cssi/SciSciGPT-SciSciNet huggingface dataset:
Development of R7BP inhibitors through cross-linking coupled mass spectrometry and integrated modeling

Protein-protein interaction (PPI) networks are known to be valuable targets for therapeutic intervention; yet the development of PPI modulators as next-generation drugs to target specific vertices, edges, and hubs has been impeded by the lack of structural information of many of the proteins and complexes involved. Building on recent advancements in cross-linking mass spectrometry (XL-MS), we describe an effective approach to obtain relevant structural data on R7BP, a master regulator of itch sensation, and its interfaces with other proteins in its network. This approach integrates XL-MS with a variety of modeling techniques to successfully develop antibody inhibitors of the R7BP and RGS7/Gβ5 duplex interaction. Binding and inhibitory efficiency are studied by surface plasmon resonance spectroscopy and through an R7BP-derived dominant negative construct. This approach may have broader applications as a tool to facilitate the development of PPI modulators in the absence of crystal structures or when structural information is limited. Adikaram et al perform protein cross-linking coupled with mass spectrometry and structural modelling to obtain a structure of R7BP, a master regulator of itch. They identify domains interacting with R7BP partners RGS7 and Gβ5 and develop R7BP antibodies that obstruct its binding to the RGS7/Gβ5 duplex.
Spatial Sustainability Assessment Framework for Civil Infrastructure Condition

Sustainability has become a prominent concept in technical, societal, and political discourse around the world and serves as a major guiding force for political actions and future societal development. Various methods have been proposed for sustainability assessment. However, only a few of them take into account all aspects of sustainability, as well as their inter-linkages and dynamic changes with time. Civil infrastructure, as the fundamental facilities and systems serving a country, city, or region, is critical to sustainable community development. Evaluating sustainability is thus key to ensuring that appropriate evaluations are integrated during the development of civil infrastructure. In order to facilitate these evaluations, it is valuable to build a framework to assess the sustainability of civil infrastructure and to provide information for the planning, design, investment and construction of new civil infrastructure systems and the rehabilitation, reuse or optimization of existing systems. In this paper, the authors proposed a spatial assessment framework for evaluating the sustainability of civil infrastructure. This framework provides a scientific based and comprehensive method to assess the sustainability of civil infrastructure at different spatial and temporal scales. It also provides multiple ways to present the sustainability assessment results clearly and effectively, so that it can assist decision-makers in determining which actions should be taken in an attempt to make civil infrastructure sustainable. The proposed framework is data-driven and can easily be used by researchers in other disciplines for other objectives.
Improving Reproducibility in Earth Science Research

Earth scientists need software technology that better integrates legacy data with current and future processing capabilities so they can assess and reproduce their colleagues' results.
Learning from Non-Causal Models

This paper defends the thesis of learning from non-causal models: viz. that the study of some model can prompt justified changes in one’s confidence in empirical hypotheses about a real-world target in the absence of any known or predicted similarity between model and target with regards to their causal features. Recognizing that we can learn from non-causal models matters not only to our understanding of past scientific achievements, but also to contemporary debates in the philosophy of science. At one end of the philosophical spectrum, my thesis undermines the views of those who, like Cartwright (Erkenntnis 70:45–58, 2009), follow Hesse (Models and Analogies in Science, Notre Dame, University of Notre Dame Press, 1963) in restricting the possibility of learning from models to only those situations where a model identifies some causal factors present in the target. At the other end of the spectrum, my thesis also helps undermine some extremely permissive positions, e.g., Grune-Yanoff’s (Erkenntnis 70(1):81–99, 2009, Philos Sci 80(5): 850–861, 2013) claim that learning from a model is possible even in the absence of any similarity at all between model and target. The thesis that we can learn from non-causal models offers a cautious middle ground between these two extremes.
Abstract IA01: Single cell analysis of CRISPR T cells

CRISPR-Cas9 gene editing provides a powerful tool to enhance the natural ability of human T cells to fight cancer. We report a first-in-human phase 1 clinical trial to test the safety and feasibility of multiplex CRISPR-Cas9 editing to engineer T cells in three patients with refractory cancer. Two genes encoding the endogenous T cell receptor (TCR) chains, TCRα (TRAC) and TCRβ (TRBC), were deleted in T cells to reduce TCR mispairing and to enhance the expression of a synthetic, cancer-specific TCR transgene (NY-ESO-1). Removal of a third gene encoding programmed cell death protein 1 (PD-1; PDCD1), was performed to improve antitumor immunity. Adoptive transfer of engineered T cells into patients resulted in durable engraftment with edits at all three genomic loci. Although chromosomal translocations were detected, the frequency decreased over time. Modified T cells persisted for up to 9 months, suggesting that immunogenicity is minimal under these conditions and demonstrating the feasibility of CRISPR gene editing for cancer immunotherapy. Citation Format: Edward Stadtmauer, Joseph Fraietta, Ansuman Satpathy, Carl H. June. Single cell analysis of CRISPR T cells [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr IA01.
Barriers to the Initiation of Home Modifications for Older Adults for Fall Prevention

