cssi/SciSciGPT-SciSciNet huggingface dataset:
Parameter estimation for two synthetic gene networks: a case study

In this paper, we use two synthetic gene networks, a transcriptional cascade and a pulse generating network, to study the efficacy of a simple statistical parameter fitting algorithm. The fitting was performed on experimental data and computer-generated data (to test how well the algorithm works under ideal conditions with perfect information). Most of the experimental parameter estimations yielded tight ranges of kinetic values for both gene networks. However, the results using simulated data indicate that the algorithm was able to provide better parameter estimates for the pulse generating network than for the transcriptional cascade. This is likely a result of the larger amount of time-series data available for the pulse generator and its greater level of phenotypical complexity, leading to tighter constraints for optimization. The variation in the magnitudes of the standard deviations between parameter estimates may give an indication of system sensitivity to specific kinetic rate constants. In the future, we also plan to verify the experimental results by constructing network variants and attempting to predict behaviors using values obtained in this study.
Stabilization of the E* form turns thrombin into an anticoagulant

Previous studies have shown that deletion of nine residues in the autolysis loop of thrombin produces a mutant with an anticoagulant propensity of potential clinical relevance, but the molecular origin of the effect has remained unresolved. The x-ray crystal structure of this mutant solved in the free form at 1.55 Å resolution reveals an inactive conformation that is practically identical (root mean square deviation of 0.154 Å) to the recently identified E* form. The side chain of Trp215 collapses into the active site by shifting >10 Å from its position in the active E form, and the oxyanion hole is disrupted by a flip of the Glu192–Gly193 peptide bond. This finding confirms the existence of the inactive form E* in essentially the same incarnation as first identified in the structure of the thrombin mutant D102N. In addition, it demonstrates that the anticoagulant profile often caused by a mutation of the thrombin scaffold finds its likely molecular origin in the stabilization of the inactive E* form that is selectively shifted to the active E form upon thrombomodulin and protein C binding.
Specificity of RCN1-mediated protein phosphatase 2A regulation in meristem organization and stress response in roots

Protein dephosphorylation by the serine/threonine protein phosphatase 2A (PP2A) modulates a broad array of cellular functions. PP2A normally acts as a heterotrimeric holoenzyme complex comprising a catalytic subunit bound by regulatory A and B subunits. Characterization of the regulatory A subunit isoforms (ROOTS CURL IN NAPHTHYLPHTHALAMIC ACID1 [RCN1], PP2AA2, and PP2AA3) of Arabidopsis thaliana PP2A has shown that RCN1 plays a primary role in controlling root and hypocotyl PP2A activity in seedlings. Here we show that hypocotyl and root growth exhibit different requirements for RCN1-mediated regulation of PP2A activity. Roots of rcn1 mutant seedlings exhibit characteristic abnormalities in cell division patterns at the root apical meristem, as well as reduced growth under ionic, osmotic, and oxidative stress conditions. We constructed chimeric A subunit genes and found that restoration of normal root tip development in rcn1 plants requires both regulatory and coding sequences of RCN1, whereas the hypocotyl elongation defect of rcn1 plants can be complemented by either RCN1 or PP2AA3 transgenes. Furthermore, the RCN1 and PP2AA3 proteins exhibit ubiquitous subcellular localization patterns in seedlings and both associate with membrane compartments. Together, these results show that RCN1-containing PP2A has unique functions that cannot be attributed to isoform-specific expression and localization patterns. Postembryonic RCN1 function is required to maintain normal auxin distribution and stem cell function at the root apex. Our data show that RCN1-regulated phosphatase activity plays a unique role in regulating postembryonic root development and stress response.
Effects of Impurities on the Optical Properties of Quantum Dots, Wires, and Multiple Wells

Identifying and understanding the effects of impurities and defects in quantum dots, wires, and multiple wells is important for the development of nanostructures with good optical properties. Simple model calculations are presented to show when and how shallow impurities affect the radiative recombination of confined electron-hole pairs. Results for nanostructures are compared with results for bulk systems. Qualitative differences between bulk and confined systems are described.
MB-37METACHRONOUS SUPRATENTORIAL INTRACRANIAL MALIGNANT TUMORS IN TWO PEDIATRIC PATIENTS WITH INFRATENTORIAL MEDULLOBLASTOMA ON HORMONE THERAPY

