cssi/SciSciGPT-SciSciNet huggingface dataset:
Fli1 Is Essential for the Maintenance of Hematopoietic Stem Cell Homeostasis and Function

Abstract The ETS family of transcription factors is known to play an essential role in hematopoietic and vascular development. One such factor that is widely expressed in all vascular beds and almost all hematopoietic lineages, extending from long term hematopoietic stem cells to terminally differentiated peripheral blood cells, is Fli1. Global deletion of Fli1 leads to embryonic lethality at E12.5 due to dramatic hemorrhaging caused by poor vascular integrity and platelet dysfunction. The role of Fli1 in adults has been explored in several different cells types ranging from megakaryocytes to B and T cells. It has also been implicated in transcriptional regulation of hematopoietic stem and progenitor cells through combinatorial analysis, however its exact contribution to stem cell maintenance and function remains unclear. We hypothesized that Fli1 plays a dual role in regulating both the seed and the soil - specifically hematopoietic stem cell (HSC) function in a cell autonomous manner as well as the niche required for nurturing these cells. In this study, we focused our attention on the cell autonomous function of Fli1. We found that global deletion of Fli1 leads to lethality as a result of complete peripheral blood failure in addition to aberrant vasculature. Using the cre-lox system and various transplantation strategies, we identify Fli1 as one of the critical regulators of adult hematopoietic stem cell function. Specific deletion of Fli1 in the hematopoietic compartment alone is sufficient to induce significant reduction in peripheral blood counts, accompanied by hemorrhage, resulting in lethality. On further inspection, Fli1-/- HSCs are unable to expand ex vivo or engraft in a competitive setting. Additionally, Fli1 is essential for hematopoietic reconstitution post radiation and its deletion abolishes the ability of stem cells to reconstitute the bone marrow and contribute to peripheral blood lineages. ChIP-seq analysis demonstrates Fli1 occupancy in almost all essential hematopoietic gene enhancers and promoters. By correlating Fli1-/- HSC RNA seq analysis with the ChIP occupancy data we can conclude that Fli1 is, in fact, one of the master regulators of the HSC transcriptional program essential to maintain the balance between self-renewal and differentiation. Taken together, our results indicate that Fli1 is required for maintenance of HSC homeostasis and function, making it one of the unique transcription factors to play a critical role in HSC function in adults as well as during development. Disclosures No relevant conflicts of interest to declare.
Shell-Model Calculations for Cu 60 and Zn 60 with Reaction Matrix Elements

Employing ${\mathrm{Ni}}^{56}$ as core, and Kuo and Brown renormalized matrix elements for the Hamada-Johnston nucleon-nucleon potential as the residual interaction, the level structure of both ${\mathrm{Cu}}^{60}$ and ${\mathrm{Zn}}^{60}$ is studied within the framework of the shell model. The four active nucleons are allowed to populate the $1{p}_{\frac{3}{2}}$, $0{f}_{\frac{5}{2}}$, and $1{p}_{\frac{1}{2}}$ single-particle orbitals. A comparison with the observed level spectra is made, and good agreement with those levels whose spins and parity are definitely known is found. Other levels whose spins and parity assignments are not definite have corresponding theoretical levels which should help in determining their spins in the future measurements.
Walking in a Crowd Full of Virtual Characters: Effects of Virtual Character Appearance on Human Movement Behavior

This paper describes a study on the effects that a virtual crowd composed of virtual characters with different appearance has on human movement behavior in a virtual environment. The study examines five virtual crowd conditions that include the following virtual characters: neutral, realistic, cartoon, zombies, and fantasy. Participants were instructed to cross a virtual crosswalk and each time, one of the examined crowd conditions shown. The movement behavior of participants was captured and objectively analyzed based on four measurements (speed, deviation, distance traveled, and interpersonal distance). It was found that the appearance of the virtual characters significantly affected the movement behavior of participants. Participants walked slower when exposed to a virtual crowd composed of cartoon characters and faster when exposed to fantasy characters. Moreover, participants deviated more when exposed to a crowd composed of fantasy characters compared to cartoon and zombie characters. Finally, the interpersonal distance between participants and fantasy characters was significantly greater compared to human and zombie characters. Our findings, limitations and future directions are discussed in the paper.
A High Efficiency High Density DC/DC Converter for Battery Charger Applications

Increased attention is being paid to the solid-state-transformer (SST) based charging station which requires a high efficiency high power density DC/DC stage. This framework would provide universal charging for all electric vehicles (EVs) no matter their battery voltage is 400 V or 800 V. In this paper, a two stage DC/DC converter consisting of a three-phase (3P) CLLC converter and four-phase interleaving Buck converter is proposed to achieve a wide output voltage range from 200 V to 800 V with bi-directional energy transfer capability. With SiC devices, a PCB winding based six-leg integrated transformer is used for the 3P transformer, and a PCB winding based EI core is used for the negative coupling inductors. The detailed design process of integrated magnetics is presented. A 12.5 kW prototype with over 97.7 % efficiency and 100 W/in3 power density is built to verify the feasibility of the proposed structure.
Soft Tactile Sensing Skins for Robotics