Introduction:Home modifications are associated with decreased risk for falls and facilitate safe aging in place. The purpose of this study was to identify barriers to procurement of home modificati...
Interpretable OR for High-Stakes Decisions: Designing the Greek COVID-19 Testing System (preprint)

In the summer of 2020, in collaboration with the Greek government, we designed and deployed Eva – the first national scale, reinforcement learning system for targeted COVID-19 testing. In this paper, we detail the rationale for three major design/algorithmic elements: Eva’s testing supply chain, estimating COVID-19 prevalence, and test allocation. Specifically, we describe the design of Eva’s supply chain to collect and process thousands of biological samples per day with special emphasis on capacity procurement. Then, we propose a novel, empirical Bayes estimation strategy to estimate COVID-19 prevalence among different passenger types with limited data and showcase how these estimates were instrumental for a variety of downstream decision-making. Finally, we propose a novel, multi-armed bandit algorithm that dynamically allocates tests to arriving passengers in a non-stationary environment with delayed feedback and batched decisions. All of our design and algorithmic choices emphasize the need for transparent reasoning to enable human-in-the- loop analytics. Such transparency was crucial to building trust and buy-in among policymakers and public health experts in a period of global crisis.
Initiation of the Cyclooxygenase Reaction via Peroxidase Enzyme Intermediates

Prostaglandin H synthase has two distinct catalytic activities: the cyclooxygenase activity generates a hydroperoxide PGG2, from arachidonic acid; the peroxidase activity reduces hydroperoxides to the corresponding alcohols like PGH2. The synthase is thus capable of both producing and destroying hydroperoxides. The metabolic progeny of PGH2 (prostaglandins, prostacyclins, thromboxanes) are known to affect many aspects of tumor growth and metastasis (reviewed in Ref. 1).
Chapter 16 – Radioactive Waste

This chapter presents a background discussion of the interaction of ionizing radiation with matter, as well as a discussion of the environmental effects of nuclear generation of electricity and of radionuclides that are accessible to humans in the environment. The chapter focuses on radioactive waste as an environmental pollutant, discusses the impact of ionizing radiation on environmental and public health, and summarizes engineering options available today for the management and disposal of radioactive waste. Biological effects of ionizing radiation may be grouped as somatic and genetic. Radiation sickness (circulatory system breakdown, nausea, hair loss, and sometimes death) is an acute somatic effect occurring after very high exposure, as from a nuclear bomb, intense radiation therapy, or a catastrophic nuclear accident. Other somatic effects include decrease in organ function and carcinogenesis. Chronic effects may include both somatic and genetic effects that may occur because ionizing radiation damages the genetic material of the cell. Radioactive wastes may contaminate air, water, soil, and vegetation. Radionuclides released and transported through the air enter the human body by the atmospheric dispersion and inhalation pathway. Radionuclides also move from deposition or contamination of ground surfaces into the human food chain. Most radioactive waste can be treated only by isolating it from the accessible environment until its radioactivity no longer poses a threat. A two-stage barrier system is used for the geologic disposal of high-level radioactive waste. Management and disposal of low-level radioactive waste include impervious packaging, compaction, incineration, and stabilization in asphalt or cement matrix.
Epidural analgesia and its effects on the "normal" progress of labor.

Abstract The effects of epidural analgesia on the duration of labor have been a controversal subject since its increased use in recent years. A total of 598 patients receiving this form of analgesia were studied as to progress in labor and eventual outcome. The mean cervical changes during epidural analgesia with a single drug, bupivacaine, 0.125 per cent, with epinephrine, 1:200,000, have been calculated. The labor curves are characterized by constant acceleration in dilatation without deceleration at approximately the same rate for nulliparous and multiparous patients after dilatation of 5 cm. has been reached. Examination of maternal and fetal profiles failed to demonstrate any consistent variables that produce abnormal labor.
Medical Simulation: Utilize, Inspire, Embrace , Verify

(Extract) I too have experienced the enthusiasm of an individual seeking to learn a new task. More years ago than I care to elaborate and before the proliferation of health care simulators, I visited the ER with a painful ache and had an interesting training experience with a youthful ER nurse. She looked around possibly to see if anyone could help or oversee her and noting that everyone else was busy and my veins were attractively prominent, she promptly asked if I would mind if she practiced drawing blood. Under duress due to pain perhaps, I agreed. I am not sure if the art and science of phlebotomy includes the part of chasing the vein with the needle under the epidermis or whether it is at the 3rd or 4th stick that phlebotomy starts to become something akin to torture but thankfully after the 4th stick, I received an apology and a surrender from the novice nurse and we waited for a more experienced practitioner. That day I wished for a better way and hoped that no one else would need to endure the painful or even perilous results of such inexperience. ...
Building Disaster Resilience: Steps toward Sustainability

