cssi/SciSciGPT-SciSciNet huggingface dataset:
Tigecycline: A glycylcycline antimicrobial agent

Abstract Background: Tigecycline, the first glycylcycline to be approved by the US Food and Drug Administration, is a structural analogue of minocycline that was designed to avoid tetracycline resistance mediated by ribosomal protection and drug efflux. It is indicated for the treatment of complicated skin and skin-structure infections and complicated intra-abdominal infections and is available for intravenous administration only. Objective: This article summarizes the in vitro and in vivo activities and pharmacologic and pharmacokinetic properties of tigecycline, and reviews its clinical efficacy and tolerability profile. Methods: Relevant information was identified through a search of MEDLINE (1966-April 2006), Iowa Drug Information Service (1966-April 2006), and International Pharmaceutical Abstracts (1970-April 2006) using the terms tigecycline, GAR-936 , and glycylcycline . Also consulted were abstracts and posters from meetings of the Infectious Diseases Society of America and the Interscience Conference on Antimicrobial Agents and Chemotherapy (1999–2006) and documents provided for formulary consideration by the US manufacturer of tigecycline. Results: Like the tetracyclines, tigecycline binds to the 30S subunit of bacterial ribosomes and inhibits protein synthesis by preventing the incorporation of amino acid residues into elongating peptide chains. In vitro, tigecycline exhibits activity against a wide range of clinically significant gram-positive and gram-negative bacteria, including multidrug-resistant strains (eg, oxacillin-resistant Staphylococcus aureus , vancomycin-resistant enterococci, extended-spectrum β-lactamase-producing Enterobacteriaceae), and anaerobes (eg, Bacteroides spp). In pharmacokinetic studies in human adults, tigecycline had a large Vd (7–9 L/kg), was moderately bound to plasma protein (71%–89%), had an elimination t 1/2 of 42.4 hours, and was eliminated primarily by biliary/fecal (59%) and renal (33%) excretion. Dose adjustment did not appear to be necessary based on age, sex, renal function, or mild to moderate hepatic impairment (Child-Pugh class A–B). In patients with severe hepatic impairment (Child-Pugh class C), the maintenance dose should be reduced by 50%. In 4 Phase III clinical trials in patients with complicated skin and skin-structure infections and complicated intra-abdominal infections, tigecycline was reported to be noninferior to its comparators (vancomycin + aztreonam in 2 studies and imipenem/cilastatin in 2 studies), with clinical cure rates among clinically evaluable patients of >80% ( P Conclusions: In clinical trials, tigecycline was effective for the treatment of complicated skin and skin-structure infections and complicated intra-abdominal infections. With the exception of gastrointestinal adverse events, tigecycline was generally well tolerated. With a broad spectrum of activity that includes multidrug-resistant gram-positive and gram-negative pathogens, tigecycline may be useful in the treatment of conditions caused by these pathogens.
Increases in the activated forms of ERK 1/2, p38 MAPK, and CREB are correlated with the expression of at-level mechanical allodynia following spinal cord injury

Rats given moderate spinal cord injury (SCI) display increases in the expression of the activated form of the transcription factor cyclic AMP responsive element binding protein (CREB) in spinal segments of dermatomes corresponding to permanent mechanical allodynia, a model of chronic central neuropathic pain (CNP; (Crown, E.D., Ye, Z., Johnson, K.M., Xu, G.Y., McAdoo, D.J., Westlund, K.N., Hulsebosch, C.E., 2005. Upregulation of the phosphorylated form of CREB in spinothalamic tract cells following spinal cord injury: relation to central neuropathic pain. Neurosci. Lett. 384, 139-144)). Given that not all rats that receive moderate SCI develop CNP, the current study was designed to further analyze changes in persistent CREB activation and in the activation state of upstream intracellular signaling cascades (e.g., mitogen-activated protein kinases [MAPKs]) in populations of rats that receive SCI and weeks later develop CNP and rats that receive SCI but do not develop CNP. The results indicate that activated kinases such as pERK 1/2, p-p38 MAPK, but not pJNK, are upregulated in injured rats that develop CNP as compared to injured rats that fail to develop CNP. In addition, the current results replicated our previous finding that activated CREB is upregulated following SCI, however, only in SCI rats that developed CNP. Taken together, these results indicate that activation of intracellular signaling cascades traditionally associated with long-term potentiation and memory is associated with the expression of chronic CNP following SCI.
Characterization of a Microfluidic Based Direct-Methanol Fuel Cell

The performance of a membraneless laminar flow micro fuel cell was evaluated under different operating conditions. The fuel cell was microfabricated in poly-dimethyl-siloxane using standard soft-lithography techniques. It used methanol solution as the fuel for the anode side, and oxygen saturated sulfuric acid for the cathode. The parameters studied were the methanol concentration and the concentration of sulfuric acid in the anode stream. The performance was characterized by V-I plots, stability of open circuit potential, and anode polarization curves. Our results show that the power output of the device decreases with increase in the methanol concentration. It is shown that these trends are caused by the cell’s internal resistance to proton transport. The addition of sulfuric acid to the fuel significantly decreases this resistance. The device open circuit potential was not stable over extended operation, and could drop by more than 150 mV in 72 hours.Copyright © 2008 by ASME
The interconversion of monosaccharide configurations: Labinose to lyxose

