cssi/SciSciGPT-SciSciNet huggingface dataset:
TPCK inhibits AGC kinases by direct activation loop adduction at phenylalanine-directed cysteine residues

N-alpha-tosyl-l-phenylalanyl chloromethyl ketone (TPCK) has anti-tumorigenic properties, but its direct cellular targets are unknown. Previously, we showed TPCK inhibited the PDKl-dependent AGC kinases RSK, Akt and S6K1 without inhibiting PKA, ERK1/2, PI3K, and PDK1 itself. Here we show TPCK-inhibition of the RSK-related kinases MSK1 and 2, which can be activated independently of PDK1. Mass spectrometry analysis of RSK1, Aktl, S6K1 and MSK1 immunopurified from TPCK-treated cells identified TPCK adducts on cysteines located in conserved activation loop Phenylalanine–Cysteine (Phe–Cys) motifs. Mutational analysis of the Phe–Cys residues conferred partial TPCK resistance. These studies elucidate a primary mechanism by which TPCK inhibits several AGC kinases, inviting consideration of TPCK-like compounds in chemotherapy given their potential for broad control of cellular growth, proliferation and survival.
Raman spectroscopic studies of the dipalmitoylphosphatidylcholine/glucagon and the dipalmitoylphosphatidylcholine/cardiolipin/insulin systems

The phospholipid hydrocarbon chain conformation has been measured in lipid/protein complexes of dipalmitoylphosphatidylcholine (DPPC)/glucagon and dipalmitoylphosphatidylcholine/cardiolipin/insulin using the conformation-sensitive CH stretching region of the Raman spectrum as a probe. In the DPPC/glucagon complex, which models hydrophobic interactions between (membrane) proteins and phospholipids, the Raman data show that the lateral interactions between phospholipid hydrocarbon chains have been greatly disrupted in the complex. The primary effect of the protein appears to be to induce a disordering of the phospholipid. The gel–liquid crystal phase transition of DPPC is reduced in temperature and is rendered less cooperative. In the DPPC/cardiolipin/insulin complex, which models the electrostatic interaction between peripheral membrane proteins and phospholipids, the primary effect of complexation is to rigidify and order the hydrocarbon chains of the phospholipids. The main interaction of the protein occurs with the cardiolipin and results in the neutralization of the excess charge. The ternary complex undergoes a broad phase separation not present in the binary phospholipid mixture.
On the Ergodic Theorem of E. Hopf

Abstract In the paper we extend the ergodic theorem of E. Hopf to a large class of Archimedean Riesz spaces. In order to obtain the extension, we define and study a new type of convergence in Archimedean Riesz spaces. The new type of convergence (which we call individual convergence) was inspired by a work of Nakano (Ann. Math.49 (1948), 538-556) (from which we also borrowed its name) and by a paper of Ornstein (in "Advances in Probability and Related Topics" (Peter Ney, Ed.), Vol. 2, pp. 85-115, Dekker, New York, 1970) on modifications and the ratio ergodic theorem.
Isolation and partial characterization of lectin-resistant F9 cells.

Cytotoxic plant lectins have been used for the single-step selection of mouse embryonal carcinoma cell mutants with altered expression of surface glycoconjugates. Following mutagenesis, several F9 and OTF9-63 cell lines resistant to the lectins from Triticum vulgarisor Ricinus communis were obtained. At least five distinct lectin-resistant (LecR) phenotypes have been identified on the basis of their relative sensitivities to four different plant lectins and their altered lectin-binding properties. None of the mutant types exhibits a significant change in the ability to bind a monoclonal antibody against the stage-specific embryonic antigen, SSEA-1. All of the mutants form aggregates when cultured in bacteriological petri dishes and appear to differentiate into endoderm-like cells following exposure to retinoic acid. However, two of the LecR cell lines exhibit an altered morphology when grown on a plastic substratum.
Misoprostol is effective for induction of labor in high risk pregnant women: A randomized controlled trial

WOMEN: A RANDOMIZED CONTROLLED TRIAL MICHAEL SCHNEIDER, RISA RAMSEY, LU KAO, KELLY ANGELA BENNETT, University of Tennessee, Maternal Fetal Medicine, Memphis, Tennessee, University of Tennessee, Obstetrics and Gynecology, Memphis, Tennessee, University of Tennessee Health Science Center, Obstetrics and Gynecology, Memphis, Tennessee, Vanderbilt University, Maternal Fetal Medicine, Nashville, Tennessee OBJECTIVE: To test the null hypothesis that administering misoprostol orally or vaginally to high risk pregnant women undergoing labor induction will result in no difference in cesarean delivery rates. STUDY DESIGN: Three hundred and eleven women with medical and obstetrical complications of pregnancy were randomized to receive either misoprostol orally (50 mg) or vaginally (25 mg) every four hours for labor induction. Sample size was calculated using a two-tailed alpha of 0.05 and power [1-b] of 80%. Student’s t test, c and Fisher’s exact tests were used in analysis. Data were analyzed on an intent-to-treat basis. RESULTS: Analysis involved 134 women in the vaginal and 162 women in the oral misoprostol group. There were 41 cesarean deliveries (30.6%) in the vaginal and 59 (36.4%) in the oral group [P = .30, relative risk [RR] 0.86, confidence interval [CI] 0.6-1.1] Cesarean delivery rates for dystocia [P = .97, RR 0.99, CI 0.7-1.3] or non reassuring fetal heart rate tracing [P = .97, RR 0.99, CI 0.5-1.7] were not different based on route of administration. Significantly more women in the vaginal group required only a single dose of misoprostol. [P = .007, RR 1.4, CI 1.1-1.8]. No neonate in this study met ACOG criteria for birth asphyxia. CONCLUSION: Misoprostol is effective for induction of labor in women with medical and obstetrical complications of pregnancy. Vaginal administration may be the preferred route when time to delivery is an important concern.
High-throughput caveolar proteomic signature profile for maternal binge alcohol consumption.