Disaster losses continue to escalate globally and in many regions human losses (death, injury, permanent displacement) often exceed the economic toll. Current disaster policies are reactive with a short-term focus―respond and rebuild as quickly as possible and in the same way after the event. Such policies ignore the longer-term approach of building disaster-resilient communities, in which investments made now show financial and social returns later by reducing the impact of disasters. This article provides a vision for resilient nations in 2030 based on three recent policy reports. It highlights the necessary steps to wards achieving sustainability using the lens of disaster resilience as the pathway towards strengthening communities' ability to prepare and plan for, absorb, respond to, and recover from present and future disasters.
Extending the Budget Enforcement Act: Revision of PAYGO Rules Necessary for Better Tax Policy

In the Federal budget process, the pay-as-you-go (PAYGO) principle as set forth in the Budget Enforcement Act (BEA) requires that all enacted direct spending and tax legislation for a fiscal year must be deficit-neutral in the aggregate. PAYGO rules have been generally praised by proponents for restraining new spending and for encouraging legislators to provide reasons for their budget decisions. Opponents have pointed to unconstrained federal spending, and frequent budget artifices as examples of the failure of PAYGO. In addition, the PAYGO rules raise excessive procedural hurdles for tax relief legislation. Numerous scholars and practitioners in the field have addressed the pros and cons of PAYGO, including the need for changing PAYGO rules or eliminating them altogether. The current PAYGO provisions are set to expire with the BEA after fiscal year 2002. This paper concludes that if the PAYGO requirements as set forth in the Budget Enforcement Act are to be extended, then at a minimum a compromise approach be adopted to reform PAYGO: to permit dynamic revenue analysis of tax legislation, or at the very least allow legislation providing appropriate tax deferrals (such as contributions to IRAs) to be exempt from PAYGO requirements. This paper discusses budget enforcement and the PAYGO concept, then identifies the problems associated with PAYGO and how PAYGO often leads to counterproductive tax policy decisions. The paper also reviews the mixed success of PAYGO in controlling federal spending. The paper then demonstrates how a reform that would allow legislation providing appropriate tax deferral to be exempt from PAYGO rules would allow both fiscal responsibility and good tax policy by promoting incentives for taxpayers to save and invest, and potentially increasing revenue to the government.
Hybrid particle-based approach for the simulation of semiconductor devices: The full-band cellular automaton/Monte Carlo method

We present a review of the particle-based methods used for the simulation of semiconductor devices. A full-band hybrid cellular automaton/Monte Carlo code far simulation of electron and hole transport in Si and GaAs is presented as well. In this implementation, the entire first Brillouin zone is discretized using a non-uniform mesh in k-space, and a transition table is generated between all initial and final states on some regions of the Brillouin zone, greatly simplifying the final state selection of the conventional Monte Carlo algorithm. Together with its impressive performance, this method allows for fully anisotropic scattering rates within the full-band scheme, at the cost of increased memory requirements for the transition table itself. Good agreement is obtained between the hybrid model and previously reported results for the velocity-field characteristics and high field distribution function, which illustrate the potential accuracy of the technique. Adaptation of the algorithm for parallel computing is discussed as weil.
Cognitive perspectives on the development of memory.

Publisher Summary This chapter deals with age-related changes found in memory. The early knowledge of memory development is quickly put to use in tests of intelligence; thus, memory is considered a part of the larger sphere of intellectual functioning. However, memory is treated more or less as a unitary construct. Experimental psychology recognize memory performance as, to a large extent, a function of the technique of measurement; but not until the advent of the information-processing models was memory pursued vigorously as a construct in its own right. The information-processing model suggests critical points in the memorial process where developmental changes occur—initial encoding, acquisition, storage, and retrieval—and where this process may be linked to other important aspects of cognition. Initial encoding involves language even in preschool-age children. Semantic information is coded for storage in a wide range of experimental tasks across a wide age range.
Angular signatures for galactic halo weakly interacting massive particle scattering in direct detectors: Prospects and challenges

Angular sensitivity can provide a key additional tool which might allow unambiguous separation of a signal due to galactic halo WIMPs from other possible backgrounds in direct detectors. We provide a formalism that allows a calculation of the expected angular distribution of events in terrestrial detectors with angular sensitivity for any incident distribution of galactic halo dark matter. This can be used as an input when studying the sensitivity of specific detectors to halo WIMPs. We utilize this formalism to examine the expected signature for WIMP dark matter using a variety of existing analytic halo models in order to explore how uncertainty in the galactic halo distribution impact on the the event rates that may be required to separate a possible WIMP signal from terrestrial backgrounds. We find that as few as 30 events might be required to disentangle the signal from backgrounds if the WIMP distribution resembles an isothermal sphere distribution. On the other hand, for certain halo distributions, even detectors with fine angular resolution may require in excess of a 100--400 events to distinguish a WIMP signal from backgrounds using angular sensitivity. We also note that for finite thresholds the different energy dependence of spin-dependent scattering cross sections may require a greater number of events to discern a WIMP signal than for spin independent interactions. Finally, we briefly describe ongoing studies aimed at developing strategies to better exploit angular signatures, and the use of N-body simulations to better model the expected halo distribution in predicting the expected signature for direct WIMP detectors.
p, d and f bonds in elemental solids

