cssi/SciSciGPT-SciSciNet huggingface dataset:
Decreased brainstem seizure thresholds and facilitated seizure propagation in mice exposed to repeated flurothyl-induced generalized forebrain seizures

Abstract We recently have described a novel model of epileptogenesis utilizing the inhalant chemoconvulsant, flurothyl (Applegate et al. 1997, Samoriski and Applegate 1997). The hallmark feature of this model is a change in behavioral seizure phenotype from a forebrain seizure, observed during the initial flurothyl exposures, to a brainstem seizure, elicited by flurothyl, after a 28-day stimulation free incubation period. In this study, we sought to establish the basis for this change in behavioral seizure response. To this end, we examined the effects of exposure to this paradigm on the generalized brainstem seizure threshold and on the propagation of forebrain seizures onto the brainstem seizure substrate. Ten mice were given flurothyl-induced generalized forebrain seizures on 8 consecutive days (induction phase). The other ten mice were not exposed to the flurothyl induction paradigm and served as controls. Minimal corneal electroconvulsive shock (mECS—20 mA) was used to assay whether there was any change in the animals' generalized brainstem seizure thresholds at 3, 14 and 28 days following the last flurothyl seizure trial. Mice that were exposed to flurothyl exhibited a progressive increase in the percentage of animals having a mECS-induced brainstem seizure when tested at 3 (40%), 14 (70%) and 28 (90%) days following the last flurothyl seizure. Control mice rarely had a brainstem seizure at any of the three time points tested, mostly forebrain seizures were observed. These results suggest that there is a significant progressive lowering of the brainstem seizure threshold, during the incubation phase of the flurothyl paradigm, which is coincident with the previously reported time course of change in the behavioral seizure phenotype observed using this flurothyl model (Applegate et al. 1997, Samoriski and Applegate 1997). Following mECS testing, mice were implanted with bipolar electrodes and kindled from the olfactory bulb (OB). Mice exposed to the flurothyl paradigm demonstrated significantly faster kindling rates, longer afterdischarge durations, and longer durations of and latencies to stage 5 seizures compared to controls. Furthermore, animals exposed to the flurothyl protocol demonstrated an increase in the expression of brainstem seizures after focally-elicited OB afterdischarges. These results suggest that there is an increased interaction between the forebrain and brainstem seizure systems after exposure to this model of epileptogenesis. Together, results indicate that the change in behavioral seizure phenotype observed following exposure to our flurothyl paradigm are promoted by both decreases in brainstem seizure thresholds and facilitated forebrain seizure propagation onto the brainstem seizure system.
Bonding, Imperfect Structure, and Properties of the Refractory Nitrides of Titanium, Zirconium, and Hafnium

Titanium, zirconium, and hafnium nitrides were investigated by chemical means and by X-ray diffraction concerning their structure. From the dissolution of the nitrides in HF (under formation of NH4 +, N2, and H2), from N2 production at elevated temperatures in vacuum and furthermore, from the heats of formation, lattice energies, hardness, and high melting points, the conclusion was drawn that the bonding in the three nitrides is of a mixed type. The bonding appears to be predominantly ionic and to some extent metallic; the cationic sublattice consists throughout of the trivalent ions (Ti3+, Zr3+, and Hf3+) and there is a nitrogen equilibrium (N ⇌ N3- + 3e) in the anionic sublattice. The partially metallic character of the bonding accounts for the high electrical conductivity, magnetic properties, metallic luster of the nitrides. Since the N atoms do not accept all the available valence electrons from the metal atoms, the average radius of the N anions must be smaller, from 1.4 to 1.425 A, (depending upon the degree of ionization of N) than that calculated for N3-. Using these values for the N ionic radius and the radii of the three trivalent cations, a good agreement between calculated and experimental lattice constants can be reached. There are vacant sides (cationic and anionic) in the three nitrides: 5.14 in the TiN, 4.59 in the ZrN (both containing an excess of N) and 12.62% in the stoichiometric HfN.
Loss of Ubr2, an E3 ubiquitin ligase, leads to chromosome fragility and impaired homologous recombinational repair.

Abstract The N-end rule pathway of protein degradation targets proteins with destabilizing N-terminal residues. Ubr2 is one of the E3 ubiquitin ligases of the mouse N-end rule pathway. We have previously shown that Ubr2−/− male mice are infertile, owing to the arrest of spermatocytes between the leptotene/zygotene and pachytene of meiosis I, the failure of chromosome pairing, and subsequent apoptosis. Here, we report that mouse fibroblast cells derived from Ubr2−/− embryos display genome instability. The frequency of chromosomal bridges and micronuclei were much higher in Ubr2−/− fibroblasts than in +/+ controls. Metaphase chromosome spreads from Ubr2−/− cells revealed a high incidence of spontaneous chromosomal gaps, indicating chromosomal fragility. These fragile sites were generally replicated late in S phase. Ubr2−/− cells were hypersensitive to mitomycin C, a DNA cross-linking agent, but displayed normal sensitivity to gamma-irradiation. A reporter assay showed that Ubr2−/− cells are significantly impaired in the homologous recombination repair of a double strand break. In contrast, Ubr2−/− cells appeared normal in an assay for non-homologous end joining. Our results therefore unveil the role of the ubiquitin ligase Ubr2 in maintaining genome integrity and in homologous recombination repair.
A poetics of nothing: Air in the early modern imagination