INTRODUCTION: Medulloblastomas are classified by the WHO as embryonal tumors and comprise the most common of the malignant pediatric brain tumors while accounting for twenty percent of all pediatric brain tumors. The phenomenon of second malignancy is uncommonly seen in cases of uniform histology and are more rare when they are of a different histological type. The authors report two cases of infratentorial medulloblastomas that subsequently developed a grade IV glioma in one case, and a second medulloblastoma in the other. PRESENTATION: An eleven year-old female had been experiencing vision difficulty with right eye deviation and emesis. MRI showed a partially-enhancing posterior fossa mass lesion. Four years later, she was discovered to have a right parietal ring-enhancing lesion on routine surveillance. A four year-old female presented to our institution with a one-month history of headaches and emesis and a posterior fossa mass lesion. Three and a half years later, subsequent routine surveillance revealed a new enhancing lesion of the left temporal region with a higher Ki-67 labeling index. TREATMENT: Our first patient underwent sub-occipital craniotomy and gross-total resection for her medulloblatoma followed by chemoradiation under a COG protocol consisting of Vincristine, Cisplatin, and Cyclophosphamide and 23.4 Gy with a posterior fossa boost of 30.6 Gy. She underwent craniotomy for the GBM with GTR followed by maintenance chemotherapy. Our second patient underwent similar therapy with GTR for both lesions then was initiated after the second resection on a COG trial consisting of Bevacizumab, Temodar, and Irinotecan. Of note, both patients were on hormone therapy: GH and Lupron. CONCLUSIONS: We report two cases of infratentorial medulloblastoma with subsequent development of supratentorial lesions with discrepant histological profiles. A second malignancy of different cellular origin is rare, and molecular profiling of the two metachronous medulloblastomas will reveal whether they represent unique entities.
Sequential Metabolism and Bioactivation of the Hepatotoxin Benzbromarone: Formation of Glutathione Adducts From a Catechol Intermediate

Benzbromarone (BBR) is a uricosuric agent that has been used as a treatment for chronic gout. Although never approved in the United States, BBR was recently withdrawn from European markets due to several clinical cases linking the drug to an idiosyncratic hepatotoxicity that is sometimes fatal. We report here a possible mechanism of toxicity that involves the bioactivation of BBR through sequential hydroxylation of the benzofuran ring to a catechol, which can then be further oxidized to a reactive quinone intermediate capable of adducting protein. NADPH-supplemented human liver microsomes generated a single metabolite that was identified as 6-OH BBR by comparison with the synthesized chemical standard. CYP2C9 was the major recombinant enzyme capable of catalyzing the formation of 6-OH BBR, although CYP2C19 also showed a lower degree of activity. Further oxidation of either 6-OH BBR or 5-OH BBR by human liver microsomes resulted in the formation of a dihydroxy metabolite with identical chromatographic and mass spectral properties. This product of sequential metabolism of BBR was identified as the catechol, 5,6-dihydroxybenzbromarone. Incubation of the catechol with liver microsomes, in the presence of glutathione, resulted in the formation of two glutathione adducts that could derive from a single ortho-quinone intermediate. Isoform profiling with recombinant human P450s suggested that CYP2C9 is primarily responsible for the formation of this reactive quinone intermediate.
Graphic-based musculoskeletal model for biomechanical analyses and animation.

Abstract The ability to combine physiology and engineering analyses with computer sciences has opened the door to the possibility of creating the ‘Virtual Human’ reality. This paper presents a broad foundation for a full-featured biomechanical simulator for the human musculoskeletal system physiology. This simulation technology unites the expertise in biomechanical analysis and graphic modeling to investigate joint and connective tissue mechanics at the structural level and to visualize the results in both static and animated forms together with the model. Adaptable anatomical models including prosthetic implants and fracture fixation devices and a robust computational infrastructure for static, kinematic, kinetic, and stress analyses under varying boundary and loading conditions are incorporated on a common platform, the VIMS (Virtual Interactive Musculoskeletal System). Within this software system, a manageable database containing long bone dimensions, connective tissue material properties and a library of skeletal joint system functional activities and loading conditions are also available and they can easily be modified, updated and expanded. Application software is also available to allow end-users to perform biomechanical analyses interactively. This paper details the design, capabilities, and features of the VIMS development at Johns Hopkins University, an effort possible only through academic and commercial collaborations. Examples using these models and the computational algorithms in a virtual laboratory environment are used to demonstrate the utility of this unique database and simulation technology. This integrated system will impact on medical education, basic research, device development and application, and clinical patient care related to musculoskeletal diseases, trauma, and rehabilitation.
Truing of vitrified-bond CBN grinding wheels for high-speed operations