Soft electronic skins (E-skins) capable of tactile pressure sensing have the potential to endow robotic systems with many of the same somatosensory properties of natural human skin. In this progress report, we review recent progress in creating soft tactile pressure sensing skins to give robots a sense of touch that resembles human skin sensing. For soft tactile pressure sensing skins, researchers have focused on five main sensing principles: (1) resistive; (2) capacitive; (3) magnetic; (4) barometric; and (5) optical. The combination of these traditional sensing techniques, along with the use of soft materials such as liquid metal and magnetic elastomers, has improved the perception capabilities and mechanical characteristics of artificial skin. In addition, the implementation of artificial intelligence and machine learning algorithms for data processing give robotic systems with these soft sensing skins an enhanced sense of touch. E-skins for tactile sensing have a central role in a range of robotic applications, from haptics and teleoperation to bio-inspired soft robots. For many of these applications, E-skins must be soft, thin, flexible, stretchable, and lightweight so that they can be mounted on a robot, incorporated into clothing, or placed on human skin without interfering with mobility or contact mechanics. Significant research has been conducted on sensing techniques that can allow a robot to achieve a sense of human touch, with important progress being made in force feedback sensing, texture recognition, and spatial acuity. We begin by covering principles of tactile sensing in humans, robotics, and human-machine interaction. This is followed by an overview of soft material transducers capable of pressure and force sensing. This includes resistive, capacitive, magnetic, barometric, and optical sensing techniques. We close with a summary of emerging trends in sensor design and implementations for applications in robotics.
Obesity Impairs Embryonic Myogenesis by Enhancing BMP Signaling within the Dermomyotome

Obesity during pregnancy leads to adverse health outcomes in offspring. However, the initial effects of maternal obesity (MO) on embryonic organogenesis have yet to be thoroughly examined. Using unbiased single-cell transcriptomic analyses (scRNA-seq), the effects of MO on the myogenic process is investigated in embryonic day 9.5 (E9.5) mouse embryos. The results suggest that MO induces systematic hypoxia, which is correlated with enhanced BMP signaling and impairs skeletal muscle differentiation within the dermomyotome (DM). The Notch-signaling effectors, HES1 and HEY1, which also act down-stream of BMP signaling, suppress myogenic differentiation through transcriptionally repressing the important myogenic regulator MEF2C. Moreover, the major hypoxia effector, HIF1A, enhances expression of HES1 and HEY1 and blocks myogenic differentiation in vitro. In summary, this data demonstrate that MO induces hypoxia and impairs myogenic differentiation by up-regulating BMP signaling within the DM, which may account for the disruptions of skeletal muscle development and function in progeny.
Quadruplex-and-Mg(2+) Connection (QMC) of DNA.

This work highlights a novel method of coupling of nucleic acids through formation of an extraordinary stable, specific and fully reversible quadruplex-and-Mg(2+) connection (QMC). QMC employs the monomolecular tetrahelical architecture of DNA and has two key components: (i) shape complementarity between QMC partners, which is introduced by specific modifications of the quadruplexes, and (ii) Mg(2+) ions. The on-rate of QMC formation is between 10(5)-10(6) M(-1) s(-1), while the off-rate is undetectable even at 80 °C. However, QMC dissociates rapidly upon removal of Mg(2+) ions (i.e., by EDTA). QMC is characterized by high specificity, as even a single-nucleotide modification of one of the connectors inhibits complex-formation. QMC has the potential to revolutionize biotechnology by introducing a new class of capture molecules with major advantages over traditional systems such as streptavidin-biotin. The advantages include reversibility, multiplexing, higher stability and specificity, longer shelf life and low cost.
Acid-base regulation of ion transport in rabbit ileum in vitro.

Abstract Changes in acid-base balance have a major influence on ion transport in the ileum. The goals of the present study were to delineate (a) the specific transport processes most affected by changes in acid-base metabolism, (b) the individual roles of pH, PCO 2 , and concentration of HCO 3 − in modulating ion transport, and (c) the relationship between acid-base sensitive and other ion-transport systems. Ion transport and electrical parameters were measured in rabbit ilea in vitro under short-circuit conditions with systematic variations of pH, PCO 2 , and concentrations of HCO 3 − . Increasing HCO 3 − concentrations, with constant PCO 2 and increasing pH, caused a decrease in electroneutral Na + and Cl − absorption. At 5 mmol/L HCO 3 − , net fluxes of Na + and Cl − were 5.9 ± 1.4 and 4.5 ± 1.1 μEq · cm −2 · h −1 , while at 50 mmol/L HCO 3 − , net Na + and Cl − fluxes were 0.7 ± 0.7 and 0.2 ± 0.6 μEq · cm −2 · h −1 . Transepithelial HCO 3 − -gradient experiments suggested that serosal HCO 3 − was the principal factor. Changes in PCO 2 showed a complex biphasic response, increasing net Cl − flux as PCO 2 increased from 11–30 mm Hg in 5 mmol/L HCO 3 − ; net Na − flux increased as PCO 2 was changed from 36 to > 100 mm Hg in 22 mmol/L HCO 3 − . In contrast, increasing pH in a bicarbonate-free N -2-hydroxyethylpiperazine- N′ -2 = ethane sulfonic acid buffer did not significantly alter Na + transport. Acidbase stimulated Na + absorption was inhibited by 10 −3 mol/L amiloride, but not by bumetanide, consistent with the involvement of Na + -H + exchange rather than Na + -Cl − cotransport. Epinephrine did not increase Na + absorption under acid-base stimulated conditions, but glucose did, suggesting that the ratelimiting step for electroneutral absorptive processes under these conditions occurs at the apical rather than the basolateral membrane. Combining all experiments, a significant correlation existed between net flux of Na + and HCO 3 − concentration ( r = −0.72, P + and pH ( r = −0.68, P r = 0.72, P + -Cl − transport in rabbit ileum in vitro.
Cycle time reduction at a major Texas Instruments wafer fab