Abstract Currently, no single marker is sensitive and specific enough to be considered a reliable biomarker for prenatal alcohol exposure. To identify a proteomic signature profile for maternal alcohol consumption, we carried out high-throughput proteomics on maternal endothelial caveolae exposed to moderate binge-like alcohol conditions. In these specialized lipid-ordered microdomains that contain a rich assembly of proteins, we demonstrate that moderate binge-like alcohol resulted in a distinctive maternal caveolar proteomic signature with important proteins being dramatically decreased/knocked out in the alcoholic profile. These proteins span from histones and basic structural proteins like α tubulin to proteins involved in trafficking, deubiquitination, cell signaling, and cell–cell adhesion. The profile also suggests an important role for the mother and the uteroplacental compartment in the pathogenesis of fetal alcohol spectrum disorders (FASD). These data demonstrate that the caveolar proteomic signature created by alcohol shows a promising direction for early detection of FASD.
A non-tactual factor in astereognosis

Abstract The classical view that astereognosis represents a modality-specific disorder of integration independent of sensory changes was examined in 65 men with penetrating brain injuries. The usual test of verbal identification of familiar objects was supplemented by a series of non-verbal tasks requiring discrimination of tactual object-qualities. Performance was evaluated in relation to basic somatosensory functions, motor status, cognitive abilities, and spatial orientation. The results failed to support the classical view. Although tactual shape perception may be impaired in the absence of somatosensory defect, such impairment is related to a spatial factor which is not specific to somesthesis.
Metabolism of tyrosine and phenylalanine in Trtpanosoma brucei gambiense

Abstract 1. 1. Soluble extracts of Trypanosoma brucei gambiense were found to contain high activity of the enzyme l -tyrosine: α-ketoglutarate aminotransferase (EC 2.6.1.5) amounting to 1.69 μmoles of tyrosine transaminated/mg. of protein/hour. 2. 2. Living, sonicated and sonicated + dialyzed preparations of this protozoan metabolized [14C] tyrosine to p-hydroxyphenylpyruvate and p-hydroxyphenyIlactate and [14C] phenylalanine to phenylpyruvate. Hydroxylation of tyrosine to 3,4-dihydroxyphenyIalanine (DOPA) and of phenylalanine to tyrosine, was not detected. 3. 3. Transamination of tyrosine by dialyzed enzyme preparations required both α-ketoglutarate and pyridoxal phosphate, while transamination of phenylalanine required only α-ketoglutarate. Two different transaminases appear to be responsible for the transamination of these two amino acids. 4. 4. Synthesis of p-hydroxyphenyllactate from [14C] tyrosine required NADH. 5. 5. Noradrenaline, DOPA and α-methyl p-tyrosine all inhibited the tyrosine aminotransferase to differing extents.
Biochemical markers as predictors for pulmonary effects of radiation

The delay in onset of clinical/radiological expression of pulmonary radiation toxicity precludes modification of radiation factors during treatment. Early detection of normal lung damage by biochemical markers that would predict for pneumonitis and/or fibrosis could allow for timely intervention. This study was undertaken to analyze changes in blood levels of surfactant apoprotein, procollagen III, and transforming growth factor β (TGF-β) in patients undergoing pulmonary radiation therapy (RT) and to determine if a correlation exists between early changes of these biochemical markers and subsequent radiographic and clinical evidence of pneumonitis and/or fibrosis. Sixteen patients with primary lung cancer undergoing thoracic irradiation were enrolled in this study and blood samples were obtained pretreatment, weekly during treatment, and at follow-up. At the same time points, patients underwent physical examination, chest X-rays, and computerized tomographic (CT) scans. Surfactant apoprotein was determined by immunodot blot analysis, procollagen III levels were determined by radioimmunoassay (RIA), and TGF-β was determined by an enzyme-linked immunosorbent assay (ELISA) kit. Radiographically, 9 of 16 patients entered developed moderate to severe evidence of acute radiation injury; 6 had mild or no changes. The mean increase in surfactant apoprotein level during treatment was different (P = 0.074) between the two groups: 6% in the moderate/severe group vs. 42% in the mild/no change group. The inverse correlation for surfactant apoprotein levels during treatment relative to radiographic changes at 2 months was statistically significant (R = −0.59, P < 0.05). Clinically, 5 of 16 developed pneumonitis. Lack of increase in surfactant apoprotein levels during treatment similarly corresponded to clinical pneumonitis. During treatment 50% (8 of 16) of the patients had procollagen III levels above the upper limit of normal. This group had increased radiographic evidence at 4–6 months posttreatment of radiation late effects (fibrosis) compared to the group with normal procollagen levels during treatment. TGF-β values pretreatment were elevated for patients developing pneumonitis and moderate to severe radiological changes, but this did not have statistical significance. Analysis of preliminary data suggests that an increase in surfactant apoprotein levels during thoracic irradiation is associated with a decreased probability of clinical and radiographic evidence of radiation-induced lung injury. Furthermore, an elevated procollagen III level during treatment may be useful in predicting the development of late radiographic evidence of more severe fibrosis than patients with normal values during treatment. The role of TGF-β as a predictor of fibrosis needs to be further investigated. These biochemical markers may prove useful as short-term endpoints to evaluate toxicity at a time when treatment factors could be modified (e.g., volume or dose) and particularly with the assessment of new modalities such as three-dimensional treatment planning. © 1995 Wiley-Liss, Inc.
Depression, self-focus, and social interaction.

