN-gamma separately (i.p.) were tumor-free. Doses of rIFN-gamma from 1-4 micrograms were more beneficial in eliminating 1-day s.c. melanomas than were higher doses, and local s.c. treatment was far superior to distant or systemic treatment. Non-adherent peritoneal or splenic cells from mice bearing 6-day-old i.p. melanomas and treated with one or both lymphokines on days 3 and 4 were used in cytotoxicity assays in vitro. Significant cytotoxicity against cultured melanoma cells was displayed by cells harvested from lymphokine-treated mice, but there was no evidence of the synergism observed with combination treatment of i.p. tumors in vivo. rIFN-gamma inhibited proliferation of melanoma cells in vitro, whereas rIL-2 stimulated proliferation at 1,000 U/ml. Plating efficiency was increased by at least 30% by culture with 100 U or 1,000 U of rIL-2/ml and both concentrations neutralized the inhibitory effect of 0.05 ng/ml of IFN-gamma, but not of 0.5 or 5.0 ng/ml.
Morbidity and Mortality of Pancreaticoduodenectomy for Benign and Premalignant Pancreatic Neoplasms

Patients with benign neoplasms of the pancreas are selected for pancreaticoduodenectomy if there is concern for malignant transformation. This study compares outcomes after pancreaticoduodenectomy for patients with premalignant and malignant pancreatic neoplasms. This retrospective cohort study included all patients who underwent pancreaticoduodenectomy for histologically confirmed benign/premalignant pancreatic neoplasms and primary pancreatic malignancy reported to National Surgical Quality Improvement Program (NSQIP) from 2005 to 2011. Patient characteristics, intraoperative and postoperative morbidity and mortality were compared. A total of 6085 patients underwent pancreaticoduodenectomy: 744 (12.2 %) for benign/premalignant and 5341 (87.8 %) for malignant pancreatic neoplasms. Patients with benign/premalignant neoplasms were more commonly female, had lower American Society of Anesthesiologists (ASA) class, and were less likely to have major comorbidities (all p ≤ 0.003). After resection, patients with benign/premalignant neoplasms were more likely to develop organ space infection (13.4 vs. 8.5 %, p < 0.001) and sepsis (12.2 vs. 9.2 %, p = 0.009). Cardiovascular, pulmonary, renal, and other organ system complications (p = 0.12) as well as 30-day mortality (3.0 vs. 2.0 %, p = 0.128) did not differ. Organ space infection and sepsis are more common after pancreaticoduodenectomy for benign/premalignant neoplasms. Planned improvements in NSQIP data capture should allow for better measurement of this morbidity. A carefully balanced risk and benefit discussion should precede resection in these patients.
Effects of stimulus frequency and intensity on habituation and sensitization in acute spinal cat

Abstract Habituation and sensitization of the flexor withdrawal reflex (tibialis anterior muscle) were studied in acute spinal cat as a function of stimulus intensity and frequency for frequencies ranging above 1 2 sec. The following relationships were consistently observed: (1) habituation is an exponential decline in response amplitude which occurs as a function of iterated stimulation of cutaneous afferents. In some instances habituation may be described as linear over much of its course; (2) habituation occurs more rapidly and to a greater degree of response decrement for higher frequencies of stimulation; (3) habituation is more pronounced for low intensities of stimulation than for high intensities, and; (4) sensitization occurs as a response increment with repetitive stimulation of cutaneous afferents under certain circumstances and may show two distinct time courses, short-term and long-term sensitization. These two phenomena may be differentiated on the basis of stimulus intensity, frequency and their interaction.
Bandwidth elasticity with dense wavelength-division multiplexing parallel wavelength bus in optical networks

Wavelength-division multiplexing (WDM) is a photonic technology that couples many optical channels (wavelengths) in a single fiber. Each wavelength represents a separate optical channel at a fixed bit rate. Thus, to increase the aggregate transportable bandwidth per fiber either the channel density must be increased or the bit rate per channel, or both. As a result, the signal quality for a given fiber length suffers due to the nonlinearity of the medium. Therefore, engineering and provisioning of WDM links to meet signal quality objectives is a complex task. Despite advancements in bit rate increase, not all applications require such high rates, as many applications require granularity finer than optical carrier n (OC-n) to increase efficiency. As a consequence, bandwidth efficiency, fine bit rate granularity, and diverse traffic type will be necessary characteristics of the next-generation WDM networks. We propose a WDM transmission method by which a high-bandwidth-capacity wavelength bus supports many clients, more than the number of wavelengths, each at different rate and of different traffic type. In addition, the method uses low bit rates and cost-effective transceivers. We examine strategies to minimize linear and nonlinear impairments over a given span, strategies to enhance the quality of signal and increase the fiber span, and strategies to reduce cost of transported bandwidth-kilometer in a variety of dense WDM (DWDM) applications. We also examine the applicability of the method in various network topologies, and aspects of network protection and restoration.
New directions in offender typology design, development, and implementation: Can we balance risk, treatment and control?

