cssi/SciSciGPT-SciSciNet huggingface dataset:
SYNTHESIS AND EVALUATION OF 2‐DIAZO‐3,3,3‐TRIFLUOROPROPANOYL DERIVATIVES OF COLCHICINE AND PODOPHYLLOTOXIN AS PHOTOAFFINITY LABELS: REACTIVITY, PHOTOCHEMISTRY, AND TUBULIN BINDING

Derivatives of the tubulin polymerization inhibitors colchicine and podophyllotoxin bearing the photoreactive 2-diazo-3,3,3-trifluoropropanoyl (DTFP) group were synthesized for evaluation as potential photoaffinity labels of the tubulin binding site. All labels were assayed for their ability to inhibit tubulin polymerization, and N-DTFP-deacetylthiocolchicine was shown to competitively inhibit tubulin-colchicine binding with a Ki of 4-5 microM. The tubulin off-rate of this analog was similar to that of podophyllotoxin, rather than to the relatively irreversibly bound colchicine. Photochemical solvent insertion reactions of the labels were investigated. Radioactive samples of the two most active labels were prepared and used in initial protein-labeling experiments, during which the fractional occupancy of tubulin and extent of covalent incorporation were determined. A rearrangement of DTFP amides was encountered which is relevant to the utility of this moiety for use in synthesis of photoaffinity labels.
Patternable Protein Resistant Surfaces for Multifunctional Microfluidic Devices via Surface Hydrophilization of Porous Polymer Monoliths Using Photografting

Surface-modified macroporous polymer monoliths that resist the adsorption of proteins have been prepared using both single- and two-step photografting of hydrophilic monomers. The adsorption of protein was measured using a fluorescence assay based on bovine serum albumin labeled with fluorescein. Acrylamide, 2-hydroxyethyl methacrylate, vinyl pyrrolidinone, and poly(ethylene glycol) methacrylate (PEGMA) monomers were grafted and evaluated for their ability to prevent protein adsorption. Photografted layers of PEGMA reduced protein adsorption to less than 2% relative to unmodified surfaces. The sequential two-step photografting process consisted in (i) the formation of covalently bound surface photoinitiator sites followed by (ii) surface-localized graft polymerization. Monomer concentration and irradiation time during photografting were found to be the most important parameters for optimization of the two-step process. For simultaneous single-step photografting, the solvent and the presence of photoinitia...
Policy Variation among Japan, Korea, England and the United States

School reform initiatives during the last two decades in Japan, Korea, England, and the United States can be understood as balancing acts. Because policymakers in England and the United States saw their school systems fragmented and student outcomes mediocre, they focused reform efforts on raising educational standards, tightening curriculum and assessment, and improving academic achievement. In contrast, policymakers in Japan and Korea, who saw their school systems overstandardized and educational processes deficient, focused their reform efforts on deregulating schools, diversifying curriculum and assessment, and enhancing whole-person education. While school reform policies were formulated and adopted in response to each countrys unique problems, they also were driven by globalization forces that fostered an international perspective. If implemented successfully, such cross-cultural policy variations (i.e., standardization vs. differentiation in curriculum, unification vs. diversification in assessment, and privatization vs. democratization in governance) would make distinctive educational systems more alike. Cultural and institutional barriers to educational convergence between the Eastern and Western school systems are discussed.
Wormholes, Non-Local Actions and a New Mechanism for Suppressing the Cosmological Constant

The connection between wormholes and non-local actions is clarified. Baum-HawkingColeman type singularities correspond to runaway vacua of unbounded actions and can be avoided by appropriate sign flips and/or integration contour rotations. Sticking to saddle points, we find a new mechanism suppressing exponentially the cosmological constant without affecting appreciably other gravitational couplings.
Correlation Between the Number of T Cell Receptors Required for T Cell Activation and TCR–Ligand Affinity

Abstract The number of T cell receptors on CTL clone 2C that are required for recognition of various peptide–MHC or superantigen–MHC ligands were measured as a function of both the ligand density on target cells and the binding affinity of the TCR. Quantitative inverse correlations were determined between the number of TCRs required for recognition and the number of ligands on target cells, and the number of TCR required and the K a of the TCR for the ligand. We propose and test predictive uses of these relationships to determine the number of endogenous peptide–MHC complexes on a target cell (when TCR affinity is known) or to determine the affinity of the TCR (when the number of ligands is known).
Surface-mediated Four-wave Mixing Microscopy

We demonstrate that four-wave mixing signals from nanostructures can be generated by traveling surface plasmon polaritons. We have chosen a counterpropagating excitation scheme in which the nanostructure is exposed only to surface excitation fields.
1,25-Dihydroxy-24-OXO-16ene-vitamin D3, a renal metabolite of the vitamin D analog 1,25-dihydroxy-16ene-vitamin D3, exerts immunosuppressive activity equal to its parent without causing hypercalcemia in vivo.

