cssi/SciSciGPT-SciSciNet huggingface dataset:
Characterization of leptomeningeal inflammation in rodent experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis.

Abstract Background Leptomeningeal inflammation, as evidenced by leptomeningeal contrast enhancement (LMCE), is associated to cortical pathology in multiple sclerosis. The temporal pattern of LMCE in experimental autoimmune encephalomyelitis (EAE) myelin oligodendrocyte glycoprotein (MOG) is unknown. Objective To investigate LMCE using serial MRI in the EAE model of MS, and its association with clinical disease progression. To characterize the relationship between LMCE and underlying histological correlates. Design Thirteen C57BL/6J mice, MOG-immunized (35–55 amino acid) and 8 saline injected animals were assessed at pre-induction and at 3, 6, 10, 20, 27, 32, 45 and 63 days post induction (dPI). LMCE scan was obtained using FLAIR-RARE sequence after post-contrast gadolinium administration on 9.4 T scanner. Brain cryo-sections were assessed for measuring cellular density of Iba1 positive macrophage/microglia at 10 dPI and 32 dPI, and for the presence of T, B and macrophage cells in the meningeal layer at 10 dPI and 63 dPI. Results All EAE-MOG animals showed presence of LMCE and none of the control mice. The peak signal intensity of LMCE was evidenced at 10dPI in the meninges and decreased through 10–63 dPI. The peak of LMCE was associated with a weight loss starting at 1 week PI and with clinical symptoms starting at 2 weeks PI. Histological analysis of the brain tissue showed a higher density of Iba1 positive microglial cells in the EAE-MOG animals, corresponding to the areas of LMCE. Meninges of EAE mice showed higher density of Iba1 stained macrophage cells relative to saline animals. EAE animals also showed the presence of T and B cells in the meninges which were absent in the saline animals. Conclusions LMCE peak intensity in the meninges corresponds to the acute inflammatory phase of EAE-MOG disease progression, and is associated with clinical symptoms and higher inflammatory cell density.
Lattice Interactions in Crystals of Soybean Trypsin Inhibitor (Kunitz) Produced by Inclusion of 1,5-Disulfonylnaphthalene

In the course of an earlier investigation into the crystallization of proteins based on the addition of intermolecular ligands, the Kunitz type trypsin inhibitor from soybean (SBTI) was crystallized as a complex with 1,5-disulfonylnaphthalene (ligand library 21D). The two molecules within the asymmetric unit of the monoclinic crystals are related by a near-exact NCS 2-fold axis and have essentially the same conformation as was found for them in previous analyses. The protein dimer is maintained through electrostatic interactions with the sulfonyl groups of four 1,5-disulfonylnaphthalene molecules, which are bound in pairs at the dimer interface and involve symmetrical pairs of arg 30 and arg 47 side chains of each SBTI molecule. The binding of the 1,5-disulfonylnaphthalene molecules at the interface is disordered in that only a coordinated single pair of 1,5-disulfonylnaphthalene molecules can be bound at any one time. There are also molecules of the MES buffer present in the crystal structure that are re...
Sublobar resection is associated with decreased survival for patients with early stage large-cell neuroendocrine carcinoma of the lung

OBJECTIVES Sublobar resection (SLR) for early non-small-cell lung carcinoma (NSCLC) has been shown to have a survival rate similar to that of lobectomy. Large-cell neuroendocrine carcinoma (LCNEC) of the lung, although treated like an NSCLC, has a poor prognosis compared to NSCLC. We sought to determine if outcomes are poor in patients with early stage LCNEC treated with SLR versus lobectomy. METHODS We searched for patients with pathological stage I LCNEC ≤3 cm within the National Cancer Database between 2004 and 2014. Propensity score matching was used to compare the 5-year overall survival rate of patients having SLR (wedge or segmentectomy) to that of patients having a lobectomy. Patients were matched for age, node sampling, comorbidity score, tumour size, insurance status and other factors. Patients who received neoadjuvant therapy were excluded. Kaplan-Meier methods were used for analysis. RESULTS A total of 1011 patients met the inclusion criteria: 263 were treated with SLR (223 wedges and 40 segmentectomies) and 748 patients, with lobectomy. Patients who received SLR were older, had more comorbidities and smaller tumours. On unadjusted Kaplan-Meier analysis, patients who had SLR had decreased 5-year overall survival compared to those who had a lobectomy (37.9% vs 56.6%, P < 0.001). Propensity score matching (1:1) across 12 demographic and tumour variables yielded 185 patients per group with 34 segmentectomies and 151 wedge resections in the SLR cohort. On Kaplan-Meier analysis of the matched cohort, patients who had SLR had a worse 5-year overall survival rate compared to those who had a lobectomy (41.5% vs 60.3%; P = 0.001). CONCLUSIONS SLR for early stage LCNEC is associated with a lower 5-year overall survival rate compared to lobectomy on unadjusted and propensity matched analyses.
Single-Nucleotide Polymorphisms Sequencing Identifies Candidate Functional Variants at Prostate Cancer Risk Loci