This paper highlights the strategic and tactical applications of simulation modeling and how it was used to reduce cycle time at a major Texas Instruments wafer fab.
Post-Adoption Service Needs of Families with Special Needs Children: Use, Helpfulness, and Unmet Needs

ABSTRACT This study was conducted to explore post-adoptive service needs of families adopting special needs children. In addition, the research examined the relationship of post-adoption service utilization to positive adoption outcomes. Two hundred forty-nine (N = 249) special needs adoptive families representing 373 children responded to a mailed survey as part of this study. Financial, medical, and dental supports, and subsidies emerged as the most frequently cited service needs. Reports of unmet needs included: counseling services and in-home supports (respite care, daycare and babysitting services). The receipt of financial supports, other supports such as social work coordination and legal services and informal supports (support groups for parents and children) were significantly associated with higher satisfaction with parenting. Unmet service needs in the form of counseling, informal supports, other supports, out of home placement needs, financial supports, and in-home supports were associated wit...
GSK-3α regulates production of Alzheimer's disease amyloid-β peptides

Alzheimer's disease is associated with increased production and aggregation of amyloid-β (Aβ) peptides1. Aβ peptides are derived from the amyloid precursor protein (APP) by sequential proteolysis, catalysed by the aspartyl protease BACE2, followed by presenilin-dependent γ-secretase cleavage3. Presenilin interacts with nicastrin4,5, APH-1 and PEN-2 (ref. 6), all of which are required for γ-secretase function. Presenilins also interact with α-catenin, β-catenin7,8 and glycogen synthase kinase-3β (GSK-3β)9,10,11, but a functional role for these proteins in γ-secretase activity has not been established. Here we show that therapeutic concentrations of lithium, a GSK-3 inhibitor12, block the production of Aβ peptides by interfering with APP cleavage at the γ-secretase step, but do not inhibit Notch processing. Importantly, lithium also blocks the accumulation of Aβ peptides in the brains of mice that overproduce APP. The target of lithium in this setting is GSK-3α, which is required for maximal processing of APP. Since GSK-3 also phosphorylates tau protein, the principal component of neurofibrillary tangles, inhibition of GSK-3α offers a new approach to reduce the formation of both amyloid plaques and neurofibrillary tangles, two pathological hallmarks of Alzheimer's disease.
On the Affective Challenges of Developing a Pedagogy of Teacher Education

This article reports on the affective challenges I experienced while attempting to develop a pedagogy of teacher education during my first three years in teacher preparation. Data were collected systematically over the course of the study in the form of written interpretive accounts of my experiences. Analysis of these accounts revealed how certain ongoing, and at times paradoxical, tensions influenced my thinking about my initial practices as a teacher educator. Even as I came to understand the content and pedagogy of my instruction in more sophisticated ways, I simultaneously exhibited fear of regression, displayed apathy or exhaustion, exhibited frustration and restlessness, and struggled to navigate interpersonal relationships with my students. The implications of these affective challenges for developing a pedagogy of teacher education are discussed and avenues for further research are considered.
Infusing legal issues into the social work curriculum

Abstract This article addresses the need for social work students to understand basic legal concepts and their application in social work. It begins with a review of recent literature on teaching law within the social work curriculum. It then reports on the authors' April 1991 survey of accredited MSW programs, which showed that few schools require MSW students to study law, but that curricula have little room to expand. Finally, the article describes a flexible approach to infusing legal content into existing social work courses by focusing on six legal precepts: the definition and regulation of practice; client issues; privacy; advocacy; conflict/liability; and precedents.
Transformation of 2-line ferrihydrite to 6-line ferrihydrite under oxic and anoxic conditions