The hormone, 1,25-(OH)2D3, is metabolized into 1,25-(OH)2-24-OXO-D3, in kidney prior to conversion to its final inactive product, calcitroic acid. Similarly, 1,25-(OH)2-24OXO-16eneD3, is produced in the kidney from the Vitamin D analog, 1,25-(OH)2-16eneD3, but resists further hydroxylation. The analog's metabolite was synthesized and its biologic activity compared to the parent compound. Naive SJL/J mice, 4 weeks old, were immunized with neuroantigen in adjuvant to induce experimental autoimmune encephalomyelitis [EAE]. Treatment with 1,25-(OH)2-24OXO-16eneD3 was given at 0.05, 0.15 and 0.3 microgram I.P., on alternate days, starting 3 days prior and for up to 5 days post immunization and compared to a similar treatment with 0.1 microgram 1,25-(OH)2D3 or 1,25-(OH)2-16eneD3. Suppression of EAE was observed with 0.15 microgram 1,25-(OH)2-24OXO-16eneD3, comparable to the suppression induced with the parent compound and more potent than 1,25-(OH)2D3. However, no hypercalcemia was seen in mice treated with 0.1...
Matrix density alters zyxin phosphorylation, which limits peripheral process formation and extension in endothelial cells invading 3D collagen matrices

This study was designed to determine the optimal conditions required for known pro-angiogenic stimuli to elicit successful endothelial sprouting responses. We used an established, quantifiable model of endothelial cell (EC) sprout initiation where ECs were tested for invasion in low (1 mg/mL) and high density (5 mg/mL) 3D collagen matrices. Sphingosine 1-phosphate (S1P) alone, or S1P combined with stromal derived factor-1α (SDF) and phorbol ester (TPA), elicited robust sprouting responses. The ability of these factors to stimulate sprouting was more effective in higher density collagen matrices. S1P stimulation resulted in a significant increase in invasion distance, and with the exception of treatment groups containing phorbol ester, invasion distance was longer in 1mg/mL compared to 5mg/mL collagen matrices. Closer examination of cell morphology revealed that increasing matrix density and supplementing with SDF and TPA enhanced the formation of multicellular structures more closely resembling capillaries. TPA enhanced the frequency and size of lumen formation and correlated with a robust increase in phosphorylation of p42/p44 Erk kinase, while S1P and SDF did not. Also, a higher number of significantly longer extended processes formed in 5mg/mL compared to 1mg/mL collagen matrices. Because collagen matrices at higher density have been reported to be stiffer, we tested for changes in the mechanosensitive protein, zyxin. Interestingly, zyxin phosphorylation levels inversely correlated with matrix density, while levels of total zyxin did not change significantly. Immunofluorescence and localization studies revealed that total zyxin was distributed evenly throughout invading structures, while phosphorylated zyxin was slightly more intense in extended peripheral processes. Silencing zyxin expression increased extended process length and number of processes, while increasing zyxin levels decreased extended process length. Altogether these data indicate that ECs integrate signals from multiple exogenous factors, including changes in matrix density, to accomplish successful sprouting responses. We show here for the first time that zyxin limited the formation and extension of fine peripheral processes used by ECs for matrix interrogation, providing a molecular explanation for altered EC responses to high and low density collagen matrices.
Carbosilane/carbosiloxane-based ADMET homopolymers and copolymers possessing latent reactivity

Reactive methoxy-functionalized carbosilane and carbosiloxane dienes can be either homopolymerized or copolymerized via acyclic diene metathesis (ADMET) polycondensation chemistry to produce reactive materials with mechanical behavior dependent on the molar ratios of the comonomers. The methoxy-functional group within the polycarbosilane repeat unit remains inert during the metathesis polymerization and can be triggered subsequently with water to generate crosslinks between polymer chains. In this way, linear, thermoplastic copolymers can be prepared with ADMET chemistry and converted into crosslinked, thermoset copolymers upon exposure to moisture. Crosslinked films containing 5–10% of the crosslinked hard segment are soft and flexible materials. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 1544–1550, 2000
The psychophysics of the kinesthetic aftereffect in the Petrie block experiment

Kinesthetic size is reported in the Petrie experiment by a simultaneous size comparison in which a standard block held between the thumb and forefinger of one hand is matched in size by moving the thumb and forefinger of the opposite hand along a wedge until the proper width is reached. After a baseline is obtained, a kinesthetic aftereffect is produced by rubbing a block of contrasting size followed by a return to the standard block. Experiments with 22 male Ss and 20 female Ss, tested in separate cycles, show that augmentation following stimulation with a block smaller than standard and reduction following stimulation with a block larger than standard are both statistically significant, and, at least for augmentation, the aftereffect persists for at least 48 h. When the data are corrected for regression there is no significant relationship between initial baseline and the amount of augmentation or reduction; reasons why such a relationship has been reported are indicated. The results suggest that when this kind of experiment is used for the study of individual differences (a) it is satisfactory to derive augmentation and reduction scores by subtracting the baseline from the absolute scores, provided the scores are corrected for regression, and (b) a counterbalanced order of presentation is not advisable in view of the carryover of augmentation from one day to the next, which is likely to make the two orders incommensurate.
IL-1 signaling modulates activation of STAT transcription factors to antagonize retinoic acid signaling and control the TH17 cell-iTreg cell balance

