cssi/SciSciGPT-SciSciNet huggingface dataset:
Enhancement and destruction of antibody function by somatic mutation: unequal occurrence is controlled by V gene combinatorial associations.

Abstract We examined the positive and negative effects of somatic mutation on antibody function using saturation mutagenesis in vitro to mimic the potential of the in vivo process to diversify antibodies. Identical mutations were introduced into the second complementarity determining region of two anti-phosphocholine antibodies, T15 and D16, which share the same germline VH gene sequence. T15 predominates in primary responses and does not undergo affinity maturation. D16 is representative of antibodies that co-dominate in memory responses and do undergo affinity maturation. We previously reported that > 50% of T15 mutants had decreased antigen binding capacity. To test if this high frequency of binding loss was unique to T15 or a consequence of random point mutations applicable to other combining sites, we analyzed the same mutations in D16. We show that D16 suffers a similar loss of function, indicating an equally high potential for B-cell wastage. However, only D16 displayed the capacity for somatic mutation to improve antigen binding, which should enhance its persistence in memory responses. Mutation of residues contacting the haptenic group, as determined by molecular modeling, did not improve binding. Instead, productive mutations occurred in residues that either contacted carrier protein or were distant from the antigen binding site, possibly increasing binding site flexibility through long-range effects. Targeting such residues for mutation should aid in the rational design of improved antibodies.
TIMP-1 Promotes the Immune Response in Influenza-Induced Acute Lung Injury.

Influenza infects millions of people each year causing respiratory distress and death in severe cases. On average, 200,000 people annually are hospitalized in the United States for influenza related complications. Tissue inhibitor of metalloproteinase-1 (TIMP-1), a secreted protein that inhibits MMPs, has been found to be involved in lung inflammation. Here, we evaluated the role of TIMP-1 in the host response to influenza-induced lung injury. Wild-type (WT) and Timp1-deficient (Timp1−/−) mice that were 8–12 weeks old were administered A/PR/8/34 (PR8), a murine adapted H1N1 influenza virus, and euthanized 6 days after influenza installation. Bronchoalveolar lavage fluid and lungs were harvested from each mouse for ELISA, protein assay, PCR, and histological analysis. Cytospins were executed on bronchoalveolar lavage fluid to identify immune cells based on morphology and cell count. WT mice experienced significantly more weight loss compared to Timp1−/− mice after influenza infection. WT mice demonstrated more immune cell infiltrate and airway inflammation. Interestingly, PR8 levels were identical between the WT and Timp1−/− mice 6 days post-influenza infection. The data suggest that Timp1 promotes the immune response in the lungs after influenza infection facilitating an injurious phenotype as a result of influenza infection.
Cross-frequency coupling of alpha oscillatory power to the entrainment rhythm of a spatially attended input stream.

Neural entrainment and alpha oscillatory power (8–14 Hz) are mechanisms of selective attention. The extent to which these two mechanisms interact, especially in the context of visuospatial attentio...
Heterogeneity in Metabolic Responses to Dietary Fructose

Consumption of fructose has dramatically increased in past few decades in children and adults. Increasing evidence indicates that added sugars (particularly fructose) have adverse effects on metabolism and lead to numerous cardiometabolic diseases. Although both fructose and glucose are components of sucrose and high fructose corn syrup, the sugars have different metabolic fates in the human body and the effects of fructose on health are thought to be more adverse than glucose. Studies have also shown that the metabolic effects of fructose differ between individuals based on their genetic background, as individuals with specific SNPs and risk alleles seem to be more susceptible to the adverse metabolic effects of fructose. The current review discusses the metabolic effects of fructose on key complex diseases and discusses the heterogeneity in metabolic responses to dietary fructose in humans.
La Parole 68

AbstractThis article analyzes communication in and on the May 1968 movement in France as found in graffiti, slogans, and a committee’s newsletter, and contrasts it with a 1998 book on 1968 publishe...
Alliance A071701: Genomically guided treatment trial in brain metastases.

TPS2573Background: Brain metastases, most commonly derived from melanoma, lung and breast cancers, are the most common brain tumor, with approximately 200,000 cases diagnosed annually in the United...
Assessment of scaled particle theory predictions of the convergence of solvation entropies

Abstract Entropy convergence is the experimental observation that the hydration entropies of families of non-polar solutes cross one another and converge at a distinct temperature above the boiling point of water. Entropy convergence has subsequently received significant theoretical and molecular simulation interest to interpret its molecular origin. Classic scaled particle theory has enjoyed success in describing entropy convergence for cavity-like, hard sphere solutes in water despite the fact it only considers water's equation-of-state and effective hard sphere diameter while neglecting liquid state inter-molecular correlations. This stands in difference to traditional interpretations of the hydrophobic effect that invoke water's three-dimensional structure when describing aqueous solutions of non-polar moieties. Here we investigate the origins of entropy convergence in classic scaled particle theory. We demonstrate convergence results from the theory's unphysical prediction that the surface tension of the solvent against a hard, flat interface exhibits a maximum as a function of temperature, indicative of a surface entropy that changes sign from negative to positive values with increasing temperature. In addition, we find that classic scaled particle theory can predict convergence like behavior in an organic liquid for which the phenomenon is unexpected.
Lower Bounds and Accelerated Algorithms for Bilevel Optimization