The accuracy of depressed and nondepressed subjects' perceptions of their own and a social interactional partner's performance was investigated. Twenty depressed and twenty nondepressed college students participated in dyadic interactions and then rated their own and their partner's social behavior. The interactions were also rated by objective coders. Depressed subjects were differentiated from nondepressed subjects on several measures by both the coders and the subjects. Depressed subjects' self-ratings were correlated with the coders' ratings more often than were the nondepressives' ratings, suggesting depressives provided more accurate self-observations. Contrary to prediction, depressives were also more accurate in judging their partner's behavior. Depressives experienced heightened levels of self-focused attention, but this attentional focus did not mediate the relationship between depression level and self-accuracy. Finally, an analysis of the verbal statements suggests that performance differences between depressives and nondepressives may be a function of the quantity, rather than the quality, of the verbal production.
Toward a definition of “bibliometrics”

The definitions of the term ‘bibliometrics’ as used in the literature are examined and evaluated. Most such definitions are held to be too broad. A new definition is proposed; then its advantages and possible defects pointed out. A crucial question is whether Zipf's law of word occurrence should be considered a part of this particular sub-discipline.
Black sheep and expectancy violation: integrating two models of social judgment

A study of race-based ingroup and outgroup judgment demonstrates the links between two models of social judgment—the ‘black sheep’ effect (Marques, Yzerbyt & Leyens, 1988) and expectancy-violation theory (Jussim, Coleman & Lerch, 1987). White participants had a live interaction with a Black or White partner who contributed to a team success or failure at a game. Partner judgments, perceived expectancy violation, and mood changes indicated a pattern of ingroup polarization, though the race differential was reliable only when targets performed poorly. Consistent with other research, this pattern was most striking among Whites who were highly identified with their racial group. We suggest that racial identification activates favorable within-group judgment standards which, when violated, produce mood decrements and negative evaluations. Copyright © 1999 John Wiley & Sons, Ltd.
Elementary derivation of the perturbation equations of celestial mechanics

The equations of celestial mechanics that govern the temporal rates of change of orbital elements are completely derived using elementary dynamics and proceeding only from Newton's equation and its solution. Two orbital equations and the four most meaningful orbital elements - semimajor axis, eccentricity, inclination, and longitude of pericenter - are written in terms of the orbital energy (E) and angular momentum (H) per unit mass. The six resulting equations are differentiated with respect to time to see the effect on the orbital elements of small changes in E and H. The usual perturbation equations in terms of disturbing-force components are then derived by computing the manner in which perturbing forces change E and H. The results are applied in a qualitative discussion of the orbital evolution of particles in nonspherical gravitational fields, through atmospheres, and under the action of tides.
Immune activation at effector and gene expression levels after measles vaccination in healthy individuals: a pilot study.

Abstract Cellular immunity to measles vaccination is not fully understood at the effector response and gene expression levels. We enrolled 15 healthy individuals (15–25 years old) previously vaccinated with two doses of measles-mumps-rubella-II vaccine to characterize their cellular immunity. We detected a spectrum of lymphoproliferative response (median stimulation indices of 3.4), low precursor frequencies of interferon-γ (median 0.11%) and interleukin-4 (median 0.05%) by Elispot, and cosecretion of Th1 and Th2 cytokines after measles virus stimulation. Further, global gene expression was examined in five subjects from this cohort after vaccination with an additional dose of measles vaccine (Attenuax, Merck) to identify the genes involved in measles immunity. Linear mixed effect models were used to identify genes significantly up or downregulated in vivo between baseline and Days 7 and 14 after measles vaccination. Measles vaccination induced upregulation of a set of 80 genes, which play a role in measles immunity, signal transduction, apoptosis, cell proliferation, and metabolic pathways. Among the 34 genes that were downregulated, only interferon-α is known to have a direct role in measles immunity. This study suggests that measles vaccination leads to activation of multiple cellular mechanisms that can override the immunosuppressant effects of the measles virus and induce immunity.
Agonistic Behavior in Organized and Disorganized Cotton Rat Populations