Interleukin 17 (IL-17)-producing helper T cells (TH17 cells) and CD4(+) inducible regulatory T cells (iTreg cells) emerge from an overlapping developmental program. In the intestines, the vitamin A metabolite retinoic acid (RA) is produced at steady state and acts as an important cofactor to induce iTreg cell development while potently inhibiting TH17 cell development. Here we found that IL-1 was needed to fully override RA-mediated expression of the transcription factor Foxp3 and induce protective TH17 cell responses. By repressing expression of the negative regulator SOCS3 dependent on the transcription factor NF-κB, IL-1 increased the amplitude and duration of phosphorylation of the transcription factor STAT3 induced by TH17-polarizing cytokines, which led to an altered balance in the binding of STAT3 and STAT5 to shared consensus sequences in developing T cells. Thus, IL-1 signaling modulated STAT activation downstream of cytokine receptors differently to control the TH17 cell-iTreg cell developmental fate.
Merely Misunderstood? Receptive, Expressive, and Pragmatic Language in Young Children With Disruptive Behavior Disorders

Children with disruptive behavior disorders (DBDs) often seem to have poorer language skills compared to same-age peers; however, language as an early risk factor for DBD has received little empirical attention. The present study provides an empirical examination of associations between normal language variation and DBD by investigating receptive, expressive, and pragmatic language skills and preschool DBD symptoms. The sample consisted of 109 preschoolers ages 3 to 6 (M = 4.77 years, SD = 1.10, 59% boys; 73% with DBD, including oppositional defiant disorder [ODD] and attention-deficit/hyperactivity disorder [ADHD]) along with their primary caregivers, who completed a clinician-administered interview, symptom questionnaires, and a questionnaire measure of pragmatic language, and teacher and/or daycare providers completed symptom questionnaires. Children completed objective tests of receptive and expressive vocabulary. Preschoolers with DBD showed poorer receptive, expressive, and pragmatic skills compared to preschoolers without DBD. Preschoolers with ADHD-only or ADHD+ODD exhibited poorer language skills, compared to ODD and non-DBD groups. Specificity analyses suggested that parent-rated hyperactivity-impulsivity were particularly associated with poorer language skills. Thus, preschoolers with DBD exhibited poorer language skills compared to preschoolers without DBD, and preschoolers with increased hyperactivity-impulsivity exhibited particular problems with language skills. This work suggests the need for early assessment of language in preschoolers, particularly those with ADHD, as well as the possible utility of tailored interventions focused on improving language skills, particularly for those with high hyperactivity-impulsivity.
Segregation of VIPergic-nitric oxidergic and cholinergic-nitric oxidergic innervation in porcine middle cerebral arteries.

The distribution of nitric oxide synthase (NOS)-, choline acetyltransferase (ChAT)-, and vasoactive intestinal polypeptide (VIP)-immunoreactivities, and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd)-reactivities in the sphenopalatine ganglia (SPG), and perivascular nerves in middle cerebral arteries of the pig was investigated by double-staining techniques using combined immunofluorescence and histochemistry methods. In the SPG, almost all ganglionic cells were NOS-immunoreactive (I) and NADPHd-positive, and both NOS immunoreactivities and NADPHd reactivities were completely co-localized. ChAT-I ganglionic cells accounted for 75%, while VIP-I ganglionic cells represented 42% of all ganglionic cells. Almost all VIP immunoreactivities were co-localized with ChAT immunoreactivities, and all ganglionic cells that were VIP-I and/or ChAT-I were NOS-I and NADPHd-reactive. None of the ganglionic cells in the SPG were immunoreactive to calcitonin gene-related peptide (CGRP). CGRP immunoreactivities, however, were found to surround some ganglionic cells. In middle cerebral arteries, all adventitial NOS-I bundles and fine fibers were coincident with NADPHd fibers. Almost all adventitial ChAT-I bundles and thin fibers, and VIP-I mesh-like fibers stained positively for NADPHd, while the mesh-like NADPHd fine fibers were not ChAT-I. Simultaneous labeling using antibodies against VIP and ChAT further indicated that VIP-I fibers were closer than ChAT-I fibers to the smooth muscle. In rare occasions, perivascular fibers were found to be stained for both ChAT and VIP, showing that most ChAT-I and VIP-I fibers were not coincident. These results suggest that ChAT and VIP are rarely co-localized in perivascular nerves in middle cerebral arteries, and point out that the neurotransmitter and the modulator that are co-localized within the same nerve cell body may distribute totally independently and differently at the terminal level. The present results also indicate that in cerebral perivascular nerves, the combination of nitric oxide (NO) and acetylcholine (ACh), as well as the combination of NO and VIP, are localized in the same nerve with different axons containing either NO plus ACh, or NO plus VIP. These findings support the hypothesis that ACh and VIP may act as modulators in regulating presynaptic release of NO, and therefore, cerebral neurogenic vasodilation, from their respective perivascular cholinergic-nitric oxidergic and VIPergic-nitric oxidergic nerves.
A Decision Support Model for Project Manager Assignments