Bilevel optimization has recently attracted growing interests due to its wide applications in modern machine learning problems. Although recent studies have characterized the convergence rate for several such popular algorithms, it is still unclear how much further these convergence rates can be improved. In this paper, we address this fundamental question from two perspectives. First, we provide the first-known lower complexity bounds of $\widetilde{\Omega}(\frac{1}{\sqrt{\mu_x}\mu_y})$ and $\widetilde \Omega\big(\frac{1}{\sqrt{\epsilon}}\min\{\frac{1}{\mu_y},\frac{1}{\sqrt{\epsilon^{3}}}\}\big)$ respectively for strongly-convex-strongly-convex and convex-strongly-convex bilevel optimizations. Second, we propose an accelerated bilevel optimizer named AccBiO, whose complexity improves the existing upper bounds orderwisely under strongly-convex-strongly-convex, convex-strongly-convex and nonconvex-strongly-convex geometries. We further show that AccBiO achieves the optimal results (i.e., the upper and lower bounds match) under certain conditions up to logarithmic factors. Interestingly, our lower bounds under both geometries are larger than the corresponding optimal complexities of minimax optimization, establishing that bilevel optimization is provably more challenging than minimax optimization. We finally discuss the extensions and applications of our results to other problems such as minimax optimization.
Lanthanum Strontium Cobaltite-Alumina Fiber Composite Contact Material for Solid Oxide Fuel Cells

Short alumina fibers were added to LSCo contact material to enhance the contact strength and improve thermal cycle stability. Alumina fiber from 2.5 v% to 20 v% were mixed with LSCo and sintered at elevated temperatures. Sintering study showed retardation in densification of LSCo matrix with increasing alumina content. Sintered bulk strength exhibited similar behavior where strength greatly reduced at high alumina v%. Coefficient of thermal expansion showed consistent results with prediction from rule of mixture. Contact strength using anode supported YSZ bilayer coupons improved greatly with the presence of small amount (2.5-5 v%) alumina fibers and no substantial reduction after 10 deep thermal cycles. Candidate LSCo-Al2O3 contact materials was validated in a generic stack test fixture for 1000h at 800oC followed by 10 thermal cycles. Results of impedance analysis showed substantial improvement in thermal cycle stability as compared to LSCo parent materials.
E-045 Early neurological improvement is independent predictor of favorable outcome following thrombectomy for basilar artery occlusion

Background Acute ischemic stroke from basilar artery occlusion (BAO) is a devastating disease with high mortality and morbidity rate. The safety and efficacy of endovascular thrombectomy in BAO is not fully understood. We aimed to evaluate the predictors of favorable clinical outcome in these patients. Methods We performed a retrospective analysis of consecutive acute stroke patients with BAO whom underwent endovascular thrombectomy. Demographics, and the rate of successful recanalization (TICI score ≥2B) were reviewed. The primary efficacy outcome was defined as 90-day modified Rankin Scale (mRS) score ≤ 2 (or no worsening of mRS at 90 days compared to pre-stroke mRS in patients with pre-stroke mRS>2). Secondary outcome included early neurological improvement (ENI) defined as ≥8 points reduction in National Institutes of Health Stroke Scale (NIHSS) score, as compared to presentation, or NIHSS score ≤4 at 24 hours. Multivariate analysis was performed to determine predictors of favorable 90-day outcome. Results Sixty-two patients were identified with mean (SD) age 67 (15), 39% women, and 24% African-American. Initial NIHSS median (IQR) was 22 (14), the mean symptoms onset to groin puncture time was 9.7 (5.7) hours. Thirty-one percent of patients were treated with intravenous thrombolytic therapy. Successful recanalization was achieved in 92% of the patients. Total of 34% of the patients had favorable 90-day outcome. Mortality at 90-day was seen in 34% of the patients. ENI was observed in 22 (35%) patients. Patients with ENI were more likely to have favorable 90-day clinical outcome, compared to those without ENI (52% vs 27%, p=0.04). Single pass successful recanalization (OR; 95% CI: 5.56; 1.61–19.81, p=0.005) and initial NIHSS score (OR; 95% CI: 1.11; 1.2–1.19, p=0.043) were independent predictors of ENI. Conclusion ENI is an independent predictor of favorable clinical outcome after BAO thrombectomy. Single pass successful recanalization is associated with higher likelihood of ENI. Disclosures S. Majidi: 1; C; SNIS Foundation. S. Matsoukas: None. R. De Leacy: None. T. Oxley: None. H. Shoirah: None. T. Shigematsu: None. C. Kellner: None. J. Mocco: None. J. Fifi: None.
Acute toxicity evaluation of a novel ceramide analog for the treatment of breast cancer

