cssi/SciSciGPT-SciSciNet huggingface dataset:
Interactions of novel dopaminergic ligands with D-1 and D-2 dopamine receptors

The interactions of three novel dopaminergic ligands, SKF38393, SKF82526 and SKF83742, with D-1 and D-2 dopamine (DA) receptors have been investigated using radioligand binding techniques and computer modeling procedures. Using the bovine anterior pituitary D-2 DA receptor system, SKF38393 and SKF82526 behave as agonists demonstrating biphasic agonist/3H-antagonist competition curves. For both drugs, the high affinity phase comprised 30% of the total displacement curve. Such findings are atypical as previously tested classical dopamine agonists demonstrated high and low affinity displacement phases in equal proportions. Such behavior exhibited by the SKF agonists may be related to their activity as partial agonists. In contrast, SKF83742 behaves as an antagonist exhibiting homogeneous monophasic competition curves. Similar results are obtained in the rat striatal membrane D-2 DA receptor system. Both SKF38393 and SKF82526 also demonstrate shallow biphasic displacement curves on rat striatal D-1 receptors labeled with 3H-flupentixol whereas SKF83742/3H-flupentixol curves are uniphasic. Of all the ligands, only SKF38393 clearly demonstrates higher affinity for 3H-flupentixol labeled D-1 receptors.
Business ties and proxy voting by mutual funds

Abstract The magnitude of mutual funds’ business ties with their portfolio firms is documented and is linked to funds’ proxy votes at specific firms and to overall voting practices. Aggregate votes at the fund family level indicate a positive relation between business ties and the propensity to vote with management. Votes at specific firms, however, reveal that funds are no more likely to vote with management of client firms than of non-clients. Because the votes took place when funds knew their votes would be publicly scrutinized, fund families with a larger client base may have adopted voting policies that led to less frequent opposition to management at all firms.
Photon-Counting Reticon TM Detector

For applications in faint-object spectroscopy at the Mt. Hopkins Observatory, a photon-counting detector has been built using a dual 936 Reticon diode array fibre-optically coupled to a high-gain image intensifier package. The electronic signal processing follows closely the design of Shectman; the diode array is scanned every millisecond, each frame is subtracted from the previous to minimize multiple counts from the tails of the P-20 phosphor decays, and the centroid of each photon event is located to recover much of the resolution of the first image intensifier. For each detected event, the corresponding address in a Nova computer is updated by a direct memory access, thus allowing simultaneous data collection, analysis, and display. Two different intensifier packages have been used, both sandwiching a 25-mm Gen II microchannel-plate tube fibre-optically between 40-mm Gen I tubes for the first and third stages. This has made possible a compact intensifier package at the expense of a poor pulse-height distribution. Our first version of the detector has been in use with the 60-inch telescope at Mt. Hopkins since February 1978. A new version using a custom dual RL1024SF Reticon is now under construction for use on the Multiple-Mirror Telescope.© (1979) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Kinetic Isotope Effect Studies on the de Novo Rate of Chromophore Formation in Fast- and Slow-Maturing GFP Variants†

The maturation process of green fluorescent protein (GFP) entails a protein oxidation reaction triggered by spontaneous backbone condensation. The chromophore is generated by full conjugation of the Tyr66 phenolic group with the heterocycle, a process that requires C-H bond scission at the benzylic carbon. We have prepared isotope-enriched protein bearing tyrosine residues deuterated at the beta carbon, and have determined kinetic isotope effects (KIEs) on the GFP self-processing reaction. Progress curves for the production of H 2O 2 and the mature chromophore were analyzed by global curve fitting to a three-step mechanism describing preoxidation, oxidation and postoxidation events. Although a KIE for protein oxidation could not be discerned ( k H/ k D = 1.1 +/- 0.2), a full primary KIE of 5.9 (+/-2.8) was extracted for the postoxidation step. Therefore, the exocyclic carbon is not involved in the reduction of molecular oxygen. Rather, C-H bond cleavage proceeds from the oxidized cyclic imine form, and is the rate-limiting event of the final step. Substantial pH-dependence of maturation was observed upon substitution of the catalytic glutamate (E222Q), indicating an apparent p K a of 9.4 (+/-0.1) for the base catalyst. For this variant, a KIE of 5.8 (+/-0.4) was determined for the intrinsic time constant that is thought to describe the final step, as supported by ultra-high resolution mass spectrometric results. The data are consistent with general base catalysis of the postoxidation events yielding green color. Structural arguments suggest a mechanism in which the highly conserved Arg96 serves as catalytic base in proton abstraction from the Tyr66-derived beta carbon.
Anti-idiotype vaccines in toxicology

