cssi/SciSciGPT-SciSciNet huggingface dataset:
Chapter 11 - Myofibrillar myopathies

Myofibrillar myopathies (MFMs) represent a group of muscular dystrophies with a similar morphological phenotype. The diagnosis is established by muscle biopsy. The MFMs are characterized by a distinct pathological pattern of myofibrillar dissolution associated with disintegration of the Z-disk, accumulation of myofibrillar degradation products, and ectopic expression of multiple proteins that include desmin, αB-crystallin, dystrophin, and sometimes congophilic material. The clinical features of MFMs are more variable. These include progressive muscle weakness that often involves or begins in distal muscles, but limb-girdle or scapuloperoneal distributions can also occur. Cardiomyopathy and peripheral neuropathy are frequent associated features. Electromyography of the affected muscles reveals myopathic motor unit potentials and abnormal irritability, often with myotonic discharges. Rarely, neurogenic motor unit potentials or slowing of nerve conduction velocities are present. To date, all MFM mutations have appeared in Z-disk-associated proteins: namely, desmin, αB-crystallin, myotilin, ZASP, filamin C, and Bag3. However, in the majority of patients with MFM, the disease gene awaits discovery.
Basalt — Seawater Interaction

The upper part of the igneous oceanic basement consists of basaltic lava. This basalt undergoes reaction with seawater over a range of temperatures, time and locale. This reaction is a major source and sink for various ions in seawater, and is a major process in buffering seawater composition and forming metalliferous ores in the marine environment.
Assessment of intra and interregional genetic variation in the Eastern Red-backed Salamander, Plethodon cinereus, via analysis of novel microsatellite markers.

The red-backed salamander (Plethodon cinereus) has long-served as a model system in ecology, evolution, and behavior, and studies surveying molecular variation in this species have become increasingly common over the past decade. However, difficulties are commonly encountered when extending microsatellite markers to populations that are unstudied from a genetic perspective due to high levels of genetic differentiation across this species’ range. To ameliorate this issue, we used 454 pyrosequencing to identify hundreds of microsatellite loci. We then screened 40 of our top candidate loci in populations in Virginia, Pennsylvania, and Ohio—including an isolated island population ~ 4.5 km off the shore of Lake Erie (South Bass Island). We identified 25 loci that are polymorphic in a well-studied region of Virginia and 11 of these loci were polymorphic in populations located in the genetically unstudied regions of Ohio and Pennsylvania. Use of these loci to examine patterns of variation within populations revealed that South Bass Island has low diversity in comparison to other sites. However, neither South Bass Island nor isolated populations around Cleveland are inbred. Assessment of variation between populations revealed three well defined genetic clusters corresponding to Virginia, mainland Ohio/Pennsylvania, and South Bass Island. Comparisons of our results to those of others working in various parts of the range are consistent with the idea that differentiation is lower in regions that were once glaciated. However, these comparisons also suggest that well differentiated isolated populations in the formerly glaciated portion of the range are not uncommon. This work provides novel genetic resources that will facilitate population genetic studies in a part of the red-backed salamander’s range that has not previously been studied in this manner. Moreover, this work refines our understanding of how neutral variation is distributed in this ecologically important organism.
Squamous cell carcinoma of the head and neck (SCCHN) in patients reporting human immunodeficiency virus (HIV) infection: A retrospective case series

5570 Background: Although Squamous Cell Carcinoma of the Head and Neck (SCCHN) is a non-AIDS defining malignancy, its risk is greater in HIV-positive populations for unclear reasons. Very limited d...
Geography and Radiology: Perfect Together

In addition to my duties as a Radiology Chairman, Program Director and Graduate Medical Education Dean, I have a second career or rather a hobby in overdrive. I am a card-carrying geographer. I earned two master’s degrees at Columbia University, attending class in my afternoon off and in the evening away from my radiology day job. Part of the tuition was paid for by the G.I. Bill as a benefit I received from serving as a radiologist with the 101st Airborne Division at the tail end of the Vietnam era.
Assessment of Software Quality

Program quality is defined as the degree to which requirements and expectations are met, or as a long-range impact on user productivity. The resulting customer satisfaction is analyzed according to measurability and predictability.
Mechanisms of Amiodarone Pulmonary Toxicity

Amiodarone pulmonary toxicity is one of the most important examples of drug-induced lung disease by non-cancer chemotherapeutic agents. Current concepts suggest that patients may clinically present with an acute illness suggestive of a hypersensitivity picture or with a more chronic indolent course mimicking a malignant process. Likewise, the mechanism of amiodarone pulmonary toxicity suggests that at least two different pathways of toxicity exist: (1) an indirect mechanism characterized by influx of inflammatory or immune effector cells to the lung and (2) a direct toxic mechanism that results in lung parenchymal cell injury and a subsequent fibrotic response. Clearly, there is the potential for much crossover and interaction between the proposed pathways of toxicity in any given patient. A better understanding of the mechanism of amiodarone pulmonary toxicity will not only improve our diagnostic approaches to patients with this serious lung disorder, but will also provide the opportunity to develop unique therapeutic strategies that control the toxicity and potentially not interfere with the intended therapeutic efficacy of the drug.
The Role of Molecular Diagnostics in the Management of Indeterminate Thyroid Nodules

This paper is a commentary on the study by Livhits et al. addressing the relative utility of two molecular diagnostic techniques for thyroid nodules indeterminate on FNA cytology.
Event-free survival (EFS) and overall survival (OS) of MYCN-amplified stage 2/3 neuroblastoma with or without autologous stem-cell transplantation (ASCT).