We have previously reported that treating triple-negative tumor bearing nude mice with intraperitoneal (ip) 10 mg/kg body weight of (S,E)-3-hydroxy-2-(2-hydroxybenzylidene)amino-N-tetradecylpropanamide, a ceramide analog, 5 days per week for 3 weeks, was shown not only to suppress tumor growth but also to reduce metastasis. Studies reported here focus on determining the toxicity of this drug in the nude mice. During the first study, treated animals (single intraperitoneal (ip) injection, 0, 40, 80 and 120 mg/kg body weight) were closely monitored for 14 days for any signs of illness or death. No mice were lost in any animal groups; however, hepatic serum enzymes were elevated, and hepatic and heart tissue damages were found in the highest dosage group. The subsequent study was performed using a lower dosage range (single ip injection, 0, 25, 50 and 75 mg/kg body weight), which resulted in no significant toxicity. All tested parameters were within normal ranges, with no observed irregularities. Our findings show that a single ip dose of this ceramide analog induced liver and heart toxicity at 120 mg/kg but not at doses of 80 mg/kg body weight or lower.
Oxidative Phosphorylation: F 1 , F 0 F 1 , and ATP Synthase

While chemiosmotic principles garnered endorsements, however reluctant, Mitchell’s mechanisms met persisting resistance, with skepticism bolstered by experimental challenges. This chapter traces the course to reformulating one of those mechanisms, that for the reversible ATPase. Although anaerobic bacteria may use this enzyme as a H+ pump (creating electrochemical gradients that drive secondary active transport systems), oxidizing and photosynthetic bacteria as well as mitochondria and chloroplasts use the enzyme routinely to make ATP: as an ATP synthase. Identifications of this ATP synthase with the reversible F0F1-ATPase, cited in preceding chapters, were also linked to the working assumption, supported by accumulating evidence, that active sites catalyzing ATP hydrolysis by F1 and by F0F1 were the active sites catalyzing ATP synthesis by F0F1.
Kinetic analysis of a mutant (His107-->Tyr) responsible for human carbonic anhydrase II deficiency syndrome.

Abstract The replacement His107-->Tyr is a cause of carbonic anhydrase II deficiency syndrome in humans (Venta, P. J., Welty, R. J., Johnson, T. M., Sly, W. S., and Tashian, R. E. (1991) Am. J. Hum. Genet. 49, 1082-1090). We have prepared this mutant of human carbonic anhydrase II by site-directed mutagenesis and expressed it in Escherichia coli. The mutant was too unstable to purify; however, we were able to stabilize and store it at 4 degrees C in cell lysates containing 1-4 mg/ml bovine serum albumin. The concentration of this mutant in the lysate was determined by titration with the tight-binding inhibitor ethoxzolamide. The stability in this preparation was sufficient to determine that this mutant of carbonic anhydrase II has kcat/Km and apparent pKa for the hydration of CO2 equivalent to that of wild-type HCA II. The maximum velocity of CO2 hydration, which is dependent on the rate of proton transfer between enzyme and solution, was 3-fold smaller than for HCA II suggesting that the proton transfer pathway in the mutant is slightly less efficient than in wild type. Preliminary conformational energy calculations show that the replacement of His107 with the larger residue Tyr results in considerable distortion of the cavity surrounding site 107 and in the loss of at least two hydrogen bonds.
Incidental oral hairy leukoplakia in immunocompetent persons. A report of two cases

In this brief article we report on two HIV-negative patients with documented oral hairy leukoplakia who had no known risk factors for HIV infection nor any evidence of other forms of immune suppression. Therefore we conclude that in some instances hairy leukoplakia can represent an isolated and innocuous Epstein-Barr virus infection.
Fluorophore-linked assays for high-performance liquid chromatography postcolumn reaction detection of biotin and biocytin.

Publisher Summary This chapter describes high-performance liquid chromatography (HPLC) postcolumn reaction detection systems in which two types of protein-binding assay principles are used. In a competitive-binding approach, the fluorescent probe 2-anilinonaphthalene-6-sulfonic acid (2,6-ANS) competes with the analyte (biotin or biocytin) for the same binding sites on avidin. Two noncompetitive binding approaches are also described, in which the interaction that takes place is between the analyte (biotin or biocytin) and avidin or streptavidin. In these cases (strept)avidin is labeled with fluorescein isothiocyanate (FITC). On binding with the analyte, the fluorescence intensity of (strept)avidin–FITC increases in a manner proportional to the concentration of the analyte. The coupling of the binding assays with HPLC results in a highly selective detection of biotin and its derivatives owing to their selective interaction with (strept)avidin. These types of approaches also lead to enhanced sensitivity because the HPLC detection is fluorescence based rather than the conventional ultraviolet (UV) absorbance-based detection. The chapter also describes an absorbance-based postcolumn reaction detection system. In this system, biotin competes with and displaces the dye 2-(4'-hydroxyphenylazo)benzoic acid (HABA), where the free and bound HABA have different absorbance characteristics.
For Whom Does the Affirmative Action Bell Toll? the Legal Deconstruction of Racial Classifications in Post-Civil Rights America