This essay explores the materiality of air in three forms: Global Winds, Embodied Breath and Nothing. Each of these three representations appears in different source texts, including Shakespeare's King Lear, early modern scientific writings, cartography, meteorology and classical philosophy. Searching for places in which invisible air pushes back against human perceptions and conception, the essay explores what air has to offer early modern ecocritics.
Economic benefits from early development of fusion

Scenarios of energy growth developed by Federal agencies and private industry place commercial generation of fusion power in the post-2000 era. The model used here estimates the potential direct economic benefits that would accrue if the development of fusion power were accelerated so that commercial generation would be achieved at some earlier date. The model is limited to electrical power generation for three resons: (1) simplicity, (2) the electrical end-use category of the energy economy is large (about 30 percent) and growing, and (3) the use of electricity requires no further adaptation on the part of the user. The evidence presented shows that in all cases of expected introductionnn of fusion and energy demand, the present value of the benefit of accelerating the introductio of fusion power is substantial. These benefits are large even when compared to the estimates of the total cost of the fusion reactor development program, which are on the order of $20 billion. The conclusion can be supported that the large economic benefit inherent in accelerating development of fusion technology warrants immediate development of a model similar to that presented in this report so as to determine the optimum funding rate for accelerating the development ofmore » fusion reactor technology. It is economically wasteful to pursue such a program at less than an optimum rate.« less
Review of the genetics of renal disease.

The results of many of human studies indicate that the genetics of the more common forms of renal disease are quite complex. There are indications that human renal disease may be both polygenic and heterogenic. There are several approaches. Some researchers studying small populations are collecting larger numbers of families with multiple affected individuals. Others are employing discordant sib-pair analysis. Also, trios (individual with renal disease and that individual's parents) have been suggested as a means of collecting larger numbers of people with renal disease.Another population of interest is the group susceptible to nephrotoxicity. At common doses of nephrotoxic drugs and common levels of exposure to environmental and occupational nephrotoxic substances, only a portion of those similarly exposed develop significant renal damage. This subset of individuals may have a genetic susceptibility to renal damage caused by toxic agents.
Afferent innervation of outer hair cells in adult cats: I. Light microscopic analysis of fibers labeled with horseradish peroxidase.

Outer spiral fibers (OSFs) were retrogradely labeled with injections of horseradish peroxidase. After the peripheral arborization patterns were reconstructed at the light microscopic level (Simmons and Liberman, '88), restricted regions of selected fibers were analyzed via electron-microscopic reconstruction of serial sections. The ultrastructural data in the present study suggested that the contact between the outer hair cell (OHC) and the terminal swellings of OSFs corresponds to the afferent synapse described in numerous other ultrastructural studies. The en passant swellings that contacted OHCs also appeared to be points of synaptic contact. However, en passant synapses were not always associated with a swelling of the OSF at the point of contact: thus, the light-microscopic reconstructions probably underestimate the numbers of synapses. OSF branches terminating well below the OHCs were seen to end most commonly in intimate contact with the Deiters' cells. Membrane specialization was occasionally seen at this point of contact; however, the specialization was sufficiently undifferentiated to preclude identification.
Effect of the duration of inoculum exposure on development of citrus canker symptoms on seedlings of Swingle citrumelo

Citrus canker (Xanthomonas citri subsp. citri, Xcc) is one of the most serious diseases citrus in Florida, and elsewhere in the world. The disease causes yield loss and some fresh fruit trade restrictions may apply. Cultural management techniques such as windbreaks may work by not only reducing wind speed, but also reducing the period of exposure of susceptible foliage or fruit to those wind speeds that support infection from incoming inoculum. To investigate the effect of exposure period to inoculum of Xcc, seedlings of canker-susceptible Swingle citrumelo were exposed to sprayed inoculum for increasing periods at different wind speeds. The incidence and severity of citrus canker was assessed. In three experiments the incidence and severity of citrus canker most often increased with longer periods of exposure to inoculum, especially so at wind speeds of ≥16 m/s compared to wind speeds of ≤5 m/s (wind speed also increased disease incidence and severity). Regression analysis demonstrated relationships between period of exposure to inoculum and the percent infected leaves per plant, the number of lesions per plant, the number of lesions per infected leaf, and for the percent of infected leaves with lesions on the petioles at wind speeds of ≥16 m/s (R2 = 0.16–0.72). Due to the effect of inoculum exposure period and wind speed, attempts should be made to minimize exposure of canker-susceptible citrus when wind speed is highest and inoculum is available. Windbreaks should help minimize periods of exposure to splashed inoculum in high winds.
O6-methylguanine-DNA methyltransferase Leu84Phe and Ile143Val polymorphisms and risk of colorectal cancer in the Nurses' Health Study and Physicians' Health Study (United States).