10553Background: The literature on MYCN-amplified stage 2/3 neuroblastoma is limited because this high-risk subset is uncommon. Its prognosis improved with ASCT. Reports on anti-GD2 immunotherapy d...
Social Support Moderates the Association Between Traumatic Life Events and Depression Among Migrant and Nonmigrant Men in Almaty, Kazakhstan

Across cultures, experiencing traumatic life events, particularly violence, is a salient predictor of depression. Some previous findings have shown that social support can serve as a buffer in the association between traumatic life events and depression (i.e., the buffering hypothesis) in that individuals with a high level of social support have a decreased or nonexistent association between traumatic life events and depression. The purpose of this study was to test the buffering hypothesis among a sample of 1,342 male migrant and nonmigrant market vendors in Almaty, Kazakhstan. Using multiple-group structural equation modeling (SEM), we identified the following results: (a) higher levels of traumatic life events were associated with higher depression scores, (b) higher social support scores were associated with decreased depression scores, and (c) social support buffered the association between traumatic life events and depression among migrants and nonmigrants. The final model accounted for 45.0% and 38.4% of the variance in depression for migrants and nonmigrants, respectively. Findings suggest that social support may be an important protective factor for men in Kazakhstan who have experienced trauma and call for an incorporation of social support interventions for migrant and nonmigrant men experiencing depression.
P82 New Jersey Healthy Kids Initiative

Objective The New Jersey Institute for Food, Nutrition, and Health (IFNH) and Child Health Institute of New Jersey (CHINJ), joined resources for New Jersey Healthy Kids Initiative (NJHKI). The initiative ensures children enter kindergarten at a healthy weight and maintain it throughout childhood, while also lowering New Jersey's percentage of childhood overweight and obesity (32%), preventing weight related morbidities later in life. Providing leadership and organizational infrastructure, NJHKI will support an integrated set of activities with the goal of improving the health of children through lifestyle optimization at the intersection of healthy weight and metabolism, nutrition and culinary education, physical fitness. Its innovative paradigm of individualized evaluations and interventions for each school's unique context and demographic will foster a culturally-responsive, customized approach. Use of Theory or Research The NJHKI approach draws upon socio-ecological and behavior change theories. Interventions are informed by relevant research. Target Audience The initiative aims to be a voice for children everywhere, especially those in communities disproportionately burdened by childhood obesity. Program Description The NJHKI team consists of a: medical director, PhD-RDN behavioral nutritionist, RDN-social media expert, program director, developer, coordinator, and co-principal investigators. First year deliverables are the development of community, scientific, and fundraising boards; building relationships with stakeholders; and building a social media presence. Second and third year deliverables include development, testing, and engagement of schools across NJ in a “culture of health model.” Evaluation Methods Mixed methods data will be collected to evaluate program effectiveness and implementation. Children's anthropometric and biometric data will be collected to measure health outcomes. School program, policies, and practices, as well as knowledge, behavior, and skills will be evaluated using document reviews, interviews, and observation. Results NJHKI has hosted the first of five symposia focused on child health and initiated partnerships with beta-site schools. Conclusions This initiative will unfold in collaboration with the public and private-sectors of New Jersey and positions the state to be a leader in child health and a voice for children everywhere. Funding Robert Wood Johnson Foundation.
Making It Stick: Teaching Students with Autism to Generalize Physical Education Skills.

Research indicates that although students with disabilities, including those with autism spectrum disorder (ASD), can be successful in acquiring motor and sport-related skills during physical educa...
PRC2 bridges non-adjacent nucleosomes to establish heterochromatin

ABSTRACT Polycomb repressive complex 2 (PRC2) maintains transcriptionally silent heterochromatin by installing and spreading repressive histone methylation marks along nucleosome arrays. Despite extensive research, the mechanism by which PRC2 engages with chromatin remains incompletely understood. Here we employ single-molecule force spectroscopy and molecular dynamics simulations to dissect the interactions of PRC2 with polynucleosome substrates. Our results reveal an unexpectedly diverse repertoire of PRC2 binding configurations on chromatin. Besides interacting with bare DNA, mononucleosomes, and neighboring nucleosome pairs, PRC2 is also found to bridge non-adjacent nucleosomes, an activity associated with chromatin compaction. Furthermore, the distribution and stability of these PRC2–chromatin interaction modes are differentially modulated by accessory PRC2 cofactors, oncogenic histone mutations, and the methylation state of chromatin. Overall, this work provides a paradigm for understanding the physical basis of epigenetic maintenance mediated by Polycomb group proteins.
Genetic backgrounds have unique seizure response profiles and behavioral outcomes following convulsant administration.