This study investigated the truing of vitrified-bond CBN grinding wheels. A rotary cup-type diamond truer was used to condition grinding wheels under positive as well as negative dressing speed ratios. Cutting speeds between 30 and 120 m/s were used in an external cylindrical grinding mode. The grinding wheel surface was recorded during all stages of truing and grinding using 2D surface topography measurements. The performance of each truing condition on wheel topography, grinding behavior, and on workpiece topography and integrity were compared. Dressing speed ratio has been found to be a suitable parameter for appropriate CBN grinding wheel preparation.
Idiopathic Hand and Arm Pain: Delivering Cognitive Behavioral Therapy as Part of a Multidisciplinary Team in a Surgical Practice.

Abstract Cognitive behavioral therapists may have a unique and growing role in orthopedics departments. In helping patients cope with pain, particularly where there is no specific biomedical treatment or cure, cognitive behavioral practitioners can help prevent, early on, the transition from an acute pain complaint to a costly, disabling, and interfering chronic pain syndrome (CPS; see Singh, M. K., Patel, J., & Galagher, R. (2005). Chronic pain syndrome. Physical Medicine and Rehabilitation. Retrieved April 25, 2008, from. http://www.emedicine.com/pmr/topic32.htm for a thorough description). Idiopathic hand and arm pain is a prevalent, costly, and distressing condition. It is defined as pain in the hand or arm that is vague, diffuse, with unclear pathology, or pain that is over and above what is expected based on an objective medical finding ([Ring, D., Katzielsky, J., Malhotra, L., Lee, S. G., & Jupiter, J. B. (2005). Psychological factors associated with idiopathic arm pain. Journal of Bone and Joint Surgery, 87, 374 --380]). Diagnosing and treating pain in general is challenging, and it is particularly challenging when there is no clear objective pathology, as in idiopathic pain. Patients with vague, diffuse, nonspecific pain complaints often present to orthopedic departments in hope of pain relief or cure via surgical procedures, yet surgeons are poorly equipped to deal with situations where pure medical management is unwarranted. This may be detrimental to patient care and lead to chronic pain syndrome. This article reviews research and common clinical issues in patients with idiopathic hand and arm pain who present to orthopedic departments; presents a multidisciplinary team approach in coordinating and providing care for these patients; and describes two case examples of the use of cognitive and behavioral interventions as part of this team approach. Utilizing cognitive and behavioral approaches may be a way to increase the quality of life of patients presenting with idiopathic arm pain, prevent transition to chronic pain syndrome, and circumvent costly and largely ineffective surgical procedures.
Ultrasonographic Assessment of the Endometrium in Rhesus Monkeys during the Normal Menstrual Cycle

This study was undertaken to determine whether cyclical changes in the endometrium of the rhesus monkey could be observed by using ultrasound. Three indices of endometrial size were examined: the antero-posterior (or ventro-dorsal), longitudinal, and transverse diameters. Changes in the ultrasonic reflectivity of the endometrium were also assessed. We have attempted to correlate these endometrial parameters with the hormonal status of the animal. Ultrasonography was performed for an average of 12 consecutive days during 19 menstrual cycles. All ultrasonic recordings were normalized to the day of the estradiol (E2) peak (Day 0). We found that the reflectivity of the endometrium was dependent on the stage of the cycle: during the follicular phase, the endometrium appeared less echogenic (darker) compared to the myometrium; in the luteal phase, the endometrium was more echogenic (lighter). During the follicular phase (Days -9 to 0), there was a linear increase in the antero-posterior (p less than 0.001), longitudinal (p less than 0.05), and transverse (p less than 0.001) diameters. In the luteal phase (Days 1-15), no significant changes were observed in these diameters. An estimated endometrial volume (EEV) was obtained by the product of the antero-posterior, longitudinal, and transverse diameters. Each animal observed during the follicular phase (n = 14) exhibited a peak in the EEV, which correlated with the day of the E2 peak (p less than 0.01). From this study, we conclude that the sonographic appearance of the endometrium of the rhesus monkey reflects the cyclical changes that occur during the menstrual cycle.(ABSTRACT TRUNCATED AT 250 WORDS)
Subgroup Detector: A System for Detecting Subgroups in Online Discussions