Abstract We study the energy gained for simple crystal structures by occupying the lower portion of tight-binding bands arising from one shell of atomic orbitals. We see that a Friedel model, based upon a rectangular density of states and the second moment of the bands, gives a reasonable account of the cohesive energy. It also predicts an equilibrium spacing proportional to the fourth root of the coordination but gives total energies independent of coordination. This depended upon an interatomic repulsion assumed to be proportional to the square of the interorbital coupling. When the variation in the repulsion is more rapid, as it tends to be lower in the periodic table, and in the simple metals, larger coordinations and simple close-packed structures are favoured. Going beyond this approximation, we find the energy lower when weakly coupled bond orbitals can be constructed, as for the [sgrave] bonds in tetrahedral semiconductors. Applying this correction to half-filled p bands favours the formation of r...
Hexamethylmelamine, methotrexate and 5-fluorouracil (HMF) for progressive ovarian carcinoma during therapy with cis-platinum, cyclophosphamide ± doxorubicin

Hexamethylmelamine, methotrexate, and 5-fluorouracil (HMF) is a second-line chemotherapy for patients with ovarian carcinoma refractory to platinum-based regimens. Two of 15 patients with tumor progression treated with HMF alone had objective complete responses while one had a 12-month disease-free interval (DFI). Among 8 patients treated with HMF and either intraperitoneal chromic phosphate and/or alternating platinum-based chemotherapy following second-look surgery which documented persistent carcinoma, 3 have experienced disease-free intervals of 19, 27, and 42 months. However, no one has been cured or had a long-term remission after HMF therapy alone.
A field-ion microscopy study of chemically vapour deposited molybdenum and tungsten thin films

Abstract Films of molybdenum and tungsten, 0–500 A thick have been chemically vapour deposited onto field-ion emitter substrates by the thermal decomposition of the appropriate hexacarbonyl. Epitaxial molybdenum films on tungsten substrates could be progressively field evaporated to reveal the interface. Molybdenum film structure and purity were found to be dependant on deposition temperature, previous substrate thermal rearrangement and vacuum conditions. Tungsten films on field evaporated molybdenum substrates were of high purity, epitaxial, and comparatively insensitive to deposition conditions whilst those on platinum were non-epitaxial but with a pronounced 〈211〉 texture.
Crafting Qualitative Research Articles on Marriages and Families

This paper aims to assist those who do qualitative research in the field of marriage and family to reduce the number of rejections received in response to article submissions. Recurring shortcomings identified by reviewers and suggestions made to authors about revising papers are organized using headings traditionally used in a research article—introduction and literature review, method, results, and discussion. Considerations stemming from the fact that data on marriages and families are produced largely through interviews also are addressed.
Autonomy or Institution? Origins and Development of Women's Studies in the United States and Germany, 1965-1981.

Die Entstehung von �Women's Studies� als akademische Disziplin wurde in den Vereinigten Staaten und Deutschland entscheidend beeinflust durch die sich in diesen Landern formierenden Frauenbewegungen. �Women's Studies �-Programme bildeten sich zunachst in den Vereinigten Staaten. Da es dort bereits eine betrachtliche Anzahl von Frauen unter den Lehrenden an den Hochschulen gab, die zum Teil ein feministisch motiviertes Interesse an diesem neuen Feld hatten, lies sich von Anfang an eine Verankerung der Programme an den Universitaten erreichen. Inspiriert durch die amerikanische Entwicklung widmeten sich in den fruhen siebziger Jahren auch in Deutschland feministische Wissenschaftlerinnen der Forschung und Lehre uber Frauen. Ihre Situation unterschied sich aber ganz wesentlich von der ihrer amerikanischen Kolleginnen. Zum einen gab es weniger Frauen im Lehrkorper der meisten Universitaten, insbesondere unter den Professoren, zum anderen war das intellektuelle Klima an vielen Fakultaten zu diesen Zeitpunkt stark durch marxistische Einflusse gepragt und feministischen Anschauungen wenig zutraglich. Aus diesem Grund unterrichteten viele feministische Wissenschaftlerinnen zunachst auserhalb der Hochschulen an Volkshochschulen oder in Gemeindeein-richtungen. Erst ab 1980 entstanden konkrete Plane fur die Durchfuhrung von Frauenforschung an den Universitaten. Diese stiesen jedoch auf gemischte Reaktionen unter Feministinnen, die geteilter Meinung waren, wenn es um den Nutzen von Programmen an Hochschulen oder auf Gemeindeebene ging. Diese Konflikte kamen zum ersten Mal bei der Konferenz zur Planung der Zentraleinrichtung zur Forderung von Frauenstudien und Frauen forschung an der Freien Universitat in Berlin zum Tragen. Seitdem pragen sowohl akademische Einrichtungen als auch kommunale Institutionen das Feld in Deutschland
Gas turbine-synchronous generator system emulation using power electronics converters