Three highly utilized strains of mice, common for preclinical genetic studies, were evaluated for seizure susceptibility and behavioral outcomes common to the clinical phenotypes of numerous psychiatric disorders following repeated low-dose treatment with either a gamma-aminobutyric acid (GABA) receptor antagonist (pentylenetetrazole (PTZ)) or a glutamate agonist (kainic acid (KA)). Effects of strain and treatment were evaluated with classic seizure scoring and a tailored behavior battery focused on behavioral domains common in neuropsychiatric research: learning and memory, social behavior, and motor abilities, as well as seizure susceptibility and/or resistance. Seizure response was induced by a single daily treatment of either PTZ (30 mg/kg, intraperitoneally (i.p.)) or KA (5 mg/kg, i.p.) for 10 days. Pentylenetetrazole-treated FVB/NJ and C57BL/6NJ strains of mice showed strong, clear seizure responses. This also resulted in cognitive and social deficits, and increased susceptibility to a high dose of PTZ. Kainic acid-treated FVB/NJ and C57BL/6NJ strains of mice had a robust seizure response, which resulted in hyperactivity. Pentylenetetrazole-treated C57BL/6J mice demonstrated mild hyperactivity, while KA-treated C57BL/6J displayed cognitive deficits and resistance to a high dose of KA but no social deficits. Overall, a uniquely different seizure response profile was detected in the C57BL/6J strain with few observable instances of seizure response despite repeated convulsant administration by two mechanisms. This work illustrated that differing background genetic strains have unique seizure susceptibility profiles and distinct social and cognitive behavior following PTZ and/or KA treatment and that it is, therefore, necessary to consider strain differences before attributing behavioral phenotypes to gene(s) of interest during preclinical evaluations of genetic mouse models, especially when outcome measures are focused on cognitive and/or social behaviors common to the clinical features of numerous neurological disorders.
Tackling Old Issues with New Approaches

Current calls to reform biology instruction, whether through NGSS, AP Biology, or Vision and Change in Undergraduate Biology Education , ask biology educators to change their teaching practices so that more students successfully complete biology courses and become scientifically literate citizens. The reforms mentioned in these documents often include focusing on the depth of content vs. breadth, understanding scientific practices, and enhancing scientific skills. Not surprisingly, recognition of these important aspects of biology instruction is not new. While reviewing some of the earliest volumes of The American Biology Teacher , first published in 1938, I found that the first three volumes address the same considerations that we have today. In the first volume, Oscar Riddle from the Carnegie Institution wrote that “a citizenship acquainted with the principles and subject matter of the life sciences is vital to our national welfare” and that “new means should be found for supplying to our people the more and better biology teaching to which they are entitled.” As early as 1938 and likely even earlier, biology instructors were concerned about teaching …
Transfusion Reactions in Pediatric and Young Adult Hematopoietic Stem Cell Transplant and Oncology Patients

Background Patients undergoing chemotherapy and especially hematopoietic stem cell transplantation (HSCT) require frequent transfusions, and thus, transfusion reaction (TR) vigilance is critical in this population. The reported incidence of TRs across all patients is 2%, and pediatric patients may experience 2-2.6 times more reactions than adults. However, the TR profile may differ in the immunocompromised population. There is a paucity of data in this area, as pediatric oncology and HSCT patients are often excluded from TR studies. Our goals were to assess the prevalence and describe TRs among immunocompromised pediatric patients and to improve recognition of TRs across this population. Methods Pediatric clinical providers completed a TR training module in May – June, 2019. A single-institution retrospective review was conducted. All TRs in patients aged less than 25 years were reviewed over a 3-month period from July 1, 2019 to October 1, 2019. Results Over a 3-month period, 1,786 transfusions were administered in our designated population. Of those, 50.4% were platelets, 44.0% were red blood cells (RBC), 3.4% were cryoprecipitate, 1.4% were thawed plasma, and 0.8% were granulocytes. Those undergoing HSCT consumed 27.7% of total transfusions. Of all transfusions, there were 48 (2.7%) reported as possible TRs by nursing. Of those, 30 (1.7% of all transfusions) were adjudicated as true TRs. Fourteen (46.7%) of these true TRs were in patients with leukemia, 9 (30.0%) with HSCT, 5 (16.7%) with solid tumors, and 2 (6.7%) with aplastic anemia. Of the 9 reactions in HSCT patients, 4 occurred in allogeneic transplant recipients (3 umbilical cord blood and one matched unrelated donor) and 5 were in those receiving autologous HSCT. In HSCT patients, 1.8% of transfusions resulted in TRs compared to 1.6% in non-HSCT patients. Of the products triggering reactions, platelets accounted for 22 TRs (73.3%) and RBCs accounted for 8 TRs (26.7%). Of all 30 TRs, 15 (50%) were classified as febrile non-hemolytic transfusion reactions (FNHTR), 14 (46.7%) were considered allergic reactions, and 1 (3.3%) was diagnosed as transfusion-associated circulatory overload. Pre-medication was given in 22 (76.7%) of transfusions causing reactions. Of the 18 reports that were not adjudicated as true TRs, most (n=15) were generated for fever, but deemed unrelated to transfusion. Conclusions Our baseline analysis revealed a higher prevalence than our historical institutional prevalence (1.7% vs. 1.3%), consistent with higher rates of TRs in the pediatric population, but lower than the 2% quoted in the literature, suggesting either underreporting or a different TR phenotype in this population. This population had a higher prevalence of FNHTR than the general pediatric population (50.0% vs. 31.5%). High rates of pre-medication and comorbidities (resulting in fevers) may influence TR presentation in this population.
An Examination of Auditor Planning Judgments in a Complex Accounting Information System Environment