The debate over affirmative action tends to scrutinize the morality and legality of the policies’ ends (the “why” question) and means (the “how” question), obscuring an equally central debate over which groups and subgroups are to be included (the “who” question). This paper examines how one strand of “colorblind” entrepreneurs is extending its attack on affirmative action by exposing what it sees as contradictions surrounding which ethno-racial groups and sub-groups are designated as beneficiaries. These colorblind leaders are beginning to find success in turning the tools of the academy against the academy, referencing the “social construction of race” to attack the racial categorization scheme on which racial diversity policies are based. The paper seeks to advance scholarship on affirmative action’s racial classifications by analyzing the Supreme Court’s 2003 Grutter v. Bollinger and Gratz v. Bollinger decisions on affirmative action at the University of Michigan along with the Court’s 2007 Parents Involved v. Seattle decision on voluntary school integration policies. I argue that the increased attention to the “who” question exposes further legal vulnerabilities for race-conscious policies. On the other hand, pro-affirmative action legal entrepreneurs have insulated affirmative action well from its predicted demise thus far by retheorizing affirmative action as an instrumental diversity policy. The Court’s continuing scrutiny of affirmative action policy beneficiaries and policy design has paradoxically bred new strains of affirmative action that appear to be resistant to judicial attack. Whether the same is the case for school integration policy remains to be seen.
Newborn Screening for Inborn Errors of Metabolism

Newborn screening was first applied to the detection of phenylketonuria (PKU) by a bacterial inhibition assay pioneered in 1961 by Guthrie, who was also responsible for the introduction of the use of a dried blood sample [1]. This was followed by further bacterial inhibition assays to detect other aminoacidopathies (maple syrup urine disease, homocystinuria, urea cycle disorders, etc.), but only screening for PKU was widely adopted. In 1975 Dussault described screening for congenital hypothyroidism (CH) [2], and since then other disorders covered in some screening programmes have included congenital adrenal hyperplasia, the galactosaemias, cystic fibrosis, biotinidase deficiency, glucose-6-phosphate dehydrogenase deficiency and many others.
The Burden of Clostridium difficile after Cervical Spine Surgery

Study Design Retrospective database analysis. Objective The purpose of this study is to investigate incidence, comorbidities, and impact on health care resources of Clostridium difficile infection after cervical spine surgery. Methods A total of 1,602,130 cervical spine surgeries from the Nationwide Inpatient Sample database from 2002 to 2011 were included. Patients were included for study based on International Classification of Diseases Ninth Revision, Clinical Modification procedural codes for cervical spine surgery for degenerative spine diagnoses. Baseline patient characteristics were determined. Multivariable analyses assessed factors associated with increased incidence of C. difficile and risk of mortality. Results Incidence of C. difficile infection in postoperative cervical spine surgery hospitalizations is 0.08%, significantly increased since 2002 ( p C. difficile infection were significantly increased in patients with comorbidities such as congestive heart failure, renal failure, and perivascular disease. Circumferential cervical fusion (odds ratio [OR] = 2.93, p C. difficile infection after degenerative cervical spine surgery. C. difficile infection after cervical spine surgery results in extended length of stay ( p p C. difficile after cervical spine surgery is nearly 8% versus 0.19% otherwise ( p C. difficile to be a significant predictor of inpatient mortality (OR = 3.99, p Conclusions C. difficile increases the risk of in-hospital mortality and costs approximately $6,830,695 per year to manage in patients undergoing elective cervical spine surgery. Patients with comorbidities such as renal failure or congestive heart failure have increased probability of developing infection after surgery. Accepted antibiotic guidelines in this population must be followed to decrease the risk of developing postoperative C. difficile colitis.
Evidence that CCK-58 has structure that influences its biological activity.

Many biologically active peptides exist in multiple molecular forms, but the functional significance of regions outside the region of bioactivity is unknown. The biological and immunological data p...
Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity.

PURPOSEThis randomized, prospective study assesses the impact of postoperative external-beam radiation therapy on local recurrence (LR), overall survival (OS), and quality of life after limb-sparing resection of extremity sarcomas.PATIENTS AND METHODSPatients with extremity tumors and a limb-sparing surgical option were randomized to receive or not receive postoperative adjuvant external-beam radiotherapy. Patients with high-grade sarcomas received postoperative adjuvant chemotherapy whereas patients with low-grade sarcomas or locally aggressive nonmalignant tumors were randomized after surgery alone.RESULTSNinety-one patients with high-grade lesions were randomized; 47 to receive radiotherapy (XRT) and 44 to not receive XRT. With a median follow-up of 9.6 years, a highly significant decrease (P2 = .0028) in the probability of LR was seen with radiation, but no difference in OS was shown. Of 50 patients with low-grade lesions (24 randomized to resection alone and 26 to resection and postoperative XRT), th...
Leibniz on Divine Concurrence