Genome-wide association studies have identified over 150 risk loci that increase prostate cancer risk. However, few causal variants and their regulatory mechanisms have been characterized. In this study, we utilized our previously developed single-nucleotide polymorphisms sequencing (SNPs-seq) technology to test allele-dependent protein binding at 903 SNP sites covering 28 genomic regions. All selected SNPs have shown significant cis-association with at least one nearby gene. After preparing nuclear extract using LNCaP cell line, we first mixed the extract with dsDNA oligo pool for protein–DNA binding incubation. We then performed sequencing analysis on protein-bound oligos. SNPs-seq analysis showed protein-binding differences (>1.5-fold) between reference and variant alleles in 380 (42%) of 903 SNPs with androgen treatment and 403 (45%) of 903 SNPs without treatment. From these significant SNPs, we performed a database search and further narrowed down to 74 promising SNPs. To validate this initial finding, we performed electrophoretic mobility shift assay in two SNPs (rs12246440 and rs7077275) at CTBP2 locus and one SNP (rs113082846) at NCOA4 locus. This analysis showed that all three SNPs demonstrated allele-dependent protein-binding differences that were consistent with the SNPs-seq. Finally, clinical association analysis of the two candidate genes showed that CTBP2 was upregulated, while NCOA4 was downregulated in prostate cancer (p < 0.02). Lower expression of CTBP2 was associated with poor recurrence-free survival in prostate cancer. Utilizing our experimental data along with bioinformatic tools provides a strategy for identifying candidate functional elements at prostate cancer susceptibility loci to help guide subsequent laboratory studies.
Spinal dural resection for oncological purposes: a systematic analysis of risks and outcomes in patients with malignant spinal tumors.

Objective Oncological outcomes for many malignant primary spinal tumors and isolated spinal metastases have been shown to correlate with extent of resection. For tumors with dural involvement, some authors have described spinal dural resection at the time of tumor resection in the interest of improving oncological outcomes. The complication profile associated with resection of the spinal dura for oncological purposes, however, and the relative influence of resecting tumor-involved dura on progression-free survival are not well defined. The authors performed a systematic review of the literature and identified cases in which the spinal dura was resected for oncological purposes in the interest of better understanding the associated risks and outcomes of this technique. Methods Electronic databases (PubMed/MEDLINE, Scopus) were systematically searched to identify studies that reported clinical and/or oncological outcomes of patients with malignant spinal neoplasms undergoing resection of tumor-involved dura at the time of surgical intervention. Results Ten articles describing 15 patients were included in the analysis. The most common tumor histologies were chordoma (3/15, 20%), giant cell tumor (3/15, 20%), epithelioid sarcoma (2/15, 13.3%), osteosarcoma (2/15, 13.3%), and metastasis (2/15, 13.3%). Procedure-related complications were reported in 40% of patients. A trend was seen toward an increased complication rate in redo (66.7%) versus index (16.7%) operations, but this trend did not reach statistical significance (p = 0.24). New, unexpected postoperative neurological deficits were seen in 3 patients (of 14 reporting, 21.4%). A single patient experienced a profound, unexpected neurological deterioration (paraparesis/paraplegia) after surgery, which reportedly improved considerably at latest follow-up. Tumor recurrence was seen in 3 cases (of 12 reporting, 25%) at a mean of 28.34 ± 21.1 months postoperatively. The overall mean radiographic follow-up period was 49.6 ± 36.5 months. Conclusions Resection of the spinal dura for oncological purposes is rarely performed, although a limited number of reports and small series have demonstrated that it is feasible. Spinal dural resection is primarily performed in patients with isolated, primary spinal neoplasms with an intent to cure. The risk associated with spinal dura resection is nontrivial and the complication profile is significant. The influence of dural resection on oncological outcomes is not well defined, and further study is needed before definitive conclusions may be drawn regarding the oncological benefit of dural resection for any particular patient or pathology.
Overapproximating Reachable Sets by Hamilton-Jacobi Projections

In earlier work, we showed that the set of states which can reach a target set of a continuous dynamic game is the zero sublevel set of the viscosity solution of a time dependent Hamilton-Jacobi-Isaacs (HJI) partial differential equation (PDE). We have developed a numerical tool—based on the level set methods of Osher and Sethian—for computing these sets, and we can accurately calculate them for a range of continuous and hybrid systems in which control inputs are pitted against disturbance inputs. The cost of our algorithm, like that of all convergent numerical schemes, increases exponentially with the dimension of the state space. In this paper, we devise and implement a method that projects the true reachable set of a high dimensional system into a collection of lower dimensional subspaces where computation is less expensive. We formulate a method to evolve the lower dimensional reachable sets such that they are each an overapproximation of the full reachable set, and thus their intersection will also be an overapproximation of the reachable set. The method uses a lower dimensional HJI PDE for each projection with a set of disturbance inputs augmented with the unmodeled dimensions of that projection's subspace. We illustrate our method on two examples in three dimensions using two dimensional projections, and we discuss issues related to the selection of appropriate projection subspaces.
Investigating association of perineural invasion on prostate biopsy with Gleason score upgrading at prostatectomy: A multi-institutional analysis.