Abstract It should come as no surprise that there is no “one-stop shopping” offender typology available that can identify the risk level, targeted treatment protocols, and control levels of the offender groups examined in this special issue: murderers, sex offenders, batterers, violent prisoners, and violent mentally ill offenders. We are in desperate need of further research establishing the links between offender risk level, offender treatment needs, and offender control requirements for each of these offender groups. This article provides a “state of the art” discussion of the key issues that must be addressed by policymakers, practitioners, and ultimately, the public, vis-a-vis the design, development, and implementation of typologies for each of these targeted groups of offenders. This is followed by our assessment of the lessons learned from the great prison classification experiment. We conclude by providing an assessment of new directions in the development of typologies of offenders and the communities in which offenders reside, based on the simple notion that offender change–not offender control–needs to be the primary focus of the next generation of correctional classification systems.
Solid Tumor Cytogenetics: Current Perspectives

Conventional cytogenetics in conjunction with Fluorescence in Situ Hybridization (FISH) continues to remain an important and integral component in the diagnosis and management of solid tumors. The ability to effectively detect the vast majority of clinically relevant chromosomal aberrations with a rapid-to-acceptable turnaround time makes them the most cost-effective screening/detection tool currently available in modern pathology. In this review, we describe a representative set of solid tumors in which chromosomal analysis and/or FISH plays a significant role in the routine clinical management of solid tumors.
ADRENOCORTICOTROPIC SUBSTANCES FROM HUMAN PLACENTA1

It has been suggested repeatedly that during pregnancy, there is an increased adrenocortical activity. Venning (1946) found a progressive rise in the excretion of corticoids beginning early in pregnancy and reaching its maximum in the last trimester of gestation. Subsequently, the same author (1954) observed still further increase in the rate of excretion of the salt retaining fraction in association with toxemia of pregnancy. Similar changes were reported by Tobian (1949) and by Lloyd and his coworkers (1952). Gemzell (1953) showed that the blood levels of 17-hydroxicorticosteroids began to rise early in pregnancy and remained high until shortly after delivery. He attributed this steady rise in part to a stimulation of the maternal adrenals by excessive amounts of estrogen present during pregnancy, and to hyperactivity of the fetal adrenals. The latter have also been held responsible for the spontaneous improvement in patients with Addison's disease usually seen during pregnancy (Samuels et al., 1943).
Obstetrician-gynaecologist knowledge of and access to information about the risks of medication use during pregnancy.

Objective. To assess opinions, knowledge, and informational resources of obstetrician–gynaecologists regarding the safety of medication use during pregnancy.Methods. A questionnaire was mailed to 770 members of the American College of Obstetricians and Gynecologists who participate in the Collaborative Ambulatory Research Network.Results. The response rate was 58%. Of these, 305 respondents provide both routine gynecologic and obstetric care and are the focus of the study. There was wide variation in obstetrician–gynaecologists' assessments of the safety for the foetus of medications ranging from aspirin to valproic acid. The Physicians' Desk Reference was most frequently (75%) cited as a source of information about medication safety. Forty-two percent of obstetrician–gynaecologists selected lack of sufficient information on medications as the greatest barrier to counselling pregnant women about their use, while only 4% selected lack of access to information as the greatest barrier. Most (79%) obstetricia...
Immunohistochemical localization of Foxa1 and Foxa2 in mouse embryos and adult tissues

Abstract Members of the Forkhead box (Fox) transcription factors family Foxa1 (Hnf-3α), Foxa2 (Hnf-3β) are known to influence gene expression in endodermally derived tissues including lung, liver, pancreas, stomach, and intestine. In the present study, we have generated highly specific antibodies for Foxa1 and Foxa2 and determined their expression patterns in the developing and adult mouse. Foxa1 and Foxa2 were detected in the nuclei of tissues derived from both foregut and hindgut endoderm (liver, lung, pancreas, stomach, intestine, prostate and bladder). Foxa2 and Foxa1 were also detected in organs deriving from ectodermal (several brain structures and olfactory epithelium) and mesodermal origins (kidney, vagina and uterus, seminal and coagulating glands) during development. Colocalization and distinct sites of expression of Foxa1 and Foxa2 indicate unique as well as overlapping roles of Foxa1 or Foxa2 during morphogenesis and in the function of different adult organs.
Solution structure and dynamics of myeloid progenitor inhibitory factor-1 (MPIF-1), a novel monomeric CC chemokine.