We present Subgroup Detector, a system for analyzing threaded discussions and identifying the attitude of discussants towards one another and towards the discussion topic. The system uses attitude predictions to detect the split of discussants into subgroups of opposing views. The system uses an unsupervised approach based on rule-based opinion target detecting and unsupervised clustering techniques. The system is open source and is freely available for download. An online demo of the system is available at: http://clair.eecs.umich.edu/SubgroupDetector/
Movement of lucifer yellow in leaves of Coleus blumei Benth

Abstract Individual spongy mesophyll cells in green areas of variegated Coleus blumei leaves were injected with the symplast-mobile dye lucifer yellow and its movement to other cell types was followed with fluorescence microscopy. In 13 trials, the dye remained in the injected cell twice, moved only to other mesophyll cells five times, and moved up to and along minor veins six times. Where extensive movement of the dye occurred, the tissue was fixed with 4% glutaraldehyde, dehydrated, embedded in plastic, sectioned at 3 μm, and examined again with fluorescence microscopy. The dye was found in abaxial bundle-sheath cells for up to 200 μm or more distant from the site of injection near the minor vein, but no convincing evidence was found for its presence in the vascular tissue itself. It thus appears that superficial whole-mount views of lucifer yellow movement along leaf minor veins cannot be taken as certain evidence for symplastic transport of the dye into and along the vascular tissues.
Glycosylphosphatidylinositol-anchored proteins are not required for crosslinking-mediated endocytosis or transfection of avidin bioconjugates into biotinylated cells

Abstract Even though glycosylphosphatidylinositol (GPI)-anchored proteins lack direct structural contact with the intracellular space, these ubiquitously expressed surface receptors activate signaling cascades and endocytosis when crosslinked by extracellular ligands. Such properties may be due to their association with membrane microdomains composed of glycosphingolipids, cholesterol and some signaling proteins. In this study, we hypothesize that GPI proteins may be required for crosslinking-mediated endocytosis of extracellular bioconjugates. To test this hypothesis, we first biotinylated the surface membranes of native K562 erythroleukemia cells versus K562 cells incapable of surface GPI protein expression. We then compared the entry of fluorescently labeled avidin or DNA condensed on polyethylenimine–avidin bioconjugates into the two biotinylated cell populations. Using fluorescence microscopy, nearly 100% efficiency of fluorescent avidin endocytosis was demonstrated in both cell types over a 24 h period. Surprisingly, plasmid DNA transfer was slightly more efficient among the biotinylated GPI-negative cells as measured by the expression of green fluorescence protein. Our findings that GPI proteins are not required for the endocytosis of avidin bioconjugates into biotinylated cells suggest that endocytosis associated with general membrane crosslinking may be due to overall reorganization of the membrane domains rather than GPI protein-specific interactions.
Body and Soul: Jazz in the 1920s

This article examines the discursive framing of jazz as it entered the musical mainstream. Voices in the contest to define the music turned to a body-centered discourse that highlighted jazz’s alle...
Spatial and Fourier Error Minimization for Motion Estimation and Segmentation

We present a new approach to motion estimation by minimizing the squared error in both the spatial and frequency domains and we show that the spatially global nature of FT leads to a motion estimation error that is much lower than that obtained via spatial motion estimation. On the other hand, spatial analysis is useful for accurate segmentation. We describe a novel, hybrid approach combining the above two estimates of motion and segmentation. We examine the robustness of minimizing the error terms in both domains, both theoretically and experimentally. Experiments with real and synthetic sequences demonstrate the capabilities of the proposed algorithm.
Metabolic Respiration Induces AMPK- and Ire1p- Dependent Activation of the p38-Type HOG MAPK Pathway