The question, "How to assign projects to project managers?" is considered to be one of the most important questions in project management. Nevertheless, methods to answer this question have not yet been sufficiently addressed in the literature. In practice, even though the question is rather common, practitioners still seek an effective project assignment methodology - especially, for the assignments of project managers of multiple concurrent projects, such as a project manager of new product development projects in typical high-technology industries. To respond to this question, we performed an inductive study to develop a theoretical framework for project assignments, including some significant assignment criteria and processes. We found that to be effective in project assignments, management should consider strategic elements of the organization in project prioritization, project requirements and competencies of project managers in project manager-to-project matching, and some organizational/personal limitations regarding the assignment. An optimization model was developed to apply this framework. This model can assist in assigning projects to project managers for the better performances of projects, project managers, and the organization.
Effectiveness of medial rectus advancement alone or in combination with resection or lateral rectus recession in the management of consecutive exotropia

Purpose To prospectively determine the long-term success of medial rectus advancement alone or in combination with other procedures in the management of consecutive exotropia. Methods All patients with consecutive exotropia who underwent medial rectus advancement alone or in combination with medial rectus resection or lateral rectus recession or both, performed by a single surgeon between 1999 and 2010, were included. Initially, a retrospective review was performed. Patients were then recalled and examined by a masked observer. Good results were defined as final alignment within 10 Δ of orthotropia. Results A total of 46 patients were enrolled in the study with a mean age of 43 ± 15.5 years (range, 14-76) and a mean exotropia of 32 ± 18 Δ (range, 10-90). Good results were achieved in 33 patients (72%) at a mean follow-up time of 2.5 years. Of the 21 patients returning for prospective examination, 15 (71%) had good alignment at an average follow-up of 4.2 years (range, 6.9 months to 8.6 years). Adduction deficits were improved in 30 of 33 (91%) patients at final follow-up. Conclusions In patients with consecutive exotropia, surgery including medial rectus advancement alone or in combination with resection or lateral rectus recession or both usually is effective.
Exercise in neuromuscular disease.

AbstractIn the past, patients with neuromuscular diseases were advised not to exercise because of the fear that too much exercise might produce “overuse weakness.” No controlled studies have demonstrated that the phenomenon of overuse weakness actually exists. Most studies of exercise training in pa
The behavior of sterols on silica surfaces and at other interfaces

The specific manner in which a molecule is oriented at an interface determines the reactions in which the molecule can participate. Sterols, being highly anisotropic molecules, present “ends” and “sides” to surfaces which differ greatly in their reactivity and interaction with the surface. Seen from the 3β-hydroxy end, as at an air-water interface, sterols are largely indistinguishable from one another in their behavior. On the other hand, at an organized interface, such as that of an absorbent, a great many differences in structure can be demonstrated. These include the distinction between nuclear and side-chain double bonds, the number and location of nuclear double bonds, the substituents in the side chain and the number of methyl groups in the molecule. We have been interested in the degree of specificity which such interaction can display because of the obvious parallel to sterol-protein interactions of a structural or enzymatic nature. Through the synthesis of a variety of sterol structures possessing the desired arrangement of double bonds and numbers of methyl groups, we have established a reproducible correlation between adsorptive interaction and double bonds in the Δ5, Δ7, Δ8, Δ5,7 and Δ7, 9 positions, as well as for the saturated stanol. These correlations have been extended for the 4α, 4β, 4,4 dimethyl and 4,4,14α trimethyl series as well. The elucidation of the structure of macdougallin as a 14α methyl sterol in which the 4,4, gem dimethyl grouping was absent prompted a further study of the 14α methyl sterols, of which the Δ7, Δ8, Δ7,9 and unsaturated varieties have been prepared and tested. The presence of a 14α methyl group in the absence of other methyl groups confers a unique behavior on the molecule in that this series does not fit into the adsorptive scheme for the other sterols. Instead, the interaction of the double bond with the surface is almost completely independent of its position, suggesting that the molecule is “perched” on the 14α methyl group when absorbed in the surface. This appears to be a highly significant feature in the orientation of the molecule, since the removal of this methyl group is usually regarded as an essential first step in the conversion of lanosterol to cholesterol.
Endothelial CD47 Promotes Vascular Endothelial-Cadherin Tyrosine Phosphorylation and Participates in T Cell Recruitment at Sites of Inflammation In Vivo