In this paper I examine G. W. Leibniz’s view on the debate between occasionalists, mere conservationists, and concurrentists. Although commentators agree that Leibniz wants to reject occasionalism and mere conservationism, there is considerable disagreement about whether Leibniz is committed to a theory of divine concurrence that differs from occasionalism and mere conservationism in principled ways. I critically assess three interpretations of Leibniz’s theory in this paper. The first two (those of Robert Adams and Sukjae Lee) differ with respect to important details, but they both assume that Leibniz straightforwardly affirms the continual creation doctrine. I argue that a coherent Leibnizian theory of divine concurrence cannot be constructed on the ontological framework that the continual creation doctrine provides. The third interpretation that I consider holds that Leibniz is willing to affirm the continual creation doctrine only to the extent that it provides an acceptable way of characterizing the dependence of finite substances on God at the level of appearances. It is suggested that Leibniz’s deep metaphysical view of creation and conservation is that in a single act God creates and conserves substances that are non-spatial and atemporal at the deepest level of metaphysical rigor. I argue that this alternative account of creation and conservation provides a promising ontological framework that can support a coherent theory of creaturely activity that does not collapse into occasionalism or mere conservationism.
An Algorithm for Computing the Degree of Controllability of a Discrete Time, Bounded Input, Regulator Problem

This paper presents an algorithm for measuring the Degree of Controllability (DOC) for the bounded input, regulator problem of a linear, discrete, time-invariant system. The computed DOC measures the size of the discrete time Recovery Region, R(N), which contains the set of inital states that can be returned to a zero state with an admissible control within a specified time period. Specifically the algorithm computes the volume of the largest approximating hyperellipsoid, E(N), which is contined in R(N). In additon, the algorithm gives an approximate characterization of R(N), since it finds in addition to the radius of E(N), the positive definite matrix which defines the largest E(N) contained in R(N). An example is given to illustrate the improvement in the characterization of the R(N) region over the previously defined DOC's which only defined an approximating hypersphere to R(N).
Content, Synthesis, and Function of Polyamines in Trypanosomatids: Relationship to Chemotherapy1,2

Polyamines are multiply amine-substituted straight-chain aliphatics; their content in different tissues may vary widely, and their functions are many. Their main routes of biosynthesis originate from ornithine and methionine. Polyamine content and biosynthesis in tryposomatid flagellates are reviewed concluding with emphasis on their possible role as critical drug targets in these parasitic protozoa so pathogenic for man in large areas of the world.
Reducing quench pressure by perforating the jacket of a cable-in-conduit superconductor

Abstract The pressure in a quenching cable-in-conduit conductor can be reduced by perforating its jacket. By adapting the method used by Miller et al. to study the peak quench pressure in unperforated conductors, we determine the pressure reduction caused by perforations as a function of their diameter and spacing.
Factors influencing manual ability to recover from an anomalous thruster input during a simulated docking maneuver

An experiment was performed in the Space Station Proximity Operations Simulator. Five test subjects were instructed to perform twenty remote docking maneuvers of an orbital maneuvering vehicle (OMV) to the Space Station in which they were located. The OMV started from an initial range of 304.8 m on the Space Station's negative velocity vector. Time and fuel to return to a nominal trajectory, total mission duration, total fuel consumption, failure rate, and time histories of commanded burns were recorded for each trial. Analyses of the results added support to the hypothesis that slow approach velocities are not inherently safer than their more rapid counterparts. Naive subjects were capable of docking successfully at velocities faster than those prescribed by the '0.1 pct Rule' even when a simulated faulty thruster disturbed the nominal trajectory.
Utilizing multi‐dimensionality in the workplace: a meta‐study

Purpose – The purpose of this paper is to describe and compare various theoretical models of decision making such as classical rational decision making, left‐brain/right‐brain dominance decision making, utilization of tacit knowledge in decision making, utilization of intuition in decision making, utilization of emotional intelligence in decision making, a systems approach to decision making, and spirit‐based decision making.Design/methodology/approach – Studies on different modalities of decision making are reviewed, discussed, and compared.Findings – The traditional assumption of the optimality of rational decision making may be improved by including other dimensions of decision making. It is posited that organizations that encourage and support multi‐dimensional decision making, which utilizes the rational, intuitional, emotional and spiritual aspects of the whole person, develop better management–employee relations, more creative problem solving, and better market place performance.Research limitation...
Possible contribution of direct exchange to the superfluidity of 3 He

The properties of normal and superfluid $^{3}\mathrm{He}$ have been described using a Hubbard model. We point out that in such a description it is natural to include a contribution from direct exchange, arising from an off-diagonal matrix element of the $^{3}\mathrm{\ensuremath{-}}^{3}$He interaction in a local orbital representation. We discuss a new derivation of an effective Hamiltonian for $^{3}\mathrm{He}$, which results in a lattice model with on-site repulsive interaction U, nearest-neighbor attraction V, and nearest-neighbor ferromagnetic exchange J. We examine the stability of p-wave and d-wave superfluid states as a function of the parameters in the Hamiltonian and the particle density, as well as the competition between superfluid and ferromagnetic states within this model. The possible relevance of these results to the physics of $^{3}\mathrm{He}$ is discussed.
A cosine approximation to the normal distribution

A cosine function is suggested to approximate the normal distribution as a device for simplifying algebraic manipulations of the latter. Numerical evaluations remain straightforward and employ only the commonly available trigonometric tables. A method of visual curve fitting requiring only an oscilloscope is also described.
Derivation of phase statistics from the Mueller matrix