Evolutionarily conserved mitogen activated protein kinase (MAPK) pathways regulate the response to stress as well as cell differentiation. In Saccharomyces cerevisiae, growth in non-preferred carbon sources (like galactose) induces differentiation to the filamentous cell type through an extracellular-signal regulated kinase (ERK)-type MAPK pathway. The filamentous growth MAPK pathway shares components with a p38-type High Osmolarity Glycerol response (HOG) pathway, which regulates the response to changes in osmolarity. To determine the extent of functional overlap between the MAPK pathways, comparative RNA sequencing was performed, which uncovered an unexpected role for the HOG pathway in regulating the response to growth in galactose. The HOG pathway was induced during growth in galactose, which required the nutrient regulatory AMP-dependent protein kinase (AMPK) Snf1p, an intact respiratory chain, and a functional tricarboxylic acid (TCA) cycle. The unfolded protein response (UPR) kinase Ire1p was also required for HOG pathway activation in this context. Thus, the filamentous growth and HOG pathways are both active during growth in galactose. The two pathways redundantly promoted growth in galactose, but paradoxically, they also inhibited each other's activities. Such cross-modulation was critical to optimize the differentiation response. The human fungal pathogen Candida albicans showed a similar regulatory circuit. Thus, an evolutionarily conserved regulatory axis links metabolic respiration and AMPK to Ire1p, which regulates a differentiation response involving the modulated activity of ERK and p38 MAPK pathways.
Increased levels of plasma anaphylatoxins in systemic lupus erythematosus predict flares of the disease and may elicit vascular injury in lupus cerebritis

We measured levels of complement anaphylatoxin split products, C3a and C5a, in the circulation of patients with systemic lupus erythematosus (SLE). In 23 SLE patients who were followed serially, the mean C3a value was 179 ng/ml during stable disease and 550 ng/ml during a disease flare. In 10 patients, C3a levels predicted disease activity, with the C3a value rising from a mean of 183 ng/ml at a time of stable disease to a mean of 242 ng/ml 1-2 months prior to a clinical exacerbation of disease. The mean C3a level in 5 patients with acute dysfunction of the central nervous system (CNS) was 1,297 ng/ml, which is significantly higher than that observed in patients with active disease but without CNS involvement (P less than 0.01). C5a levels were also significantly elevated in 4 patients with acute CNS disease. Pathologic specimens from 2 patients who died during an acute lupus flare revealed neutrophils occluding the cerebral and intestinal vessels. Fluorescein angiography in a patient with CNS lupus revealed vasoocclusive retinopathy. In 5 of 7 SLE patients who were pregnant, C3a levels were elevated, with a group mean value of 310 ng/ml. There was a negative correlation (r = -0.59) between C3a and C3 levels in pregnant patients with SLE, and this finding is consistent with complement activation as the cause of decreasing C3 levels. We suggest that serial measurements of C3a can predict flares of disease in lupus patients and can demonstrate complement activation during pregnancy in women with SLE. In addition, release of C3a and C5a (mediators of inflammation) into the circulation may elicit vascular injury, particularly in patients with lupus cerebritis.
The Devastating Impact of the Initiative Process on Latino and Immigrant Communities

This article is forthcoming in a symposium issue of the California Law Review. Although popular in many states, direct democracy remains alive and well. Recent years have seen a fascinating twist in the deployment of initiatives. In pursuit of a conservative political agenda, activists have begun to employ initiatives as a last resort to head off civil rights gains of racial and other minorities. Showcase examples include the rejection of affirmative action by the voters of California and Michigan through initiatives after courts declined to bury race-conscious admissions in higher education. Similarly, in response to governmental policies believed by many voters to be too liberal, immigrants - disproportionately Latina/o in modern time - also have suffered initiative setbacks with reduced access to public benefits and services, English-only laws, and the elimination of bilingual education in the public schools.This article focuses on the devastating impacts of lawmaking by initiative on Latina/os and immigrants. The question is whether there is anything to be done to help ensure fundamentally fair treatment of political minorities, especially discrete and insular minorities who may be discriminated against and punished with impunity by the majority in the electoral process. Latina/os are minorities who often have suffered the disfavor of the majority in the political process. Their lack of political power as a minority is exacerbated by the fact that a significant portion of the community is composed of noncitizens, who lack the right to vote. Immigrants themselves historically have been nothing less than sitting ducks for fear and loathing, which has repeatedly resulted in their harsh treatment in U.S. history.Part I of the article outlines the special political process defects that severely handicap Latina/os and immigrants in the United States. Part II offers concrete illustrations of the operation of the process defects. The article demonstrates that the political difficulties facing Latina/os and immigrants, many of whom are barred from voting and thus experience the diminution of their raw political power, are greater in direct democracy than those facing racial and other minority groups that lack a significant noncitizen component. To ameliorate the political process defects diluting the electoral power of people of color and immigrants, Part III advocates more scrutinizing - and less deferential - judicial review of initiatives that implicate the rights of Latina/os, as well as other racial minorities, and immigrants.
A Pediatric Decannulation Protocol: Outcomes of a 10-Year Experience.