At sites of inflammation, endothelial adhesion molecules bind leukocytes and transmit signals required for transendothelial migration (TEM). We previously reported that adhesive interactions between endothelial cell CD47 and leukocyte signal regulatory protein γ (SIRPγ) regulate human T cell TEM. The role of endothelial CD47 in T cell TEM in vivo, however, has not been explored. In this study, CD47−/− mice showed reduced recruitment of blood T cells as well as neutrophils and monocytes in a dermal air pouch model of TNF-α–induced inflammation. Reconstitution of CD47−/− mice with wild-type bone marrow cells did not restore leukocyte recruitment to the air pouch, indicating a role for endothelial CD47. The defect in leukocyte TEM in the CD47−/− endothelium was corroborated by intravital microscopy of inflamed cremaster muscle microcirculation in bone marrow chimera mice. In an in vitro human system, CD47 on both HUVEC and T cells was required for TEM. Although previous studies showed CD47-dependent signaling required Gαi-coupled pathways, this was not the case for endothelial CD47 because pertussis toxin, which inactivates Gαi, had no inhibitory effect, whereas Gαi was required by the T cell for TEM. We next investigated the endothelial CD47-dependent signaling events that accompany leukocyte TEM. Ab-induced cross-linking of CD47 revealed robust actin cytoskeleton reorganization and Src- and Pyk-2–kinase dependent tyrosine phosphorylation of the vascular endothelial-cadherin cytoplasmic tail. This signaling was pertussis toxin insensitive, suggesting that endothelial CD47 signaling is independent of Gαi. These findings suggest that engagement of endothelial CD47 by its ligands triggers outside-in signals in endothelium that facilitate leukocyte TEM.
Mechanistic insights into isoform-dependent and species-specific regulation of bile salt export pump by farnesoid X receptor

Expression of bile salt export pump (BSEP) is regulated by the bile acid/farnesoid X receptor (FXR) signaling pathway. Two FXR isoforms, FXRα1 and FXRα2, are predominantly expressed in human liver. We previously showed that human BSEP was isoform-dependently regulated by FXR and diminished with altered expression of FXRα1 and FXRα2 in patients with hepatocellular carcinoma. In this study, we demonstrate that FXRα1 and FXRα2 regulate human BSEP through two distinct FXR responsive elements (FXRE): IR1a and IR1b. As the predominant regulator, FXRα2 potently transactivated human BSEP through IR1a, while FXRα1 weakly transactivated human BSEP through a newly identified IR1b. Relative expression of FXRα1 and FXRα2 affected human BSEP expression in vitro and in vivo. Electrophoretic mobility shift and chromatin immunoprecipitation assays confirmed the binding and recruitment of FXRα1 and FXRα2 to IR1b and IR1a. Sequence analysis concluded that IR1b was completely conserved among species, whereas IR1a exhibited apparent differences across species. Sequence variations in IR1a were responsible for the observed species difference in BSEP transactivation by FXRα1 and FXRα2. In conclusion, FXR regulates BSEP in an isoform-dependent and species-specific manner through two distinct FXREs, and alteration of relative FXR isoform expression may be a potential mechanism for FXR to precisely regulate human BSEP in response to various physiological and pathological conditions.
Submarine encrustation of a Byzantine nail

Virtually all iron objects recovered from a 7th century Byzantine shipwreck off the coast of Turkey were encrusted with a carbonate-rich layer. Mineralogical and chemical examination reveals limonite, siderite, and aragonite as dominant authigenic phases. The encrustations can be explained by oxidation (corrosion) of the metal in sea water. Analogous processes are suggested for many concretions formed around metallic nuclei in sea water.
The Metal Homeostasis Protein, Lsp, of Streptococcus pyogenes Is Necessary for Acquisition of Zinc and Virulence

“Cluster 9” family lipoproteins function as ligand-binding subunits of ABC-type transporters in maintaining transition metal homeostasis and have been implicated in the virulence of several bacteria. While these proteins share high similarity, the specific metal that they recognize and whether their role in virulence directly involves metal homeostasis cannot be reliably predicted. We examined the cluster 9 protein Lsp of Streptococcus pyogenes and found that specific deletion of lsp produced mutants highly attenuated in a murine model of soft tissue infection. Under standard in vitro conditions, growth of the Lsp− mutant was indistinguishable from that of the wild type, but growth was defective under zinc-limited conditions. The growth defect could be complemented by plasmids expressing wild-type Lsp but not Lsp engineered to lack its putative lipidation residue. Furthermore, Zn2+ but not Mn2+ rescued Lsp− growth, implicating Zn2+ as the physiological ligand for Lsp. Mutation of residues in the putative Zn2+-binding pocket generated variants both hypo- and hyperresistant to zinc starvation, and both mutant classes displayed attenuated virulence. Together, these data suggest that Lsp is a ligand-binding component of an ABC-type zinc permease and that perturbation of zinc homeostasis inhibits the ability of S. pyogenes to cause disease in a zinc-limited host milieu.
From Stills to Video: Face Recognition Using a Probabilistic Approach

While it is generally possible to do recognition from video sequences, the training process is usually done over static images. This is due to the fact that, in many applications (e.g., homeland security), one does not have large video sequences which can be used for training. For example, law enforcement agencies generally have a frontal and a profile view of wanted individuals, but do not usually keep video sequences in file. Nonetheless, in these applications, it is still possible to analyze the information of video sequences for subsequent recognition tasks. This paper presents a probabilistic algorithm that learns from small sets of static images and then recognizes faces from video sequences. The proposed algorithm is robust to partial occlusions, different orientations and expression changes and does not require of precise face localizations. Our preliminary results with a small database show that the proposed method is more robust to such changes than static-to-static recognition of faces.
Biological Media - Their Advantages and Pitfalls when used in Biological Monitoring - Feces