Abstract Selective oxidation of the primary hydroxyl group of 1,3-O-benzylidene- D -arabinitol (1) with methyl sulfoxide-N,itN′-dicyclohexylcarbodiimide-pyridinium trifluoroacetate (Pfitzner–Moffatt reagent), followed by debenzylidenation, provided a route for configurational conversion of D -arabinose into D -lyxose (4). The same reaction-sequence was then used for the synthesis of the L enantiomers. The sugars prepared were purified by ion-exchange column chromatography and characterized by o.r.d., n.m.r., t.l.c., and g.l.c.
A model of geomagnetic secular variation for 1980–1983

Abstract We developed an updated model of the secular variation of the main geomagnetic field during 1980 through 1983 based on annual mean values for that interval from 148 worldwide magnetic observatories. The model consists of a series of 80 spherical harmonics, up to and including those of degree and order 8. We used it to form a proposal for the 1985 revision of the International Geomagnetic Reference Field (IGRF). Comparison of the new model, whose mean epoch is approximately 1982.0, with the Provisional Geomagnetic Reference Field for 1975–1980 (PGRF 1975), indicates that the moment of the centered-dipole part of the geomagnetic field is now decreasing faster than it was 5 years ago. The rate (in field units) indicated by PGRF 1975 was about −25 nT a−1, while for the new model it is −28 nT a−1.
Pat-hological dynamic behavior of forced periodic chemical processes

Abstract Nonlinear chemical process systems which are periodically forced do not necessarily have unique, stable periodic responses with the same period as the input, although such behavior has been widely assumed previously. Theory for the as symptotic case of very fast forced cycling indicates that systems which possess multiple steady-states or self-oscillations under unforced conditions may exhibit unusual dynamic phenomena under forced periodic operation. Simulations of a periodically forced CSTR reveal several jumps in forced system qualitative behavior as the forcing frequency is altered. Among the pathological responses obtained for the CSTR example are multiple stable forced states, subharmonic oscillations, and almost periodic outputs.
Multiplexed sensing based on Brownian relaxation of magnetic nanoparticles using a compact AC susceptometer.

A novel multiplexed sensing scheme based on the measurement of the magnetic susceptibility of the affinity captured target molecules on magnetic nanoparticles in liquid suspension is proposed. The AC magnetic susceptibility provides a measurement of Brownian relaxation behavior of biomolecules bound to magnetic nanoparticles (MNPs) that is related to its hydrodynamic size. A room temperature, compact AC susceptometer is designed and developed to measure complex AC magnetic susceptibility of such magnetic nanoparticles. The AC susceptometer exhibits high sensitivity in magnetic fields as low as 10 µT for 1 mg ml−1 concentration and 5 µl volume, and is fully software programmable. The capability of biological sensing using the proposed scheme has been demonstrated in proof of principle using the binding of biotinylated horseradish peroxidase (HRP) to streptavidin-coated MNPs. The proposed technique and instrument are readily compatible with lab-on-chip applications for point-of-care medical applications.
Unblocking in a runway discrimination problem produced by a surprising reduction in S— reward magnitude: The role of generalization decrement

Blocking and unblocking groups were trained in Phase 1 on an instrumental discrimination task in which internal cues were relevant and brightness cues were irrelevant. The blocking group received large reward (L) in S+ and nonreward (N) in S− in both Phase 1 and Phase 2 and failed to learn about brightness when brightness cues were added as relevant, but redundant, discriminanda in Phase 2. Groups Unblocking:S and Unblocking:S+N received small reward (S) or a mixture of S and N trials, respectively, in S− in Phase 1, but otherwise were trained in the same manner as the blocking group. Both unblocking groups experienced a shift to all N trials in S− coincident with the addition of brightness as a relevant cue at the beginning of Phase 2. Brightness cues acquired very substantial, and equal, discriminative control in both unblocking groups and a control group trained only in Phase 2 with internal cues and brightness cues simultaneously relevant.
Pituitary Responsiveness to Aqueous Vasopressin in Patients with Congenital Vasopressin-Resistant Diabetes Insipidus

ABSTRACT Pituitary responsiveness to aqueous vasopressin has been shown in four patients with congenital vasopressin-resistant diabetes insipidus with plasma cortisol rises greater than 4 μg/100 ml following a 10-unit im dose. Current evidence suggests that ACTH release occurs through a cyclic AMP mechanism. Thus, we have observed an extra-renal system in which the vasopressin-adenylate cyclase-cyclic AMP response sequence appears to be intact.
Towards the comparative exploration of public housing segregation in England and the United States

Abstract This paper is an exploration of the treatment of racial minorities by public sector housing agencies in Britain and the United States over the last several decades, with the objective of describing empirical and policy differences and similarities. Public housing programmes in each country have been, at differing points in time, important cornerstone's of the welfare state but each has become a residualised sector of the housing delivery system. In the context of such residualisation, the key issue to consider is whether British council housing is likely to reproduce the patterns of racial segregation, impoverishment, and discrimination which are endemic in the American public housing system. A variety of administrative agency reports and data, court cases, as well as case studies of race and public housing policies in the US and England have been used in this paper (Smith and Whalley, 1975; Commission for Racial Equality seriatim; Hirsch, 1983; Bauman, 1987; Department of the Environment; Smith,...
A discrete-state discrete-time model using indirect observation