O6-methylguanine-DNA methyltransferase (MGMT) removes mutagenic adducts from the O6-position of guanine in DNA. Unrepaired O6-methylguanines result in G:C to A:T transitions in mutated K-ras and p53 in colorectal tumors. Two non-synonymous MGMT coding region variants, Leu84Phe and Ile143Val, lie in close proximity to the reactive 145Cys residue and to a conserved estrogen receptor interacting helix. We assessed the association between the MGMT Leu84Phe and Ile143Val polymorphisms and risk of colorectal cancer in two nested case–control studies: one each in the Nurses’ Health Study (NHS) and the Physicians’ Health Study (PHS) cohorts. Among 197 female cases and 2,500 controls from the NHS, the variant 143Val allele was significantly associated with reduced risk of colorectal cancer [odds ratio (OR)=0.52, 95% confidence interval (CI) 0.33–0.80]. In women, statistically significant gene-environment interactions were found between the Leu84Phe polymorphism and alcohol intake (P=0.03), BMI (P=0.04) and postmenopausal hormone use (P=0.03). The Leu84Phe and Ile143Val polymorphisms were not significantly associated with risk of colorectal cancer among 271 male cases and 451 controls from the PHS. Our results suggest that the common Leu84Phe and Ile143Val polymorphisms in MGMT influence risk of colorectal cancer in women possibly through modulating estrogen receptor-dependent transcriptional activation, which has previously been shown to occur in response to DNA alkylation damage.
Direct Simulation Monte Carlo Investigation of Hyperthermal Oxygen Beam Exposures

Pulsed sources of hyperthermal O-atoms are now being extensively used to simulate low-Earth-orbit (LEO) surface exposure environments. The peak flux of these sources is many orders of magnitude larger than the corresponding LEO flux. Although it is desirable to accelerate the test by using higher fluxes than found in LEO, even commonly used fluxes are large enough to produce multicollision effects by causing a buildup of gas at the sample surface. We characterize the physical consequences to the experiment using the direct simulation Monte Carlo (DSMC) method. DSMC allows us to extract the distributions of energy and impact angle for the O-atoms that reach the surface and to record how strongly the gas buildup at the target assembly deflects flux from downstream instrumentation. By considering a range of source fluxes, we determine the onset conditions and severity of these multicollision effects. We find that, depending on the target properties, even at common experimental fluxes with a normally incident beam striking a flat surface sample, the energy distribution of incident O-atoms can broaden and develop a significant low-energy tail. The distribution of the angle of impact can also broaden significantly, and the number of O-atoms that reach downstream instrumentation can be attenuated by as much as ∼50%. These simulations will aid in the calibration of ground-based O-atom measuremehts and provide a model for the energy and angular distributions of O-atoms that actually impinge on surface samples.
An Exploration of Deception as a Communication Construct

Even though most of us lie from time to time, it is really quite surprising how little is known about such behaviors. Through controlled observation and laboratory testing, this study attempted to determine what verbal and nonverbal behaviors were characteristic of intentionally deceptive communicators. Seventy-six videotaped interviews provided a data base for the analysis of 32 dependent measures. In addition to analyses of specific behavioral differences between deceivers and nondeceivers, the authors provide a conceptual framework for the study of deception—predicting that deceivers will exhibit significantly more uncertainty, vagueness, nervousness, reticence, dependence, and unpleasantness than nondeceivers.
Vibrational properties of hydrogenated amorphous GaAs

Abstract The vibrational spectra and the characteristics of hydrogen evolution upon heating of a series of amorphous GaAs1−xHx films prepared by rf sputtering are presented. Some films were deuterated, and in another series nitrogen was included in addition to hydrogen. The first and second order vibrations of the underlying network, as well as other modes due to hydrogen incorporation, have been observed in Raman and IR measurements. Annealing at temperatures selected by the features of the hydrogen evolution leads to the selective disappearance of certain vibrational modes assigned to hydrogen bonding. IR studies on rehydrogenated films were not conclusive.
Landscape connectivity and seed dispersal characteristics inform the best management strategy for exotic plants

Exotic plant invasions have triggered environmental and economic problems throughout the world. Our ability to manage these invasions is hindered by the difficulty of predicting spread in fragmented landscapes. Because the spatial pattern of invasions depends on the dispersal characteristics of the invasive species and the configuration of suitable habitat within the landscape, a universal management strategy is unlikely to succeed for any particular species. We suggest that the most effective management strategy may be an adaptive one that shifts from local control to landscape management depending on the specific invader and landscape. In particular, we addressed the question of where management activities should be focused to minimize spread of the invading species. By simulating an invasion across a real landscape (Antietam National Battlefield in Maryland, USA), we examined the importance of patch size and connectivity to management success. We found that the best management strategy depended on the dispersal characteristics of the exotic species. Species with a high probability of random long-distance dispersal were best managed by focusing on the largest patches, while species with a lower probability of random long-distance dispersal were best managed by considering landscape configuration and connectivity of the patches. Connectivity metrics from network analysis were useful for identifying the most effective places to focus management efforts. These results provide insight into invasion patterns of various species and suggest a general rule for managers in National Parks and other places where invasive species are a concern.
Fluoroacrylate copolymer-supported rhodium catalysts for hydrogenation reactions in supercritical carbon dioxide