In this paper, two methods which can be utilized to emulate any gas turbine synchronous generator (GT-SG) setup with the use of power electronics converters, regardless of power level, is provided. The dynamic equations of the GT and SG are utilized to construct their models, and are implemented in MATLAB/Simulink®. An active-front-end (AFE) and inverter (INV) are utilized to emulate the gas turbine and synchronous generator dynamics, respectively. Controls are set up for the GT-SG model and their control signals are utilized to provide the switching commands for the AFE and INV, respectively, to perform the emulation. Parameter duality between the GT-SG model and the AFE-INV model are provided.
Effect of the width of regions with severed microtubules on transport of organelles down the axon

Abstract This paper investigates the effects of structural changes in the microtubule system on traffic jam formation in fast axonal transport and on inhibiting transport of organelles down the axon. Understanding this process is important for understanding the underlying reasons for many neurodegenerative diseases, such as Alzheimer's disease. In particular, the effect of the width of regions with severed microtubules (also called organelle traps) on the amount of organelles delivered to the synapse of the axon is investigated. Three cases with a different degree of microtubule polar mismatching in the microtubule swirl region are investigated. It is demonstrated that in all three cases increasing the width of organelle trap regions significantly decreases the flux of organelles down the axon compared to that in a healthy axon, in which case organelle traps are absent.
LARGE-SCALE ISOLATION OF EQUINE ZONAE PELLUCIDAE

A simple and rapid method is described for the large-scale isolation of cumulus cell-free, zona pellucida-intact equine oocytes. Aspiration of palpable antral follicles present on frozen-thawed equine ovaries was accomplished using a constant vacuum source. The resultant follicular fluid, oocytes, and particulate matter were then filtered through a series of nylon screens of alternating mesh openings in combination with sodium citrate-containing buffer to a final volume of approximately 20 ml. This fluid was transferred to scored Petri dishes and a stereomicroscope was used to locate the oocytes for futher processing or storage. The methodology described is inexpensive, time-efficient, and the recovery rate is similar to or better than other methods previously described for equine oocyte recovery. Collected oocytes are adequate for biochemical evaluation of the equine zona pellucida (EZP) as well as sperm-egg binding assays.
Gross spatial changes in the turkey blastoderm following extended pre-incubation storage.

SummaryThrough a window in the shell, two sets of observations and linear measurements were made on the blastoderms of turkey (Broad Breasted Bronze) eggs held for 14 days at 13°C: one before and the other at the end of the holding period. At both times, free hand sketches were made of the gross morphology of the germ disc and its diameter was measured. The eggs were then incubated for 40 hours at 37.5°C and the blastoderm and the area pellucida were measured. A parallel series of observations was made on eggs in which the outer limits of the germ disc were marked (“tattooed”) before storage. During the holding period marked changes in the gross morphology of the turkey germ disc usually could be observed. The diameter of the germ disc also changed (“fluxed”) in most cases. Subsequently, early blastoderm growth at 37.5°C was favored by these changes.
Increased affinity of platelet dopamine-binding to D2-receptors in migraineurs: implications of the dopaminergic system in migraine

Evaluation of: Shukla R, Kanna VK, Vinod P, Sankhwar ML, Yadav RS: Platelet dopamine: D2-receptor binding in patients with migraine. Cephalalgia DOI: 10.1111/j.1468-2982.2008.01760.X (2009) (Epub ahead of print). This study aimed to measure the level of platelet dopamine binding to the dopamine D2 receptor in migraineurs, using 3H-spiperone as a radioligand, and compared samples with control subjects. Patients adhering to the International Headache Society classification of migraine were shown to have significantly reduced dissociation constant (Kd: 1.71 ± 0.19 nM) for D2-receptor binding compared with controls. There was no relationship between Kd and other specific clinical features, such as migraine type, frequency and vomiting. The findings point to a relationship between dopamine binding and migraine, however further studies with larger patient groups are necessary to evaluate the exact role of dopamine and specific clinical features.
Incidence of venous thromboembolism after inferior vena cava injury.

Abstract Background Complications after inferior vena cava (IVC) injury, including venous thromboembolism (VTE), are expected, but the exact incidence is poorly defined. The purpose of this study is to examine the VTE rate following ligation versus repair of IVC injuries. Materials and methods The California State Inpatient Database was queried for all adult patients (age >14 y) admitted between 2005 and 2008 with IVC injuries. Demographic data, mechanism of injury, operative technique (ligation versus repair), and outcomes were recorded. Outcomes were compared according to operative technique. Results A total of 308 patients with IVC injuries were evaluated. The study population was mostly male (81.2%), young (median age 24 y), and Hispanic (43.2%). Overall mortality was 37.3%. The mechanisms of injury included gunshot wounds (52.3%), stab wounds (14.0%), and motor vehicle collisions (14.9%). Associated injuries were present in 100% of cases, with duodenal injuries being the most common. The majority of injuries were managed by primary repair (76.6%), with ligation performed in 23.4%. Patients who underwent ligation had a longer hospital stay (median 9 versus 6 d, P = 0.04) and a trend towards a higher mortality (45.8% versus 34.8%, P = 0.10), with no difference in VTE rate (4.2% versus 1.7%, P > 0.99). Conclusions As expected, IVC injuries carry a very high mortality rate and are always associated with other injuries. We demonstrated a surprisingly low rate of VTE after operative management for IVC injury, which was similar for patients undergoing ligation and repair.
Activation of resorption in fatigue-loaded bone involves both apoptosis and active pro-osteoclastogenic signaling by distinct osteocyte populations.