Under usual circumstances, fecal metal reflects predominantly metal that has been swallowed and remains unabsorbed. This is so because, typically, swallowed metals are poorly absorbed from the gastrointestinal tract. There are exceptions, of course, such as methyl mercury. In such exceptional cases, fecal metal reflects the internal dose resulting from accumulation by all routes of absorption. When the metal is poorly absorbed, however, it reflects current intake by way of the gastrointestinal tract. Other major indicators reflect cumulative exposure and, further, do not provide information as to the likely route of absorption. The distinction between current and cumulative exposure is particularly important in the case of metals because metals generally have very slow rates of clearance from the body with consequent pronounced accumulation. This situation is quite unlike that which applies to most other classes of toxic substances which are cleared from the body with half-times of the order of hours to a few days.
Resistance to herbicides caused by single amino acid mutations in acetyl-CoA carboxylase in resistant populations of grassy weeds.

Summary Eleven spontaneous mutations of acetyl-CoA carboxylase have been identified in many herbicide-resistant populations of 42 species of grassy weeds, hampering application of aryloxyphenoxypropionate, cyclohexadione and phenylpyrazoline herbicides in agriculture. IC50 shifts (resistance indices) caused by herbicide-resistant mutations were determined using a recombinant yeast system that allows comparison of the effects of single amino acid mutations in the same biochemical background, avoiding the complexity inherent in the in planta experiments. The effect of six mutations on the sensitivity of acetyl-CoA carboxylase to nine herbicides representing the three chemical classes was studied. A combination of partially overlapping binding sites of the three classes of herbicides and the structure of their variable parts explains cross-resistance among and between the three classes of inhibitors, as well as differences in their specificity. Some degree of resistance was detected for 51 of 54 herbicide/mutation combinations. Introduction of new herbicides targeting acetyl-CoA carboxylase will depend on their ability to overcome the high degree of cross-resistance already existing in weed populations.
The Radial Bias: A Different Slant on Visual Orientation Sensitivity in Human and Nonhuman Primates

It is generally assumed that sensitivity to different stimulus orientations is mapped in a globally equivalent fashion across primate visual cortex, at a spatial scale larger than that of orientation columns. However, some evidence predicts instead that radial orientations should produce higher activity than other orientations, throughout visual cortex. Here, this radial orientation bias was robustly confirmed using (1) human psychophysics, plus fMRI in (2) humans and (3) behaving monkeys. In visual cortex, fMRI activity was at least 20% higher in the retinotopic representations of polar angle which corresponded to the radial stimulus orientations (relative to tangential). In a global demonstration of this, we activated complementary retinotopic quadrants of visual cortex by simply changing stimulus orientation, without changing stimulus location in the visual field. This evidence reveals a neural link between orientation sensitivity and the cortical retinotopy, which have previously been considered independent.
Regression simulation: applying path-based learning in delay test and post-silicon validation

This paper presents a novel path-based learning methodology to achieve timing regression simulation. The methodology can be applied for two purposes: (1) In pre-silicon phase, regression simulation can be used to produce a fast and approximate timing simulator to avoid the high cost associated with statistical timing simulation. (2) In post-silicon phase, regression simulation can be used as a vehicle to deduce critical paths from the pass/fail behavior observed on the test chips. Our path-based learning methodology consists of four major components: a delay test pattern set, a logic simulator, a set of selected paths as the basis for learning, and a machine learner. We summarize the key concepts in our regression simulation approach and present experimental results.
Controlled chemical functionalization of water-soluble nanoprobes for site-specific biomedical diagnosis

We propose mono-, di-, or tri-probe functionalized water-soluble gold nanoparticles (AuNPs) (∼ 2 nm) based on our aqueous-phase serial solid-phase monofunctionalization (monof-) approach. They exhibit both electrical and optical sensing capabilities when specifically coupled with distinctive one- or diametric-functionality. Using ferrocene redox derivative for electrical detection scheme, the monof-, bif-, and trif-NPs show distinctively proportionated current peaks, which could allow quantitative biosensing as well as precise bioconjugation. TEM images verified the covalent bond-directed assembly of 1D and 2D structures. While typical individual AuNPs are not NIR responsive, the assembled nanosensing units exhibit longitudinal surface plasmon resonance, indicating their high promises for the high functional NIR-based medical applications. These exemplify a significant stride towards ‘multiplex’ nanosensors with enhanced functionality, selectivity, and complexity.
Plumage brightness predicts male mating success in the lekking golden-collared manakin, Manacus vitellinus