The majority of naturally occurring biological and chemical toxins are highly lethal, nonproteinaceous, low molecular weight substances which exert their toxicity through a variety of mechanisms. Their relative small size and extreme in vivo toxicity have hampered the development of protective vaccines. We have investigated the feasibility of anti-idiotype-based vaccines which utilize antibodies for inducing a systemic and protective immunity against the in vivo toxicity of some of these toxic substances. A murine IgG1 monoclonal anti-T-2 mycotoxin antibody protective against mycotoxin toxicity was generated. This antibody was used to produce a second generation monoclonal anti-idiotype antibody which was capable of serologically mimicking the tertiary conformation of the nominal antigen, i.e., T-2 mycotoxin. Administration of the monoclonal anti-idiotype antibody to mice induced a circulating and protective antibody response against the in vitro and in vivo toxicity of T-2 mycotoxin. Antibody-based vaccines may represent the only safe and effective strategy for the design of protective vaccines against small nonproteinaceous toxic compounds whose extreme toxicity prevents their use as safe immunogens. The potential of antibody-based vaccines for producing protective immunity against low molecular weight chemical and biological toxins is discussed.
Diagnostic Accuracy of Retrograde and Spontaneous Voiding Trials for Postoperative Voiding Dysfunction: A Randomized Controlled Trial

OBJECTIVE:To compare the diagnostic accuracy of two voiding trial methods to predict postoperative voiding dysfunction.METHODS:Women undergoing operations for urinary incontinence, prolapse, or both urinary incontinence and prolapse from November 2009 and March 2010 were randomized into one of two g
A Cyber-Physical Management System for Delivering and Monitoring Surgical Instruments in the OR:

Background. The standard practice in the operating room (OR) is having a surgical technician deliver surgical instruments to the surgeon quickly and inexpensively, as required. This human “in the loop” system may result in mistakes (eg, missing information, ambiguity of instructions, and delays). Objective. Errors can be reduced or eliminated by integrating information technology (IT) and cybernetics into the OR. Gesture and voice automatic acquisition, processing, and interpretation allow interaction with these new systems without disturbing the normal flow of surgery. Methods. This article describes the development of a cyber-physical management system (CPS), including a robotic scrub nurse, to support surgeons by passing surgical instruments during surgery as required and recording counts of surgical instruments into a personal health record (PHR). The robot used responds to hand signals and voice messages detected through sophisticated computer vision and data mining techniques. Results. The CPS was t...
Protein-Ligand Interactions: Thermodynamic Effects Associated with Increasing the Length of an Alkyl Chain.

Thermodynamic parameters were determined for complex formation between the Grb2 SH2 domain and tripeptides of the general form Ac-pTyr-Xaa-Asn in which the Xaa residue bears a linear alkyl chain varying in length from 1–5 carbon atoms. Binding affinity increases upon adding a methylene group to the Ala derivative, but further chain extension gives no extra enhancement in potency. The thermodynamic signatures of the ethyl and n-propyl derivatives are virtually identical as are those for the n-butyl and n-pentyl analogues. Crystallographic analysis of the complexes reveals a high degree of similarity in the structure of the domain and the bound ligands with the notable exception that there is a gauche interaction in the side chains in the bound conformations of ligands having n-propyl, n-butyl, and n-pentyl groups. However, eliminating this unfavorable interaction by introducing a Z-double bond into the side chain of the n-propyl analogue does not result in an increase in affinity. Increases in the amount o...
Management of hepatocellular carcinoma

Hepatocellular carcinoma (HCC), a common cause for cancer-related death, is increasing worldwide. Over the past decade, survival and quality of life of HCC patients have significantly improved due to better prevention strategies, early diagnosis, and improved treatment options. We performed this narrative review to synthesize current status on the HCC management. Literature search for publications especially over the last decade, which has changed the paradigm on the management of HCC. Hepatitis B vaccination and treatment of chronic hepatitis B and C are important measures for HCC prevention. Screening and surveillance for HCC using ultrasonogram and alpha-fetoprotein estimation are directed toward cirrhotics and hepatitis B patients at high risk of HCC. If detected at an early stage, curative treatments for HCC can be used such as tumor resection, ablation and liver transplantation. HCC patients without curative options are managed by loco-regional therapies and systemic chemotherapy. Loco-regional treatments include trans-arterial chemoembolization, radioembolization and combinations of loco-regional plus systemic therapies. Currently, sorafenib is the only FDA-approved systemic therapy and newer better chemotherapeutic agents are being investigated. Palliative care for terminally ill patients with metastatic disease and/or poor functional status focusses on comfort care and symptom control. In spite of significant advancement in HCC management, its incidence continues to rise. There remains an urgent need to continue refining understanding of HCC and develop strategies to increase utilization of the available preventive measures and curative treatment modalities for HCC.
Measurements of spray at an air-water interface

Abstract The spray content in the surface boundary layer above an air—water interface was determined by a series of measurements at various feteches and wind speeds in a laboratory facility. The droplet flux density N(z) can be described in terms of the scaling flux density N ∗ and von Karman constant K throguh the equation, N(z)/N ∗ = −(1/K) ln (z/z 0d ) where z is height above the mean water level and z0d is the droplet boundary layer thickness. N ∗ is given by a unique relationship in terms of the roughness Reynolds number u ∗ σ/ν where σ is the root-mean-square surface displacement. Spray inception occurred for u ∗ ⪸ 0.3 . The dominant mode of spray generation in the present and most other laboratory tests, as well as in available field data, appears to be bubble bursting.
When back pain becomes disabling: a regional analysis.