We have attached a homogeneous rhodium catalyst to a fluoroacrylate copolymer backbone, making it soluble in supercritical carbon dioxide. The polymer was synthesized by the polymerization of 1H,1H,2H,2H-heptadecafluorodecyl acrylate monomer (zonyl TAN) (I), available from Dupont, and N-acrylosuccinimide (NASI), the former increasing the solubility in supercritical carbon dioxide and the latter providing attachment sites for the catalyst. Diphenylphosphinopropylamine, NH2(CH2)3PPh2 (DPPA), was used to exchange the NASI groups in the polymer, which was then reacted with [RhCl(COD)]2 to obtain the catalyst. We determined that the catalyst is soluble in supercritical carbon dioxide and evaluated its hydrogenation activity using 1-octene and cyclohexene hydrogenation as model reactions. The synthesis route for the catalyst is reproducible, as shown by reaction activity studies on different batches of catalyst. The catalyst was evaluated at different substrate-to-rhodium molar ratios and at different temperatu...
The Peace Scale: Conceptualizing and Operationalizing Non-Rivalry and Peace:

Most efforts in international relations scholarship focus on understanding war and conflict. To the extent that peace is considered, it is often treated as an afterthought or a control condition. In this paper, we construct a five-level scale of dyadic peace. We then operationalize the scale using indicators suggested by different scholarly literatures as well as measures derived from case studies. Further, we advocate the use of “anchor cases” and pair-wise comparisons to code dyadic peace in non-rivalry periods. We conclude with a pilot study of the scale, as applied to pairs of states over the period From 1816 to 2006.
ERK2 but Not ERK1 Induces Epithelial-to-Mesenchymal Transformation via DEF Motif-Dependent Signaling Events

Hyperactivation of Ras-ERK1/2 signaling is critical to the development of many human malignancies, but little is known regarding the specific contribution of ERK1 or ERK2 to oncogenic processes. We demonstrate that ERK2 but not ERK1 signaling is necessary for Ras-induced epithelial-to-mesenchymal transformation (EMT). Further, ERK2 but not ERK1 overexpression is sufficient to induce EMT. Many ERK1/2-interacting proteins contain amino acid motifs, e.g., DEF or D-motifs, which regulate docking with ERK1/2. Remarkably, ERK2 signaling to DEF motif-containing targets is required to induce EMT and correlates with increased migration, invasion, and survival. Importantly, the late-response gene product Fra1 is necessary for Ras- and ERK2-induced EMT through upregulation of ZEB1/2 proteins. Thus, an apparent critical role for ERK2 DEF motif signaling during tumorigenesis is the regulation of Fra1 and the subsequent induction of ZEB1/2, suggesting a potential therapeutic target for Ras-regulated tumorigenesis.
LU Factorization of Non-standard Forms and Direct Multiresolution Solvers

Abstract In this paper we introduce the multiresolution LU factorization of non-standard forms (NS-forms) and develop fast direct multiresolution methods for solving systems of linear algebraic equations arising in elliptic problems. The NS-form has been shown to provide a sparse representation for a wide class of operators, including those arising in strictly elliptic problems. For example, Green's functions of such operators (which are ordinarily represented by dense matrices, e.g., of size N by N ) may be represented by −log ϵ· N coefficients, where ϵ is the desired accuracy. The NS-form is not an ordinary[fn9] matrix representation and the usual operations such as multiplication of a vector by the NS-form are different from the standard matrix–vector multiplication. We show that (up to a fixed but arbitrary accuracy) the sparsity of the LU factorization is maintained on any finite number of scales for self-adjoint strictly elliptic operators and their inverses. Moreover, the condition number of matrices for which we compute the usual LU factorization at different scales is O (1). The direct multiresolution solver presents, therefore, an alternative to a multigrid approach and may be interpreted as a multigrid method with a single V-cycle. For self-adjoint strictly elliptic operators the multiresolution LU factorization requires only O ((−log ϵ) 2 ·N ) operations. Combined with O ( N ) procedures of multiresolution forward and back substitutions, it yields a fast direct multiresolution solver. We also describe direct methods for solving matrix equations and demonstrate how to construct the inverse in O ( N ) operations (up to a fixed but arbitrary accuracy). We present several numerical examples which illustrate the algorithms developed in the paper. Finally, we outline several directions for generalization of our algorithms. In particular, we note that the multidimensional versions of the multiresolution LU factorization maintain sparsity, unlike the usual LU factorization.
Teaching motion planning concepts to undergraduate students