Background The significance of perineural invasion (PNI) in prostate cancer (PC) is unclear. A recent report of patients with pT2N0R0 PC found that PNI at prostatectomy was independently associated with higher Gleason score and more diffuse prostatic disease. We aimed to test our hypothesis that PNI on prostate biopsy in pT2N0R0 patients is associated with increased Gleason score upgrading at prostatectomy. Methods We identified 2892 patients status post prostatectomy with pT2N0R0 PC from three institutions, diagnosed between 1 January 2008 and 31 December 2014. Multivariable logistic regression (MVA) was used to evaluate the association between prostate biopsy PNI status and surgical Gleason upgrading, while controlling for potential confounders. Results Of the 2892 patients identified, 14% had PNI on biopsy, of whom 21% had surgical Gleason upgrading, while 28% without PNI on biopsy had such upgrading (P 4 ng/mL (OR 1.26, P = .02). Conclusions In post-prostatectomy patients with favorable-risk PC, PNI on prostate biopsy was not associated with surgical Gleason score upgrading. This may be due to the association of PNI with more diffuse disease, leading to increased biopsy tumor yield and grading accuracy. These findings suggest that in this setting, biopsy PNI alone should not be a concern for more aggressive disease requiring pathologic confirmation or intervention. This may help guide treatment decision-making for men debating active surveillance, radiation, and surgery.
A head-worn display ("smart glasses") has adverse impacts on the dynamics of lateral position control during gait.

Abstract Background Head-worn displays (e.g., “smart glasses”) are an emerging technology to provide information, and in many situations they might be used while walking. However, little evidence exists regarding the effects of head-worn displays on walking performance. We found earlier that “smart glasses” had smaller adverse effects on measures of gait variability in the anterior-posterior direction vs. other types of information displays. Participants, however, complained about motion sickness and perceived instability while using smart glasses. Research question Were the participants’ complaints a result of adverse effects of the smart glasses on the dynamics of lateral stepping and gait stability? Methods Twenty individuals walked on a treadmill in four different conditions; single-task walking, and three dual-task walking conditions, the latter using smart glasses, smartphone, and a paper-based system to provide secondary cognitive tasks. We assessed the dynamics of lateral stepping and gait stability using the goal equivalent manifold and maximum Lyapunov exponent, respectively. Results The dynamics of the lateral stepping were more adversely affected using smart glasses compared to the other types of information displays. However, stability measures revealed that the participants were more unstable when they used the smartphone and paper-based system. Significance Promising results in terms of stability and adaptability suggest that head-worn display technology is a potentially useful alternative to smartphones and other types of information displays for reducing the risk of a fall. Results regarding perceptions of instability and a loss of control over lateral stepping, however, imply that this technology requires further development prior to real-work implementations.
Labyrinthine radicality: in dialogue with Martin Mulsow’s Radikale Frühaufklärung in Deutschland 1680–1720

Twice in his life, Richard Popkin had his suitcase stolen from him. If we can trust his memoirs, both incidents happened within a few years, and in each instance, the suitcase contained valuable re...
Jitter-induced Max-of-N fluence distribution at the National Ignition Facility

Max-of-N fluence is the maximum peak fluence at a given location over N number of shots and is important for calculating fluence dependence for intrinsic laser-induced optic damage. Previously, we observed the Max-of-N effect on the National Ignition Facility and developed an ad-hoc model to calculate its effect. In this work, we attempt to understand the fundamental mechanism that causes this Max-of-N effect. We conclude that the primary fundamental mechanism responsible for this effect is dominated by the combination of fluence variations and pointing jitter of the laser. This discovery both strengthens our model for predicting optics longevity and gives us insight into how to mitigate this effect.
Does the frailty index predict discharge disposition and length of stay at the hospital and rehabilitation facilities

Abstract Introduction Many geriatric hip fracture patients utilize significant healthcare resources and require an extensive recovery period after surgery. There is an increasing awareness that measuring frailty in geriatric patients may be useful in predicting mortality and perioperative complications and may be useful in helping guide treatment decisions. The primary purpose of the study is to investigate whether the frailty index predicts discharge disposition from the hospital and discharge facility and length of stay. Methods In this retrospective cohort study, patients aged 65 years and older presenting to a level 1 trauma center with a hip fracture and a calculated frailty index were eligible for inclusion. The primary outcome was discharge disposition. Secondary outcomes were hospital and discharge facility length of stay, 90-day hospital mortality and readmissions, and return to home. Results A total of 313 patients were included. The frailty index was a robust predictor of discharge to a skilled nursing facility (OR 1.440 per 0.1 point increase). Patients with a higher frailty index were at higher risk of 90-day mortality and less likely to return to home at the end of follow-up. There was a very weak correlation between the frailty index and hospital length of stay (ρ=0.30) and rehab length of stay (ρ=0.26). Conclusion The frailty index can be used to predict discharge destination from both the hospital and rehabilitation facility, 90-day mortality, and return to home after rehabilitation. In this study, the frailty index had a very weak correlation with length of stay in the hospital and in discharge destination. The frailty index can be used to help guide medical decision making, goals of care discussions, and to determine which patients benefit from intensive rehabilitation.
The choice among bank debt, non-bank private debt, and public debt: evidence from new corporate borrowings☆