In complex accounting information system (AIS) environments, auditor planning judgments are affected by the quality of work supplied by both computer assurance specialists (CAS) and auditors. Prior research has indicated that there are concerns about CAS competence in practice and the profession has acknowledged that auditors need to expand their expertise in the AIS domain. In this study, we investigate the effects of CAS competence and auditor AIS expertise on auditor planning judgments in a complex AIS environment. We find both CAS competence and auditor AIS expertise significantly affected auditor risk assessments. More importantly, auditors' AIS expertise levels moderated their ability to effectively incorporate CAS evidence into their planned substantive testing. Specifically, when CAS competence was low, auditors with higher AIS expertise effectively expanded the scope of their audit testing beyond the scope set by auditors with lower AIS expertise. The effect of AIS expertise diminished when auditors received evidence from a highly competent CAS. A mediation analysis indicates the ability to identify potential AIS-specific risks as a mechanism behind the moderating effect of auditor AIS expertise. Our results suggest auditors' AIS expertise can play a significant role in complex AIS settings and in their ability to compensate for CAS competence deficiencies.
A bioinspired navigation strategy that uses magnetic signatures to navigate without GPS in a linearized northern Atlantic ocean: a simulation study.

Certain animal species use the earth's magnetic field (i.e., magnetoreception) in conjunction with other sensory modalities, to navigate long distances. It is hypothesized that several animals use combinations of magnetic inclination and intensity as unique signatures for localization, enabling migration without a pre-surveyed map. However, it is unknown how animals use magnetic signatures to generate guidance commands, and the extent to which species-specific capabilities and environmental factors affect a given strategy's efficacy or deterioration. Understanding animal magnetoreception can aid in developing better engineered navigation systems that are less reliant on satellites, which are expensive and can become unreliable or unavailable under a variety of circumstances. Building on previous studies, we implement an agent-based computer simulation that uses two variants of a magnetic signatures-based navigation strategy. The strategy successfully migrates to eight specified goal points in an environment that resembles the northern Atlantic Ocean. In particular, one variant reaches all goal points with faster ocean current velocities while the other variant reaches all goal points with slower ocean current velocities. We also employ dynamical systems tools to examine the stability of the strategy as a proxy for whether it is guaranteed to succeed. The findings demonstrate the efficacy of the strategy and can help to develop new navigation technologies that are less reliant on satellites and pre-surveyed maps.
Empirical Study of the Impacts of Bicycles on Passenger Car Speeds on Urban Roads without Bicycle Lanes

Higher bicycle mode share has been suggested as part of a solution to reduce the burden of congestion in urban areas. As strategies to promote cycling are implemented, concerns have been raised by ...
Mental Health in Lifestyle Medicine: A Call to Action:

Mental health symptoms are pervasive, with 1 in 5 American adults experiencing a mental disorder. Poor mental health is associated with a significant global cost burden, from disability to economic...
Outreach librarian to black students

While some predominantly white institutions can offer unique and laudable educational experiences to Black college students, they can also lack resources that provide these same students with a culturally affirming milieu. Black faculty and staff can organize their time, energy and resources to offer culturally enriching experiences for Black students. However, this additional labor is not systematically seen, cataloged or recognized as a core or essential duty. The author describes some effective forms of outreach from her personal experience and simultaneously asks whose job it is to meet the cultural needs of this population.
Testing the Bulk Volume Classification Algorithm

We document that the existing evidence that bulk volume trade classification (BVC) measures informed trading arises largely due to mis-specified tests. Simulations show that these tests detect spurious relationships in data containing only uninformed liquidity trades. We also assess the performance of BVC order imbalances in the NASDAQ HFT dataset, showing that BVC order imbalances underperform conventional order imbalance measures in detecting informed trading. The component of order flow designated by BVC as passive informed trading fails to predict returns with the correct sign. On balance, our evidence supports the use of conventional order imbalance measures to identify informed trading.
The Authoritarian Dynamic