Abstract Back pain is a common condition and in most cases is not disabling. We have investigated disabling back pain that leads to health care utilization, time lost from work, and high costs. Disabling back pain remains of obscure origin because the focus in studying it has been too narrow. Our indicator of disability is the industrial insurance claim rate for back sprain by county (N = 39) in the State of Washington. After controlling for the size of the labor force and the proportion of workers in occupations that are particularly at risk of back sprain, we determined the effect of 3 socioeconomic factors on the claim rate: the unemployment rate, percentage receiving food stamps, and per capita income. For 2 of the 3 years studied, socioeconomic factors accounted for about one-third of the variance in the claim rate. Even though claimants of industrial insurance are employed, the unemployment rate was significantly related to the claim rate in the 3 years studied. Our interpretation is that disability is a symptom of distress. Where there is a rise in job insecurity and an attendant rise in economic insecurity, there is a greater likelihood that back pain will become disabling.
Mechanisms of Brain Injury after Global Cerebral Ischemia

Cerebral ischemia results in a rapid depletion of energy stores that triggers a complex cascade of cellular events such as cellular depolarization and Ca2+ influx, resulting in excitotoxic cell death. The critical determinant of severity of brain injury is the duration and severity of the ischemic insult and early restoration of CBF. Induced therapeutic hypothermia following CA is the only strategy that has demonstrated improvement in outcomes in prospective, randomized clinical trials. Although pharmacologic neuro-protection has been disappointing thus far in a variety of experimental animal models, further research efforts are directed at using some agents that demonstrate marginal or moderate efficacy in combination with hypothermia. Although the signal transduction pathways and intracellular molecular events during cerebral ischemia and reperfusion are complex, potential therapeutic neuroprotective strategies hold promise for the future.
Surface reconstruction as a source of growth steps

Abstract The surface reconstruction on the treads of a growing crystal surface may provide the source of growth steps required for the growth to proceed at low supercooling or supersaturation. It is proposed that this mechanism obtains in the growth of those semiconducting materials, including dislocation-free Si and GaAs, for which no evidence for the screw dislocation mechanism has been found. Experiments supporting this proposal are mentioned.
Method or Madness: Phenomenology as Knowledge Creator

This article reviews the research method of phenomenology and its use in understanding human experience. This is conceptualized in the context of a research study performed with nine participants and their experience of finding their “calling.” Their experiences are used as the medium through which Husserl's method is explored. Questions and concerns about this alternative and nontraditional approach to creating and understanding new social knowledge are considered. Reflexivity and the researcher's psychological integrity in application of the method are explored.
Study of valproic acid-induced endogenous and exogenous metabolite alterations using LC–MS-based metabolomics

Background: Valproic acid (VPA; an anticonvulsant drug) therapy is associated with hepatotoxicity as well as renal toxicity. An LC–MS-based metabolomics approach was undertaken in order to detect urinary VPA metabolites and to discover early biomarkers of the adverse effects induced by VPA. Results: CD-1 mice were either subcutaneously injected with 600-mg VPA/kg body weight or vehicle only, and urine samples were collected at 6, 12, 24 and 48 h postinjection. A metabolomics approach combined with principal component analysis was utilized to identify VPA-related metabolites and altered endogenous metabolites in urine. Some VPA metabolites indicated potential liver toxicity caused by VPA administration. Additionally, some altered endogenous metabolites suggested that renal function might be perturbed by VPA dosing. Conclusion: LC–MS-based metabolomics is capable of rapidly profiling VPA drug metabolites and is a powerful tool for the discovery of potential early biomarkers related to perturbations in liver...
Granulocytes: new roles for basophils.

Expression of high-affinity IgE receptors (FceRI) and histamine-containing granules are hallmarks of basophils, which highlights their similarity to mast cells. Historically, it is this similarity that has focused investigation into the biology of basophils and kept attention on its role in hypersensitivity reactions. Is it possible that there is more to the life of the basophil? Are they more than just terminally differentiated cannon fodder cells rapidly mobilized to repel ecto-parasites using their surface-bound IgE to bind parasite antigens that induce the release of potent mediators? Recent studies of murine basophils by Mack and co-workers published in Nature Immunology1 have begun to suggest that the answer to these questions is yes (Figure 1).
An Assessment of the Quantitative Skills of Students Taking Introductory College Biology Courses.