SUMMARY This research was motivated by a desire to model the progression of a chronic disease through various disease stages when data are not available to directly estimate all the transition parameters in the model. This is a common occurrence when time and expense make it infeasible to follow a single cohort to estimate all the transition parameters. One diculty of developing a model of chronic disease progression from such data is that the available studies often do not include the transitions of interest. For example, in our model of diabetic nephropathy, many clinical studies did not dierentiate between patients without nephropathy and those who had microalbuminuria (a pre-clinical stage of nephropathy). Another diculty was a lack of data to directly estimate parameters of interest. We consider models which can accommodate such diculties. In this paper we consider the problem of estimating parameters of a discrete-time Markov process when longitudinal data describing the entire process are not available. First, we present a likelihood approach to estimate parameters of a discrete-time Markov model. Next, we use simulation to investigate thenite- sample behaviour of our approach. Finally, we present two examples: a model of diabetic nephropathy and a model of cardiovascular disease in diabetes. Copyright ? 2006 John Wiley & Sons, Ltd.
Visual analysis of multiple baseline across participants graphs when change is delayed.

A within-subjects group experimental design was used to test whether three manipulated characteristics of multiple baseline across participants (MBL-P) data showing at least a month delayed change in slope affected experts’ inference of a functional relation and agreement on this judgment. Thirty-six experts completed a survey composed of 16 MBL-P graphs. Graphs with steep slopes, once change began, were far more likely to be judged as showing a functional relation. Generally, experts disagreed with each other regarding functional relation judgments. Implications for the types of dependent variables that fit the requirements of MBL-P are discussed.
Heme Oxygenase-1 is Induced in Glia Throughout Brain by Subarachnoid Hemoglobin

The heme oxygenase-1 gene, HO-1, induced by heme, ischemia, and heat shock, metabolizes heme to biliverdin, free iron, and carbon monoxide. Though the distribution of HO-1 has been described in normal rat brain, little is known about how extracellular heme proteins in the subarachnoid space distribute in brain. To address this issue, hemoglobin was injected into the cisterna magna of adult rats. Expression of HO-1 in these animals was compared with saline-injected, BSA-injected, and uninjected controls. Western blot analysis showed that 24 hours after injection oxyhemoglobin increased HO-1 levels approximately four- to fivefold in all brain regions studied compared with saline-injected and BSA-injected controls. In the brain, HO-1 immunoreactivity was evident at 4 hours and peaked at 24 hours after oxyhemoglobin injections, returning to control levels by 4 to 8 days. This HO-1 induction was detected mainly in cells with small, rounded somas bearing two to four truncated processes, a morphology consistent with that of microglia. These cells were double-stained with the microglial marker, OX42, in every brain region examined. It is proposed that subarachnoid hemoglobin may be taken up into microglia wherein heme induces HO-1.
Ternary phase equilibria for the sodium chloride–sodium sulfate–water system at 200 and 250 bar up to 400°C

Abstract Phase equilibria in the NaCl–Na2SO4–H2O system were investigated at 200 and 250 bar for total salt concentrations ranging from 5 to 20 wt.% total salt over temperatures ranging from 320 to 400°C. In addition to providing data for this ternary system, the experiments also added information on the phase behavior of the two binary systems: NaCl–H2O and Na2SO4–H2O. For salt mixture compositions which were rich in sodium sulfate, a solid phase was observed to nucleate from the homogeneous liquid phase. Salt mixture compositions which had a high fraction of sodium chloride exhibited a vapor separation from a homogeneous liquid phase. By fitting curves to the solid–liquid and vapor–liquid separation temperatures, the temperature and composition of a constrained invariant point where liquid, solid salt and vapor are in equilibrium were estimated. These estimates were performed at discrete compositions of 5, 10, 15 and 20 wt.% total salt at pressures of 200 and 250 bar. The temperature and composition of the invariant point increased with increasing pressure following a simple thermodynamic model for boiling point elevation in a nearly ideal solution.
Photodynamic therapy using rhodamine‐123 as a new laser dye: Biodistribution, metabolism and histology in new zealand rabbits

Rhodamine-123 (Rh-123) has been tested recently as a new laser dye for photodynamic therapy of human tumors in vitro and in vivo. Prior to initiation of clinical studies of this technique, we evaluated the biodistribution, metabolism, and pathological changes of Rh-123 in rabbits after systemic, repetitive injections of the dye in escalating doses. At doses between 0.1 to 1 mg/kg of Rh-123 injected intramuscularly (IM) daily for 5 days, no local or systemic toxicity was observed during the 4 weeks of follow-up. The peak concentrations of Rh-123 in micrograms/g of tissue was distributed as follows: kidney (3.24) greater than heart (2.24) greater than spleen (1.77) greater than lung (0.61) greater than liver (0.38) greater than skin (0.30) greater than skeletal muscle (0.17) greater than genitals (0.13) greater than brain (0.04). The elimination of Rh-123 was very rapid, with the dye falling to 2.7% of peak concentration at 72 hours in the kidneys, and to undetectable levels at 240 hours postinjection in all organs, except the skin, which retained 3% of the peak level at 240 hours. The low toxicity and rapid metabolism of Rh-123 in this preclinical model suggests that the dye and Argon laser may represent an effective combination for treatment of superficial malignancies.
Reviving a Dying Language