Motion planning is a central problem in robotics. Although it is an engaging topic for undergraduate students, it is difficult to teach, and as a result, the material is often only covered at an abstract level. Deep learning could be achieved by having students implement and test different algorithms. However, there is usually no time within a single class to have students completely implement several motion planning algorithms as they require the development of many lower-level data structures. We present an ongoing project to develop a teaching module for robotic motion planning centered around an integrated software environment. The module can be taught early in the undergraduate curriculum, after students have taken an introductory programming class. I. INTRODUCTION Robots play an increasingly important role in our daily lives. For many familiar applications such as urban search-and-rescue, planetary exploration, and household chores it is critical that robots efficiently find paths (i.e., motion plans) from starting locations to desired goals. Although motion planning at an abstract level is a fairly intuitive concept, it is a topic that is difficult to teach. The difficulty arises because deep understand- ing of motion planning concepts requires hands-on experience with different algorithms. However, the low-level programming details in the implementation of these algorithms can often obscure high-level concepts, which are necessary for a solid understanding of the subject. This paper describes an ongoing project that aims to provide the software tools and curricular material that will help fill some of the gaps in undergraduate robotics education. Many colleges offer introductory robotics classes early in the curriculum, often to attract students to Science, Technology, Engineering, and Mathematics (STEM) disciplines. However, any subsequent robotics classes are often only available at the senior undergraduate level or beginning graduate level. They tend to include many topics in an effort to teach the students as much as possible about an extremely diverse area. Available robotics textbooks (1-3) cover many topics and challenge the student as well as the instructor to keep up. The project described herein focuses exclusively on one core concept in robotics: motion planning. Motion planning is a mature field within robotics and often comprises a significant part of advanced robotics classes. In two recent robotics M. Moll, I. Sucan, and L. Kavraki are with the Department of Com-
Development and evaluation of a novel marine sediment pore water toxicity test with the polychaete dinophilus gyrociliatus

As a candidate for future use in the National Status and Trends Program, a novel marine sediment pore water toxicity test procedure was developed and evaluated. The test procedure involves obtaining sediment pore water with a pressurized squeeze-extraction device, and then conducting a life-cycle toxicity test with the polychaete Dinophilus gyrociliatus. Recent studies have demonstrated that for certain nonpolar organic contaminants, the key route of exposure is from the interstitial (pore) water. Sediment samples were collected from 15 different stations in the San Francisco Bay area with varying amounts of contamination. The results from the San Francisco study and other studies conducted during the development of this test procedure are reported.
Timber harvest interacts with broad-scale forest mortality to affect site occupancy dynamics of a vertebrate seed predator

Abstract Extensive ecological disturbances can interact with spatial heterogeneity produced by previous disturbances, influencing responses of vertebrates to environmental change. Recent and ongoing outbreaks of bark beetles (including Dendroctonus spp. and Dryocoetes confuses) in the Rocky Mountains produced an opportunity to investigate effects of broad-scale tree mortality on an important seed predator in Nearctic coniferous forests, the red squirrel (Tamiasciurus hudsonicus), and to evaluate whether those effects interact with forest heterogeneity produced by previous timber harvest. Our study characterized site occupancy dynamics for red squirrels in relation to patch-cutting, a type of group-selection cut, and the bark-beetle outbreak, and evaluated whether patch cutting influenced subsequent effects of bark beetles on these squirrels. We used multi-season occupancy models and covariates for harvest- and outbreak-related habitat characteristics to describe extinction and colonization rates of red squirrels over a 27-yr period in Wyoming, USA. We observed effects of year, patch-cutting, and the bark beetle outbreak on the probability of detecting a red squirrel. We observed a negative association between local extinction rate and increasing snag density, but only to a threshold of 5 snags/0.04 ha. Local colonization rate was positively associated with the basal area of live trees. Annual site occupancy varied across years (range pre-harvest: 0.76–0.89; post-harvest: 0.84–0.99), and was lowest (0.70–0.72) during the two years sampling occurred approximately 14 years after the bark beetle outbreaks began. Tree mortality was lowest near patch cuts; this pattern was especially pronounced for mature trees (>30 cm diameter at breast height), which tend to produce the most cones and would likely contribute the most to red squirrel survival. Strong habitat effects on occupancy dynamics suggest that previously-harvested areas may provide refugia for red squirrels in post-outbreak forests. Our results support managing for uneven-aged stands of mixed species composition in subalpine forests of the Rocky Mountains.
Effectiveness of prophylactic mastectomy in the prevention of breast tumors in C3H mice

The effectiveness of prophylactic mastectomy in the prevention of breast tumors was studied in spontaneous breast-tumor-forming C3H mice. Prolactin levels were assayed to determine if this hormone was related to the incidence of mammary tumors. Two-hundred and fifty-six 1-month-old C3H mice were divided into four groups (control, 1; sham surgery, 2; mammectomy 50 percent, 3; and mammectomy 100 percent, 4). At the time of sacrifice (0 to 1 year postoperatively) estrus cycles were determined, ventral skin (breast) and ovaries were removed for histology, and serum was collected for prolactin assays. Prolactin levels 24 hours postoperatively were significantly elevated (p less than 0.01) in groups 2 to 4 when compared with group 1. Six months postoperatively, prolactin levels were significantly higher (p less than 0.05) in mice with tumors compared with those without tumors in groups 3 and 4. There were no differences in tumor incidence between the four groups. At 12 months postoperatively, no differences in prolactin levels were noted, but group 2 animals had the highest incidence of mammary tumors (89 percent; p less than 0.01) when compared to groups 3 and 4. Mammary tumor incidence was not decreased by 50 percent or 100 percent mammectomy in C3H mice. Prolactin levels rose in response to surgery and/or anesthesia and remained elevated only in tumor-bearing mice who underwent mammectomy, an occurrence similar to that reported in humans.
Systematic approach to generate near-perfect periodic continuous random network models: Application to amorphous Si3N4.