Abstract Using a sample of 1,560 new debt financings, we examine the choice among bank debt, non-bank private debt, and public debt. The primary determinant of the debt source is the credit quality of the issuer. Firms with the highest credit quality borrow from public sources, firms with medium credit quality borrow from banks, and firms with the lowest credit quality borrow from non-bank private lenders. Non-bank private debt thus plays a unique role in accommodating the financing needs of firms with low credit quality. In addition, the choice of debt source is (weakly) influenced by managerial discretion.
Political Competition and Attitudes Toward Immigration in Africa

Connected directly to this year’s conference theme of “Mobility, Migration, and Flows,” this paper explores how political competition shapes attitudes toward immigration in Africa. Employing multilevel logistic regression analysis with survey data from eleven African countries, the paper finds strong evidence that opposition to immigration is more likely among individuals in countries that are more democratic, that have dominant party systems, and when the survey is conducted close to a national election. These results provide empirical support for the notion that attitudes toward immigration are shaped in part by political competition. Our analysis also shows that the African experience contradicts previous research from other regions. Specifically, opposition to immigration is more likely in African countries with higher levels of economic development and higher levels of ethnic diversity. These findings are subsequently explored in a case study of South Africa, where negative attitudes and violence toward foreigners have attracted global attention. In the end, the paper suggests a need to revisit broader comparative theories about immigration attitudes and to give greater attention to political factors.
Strategic ratification

Previous models of ratifier effects have relied on restrictive assumptions regarding the dimensionality of the choice space and the preferences and rationality of actors. These assumptions can lead to an underestimation of the importance of ratifiers and a mischaracterization of their role. A model presented here responds to these concerns and finds that when ratifiers are strategic, ratification requirements consistently aid negotiators in settings where previous models find no effects. Furthermore, new relations between the types of ratifier and the strength of their influence are identified. Negotiators benefit from in-group homogeneity on dimensions along which negotiators agree and from internal dissension on dimensions along which negotiators disagree.
Early Detection of Alzheimer's Disease Benefits Research, Quality of Life, and End-of-Life Planning.

McKeown, Malhi, and Singh (2021) argue that early intervention in Alzheimer’s Disease (AD) threatens the boundaries between primary and secondary prevention, raising ethical concerns. The authors m...
Interactions among vertebrate helix-loop-helix proteins in yeast using the two-hybrid system

The helix-loop-helix (HLH) motif is contained in a rapidly growing family of transcription factors and has been shown to mediate dimerization among heterologous HLH-containing proteins. E12 is a widely expressed HLH protein that preferentially forms heterodimers with cell type-specific HLH proteins such as MyoD, myogenin, and the achaete-scute gene products. As a first step toward screening for novel cell type-specific partners of E12, we used a modification of the two-hybrid assay for detection of protein-protein interactions in vivo to determine whether dimerization of HLH proteins with E12 can occur in yeast. Using the GAL4 DNA-binding domain fused to the E12 HLH motif and the GAL4 transcription activation domain fused to MyoD, we show that E12 and MyoD can efficiently dimerize in yeast and reconstruct a hybrid transcription factor that activates reporter genes linked to the GAL4 DNA-binding site. The GAL4 DNA-binding domain fused to E12 was used to screen a mouse T-cell cDNA library in which the cDNA was fused to the GAL4 activation domain. Several cDNA clones encoding proteins that interact with E12 were isolated, one of which corresponded to the HLH protein Id-2. Given the ability of E12 to dimerize preferentially with cell type-specific HLH proteins, this strategy should be useful for cloning novel partners for E12 from a variety of cell types.
Broken Scales: Obesity and Justice in America

This Article provides a broad assessment of the American obesity epidemic from the perspective of "critical realism," an innovative approach to legal analysis developed by the authors in previous articles. The article is focused on exploring the vast divergence between common sense views of the sources of obesity - which typically attribute the phenomena to the individual, private choices of consumers - and the very different conception of the sources of obesity that emerges from the social sciences, which are typically much more focused on environmental influences on consumption behavior. The article endeavors to develop an approach to the legal analysis of obesity that is responsive to the social scientific findings, rather than merely patronizing to the common sense view. Further, the Article examines the ways in which the food industry has exercised powerful influence, often in unseen ways, over consumer behavior in the food market, even as the industry has evaded responsibility for the ensuing obesity epidemic by promoting to regulators, as well as to consumers themselves, the view that consumer behavior in the food market reflects the preference driven choices of individual consumers, which the industry claims merely to satisfy.
An Intelligent Agent Validation Architecture for Distributed Manufacturing Organizations