A N ESSENTIAL part of the educational aim of the Irish Government as announced in 1922 was "the strengthening of the national fibre by giving the language, history, music and tradition of Ireland their natural place in the life of Irish Schools." The foundation for the attainment of this aim is, of course, the teaching of the language. As most teachers knew little or nothing of the Irish language, it was necessary to teach the teachers. In the summers from 1922 to 1929 classes in Irish were held under the direct supervision of the newly-formed Department of Education. Teachers under forty-five years of age were required to attend these sessions. Teachers over this age were "eligible" to attend the courses and were "expected" to do so unless prevented by special circumstances. Examinations were held under the direct administration of the Department and not of the professors in charge of the courses. The highest attendance was 14,000 in 1923 and the lowest was 5,879 in 1928. After seven summers, it was felt that ample time had been given to teachers for acquiring the language. Those below the Department's standards were urged to study at the new Irish colleges or spend vacations in the Irish-speaking districts. The entire cost of instruction, including cost of travelling to teachers living six or more miles from the nearest centres, was borne by the Department of Education. The State expenditures varied from approximately $290,000 in 1922 to $125,000 in later years. This was a huge expenditure by a small and poor state and indicates the whole-hearted manner in which this problem was approached by the Irish Government. The task begun by Irish leaders and scholars is a prodigious one. Text books in all school subjects in the Irish language had to be prepared. The aim is to make the Irish language the basic language of the school. Irish is to be studied not simply as a subject, but the ultimate aim is to use it as the medium of instruction in all teaching. English is to be a secondary language with a position similar to that of French, German or Spanish. To attain this goal will require several decades. What has already been accomplished? By June 1942 sixty-seven per cent of the primary teachers held the bilingual or higher certificates. In the secondary schools sixty-four .per cent of the total number of pupils enrolled were receiving all or part of the instruction through the medium of the Irish language. Forces operating against the use of the Irish language are many. In some
A comparison of the expected costs of high dose rate brachytherapy using 252Cf versus 192Ir.

Abstract A cost analysis to compare high dose rate (HDR) brachytherapy using either californium-252 ( 252 Cf) or 192 Ir was performed to determine the prospects of widespread clinical implementation of HDR 252 Cf. Interest in the neutron-emitting 252 Cf radioisotope as a radiotherapy nuclide has undergone a resurgence given recent efforts to fabricate HDR remotely afterloaded sources, and other efforts to create a miniature source for improved accessibility to a variety of anatomic sites. Therefore, HDR 252 Cf brachytherapy may prove to be a potential rival to the use of HDR 192 Ir remotely afterloaded brachytherapy—the current standard-of-care treatment modality using HDR brachytherapy. Considering the possible improvements in clinical efficacy using HDR 252 Cf brachytherapy and the enormous costs of other high-LET radiation sources, the cost differences between 252 Cf and 192 Ir may be well-justified.
NEUTRINO EMISSION PROCESSES, STELLAR EVOLUTION, AND SUPERNOVA. PART II

Abstract A general qualitative discussion of evolution of stars of masses ⊙ is presented. The role of gravitational contraction has been emphasized with respect to element synthesis. It is found that most of the stars with masses above a few tenths solar mass will proceed through all phases of element synthesis and consequently will become a supernova. The URCA process suggested by Gamow and Schonberg in 1941 will change this picture. During the α-process of element synthesis the rate of gravitational energy release is of the same order as that lost due to URCA neutrinos, and the critical mass for supernova is not certain, although the upper limit of it is less than the Chandrasekhar mass limit for degenerate gas spheres. The URCA process energy dissipation rates of a number elements have been calculated for T = 6 × 10 8 , 1.2 × 10 9 , 2.4 × 10 9 , and 6 × 10 9 °K, respectively.
In-vivo estimations of the nonlinear pressure-volume relationship of the aorta and instantaneous left ventricular volume.

A method is presented in this paper for the in-vivo estimation of the nonlinear pressure-volume relationship of the human aorta. The method is based on nonlinear elastic reservoir theory and utilizes clinical data that can be obtained with a high degree of accuracy, namely stroke volume, end diastolic ventricular volume and aortic pressure trace data. The computational procedure is described and then carried out for six cardiac patients. A method for the estimation of instantaneous left ventricular volume during the ejection period based on the considered nonlinear elastic reservoir theory is also presented. The method is applied for the six cardiac patients cited and the results compared with those obtained for the same subjects by a method of estimation based on linear elastic reservoir theory described in a previous paper by the author (1969).
Multi-finger interaction during involuntary and voluntary single finger force changes