MPIF-1, a CC chemokine, is a specific inhibitor of myeloid progenitor cells and is the most potent activator of monocytes. The solution structure of myeloid progenitor inhibitor factor-1 (MPIF-1) has been determined by NMR spectroscopy. The structure reveals that MPIF-1 is a monomer with a well defined core except for termini residues and adopts the chemokine fold of three β-strands and an overlying α-helix. In addition to the four cysteines that characterize most chemokines, MPIF-1 has two additional cysteines that form a disulfide bond. The backbone dynamics indicate that the disulfide bonds and the adjacent residues that include the functionally important N-terminal and N-terminal loop residues show significant dynamics. MPIF-1 is a highly basic protein (pI >9), and the structure reveals distinct positively charged pockets that could be correlated to proteoglycan binding. MPIF-1 is processed from a longer proprotein at the N terminus and the latter is also functional though with reduced potency, and both proteins exist as monomers under a variety of solution conditions. MPIF-1 is therefore unique because longer proproteins of all other chemokines oligomerize in solution. The MPIF-1 structure should serve as a template for future functional studies that could lead to therapeutics for preventing chemotherapy-associated myelotoxicity.
Influence of root colonizing bacteria on the defense responses of bean

Colonization of plant roots by fluorescent pseudomonads has been correlated with disease suppression. One mechanism may involve altered defense responses in the plant upon colonization. Altered defense responses were observed in bean (Phaseolus vulgaris) inoculated with fluorescent pseudomonads. Systemic effects of root inoculation by Pseudomonas putida isolate Corvallis, P. tolaasii (P9A) and P. aureofaciens REW1-I-1 were observed in bean leaves from 14-day-old plants. SDS- polyacrylamide gel electrophoresis demonstrated that levels of certain acid-soluble proteins increased in the leaf extracts of inoculated plants. Plants inoculated with REW1-I-1 produced more of a 57 Mr protein, and plants inoculated with isolates P9A and REW1-I-1 produced more of a 38 Mr protein. Northern hybridization revealed enhanced accumulation of mRNAs, that encode the pathogenesis-related protein PR1a, in leaves of plants inoculated with P. putida and REW1-I-1. Only REW1-I-1, but not P9A or P. putida induced symptoms of an hypersensitive response on tobacco leaves, bean cotyledons, and in bean suspension cultures. Phenolics and phytoalexins accumulated in bean cotyledons exposed to REW1-I-1 for 24 h but little change in levels of these compounds occurred in cotyledons inoculated with P9A and P. putida. Both suspension culture cells and roots treated with REW1-I-1 rapidly evolved more hydrogen peroxide than those exposed to P9A and P. putida. However, roots from 14-day-old plants colonized by P9A, P. putida or REW1-I-1 did not have higher levels of phenolics, phytoalexins or mRNAs for two enzymes involved in phenolic biosynthesis, phenylalanine-ammonia lyase and chalcone synthase. A selective induction of plant defense strategies upon root colonization by certain pseudomonads is apparent.
Automated Management of Disaster Recovery Systems Using Adaptive Scheduling

Disaster recovery (DR) is an extremely important solution for all organizations. All DR solutions have a myriad of solution specific tweaks, however, each of them have a set of common underlying routine processes/tasks, namely, i) data backup/archive, ii) secondary/offsite replica generation, iii) data migration across storage pools, iv) metadata expiration and v) tape-reclamation. A complete solution needs to judiciously run the above mentioned tasks in the most effective manner. The problem of architecting a balanced schedule considering the constraints of time and bandwidth along with the relative importance of each process/task is a non-trivial one. Designing of schedules is a labor intensive task and often the schedules are far from optimal. In this work we have proposed a solution which automatically generates the most beneficial schedule based on an optimization problem with resource outage risk minimization as the objective and available time and resource capacities as the constraints. The solution is driven by models of the common underlying processes and their relative importance to keep the service up and running.
Analysis of Coma Dust Optical Properties in Comet C/1995 O1 (Hale–Bopp): II. Effects of Polarization

Abstract Efforts to apply a single-scattering polarized radiative transfer code to interpret photopolarimetric measurements of coma dust optical properties in Comet Hale–Bopp corroborate previous photometrically derived conclusions concerning the predominance of small sized particles in Hale–Bopp's coma. Calculations of the degree of linear polarization (DP) as a function of observation phase angle (α) produced by prolate spheroidal crystalline olivine particles with effective radii (a=0.216 μm) are compatible with the comet's measured polarization in standard filters at λ=0.4845 and 0.684 μm. Our rudimentary “trade-off” studies highlight the extreme sensitivity of DP to dust particle size and shape. A combination of viewing geometry effects in association with enhanced multiple scattering might provide a quantitative explanation of the negative polarization for 0°≤α≤20° seen in Hale–Bopp and other comets.
Factors influencing pursuit of residency training.