Abstract Osteocyte apoptosis is required to initiate osteoclastic bone resorption following fatigue-induced microdamage in vivo; however, it is unclear whether apoptotic osteocytes also produce the signals that induce osteoclast differentiation. We determined the spatial and temporal patterns of osteocyte apoptosis and expression of pro-osteoclastogenic signaling molecules in vivo. Ulnae from female Sprague–Dawley rats (16–18 weeks old) were cyclically loaded to a single fatigue level, and tissues were analyzed 3 and 7 days later (prior to the first appearance of osteoclasts). Expression of genes associated with osteoclastogenesis (RANKL, OPG, VEGF) and apoptosis (caspase-3) were assessed by qPCR using RNA isolated from 6 mm segments of ulnar mid-diaphysis, with confirmation and spatial localization of gene expression performed by immunohistochemistry. A novel double staining immunohistochemistry method permitted simultaneous localization of apoptotic osteocytes and osteocytes expressing pro-osteoclastogenic signals relative to microdamage sites. Osteocyte staining for caspase-3 and osteoclast regulatory signals exhibited different spatial distributions, with apoptotic (caspase 3-positive) cells highest in the damage region and declining to control levels within several hundred microns of the microdamage focus. Cells expressing RANKL or VEGF peaked between 100 and 300 μm from the damage site, then returned to control levels beyond this distance. Conversely, osteocytes in non-fatigued control bones expressed OPG. However, OPG staining was reduced markedly in osteocytes immediately surrounding microdamage. These results demonstrate that while osteocyte apoptosis triggers the bone remodeling response to microdamage, the neighboring non-apoptotic osteocytes are the major source of pro-osteoclastogenic signals. Moreover, both the apoptotic and osteoclast-signaling osteocyte populations are localized in a spatially and temporally restricted pattern consistent with the targeted nature of this remodeling response.
Quasi-One-Dimensional and Quasi-Two-Dimensional Magnetic Systems: Determination of Crossover Temperature and Scaling with Anisotropy Parameters

Magnetic systems of lattice dimensionality $\overline{d}$ are considered, with interaction strength $J$ in $d$ lattice directions and $RJ$ in the remaining ($\overline{d}\ensuremath{-}d$) directions; recent experimental work on quasi-one-dimensional and quasi-two-dimensional systems are germane to the cases $d=1,2$, respectively (and $\overline{d}=3$). Rigorous relations are established for the first few derivatives with respect to $R$ of the susceptibility $\ensuremath{\chi}(R)$, the second moment of the correlation function ${\ensuremath{\mu}}_{2}(R)$, and the specific heat ${C}_{H}(R)$. These results permit detailed statements about the coefficients in the expansions of $\ensuremath{\chi}(R)$, ${\ensuremath{\mu}}_{2}(R)$, and ${C}_{H}(R)$ in Taylor expansions in $R$ about the $d$-dimensional limit ($R=0$), and thus permit estimates concerning the temperatures at which each of these functions exhibits significant departures as $T\ensuremath{\rightarrow}{T}_{c}^{+}$ from its high-temperature $d$-dimensional behavior. These are the first estimates of the "crossover temperature" at which the system crosses over to $\overline{d}$-dimensional behavior from its limiting high-temperature behavior (at which the weak interactions $RJ$ are ineffective compared to the strong interactions $J$ in the $d$ lattice directions). In particular, they emphasize the fact that the crossover temperature depends upon the function being considered as well as upon the system and the value of $R$. These results also give strong support to the generalized scaling hypothesis in which $R$ is scaled.
Optical Matrix-Vector Laboratory Data For Finite Element Problems

We detail the use of an optical linear algebra processor for a finite element processing application. A linear time-varying structural mechanics finite element earthquake case study is described. The structure response under earthquake loading is considered, and the solution is obtained with the Newmark direct integration algorithm. The optical architecture for performing the required computationally burdensome banded matrix-vector operations is reviewed. The case study was solved on a laboratory version of the optical processor, and the results are presented.
Memory for Frequency of Bizarre and Common Stimuli: Limitations of the Automaticity Hypothesis

In 2 experiments, the influence of intention to process frequency on accuracy of memory for frequency of bizarre and common sentences was investigated. The results from multiple regression analyses indicated that intentional processing increased the accuracy of frequency judgments when memory for frequency was tested after a 2-min (Experiment 1) and after a 48-hr (Experiment 2) retention interval. Furthermore, the results of Experiment 2 indicated that unintentional processors tended to overestimate frequencies of bizarre relative to common items after a delay. The implications of the results are discussed with regard to L. Hasher and R. T. Zacks's (1984) automaticity hypothesis, human performance, and the accuracy of judgments of frequency of occurrence of unusual events.
A general approach to surface modelling applied to molecular graphics