Twenty-three mathematical competencies were identified and a 46-item multiple choice test was developed to measure the extent to which students entering introductory college biology courses possessed these competencies. Students enrolled in semester-long introductory courses for science majors and non-science majors were given the test at the beginning and end of the courses. The relationships between the mathematical competencies possessed by students at the beginning of the semester and 15 variables dealing with student characteristics were examined. Also investigated was the relationship between test scores and the type of mathematics courses taken during the semester students were enrolled in the introductory biology courses.
The cooling rates and parent planets of several iron meteorites

Abstract The Widmanstatten structure in octahedries can be understood in detail and quantitatively as the result of solid state transformations that would occur in slowly cooling NiFe alloys. High pressure is not needed to account for the presence of plessite instead of Widmanstatten structures in those meteorites where Ni > ∼13% Ni, or in those regions of octahedrites where ∼22% > Ni > ∼13%. Experiments show that NiFe alloys tend to remain in the form of metastable γ phase when cooled from the γ stability field into the α + γ field, but transform promptly from the metastable α2 state into α + γ. Plessite was formed when meteoritic alloys supercooled as metastable γ phase to such an extent that they transformed to α2; thereafter they decomposed to fine, non-Widmanstatten α + γ, i.e., plessite. Electron probe profiles were made of the characteristic Ni diffusion gradients in taenite-plessite regions of 11 octahedrites. A digital computer program was set up to generate artificial diffusion gradients by solving the equation for diffusion of Ni in γ alloys under differing circumstances, i.e., for systems with various bulk Ni contents, nucleation spacings, nucleation temperatures, and cooling rates. It was found possible to artificially duplicate the measured gradients only if an α/(α + γ) phase boundary somewhat different from the generally accepted Owen and Liu (1949) version was used in the program. Results of a single annealing experiment supported use of this amended boundary. Comparisons of computed and measured structures permitted conclusions to be drawn about thermal histories of the octahedrites studied. Most cooled to ∼100°C beneath the γ/(α + γ) boundary before Widmanstatten structure was precipitated. A correlation between cooling rates, structural types, and probably Ga-Ge groups appears to exist. The medium, fine, and finest octahedrites Grant, Trenton, Duchesne, Santa Apolonia, and probably Bristol cooled at ∼10°C/million years. The coarse and coarsest octahedrites Arispe, Canon Diablo, and Odessa, and the medium octahedrite Toluca cooled at ∼1°C/million years. Anoka, a fine-finest octahedrite, cooled at an anomalous 1°C/million years. These are cooling rates appropriate to the centers of asteroids, 50–90 km in radius for the first group and 130–260 km in radius for the second. Two Ni-rich ataxites studied (Pinon, Monahans) precipitated scattered kamacite crystals under circumstances of very rapid cooling, excessive supercooling, or both.
Toxic effects of warfarin in rats fed different diets.

Abstract Toxic doses of warfarin were administered (0.8 mg/kg, po) daily for 5 days to one group of rats (250–300 g) fed oat groats and to another fed Purina laboratory chow. Five rats from each dietary group were sacrificed at 5, 29, 53, 77 and 101 hr after the initial dose. The plasma warfarin concentration increased more rapidly in the oat-fed rats than in those fed chow; however, the liver warfarin: plasma warfarin ratio following the first dose of warfarin indicated that the chow-fed rats were removing the warfarin from the plasma more rapidly. Presumably, the rate of metabolism of warfarin was more rapid in the chow-fed than in the oat-fed rats because the prothrombin times in the former increased at a slower rate. Apparently, less liver damage occurred in the chow-fed rats because they had lower plasma fibrinogen concentrations than those fed oats. There was a 50% decline in the hematocrit values in both groups. The linear decline in the total plasma protein in each group was a function of linear declines in plasma albumin and α-globulin. In both groups, the β- and γ-globulins remained stable until 101 hr, at which time they increased. It was concluded that the response of rats to repeated toxic oral doses of warfarin was influenced by protein in the diet; rats fed higher protein diets were more tolerant to warfarin.
Do explanation formats in elementary chemistry depend on agent causality

By setting out the grammar of event causality, as developed by Hume and Mackie, in contrast to the grammar of agent causality in the natural sciences, a kind of hybrid hierarchical format for chemical explanations is sketched. From this starting point the history of agentive concepts in chemistry is displayed as a progression from Newton’s ‘forces’, through the nineteenth century concepts of ‘affinity’ and ‘valency’ to recent theories of molecular binding in terms of the migration of electrons and protons as powerful particulars. The final stage of this development is the rewriting of chemical theory in terms of energy.
Bande Mataram: Bankimchandra Chattopadhyay's nationalist thought revisited∗

(2002). Bande Mataram: Bankimchandra Chattopadhyay's nationalist thought revisited. South Asia: Journal of South Asian Studies: Vol. 25, No. 1, pp. 121-142.
Spatially-Resolved Measurements of Bacillus Subtilis Cell Wall Growth Dynamics during Elongation and Division

The cell wall, a cross-linked 3D network of peptidoglycan, is the key structural element that dictates cell shape and counter-balances turgor forces in prokaryotes. During cell growth and division, the wall undergoes a coordinated series of addition and remodeling events that enable the cell shape to change in a stereotyped manner. Recent studies suggest that the spatial insertion pattern of new material into the peptidoglycan network, guided by the bacterial cytoskeleton, is critical for cell shape maintenance. In this work, we use a high-density of quantum dots (QDs) on the B. subtilis cell surface to track the local motions of the wall in three-dimensions during cell growth and division. From a 2D projection of the QD distribution onto the cylindrical cell surface, we obtain the local stretching and shearing rates on multiple spatial scales. The homogeneity of insertion and cell wall twist during elongation and division can then be quantified from these growth maps.
Parallel branch-and-bound for two-stage stochastic integer optimization