Agonistic interaction rate is significantly lower in groups of caged cotton rats (Sigmodon hispidus) from naturally occurring organized populations than in groups composed of strangers. Some type of social structure is apparently present between animals sharing a common area under natural conditions. After a 24-hour period, there is no significant difference in the behavior of the two groups, an indication that a social structure is rapidly formed in the disorganized groups.
Phase coherence and superfluid-insulator transition in a disordered Bose-Einstein condensate

We have studied the effects of a disordered optical potential on the transport and phase coherence of a Bose-Einstein condensate (BEC) of $^{7}\text{L}\text{i}$ atoms. At moderate disorder strengths $({V}_{D})$, we observe inhibited transport and damping of dipole excitations, while in time-of-flight images, random but reproducible interference patterns are observed. In situ images reveal that the appearance of interference is correlated with density modulation, without complete fragmentation. At higher ${V}_{D}$, the interference contrast diminishes as the BEC fragments into multiple pieces with little phase coherence.
Electronic Constant-Current Motor Systems

As an adjustable speed drive the electronic constant-current motor system has the same characteristics as the variable voltage system but with a minimum complement of power tubes. Its constant torque characteristics simplify its use for certain classes of application, such as maintenance of tension. These installations range in size from 1/4 horsepower to 7 1/2 horsepower and have a definite advantage in use with electronic control.
Desorption of soy oil lutein from rice hull cristobalite with polar solvents

The effectiveness of sequential isopropanol/hexane washes of increasing polarity for desorbing soy oil pigment (lutein) from alkaline and acid rice hull ash was studied. Increasing the polarity promoted desorption of pigment. However, the amount of pigment desorbed with each extraction decreased after washing with 2% isopropanol. More lutein was desorbed as the amount of adsorbed lutein increased. Desorption from acid ash was greater than that from alkaline ash, which may be due to the absence of potassium from acid ash. The data suggest that the adsorption sites, occupied by lutein, are not all equally accessible to isopropanol, probably because of the irregular structure of the ash.
C ONQUEST : A Coarse-Grained Algorithm for Constructing Summaries of Distributed Discrete Datasets

In this paper we present a coarse-grained parallel algorithm, CONQUEST, for constructing bounded-error summaries of high-dimensional binary attributed data in a distributed environment. Such summaries enable more expensive analysis techniques to be applied efficiently under constraints on computation, communication, and privacy with little loss in accuracy. While the discrete and high-dimensional nature of the dataset makes the problem difficult in its serial formulation, the loose-coupling of distributed servers hosting the data and the heterogeneity in network bandwidth present additional challenges. CONQUEST is based on a novel linear algebraic tool, PROXIMUS, which is shown to be highly effective on a serial platform. In contrast to traditional fine-grained parallel techniques that distribute the kernel operations, CONQUEST adopts a coarse-grained parallel formulation that relies on the principle of sampling to reduce communication overhead while maintaining high accuracy. Specifically, each individual site computes its local patterns independently. Various sites cooperate in dynamically orchestrated work groups to construct consensus patterns from these local patterns. Individual sites may then decide to continue their participation in the consensus or leave the group. Such parallel formulation implicitly resolves load-balancing and privacy issues while reducing communication volume significantly. Experimental results on an Intel Xeon cluster demonstrate that this strategy is capable of excellent performance in terms of compression time, ratio, and accuracy with respect to post-processing tasks.
Estimation of mixed venous oxygen saturation

Pulmonary artery oxygen saturation (PA) was measured directly and estimated from venal cavae samples in 175 adults without intracardiac shunts to ascertain which of four formulas (MV1, MV2, MV3, or MV4) best estimated mixed venous oxygen saturation. Because the formula MV1, which favored IVC samples, most closely approximated pulmonary artery saturation, we recommend its use to estimate systemic flow in patients with left-to-right shunts. In addition, a difference between directly measured PA and calculated MV1 of 6% or greater indicates the presence of a left-to-right shunt in 97% of cases.
Classes of programmed cell death in plants, compared to those in animals

Relatively little is known about programmed cell death (PCD) in plants. It is nonetheless suggested here that tonoplast rupture and the subsequent rapid destruction of the cytoplasm can distinguish two large PCD classes. One class, which is here called ‘autolytic’, shows this feature, whilst the second class (called ‘non-autolytic’) can include tonoplast rupture but does not show the rapid cytoplasm clearance. Examples of the ‘autolytic’ PCD class mainly occur during normal plant development and after mild abiotic stress. The ‘non-autolytic’ PCD class is mainly found during PCD that is due to plant–pathogen interactions. Three categories of PCD are currently recognized in animals: apoptosis, autophagy, and necrosis. An attempt is made to reconcile the recognized plant PCD classes with these groups. Apoptosis is apparently absent in plants. Autophagic PCD in animals is defined as being accompanied by an increase in the number of autophagosomes, autolysosomes, and small lytic vacuoles produced by autolysosomes. When very strictly adhering to this definition, there is no (proof for) autophagic PCD in plants. Upon a slightly more lenient definition, however, the ‘autolytic’ class of plant PCD can be merged with the autophagic PCD type in animal cells. The ‘non-autolytic’ class of plant PCD, as defined here, can be merged with necrotic PCD in animals.
Beamformed Flow-Acoustic Correlations in a Supersonic Jet