Objectives(1) Describe an institutional protocol that focuses on the essential steps for decannulation of pediatric patients with long-term tracheostomies. (2) Discuss the preliminary observations ...
Neuroadaptive processes associated with palatable food intake: Present data and future directions

Ingestive behavior is a complex decision-making process involving the integration of homeostatic and hedonic systems. Human neuroimaging studies have provided considerable insight into aspects of hedonically-motivated food intake. Here, we review reports that examine brain response patterns to food stimuli (food cues and during food intake) that vary by weight status, habitual ingestive behavior, and weight change, as well as investigations that use neuroimaging techniques to predict food intake. Secondly, we discuss the application of decision-making theory stemming from computational neuroscience to better understand the basis of habit formation in the context of food intake. This framework may provide insight into the neuroadaptive processes that drive the transition from infrequent, moderate intake of energy-dense foods to habitual overconsumption.
Decision Making for Affective Agents in Assistive Environments

In this paper, we discuss the Decision Making and Learning ability of Affective Agents to make human-like decisions. This work is in the context of Assistive Living Environments (ALE) applications, where an agent is capable of assisting a human in physical and cognitive rehabilitation through multimodal and adaptive interaction. The goal of this research is to investigate what role multimodality plays in producing a natural and effective interaction using Reinforcement Learning. We propose a hierarchical decision making framework for affective agents doing complex tasks. This framework incorporates an internal reward mechanism to make the learning more efficient.
A Tripodal Ligand Constructed from Mesoionic Carbene Donors

A tripodal ligand constructed solely from mesoionic carbene donors is reported. The donor strength of this ligand is lower than most imidazol-2-ylidene-based tris(carbene)borate ligands, as measured by IR spectroscopy of {NiNO}10 and {Mn(CO)3}+ derivatives. The attenuated donor strength is proposed to be due to the collective electron-withdrawing effect of the ligand’s aryl substituents.
Early action of prolactin on ornithine decarboxylase activity is not essential for the subsequent actions of prolactin on casein and lipid biosynthesis.

AbstractThe actions of prolactin (PRL) on casein and lipid biosynthesis in cultured mouse mammary gland explants require the ongoing synthesis of the polyamines. This is supported by the fact that (MGBG) methylglyoxal bis(guanylhydrazone), a drug that inhibits the conversion of putrescine to spermidine, abolishes the effects of PRL on casein and lipid biosynthesis; the inhibitory effects of MGBG are reversed by the addition of spermidine to the culture medium. α-Difluoro methyl ornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase activity, reduces the PRL-stimulated ornithine decarboxylase (ODC) activity by more than 95%, and yet does not suppress the effects of PRL on RNA, casein or lipid synthesis. These observations suggest that PRL's early action on ODC activity is not essential for the subsequent actions of PRL on the synthesis of certain of the components of milk.
Morality and Entertainment: The Origins of the Motion Picture Production Code

Few new technologies have affected communication and society more profoundly than motion pictures. A "far more elastic medium" than the stage, movies made ideas previously restricted to comparatively small groups of readers and urban theatergoers accessible to virtually everyone by projecting them on film screens everywhere, from the largest city to the smallest village.' By speaking to mass audiences directly, movies all too easily bypassed traditional agencies of socialization the church, the school, the family. For many they came to symbolize the important changes taking place in the structure of power and influence in the early twentiethcentury United States, and those groups who feared that their own influence in society was diminishing viewed them as a threat. Fierce debates over the content and control of this new medium arose in the early days of silent film and intensified with the advent of sound technology. Out of these controversies emerged efforts to regulate motion picture entertainment, efforts that culminated in the Motion Picture Production Code of 1930, an attempt to bind movies to Judeo-Christian morality.2
Pathogenesis and treatment of virus-induced autoimmune diabetes: novel insights gained from the RIP-LCMV transgenic mouse model