Experimental observations show a strong dependence of phase differences of scattering matrix elements on the physical parameters of random media. Here, the statistical behavior of the phase differences is studied for distributed targets. The pdfs of the phase differences are derived from the Mueller matrix of the target. In deriving the density functions, it is assumed that the real and imaginary parts of the copolarized and cross-polarized terms of the scattering matrix are jointly Gaussian and their covariance matrices are found in terms of the Mueller matrix elements. The functional forms of the copolarized and cross-polarized density functions are similar and are obtained independently. It is shown that the density function of the phase difference is completely determined in terms of only two parameters.
Demographic Theory for an Open Marine Population with Space-Limited Recruitment

We introduce a demographic model for a local population of sessile marine invertebrates that have a pelagic larval phase. The processes in the model are the settling of larvae onto empty space, and the growth and mortality of the settled organisms. The rate of settlement per unit of unoccupied space is assumed to be determined by factors outside of the local system. The model predicts the number of animals of each age in the local system through time. The model is offered in both discrete and continuous—time versions. The principal result is that the growth of the settled organisms is destabilizing. In the model, there is always a state where recruitment balances mortality. However, growth can interfere with recruitment and can destabilize this steady state, provided also that the settlement rate is sufficiently high. The model suggests that two qualitatively distinct pictures of population structure result, depending on the settlement rate. In the high settlement limit, the intertidal landscape is a mosaic of cohorts, punctuated with occasional gaps of vacant substrate. In the low settlement limit, the intertidal landscape has vacant space and organisms of all ages mixed together and spatial variation in abundance is caused by microgeographic variation in settlement and mortality rates.
Drosophila homeobox gene eve enhances trol, an activator of neuroblast proliferation in the larval CNS

The regulation of stem cell division by developmental cues is critical for the assembly and function of multicellular organisms. Stem cell division in the Drosophila brain is controlled by trol, which is required for activation of proliferation by quiescent neuroblasts at the appropriate stage of larval development. We show that the transcriptional regulator eve is part of the trol activation pathway by identifying eve as a dominant enhancer of a weak trol allele, trolb22. Known eve mutations are capable of enhancing the lethality of trolb22 and uncovering a defective neuroblast proliferation phenotype. Additionally, genetic and molecular analysis reveals that an independent mutation which acts as a dominant enhancer of trol is also an allele of eve. The enhancement of trolb22 lethality can be suppressed by the presence of an eve transgene. Interestingly, extra copies of eve supplied by the eve transgene also enhance trolb22 lethality, suggesting that the level of Eve protein may be critical for neuroblast activation. Finally, activation of neuroblast proliferation is normal in eve4 heterozygotes, suggesting that the proliferation defect observed in trolb22;eve/+ animals is due to a synergistic interaction.
MODIFICATIONS TO SENSORY DIFFERENCE TEST PROTOCOLS: THE WARMED UP PAIRED COMPARISON, THE SINGLE STANDARD DUO‐TRIO AND THE A‐NOT A TEST MODIFIED FOR RESPONSE BIAS

. Modifications were made to difference tests on the basis of psychophysical theory and tested using a model system. The A-not A test was modified by the addition of sureness judgements to free the test from response bias; ‘warm-up’improved test sensitivity. Regular duo-trio tests were modified by using the weaker stimulus as the standard, increasing test sensitivity. The paired comparison cannot be used unless the dimension of the difference can be described. However, the warm-up procedure allows opportunity for judges to describe the difference and their own words can then be used for the test. The resulting warmed-up paired comparison was more sensitive than any modification of the duo-trio.
Microbial ore leaching in developing countries

Abstract Microbial leaching processes are being considered as an economical and technically viable alternative for processing low-grade ores and wastes in developing countries. The research and development programs in developing countries aim to design appropriate technologies for the large scale exploitation of local mines. In most cases mining companies, universities, research institutes and governmental and international agencies are all involved, demonstrating a widespread confidence in the application of this technology.
Vapor-liquid equilibria of binary and ternary mixtures containing methane, ethane, and carbon dioxide from Gibbs ensemble simulations

Simulations are presented of the liquid-phase−vapor-phase equilibria of binary mixtures (methane + ethane, methane + carbon dioxide, ethane + carbon dioxide) and ternary mixtures (methane + ethane + carbon dioxide) in the Gibbs ensemble. Methane, ethane, and carbon dioxide are described with molecular models of the types 1CLJ, 2CLJ, and 2CLJQ, respectively. The equality of the chemical potentials in the two phases is maintained by transfer of the smallest molecule and exchange for the remaining molecules. The successful acceptance ratio of exchange is usually more than 10 times larger than that for transfer. The results are in relatively good agreement with experimental and other simulation data.
Application of OODB and SGML techniques in text database: an electronic dictionary system