Mineralogical transformations of 2-line ferrihydrite were studied under oxic and Fe3+-reducing conditions to establish the role, if any, of 6-line ferrihydrite (“well” organized ferrihydrite) in the reaction pathway and as a final product. In oxic experiments, concentrated suspensions (0.42 mol/L Fe3+ in 0.1 mol/L NaClO4) of freshly synthesized 2-line ferrihydrite, with and without 3% Ni2+, were aged at an initial pH = 7.2 (unbuffered and unadjusted) and 25 °C for more than three years. X-ray diffraction, transmission electron microscopy, and Mossbauer spectroscopy measurements were performed on the solids after different aging periods. The primary mineralogical products observed were 6-line ferrihydrite and goethite, with minor hematite. Aggregation and crystallization of the 2-line ferrihydrite liberated protons and depressed suspension pH, but coprecipitated Ni2+ retarded this process. The joint, interrelated effects of Ni and pH influenced both the extent of conversion of 2-line ferrihydrite and the identity of the major transformation products. Six-line ferrihydrite dominated in the Ni ferrihydrite suspension, whereas goethite dominated in the absence of Ni. Aggregation-induced crystallization of 2-line ferrihydrite particles seemed responsible for 6-line ferrihydrite formation. Mineralogical changes to Ni ferrihydrite under anaerobic conditions were investigated at circumneutral pH using the Fe3+-reducing bacterium Shewanella putrefaciens . Residual 6-line ferrihydrite dominated bioreduced samples that also contained goethite and magnetite. The conversion of 2-line ferrihydrite to 6-line ferrihydrite was considerably more rapid under anaerobic conditions. The sorption of biogenic Fe2+ apparently induced intra-aggregate transformation of 2-line ferrihydrite to 6-line ferrihydrite. Collectively, abiotic and biotic studies indicated that 6-line ferrihydrite can be a transformation product of 2-line ferrihydrite, especially when 2-line ferrihydrite is undergoing transformation to more stable hematite or magnetite.
Alpha chain crosslinking of human fibrin: Purification and radioimmunoassay development for two Aα chain regions involved in crosslinking

Abstract Rapid and efficient purification methods that include hydrophobic chromatography on Phenyl Sepharose CL-4B have been developed for the peptides that span residues 241–476 (CNBr VIII), and 518–584 (CNBr X) in the Aα chain of human fibrinogen. Amino acid analysis, NH 2 -terminal sequence determination, and SDS-PAGE indicated that greater than 95% purity of each peptide was achieved. Sensitive and specific radioimmunoassays capable of detecting antigen in the range of 0.1–10.0 pmol/ml have also been developed for CNBr VIII and CNBr X. These assays have been characterized and successfully applied in studies designed to localize the two COOH-terminal Aα chain regions in column effluents of CNBr-digested fibrinogen and crosslinked fibrin. When these immunoassays were used to study purified preparations of a high molecular weight, crosslink-containing CNBr derivative of α polymer, the data provided immunologic confirmation for the involvement of CNBr VIII and CNBr X in α chain crosslinking.
Heterogeneous degradation of carbon tetrachloride : Breaking the carbon-chlorine bond with activated carbon surfaces

Destruction of carbon tetrachloride was found to be 94% ± 1% at 300 °C for a single pass through activated carbon. Product analysis indicates that conversion was limited to low molecular weight gases. No formation of toxic halogenated organic compounds, such as phosgene, dioxins, dibenzo-p-dioxins, or dibenzofurans, were observed in the degradation process. Isotopic labeling experiments suggest that the activated carbon acts as a reagent and that carbon from the activated carbon may initiate the breaking of the carbon−chlorine bond in carbon tetrachloride.
A large neighborhood search heuristic for the longest common subsequence problem

Given a set S={S 1,?,S k } of finite strings, the k-Longest Common Subsequence Problem (k-LCSP) seeks a string L * of maximum length such that L * is a subsequence of each S i for i=1,?,k. This paper presents a large neighborhood search technique that provides quality solutions to large k-LCSP instances. This heuristic runs in linear time in both the length of the sequences and the number of sequences. Some computational results are provided.
Assessing the Role of the Courts in Addressing the Educational Problems Caused by Racial Isolation in School Finance Litigation

Since the separate-but-equal era, students attending schools with high concentrations of Black students have attempted to improve the quality of their educations through school finance litigation. Because of the negative effects of racial isolation, Black students might consider mounting school finance litigation to force states to explicitly address the problems experienced by school districts with high concentrations of Black students (Green, Baker, & Oluwole, 2008). This article assesses the role of the courts in remedying the disparities experienced by high-concentration Black school districts through school finance litigation. The first section provides a brief overview of prior attempts to challenge racial funding disparities in the federal courts. The second section discusses the importance of considering race in future school finance litigation. The third section assesses whether plaintiffs from high-concentration Black school districts can obtain equal educational opportunity through state courts.
The Sensitivity of Saturation Transfer Electron Paramagnetic Resonance Spectra to Restricted Amplitude Uniaxial Rotational Diffusion

Computational methods have been developed to model the effects of constrained or restricted amplitude uniaxial rotational diffusion (URD) on saturation transfer electron paramagnetic resonance (ST-EPR) signals observed from nitroxide spin labels. These methods, which have been developed to model the global rotational motion of intrinsic membrane proteins that can interact with the cytoskeleton or other peripheral proteins, are an extension of previous work that described computationally efficient algorithms for calculating ST-EPR spectra for unconstrained URD (Hustedt and Beth, 1995, Biophys. J. 69:1409-1423). Calculations are presented that demonstrate the dependence of the ST-EPR signal (V'(2)) on the width (Delta) of a square-well potential as a function of the microwave frequency, the correlation time for URD, and the orientation of the spin-label with respect to the URD axis. At a correlation time of 10 micros, the V'(2) signal is very sensitive to Delta in the range from 0 to 60 degrees, marginally sensitive from 60 degrees to 90 degrees, and insensitive beyond 90 degrees. Sensitivity to Delta depends on the correlation time for URD with higher sensitivity to large values of Delta at the shorter correlation times, on the microwave frequency, and on the orientation of the spin-label relative to the URD axis. The computational algorithm has been incorporated into a global nonlinear least-squares analysis approach, based upon the Marquardt-Levenberg method (Blackman et al., 2001, Biophys. J. 81:3363-3376). This has permitted determination of the correlation time for URD and the width of the square-well potential by automated fitting of experimental ST-EPR data sets obtained from a spin-labeled membrane protein and provided a new automated method for analysis of data obtained from any system that exhibits restricted amplitude URD.
Optical Modified Signed Digit Adder Using Polarization-Coded Symbolic Substitution