1. Introduction: the authoritarian dynamic 2. Kindred spirits, common spark: the theory of the authoritarian dynamic 3. Manipulating threat and reassurance: data and methods 4. The authoritarian dynamic and the politics of fear: putting the pieces of the puzzle together 5. Authoritarianism and conservatism across cultures 6. Authoritarianism and conservatism: how they differ and when it matters 7. One true people: putting a dace on the theory 8. One right way: fleshing out the portrait 9. Manning the barricades: racism and Intolerance under conditions of normative threat 10. The authoritarian dynamic: implications.
WE-D-303-05: Dosimetric Accuracy of CBCT Images Estimated by a Motion Modeling and Free-Form Deformation Technique for Radiotherapy of Lung Cancer

Purpose: To investigate the dosimetric accuracy of CBCTs estimated by a motion modeling and free-form deformation(MM-FD) technique for radiotherapy of lung cancer. Methods: Various inter-fractional variations featuring patient motion pattern change, tumor size change and tumor average position change were simulated from planning-CT to on-board images using both digital and physical motion phantoms. The doses calculated on the planning-CT (planned doses), the on-board CBCT estimated by MM-FD (MM-FD doses) and the on-board CBCT reconstructed by the conventional Feldkamp-Davis-Kress(FDK) algorithm (FDK doses) were compared to the on-board dose calculated on the ‘gold-standard’ on-board images (gold-standard doses). The absolute deviations of minimum dose (dDmin), maximum dose (dDmax), mean dose (dDmean) and dose coverage (dV100%) of PTV were evaluated. In addition, 4D on-board dose accumulations were performed using the 4D-CBCT images estimated by MM-FD. The accumulated doses were compared to measurements using OSL detectors and radiochromic films. Results: Of all the 50 scenarios simulated, the average(± standard deviation) dDmin, dDmax, dDmean and dV100% (values normalized by the prescription dose or the PTV volume) between the planned and the gold-standard PTV doses were 34.8% (± 29.2%), 3.2% (± 3.8%), 3.5% (± 3.5%) and 13.0% (± 11.4%), respectively. The corresponding values of FDK PTV doses were 3.1% (± 3.7%), 1.4% (± 1.1%), 2.1% (± 0.8%) and 14.5% (± 14.2%), respectively. In contrast, the corresponding values of MM-FD PTV doses were 0.4% (± 0.5%), 0.9% (± 0.7%), 0.6% (± 0.4%) and 0.9% (± 0.8%), respectively.For the 4D dose accumulation study, the average(± standard deviation) absolute dose deviation (normalized by local doses) between the accumulated doses and the OSL measured doses was 3.0% (± 2.4%). The average gamma pass-rate(3%/3mm) between the accumulated doses and the radiochromic film measured doses was 96.1%. Conclusion: MM-FD estimated CBCT enables accurate on-board dose calculation and accumulation for lung radiation therapy. The research was funded by the National Institutes of Health Grant No. R01-CA184173 and a grant from Varian Medical Systems.
SU-D-210-01: Automated Depth of Penetration Measurements for Quality Assurance in Ultrasound

Purpose: Subjective assessment of image quality metrics is a current limitation of most ultrasound quality assurance (QA) programs. Here, depth of penetration (DOP) assessments for sensitivity checks are routinely done. We demonstrate the performance of an automated method for DOP measurement for ultrasound QA. Methods: Subjective DOP was assessed by examining an image of a QA phantom and determining the depth where the echo data fades into noise. To assess DOP objectively, a phantom image was recorded followed by a second, “noise image” with the transducer held in air. Phantom and noise images were laterally averaged; the DOP was the depth where phantom image pixel value intersected 1.4X noise image values. During annual QA, DOP was evaluated subjectively by a single observer on a number of probes and compared with objective DOP measurements. Additionally, the objective method’s measurement variance and sensitivity to transmit power was examined using a linear-array transducer. To examine variance, the DOP measurement was repeated with 25 phantom images recorded at uncorrelated planes with transmit power at either 100% or 1%. DOP was also measured as the transmit power was varied in fine steps between 0.1% and 100%. Results: Agreement within 10% of the mean DOP was found between objective and subjective methods for most cases. A small number of cases showed a difference between 10% and 18%. Using the linear-array, DOP was found to fall off as a power law with the transmit power. At 100% and 1% transmit power, the standard deviation of the DOP measurement was found to be 0.9 mm at DOP’s of 8.16 and 6.30 mm on average. Conclusion: Objective image quality assessment is necessary to improve the utility of routine ultrasound QA. We found that objective DOP measurements show good agreement with subjective assessments of DOP while showing little variance.
Gaddum Memorial Lecture 2014: receptors as an evolving concept: from switches to biased microprocessors