An electronic dictionary system (EDS) is developed with object-oriented database techniques based on ObjectStore. The EDS is composed of two parts: the Database Building Program (DBP), and the Database Querying Program (DQP). DBP reads in a dictionary encoded in SGML tags, and builds a database composed of a collection of trees which holds dictionary entries, and several lists which contain items of various lexical categories. With text exchangeability introduced by the SGML, DBP is able to accommodate dictionaries of different languages with different structures, after easy modification of a configuration file. The tree model, the Category Lists, and an optimization procedure enables DQP to quickly accomplish complicated queries, including context requirements, via simple SQL-like syntax and straightforward search methods. Results show that compared with relational database, DQP enjoys much higher speed and flexibility. With EDS this paper demonstrates how to apply OODBMS's to systems that handle text information with strong yet varied intrinsic hierarchies.
Grain size determination in nano-scale polycrystalline aggregates by precession illumination-hollow cone dark field imaging in the transmission electron microscope

Abstract Precession illumination hollow cone dark field (PI-HCDF) transmission electron microscopy (TEM) provides high contrast multi-beam dark field images, which are suitable for effective and robust grain size measurements in nano-scale polycrystalline aggregates. Precession illumination with slightly converged electron beam probes and precession angles up to 3° has been produced using a computer-controlled system using a JEOL JEM 2000FX TEM instrument. Theoretical and practical aspects of the experimental technique are discussed using example precession illumination hollow cone diffraction patterns from single crystalline NiAl and the importance of selecting the appropriate precession angle for PI-HCDF image formation and interpretation is described. Results obtained for precession illumination are compared with those of conventional parallel beam illumination experiments. Nanocrystalline Al has been used to evaluate the influence of the precession angle on PI-HCDF image contrast with a focus on grain size analysis. PI-HCDF imaging has been applied for grain size measurements in regions of a nanocrystalline Al thin film adjacent to the edge of a pulsed laser melted and rapidly solidified region and determined the dimensions of a heat-affected zone.
Dynamics of Membrane Rafts, Talin, and Actin at Nascent and Mechanically Perturbed Focal Adhesions

A single endothelial cell was deformed at the apical surface by binding a functionalized nanoelectrode probe to a predetermined location on the surface of the cell. After identifying the point of contact, as recognized by the electronic signature of the nanoelectrode, and allowing binding to the cell of the fibronectin-functionalized tip, a focal adhesion site was induced at the probe site. The probe was displaced thereby applying a prescribed shear deformation to the surface of the cell. Locations of membrane rafts were identified by cholera toxin, and focal adhesion proteins were assessed using RFP-talin, and GFP-actin. Mechanical coupling and kinetics of assembly of these labeled proteins were measured using time-lapse fluorescent images taken under 60X with a multi-point confocal scanner. Raft marker GM1, Actin, and Talin were observed to sequentially accumulate at probe site with different kinetics not only upon probe contact but also upon deformation. Following deformation, later transient motion of rafts in the opposite direction of initial deformation was observed suggesting that rafts recoil. In conclusion, we report a novel nanoelectrode-based method for controlled manipulation of the cell surface and observed mechanical coupling of focal adhesions and cross-linked lipid rafts.Copyright © 2011 by ASME
Intramolecular Nucleophilic Amino Attack in a Monobactam: Synthesis and Stability of (S,3S(-3-[(2R)-2-Amino-2-phenylacetamido[-2-methyl-4-oxo-1-Azetidinesulfonic Acid

The potentially orally bioavailable arylglycine-substituted monobactam, (2S,3S)- 3-[(2R)-2-amino-2-phenylacetamido]-2-methyl-4-oxo-1- azetidinesulfonic acid, was prepared as a crystalline solid. No significant antibacterial activity [i.e., MICs were greater than 128 (micrograms/mL)] was found when the monobactam was tested against Gram positive and Gram negative bacteria. Solution instability (greater than 2,000 times less stable than aztreonam) due to intramolecular nucleophilic amine attack on the beta-lactam is believed to be a contributing factor to the poor microbiological activity.
Low Density Lipoprotein Receptors Mediate Intracellular Calcium Signals in Microalbuminuric Hypertensives

Hyperlipidemia is an established risk factor for progressive renal damage and proteinuria. Platelets and vascular smooth muscle cells (VSMC) are known to possess low density lipoprotein (LDL) cholesterol receptors. We used platelet LDL receptors to investigate the hypothesis that elevated lipids could activate intracellular calcium [Ca2+]i signals, leading to altered vascular tone and permeability. We divided essential hypertensives into microalbuminuric positive (MA+) and negative (MA-) groups and measured baseline and LDL stimulated levels of [Ca2+]i. The MA+ group demonstrated a significantly higher mean baseline [Ca2+]i level (119.0 +/-24.5 v 86.2 +/- 25.4 micromol/mL, P = .001). The MA+ group also displayed greater elevations in [Ca2+]i levels after stimulation with LDL in concentrations of 10 and 25 microg/mL (100.9 +/- 54.8 v 40.9 +/- 20.2, P = .04 and 111.6 +/- 51.0 v 52.9 +/- 39.9 micromol/mL, P = .03, respectively). Our data indicate that hypertensive patients with early glomerular capillary injury display exaggerated influx of [Ca2+]i after LDL receptor stimulation. Heightened LDL receptor sensitivity may facilitate LDL mediated [Ca2+]i signals, leading to increased VSMC tone and proliferation and progressive renal disease.
Mechanical reliability of 8-m class ULE glass telescope blanks during manufacturing