Many real-world planning problems require searching for an optimal solution in the face of uncertain input. One approach to is to express them as a two-stage stochastic optimization problem where the search for an optimum in one stage is informed by the evaluation of multiple possible scenarios in the other stage. If integer solutions are required, then branch-and-bound techniques are the accepted norm. However, there has been little prior work in parallelizing and scaling branch-and-bound algorithms for stochastic optimization problems. In this paper, we explore the parallelization of a two-stage stochastic integer program solved using branch-and-bound. We present a range of factors that influence the parallel design for such problems. Unlike typical, iterative scientific applications, we encounter several interesting characteristics that make it challenging to realize a scalable design. We present two design variations that navigate some of these challenges. Our designs seek to increase the exposed parallelism while delegating sequential linear program solves to existing libraries. We evaluate the scalability of our designs using sample aircraft allocation problems for the US airfleet. It is important that these problems be solved quickly while evaluating large number of scenarios. Our attempts result in strong scaling to hundreds of cores for these datasets. We believe similar results are not common in literature, and that our experiences will feed usefully into further research on this topic.
Dephasing by extremely dilute magnetic impurities revealed by Aharonov-Bohm oscillations.

We have probed the magnetic field dependence of the electron phase coherence time ${\ensuremath{\tau}}_{\ensuremath{\varphi}}$ by measuring the Aharonov-Bohm conductance oscillations of mesoscopic Cu rings. Whereas ${\ensuremath{\tau}}_{\ensuremath{\varphi}}$ determined from the low-field magnetoresistance saturates below 1 K, the amplitude of Aharonov-Bohm $h/e$ oscillations increases strongly on a magnetic field scale proportional to the temperature. This provides strong evidence that a likely explanation for the frequently observed saturation of ${\ensuremath{\tau}}_{\ensuremath{\varphi}}$ at low temperature in weakly disordered metallic thin films is the presence of extremely dilute magnetic impurities.
THE LOCALIZATION AND PROPERTIES OF AN AMINOPEPTIDASE IN ESCHERICHIA COLI B

Two types of intracellular aminopeptidase activity are present in E. coli B. One type, present in the 'soluble' fraction, is completely inactivated by chymotrypsin or trypsin; the other, in the par...
A Conditional Mouse Model for Measuring the Frequency of Homologous Recombination Events In Vivo in the Absence of Essential Genes

The ability to detect and repair DNA damage is crucial to the prevention of various diseases. Loss of function of genes involved in these processes is known to result in significant developmental defects and/or predisposition to cancer. One such DNA repair mechanism, homologous recombination, has the capacity to repair a wide variety of lesions. Knockout mouse models of genes thought to be involved in DNA repair processes are frequently lethal, making in vivo studies very difficult, if not impossible. Therefore, we set out to develop an in vivo conditional mouse model system to facilitate investigations into the involvement of essential genes in homologous recombination. To test our model, we measured the frequency of spontaneous homologous recombination using the pink-eyed unstable mouse model, in which we conditionally excised either Blm or full-length Brca1 (breast cancer 1, early onset). These two genes are hypothesized to have opposing roles in homologous recombination. In summary, our in vivo data supports in vitro studies suggesting that BLM suppresses homologous recombination, while full-length BRCA1 promotes this process.
Habitat characteristics of juvenile cowcod, Sebastes levis (Scorpaenidae), in Southern California

We characterized habitat requirements of juvenile cowcod, Sebastes levis, using information from surveys conducted aboard the manned research submersible Delta. We conducted 303 dive surveys on rocky banks and outcrops in water depths between 28 and 365 m in southern and central California, covering 483 km (963,940 m2) of seafloor. We counted 549,263 fishes from at least 134 species; 216 individuals were juvenile cowcod, S. levis, of 45 cm or less in total length (TL). Juvenile cowcod occupied depths between 52 and 330 m and demonstrated ontogenetic shifts in their habitat associations. Small fish (5–20 cm TL) lived primarily among cobbles or cobbles and small boulders. As fish grew, they moved into high-relief rock habitats, including boulder fields and rock ridges. Small cowcods were found with pygmy, Sebastes wilsoni, and swordspine, Sebastes ensifer, rockfishes. Larger juveniles often associated with juvenile bocaccio, Sebastes paucispinis, juvenile widow rockfish, Sebastes entomelas, and squarespot rockfish, Sebastes hopkinsi. Our study resulted in a characterization of seafloor habitats on a small spatial scale that is relevant to juvenile cowcod nursery areas, which is important when considering effective management strategies for this overfished species.
Comparative In Vitro Activities of Amoxicillin-Clavulanate against Aerobic and Anaerobic Bacteria Isolated from Antral Puncture Specimens from Patients with Sinusitis