The design of a processor can vary considerably with the type of technology (optical or electronic, analog or digital), the number system, and the coding scheme used for the number representation. Binary number representation is accepted as the best suited for electronic computers. However, the delay due to carry propagation in binary arithmetic makes the binary number representation a very weak candidate for an optical processor that is inherently parallel. The modified signed digit (MSD) number representation satisfies the requirements of totally parallel addition using modular or identical units and allows the addition of any two numbers in three successive steps. In this paper, we show the design of a parallel optical adder based on MSD number representation using the method of symbolic substitution originally proposed by Karl-Heinz Brenner [Appl. Opt. 25(18), 3061-3064 (1986)] and Alan Huang [Proc. IEEE Int. Optical Computing Conf., pp. 13-17 (1983)]. Polarized light is used to code the inputs and outputs. We also discuss the use of this adder along with barrel shifters to efficiently implement multiplication.
A Longitudinal Assessment of Wall Shear Stress Variation on Arteriovenous Fistula Maturation

Arteriovenous (AV) fistula is the most preferred form of vascular access for end-stage renal disease patients. Acute changes in hemodynamics and in particular wall shear stress (WSS) immediately after fistula placement are followed by the dilation of the vasculature luminal area to recover the normal physiological condition before surgery. However, vasodilation in AV fistula is not well understood and thus, the major goal of this study is to assess the longitudinal effect of wall shear stress on fistula maturation. Six AV fistulae with curved (n = 3) and straight (n = 3) configurations are created between the femoral artery and vein of three Yorkshire pigs. Anatomical configuration and flow measurements are performed at 2D (D: days), 7D, and 28D post-surgery. It is shown that fistulae with relatively higher baseline axial WSS may result in better maturation as compared to the ones with lower levels of baseline axial WSS. This finding is novel and hasn’t been reported in previous studies. Moreover, it is found that the longitudinal variation of WSS is also of high importance in prediction of the maturation of AV fistula. Fistulae whose mean axial WSS decreases over time achieve larger mean area, and therefore, favorable remodeling, while an increasing trend of axial WSS is detrimental to fistulae maturation. Also, it is found that curved fistula as compared to the straight configuration results in larger luminal area over time and thus, is the preferred form of AV fistula.Copyright © 2011 by ASME
Skills Needed to Survive and Thrive as a Scholar in the 21st Century: Information, Knowledge, and Publication Management

The changes in the way our work is created, published, and disseminated have implications for our own professional development and require us to be aware of the necessary skills. In this article, I...
I Have a Solution to Share: Learning Through Equitable Participation in a Mathematics Classroom

Student participation is an issue of equity. Without participation there can be no learning. This study focuses on the participation (and therefore learning) of struggling students (those with individual education plans [IEPs]) during the implementation of a relational thinking routine in a third-grade inclusion classroom. Students with IEPs often initially used direct modeling with linking cubes as a resource for presenting their thinking. In this way, they were able to demonstrate their ability to think relationally. As the year progressed, these students, who had earlier been reluctant to share and had done so only by using several of the resources that the participation structure of the routine provided, often showed a growth in their abilities to explain their thinking verbally.
The Public Decides about Weather Modification

Planned weather modification is a potentially significant phenomenon being introduced in many area of this and other countries. Evidence is beginning to accumulate suggesting that where organized r...
GABRIEL: Gis Activity-Based tRavel sImuLator. Activity Scheduling in the Presence of Real-Time Information

A series of travel simulators have been developed in the past two decades under the Intelligent Transportation Systems (ITS) umbrella. They have addressed issues such as reactions to advisory radio and variable message signs, use of navigation systems, route diversion, and mode choice. The objective of this paper is to present the design and implementation of a different kind of travel simulator. GABRIEL (Gis Activity-Based tRavel sImuLator) has as a foundation the activity-based approach and makes use of geographic information systems (GIS) as a development environment. The simulation scenario consists of a commute trip where two activities take place. En-route to the first destination, congestion occurs and subjects are requested to take action based on a set of alternatives. The simulator provides re-routing, destination substitution, dynamic geographic information and real-time information to aid users in their decision-making process. As a result it helps subjects in developing their ability to adapt given a particular scenario and allow researchers in understanding trip making, activity rescheduling, and the decision-making process from a comprehensive perspective.
Direct lineage reprogramming of post-mitotic callosal neurons into corticofugal neurons in vivo