Residency training may ease the transition from pharmacy student to practitioner by enhancing knowledge and skills and fostering relationships with mentors. Although residencies are known to expand and advance the profession of pharmacy and enable future leadership, only 14% of graduating students
The distribution of the sphericity test criterion

Abstract The exact distribution of Mauchly's sphericity test criterion W = | S |/[tr S /p] p , when S is the sum of product matrix from a sample of size N taken from a p -variate normal population, is obtained using contour integration and methods similar to those of Nair and Box. Tables of percentage points for p = 4(1)10, α = 0.01 and 0.05, and various values of N (including small) are given and comparisons made with approximate percentage points using methods of Box, Mauchly, Tukey and Wilks, and Davis.
Sequential games and medical diagnosis

Abstract Previous models of medical diagnosis as a sequential decision process have assumed that there is a single decision maker whose values are maximized. The model presented here assumes that there are two or more decision makers, e.g., physician and patient, who engage in a series of cooperative games to jointly maximize their utilities. Myopic structure is assumed at each decision point. A pilot application to valvular heart disease is presented.
THE MOLECULAR MECHANISM UNDERLYING THE RARE ALLELE PHENOMENON IN A SUBSPECIFIC HYBRID ZONE OF THE CALIFORNIA FIELD MOUSE, PEROMYSCUS CALIFORNICUS

Natural hybrid zones are known to have unusually high levels of novel or otherwise rare electrophoretic variants (the “rare allele phenomenon”). These variant alleles are most likely the result either of high levels of unique mutations in hybrids or of intragenic recombination between divergent alleles from the parental populations. This study uses DNA sequence comparisons to determine which process has produced a rare allele of the 6-phosphogluconate dehydrogenase (6PGD) gene in a subspecific hybrid zone of the California field mouse (Peromyscus californicus).
Occupation time densities for stable-like processes and other pure jump Markov processes

Abstract Pure jump Markov processes Xt on the line associated to the operators A ƒ(x)= ∫[ƒ(x+h)−ƒ(x)−ƒ′(x)hl ([-1,1]) (h)]ν(x,dh) are considered. Sufficient conditions for Xt to have local times that serve as occupation time densities are given. In the case where ν(x,dh)= |h|−(1+α(x)), the stable-like case, these conditions reduce to: inf α(x)>1 and α(x) Dini continuous.
The molecular mechanisms that control function and death of effector CD4+ T cells

This review features two areas of our research interests. First, our laboratory is interested in elucidating the molecular mechanisms that control generation, effector function, and fate of TH1 cells during inflammatory responses. We have been particularly interested in the role of the growth arrest and DNA damage-inducible protein 45 (GADD45) gene family in TH1-mediated immune responses. We and others have shown that, in TH1 cells, Gadd45b and Gadd45g are induced by TCR signaling or IL-12 and IL-18. Gadd45b and Gadd45g are very important for the activation of p38 MAP kinases in TH1 cells and for effector functions of TH1 cells. We have found that deletion of Gadd45b and Gadd45g genes in mice results in a drastically reduced number of TH1 cells against Listeria monocytogenes. The critical role of Gadd45b and Gadd45g in TH1 responses in this acute infectious model has led us to hypothesize that they promote TH1-mediated autoimmune diseases. We therefore decided to test this hypothesis in experimental allergic encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). Expecting low numbers of TH1 cells, we were surprised to see that Gadd45b deletion resulted in exacerbated chronic phase of EAE. In contrast to the reduction of TH1 cells we saw in acute L. monocytogenes infection, during the chronic phase of EAE we observed increased TH1 cells in the inflamed CNS when Gadd45b was deleted. Gadd45b deletion also resulted in enlarged spleens in older mice. Gadd45b/Gadd45g greatly enlarged spleens in older mice compared with Gadd45b single deletion. The enlargement of spleens was due to the accumulation of CD4+ T cells with an activated phenotype and B cells. In addition, we have found that Gadd45b and Gadd45g inhibit proliferation and promote apoptosis of activated CD4+ T cells. Therefore, Gadd45b and Gadd45g play a critical role as a molecular "doubleedged sword" in TH1-type immune responses to ensure a prompt, robust but self-limiting TH1 response. The second area of research in our laboratory focuses on the role of autophagy in T cells. We have recently discovered that autophagy is induced in TH1 and TH2 cells. There are more effector TH2 cells than TH1 cells that undergo autophagy. We have used RNAi strategy to "knockdown" autophagy in TH2 cell lines and found that autophagy is required for growth factor-withdrawal cell death.
Patterns of inheritance of colonic polyps

While the inheritance pattern of familial polyposis coli is established as an autosomal dominant pattern, the expression of the various extracolonic manifestations associated with the neoplastic polyposis is less well understood. The discrete polyp cancer syndrome may not be recognized unless both polyps and colon cancer are considered in the inheritance pattern. The hamartomatous polyps follow a Mendelian-dominant inheritance pattern for the Peutz-Jeghers syndrome, while the inheritance pattern for the juvenile polyposis syndromes is less clear. Cowden's disease appears in a Mendelian dominant pattern, but the occurrence of colonic polyps is less well documented. The ganglioneuromas follow a mendelian dominant inheritance pattern, while the relationship and occurrence of colonic polyps in association with Torre's syndrome is uncertain. The Mendelian dominant inheritance pattern for the cancer family syndrome is documented; the role of colon polyps in this syndrome is less well understood. A further understanding of the inheritance patterns of these various colon polyps will lead to more understanding of the basic disease and help in prevention and early detection for treatment and cure.
Identification Through X-Ray Fluorescence Analysis of Dental Restorative Resin Materials: A Comprehensive Study of Noncremated, Cremated, and Processed-Cremated Individuals*