By an agar dilution method, the antimicrobial susceptibilities of antral sinus puncture isolates were studied. Pneumococci were generally susceptible to amoxicillin, azithromycin, and clarithromycin, but 17% of pneumococcal isolates were resistant to cefuroxime. Haemophilus influenzae isolates were resistant to amoxicillin and clarithromycin. beta-Lactamase production occurred in 69% of Prevotella species. One-third of Peptostreptococcus magnus isolates were resistant to azithromycin and clarithromycin. Cefuroxime had limited activity against Prevotella species and P. magnus. Levofloxacin was active against most isolates except peptostreptococci. Amoxicillin-clavulanate was active against all isolates, with the MIC at which 90% of the isolates were inhibited being < or = 1 microgram/ml.
A Noncanonical Mechanism of Nrf2 Activation by Autophagy Deficiency: Direct Interaction between Keap1 and p62

In response to stress, cells can utilize several cellular processes, such as autophagy, which is a bulk-lysosomal degradation pathway, to mitigate damages and increase the chances of cell survival. Deregulation of autophagy causes upregulation of p62 and the formation of p62-containing aggregates, which are associated with neurodegenerative diseases and cancer. The Nrf2-Keap1 pathway functions as a critical regulator of the cell's defense mechanism against oxidative stress by controlling the expression of many cellular protective proteins. Under basal conditions, Nrf2 is ubiquitinated by the Keap1-Cul3-E3 ubiquitin ligase complex and targeted to the 26S proteasome for degradation. Upon induction, the activity of the E3 ubiquitin ligase is inhibited through the modification of cysteine residues in Keap1, resulting in the stabilization and activation of Nrf2. In this current study, we identified the direct interaction between p62 and Keap1 and the residues required for the interaction have been mapped to 349-DPSTGE-354 in p62 and three arginines in the Kelch domain of Keap1. Accumulation of endogenous p62 or ectopic expression of p62 sequesters Keap1 into aggregates, resulting in the inhibition of Keap1-mediated Nrf2 ubiquitination and its subsequent degradation by the proteasome. In contrast, overexpression of mutated p62, which loses its ability to interact with Keap1, had no effect on Nrf2 stability, demonstrating that p62-mediated Nrf2 upregulation is Keap1 dependent. These findings demonstrate that autophagy deficiency activates the Nrf2 pathway in a noncanonical cysteine-independent mechanism.
An Electron Microscopy Study of the Microstructure and Microarchitecture of the Strombus Gigas Shell

A scanning and transmission electron microscopy study is presented of the microstructure of the Strombus gigas shell. The hierarchical nature of this crossed-lamellar structure and the defect content of the mineral component are described. The mineral component consists of small single crystal grains of aragonite, the metastable orthorhombic polymorph of CaCO{sub 3}. The habit and morphology of the grains discussed here have not been determined previously. The observed habit and defect structure suggest that the organic matrix exerts a high degree of control over the crystal growth of the mineral phase and is responsible for the long range order in the microarhitecture. Electron beam heating of the mineral component leads to certain phase changes and these are discussed. 15 refs., 6 figs.
The Impact of Donor Age on Survival After Heart Transplantation: An Analysis of the United Network for Organ Sharing (UNOS) Registry

Background Data are limited regarding the influence of donor age on outcomes after heart transplantation. We sought to determine if advanced donor age is associated with differences in survival after heart transplantation and how this compares to waitlist survival. Methods All adult heart transplants from 2000 to 2012 were identified using the United Network for Organ Sharing database. Donors were stratified into four age groups: 18–39 (reference group), 40–49, 50–54, and 55 and above. Propensity scoring was used to compare status IA waitlist patients who did not undergo transplantation with IA recipients who received hearts from advanced age donors. The primary outcome of interest was recipient survival and this was analyzed with multivariate Cox regression analysis and the Kaplan–Meier method. Results A total of 22,960 adult heart transplant recipients were identified. Recipients of hearts from all three older donor groups had significantly increased risk of mortality (HR, 1.187–1.426, all p < 0.001) compared to recipients from donors age 18 to 39. Additionally, propensity-matched status IA patients managed medically without transplantation had significantly worse adjusted survival than status IA recipients who received hearts from older donors age ≥55 (HR, 1.362, p < 0.001). Conclusions Compared to donors aged 18–39, age 40 and above is associated with worse adjusted recipient survival in heart transplantation. This survival difference becomes more pronounced as age increases to above 55. However, the survival rate among status IA patients who receive hearts from advanced age donors (≥55) is significantly better compared to similar status IA patients who are managed without transplantation. doi: 10.1111/jocs.12406 (J Card Surg 2014;29:723–728)
Nonlinear dynamic properties of hydraulic suspension bushing with emphasis on the flow passage characteristics

Hydraulic bushings, which are often employed in vehicle suspension systems, exhibit significant excitation-dependent properties. However, previous analyses were mainly based on the linear system theory. To overcome this void, nonlinear characteristics of common hydraulic bushing configurations are examined in this article, with focus on the component properties as excited by sinusoidal or step displacements of various amplitudes. First, a nonlinear model for a laboratory prototype with a long passage and a short passage (in parallel) is developed using a lumped-parameter approach. Then the system parameters and nonlinearities are identified using experimental and computational methods, with an emphasis on characterization of the flow passage resistances. Steady-state harmonic and transient step experiments are conducted on the prototype, and the dynamic pressures inside two fluid chambers and the force transmitted to the base are measured. Numerical solution of the nonlinear model shows that the proposed ...
Differential information use for near and distant decisions