Anexperimental studyofsimultaneousmultipointmeasurements inthe flowfieldandacoustic fieldofaMach1.75 cold-air jet is presented. A series of four optical-deflectometer probes measured turbulent fluctuations in or near the jet flow, and eight microphones recorded the far-field pressure in the direction of peak emission. The correlation methodology involves the coherence between the delay-and-sum beamformer outputs of the optical-deflectometer probes and the microphones. This procedure yields results with greater fidelity and higher coherence levels than obtainedwithindividualoptical-deflectometer-to-microphonecorrelations.Withtheoptical-deflectometerprobesin the jet shear layer, there is a significant correlation, on the order of 0.1, between the turbulent fluctuations and farfield noise. As the optical-deflectometer probe moves transversely away from the jet, its correlation with the microphone beamformer first drops and then increases. This trend signifies the transition from hydrodynamic to acoustic pressure fields. In the vicinity of the nozzle exit, the peak coherence between the beamformed opticaldeflectometer and microphone signals coincides with the physical location of the optical-deflectometer probe. However, as the shear layer thickens downstream, the peak coherence generally lags the probe location, which is a probable result of acoustic refraction by the mean flow.
Factors influencing internet use—A policy model for electronic government information provision

Abstract Collaborative efforts have fostered the development, maintenance, and expansion of the Internet. Historically, public, non-profit, and private sector institutions have made significant contributions. By reviewing the literature that discusses the contributions, roles, and responsibilities of public, non-profit, and private sector institutions, four categories of factors that influence access to and use of the Internet are identified and discussed at length. These factors include: the technical characteristics of information technologies; user preferences for information resources; the institutional arrangements that define, govern, and constrain provider/user relationships; and psychological factors affecting information processing.
In situ friction measurement on murine cartilage by atomic force microscopy.

Articular cartilage provides a low-friction, wear resistant surface for the motion of diarthrodial joints. The objective of this study was to develop a method for in situ friction measurement of murine cartilage using a colloidal probe attached to the cantilever of an atomic force microscope. Sliding friction was measured between a chemically functionalized microsphere and the cartilage of the murine femoral head. Friction was measured at normal loads ranging incrementally from 20 nN to 100 nN with a sliding speed of 40 μm/s and sliding distance of 64 μm. Under these test conditions, hydrostatic pressurization and biphasic load support in the cartilage were minimized, providing frictional measurements that predominantly reflect boundary lubrication properties. Friction coefficients measured on murine tissue (0.25±0.11) were similar to those measured on porcine tissue (0.23±0.09) and were in general agreement with measurements of boundary friction on cartilage by other researchers. Using the colloidal probe as an indenter, the elastic mechanical properties and surface roughness were measured in the same configuration. Interfacial shear was found to be the principal mechanism of friction generation, with little to no friction resulting from plowing forces, collision forces, or energy losses due to normal deformation. This measurement technique can be applied to future studies of cartilage friction and mechanical properties on genetically altered mice or other small animals.
Effect of Holding Condition on the Development of Salmonellae in Artificially Inoculated Hens’ Eggs

Abstract THE contents of the egg as laid by the normal healthy hen are sterile and it is possible that the shell may not be contaminated during the act of laying (Stuart and McNally, 1943). However, the ovaries may occasionally become infected with Salmonellae which may be transferred to the egg contents (Scott, 1930). Consequently, the incidence of Salmonellae on or in shell eggs depends upon three factors: the environmental condition of the eggs, handling and storage, and the physical structure of the shell. Studies have been made on the ability of egg spoilage bacteria to utilize the material of the shell membranes for growth (Stokes and Osborne, 1956; Elliott and Brant, 1957; Garibaldi and Stokes, 1958; Board et al., 1964). Lancaster and Crabb (1953) demonstrated that although bacteria penetrated the shell, only rarely did organisms pass through the shell membrane into the white of the eggs. Stokes and Osborne (1956) …
Teaching Elementary-Age Youth Catching Skills Using Theoretically Based Motor-Development Strategies.

Participating in general physical activity during childhood may not be the strongest predictor of lifetime physical activity. Children must develop motivation to participate in physically active endeavors and become excited about being active. These feelings toward physical activity may be best obtained by teaching with a more deliberate emphasis on the developmental stages of skill acquisition. This article describes a method for teaching catching skills that is grounded in the cognition and motor-development tenets of refinement and proximodistal development. The preparatory body movement skills — the focus stage — should be a primary objective for physical education teachers and their early elementary-age students during catching instruction. The focus stage includes information gathering, foot movements, body adjustment, and arm motions. Focusing on the actual catch — the control stage — skips vital aspects of a mature catching skill that likely would lead to greater understanding and skill in the fut...
Ideal Amino Acid Profile for Chicks During the First Three Weeks Posthatching

Abstract Two chick bioassays with chemically defined amino acid (AA) diets were conducted to compare three different AA profiles: the NRC 1984 and NRC 1994 requirement profile and the Illinois Ideal Chick Protein (IICP) AA profile. The two battery studies involved chicks during the 2nd and 3rd wk after hatching. In Assay 1, indispensable AA (including glycine and proline) were ratioed to lysine according to requirement ratios present in NRC 1984 and NRC 1994, with digestible lysine set at either deficient (.80% of diet) or superadequate (1.12% of diet) levels for the purified diet in question. All diets were kept isonitrogenous (2.83% N) by varying the level of L-glutamic acid. At .80% lysine, chicks fed the NRC 1994 AA profile gained 60% faster (P
DOSIMETRY GUIDELINES TO MINIMIZE URETHRAL AND RECTAL MORBIDITY FOLLOWING TRANSPERINEAL I-125 PROSTATE BRACHYTHERAPY