Once programmed to acquire a specific identity and function, cells rarely change in vivo. Neurons of the mammalian central nervous system (CNS) in particular are a classic example of a stable, terminally differentiated cell type. With the exception of the adult neurogenic niches, where a limited set of neuronal subtypes continue to be generated throughout life, CNS neurons are born only during embryonic and early postnatal development. Once generated, neurons become permanently post-mitotic and do not change their identity for the lifespan of the organism. Here, we have investigated whether excitatory neurons of the neocortex can be instructed to directly reprogram their identity post-mitotically from one subtype into another, in vivo. We show that embryonic and early postnatal callosal projection neurons of layer II/III can be post-mitotically lineage reprogrammed into layer-V/VI corticofugal projection neurons following expression of the transcription factor encoded by Fezf2. Reprogrammed callosal neurons acquire molecular properties of corticofugal projection neurons and change their axonal connectivity from interhemispheric, intracortical projections to corticofugal projections directed below the cortex. The data indicate that during a window of post-mitotic development neurons can change their identity, acquiring critical features of alternative neuronal lineages.
Categorical system theory and the phenomenological calculus

The mathematical theory of categories is used as a tool in the description of the structure and function of natural systems. The connections between the category of natural systems, with observables and dynamics, and the phenomenological calculus of response tensors, duality- and adjoint-invariance diagrams are established. The unified theory is applied to the analysis of hierarchies, pattern generation and the structure and dynamics of proteins.
Exited state electron and energy transfer in molecular assemblies

Abstract The metal-to-ligand charge transfer (MLCT) excited states of polypyridyl complexes of the d 6 ions Ru(II), Os(II), and Re(I) have provided the basis for many studies on photochemical electron and energy transfer. In this account, a brief review of photochemical electron transfer by [Ru(bpy) 3 ] 2+* is given, followed by an update on MLCT excited state molecular and electronic structure, and an introduction to photochemical electron and energy transfer in molecular assemblies. The majority of the account is devoted to describing the evolution of two approaches to preparing complex molecular assemblies for the study of photochemical electron and energy transfer both inspired by the demands of achieving artificial photosynthesis. The first approach involves the derivatization of preformed polystyrene by added chromophores and electron or energy transfer donors or acceptors and three generations of polymers differing in polymer content and linkage strategies. The second approach has exploited solid-state peptide synthesis and the stepwise preparation of oligopeptides with spatial control of added groups and alignment on the resulting helical scaffolds.
Analysis of p‐aminosalicylic acid, its salts and dosage forms, by nonaqueous titration

Abstract p -Aminosalicylic acid, its salts, and its dosage forms are determined by visual or potentiometric titration with sodium methoxide in benzene-methanol using dimethylformamide as the titration solvent. p -Aminosalicylic acid and its decomposition product m -aminophenol may be differentiated with this titration system. Salts of p -aminosalicylic acid are converted to the acid form by ion-exchange chromatography prior to titration. The procedure is applied to several dosage forms.
Motional averaging of ions for control of magnetron motion in fourier transform ion cyclotron resonance open-geometry trapped-ion cells

Abstract Open trapped-ion cell geometries have been utilized extensively in external source Fourier transform ion cyclotron resonance (FTICR) applications. A fundamental difference between open and closed cells is that in open cells the radial electric field undergoes a shift in orientation as a function of z displacement. Ions confined near the cell radial centerline in the z center of the cell experience an outward-directed destabilizing field gradient force whereas ions at large axial amplitude encounter an inward-directed stabilizing force. Radial destabilization at the center of the cell is compensated by radial stabilization at increased z amplitude through motional averaging along the z axis. This suggests that conditions can be created in the open cell for which deleterious effects due to magnetron motion can be minimized. This contrasts with the closed cell, for which the radial electric field is outward directed at every point along the z axis. This unique aspect of the open geometry trapped-ion cell is demonstrated to reduce radial drift by control of the axial amplitude of the ion cloud. Suspended trapping and resonance excitation of the trapping motion are used to increase the ion z amplitude. For ions with increased z amplitude, the effective cyclotron frequency (ω+) approaches the unperturbed cyclotron frequency (ωc) with virtual elimination of the magnetron frequency (ω−). This is observed in benzene for which ω+ is observed only 16 Hz below ωc. Additionally, resonant excitation at the trapping frequency (2ωt) was used to increase the axial extent of the ion cloud, raising cyclotron frequency up to 550 Hz. The cyclotron frequency shift also occurs without peak broadening. This radial trajectory stabilizing characteristic of the open cell was maximized using shallow trapping wells in nested traps that yielded cyclotron frequency shifts 300 Hz higher than the unperturbed cyclotron frequency. This is a result of longer ion residence time at the turnaround points in the trapping well (where the inward-directed radial electric field is greatest in magnitude), increased axial extent of the ion cloud due to ion Coulomb repulsion, and the shallower trapping well. The presence of large numbers of charges (electrons, negative ions) in the outer trapping wells of polarity opposite the positive ions in the central trapping well may compensate for the depression of cyclotron frequency due to space charge.
Comparison of detoxification enzyme systems in Argyrotaenia citrana (Lepidoptera: Tortricidae) and the ectoparasite, Oncophanes americanus (Hymenoptera: Braconidae).