Whether choosing a cell phone, a senator, or a kitchen appliance, consumers today quickly find themselves awash in information from commercials, magazines, and websites. Whereas some of this information is broad, decontextualized, and abstracted across multiple individuals and instances, other information is more closely tied to a single experience within one specific context. The present research asks: under what circumstances do people rely on abstracted averages, and when are they swayed by another individual’s particular experience? Across three studies, we show that temporal distance increases the relative weight placed on aggregate vs. individualized information when participants are asked to choose between two sleeping pills, migraine medications, or kitchen appliances, and that this process impacts not only evaluation but also willingness to pay and choice. Potential implications for evaluation, decision-making, and base-rate utilization are discussed.
Social Welfare and Business: The Krupp Welfare Program, 1860–1914

Wolf Schneider has written that no other great industrialist of the nineteenth century “esteemed the personal freedom of his workers so little and their material well-being so highly” as did Alfred Krupp. Professor McCreary examines this counterpoint of humanitarianism and self-interest which produced some of Germany's “first steps toward industrial social responsibility.”
Subjective Text Difficulty: An Alternative Approach to Defining the Difficulty Level of Written Text

This paper outlines three operationalizations of the notion of text difficul- ty; text-based (objective), performance-based (behavioral), and a combination of the two (subjective). Text-based approaches such as readability formulae view "difficulty" as a characteristic residing in the text itself. Behavioral approaches disregard the text and focus solely on the performances of individual readers. The subjective approach outlined here matches a priori estimates of reading ability to ob- jective measures of text difficulty to establish a criterion for each individual reader. Texts falling below the criterion according to the objective difficulty scale are defin- ed as subjectively "easy", those above the criterion are defined as subjectively "hard". It is argued that individual performance characteristics are in part a function of subjective difficulty and that psychological research linking reading performance with general individual difference factors must therefore control for the subjective difficulty of texts used in research studies. Traditional measures of text difficulty involve analysis of the syntax, vocabulary, and/or content of texts using objective criteria. Difficulty (usually term- ed readability) is an invariant attribute of the text and remains constant no matter what the ability of the individual actually reading the text (e. g. Flesch, 1949; Dale & Chall, 1948). An observer monitoring or evaluating a specific individual reading a specific text, however, may define text difficult in strictly behavioral, reader-based terms. For example, an observer of oral reading may define texts eliciting many er- rors as "hard" and texts eliciting few errors as "easy". Similarly, the decision could be based on subsequent passage recall, performance on a comprehension text, or some other quantifiable and observable behavior. A third approach, the one termed "subjective text difficulty" in this paper, combines considerations of the text quality with consideration of the individual reader. Estimates of overall reading difficulty, above which the reader will find the text "hard" (and possibly, but not necessarily, make more errors) and below which the reader will find the text "easy" (and possibly make fewer errors).
Zur Biographie Thomas Manns: Erkenntnisse aus Biographien der Familienmitglieder

Es gibt viel ungedrucktes Material zur Biographie der Familienmitglieder, das noch mehr direktes und indirektes Licht auf die Biographie Thomas Manns werfen konnte. Dieser Bericht will nur skizzieren, was sich aus der kritischen Betrachtung der bisherigen Biographien der Familienmitglieder fur Thomas Manns Biographie ergibt, er enthalt darum keine Urteile uber die Behandlung der Werke der Kinder in deren Biographien.
Sub-Phonetic Modeling For Capturing Pronunciation Variations For Conversational Speech Synthesis

In this paper we address the issue of pronunciation modeling for conversational speech synthesis. We experiment with two different HMM topologies (fully connected state model and forward connected state model) for sub-phonetic modeling to capture the deletion and insertion of sub-phonetic states during speech production process. We show that the experimented HMM topologies have higher log likelihood than the traditional 5-state sequential model. We also study the first and second mentions of content words and their influence on the pronunciation variation. Finally we report phone recognition experiments using the modified HMM topologies.
The vascular calcification-cutaneous necrosis syndrome

Abstract Background : Although medial calcification of larger elastic arteries in chronic kidney failure and with advancing age is relatively common, calcification of the cutaneous vascular system is rare. Objective : Our purpose was to describe three patients with the vascular calcification-cutaneous necrosis syndrome and review the cause, clinical and pathologic features, and treatment of this syndrome. Methods : We describe three patients with ischemic necrotic ulcers and underlying cutaneous vascular calcification. The clinical setting was abnormal calcium metabolism from either chronic kidney failure or excessive vitamin D intake. Results : The clinical findings in all patients consisted of multiple tender livedoid nodules and ulcerative plaques on the thighs and legs, which developed in the setting of abnormal calcium metabolism from either chronic kidney failure or excessive vitamin D intake. Histologic study demonstrated vascular calcification. Although this syndrome usually has a chronic course with significant morbidity and mortality, subtotal parathyroidectomy followed by kidney transplantation resulted in complete resolution in one of our patients. Conclusion : The clinical and histopathologic findings in the vascular calcification-cutaneous necrosis syndrome are unique. The pathogenesis is likely multifactorial. Treatment for the skin lesions is largely supportive.
Ampliando los límites de la integración social: género e historia judía contemporánea