Tooth-colored restorative materials are increasingly being placed in the practice of modern dentistry, replacing traditional materials such as amalgam. Many restorative resins have distinct elemental compositions that allow identification of brand. Not only are resins classifiable by elemental content, but they also survive extreme conditions such as cremation. This is of significance to the forensic odontologist because resin uniqueness adds another level of certainty in victim identification, especially when traditional means are exhausted. In this three-part study, unique combinations of resins were placed in six human cadavers (total 70 restorations). Simulated ante-mortem dental records were created. In a blind experiment, a portable X-ray fluorescence (XRF) unit was used to locate and identify the resin brands placed in the dentition. The technique was successful in location and brand identification of 53 of the restorations, which was sufficient to enable positive victim identification among the study group. This part of the experiment demonstrated the utility of portable XRF in detection and analysis of restorative materials for victim identification in field or morgue settings. Identification of individuals after cremation is a more difficult task, as the dentition is altered by shrinkage and fragmentation, and may not be comparable with a dental chart. Identification of processed cremains is a much greater challenge, as comminution obliterates all structural relationships. Under both circumstances, it is the nonbiological artifacts that aid in identification. Restorative resin fillings can survive these conditions, and can still be named by brand utilizing elemental analysis. In a continuation of the study, the cadavers were cremated in a cremation retort under standard mortuary conditions. XRF was again used to analyze retrieved resins and to identify the individuals based on restorative materials known to exist from dental records. The cremains were then processed and the analysis was repeated to determine whether restorative resins could be found under this extreme condition. Under both circumstances, sufficient surviving resin material was found to distinguish positively each individual in the study group. This study showed the utility of XRF as an analytical tool for forensic odontology and also the significance of the role of restorative resins in victim identification, even after cremation.
A discussion of recommended standards for lighting in the newborn intensive care unit

Recently, the Consensus Committee to Develop Recommended Standards for Newborn Intensive Care Unit (NICU) Design has developed recommended lighting standards for the NICU. One objective of these standards are to propose lighting standards that reflect the general principles of good lighting, and to chart new directions for lighted environments in the NICU that are consistent with the latest scientific literature. Rationales for the latest recommended standards in NICUs as they pertain to the ambient lighting in infant care areas, procedure lighting in infant care areas, illumination of support areas, daylighting and floor surfaces are discussed. This article is intended to serve as a bridge between health care and building professionals interested in quality lighting in the NICU environment.
Clinical Mechanisms of Nitrate Action

Nitrates are a cornerstone in the therapy of coronary artery disease and congestive heart failure. Through the years, their utility in the management of angina of effort, unstable angina, acute and chronic heart failure, and acute myocardial infarction has become well recognized. They act at the organ level by a vasodilatory effect on the venous circulation and the large coronary arteries. Nitrates also possess antiplatelet effects and antithrombotic properties and thus have a variety of actions that are useful in the management of coronary artery disease and congestive heart failure. The use of nitrates in the treatment of stable and unstable angina pectoris and congestive heart failure is reviewed.
A Geometric Treatment of Implicit Differential-Algebraic Equations

Abstract A differential-geometric approach for proving the existence and uniqueness of implicit differential-algebraic equations is presented. It provides for a significant improvement of an earlier theory developed by the authors as well as for a completely intrinsic definition of the index of such problems. The differential-algebraic equation is transformed into an explicit ordinary differential equation by a reduction process that can be abstractly defined for specific submanifolds of tangent bundles here called reducible π-submanifolds. Local existence and uniqueness results for differential-algebraic equations then follow directly from the final stage of this reduction by means of an application of the standard theory of ordinary differential equations.
The effects of phospholipase A2 inhibition on experimental infarct size, left ventricular hemodynamics and regional myocardial blood flow.

Abstract It has been reported that activation of phospholipase A 2 and the subsequent degradation of membrane phospholipids are responsible for irreversible myocardial injury. Thus, we examined whether a phospholipase A 2 inhibitor 1-(benzylmethyl-amino)-3-[(α,α,α-trifluoro-m-tolyl)oxy]-2-propanol hydrochloride, can reduce myocardial necrosis after coronary artery occlusion. In 14 anesthetized dogs, 1 minute after coronary occlusion, 99m Tc-labeled albumin microspheres (8 mCi) were injected into the left atrium for future assessment of the hypoperfused zone. After 15 minutes, the dogs were randomized to a control group ( n = 7) and a treated group ( n = 7, 2 mg/kg i.v.). After 6 hours, infarct size and hypoperfused zones were measured using triphenyltetrazolium chloride staining and autoradiography, respectively. The hypoperfused zone, as a percentage of the left ventricle, was 26 ± 3% and 23 ± 1% in the control and the treated groups (NS), respectively. The percentage of the hypoperfused zone that evolved to necrosis was 98 ± 4% in the control group and 45 ± 10% in the treated group ( P P 2 inhibitor did not acutely change heart rate, aortic pressure, left ventricular end-diastolic and systolic pressures, left ventricular dPdt and regional myocardial blood flow. Thus, phospholipase A 2 inhibitor salvaged the acutely ischemic myocardium, reducing necrosis by over 50% in the canine model. It is postulated that since this effect was not related to the studied hemodynamic parameters and regional myocardial blood flow, it may be related to the preservation of membrane integrity.
Effect of N-2-acetylaminofluorene and 2-aminofluorene adducts on DNA binding and synthesis by yeast DNA polymerase η