In this paper, we focus on validation of Multi-Agent System (MAS) behavior. We describe the simulation architecture and the system design methodology to accomplish the appropriate agent behavior for controlling a real-life automation system. The architecture is explained in the context of an industrial-sized water cooling system. Nevertheless, it is intended to operate in a wide spectrum of control domains. In general, after the design of the control system is accomplished, a set of validation procedures takes place. The current needs are to validate both the control and the agent levels as integrated parts. Hence there is a need to establish a general architecture and methodology for easing the commissioning process of the control solution.
A unified approach to the selection of structures for digital filters

Any digital transfer function can be realized in a multitude of configurations (structures). Several procedures for analyzing the quantization characteristics have appeared in literature. This paper unifies these analysis procedures to select an optimum structure for a given transfer function. The procedure scales the filter modules to prevent overflow, selects the coefficient word lengths by sensitivity considerations, selects the quantizer step lengths to balance the quantization errors between the quantizers and uses the quantization error at the output as the quality factor for the structure. Simulation results are provided to prove the validity of the procedure.
Optimal power dispatch and control of a wind turbine and battery hybrid system

In this paper, a new power dispatch and control methodology is proposed for a hybridized wind turbine and battery system to supply consistent power within each 30min. First, the desired battery state of charge (SOC) is determined as a function of wind speed offline using an probabilistic analysis of historical wind data. With this information, a one-step ahead model predictive optimization approach is developed for scheduling the hybrid system power output for the next 30min. Compared to conventional multi-step-ahead model predictive optimizations, the proposed one-step ahead optimization with offline-obtained desired SOC obviates calculations with inaccurate multi-step-ahead wind predictions, hence it is more reliable and computational efficient. Second, a real-time controller is developed to make the actual hybrid system power output match the scheduled target. It determines the reference power set point for wind turbine by a steady state optimization approach and subsequently applies an active power controller to track this set point. Simulation results show that, compared to the conventional heuristic scheduling approach and standard real-time control, implementing the new methodology significantly reduces the ramp rate, generator torque changing rate, battery charging rate and the power output deviation from the scheduled target.
Nuclear Fossils in Stardust

In the 1950s, observation of the radioactive element technetium in stars led to the modern theory of nucleosynthesis that explains how elements are created. In his Perspective, [Nittler][1] discusses results reported [ Savina et al. ][2] in which highly sensitive mass spectroscopy was used to measure the isotopic abundance of ruthenium, a technetium decay product, in silicon carbide dust grains from meteorites. Such grains are believed to have been created in the envelopes of particular giant stars. Savina et al . find that the measured isotopic ratios agree very well with models of these stars if radioactive technetium is assumed to have been a component of the dust grains during their formation. As a result of these measurements, modern stellar models can be quantitatively tested with high accuracy and precision. [1]: http://www.sciencemag.org/cgi/content/full/303/5658/636 [2]: http://www.sciencemag.org/cgi/content/short/303/5658/649
High Angle Dips at Erosional Edge of Overthrust Faults

ABSTRACT Passive crystalline basement, parallelism of fault and stratigraphic surfaces, and drill data in overthrust belts, indicate that major overthrust fault surfaces commonly dip less than 15° over broad areas. High dips of 30° to 80°, in many instances observed at the trace, are probably not representative of the fault as whole. Some proposed mechanisms of overthrusting, particularly gravitational gliding, may be suspect owing to frequency of observation of high dips. One reason for the occurrence of these steep dips is the tendency for fault segments subparallel with the ground surface to disappear quickly by erosion relative to steep segments in the toe and steps. Another is toreva block faulting at erosional edges of thrust plates. Overthrusting generally brings older, indurated beds over younger, weak strata. Frontal scarps steepen, toreva blocks form and rotate when displaced downward along the curved fault surfaces. Thus, the truncated overthrust fault is rotated and steepened. As examples, the Absaroka overthrust fault is steepened from 18° to 90° in a large, half-toreva block 18 miles north of Kemmerer, Wyoming, and Cambrian rocks overlying the Hogsback overthrust are rotated at Hogsback Mountain near La Barge, Wyoming. Four additional toreva blocks are preserved in autochthonous Cretaceous Adaville Formation east of the Hogsback trace, indicating the overthrust surface has been repeatedly rotated and steepened as the erosional edge of the allochthon receded westward.
Beam species mix as a function of DIII-D neutral beam ion source operation parameters