El presente texto invita a incorporar la historiografia de genero desde Europa y Estados Unidos a la historia judia. Es una reflexion sobre lo que se obtiene al ampliar los limites que se han considerado sobre como se construyen las comunidades judias, y tambien un esfuerzo para integrar esta conversacion al espacio de la historiografia latinoamericana. Finalmente, es un pequeno homenaje a la historiadora Paula Hyman, quien aporto desde la teoria y la practica, diversos elementos para el desarrollo de la historia de genero desde el mundo judio.
Overexpression of the kinetochore-associated proteins SKAP and astrin in human breast cancer

Abstract. The faithful alignment and segregation of chromosomes during mitosis is essential for the prevention of aberrant chromosome numbers that can lead to cancer. This process is mediated by the mitotic spindle, which forms stable attachments to the chromosomal centromere through the kinetochore structural intermediate. Small kinetochore-associated protein (SKAP) is a recently described component to the kinetochore that complexes with other kinetochore-associated proteins including astrin, CENP-E, and CEP55. SKAP is required for proper chromosome segregation and the metaphase to anaphase transition as its depletion results in activation of the spindle assembly checkpoint and mitotic delay. Here, we show that overexpression of SKAP in cultured cells speeds cell division in a colony formation assay. We also show that SKAP along with the interacting proteins CEP55 and astrin are overexpressed in human breast carcinoma. These data suggest that aberrant overexpression of SKAP and the astrin-SKAP complex ma...
A cysteine residue in the helix-loop-helix domain of Id2 is critical for homodimerization and function.

Id proteins are negative regulators of basic helix-loop-helix (bHLH) transcription factors. In this study, we compared the expression of Id2 mRNA in proliferating (fetal) and nonproliferating (adult) alveolar epithelial cells (AECs). The expression of Id2 was higher in adult AECs than in the corresponding fetal cells, suggesting that Id2 might play a functional role in developmental regulation of lung epithelial cell proliferation. By screening a mouse embryo cDNA library in the yeast two-hybrid system, Id2 was identified as a self-associating protein. Structural analysis by deletion and site-directed mutagenesis demonstrated that the HLH domain and a cysteine residue within the HLH domain are essential for Id2 homodimerization. Furthermore, in vitro synthesized Id2 homodimers became monomers under reducing conditions, indicating that the formation of an intermolecular disulfide bond is critical for Id2 homodimerization. Transient transfection assays in A549 cells showed that wild-type Id2 down-regulated the activity of the cyclin A promoter by 70%, while mutating the cysteine critical for Id2 homodimerization abolished the inhibitory effect of wild-type Id2.
Bevacizumab in lung cancer: Lackluster performance and unjustified expense?

A recent retrospective analysis of a large cohort of patients aged 65 and older with advanced non-small cell lung cancer failed to demonstrate any improvement in survival with the addition of bevacizumab to the platinum doublet in the first-line therapy. A few points have to be made: 1) a vast majority of patients with lung cancer are 65 and older; 2) important including fatal toxicity can occur with the use of bevacizumab; and 3) costs of bevacizumab are significant. Integrating the conclusions of this study into clinical practice and further analysis of underlying physical, psychosocial, and economic hurdles of bevacizumab use in lung cancer patients are certainly justified.
Erroneous interpretation of magnetic resonance images of a fracture of the first rib with non-union. Two case reports.

The first rib is the highest, strongest, flattest, and most curved of all of the ribs. Fractures from direct trauma are rare and usually are associated with major chest and abdominal injuries. Isolated stress fractures with non-union of the first rib, particularly as a result of sports activities, have been described in several reports. The diagnosis of a fracture of the first rib traditionally has been made from plain radiographs and bone scans. However, because of the rarity of the fracture and a general unfamiliarity with it, a physician is likely to obtain a magnetic resonance image to aid in the diagnosis of a lesion of the first rib because that modality offers superb soft-tissue contrast and a high sensitivity to changes in intraosseous signal intensity. The purpose of this paper is to report our experience with two patients who had a fracture of the first rib with non-union ; the interpretation of the magnetic resonance images led to an overestimation of the seriousness and the extent of the lesions, with resultant confusion regarding the diagnosis.
Effective Implementation Strategies of Differential Response in Child Welfare: A Comparative Case Analysis

Differential response is a growing approach in child welfare that aims to maintain children safely in their homes when possible. This study examined how the implementation of differential response varies between counties with improved child safety outcomes compared to counties with poorer outcomes. Data was collected from nine counties through semi-structured focus groups with workers and interviews with supervisors. Results indicated that counties with improved outcomes had integrated the following implementation strategies: use of comprehensive assessment protocols; integrated supervisory support and on-going coaching of effective practices; and increased mobilization of resources, including enduring supports for parents, supports to help families meet basic needs and culturally responsive services for families.