Two types of finger interaction are characterized by positive co-variation (enslaving) or negative co-variation (error compensation) of finger forces. Enslaving reflects mechanical and neural connections among fingers, while error compensation results from synergic control of fingers to stabilize their net output. Involuntary and voluntary force changes by a finger were used to explore these patterns. We hypothesized that synergic mechanisms will dominate during involuntary force changes, while enslaving will dominate during voluntary finger force changes. Subjects pressed with all four fingers to match a target force that was 10% of their maximum voluntary contraction (MVC). One of the fingers was unexpectedly raised 5.0 mm at a speed of 30.0 mm/s. During finger raising the subject was instructed “not to intervene voluntarily”. After the finger was passively lifted and a new steady-state achieved, subjects pressed down with the lifted finger, producing a pulse of force voluntarily. The data were analyzed in terms of finger forces and finger modes (hypothetical commands to fingers reflecting their intended involvement). The target finger showed an increase in force during both phases. In the involuntary phase, the target finger force changes ranged between 10.71 ± 1.89% MVC (I-finger) and 16.60 ± 2.26% MVC (L-finger). Generally, non-target fingers displayed a force decrease with a maximum amplitude of −1.49 ± 0.43% MVC (L-finger). Thus, during the involuntary phase, error compensation was observed—non-lifted fingers showed a decrease in force (as well as in mode magnitude). During the voluntary phase, enslaving was observed—non-target fingers showed an increase in force and only minor changes in mode magnitude. The average change in force of non-target fingers ranged from 21.83 ± 4.47% MVC for R-finger (M-finger task) to 0.71 ± 1.10% MVC for L-finger (I-finger task). The average change in mode of non-target fingers was between −7.34 ± 19.27% MVC for R-finger (L-finger task) and 7.10 ± 1.38% MVC for M-finger (I-finger task). We discuss a range of factors affecting force changes, from purely mechanical effects of finger passive lifting to neural synergic adjustments of commands to individual fingers. The data fit a recently suggested scheme that merges the equilibrium-point hypothesis (control with referent configurations) with the idea of hierarchical synergic control of multi-element systems.
Losing the electoral battles and winning the policy wars: Ethnoregional conflict in Belgium

Several ethnoregional political parties achieved dramatic electoral successes in industrialized democracies in the 1960s and 1970s. Some of the most successful and prominent of these parties were the Belgian ethnoregional parties, the Volksunie (VU) in Flanders, the Rassemblement Wallon (RW) in Wallonia, and the Front Democratique des Francophones (FDF) in Brussels. These three parties have declined dramatically since the late 1970s. Although they appear to be electoral failures they have experienced impressive policy successes. The major Belgian parties had always been skeptical of the ethnoregional parties’ proposals for the federalization of the centralized state. Yet, in the years following the electoral decline of the ethnoregional parties, Belgium has federalized. Survey data and comparative analysis are used to account for the electoral failures and policy successes of the ethnoregional parties in Belgium. The conclusion generalizes from the Belgian cases to the successes and failures of other ethn...
The third dimension in social casework: Mary E. Richmond's contribution to family treatment

This article traces the development of family group treatment as conceptualized by Mary E. Richmond (1861–1928). While the main course of social work was following the new individual psychology from Europe after World War I, Richmond was paving the path for a clinical approach that was not to be realized until 30 years later.
On the salience of political issues: The problem with ‘most important problem’ ☆

Abstract Salience is an important concept throughout political science. Traditionally, the word has been used to designate the importance of issues, particularly for voters. To measure salience in political behavior research, scholars often rely on people's responses to the survey question that asks about the “most important problem” (MIP) facing the nation. In this manuscript, I argue that the measure confuses at least two different characteristics of salience: The importance of issues and the degree to which issues are a problem . It even may be that issues and problems are themselves fundamentally different things, one relating to public policy and the other to conditions. Herein, I conceptualize the different characteristics of MIP. I then undertake an empirical analysis of MIP responses over time in the US. It shows that most of the variation in MIP responses reflects variation in problem status. To assess whether these responses still capture meaningful information about the variation in importance over time, I turn to an analysis of opinion-policy dynamics, specifically on the defense spending domain. It shows that changes in MIP mentions do not structure public responsiveness to policy or policymaker responsiveness to public preferences themselves. Based on the results, it appears that the political importance of defense has remained largely unchanged over time. The same may be true in other domains. Regardless, relying on MIP responses as indicators of issue importance of any domain is fundamentally flawed. The responses may tell us something about the “prominence” of issues, but we simply do not know. The implication is clear: We first need to decide what we want to measure and then design the instruments to measure it.
Analysis of micro void formation at grain boundary triple points in monotonically strained AA6022-T43 sheet metal

This study reports on the micro voids formed in a 1 mm thick sheet of rolled aluminum alloy AA6022 subjected to monotonic tensile loading. In this research micro voids were found to occur at certain grain boundary triple point (GBTP) junctions. The orientations of the grains at various GBTP junctions were determined using an electron backscatter diffraction detector mounted in a field-emission scanning electron microscope. Because damage evolution and eventual final failure are driven by local tensile hydrostatic stresses arising from microhetereogenities, the hydrostatic stress state surrounding the GBTP junction was evaluated using a crystal plasticity material model implemented in a finite element analysis code. Grain orientations that result in a local hydrostatic state of tension surrounding the GBTP junction were found to have a tendency to form micro voids.
Differentiation of coital behavior in mammals: A comparative analysis