The evolution of colorful plumage has been dramatic in lekking species. Several studies show that the size of colorful traits influence female choice in leks; however, relatively little is known about the specific function of color, in particular its spectral properties, in lekking taxa. To determine the importance of color in a lekking species, we monitored the mating success of male golden-collared manakins, Manacus vitellinus, and related this to spectral measures of their colorful plumage, as well as other morphological and behavioral traits shown to be important in other lekking species. We found that lek centrality, male body size, and plumage brightness were associated with male mating success. Only plumage brightness, however, entered a multiple regression model, indicating that plumage is the overall best predictor of mating success. These results provide evidence that the spectral properties of colorful plumage predict male mating success in a lekking species and provide important insight into why many lekking birds are dichromatic and elaborate in coloration. Copyright 2006.
Fluorescently labeled carbon nanohorns as intracellular drug delivery vehicles

Nanomaterials have been investigated for biomedical applications due to their unique properties. Their shape, size, surface, and material can be altered specifically for the type of application. Carbon nanomaterials (CNMs) have been effectively utilized as photoabsorbers to enhance laser-based therapies [1] and can be easily loaded with drugs or targeting moieties [2, 3]. The strong carbon bonds in this material provide a chemical and mechanical inertness that can serve as a barrier to protect chemotherapeutic agents from degrading quickly as they are transported to the site of interest [2].Copyright © 2012 by ASME
Financial Innovation, Organizations, and Small Business Lending

Technological innovation and changes in bank organizational structure have each had a significant effect on small business lending. Both of these phenom- ena have a spatial dimension. Technological innovation may allow banks to lend at a longer distance if it significantly diminishes the importance of direct customer contact. If consolidation produces fewer banking offices, then the average distance between borrowers and lenders will necessarily increase. The impact of these effects on small business lending, however, greatly depends on the extent to which hard information about borrower quality is a good substitute for soft information. This chapter assesses the theoretical and empirical evidence on the extent to which these changes will likely effect small business lending.
A Switched Gaussian Process for Estimating Disparity and Segmentation in Binocular Stereo

This paper describes a Gaussian process framework for inferring pixel-wise disparity and bi-layer segmentation of a scene given a stereo pair of images. The Gaussian process covariance is parameterized by a foreground-background-occlusion segmentation label to model both smooth regions and discontinuities. As such, we call our model a switched Gaussian process. We propose a greedy incremental algorithm for adding observations from the data and assigning segmentation labels. Two observation schedules are proposed: the first treats scanlines as independent, the second uses an active learning criterion to select a sparse subset of points to measure. We show that this probabilistic framework has comparable performance to the state-of-the-art.
Molecular identification of individual nano-objects.

Secondary ion mass spectrometry (SIMS) run in the event-by-event bombardment/detection mode provides a unique ability to obtain molecular information from single nano-objects, since assays are based on secondary ion coemission from single impacts. The characterization of individual nano-objects is demonstrated with negatively charged polymer spheres that are attracted to and retained by nanoalumina whiskers. The whiskers, 2 nm in diameter and ∼250 nm in length, are grafted to a microglass fiber with an average diameter of ∼0.6 μm and several millimeters long. The spheres are monodisperse polystyrene nanoparticles (30 nm diameter). Massive Au projectiles, specifically 136 keV Au4004+, were utilized to bombard analyte surfaces due to its high efficiency for producing multi-ion emission identified by time-of-flight mass spectrometry. Our results show that this mode of mass spectrometry can provide information on the nature, size, relative location, and abundance of nano-objects in the field of view. The key ...
Transcriptome analysis and gene expression atlas for Panicum hallii var. filipes, a diploid model for biofuel research

Summary Panicum hallii is an emerging model for genetic studies of agronomic traits in Panicum, presenting a tractable diploid alternative study system to the tetra- or octaploid biofuel crop switchgrass (Panicum virgatum). To characterize the gene complement in P. hallii var. filipes and enable gene expression analysis in this system we sequenced, assembled, and annotated the transcriptome. Over 300 Mb of normalized cDNA prepared from multiple tissues and treatments was sequenced using 454-Titanium, producing an annotated assembly including 15 422 unique gene names. Comparison with other grass genomes identified putative P. hallii homologs for >14 000 previously characterized genes. We also developed an atlas of gene expression across tissues and stages using RNA-Seq (the quantitative analysis of short cDNA reads). SOLiD sequencing and quantitative analysis of more than 40 million cDNA tags identified substantial variation in expression profiles among tissues, consistent with known functional differences. Putative homologs were found for all enzymes in the phenylpropanoid pathway leading to lignin biosynthesis, including genes with known effects on biomass conversion efficiency. The resources developed here will enable studies of the genes underlying variation in cell wall composition, drought tolerance, and biomass production in Panicum.
The Impact of Political Talk Radio Exposure on Attributions About the Outcome of the 1996 U.S. Presidential Election

This study investigates the media's potential to affect audiences' interpretations of news events. It compares perceptions of the causes of the 1996 presidential election outcome across four media consumption groups: listeners to the program of Rush Limbaugh, listeners to other political talk radio, consumers of mainstream news media, and nonconsumers of news media. Limbaugh listeners were more likely to discount substantive election explanations than were consumers of other types of political talk radio, consumers of mainstream news media, and nonconsumers of news media. These differences in interpretation parallel differences between the content of his program and that of other media.
Asymptotic Solutions of nth Order Dynamic Equation and Oscillations