The well-studied aromatic amine carcinogen, N-2-acetylaminofluorene (AAF), forms adducts at the C8 position of guanine in DNA. Unlike replicative polymerases, Y-family polymerases have been shown to have the ability to bypass such bulky DNA lesions. To better understand the mechanism of translesion synthesis by the yeast DNA polymerase η (yPolη), a gel retardation technique was used to measure equilibrium dissociation constants of this polymerase for unmodified DNA or DNA containing dG-C8-AAF or the related deacylated dG-C8-AF adduct. These results show that the binding of yPolη to the unmodified primer-template is substantially stronger in the presence of the next correct nucleotide than when no or an incorrect nucleotide is present. In addition, binding of yPolη to either dG-C8-AAF or AF-modified templates is also stronger in the presence of dCTP. Finally, the yPolη complex is destabilized if the primer extends to a position across from the adduct, and stronger binding is not observed in the presence of...
Energy‐linearized variational cellular method for large molecules and solids

Multiple scattering theory (MST) is the mainstay of Kohn–Sham calculations of the electronic structure of solids and alloys. MST formalism solves one-electron equations within each atomic cell, using a Green function to propagate solutions across cell boundaries, while standard methodology for molecules expands wave functions in a Gaussian orbital basis. An energy-linearized version of MST (LMTO) is efficient but restricted to an atomic-sphere model. Full-potential MST extends the formalism to space-filling Wigner–Seitz polyhedra. The variational cellular method (VCM) solves full-potential equations, replacing Green-function propagation (structure constants) by variational matching at the interfaces of adjacent atomic cells. VCM provides a common formalism for molecules and solids but cannot easily be converted to an energy-linearized method. A new variational principle is derived here that extends the VCM to a straightforward procedure for energy linearization. This formalism eliminates false solutions from the VCM. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
Pharmacokinetics of Intravenous Nitrosylcobalamin, an Antitumor Agent, in Healthy Beagle Dogs: A Pilot Study

Background/Aim: Nitrosylcobalamin (NO-Cbl) is a cobalamin-based anti-tumor agent. This study evaluated the pharmacokinetic parameters of NO-Cbl following intravenous administration in dogs. Materials and Methods: Four dogs received 10 mg/kg, 20 mg/kg and 40 mg/kg intravenous bolus doses of NO-Cbl, with a 14-day washout period between doses. Blood samples were collected at baseline and post-dosing, and noncompartmental pharmacokinetic parameters were determined. Results: Average peak serum concentrations of 2265, 5523 and 13,866 pg/mL were achieved following single-dose bolus intravenous administration of 10 mg/kg, 20 mg/kg and 40 mg/kg of NO-Cbl respectively. The average area under the curve was 12,697 h ? pg/mL, 24,497 h ? pg/mL and 44,976 h ? pg/mL respectively, with an average elimination half-life of 16.2 h, 13.5 h and 13.1 h respectively. Conclusion: These results can be used to determine the dose and dosing intervals for clinical trials evaluating NO-Cbl in humans and companion animals.
Uniform Asymptotic Expansions for the Reverse Generalized Bessel Polynomials, and Related Functions

The generalized Bessel polynomials yn(z; a) are generalizations of the well-known modified Bessel functions $K_{\nu}(z)$. In this paper a study is undertaken of the reverse generalized Bessel polynomials, which are defined by $\theta_n(z; a) = z^ny_n(z^{-1}; a)$, and their asymptotic behavior as the degree $n \rightarrow \infty$ is comprehensively determined. This is achieved by an application of two general asymptotic theories, due to F. W. J. Olver, to an ordinary differential equation satisfied by $\theta_n(z; a)$: one for the case of complex domains which are free of turning points (yielding Liouville--Green expansions), and the other for complex domains containing a simple turning point (yielding Airy function expansions). The approximations are uniformly valid for z lying in certain unbounded subdomains of the complex plane and are complete with explicit error bounds. Together the domains of validity cover the whole complex plane. Moreover, all the results are uniformly valid for real or complex a, ...
DIGITAL RECORDER FOR AQUIFER TESTS

Data loggers, in combination with appropriate electronic measuring devices, can improve pumping-test data by reducing cost and by increasing accuracy, precision, speed, and computational convenience. The data logger (digital recorder) described herein was tested and found to work well. Sensitivity to blowing sand and freezing temperatures, excessive power consumption, and poor display legibility in bright sunlight are minor design deficiencies that slightly restrict the usefulness of this data logger. These problems can be easily corrected.
Studying alternative splicing regulatory networks through partial correlation analysis