This review is based on the JR Vane Medal Lecture presented at the BPS Winter Meeting in December 2014 by T. Kenakin. A recording of the lecture is included as supporting information and can also be viewed online here: https://www.youtube.com/watch?v=xrP81AQ8l-8. Pharmacological models used to describe drug agonism and antagonism have evolved over the past 20 years from a parsimonious model describing single active and inactive receptor states to models of multiconformational receptor systems modified by ligand conformational selection. These latter models describe the observed, presently underexploited, pharmacological mechanism of ligand-directed biased signalling. Biased signals can be quantified with transduction coefficients (ΔΔLog(τ/KA) values), a scale grounded in the Black/Leff operational model; this enables the optimization of biased profiles through medicinal chemistry. The past decades have also brought the availability of new technologies to measure multiple functional effects mediated by seven transmembrane receptors. These have confirmed that drugs can have many efficacies, which may be collaterally linked, that is there is no linear sequence of activities required. In addition, new functional screening assays have introduced increasing numbers of allosteric ligands into drug discovery. These molecules are permissive (they do not necessarily preclude endogenous signalling in vivo); therefore, they may allow better fine tuning of pathological physiology. The permissive quality of allosteric ligands can also change the quality of endogenous signalling efficacy (‘induced bias’) as well as the quantity of signal; in this regard, indices related to ΔΔLog(τ/KA) values (namely ΔLog(αβ) values) can be used to quantify these effects for optimization in the drug discovery process. All of these added scales of drug activity will, hopefully, allow better targeting of candidate molecules towards therapies.
Roppongi Crossing: The Demise of a Tokyo Nightclub District and the Reshaping of a Global City. Roman Cybriwsky

Roppongi—anyone somewhat familiar with Tokyo will recognize the name as that of a famous entertainment district. From the 1960s to the 2000s, Roppongi referred to a nightlight district with numerou...
In vitro responses of rat lymphocytes following adult thymectomy. II. Increased inhibition by splenic adherent cells of responses to phytohemagglutinin.

Abstract Adult thymectomy in rats results in a marked fall of spleen cell responsiveness to PHA over a period of days to weeks. Examination of dose-response curves showed that, with high PHA dose or ≥ 10 6 cells/ml, there is a profound inhibition of the response with spleen cells from thymectomized animals compared with cells of matched sham-operated controls. However, when adherent cells are removed from the cell suspensions, the remaining nonadherent cells give an almost linear dose-response relationship with increasing PHA similar to that exhibited by the nonadherent cells of the controls or sometimes a slightly decreased response. Similarly, when increasing numbers of spleen cells from these animals are cultured (with admixed thymocytes to make a constant total of 2 × 10 6 cells/ml) with PHA, the linear portion of the doseresponse curve can be extrapolated to give a similar value for the maximal potential response, which again is the same as or somewhat less than the corresponding value for sham-operated controls. A difference in inhibitory capacity is also shown in mixtures of the two spleen cell populations with LNC or with purified spleen cells. It is concluded that adult thymectomy results in increased “suppressor” activity in the spleen within a few days and may reduce slightly the number of T lymphocytes in the spleen reactive with PHA.
Mechanical actions of compartments of the cat hamstring muscle, biceps femoris.

Publisher Summary Movement is produced as a result of an interaction of circuits in the central nervous system (CNS) and elements of the musculoskeletal system. The elements of the musculoskeletal system with which spinal circuits interact are usually described as muscles. Individual muscles have distinct morphologies and well-documented bony attachments. They receive exclusive innervation from groups of motoneurons whose axons are fasciculated to form distinct muscle nerves and have distinct mechanical actions. These attributes form much of the rationale for considering muscles as output elements, the targets for interaction with neuronal circuits. For a neuromuscular compartment to be an output element, it must have a distinct mechanical action. More precisely, different compartments within a muscle must exert different mechanical actions on the skeletal structures to which they attach. If different compartments produce the same mechanical action, then their role as output elements would be more difficult to support. This chapter describes the mechanical actions of the cat biceps femoris (BF) muscle. This muscle is subdivided into different compartments by the branches of its nerves that are arranged roughly in parallel from anterior or rostral to posterior or caudal. During the application of postural perturbations, a rostral to caudal gradient of the activation of different compartments has been found at the change of direction of the perturbation. Thus, motor units in different parts of this single muscle are activated independently. This chapter reports the results of experiments aimed at testing this hypothesis. Different compartments of BF have been found to produce different mechanical actions.
Site-specific methylation inhibits transcriptional activity of platelet-derived growth factor A-chain promoter

Expression of the platelet-derived growth factor (PDGF) A-chain gene is temporally and spatially restricted in development and highly regulated in selected normal and tumor cell lines. Because DNA methylation appears to be important in regulating tissue specific gene expression, we tested the influence of in vitro methylation of the human PDGF A-chain promotor on its activity in vivo in transient transfection assays. We now report that PDGF A-chain promoter activity is strongly repressed by DNA methylation in a DNA sequence-specific manner and that the repression of promoter activity by methylation requires a methyl CpG-binding protein(s). We also report that incubation of HeLa cells with 5-azacytidine sharply increases levels of endogenous PDGF A-chain gene transcripts. These results indicate that the promoter activity of the PDGF A-chain gene is sharply and selectively reduced by in vitro DNA methylation and that DNA methylation in vivo also may reduce its function in selected cell lines.
Recovery of myelination in rat optic nerve after developmental retardation by cortisol