We establish a new asymptotic theorem for the nth order nonautonomous dynamic equation by its transformation to the almost diagonal system and applying Levinson's asymptotic theorem. Our transformation is given in the terms of unknown phase functions and is chosen in such a way that the entries of the perturbation matrix are the weighted characteristic functions. The characteristic function is defined in the terms of the phase functions and their choice is exible. Further applying this asymptotic theorem we prove the new oscillation and nonoscillation theorems for the solutions of the nth order linear nonautonomous differential equation with complex-valued coefficients. We show that the existence of the oscillatory solutions is connected with the existence of the special pairs of phase functions.
Macroporous Silicon Sensor Arrays for Chemical and Biological Detection

A new class of silicon-based chemical and biological sensors that offer an electrical response to a variety of substances is described. The devices utilize silicon flow-through sensing membranes with deep trench structures formed to depths up to 100μm, fabricated by electrochemical etching which transforms the silicon into macro-porous silicon (MPS). The sensors have demonstrated the ability to detect the presence of certain chemical and biological materials. Although the principle of operation of the devices is fairly complex, the transduction mechanisms can be compared to chemiresistors and chemically sensitive field-effect transistors (chemFETs). The electrical responses that have shown the most sensitivity are AC conductance and capacitance. Previous work has demonstrated that upon exposure to organic solvents (i.e. ethanol, acetone, benzene) the devices exhibit a characteristic impedance signature. The devices have also shown the ability to detect the hybridization of complementary DNA. The incorporation of other materials that have demonstrated sensitivity to low ambient levels of contaminants is also under investigation. The sensors have been designed and fabricated in linear array configurations; a microfluidic transport chip/package co-design is currently in progress.
Regulation in the Pulp and Paper: Costs and Consequences

The paper and pulp industry is one of the most heavily regulated industries in the United States. This working paper investigates the extent to which environmental and workplace regulations affect the industry and evaluate the impact of these regulations on the industry, its customers, its employees and society in general. A review of literature on this topic reveals that numerous scholars have attempted to discern the effects of specific regulations on the industry or attempted to place a dollar value on what pollution abatement costs paper manufacturers. In this paper, we will take their findings into account, identify which regulations affect the industry, and describe the total cost these regulations impose on society. We investigate the tangible and direct costs of regulation, meaning the amount that regulation actually costs companies within the industry in dollar terms, as well as the less-visible, non-monetary costs resulting from regulation. Regulation also inevitably creates unforeseen costs that neither the regulators nor participants in the market could have anticipated, and those unanticipated consequences of regulation often create the very types of problems the regulators intended to reduce or eliminate. Although the paper and pulp industry incurs a relatively high regulatory burden, firms in the industry also tend to be quite large, which gives them the advantage of being able to disperse the costs of regulation over more units. It therefore remains unclear whether regulation affects firms in this industry to a greater or lesser extent than the average firm in the United States in absolute terms, but the industry nonetheless serves as an example of the costs and consequences of government regulation.
Co-Delivery of Protein and Small Molecule Therapeutics Using Nanoparticle-Stabilized Nanocapsules

Combination therapy employing proteins and small molecules provides access to synergistic treatment strategies. Co-delivery of these two payloads is challenging due to the divergent physicochemical properties of small molecule and protein cargos. Nanoparticle-stabilized nanocapsules (NPSCs) are promising for combination treatment strategies since they have the potential to deliver small molecule drugs and proteins simultaneously into the cytosol. In this study, we loaded paclitaxel into the hydrophobic core of the NPSC and self-assembled caspase-3 and nanoparticles on the capsule surface. The resulting combination NPSCs showed higher cytotoxicity than either of the single agent NPSCs, with synergistic action established using combination index values.
Local and global interpolation inequalities on the Folland-Stein Sobolev spaces and polynomials on stratified groups

We derive both local and global Sobolev interpolation inequalities of anyhigher orders for the Folland-Stein Sobolev spaces on stratified nilpotent Lie groups G and on domains satisfying a certain chain condition. Weighted versions of such inequalities are also included for doubling weights satisfying a weighted Poincare inequality. This paper appears to be the first one to deal with gen- eral Sobolev interpolation inequalities for vector fields on Lie groups; Despite the extensive research for Poincare type inequalities for vector fields over the years, interpolation inequalities given here even in the nonweighted case appear to be new. Such interpolation inequalities have important applications to subelliptic or parabolic pde's involving vector fields. The main tools to prove such inequalities are approximating the functions bypolynomials on G. Some veryuseful proper- ties for projections of polynomials associated with the functions are given here and theyappear to have independent interests in their own rights. Main ideas of the proofs of the theorems are explained here. Detailed proofs of the results pre- sented here are given in the paper "Polynomials on stratified groups and Sobolev interpolation inequalities on nonisotropic Folland-Stein spaces" bythe author.