Comparative toxicity tests showed adult, late larvae, and early larvae of the host tortricid, Argyrotaenia citrana (Fernald), less susceptible to propoxur than similar life stages of the braconid ectoparasite Oncophanes americanus. However, propoxur was not less synergized by piperonyl butoxide (PBO) for all of these same life stages of the host versus the parasite. Levels of aldrin epoxidase were low in life stages of both species when measured in whole-body assays; however, gut assays of host larvae demonstrated high levels of this enzyme. Higher levels of MFO (cytochrome P-450 monooxygenase) activity were observed when a tyrosinase inhibitor was added to host aldrin epoxidation reactions, but not in the parasite test. Considering data from whole-body, gut, and inhibitor tests, we concluded that aldrin epoxidase levels were probably higher in the lepidopteran life stages than in the braconid life stages. Similar levels of trans -epoxidase hydrolase, glutathione transferase, and general esterases, but lower levels of cis -epoxide hydrolase were found in the lepidopteran host as opposed to the braconid life stages. The consistently higher ratios of trans/cis epoxide hydrolase in the herbivore versus entomophage are similar to data found earlier in detoxification comparisons between several species of prey and predators. The epoxide hydrolase enzyme system may be an appropriate target site for exploiting selectivity differences between pests and natural enemies.
The synthetic 87–99 peptide of myelin basic protein is encephalitogenic in Buffalo rats

A synthetic peptide corresponding to residues 87-99 (S87-99) of myelin basic protein (BP) induced the proliferation of an encephalitogenic, BP-specific T cell line selected in vitro from inbred Buffalo-strain rats (RT1b). Active immunization with guinea pig (GP)-BP or S87-99 in complete Freund's adjuvant (CFA) and intravenous pertussigen induced acute experimental autoimmune encephalomyelitis (EAE) 10-12 days after immunization. Fifty percent of recovered rats developed a single relapse 17-21 days after immunization. T lymphocytes selected in vitro with S87-99 transferred acute, non-relapsing EAE into naive recipients. Histological examination during acute EAE revealed foci of inflammatory cells associated with demyelination in the spinal cords and peripheral nerve roots. Thus, as in several other rodent strains, the 87-99 region of BP is antigenic and encephalitogenic in the inbred Buffalo-strain rat. Additionally, the 87-99 sequence of GP-BP was predicted to be antigenic by two different methods. These results suggest that the 87-99 region of BP, which is highly conserved among mammalian species, may be widely encephalitogenic due to antigen-intrinsic properties.
Biological structure of lignocellulose and its degradation in the rumen

Abstract Variations in lignification and digestibility occur among the lignocelulosic fibres in forages. Tissues which stain positive for lignin with acid phloroglucinol (i.e., mestome sheath and xylem in grass leaf blades; epidermis, sclerenchyma ring and xylem in grass stems) are totally inert to microbial attack and attachment for the most part. Conversely, tissues which stain for lignin with the chlorine sulphite test (i.e., sclerenchyma in grass leaves and parenchyma in grass stems) are not as resistant to attack, although these tissues are rigid and poorly degraded. Chemical treatment appears to make the chlorine sulphite fibre available for microbial attack, but not the acid phloroglucinol fibre. It is suspected that the predominant phenolic monomers in these two types of lignin differ and this difference influences the availability of the fibres. Polymeric lignin binds structural carbohydrates, rendering the sugars unavailable for microbial fermentation. In addition, low molecular weight phenolic compounds (e.g., phenolic acids) also appear to bind glucans and xylans in an undigestible complex. p-Coumaric acid seems to be especially detrimental to forage digestibility and this acid is also toxic to remen micro-organisms at lower concentrations than other acids. Brown midrib mutants in maize and sorghum are higher in digestibility than their normal counterparts and have lower lignin contents and less p-coumaric acid. In general, rumen bacteria and fungi colonize rigid plant tissue prior to degradation and their enzymes are then able to degrade the structural carbohydrates. Rumen fungi are better able to degrade leaf blade sclerenchyma than the bacteria and under specific conditions can slightly degrade xylem fibre, indicating a greater potential to break down lignocellulosic material.
Ice erosion of a sea-floor knickpoint at the inner edge of the stamukhi zone, Beaufort Sea, Alaska

Abstract In 1981 and 1982, detailed bathymetric and side-scan sonar surveys were made of an area of the sea floor north of Prudhoe Bay, Alaska, to study the changing characteristics of the seabed at the inner boundary of the stamukhi zone, the coast-parallel zone of grounded ice ridges that occurs in water depths between 15 and 50 m in the arctic. The fathograms and sonographs resolved 10-cm features and electronic navigation gave relocations accurate to about 10 m. Year after year an ice boundary develops at the inner edge of the stamukhi zone where major shear and pressure deformation occur in about the same location. Associated with this ice boundary, the bathymetry shows a pronounced break in slope — the knickpoint — on the shelf profile at about 20 m depth. The 2–3 m-high knickpoint is cut in a consolidated gravelly mud of pre-Holocene age. A well-defined gravel and cobble shoal a few meters high usually occurs at the inshore edge of the knickpoint. The sonograph mosaic shows that seaward of the knickpoint, ice gouges saturate the sea floor and are well defined; inshore the gouges are fewer in number and are poorly defined on the records. Few gouges can be traced from the seaward side of the knickpoint across the shoals to the inshore side of the knickpoint. Studies of ice gouging rates in two seabed corridors that cross the stamukhi zone reveal the highest rates of gouging seaward of the knickpoint. We believe that the knickpoint results from ice erosion at the inner boundary of the stamukhi zone. Intensified currents associated with this boundary winnow away fine sediments. Ice bulldozing and currents shape the shoals, which perch atop the knickpoint. The knickpoint helps to limit ice forces on the seabed inshore of the stamukhi zone.
Principles for the Prevention and Intervention of Mathematics Difficulties