Oligodendrocyte formation and myelination in the optic nerve of rats treated with cortisol on postnatal days 7 and 18 were investigated at 21 and 60 days by autoradiographic and morphometric methods. At 21 days, the amount of myelin in the optic nerve of treated rats was reduced by 42%. This reduction was accompanied by a 39% decrease in the number of myelinated axons. In addition, the myelin/axon area ratio was reduced 22% for those axons which were myelinated. At 60 days, the amount of myelin, the number of axons myelinated, the average axonal size, and the average amount of myelin per axon had completely recovered to normal values. Tritiated thymidine-labeling experiments showed that the genesis of oligodendrocytes was enhanced following the cessation of treatment. Since the number of oligodendrocytes in the optic nerve of treated rats was normal at 60 days, it is suggested that the retarding effect of cortisol on myelination in the optic nerve may be mediated, at least in part, by inhibited formation of oligodendrocytes during treatment.
Learning evaluation functions to improve optimization by local search

This paper describes algorithms that learn to improve search performance on large-scale optimization tasks. The main algorithm, STAGE, works by learning an evaluation function that predicts the outcome of a local search algorithm, such as hillclimbing or Walksat, from features of states visited during search. The learned evaluation function is then used to bias future search trajectories toward better optima on the same problem. Another algorithm, X-STAGE, transfers previously learned evaluation functions to new, similar optimization problems. Empirical results are provided on seven large-scale optimization domains: bin-packing, channel routing, Bayesian network structure-finding, radiotherapy treatment planning, cartogram design, Boolean satisfiability, and Boggle board setup.
Porphyrias: photosensitivity and phototherapy.

Publisher Summary Porphyrias are a heterogeneous group of inherited or acquired metabolic disorders, all of which result from partial deficiencies in the activity of enzymes regulating heme biosynthesis. Individuals with some of the several porphyric syndromes may exhibit cutaneous sensitivity to visible light exposure as a major clinical manifestation. Light-induced skin lesions of patients with porphyrias result from oxygen-mediated photochemical reactions. These reactions are initiated by the photoexcitation of porphyrin molecules that are produced in large quantities during faulty operation of the heme synthetic pathway. Medical management of porphyrin-sensitized phototoxicity in patients with various forms of porphyrias usually begins with recommendations for avoidance of sunlight by lifestyle changes, by physical means of light attenuation such as hats, gloves, and long-sleeved clothing or plastic filtering films applied to windows, and by application to the skin of topical sunblock formulations containing agents that reflect visible light. In many cases, however, such relatively risk-free measures are impractical and/or insufficient, stimulating ongoing searches for additional means of increasing light tolerance. Ingestion of energyquenching agents such as r-carotene or cysteine has improved the light tolerance of some patients with some porphyrias with photocutaneous manifestations, but the degree of protection gained has not been equal in all porphyrias or in all patients with any porphyria. Undesirable side effects of such systemic photoprotective agents may also discourage their use in some cases. These considerations have led to the investigation of the rather paradoxical application of phototherapies in porphyrias. Contemporary methods of phototherapy for skin diseases involve deliberate exposure of skin to selected wavelengths of ultraviolet radiation, including longer ultraviolet wavelengths near the visible light spectrum in which the action spectrum for phototoxicity in patients with porphyrias is maximal. This chapter discusses the pathophysiology of photosensitivity in porphyrias and the theory and practice of application of ultraviolet phototherapy as its treatment.
Chronic Noncorrespondence between Elementary Math Curricula and Arithmetic Tests

The content match of two elementary mathematics curricula (Distar Arithmetic and Scott Foresman Mathematics) and two arithmetic tests (KeyMath and the Iowa Tests of Basic Skills) was examined for Grades I through 3. Correspondence was assessed for content (material and operation) as well as the types of learning that were required of the student (i.e., knowledge, computation, comprehension, application). Eighty-one of the 90 comparisons were significant at the .001 level. Thus, a consistent lack of content correspondence was found among curricula and tests at all levels.
Thirteen Patients with MAT1A Mutations Detected Through Newborn Screening: 13 Years' Experience.

Background: Methionine adenosyltransferase I/III (MATI/III) deficiency is the most common genetic cause of persistent isolated hypermethioninemia.
Dynamics of hydrogen bromide dissolution in the ground and excited states.