The evidence reviewed suggests that in all mammalian species the adult male's ability to display masculine coital behavior depends in part on exposure of the developing brain to testicular testosterone or its metabolites. In many mammals, particularly rodents, ruminants, and some carnivores, perinatal exposure to androgen also causes behavioral defeminization, i.e., reduced capacity to display typically feminine coital behavior in response to gonadal hormones in adulthood. The data reviewed suggest that no such process occurs in certain other mammalian species, including ferret, rhesus monkey, marmoset, and man. Testicular androgen may cause behavioral defeminization only in those species in which expression of feminine sexual behavior normally depends on the neural action of progesterone, acting synergistically with estradiol; new data support this claim in the ferret. The possible contribution of estrogenic and 5 alpha-reduced androgenic metabolites of testosterone to the occurrence of behavioral masculinization and defeminization is considered in those mammalian species for which data are available.
Racial consciousness and Afro‐diasporic experiences: Antonio Gramsci reconsidered

(1991). Racial consciousness and Afro‐diasporic experiences: Antonio Gramsci reconsidered. Socialism and Democracy: Vol. 7, No. 3, pp. 83-106.
A prospective analysis of positron emission tomography and conventional imaging for detection of stage IV metastatic melanoma in patients undergoing metastasectomy.

Background: Positron emission tomography with 2-deoxy-2-[18F]fluoro-d-glucose (FDG-PET) is available for evaluation of patients with melanoma. This study evaluates the potential of FDG-PET to improve on conventional imaging (CI) in patients with stage IV melanoma undergoing metastasectomy. Methods: This was a prospective study comparing radiological evaluation of patients who underwent metastasectomy for palliation or cure. Patients underwent preoperative evaluation by physical examination, CI by computed tomography and/or magnetic resonance imaging, and FDG-PET. Independent observers performed three separate analyses of CI alone, FDG-PET alone, or FDG-PET read with knowledge of CI (FDG-PET + CI). Abnormalities were reported as benign or malignant and assessed by pathologic analysis or by clinical outcome determined by disease progression detected on serial evaluations. Results: Ninety-four lesions were noted in 18 patients who underwent preoperative assessment, metastasectomy, and long-term follow up (median, 24 months). Lesion-by-lesion analysis for CI demonstrated a sensitivity of 76%, a specificity of 87%, a positive predictive value (PPV) of 86%, and a negative predictive value (NPV) of 76%. FDG-PET demonstrated a sensitivity of 79%, a specificity of 87%, a PPV of 86%, and an NPV of 80%. For FDG-PET + CI, the sensitivity was 88%, specificity was 91%, and PPV and NPV were 91% and 88%, respectively. Conclusions: Combined use of FDG-PET and CI may be an accurate strategy to identify sites of disease in patients with stage IV melanoma being considered for metastasectomy. Interpreted independently, FDG-PET and CI seemed to be equivalent modalities. FDG-PET + CI had both the highest sensitivity on lesion-by-lesion analysis and the best accuracy on patient-by-patient analysis.
Microarraying the cellular microenvironment

Mol Syst Biol. 2: 39 The in vivo stem cell microenvironment or niche is composed of an intricate blend of extracellular matrix proteins, soluble protein factors, immobilized protein factors, proteoglycans, small molecule signals, in some cases mineralized tissue, and numerous adjacent cell types, all of which likely vary in space and time. In concert, these many components present the cells with an ‘array’ of biochemical and biomechanical signals, such that the cell is continually faced with the complex tasks of sensing these inputs, processing the signals through complex signal transduction and gene regulation networks, and executing cell behavioral or fate choices. This native microenvironment therefore poses a daunting challenge to the fields of stem cell biology and engineering: how does one analyze the relative importance of the individual signals of this medley in regulating cell function? In addition to advancing our basic knowledge of the central question of stem cell fate choice, addressing this question will be necessary to achieve the control over cell behaviors needed for regenerative medicine efforts. Reductionist biological approaches have consistently made major strides in elucidating the importance of individual signaling factors; however, cells …
Linking vascular disorders and Alzheimer's disease: Potential involvement of BACE1

The etiology of Alzheimer's disease (AD) remains unknown. However, specific risk factors have been identified, and aging is the strongest AD risk factor. The majority of cardiovascular events occur in older people and a close relationship between vascular disorders and AD exists. Amyloid plaques, composed of the beta amyloid peptide (Aβ), are hallmark lesions in AD and evidence indicates that Aβ plays a central role in AD pathophysiology. The BACE1 enzyme is essential for Aβ generation, and BACE1 levels are elevated in AD brain. The cause(s) of this BACE1 elevation remains undetermined. Here we review the potential contribution of vascular disease to AD pathogenesis. We examine the putative vasoactive properties of Aβ and how the cellular changes associated with vascular disease may elevate BACE1 levels. Despite increasing evidence, the exact role(s) vascular disorders play in AD remains to be determined. However, given that vascular diseases can be addressed by lifestyle and pharmacologic interventions, the potential benefits of these therapies in delaying the clinical appearance and progression of AD may warrant investigation.
Role of primary site local management for advanced breast cancer patients