By measuring the Balmer-alpha emission for deuterium, Doppler-shifted spectroscopy (DSS) can give relative fractions of the ions D/sup +/, D/sup 2+/, D/sup 3+/ (species mix) produced by the DIII-D neutral beam ion sources. The species mix varies with beam energy, arc power, gas flow rates, and time within a beam pulse. The full energy species fraction gets larger and tends to become constant with increasing beam energy while the third energy species tends to decrease. Varying the neutralizer flow rate between 0 and 20 torr-l/sec causes the full energy species fraction to decrease by /spl sim/0.04 in favor of more third energy particles. Measurements made at various times within a beam pulse showed that the species fraction normally varies by about 0.02 but can have a variation of as much as 0.14. The effect of the beam parameters on the species mix varies slightly between ion sources. Each of the beam species has a different neutralization efficiency. Thus, the neutral beam power injected into the tokamak depends on the species mix. The neutralization fraction (and the total injected power) obtained using beam species as measured by DSS at a beam energy of 80 keV is 4% lower than previously believed. This difference becomes smaller with decreasing beam energy until they converge at 50 keV.
Computational reprogramming of homing endonuclease specificity at multiple adjacent base pairs

Site-specific homing endonucleases are capable of inducing gene conversion via homologous recombination. Reprogramming their cleavage specificities allows the targeting of specific biological sites for gene correction or conversion. We used computational protein design to alter the cleavage specificity of I-MsoI for three contiguous base pair substitutions, resulting in an endonuclease whose activity and specificity for its new site rival that of wild-type I-MsoI for the original site. Concerted design for all simultaneous substitutions was more successful than a modular approach against individual substitutions, highlighting the importance of context-dependent redesign and optimization of protein–DNA interactions. We then used computational design based on the crystal structure of the designed complex, which revealed significant unanticipated shifts in DNA conformation, to create an endonuclease that specifically cleaves a site with four contiguous base pair substitutions. Our results demonstrate that specificity switches for multiple concerted base pair substitutions can be computationally designed, and that iteration between design and structure determination provides a route to large scale reprogramming of specificity.
Coupled photocatalytic-biodegradation of 2,4,5-trichlorophenol: Effects of photolytic and photocatalytic effluent composition on bioreactor process performance, community diversity, and resistance and resilience to perturbation

Sequentially coupled advanced oxidation-biodegradation systems have proven effective for treating a variety of wastewaters, but in several cases the pretreatment did not improve, or even hindered, subsequent biodegradation. Therefore, investigating the relationship between advanced oxidation pretreated effluent and subsequent bioreactor performance can help to optimize these systems. Here, a photocatalytic reactor was used to produce four unique effluents from 2,4,5-trichlorophenol (TCP) by varying light wavelength, catalyst presence, and reaction time, demonstrating that the conditions of photocatalytic pretreatment can be tuned to achieve a variety of treatment objectives. The photocatalytic effluents were characterized for chemical oxygen demand (COD), chloride release, aromaticity, and residual TCP concentration. The four effluents were normalized to 40 mg COD/L, combined with biological medium components, and fed to continuous bioreactors. Bioreactors were assayed for COD removal, TCP removal, optical density (OD), and microbial diversity via denaturing gradient gel electrophoresis. In general COD removal in the bioreactors increased as aromatic character of the photoeffluent decreased, but the least aromatic effluent performed poorly indicating the nuanced relationship between photoreactor effluent composition and bioreactor performance. While neither indicator of community diversity, richness nor evenness, correlated with COD removal or biomass accumulation, each effluent produced a unique community as indicated through similarity indices. All conditions demonstrated strong overall TCP removal. After two weeks at steady state, the reactors were perturbed with a 120-μM spike of TCP. Overall the most aromatic photoeffluent produced the most resistant community to the perturbation, while the optimum effluents at steady state produced communities with poor resistance in terms of biomass accumulation and COD removal. These results highlight the tradeoffs between steady state performance and resistance to perturbation that are necessary to optimize a combined advanced oxidation-biodegradation treatment strategy.
In-situ electrochemical synthesis of 1-dimensional alumina nanostructures

One dimensional (1-D) alumina nanostructures were electrochemically synthesized on the surface of a porous anodic aluminium oxide (p-AAO) membrane by carefully controlling the temperature, voltage and time for anodization of aluminium foil. These nanostructures were characterized by scanning electron microscopy, field emission scanning electron microscopy, and transmission electron microscopy. X-Ray diffraction and selected area electron diffraction patterns prove that the as-prepared materials are amorphous. Anodizations of Al foil at different conditions were carried out as control experiments. A possible mechanism of formation (electric-field-assisted chemical dissolution) is postulated.
Study of the Li / Li3 N Electrode in an Organic Electrolyte

Lithium nitride has been studied as a possible solid‐electrolyte interphase between the lithium electrode and an organic electrolyte. The electrode has been obtained by exposing lithium to a pure nitrogen atmosphere at ambient temperature. This procedure is found to lead to the formation of a porous lithium nitride film, resulting from a decrease in the molar volume during the reaction. The impedance behavior of the electrode can be interpreted by a porous‐film model deduced from a transmission‐line model. The slow filling of the micropores of the film and reaction of lithium with the electrolyte at the pore bases are responsible for changes of impedance and open‐circuit potential with time and under cycling.
Sensors searching for interesting things: Extremum seeking control on entropy maps