Background: Alternative pre-mRNA splicing is an important gene regulation mechanism for expanding proteomic diversity in higher eukaryotes. Each splicing regulator can potentially influence a large group of alternative exons. Meanwhile, each alternative exon is controlled by multiple splicing regulators. The rapid accumulation of high-throughput data provides us with a unique opportunity to study the complicated alternative splicing regulatory network. Results: We propose the use of partial correlation analysis to identify association links between exons and their upstream regulators or their downstream target genes (exon-gene links) and links between co-spliced exons (exon-exon links). The partial correlation analysis avoids taking the ratio of two noisy random variables, exon expression level and gene expression level, so that it achieves a higher statistical power. We named this analysis procedure pCastNet (partial Correlation analysis of splicing transcriptome Network). Through studies of known alternative exons, conservation patterns, relative positions, functional annotations, and RT-PCR experiments, we concluded that pCastNet can effectively identify exon-gene or exon-exon links. We further found that gene pairs with exon-gene or exon-exon links tend to have similar functions or are present in the same pathways. More interestingly, gene pairs with exon-gene or exon-exon links tend to share ciselements in promoter regions and microRNA binding elements in 3' untranslated regions, which suggests the coupling of co-alternative-splicing, co-transcription-factor-binding, and co-microRNAbinding.
Speciation of mercury in eelgrass (Zostera marina L.): a seasonal study in the Great Bay Estuary, New Hampshire

The first detailed determination of mercury(II) [Hg(II)] and monomethylmercury cation (MeHg+) concentrations in eelgrass (Zostera marina L.) is described. The rapid and simple method includes digestion by the new reagent tetrabutylammonium bromide/potassium hydroxide, derivatization by sodium borohydride and detection by hydride generation–cold vapor atomic fluorescence spectrometry. Mercury in leaves/stems and roots/rhizomes of eelgrass samples collected near Adams Point of the Great Bay Estuary, NH, from May to November of the 1997 growing season was speciated. The seasonal ranges of concentrations in leaves and stems of eelgrass are: Hg(II), 14.9–40.4 ng Hg g−1 dry weight; MeHg+, 1.06–3.89 ng Hg g−1 dry weight. MeHg+ content averaged 6.9% of total mercury. Analogous values for roots and rhizomes are: Hg(II) 15.4–57.7 ng Hg g−1 dry weight; MeHg+ 0.91–2.41 ng Hg g−1 dry weight; MeHg+ averaged 6.4% of total mercury. The non-parametric Kendall test showed that Hg(II) and MeHg+ concentrations in leaves and stems increased from May to July, then decreased. For roots and rhizomes the Kendall test showed that Hg(II) concentrations were unchanged from May to August, then decreased, and that MeHg+ concentrations decreased throughout the growing season. The non-parametric Wilcoxon Signed-Ranks method showed no systematic difference in Hg(II) or MeHg+ concentrations between leaves/stems and roots/rhizomes. Copyright © 1999 John Wiley & Sons, Ltd.
Comparison of measurement methods with a mixed effects procedure accounting for replicated evaluations (COM3PARE): method comparison algorithm implementation for head and neck IGRT positional verification

Comparison of imaging measurement devices in the absence of a gold-standard comparator remains a vexing problem; especially in scenarios where multiple, non-paired, replicated measurements occur, as in image-guided radiotherapy (IGRT). As the number of commercially available IGRT presents a challenge to determine whether different IGRT methods may be used interchangeably, an unmet need conceptually parsimonious and statistically robust method to evaluate the agreement between two methods with replicated observations. Consequently, we sought to determine, using an previously reported head and neck positional verification dataset, the feasibility and utility of a Comparison of Measurement Methods with the Mixed Effects Procedure Accounting for Replicated Evaluations (COM3PARE), a unified conceptual schema and analytic algorithm based upon Roy’s linear mixed effects (LME) model with Kronecker product covariance structure in a doubly multivariate set-up, for IGRT method comparison. An anonymized dataset consisting of 100 paired coordinate (X/ measurements from a sequential series of head and neck cancer patients imaged near-simultaneously with cone beam CT (CBCT) and kilovoltage X-ray (KVX) imaging was used for model implementation. Software-suggested CBCT and KVX shifts for the lateral (X), vertical (Y) and longitudinal (Z) dimensions were evaluated for bias, inter-method (between-subject variation), intra-method (within-subject variation), and overall agreement using with a script implementing COM3PARE with the MIXED procedure of the statistical software package SAS (SAS Institute, Cary, NC, USA). COM3PARE showed statistically significant bias agreement and difference in inter-method between CBCT and KVX was observed in the Z-axis (both p − value<0.01). Intra-method and overall agreement differences were noted as statistically significant for both the X- and Z-axes (all p − value<0.01). Using pre-specified criteria, based on intra-method agreement, CBCT was deemed preferable for X-axis positional verification, with KVX preferred for superoinferior alignment. The COM3PARE methodology was validated as feasible and useful in this pilot head and neck cancer positional verification dataset. COM3PARE represents a flexible and robust standardized analytic methodology for IGRT comparison. The implemented SAS script is included to encourage other groups to implement COM3PARE in other anatomic sites or IGRT platforms.
More Than the Work Race and Gender Differences in Caregiving Burden