s / The Breast 20 (2011) S12–S55 S20 Multiple, randomised controlled trials over the past two decades have clearly demonstrated that bisphosphonates (BPs) are effective in reducing skeletal morbidity from metastatic cancer. Zoledronic acid is the most potent BP, and has shown superior efficacy to pamidronate in the prevention of skeletal complications in breast cancer, and is the only agent to show clear benefit in the management of metastatic bone disease from prostate cancer (castrate resistant), lung cancer and other solid tumours. Oral agents such as ibandronate and clodronate provide a useful alternative for some clinical situations. Denosumab is a fully humanised monoclonal antibody that inhibits RANKL. A dose of 120mg 4 weekly administered by subcutaneous injection has been defined for the treatment of advanced malignancy. Preclinical data suggest that denosumab is a more complete inhibitor of osteoclast function than the BPs. Additionally, a randomised phase II study in patients with increased bone resorption, despite ongoing BPs, has compared changing to denosumab to continuation of the BP; rapid and sustained biochemical response was seen in >80% of patients switched to denosumab compared with 5,000), denosumab was more effective, easier to administer and had some safety advantages. The bone-targeted agents are an important component of management in advanced malignancy. Combined with systemic cancer therapy, effective symptom control and appropriate surgical and radiological interventions, modern multi-disciplinary care has transformed the care of patients with metastatic bone disease.
Orbital control of western North America atmospheric circulation and climate over two glacial cycles

A palaeoclimate record from Devils Hole, North America, has long called into question the theory of orbital-scale climate variability. Lachniet et al. present a new, well-dated, speleothem record and reveal evidence for strong orbital forcing of palaeoclimate in this region for at least the past 175 kyrs.
Parallel dose–response studies of the voltage-dependent Na+ channel antagonist BW619C89, and the voltage-dependent Ca2+ channel antagonist nimodipine, in rat transient focal cerebral ischaemia

Abstract We have compared two classes of putative neuroprotectants, the voltage-dependent Na+ channel antagonist BW619C87 [4-amino-2-(4-methyl-1-piperazinyl)-5-(2,3,5-trichlorophenyl) pyrimidine], and the voltage-dependent Ca2+ channel antagonist nimodipine, in a rat model of transient focal cerebral ischaemia. BW619C87 (10–50 mg/kg) or nimodipine (10–100 μg/kg) were injected intravenously 5 min before induction of 2 h transient focal cerebral ischaemia via intraluminal thread occlusion of the middle cerebral artery. BW619C87 was a potent neuroprotectant over the range tested, maximally reducing the volume of hemispheric ischaemic damage by 51% at the 50 mg/kg dose. Nimodipine maximally reduced ischaemic damage by 33% at the 50 μg/kg dose, although the maximal level of neuroprotection afforded by BW619C89 and nimodipine was not significantly different. This is the first study to compare these two classes of drug directly in a model of middle cerebral artery occlusion with reperfusion, and it supports the effectiveness of both as neuroprotectants.
The significance of transarterial embolization for advanced hepatocellular carcinoma in liver transplantation.

Abstract Introduction Transarterial embolization (TAE) is the treatment of choice for advanced HCC to control or even induce tumor shrinkage. The aim of this study was to evaluate the effect of pretransplantation TAE for treatment of advanced HCC. Material and methods From 1996 to 2002, we studied 12 cirrhotic patients with HCC, including six who met and six who exceeded the Milan criteria. All patients had sufficient hepatic function to undergo TAE. Liver transplantations were performed subsequently and they were followed prospectively for a median of 22 months (range = 12 to 53 months). Results The explanted livers from the 12 patients who had undergone TAE were noted to have extensive tumor necrosis. The pathological specimens at LT showed downstaging of the HCC, which allowed those six patients to meet the Milan criteria. The overall 1- and 2-year survival rates were 92% and 73%, respectively. The overall 1- and 2-year disease-free survival rates were 92% and 73%, respectively. One death unrelated to liver disease at 2 years after LT was noted in the downgraded group. One patient of the initially eligible group developed lung metastasis at 6 months and died at 12 months after LT. Conclusion TAE is effective to downstage advanced HCC and reduce the dropout rate on the LT waiting list. Pre-LT TAE may be considered as a better therapeutic strategy for patients with advanced HCC.
Insights into cardiac pacemaker and defibrillator revision/upgrades

Implantation of cardiac implantable electronic device (CIEDs), both pacemakers (PM) and implantable cardioverter defibrillators (ICDs) has dramatically increased in recent years. Cardiovascular disease causes an estimated 30% of all deaths worldwide. In a 14-month period, a consecutive series of 121 devices (76 ICDs and 45 PMs) were collected as part of an IRB-approved device retrieval program. The criteria for devices to be reprocessable are PMs with remaining projected longevity of greater than 4 years and ICDs with battery voltage greater than 2.95V were noted. Our data suggests that 17–20% of device removals in a teaching hospital may be suitable for re-use in countries with developing economies.
BIOLOGICAL STUDIES OF BUD MINING SAWFLIES, PLERONEURA SPP. (HYMENOPTERA: XYELIDAE), ON WHITE FIR IN THE CENTRAL SIERRA NEVADA OF CALIFORNIA: II. LARVAL DISTRIBUTION WITHIN TREE CROWNS