Abstract A program is described that produces realistic representations of surfaces on a raster graphics terminal. The program uses a spatial subdivision algorithm similar to that of Woodwork and Quinlan. Simple geometric primitives, such as spheres, cones, cylinders and cuboids, are combined to build more complex pictures. This paper describes the program and how it is applied to molecular graphics. Examples of several applications are given.
“Neutral theory” and the dynamics of the evolution of “Modern” human morphology

There is a widespread assumption, even among those who reject the Synthetic Theory of Evolution, that the form of “modern”Homo sapiens is somehow superior to that of archaicHomo sapiens (Tattersall 2000). Those who accept the general outlook of evolutionary biology also tend to assume that “modern” form emerged because it was selected for, which also implies that it was better than that which preceded it. However, after years of using craniofacial measurements to compare human populations, I finally came to realize that, with only a few exceptions, the dimensions measured have no relation to differences in adaptation (Brace 1989, 1996, 2000; Brace et al., 1993). Elsewhere the conclusion has been supported that what is shown by craniometrics is selectively neutral on the average (Relethford 2002). With the documentation that approximately 95% of the genome is not functional, molecular genetics has proved to be useful in documenting the length of time of separation of related human populations by investigating the differences that have accumulated in the neutral parts of the genome. Not surprisingly, the picture revealed by the study of genetic differences is very similar to the one revealed by the study of craniometric differences (Brace et al., 2001). For this reason, the logic behind the “neutral theory” in molecular genetics is very similar to that applied to what happens to morphological characteristics when selection ceases (Brace 1963; Kimura 1968). The difference is that random changes in the neutral part of the genome have no other consequences. However, random changes in the genes that produce specific aspects of morphology will be visible even when selection is no longer controlling the particular trait in question. From an assessment of what random changes in genes controlling morphological traits are likely to do, it follows that the most likely change will probably be a reduction in the trait in question, i.e. the Probable Mutation Effect will produce structural reduction. When survival in the temperate zone during the last glaciation dependend on “obligatory cooking”, one of the unintended consequences was a reduction in the selective pressures maintaining a Middle Pleistocene-sized dentition. The result was a gradual reduction in tooth size and a conversion, of a Neanderthal-sized face into one of “modern” dimensions. The manufacture and use of string for snares and nets similarly reduced the selective pressures maintaining post-cranial levels of robustness and muscularity. The reduction in the latter resulted in the emergence of moderm post-cranial robustness out of what had been a Neanderthal level,in situ wherever the technology can be documented and without any need for invasions and replacements.
Lexical-phonological processing of functors: evidence from fluent aphasia.

Abstract The purpose of this study was to investigate how functors are processed at the lexicalphonological level. Four fluent aphasics with impaired ability to fully activate entries in the phonological lexicon, as revealed by their noun production, were asked to repeat and read aloud individual functors. Similarities between their functor and noun production (e.g., level of performance, production of phonological errors) indicated that functors are stored along with content words in the phonological lexicon, and are stored with a similar abstract structure. We also considered whether the sentence-planning system can facilitate the phonological encoding of functors presented in isolation.
A simulation of hand impairments: Effects on upper extremity function and implications toward medical impairment rating and disability determination

Abstract Objectives: To determine whether simulation of significant impairment of the hand will have a predictable impact on degree of functional loss at the wrist and hand. Design: Single subject repeat measures using before-after trial comparisons and healthy volunteer subjects. Setting: Occupational therapy section of a large academic medical center. Other Participants: Twenty adult volunteer student subjects from an occupational therapy education (OTE) department were included. All were between ages 18 and 43 years, right hand dominant, and in excellent general health. There were 19 women and 1 man, reflecting gender distribution of the OTE student body. Intervention: A simulated fusion of the carpometacarpal (CMC) joint of the thumb was achieved by immobilization in an individually fabricated splint designed to maximally restrict motion at the first CMC joint. Impairment ratings (baseline vs splinted) according to the AMA Guides were obtained by Greenleaf testing, and upper extremity function was quantitatively assessed before and after splinting. Main Outcome Measures: Measures of upper extremity function included grip and pinch strength, wrist torque, and speed of performance on the Valpar Small Tools test, Jebsen Hand Function test, and an exploratory measure, the Functional Life Activity Test (FLAT). Results: Significant impairments were achieved for all subjects after splinting and according to Greenleaf testing. Splinting resulted in significant reductions in grip and pinch strength, wrist torque, and significant slowing of performance on the Valpar, Jebsen, and FLAT tests. Regressions of degree of impairment on degree of functional loss after splinting, and according to each of the above measures, were not significant. Conclusions: Impairment of the hand was simulated to a mild-to-moderate degree as measured according to the AMA Guides . This imposed significant reductions in motion at key joints of the wrist and hand as well as significant reductions in grip and pinch strength and wrist torque. A corresponding and significant slowing of performance on a variety of measures of upper extremity function of an industrial and nonindustrial nature was also seen. However, and for the first time, correlation and regression reveals that it is not possible to predict degree of functional loss attributable to degree of impairment for the hand. It thus appears that, for mild-to-moderate clinical impairments, the associated impairment rating is a poor estimator of functional loss at the hand and should be used cautiously, if at all, as a criterion for disability determination.
Test-retest assessment of functional near-infrared spectroscopy to measure risk decision making in young adults