PURPOSE: To establish dosimetry guidelines to minimize urethral and rectal morbidity following permanent I-125 prostatic brachytherapy. METHODS AND MATERIALS: Dosimetric parameters were correlated with long-term morbidity for 65 patients following transperineal I-125 implantation for Stage T1/T2 prostatic carcinoma. The prescribed minimum prostatic dose was 150 Gy. The median total activity used was 48 mCi (range: 32-77 mCi). Patients were followed for 1-5 years (median follow-up: 2 years). Postimplant computerized tomography (CT)-based dosimetry was performed for 45 patients. Morbidity was evaluated using a modification of the RTOG grading system, with a scale of grade 0-5. RESULTS: The incidence of grades 2 and 3 urinary morbidity was associated with the maximum central urethral dose (p = 0.03), and with the length of urethra that received greater than 400 Gy (p = 0.07). Patients with larger prostates had more long-term urinary morbidity (p = 0.06). Rectal bleeding (RTOG grade 1) or ulceration (RTOG grade 2) was associated with irradiation of the rectal wall to doses in excess of 100 Gy (p = 0.02). There was no relationship between the matched peripheral dose (MPD), mCi/source or total mCi implanted and long-term morbidity. CONCLUSIONS: Postimplant, CT-based dosimetry can predict which patients are at higher risk of radiation-related morbidity. More simplistic parameters including the MPD, total activity implanted, or mCi/source, had no relationship with morbidity. To decrease the risk of long-term morbidity, an effort should be made to keep the central urethral dose below 400 Gy, and the rectal surface dose below 100 Gy. Language: en
Primary and secondary prevention of coronary artery disease: trials of lipid lowering with statins.

E year in the United States .600,000 people develop coronary artery disease (CAD). Estimated treatment costs for these patients in the first year are $5.54 billion. The total costs for direct medical care for all CAD amounts to approximately $16.2 billion each year.1 Any intervention that can prevent or delay the onset of coronary disease can have a profound impact on the economy and on public health. Lowering cholesterol by 10% causes a 15% reduction in CAD mortality and an 11% reduction in total mortality.2 The best evidence to date for the benefits of cholesterol-lowering therapy comes from 5 large trials of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins. These trials—the Scandinavian Simvastatin Survival Study (4S),3 the West of Scotland Coronary Prevention Study (WOSCOPS),4 the Cholesterol and Recurrent Events (CARE) Study,5 the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) trial,6 and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)7—enrolled .30,000 patients, providing definitive evidence of the benefits of statin therapy for primary and secondary prevention of CAD-related events in patients with both elevated and average baseline cholesterol levels (Table I). These trials will be summarized below according to the degree of risk for a major coronary event in the patient populations enrolled; that is, the first trial discussed, 4S, studied patients at high risk for an event, whereas AFCAPS/TexCAPS studied a lower-risk population with baseline cholesterol levels similar to those generally characteristic of the US population.
Verification and validation of renormalization group inspire particle weights for PIC codes

Simulations of dense kinetic plasmas are an area of active research. A variety of devices from high power microwave devices to Hall thrusters involve situations with dense fluidlike plasmas coexisting with important kinetic non-Maxwellian particle distributions. These plasmas exhibit a range of length and time scales, making accurate simulation a challenging and computationally intensive task. Currently, we are applying renormalization group methods to provide a systematic means to investigate multi-scale plasma behavior from the kinetic to the MHD regime. One development has been the discovery of a relationship between traditional particle-in-cell weights and the renormalized charge associated with Debye shielding. The development of algorithms to handle these multi-scale circumstances is facilitated by high-fidelity test problems suitable for verification and validation studies. Specifically, we report on the development of ordinary differential equations appropriate for studying kinetic plasmas with short Debye lengths relative to the system size. Via analytic and numerical solutions, we study the impact of collective shielding on Langmuir waves. Both our analytic and PIC simulations indicate the existence of harmonic mixing driven by nonlinear excitation of Langmuir waves in highly shielded (dense) plasmas.
Repeated valproate treatment facilitates fear extinction under specific stimulus conditions

Single dose treatment with histone deacetylase inhibitor (HDACi) agents has been shown to enhance extinction learning in rodent models under certain conditions. The present novel studies were designed to examine the effects of repeated HDACi treatment, with valproate or sodium butyrate, on the extinction of conditioned fear. In Experiments 1 and 2, short duration CS exposure (30s) in combination with vehicle administration progressively attenuated conditioned fear responses over 40 or more sessions. This effective extinction training was not augmented by HDACi treatments. In Experiment 3, we used a long duration CS exposure (120 s) to weaken extinction training. With these extinction parameters, repeated valproate treatment substantially facilitated the acquisition and retention of fear extinction. Results of this study extend previous work suggesting that HDACi's have utility in augmenting the efficiency of fear extinction, although their apparent benefits are critically dependent upon specific parameters of extinction training.
Growth arrest and DNA damage inducible gene 45 (GADD45) is induced by laminar shear stress as identified by using DNA microarray technology