The dissolution of acids is one of the most fundamental solvation processes, and an important issue is the nature of the hydration complex resulting in ion pair formation. We used femtosecond pump-probe spectroscopy to show that five water molecules are necessary for complete dissolution of a hydrogen bromide molecule to form the contact ion pair H+·Br–(H2O)nin the electronic ground state. In smaller mixed clusters (n
Irreversible gene repression model for control of development

As the pluripotent cells of early embryos differentiate, each progressively loses the potency to develop into several phenotypes. Ultimately, each cell becomes irreversibly restricted to the expression of a single phenotype. Although in many instances details regarding those restriction events are well known, there is little information concerning the nature of the gene transcription changes involved. A model that accounts for the diminution of developmental potential as resulting from progressive, irreversible repression of previously active genes is presented. A scheme of progressive gene repression, rather than selective gene activation, is most consistent with observations from experimental embryology as well as from more recent biochemical experimentation.
Managing group process in nonprocess groups: Working with the theme-centered psychoeducational group

While there has been a recent proliferation of groups for consultative and psychoeducational purposes, little has been written about using the group process in these nonprocess groups. This paper investigates the management of various group processes in a group whose contracted focus is teaching stress management skills. Distinctions are made between psychotherapeutic and theme-centered psychoeducational process management. Many group processes can be predicted given the group's normal developmental stages, while other ongoing group processes arise spontaneously. A working dialogue between the presented content and the emerging process is necessary in order for psychoeducation to be personalized and most fully assimilated. A clinical vignette follows the evolution of a stress management group conducted for high-level executives who have been identified as manifesting Type-A behaviors. For each session, the format and material content are briefly outlined, the emerging group process is described, and the clinical interventions involved in the process management are discussed.
Synthesis and mechanical properties of TiO2-epoxy nanocomposites

New developments in the synthesis of nanometer scale TiO2 particles have enabled the processing of exciting new nanoparticle/epoxy composites. An ultrasonic method was used to disperse the nanoparticles in epoxy, thus eliminating the need for solvent without sacrificing the ease of processing. Composites were processed at the 5, 10, 15 and 20 weight percent level and were characterized by SEM, tensile tests and scratch tests. These results at 10 percent loading were also compared with an equal loading of micron-size TiO2 fillers in epoxy to evaluate the strain-to-failure and scratch resistance.
Simulation of underground gravity gradients from stochastic seismic fields

We present results obtained from a finite-element simulation of seismic displacement fields and of gravity gradients generated by those fields. The displacement field is constructed by a plane-wave model with a 3D isotropic stochastic field and a 2D fundamental Rayleigh field. The plane-wave model provides an accurate representation of stationary fields from distant sources. Underground gravity gradients are calculated as the acceleration of a free test mass inside a cavity. The results are discussed in the context of gravity-gradient noise subtraction in third generation gravitational-wave detectors. Error analysis with respect to the density of the simulated grid leads to a derivation of an improved seismometer placement inside a 3D array which would be used in practice to monitor the seismic field.
Embracing Chaos and Complexity: A Quantum Change for Public Health

Public health research and practice have been guided by a cognitive, rational paradigm where inputs produce linear, predictable changes in outputs. However, the conceptual and statistical assumptions underlying this paradigm may be flawed. In particular, this perspective does not adequately account for nonlinear and quantum influences on human behavior. We propose that health behavior change is better understood through the lens of chaos theory and complex adaptive systems. Key relevant principles include that behavior change (1) is often a quantum event; (2) can resemble a chaotic process that is sensitive to initial conditions, highly variable, and difficult to predict; and (3) occurs within a complex adaptive system with multiple components, where results are often greater than the sum of their parts.
Combining ergometer exercise and artificial gravity in a compact-radius centrifuge

Abstract Humans experience physiological deconditioning during space missions, primarily attributable to weightlessness. Some of these adverse consequences include bone loss, muscle atrophy, sensory-motor deconditioning, and cardiovascular alteration, which may lead to orthostatic intolerance when astronauts return to Earth. Artificial gravity could provide a comprehensive countermeasure capable of challenging all the physiological systems at once, particularly if combined with exercise, thereby maintaining overall health during extended exposure to weightlessness. A new Compact Radius Centrifuge (CRC) platform was designed and built on the existing Short Radius Centrifuge (SRC) at the Massachusetts Institute of Technology (MIT). The centrifuge has been constrained to a radius of 1.4 m, the upper radial limit for a centrifuge to fit within an International Space Station (ISS) module without extensive structural alterations. In addition, a cycle ergometer has been added for exercise during centrifugation. The CRC now includes sensors of foot forces, cardiovascular parameters, and leg muscle electromyography. An initial human experiment was conducted on 12 subjects to analyze the effects of different artificial gravity levels (0 g, 1 g, and 1.4 g, measured at the feet) and ergometer exercise intensities (25 W warm-up, 50 W moderate and 100 W vigorous) on the musculoskeletal function as well as motion sickness and comfort. Foot forces were measured during the centrifuge runs, and subjective comfort and motion sickness data were gathered after each session. Preliminary results indicate that ergometer exercise on a centrifuge may be effective in improving musculoskeletal function. The combination is well tolerated and motion sickness is minimal. The MIT CRC is a novel platform for future studies of exercise combined with artificial gravity. This combination may be effective as a countermeasure to space physiological deconditioning.
A general asset pricing model

Abstract With only minimal assumptions, a general version of the security market line is obtained. In addition, it is suggested that instead of concentrating on the relationship between risk and return, the testable theories of capital market equilibrium should contain specific hypotheses about the true aggregate demands and supplies of risky assets.