A systematic method to generate periodic continuous random network models for covalent glasses is described. The method is based on the judicious choice of elementary subunits which satisfy local bonding. By connecting the subunits carefully to meet the bonding requirements of the corner atoms, an initial model with proper topological structure is formed. Randomness is introduced through the random distribution of different subunit types. The model is then relaxed by suitable potential functions to minimize the distortions. The method has been successfully applied to obtain amorphous Si{sub 3}N{sub 4} models of various sizes. {copyright} {ital 1996 The American Physical Society.}
Behavior “recovery” during chronic reserpine treatment: Effect of dose of reserpine

Various doses of reserpine were administered chronically to rats which were tested for rotarod performance and spontaneous locomotor activity. Doses of 0.0625, 0.125 and 0.25 mg/kg/day produced depression of rotarod performance after varying periods of treatment. No evidence of recovery of performance was observed during treatment with any dose. Doses of 0.125, 0.25 and 0.5 mg/kg/ day produced depression of spontaneous locomotor activity after varying periods of treatment. “Recovery” of activity was observed after the initial depression. A subsequent phase of hyperactivity occurred during treatment with 0.5 and 0.25 mg/kg while activity of the animals treated with 0.125 mg/kg became depressed and remained depressed during another 32 days of treatment. It is suggested that more than one action of reserpine should be considered in the explanation of these results.
The changing etiology of constrictive pericarditis in a large referral center

Abstract Constrictive pericarditis (CP) has classically been attributed to tuberculous infection, 1,2 purulent pericarditis or a nonspecific antecedent pericardial disease. In recent decades, with the advent of effective infectious disease prophylaxis and antimicrobial therapy, the incidence of purulent pericarditis has dramatically declined. 3 The incidence of tuberculous pericarditis and resultant CP has paralleled this decline. 4–8 Because f an increasingly older population the incidences of coronary atherosclerosis, senile valvular disease, chronic renal disease and neoplasms of the chest have increased. These diseases and their surgical and nonsurgical therapies have occasionally resulted in CP. Thus, infection control, increasing longevity and the therapeutic modalities to manage the diseases of an aging population have changed the etiology of CP in the United States. This study delineates the origin of CP at the Cleveland Clinic from October 1983 through September 1984.
Tolerancing and alignment of a three-mirror off-axis telescope

When the optical elements of a system are not collinear, there are advantages to aligning all elements simultaneously. This paper presents the steps taken to prepare for system alignment and the alignment plan for such a system. A tolerance analysis of the system defines the compensators necessary for system alignment and allows an estimate of the expected magnitude of initial aberrations present in the system. Polarization and pupil aberrations are characterized in order to further understand expected system aberrations before alignment. A two step alignment plan is outlined. First, a CCD array placed at the focal plane indicates spot size and shape as elements are aligned. Once spot size is minimized, the CCD array is replaced by a ball bearing for retroreflection. Useful interferograms can be obtained with which remaining aberrations can be minimized. This technique is presented as the alignment plan for an off-axis telescope system consisting of one spherical and two ellipsoidal mirrors.
Assembly of Outer Membrane β-Barrel Proteins: the Bam Complex

The major class of integral proteins found in the outer membrane (OM) of E. coli and Salmonella adopt a β-barrel conformation (OMPs). OMPs are synthesized in the cytoplasm with a typical signal sequence at the amino terminus, which directs them to the secretion machinery (SecYEG) located in the inner membrane for translocation to the periplasm. Chaperones such as SurA, or DegP and Skp, escort these proteins across the aqueous periplasm protecting them from aggregation. The chaperones then deliver OMPs to a highly conserved outer membrane assembly site termed the Bam complex. In E. coli, the Bam complex is composed of an essential OMP, BamA, and four associated OM lipoproteins, BamBCDE, one of which, BamD, is also essential. Here we provide an overview of what we know about the process of OMP assembly and outline the various hypotheses that have been proposed to explain how proteins might be integrated into the asymmetric OM lipid bilayer in an environment that lacks obvious energy sources. In addition, we describe the envelope stress responses that ensure the fidelity of OM biogenesis and how factors, such as phage and certain toxins, have coopted this essential machine to gain entry into the cell.
Population biology: The prodigal fish

It used to be thought that fish larvae, at the mercy of the currents, drifted vast distances through the open ocean. But two studies of reef fish show that a surprisingly high proportion of them never leave the waters in which they were spawned. This finding has implications for the management of marine ecosystems.
The ponto-cerebellar projection in the rat: differential projections to sublobules of the uvula.