This paper presents a novel approach to increasing the information content in sensor measurements, with special applications in images or video. The entropy of a signal gives a measurement of the information content. In the case of images, entropy is low when large parts of an image are uniformly colored or shaded. This can occur due to poor camera settings, poor lighting conditions, or the camera is facing a scene with little interest or activity. Minor camera motions can often alleviate these problems. We employ methods of extremum seeking control to find a local maximum in the entropy map surrounding the camera. Entropy maps often have local maxima that do not correspond to a global maximum. Therefore we combine the global properties of simplex optimization methods with the local search properties and dynamic response of extremum seeking control to create a novel algorithm that is more likely to find a global maximum than conventional extremum seeking control. Simulations and experiments are presented to show the strength of this approach.
Some Reflections on the Role of a Political Opposition in New Nations

The role of a political opposition has proved ambiguous in most newly independent nations. New governments rarely see the necessity for a regular opposition party nor do they always accept the idea of opposition as a normal feature of government. There are many reasons why this is so. Most new nations have come into being after a prolonged period of struggle with colonial authorities which has caused nationalist leaders to monopolize loyalties. Also, opposition groups having themselves been associated with nationalism at some stage of their existence, often have an anti-government reflex common to those whose political actions have been aimed at changing the fundamental character of a country rather than accepting well established rules of political life and working within them. Indeed, many opposition leaders in new nations regard the new government much as they did their colonial nredecessors, i.e. as basically illegitimate.
The Spectrum of MR Imaging in Athletic Pubalgia

Many athletes struggle with groin pain for years without ever receiving a clear diagnosis or being offered an effective treatment plan. Confusion among treatment providers can also frequently lead to suboptimal surgeries for presumed hernias or nerve entrapment syndromes. Imaging, and in particular magnetic resonance (MR) imaging, should play a primary role in the workup, diagnosis, and treatment of athletic pubalgia. This review outlines standard of care, cutting-edge MR imaging techniques for athletic pubalgia, and reviews the spectrum of imaging findings that are encountered in this patient group.
Morphology and deformation behavior of “row-nucleated” polyoxymethylene film

Abstract Crystallization from a stressed polymer melt produces not the familiar randomly nucleated spherulitic structures, but instead a highly oriented “row-nucleated” morphology. We have crystallized films of polyoxymethylene from stressed melts; just as polyethylene, the surfaces are covered with protruding lamellar edges highly oriented in the extrusion direction. There is no evidence for the more familiar spherulitic morphology. Electron microscopy directly revealed for the first time that the row nuclei are fibers, only about 200 to 300 A in diameter, extending for distances up to 10 mU. Although comprising a negligibly small amount of total sample volume, they are of prime importance in influencing how the sample will crystallize. Their presence determines, more than any other single factor, whether the sample will crystallize spherulitically or into a row-nucleated morphology. When deformed in the extrusion direction, the twisted lamellar bundles open up to form a fishnetlike structure. Simultaneo...
Extensive vascular remodeling in the spinal cord of pre-symptomatic experimental autoimmune encephalomyelitis mice; increased vessel expression of fibronectin and the α5β1 integrin.

Abstract Alterations in vascular structure and function are a central component of demyelinating disease. In addition to blood–brain barrier (BBB) breakdown, which occurs early in the course of disease, recent studies have described angiogenic remodeling, both in multiple sclerosis tissue and in the mouse demyelinating model, experimental autoimmune encephalomyelitis (EAE). As the precise timing of vascular remodeling in demyelinating disease has yet to be fully defined, the purpose of the current study was to define the time-course of these events in the MOG 35–55 EAE model. Quantification of endothelial cell proliferation and vessel density revealed that a large part of angiogenic remodeling in cervical spinal cord white matter occurs during the pre-symptomatic phase of EAE. At the height of vascular remodeling, blood vessels in the cervical spinal cord showed strong transient upregulation of fibronectin and the α5β1 integrin. In vitro experiments revealed that α5 integrin inhibition reduced brain endothelial cell proliferation under inflammatory conditions. Interestingly, loss of vascular integrity was evident in all vessels during the first 4–7 days post-immunization, but after 14 days, was localized predominantly to venules. Taken together, our data demonstrate that extensive vascular remodeling occurs during the pre-symptomatic phase of EAE and point to a potential role for the fibronectin–α5β1 integrin interaction in promoting vascular remodeling during demyelinating disease.
Role of Cytoplasmic Dynein in Perinuclear Aggregation of Phagocytosed Melanosomes and Supranuclear Melanin Cap Formation in Human Keratinocytes