Investigation of the reliability and reproducibility of the hemodynamic response is important for interpretation and understanding of the results of functional near-infrared spectroscopy (fNIRS). It measures optical signals absorbed by the brain tissue and reflects the neuronal activities indirectly. Here we described an fNIRS study measured in the prefrontal region (Brodman area 9, 10, part of 46)to examine the risk decision-making behavior in nine young adults. The Balloon Analog Risk Task (BART) is widely used to test the level of risk taking ability in the field of psychology. BART was a protocol utilized in this study to evoke a risk-taking environment with a gambling-like balloon game in each subject. Specifically, we recorded the brain oxygenated-hemoglobin (HbO) and deoxygenated-hemoglobin (HHb) changes during the two repeated measurements within a time interval of 3 weeks. The results demonstrate that the changes in HbO2 amplitudes have high reliability at the group level, and that the spatial patterns of the tomographic images have high reproducibility in size and a moderate degree of overlap. Overall, this study confirms that the hemodynamic response to risk decision-making (i.e., BART) seen by fNIRS is highly reliable and reproducible.
Intergroup contact: The typical member and the exception to the rule

Abstract Three studies examined the role of the perceived typicalness of an out-group member on her effectiveness in improving evaluations of her group. Subjects were students at two adjacent colleges. In the first study they interacted with a member of the out-group college. The interaction was either pleasant or unpleasant, and the contact person either confirmed or disconfirmed several stereotypes of the out-group (typicalness manipulation). Subjects evaluated the out-group most favorably when they interacted with the typical-pleasant member of the out-group. The second study demonstrated that contact with a highly typical member is not beneficial if her typicalness is based on stereotypes that reflect negatively on the subject's in-group. Several explanations of the typicalness findings were considered in a third study. Support was found for the hypothesis that the more typical member is perceived to be more predictive of the personality and actions of other out-group members.
Fast-neutron spectrometry using a 3He ionization chamber and digital pulse shape analysis

Digital pulse shape analysis (dPSA) has been used with a Cuttler-Shalev type (3)He ionization chamber to measure the fast-neutron spectra of a deuterium-deuterium electronic neutron generator, a bare (252)Cf spontaneous fission neutron source, and of the transmitted fast neutron spectra of a (252)Cf source attenuated by water, graphite, liquid nitrogen, and magnesium. Rise-time dPSA has been employed using the common approach for analyzing n +(3)He→(1)H+(3)H ionization events and improved to account for wall-effect and pile-up events, increasing the fidelity of these measurements. Simulations have been performed of the different experimental arrangements and compared with the measurements, demonstrating general agreement between the dPSA-processed fast-neutron spectra and predictions. The fast-neutron resonance features of the attenuation cross sections of the attenuating materials are clearly visible within the resolution limits of the electronics used for the measurements, and the potential applications of high-resolution fast-neutron spectrometry for nuclear nonproliferation and safeguards measurements are discussed.
Three-Dimensional Discrete Element Method of Analysis of Clays

Particles of cohesive soils such as clays are platelike and very small in size (e.g., cuboids of dimensions 1.0μm×1μm×0.06μm). There are not only mechanical interactions between two clay particles, but also physico–chemical interactions. Properties such as the stress–strain behavior and shear strength of such a material result from a complex microscopic interactions of particles and interparticle forces. Development of physically meaningful mathematical models requires a microlevel understanding of these interactions. These interactions are difficult to observe experimentally, owing primarily to the minute size of particles. Numerical simulation studies have been conducted in the past, but using two-dimensional idealizations of particles. In the present study, a three-dimensional discrete element method is developed and implemented into a computer program. The method is used to conduct one-dimensional compression of an assembly of particles, and the macroscopic and microscopic results are presented and di...
The design of SWIR imaging lenses using plastic optics

Plastic lenses are widely used in visible imaging systems and provide a number of advantages including reduced weight. However, their use in the short-wave infrared (SWIR) has been limited due to the presence of strong material absorption bands occurring at wavelengths above 1 micron. This paper explores the viability of using plastic optics in broadband SWIR imaging applications and the efficacy of using plastic lenses as a method of weight reduction. A design study is presented to reveal combinations of plastic and glass lenses suitable for aberration correction. Weight savings is quantified via a comparison to glass lenses to investigate the trade-off between using lower density plastic materials and the faster F/#s (i.e. larger lenses) required to compensate for the signal loss caused by their absorption.