This study examines race and gender differences in the burden experienced by family caregivers of the elderly using data from the 1990 Informal Caregivers Survey. Social exchange theory predicts burden to a certain extent based on the caregiving context (e.g., psychological difficulties of the elder and positive aspects of caregiving) and work performed (e.g., hours per week and specific tasks), but race and gender differences independent of the context suggest that feeling burdened also depends on identities embodied in gender roles and African American culture. Also predictive of burden is the interaction between race and gender, and although African American and White women face similar caregiving situations, African American women report less burden than White women or men of either race.
Navigating complex patients using an innovative tool: the MTM Spider Web.

Objective: To introduce a teaching tool that can be used to assess the complexity of medication therapy management (MTM) patients, prioritize appropriate interventions, and design patient-centered care plans for each encounter. Summary: MTM patients are complex as a result of multiple comorbidities, medications, and socioeconomic and behavioral issues. Pharmacists who provide MTM services are required to synthesize a plethora of information (medical and nonmedical), evaluate and prioritize the clinical problems, and design a comprehensive patient-centered care plan. The MTM Spider Web is a visual tool to facilitate this process. A description is provided regarding how to build the MTM Spider Web using case-based scenarios. This model can be used to teach pharmacists, health professional students, and patients. Conclusion: The MTM Spider Web is an innovative teaching tool that can be used to teach pharmacists and students how to assess complex patients and design a patient-centered care plan to deliver the most appropriate medication therapy.
Micromechanically based poroelastic modeling of fluid flow in Haversian bone.

To explore the hypothesis that load-induced fluid flow in bone is a mechano-transduction mechanism in bone adaptation, unit cell micro-mechanical techniques are used to relate the microstructure of Haversian cortical bone to its effective poroelastic properties. Computational poroelastic models are then applied to compute in vitro Haversian fluid flows in a prismatic specimen of cortical bone during harmonic bending excitations over the frequency range of 10 0 to 10 6 Hz. At each frequency considered, the steady state harmonic response of the poroelastic bone specimen is computed using complex frequencydomain finite element analysis. At the higher frequencies considered, the breakdown of Poisueille flow in Haversian canals is modeled by introduction of a complex fluid viscosity. Peak bone fluid pressures are found to increase linearly with loading frequency in proportion to peak bone stress up to frequencies of approximately 10 kHz. Haversian fluid shear stresses are found to increase linearly with excitation frequency and loading magnitude up until the breakdown of Poisueille flow. Tand values associated with the energy dissipated by load-induced fluid flow are also compared with values measured experimentally in a concurrent broadband spectral analysis of bone. The computational models indicate that fluid shear stresses and fluid pressures in the Haversian system could, under physiologically realistic loading, easily reach the level of a few Pascals, which have been shown in other works to elicit cell responses in vitro. © 2003 American Institute of Physics. @DOI: 10.1115/1.1535191#
NK Cell Tolerance of Self-Specific Activating Receptor KIR2DS1 in Individuals with Cognate HLA-C2 Ligand

NK cells are regulated by inhibiting and activating cell surface receptors. Most inhibitory receptors recognize MHC class I Ags and protect healthy cells from NK cell-mediated autoaggression. However, certain activating receptors, including the human activating killer cell Ig-like receptor (KIR) 2DS1, also recognize MHC class I. This fact raises the question of how NK cells expressing such activating receptors are tolerized to host tissues. We investigated whether the presence of HLA-C2, the cognate ligand for 2DS1, induces tolerance in 2DS1-expressing NK cells. Anti-HLA-C2 activity could be detected in vitro in some 2DS1 positive NK clones irrespective of the presence or absence of HLA-C2 ligand in the donor. The frequency of anti-HLA-C2 reactivity was high in donors homozygous for HLA-C1. Surprisingly, no significant difference was seen in the frequency of anti-HLA-C2 cytotoxicity in donors heterozygous for HLA-C2 and donors without HLA-C2 ligand. However, donors homozygous for HLA-C2, compared with all other donors, had significantly reduced frequency of anti-HLA-C2 reactive clones. The 2DS1 positive clones that express inhibitory KIR for self-HLA class I were commonly noncytotoxic, and anti-HLA-C2 cytotoxicity was nearly exclusively restricted to 2DS1 single positive clones lacking inhibitory KIR. 2DS1 single positive NK clones with anti-HLA-C2 reactivity were also present posttransplantation in HLA-C2 positive recipients of hematopoietic stem cell transplants from 2DS1 positive donors. These results demonstrate that many NK cells with anti-HLA-C2 reactivity are present in HLA-C1 homozygous and heterozygous donors with 2DS1. In contrast, 2DS1 positive clones from HLA-C2 homozygous donors are frequently tolerant to HLA-C2.