Cytoplasmic dynein is a microtubule-associated motor molecule involved in the retrograde transport of membrane-bound organelles. To determine whether the supranuclear melanin cap of transferred, phagocytosed melanosomes in keratinocytes is associated with cytoplasmic dynein, we performed immunofluorescent confocal microscopy on human keratinocytes in situ. We identified the intermediate chain of cytoplasmic dynein by immunoblotting and examined its distribution by confocal microscopy in relation to microtubules and melano-phagolysosomes in vitro. We also used antisense and sense oligonucleotides of the cytoplasmic dynein heavy chain 1 (Dyh1) and time-lapse and microscopy. The intermediate chain of cytoplasmic dynein was identified in extracts of human foreskin epidermis and in isolated human keratinocytes. The intermediate chain localized with the perinuclear melano-phagolysosomal aggregates in vitro and the supranuclear melanin cap in situ. Antisense oligonucleotides directed towards Dyh1 resulted in dispersal of the keratinocyte perinuclear melano-phagolysosomal aggregates after 24 to 48 h, whereas cells treated with diluent or sense oligonucleotides maintained tight perinuclear aggregates. Taken together, these findings indicate that in human keratinocytes, the retrograde microtubule motor cytoplasmic dynein mediates the perinuclear aggregation of phagocytosed melanosomes, participates in the formation of the supranuclear melanin cap or "microparasol" and serves as a mechanism to help protect the nucleus from ultraviolet-induced DNA damage.
Phase reversal of somatosensory evoked potentials triggered by gracilis tract stimulation: case report of a new technique for neurophysiologic dorsal column mapping.

Background and importance : Reliable visual identification of the median raphae, essential for the preservation of function of the posterior dorsal columns during intramedullary spinal cord tumor resection, is not possible in many cases, because of distorted local anatomy. In such cases, intraoperative neurophysiologic mapping of the dorsal columns offers invaluable information to the surgeon, and guides the myelotomy. We hereby describe such a new technique. Clinical presentation : A 41-year-old man with a C3-C4 intramedullary spinal cord tumor underwent successful myelotomy and tumor resection. Dorsal column mapping was performed by use of an 8-contact minielectrode strip placed on the dorsal spinal cord. Direct electrical stimulation was applied via 2 adjacent contacts of the strip at a time, in an attempt to stimulate in succession the left and right dorsal columns. Somatosensory evoked potentials (SSEPs) were recorded after each stimulation, via scalp electrodes. A sharp change in polarity of the recorded scalp SSEPs (phase reversal) indicated when the stimulation of the opposite dorsal column occurred. Myelotomy was performed in between the minielectrode contacts identified as being situated closest to the raphe. The posterior tibial SSEPs were continuously monitored during and after myelotomy and until the dura closure. No changes from premyelotomy SSEPs were present. Postoperatively, the patient had preservation of the posterior column function. Conclusion : SSEP phase-reversal technique is a promising new method to identify the neurophysiologic midline in intramedullary tumor resection. Fast and easy to perform, its final role in neurophysiologic dorsal column mapping awaits confirmation in future applications.
Images in clinical medicine. Occult hip fracture.

An 87-year-old man tripped and fell; subsequently, persistent pain developed in the left hip. A radiograph of the left hip 2 weeks after the fall revealed no evidence of fracture.
On financial disclosure and the behavior of security prices

Abstract The paper addresses the question: what impact does a change of a firm's information-disclosure environment have on its stock price behavior? Assuming that disclosure does not have any effects on production financing programs, that the CAPM obtains, and information can be characterized as ‘linear’, a number of results are provided. It is shown that disclosure leads to increased variability in stock price; the result is consistent with several empirical studies [Beaver (1968), May (1971), and Patell and Wolfson (1979)]. Further, the price that would be expected in a richer information environment is simply equal to the price that actually obtains in a less rich environment. Finally, risk and return parameters are essentially independent of changes in the disclosure environment.
What teachers report about their inquiry practices

Based on an analysis of teachers’ responses to a rated closed-ended survey on their inquiry practices, which was crosschecked with open-ended qualitative responses, they were using several different science research skills during instruction; however, teachers reported use of inquiry research skills likely occurred during guided inquiry projects with little evidence to support that they used full inquiry as suggested in theNational Science Education Standards (NSES) (NRC, 1996).
A Ge(Li)-Ge(Li)-NaI(Tl) coincidence spectrometer system for (n,γ) studies

Abstract A spectrometer system has been constructed to study 0.06–12 MeV neutron-capture γ-rays produced at the thermal-beam facility of the Livermore Pool Type Reactor. The system consists of two spectrometers, designed to cover the low-energy (0.06–2.5 MeV) and high-energy (2–12 MeV) portions of the spectrum. The low-energy system consists of a Ge(Li) detector surrounded by a NaI(Tl) anti-Compton shield, operated in anticoincidence. The high-energy system consists of a Ge(Li) detector flanked by two NaI(Tl) counters and operated in the coincidence mode as a “three-crystal pair spectrometer”. These systems are operated independently, or in coincidence. In the latter case, certain NaI(Tl) modes must be disengaged to obtain adequate coincidence efficiency. An automated pulser is used for linearity calibration and stabilization. Coincidence data is processed by a 4096-channel three-parameter pulse-height analyzer, buffered onto magnetic tape, and analyzed off-line by digital computers.