Microinjections of horseradish peroxidase (HRP) were made in different sublobules of the uvula (lobule IX, a, b, and c of Larsell, 1952) of the cerebellar cortex in the rat. These injections resulted in retrograde labeling of cells located in the pontine nuclei. Sublobule IXa receives a predominant input from a single column of cells situated in a dorsointermediate position in the caudal pontine nuclei. Sublobules IXb and IXc receive a pontine projection from two different columns of cells, one medial and one lateral. The location of the labeled cells in the lateral part of the caudal pons suggests a topographic projection to the subdivisions of the uvula. Sublobule IXa receives a projection from a distinct dorsointermediate region and sublobule IXb and IXc receive a projection from partially overlapping ventral regions. The cells of origin in the medial pons are organized such that more dorsally located cells project to sublobule IXc and ventrally located cells project to sublobule IXb with extensive overlap. These differential patterns of projections to the sublobules of the uvula along with other data in the literature suggest that sublobule IXa may be involved with different functional correlates than sublobules IXb and IXc.
Predictors and pathways to civic involvement in emerging adulthood: neighborhood, family, and school influences.

Understanding the developmental precursors to civic involvement in emerging adulthood is important to help cultivate and sustain youth’s civic involvement. Guided by Bronfenbrenner’s ecological theory of human development and social capital theory, this study examined the pathways that link childhood neighborhood attributes, changes in family and school social capital during adolescence, and civic involvement in emerging adulthood. Three waves of data from the National Longitudinal Study of Adolescent Health (n = 7,209, 54 % female, 63 % white, 18 % African-American, 11 % Hispanic) and multi-level models were used to examine the research questions set forth in this study. Findings revealed that increases in family and school social capital during adolescence had direct influences on emerging adult’s civic involvement 7 years later. The effect of childhood neighborhood attributes was only weakly mediated by family and school social capital. However, the expression of family and school influences on emerging adult’s civic involvement was found to differ by neighborhood groups, gender, and race. These results help to illustrate the importance of examining multi-contextual as well as demographic influences on civic involvement in emerging adulthood. In addition, the results from this study can inform efforts to strengthen the theory of adolescent civic involvement and policies on how to educate youth and communities on civic involvement and its benefits.
Biological components of Ross Sea short-term particle fluxes in the austral summer of 1995–1996

Abstract The Ross Sea, a region of high seasonal production in the Southern Ocean, is characterized by blooms of the haptophyte Phaeocystis antarctica and of diatoms. The different morphology, structural composition and consumption of these two phytoplankton by grazing zooplankton may result in different carbon cycling dynamics and carbon flux from the euphotic zone. We sampled short-term (∼2 days) particle flux at 5 sites from 177.6°W to 165°E along a transect at 76.5°S with traps placed below the euphotic zone at 200 m during December 1995–January 1996. We estimated carbon flux of as many eucaryotic organisms and fecal pellets as possible using microscopy for counts and measurements and applying volume:carbon conversions from the literature. Eucaryotic organisms contributed about 20–40% of the total organic carbon flux in both the central Ross Sea polynya and in the western polynya, and groups of organisms differed in contribution to the carbon flux at the different sites. Algal carbon flux ranged from 4.5 to 21.1 mg C m −2 day −1 and consisted primarily of P. antarctica (cell plus mucus) and diatom carbon at all sites. Different diatom species dominated the diatom flux at different sites. Carbon fluxes of small pennate diatoms may have been enhanced by scavenging, by sinking senescent P. antarctica colonies. Heterotrophic carbon flux ranged from 9.2 to 37.6 mg C m −2 day −1 and was dominated by athecate heterotrophic dinoflagellate carbon in general and by carbon flux of a particular large athecate dinoflagellate at two sites. Fecal pellet carbon flux ranged from 4.6 to 54.5 mg C m −2 day −1 and was dominated by carbon from ovoid/angular pellets at most sites. Analysis of fecal pellet contents suggested that large protozoans identified by light microscopy contributed to ovoid/angular fecal pellet fluxes. Carbon flux as a percentage of daily primary production was lowest at sites where P. antarctica predominated in the water column and was highest at sites where fecal pellet flux was highest. This indicates the importance of grazers in carbon export.
Stoichiometry and geometry of the CXC chemokine receptor 4 complex with CXC ligand 12: Molecular modeling and experimental validation

Chemokines and their receptors regulate cell migration during development, immune system function, and in inflammatory diseases, making them important therapeutic targets. Nevertheless, the structural basis of receptor:chemokine interaction is poorly understood. Adding to the complexity of the problem is the persistently dimeric behavior of receptors observed in cell-based studies, which in combination with structural and mutagenesis data, suggest several possibilities for receptor:chemokine complex stoichiometry. In this study, a combination of computational, functional, and biophysical approaches was used to elucidate the stoichiometry and geometry of the interaction between the CXC-type chemokine receptor 4 (CXCR4) and its ligand CXCL12. First, relevance and feasibility of a 2:1 stoichiometry hypothesis was probed using functional complementation experiments with multiple pairs of complementary nonfunctional CXCR4 mutants. Next, the importance of dimers of WT CXCR4 was explored using the strategy of dimer dilution, where WT receptor dimerization is disrupted by increasing expression of nonfunctional CXCR4 mutants. The results of these experiments were supportive of a 1:1 stoichiometry, although the latter could not simultaneously reconcile existing structural and mutagenesis data. To resolve the contradiction, cysteine trapping experiments were used to derive residue proximity constraints that enabled construction of a validated 1:1 receptor:chemokine model, consistent with the paradigmatic two-site hypothesis of receptor activation. The observation of a 1:1 stoichiometry is in line with accumulating evidence supporting monomers as minimal functional units of G protein-coupled receptors, and suggests transmission of conformational changes across the dimer interface as the most probable mechanism of altered signaling by receptor heterodimers.
Studies on the crustacean cardiac ganglion.