Three levels of prevention and intervention in the area of mathematics are addressed: (a) primary prevention focusing on universal design, (b) secondary prevention focusing on adaptations, and (c) tertiary prevention focusing on intensive and explicit contextualization of skills-based instruction. The purpose of this paper is to identify and discuss principles of prevention and intervention in the area of mathematics. First, we identify research-based principles associated with primary prevention. Second, we turn our attention to secondary prevention, with a focus on prereferral intervention. We identify principles that serve to differentiate primary and secondary prevention and specify instructional variables that are promising for use within a secondary prevention mode. Finally, we discuss intervention. We identify principles of effective intervention, which include individually referenced decision making, instructional intensity, and deliberate contextualization of skills-based instruction.
Prognostic implications of ploidy and proliferative activity in human solid tumors.

Ploidy and cell cycle compartment distribution were measured by DNA flow cytometry in 261 patients with a variety of different tumors. Eighty-one percent of all tumors were aneuploid, and 72% were hyperdiploid. Ploidy levels spanned a wide range from hypodiploid (maximum 30% < diploid controls) to hyperoctaploid (440% in excess of diploid controls) with mean and median values coinciding at a near-triploid DNA content. The proportion of cells with G1 DNA content decreased with increasing hyperdiploid abnormality. While unrelated to biopsy site and to a number of host factors such as age, sex and race, both ploidy and cytokinetic parameters were markedly affected by histopathologic diagnosis. Patients with metastatic lung, breast, and GI cancer had higher ploidy levels than individuals with the corresponding primary tumors. Ploidy (except for one patient) remained constant, and G1/0 proportions showed only minor variation by disease site and over a median observation time of 6 months. Prognostic factor analysis was performed in the subgroup of patients studied within 6 months from diagnosis. The adverse impact of low tumor G1/0 proportion on survival was lost as the proportional hazard analysis was extended to include diagnostic subgroups. Accounting for histopathologic diagnosis, stage of disease, ploidy, and the proportion of tumor G1/0 cells, the following sequence of adverse prognostic factors in order of their relative ranks was established: (1) absence of breast cancer (p = 0.001), (2) hypertriploid DNA index (p = 0.049), and (3) presence of metastatic disease (p = 0.079). Our study demonstrates that DNA content-derived information on instrinsic tumor cell features pertaining to cytogenetics and cytokinetics may provide an objective means of biologically relevant cancer classification.
Jeroo: a tool for introducing object-oriented programming

Jeroo is a tool that has been developed to help students in beginning programming courses learn the semantics of fundamental control structures, learn the basic notions of using objects to solve problems, and learn to write methods that support a functional decomposition of the task. Jeroo is similar to Karel the Robot and its descendants, but has a narrower scope than Karel's descendants and has a syntax that provides a smoother transition to either Java or C++. Jeroo has been class tested at Northwest Missouri State University, and has proven to be an effective tool for working with students in a beginning programming class. Jeroo and user documentation are available at http://www.nwmissouri.edu/~sanders/Jeroo/Jeroo.html.
TEST INSTRUCTIONS AND IDENTIFICATION OF CREATIVE SCIENTIFIC TALENT

The performance of 16 scientists told to “Be creative” in working on three open-ended tasks was compared with the performance of 15 scientists given neutral instructions. Under neutral instructions...
Protective effects of a soy diet in preventing obesity-linked renal disease

Protective effects of a soy diet in preventing obesity-linked re- Health problems associated with obesity are the devel- nal disease. opment of insulin resistance and glucose intolerance, Background. Hypertension, hyperlipidemia, hyperfiltration, hypertension, hypercholesterolemia, and hypertriglycer- hyperinsulinemia, glomerular hypertrophy, and ultimately glo- idemia (1-13). In the kidney these are all risk factors merular injury and renal failure are associated with obesity in for the development of glomerular injury and obesity is the Zucker rat. Evidence from other laboratories suggests that soy protein might offer renal protection. associated with a marked acceleration of age-associated Methods. At five weeks of age obese rats were placed on diets glomerular injury (1, 8, 14), particularly in the male rat containing either soy or casein as a protein source and studied (2). The obese Zucker rat has a missense mutation of until 24 weeks of age. At six weeks of age and every four weeks the brain leptin receptors leading to a greater appetite thereafter, 24-hour urine collections were obtained along with measurements of systolic blood pressure (tail cuff) and blood (15) and these animals develop all of the problems seen from the tail vein. At the end of the study the kidneys were in human obesity. Glomerular filtration rate (GFR), glo- fixed and sectioned for histology.