The manufacture of 8m class ULETM glass telescope mirror blanks involves multiple steps each of which can induce both stresses and flaws. To ensure the mechanical reliability of such large mirror blanks, both during and post-manufacturing, extreme care is required in the various process steps (including handling, grinding, finishing, and transportation) so as to limit the stress and flaw severity to below the threshold level for the specific surface finish. This paper examines the critical stress/time histories the blanks experience during manufacturing and their ability to initiate slow crack growth from grinding flaws. Two different surface finishes, namely 120 grit and 270/325 grit, with and without acid etching are characterized with respect to strength, flaw, and fatigue behavior. These data show that the 270/325 grit finish with acid etching is appropriate for the sagging step which imposes a static stress of 650 psi in the center region of the mirror blank over a two-week sag period. Similarly, the 120 grit surface finish is adequate for grinding, packaging, and transporting steps which impose a static stress of 435 psi in the support pad region for a three month period. These predictions, based on power law fatigue model, were verified by conducting static fatigue tests (at appropriate stress levels) on a large sample of 6 inch diameter ULETM discs (with appropriate surface finish) at 25 degrees C and 100% RH. A comparison of strength distribution of the discs, before versus after static fatigue tests, showed no changes in strength indicating absence of slow crack growth at stresses and environment representative of manufacturing process. Such a verification is imperative for selecting appropriate surface finishes for the mirror blanks to ensure their mechanical reliability during manufacturing.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Trace element mineral transformations associated with hydration and recarbonation of retorted oil shale

A laboratory study was conducted to evaluate the influence of hydration and recarbonation on the solidphase distribution of trace elements in retorted oil shale. The oil shale samples were retorted by the Paraho direct heating process and equilibrated with deionized—distilled water under controlled carbon dioxide conditions. A sequential extraction technique was then used to fractionate trace elements into soluble, KNO3-extractable (easily exchangeable), H2O-extractable (easily adsorbed), NaOh-extractable (organic), EDTA-extractable (carbonate), HNO3-extractable (sulfide), and residual (nonextractable silicate) phases. The chemical fractions present in retorted oil shale and hydrated and recarbonated retorted oil shale were compared to identify trace element mineralogical changes that may occur in retorted oil shale disposal environments.
Abstract SY31-02: Building highly effective anti-tumor T cells

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Many tumors contain relatively undifferentiated transformed progenitors termed ‘cancer stem cells’ (CSC). Stem cells are defined by the ability to self-renew and generate differentiated progeny, qualities maintained by evolutionarily conserved pathways that can lead to cancer when deregulated. The existence of stem cells has been documented across multiple tissues both during development on into adulthood including the hematopoietic and central nervous systems, intestine, skin, cardiac muscle and lung. All of these sites employ the presence of limited numbers of stem cells in tissues enable a few daughter cells to retain a regenerative potential while the majority of daughter cells enter an irreversible process of differentiation culminating in the generation of specialized cell types. Recently, we have found evidence supporting the existence and function of stem cells within the adaptive immune system in both the CD8+ and CD4+ T cell lineages. This stem cell-like population has been termed ‘T memory stem cells’ (TSCM). In preclinical models using both mouse and human cells, TSCM can overcome many limitations of currently employed T cell-based immunotherapies, especially in the setting of adoptive T cell transfer, including inefficient T cell engraftment, persistence, and ability to mediate prolonged immune attack. Conferring stemness to anti-tumour T cells might unleash the full potential of cellular therapies. Our goal is to trigger stem cell-like pathways in tumor-reactive T cells or to reprogram terminally differentiated tumor-infiltrating lymphocytes (TILs) to confer stem cell-like properties to augment immunotherapies against cancer and CSC, akin to fighting ‘fire with fire.’ In new work from our laboratory (1) as well as unpublished experiments, we have identified several candidate transcription factors that are differentially expressed in stem cell-like T cells. In addition, new experiments have shed significant light on the metabolic properties of highly effective stem cell-like T cell subsets. Reference 1. Roychoudhuri, R, et al, Nature, 2013. Citation Format: Nicholas P. Restifo. Building highly effective anti-tumor T cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr SY31-02. doi:10.1158/1538-7445.AM2014-SY31-02
The bubble-like interior of the core-collapse supernova remnant Cassiopeia A

The death of massive stars is believed to involve aspheric explosions initiated by the collapse of an iron core. The specifics of these catastrophic explosions remain uncertain, due partly to limited observational constraints on asymmetries deep inside the star. Here we present near-infrared observations of the young supernova remnant Cassiopeia A, descendant of a type IIb core-collapse explosion, and a three-dimensional map of its interior unshocked ejecta. The remnant’s interior has a bubble-like morphology that smoothly connects to and helps explain the multiringed structures seen in the remnant9s bright reverse-shocked main shell of expanding debris. This internal structure may originate from turbulent mixing processes that encouraged outwardly expanding plumes of radioactive 56 Ni-rich ejecta. If this is true, substantial amounts of its decay product, 56 Fe, may still reside in these interior cavities.