Abstract 1. An overview of studies on the decapod crustacean cardiac ganglion is given emphasizing contributions to questions of general interest in cellular neurophysiology. 2. John Welsh, in 1951, introduced this 9-celled, semi-autonomous ganglion as a preparation offering physiologists unique experimental possibilities. 3. It exhibits remarkable reliability and stability in rhythmic pattern generation. The neurons show endogenous burst-forming capability mediated by “driver potentials”. 4. These regenerative, Ca-mediated potentials are restricted to the soma, while impulse-generating membrane is segregated to the distal axon. 5. Thus, voltage-clamp analysis of the ionic currents underlying the burst-forming potentials is possible by isolating the soma with a ligature. 6. The isolated ganglion is spontaneously active, but the normal mechanism of pacemaking remains to be clarified, including the possible contribution of stretch-sensitive dendrites. 7. The activity of the ganglion is subject to modulation by neurohumors. These include the transmitter at intraganglionic synapses, transmitters of the pair of inhibitory and the two pairs of acceleratory fibers, and neurohormones released from the pericardial organs. The transmitters are not established. 8. Effects on the ganglion of substances isolated from the pericardial organs have been described. 9. These include 5-hydroxytryptamine, dopamine, octopamine, and two peptides. 10. One of these, proctolin, produces a long-lasting sequence of effects. 11. The work continues to raise new questions for which the ganglion offers excellent research material.
Synthesis of Macroheterocycles through Intramolecular Oxidative Coupling of Furanoid β-Ketoesters

Furanocembranoids are an intriguing class of marine diterpenoids characterized by a C14 cembrane skeleton with an embedded furan heterocycle.[1] Derived from these structures are various more advanced secondary metabolites arising through biooxidation of their furan moieties into more complex cembranoids which often undergo transannular transformations involving carbon–carbon and/or carbon–oxygen bond formations.[1] Bielschowskysin (1),[2] verrillin (2),[3] and plumarellide (3)[4] are three such molecules (Figure 1a). Their origins can be traced back to exo-enol ether/cyclic hemiacetal precursors 4, 5, and 6, respectively, as shown in Figure 1a. Methods for the synthesis of the latter precursors are, therefore, crucial to testing such biosynthetic hypotheses and to synthetic strategies toward these natural products. In addition to the cytotoxic and antimalarial properties that many furanocembranoids exhibit,[1a] these macrocyclic exo-enol ether/cyclic hemiacetal structural motifs (see A, Figure 1b) may be of interest to chemical biology and medicinal chemistry as novel molecular diversity whose biological properties remain largely unexplored.
Comparison of Usefulness of Left Ventricular Diastolic Versus Systolic Function as a Predictor of Outcome Following Primary Percutaneous Coronary Angioplasty for Acute Myocardial Infarction

Left ventricular (LV) diastolic function is an important predictor of morbidity and mortality after acute myocardial infarction (AMI). We evaluated the role of diastolic function in predicting in-hospital events and LV ejection fraction (EF) 6 months after a first AMI that was treated with primary percutaneous coronary intervention (PCI). We prospectively enrolled 59 consecutive patients who were 60 +/- 15 years of age (48 men), presented at our institution with their first AMI, and were treated with primary PCI. Patients underwent 2-dimensional and Doppler echocardiography, including tissue Doppler imaging of 6 basal mitral annular regions within 24 hours after primary PCI and were followed until discharge. Clinical and echocardiographic variables at index AMI were compared with a combined end point of cardiac death, ventricular tachycardia, congestive heart failure, or emergency in-hospital surgical revascularization. Follow-up echocardiographic assessment was performed at 6 months in 24 patients. During hospitalization, 3 patients died, 7 developed congestive heart failure, 4 had ventricular tachycardia, and 1 required emergency surgical revascularization. Stepwise logistic regression analysis showed the ratio of early mitral inflow diastolic filling wave (E) to peak early diastolic velocity of non-infarct-related mitral annulus (p < 0.01) (E') and mitral inflow E-wave deceleration time (p < 0.02) to be independent predictors of in-hospital cardiac events (generalized R2 = 0.66). In a stepwise multiple linear regression model, independent predictors of follow-up LVEF were mitral inflow deceleration time (R2 = 0.39, p = 0.002), baseline LVEF (R2 = 0.54, p < 0.02), and mitral inflow peak early velocity/mitral annular peak early velocity (or E/E') of infarct annulus (R2 = 0.66, p = 0.02). In conclusion, in patients who are treated with primary PCI for a first AMI, E/E' velocity ratio and mitral inflow E-wave deceleration time are strong predictors of in-hospital cardiac events and of LVEF at 6-month follow-up.