Laminar shear stress inhibits endothelial cell proliferation in vitro. Using DNA microarray technology, we found that many genes involved in growth arrest were up-regulated by laminar shear stress, including the Growth Arrest and DNA Damage Inducible Gene 45 (GADD45). The mRNA and protein levels of GADD45 were both increased in response to laminar flow, as shown by Northern blot and Western blot, respectively. The induction of GADD45 promoter by laminar shear stress was regulated by the tumor suppressor gene p53. These results provide a molecular basis for the inhibition of endothelial cell proliferation by laminar shear stress.
Linkage specificity and role of properdin in activation of the alternative complement pathway by fungal glycans.

ABSTRACT Fungal cell walls are predominantly composed of glucans, mannans, and chitin. Recognition of these glycans by the innate immune system is a critical component of host defenses against the mycoses. Complement, an important arm of innate immunity, plays a significant role in fungal pathogenesis, especially the alternative pathway (AP). Here we determine that the glycan monosaccharide composition and glycosidic linkages affect AP activation and C3 deposition. Furthermore, properdin, a positive regulator of the AP, contributes to these functions. AP activation by glycan particles that varied in composition and linkage was measured by C3a generation in serum treated with 10 mM EGTA and 10 mM Mg2+ (Mg-EGTA-treated serum) (AP specific; properdin functional) or Mg-EGTA-treated serum that lacked functional properdin. Particles that contained either β1→3 or β1→6 glucans or both generated large and similar amounts of C3a when the AP was intact. Blocking properdin function resulted in 5- to 10-fold-less C3a production by particulate β1→3 glucans. However, particulate β1→6 glucans generated C3a via the AP only in the presence of intact properdin. Interestingly, zymosan and glucan-mannan particles (GMP), which contain both β-glucans and mannans, also required properdin to generate C3a. The β1→4 glycans chitin and chitosan minimally activated C3 even when properdin was functional. Finally, properdin binding to glucan particles (GP) and zymosan in serum required active C3. Properdin colocalized with bound C3, suggesting that in the presence of serum, properdin bound indirectly to glycans through C3 convertases. These findings provide a better understanding of how properdin facilitates AP activation by fungi through interaction with the cell wall components. IMPORTANCE Invasive fungal infections have increased in incidence with the widespread use of immunosuppressive therapy and invasive procedures. Activation of the complement system contributes to innate immunity against fungi by generating chemoattractants that recruit white blood cells and by coating the pathogen with complement fragments that “mark” them for phagocytosis. The fungal cell wall activates complement in an antibody-independent manner through the alternative pathway (AP). Properdin is a positive regulator of the AP. This study elucidates how the specificity of cell wall glycan linkages affects AP activation and the role properdin plays in this process. Particulate β1→3 glucans activated the AP even in the absence of properdin, while β1→6 glucans required properdin for AP activation. In contrast, the β1→4 glycans chitin and chitosan failed to activate the AP. These findings enhance our mechanistic understanding of how fungi activate complement and have implications for the use of glycans in biomedical applications.
A novel preclinical model of human malignant melanoma utilizing bioreactor rotating-wall vessels

Abstract Malignant melanoma poses a serious health risk which is becoming more crucial as the incidence of this disease steadily increases. The development of appropriate in vitro models that reflect the in vivo tumor environment is a key factor for the study of this malignancy. The local tumor microenvironment plays a critical role in the ability of tumor cells to proliferate and metastasize. While interactions among various cell types are known to be important for tumor growth, most in vitro models utilize only tumor cells, ignoring the importance of tumor–stroma interactions, as well as the contribution of immune cells, which may be important for potential therapies. In addition, the cellular architecture found in vivo, known to be involved in changes in gene expression, is not reflected in standard two-dimensional culture systems. In this study, we have utilized rotating-vessel bioreactors to culture minced human melanoma specimens, allowing the culture of three-dimensional structures which reflect th...
Failure of Immune Serum Globulin to Prevent Hepatitis B Virus Infection in Infants Born to HBsAg-Positive Mothers

Abstract Twelve infants, born to mothers with hepatitis B virus infection, were inoculated within 7 days of birth with immune serum globulin containing antibody to hepatitis B surface antigen (HBsAg) titers of 1:32 to 1:64 as measured by passive hemagglutination. Six of nine infants (66.7%) born to HBsAg-positive carrier mothers became HBsAg-positive within 3 mo of age. In addition, two of three treated infants born to mothers with acute hepatitis B during the delivery period also developed HBsAg. The hepatitis e antigen was detected in four of five carrier mothers and in two mothers with acute hepatitis, whose infants subsequently became HBsAg positive. In addition, hepatitis B-specific DNA polymerase activity was detected in the seven HBsAg-positive mothers who transmitted the virus io their infants. All eight infants have remained persistently HBsAg positive. Thus, the immune serum globulin containing low-titer antibody to HBsAg is not protective when given to infants born to HBsAg carrier mothers or to mothers with acute hepatitis B during the delivery period.
The Right and the Good