The within crown distribution of three species of Pleroneura and their food source (active buds) was determined on white fir trees 5–30 ft tall. Over 90% of all active buds and 94% of all infested buds occur in the outer half of the crown. Over 50% of the total active and infested buds occur in the middle third of the crown. Percentage infestation within the crown increases from bottom to top. Percentage infestation per tree decreases as tree size increases.
Performance Evaluation of Algorithms for Soft Evidential Update in Bayesian Networks: First Results

In this paper we analyze the performance of three algorithms for soft evidential update, in which a probability distribution represented by a Bayesian network is modified to a new distribution constrained by given marginals, and closest to the original distribution according to cross entropy. The first algorithm is a new and improved version of the big clique algorithm [1] that utilizes lazy propagation [2]. The second and third algorithm [3] are wrapper methods that convert soft evidence to virtual evidence, in which the evidence for a variable consists of a likelihood ratio. Virtual evidential update is supported in existing Bayesian inference engines, such as Hugin. To evaluate the three algorithms, we implemented BRUSE (Bayesian Reasoning Using Soft Evidence), a new Bayesian inference engine, and instrumented it. The resulting statistics are presented and discussed.
Catastrophic windstorm and fuel-reduction treatments alter ground beetle (Coleoptera: Carabidae) assemblages in a North American sub-boreal forest

We studied the short-term effects of a catastrophic windstorm and subsequent salvage-logging and prescribed-burning fuel-reduction treatments on ground beetle (Coleoptera: Carabidae) assemblages in a sub-boreal forest in northeastern Minnesota, USA. During 2000–2003, 29,873 ground beetles represented by 71 species were caught in unbaited and baited pitfall traps in aspen/birch/conifer (ABC) and jack pine (JP) cover types. At the family level, both land-area treatment and cover type had significant effects on ground beetle trap catches, but there were no effects of pinenes and ethanol as baits. Six times more beetles were trapped in the burned forests than in the other land-area treatments; more beetles were caught in undisturbed than in wind-disturbed sites, and one-third more beetles were caught in the ABC than in the JP cover type. Thus, the windstorm generally reduced the activity-abundance of the beetles, but prescribedburning increased it. Both salvaged and burned forest plots (especially in the ABC cover type) had the greatest species richness, diversity, and the most unique species assemblages. There was a highly similar ground beetle species composition (nearly 100%) between the ABC and JP burned forests, indicating that burning was a more primary driver of composition than cover type. At the species level, Pterostichus melanarius ,a n invasive ground beetle from Europe and a cover type generalist, was the most abundant beetle in the study (one-third of the total catch), and was caught in greatest numbers in burned forests. Removal of P. melanarius from the species composition analyses altered similarities among cover types and land-area treatments. Sphaeroderus nitidicollis brevoorti and Myas cyanescens were caught exclusively in the ABC and JP cover type, respectively; two rare pyrophilous species, Sericoda obsoleta and Sericoda quadripunctata, were only caught in burned sites; three forest species, Pterostichus coracinus, P. pensylvanicus ,a ndSphaeroderus lecontei, were caught more often in undisturbed JP sites; and two frequently trapped, open-habitat species, Agonum cupripenne and Poecilus l. lucublandus, were nearly absent from the undisturbed and wind-disturbed sites, as salvage-logging had a significant positive effect on their activity-abundance. Most species of Amara and Harpalus were trapped only in the salvaged or burned sites, indicating invasion of these disturbed sites by open-habitat species. We conclude that both the combined effect of fuel-reduction activities subsequent to the wind event and the numerical response of the invasive P. melanarius to habitat disturbances can alter the short-term succession of ground beetle assemblages in the sub-boreal forest. Published by Elsevier B.V.
Counting local systems with principal unipotent local monodromy

Let X1 be a curve of genus g, projective and smooth over Fq. Let S1 X1 be a reduced divisor consisting of N1 closed points of X1. Let (X;S) be obtained from (X1;S1) by extension of scalars to an algebraic closure F of Fq. Fix a primel not dividingq. The pullback by the Frobenius endomorphism Fr ofX induces a permutation Fr of the set of isomorphism classes of rank n irreducible Ql-local systems on X S. It maps to itself the subset of those classes for which the local monodromy at each s2 S is unipotent, with a single Jordan block. Let T (X1;S1;n;m) be the number of xed points of Fr m acting on this subset. Under the assumption that N1 2, we show that T (X1;S1;n;m) is given by a formula reminiscent of a Lefschetz xed point formula: the function m 7! T (X1;S1;n;m) is of the form P ni m for suitable integers ni and \eigenvalues" i. We use Laorgue
Teaching Evolution & the Nature of Science Via the History of Debates about the Levels at Which Natural Selection Operates

Students should not graduate from high school without understanding that scientific debates are essential components of scientific methodology. This article presents a brief history of ongoing debates regarding the hypothesis that group selection is an evolutionary mechanism, and it serves as an example of the role that debates play in correcting faulty ideas and stimulating new research in the pursuit of extending scientific knowledge.
Applicants for a Faculty Position Do Not Emphasize Teaching.

Cover letters, curricula vitae, and teaching statements of 82 doctoral candidates and 74 PhD applicants for an assistant professor position were examined for teaching-related content. Applicants presented little teaching information. The discussion focuses on understanding this lacuna and offers recommendations for correcting the problem.