This is a chapter for a political philosophy handbook being edited by Antonella Besussi for Ashgate Publishing. The chapter aims to set out the conceptual and theoretical landscape regarding the right and the good in a manner useful to political philosophers unfamiliar with it.
Targeted Therapy for Melanoma

Vemurafenib and dabrafenib, two potent tyrosine kinase inhibitors (TKIs) of the BRAF(V600E) kinase, are highly effective in the treatment of a BRAF (V600) -mutant metastatic melanoma. These are selective type I inhibitors (functional against the active conformation of the kinase) of the RAF kinases, which are key players in the mitogen-activated protein kinase (MAPK) pathway. BRAF (V600) mutations are present in approximately 7 % of all cancers, including high frequencies of mutations reported in 50 % of advanced melanomas and 100 % of hairy cell leukemias. As with most targeted therapies, resistance to BRAF inhibitors is an issue, and mechanisms of resistance are varied. Combining BRAF inhibitors with MEK inhibitors such as trametinib delays the development of resistance. Rationally combining targeted therapies to address the mechanism of resistance or combining BRAF inhibitors with other effective therapies such as immunotherapy may result in further improvement in outcomes for patients.
Activation of the kynurenine pathway leads to reactive oxygen species-mediated apoptosis of human retinal endothelial cells: Implications for diabetic retinopathy

Purpose: In this study we investigated the role of the indoleamine 2,3-dioxygenase (IDO)-initiated kynurenine pathway in human retinal endothelial cell (HREC) apoptosis. Methods: HREC were treated with 1 to 5 units of IFN-γ in the presence or absence 25 mM glucose (HG) for 48 hrs. The IDO expression and activity were assessed by western blotting and HPLC. ROS was measured using CM-H2DCFDA and apoptosis was determined by Hoechst staining. Diabetes in wild type (WT) and IDO knockout animals was induced by streptozotocin injection. Retinal capillary degeneration was assessed after 8 months of diabetes Results: IFN-γ upregulated IDO in HREC. High glucose sensitized HREC to IFN-γ-mediated signaling by upregulating IDO. IDO-mediated tryptophan oxidation led to the formation of reactive oxygen species (ROS) through 3OH-kynurenine and resulted in apoptosis of HRECs. Blockade of IDO or 3OH-kynurenine monooxygenase led to a significant inhibition ROS formation and apoptosis in HREC. Capillary degeneration, a common manifestation in diabetic retinopathy in mice, was significantly reduced in diabetic IDO knockout mice when compared with diabetic WT mice. Conclusion: The results suggest that ROS produced from the kynurenine pathway plays an important role in the inflammatory damage in the diabetic retina.
Prediction of Transport Properties of Nanosystems and Their Use for Virtual Fabrication of Nanomaterials

Fundamental statistical-mechanical expressions for transport coefficients describing transport processes in spatially inhomogeneous systems (such as nanofluids, interfacial systems, atomic clusters, etc.) and derived by the use of the functional perturbation theory (FTP) due to Pozhar and Gubbins (PG) are simplified for the use in engineering and technology. Together with explicit expressions for the charge transport properties of quantum inhomogeneous systems (such as semiconductor quantum dots, wells and wires, artificial atoms/molecules etc.) derived recently, these expressions form a basis for development of algorithms and codes to realize a virtual (i.e., fundamental theory-based, computational) synthesis of nanomaterials with predesigned transport properties for novel nanocluster- or nanopore- based catalysts and adsorbents, integrated nanocircuits, nanoheterostructures, etc.
ET-36HYPERTHERMIA IMPROVES THE RADIOSENSITIVITY OF GLIOMA STEM CELLS BY INHIBITION OF AKT SIGNALING

Glioblastoma (GBM) is the most prevalent and fatal type of primary brain tumor. Radiation is the most effective adjuvant therapy. Glioma stem cells (GSCs) are a subpopulation of cells that survive to self-renew and recapitulate the tumor. Hyperthermia is one of the most potent radiosensitizers and is re-emerging as a treatment option for patients with GBM. To determine mechanisms behind hyperthermic radiosensitization, we performed a screen by phospho-kinase array analysis. We identified suppression of AKT activation as a major mechanism for thermoradiosensitization of GSCs. Whereas GSCs exhibited increased AKT activity after irradiation, hyperthermia abrogated radiation-induced AKT activation to impair proliferation and promote apoptosis. Expression of a constitutively activated form of AKT in GSCs was able to restore radioresistance even with thermoradiotherapy. Pharmacologic inhibition of the AKT regulator PI3K further enhanced thermoradiosensitization. In a preclinical orthotopic xenotransplantation model of GBM, thermoradiotherapy suppressed the phosphorylation of the AKT downstream effector ribosomal protein S6, reduced tumor growth and extended animal survival. Together, these data support the use of combined hyperthermia and radiation for the treatment of glioblastoma.
Effect of Some Carbon Sources on Production of A Chlorosis-Inducing Agent by Alternaria Tenuis

Twelve sugars were used as carbon sources for Alternaria tenuis to determine their effects on the production of a toxin by the fungus that induces chlorosis in the seedlings of numerous dicotyledon...