Juvenile onset insulin-dependent diabetes mellitus (IDDM) is a serious health problem that affects several million people each year [l-31. In IDDM, pancreatic /?-cells are destroyed by a cellular infiltrate consisting of CD4’ and CD8’ lymphocytes, which are believed to react with islet cell antigens (ICAs). The aetiology of this autoimmune reaction is not known, and at the present time no permanent cure is available [ 1,4]. Among factors involved in triggering IDDM, a genetic correlation to certain HLA-DR alleles (MHC class 11) has been observed [5-91. However, a genetic predisposition alone is not sufficient to result in IDDM, since a discordance occurs in monozygotic twins [6,8]. Further, IDDM correlates with geographic location [6,8,10]. Thus environmental factors are believed to play a role in triggering the disease. These are primarily microbial infections [ 1 1-1 51. This could happen as follows. Potentially autoreactive, but under normal circumstances non-active or unresponsive, lymphocytes that are present in every individual [16-181 could be activated by a viral infection either through direct crossreactivity (molecular mimicry) with viral epitopes or through bystander activation [ 19,201 by secretion of inflammatory cytokines. These lymphocytes would then be able to recognize self-antigens expressed on /?-cells. This scenario could potentially be aggravated if the viral infection specifically assaults /?-cells and thus either makes them more sensitive to destruction by self-reactive lymphocytes or results in expression of viral proteins in the islets, so that an immune response against the virus occurs at the level of the /?-cell. Along these lines, several viral infections are known to target ,%cells, and viruses, for example Coxsackie virus, have been isolated from islets of individuals with IDDM [15,21].
The Strickler Technique of Ureterosigmoidostomy

AbstractWe herein report on the use of the Strickler technique of ureterosigmoidostomy in 28 patients at our hospital since 1965. The operative technique is reviewed, complications are discussed and pertinent followup data are given.
Dialogue Act Classification In Human-to-Human Tutorial Dialogues

We present in this paper preliminary results with dialogue act classification in human-to-human tutorial dialogues. Dialogue acts are ways to characterize the actions of tutors and students based on the language-as-action theory. This work serves our larger goal of identifying patterns of tutors’ actions, in the form of dialogue acts, that relate to learning. The preliminary results we obtained for dialogue act classification using a machine learning approach are promising.
Footbinding, Industrialization, and Evolutionary Explanation : An Empirical Illustration of Niche Construction and Social Inheritance.

The incorporation of niche construction theory (NCT) and epigenetics into an extended evolutionary synthesis (EES) increases the explanatory power of evolutionary analyses of human history. NCT allows identification of distinct social inheritance and cultural inheritance and can thereby account for how an existing-but-dynamic social system yields variable influences across individuals and also how these individuals’ microlevel actions can feed back to alter the dynamic heterogeneously across time and space. An analysis of Chinese footbinding, as it was ending during the first half of the twentieth century and China was industrializing, illustrates the evolutionary dynamics of niche construction across inheritance tracks and explains regional heterogeneity as well as the persistence of a cultural belief that was socially inaccurate. Incorporating anthropological and sociological insights into an EES with NCT has the potential to proffer source laws for relationships between individual actions and macro-patterns in beliefs, structures, climate, and demography.
Impacts of crop insurance on water withdrawals for irrigation

Abstract Agricultural production remains particularly vulnerable to weather fluctuations and extreme events, such as droughts, floods, and heat waves. Crop insurance is a risk management tool developed to mitigate some of this weather risk and protect farmer income in times of poor production. However, crop insurance may have unintended consequences for water resources sustainability, as the vast majority of freshwater withdrawals go to agriculture. The causal impact of crop insurance on water use in agriculture remains poorly understood. Here, we determine the empirical relationship between crop insurance and irrigation water withdrawals in the United States. Importantly, we use an instrumental variables approach to establish causality. Our methodology exploits a major policy change in the crop insurance system – the 1994 Federal Crop Insurance Reform Act – which imposed crop insurance requirements on farmers. We find that a 1% increase in insured crop acreage leads to a 0.223% increase in irrigation withdrawals, with most coming from groundwater aquifers. We identify farmers growing more groundwater-fed cotton as an important mechanism contributing to increased withdrawals. A 1% increase in insured crop acreage leads to a 0.624% increase in cotton acreage, or 95,602 acres. These results demonstrate that crop insurance causally leads to more irrigation withdrawals. More broadly, this work underscores the importance of determining causality in the water-food nexus as we endeavor to achieve global food security and water resources sustainability.
Special Papers on the History of Sciences- I John Leonard Riddell

It is rare that a man combines careers in science and politics. It is more unusual when his scientific achievements cover five distinct fields - medicine, botany, chemistry, geology, and physics. John Leonard Riddell was such an unique individual and his place as a leader in science in the deep South during the nineteenth century has been firmly established.
Age-Related Repetitive Transcranial Magnetic Stimulation Effects on Executive Function in Depression: A Systematic Review

Objective The aims of the current review were to: 1) examine whether the rTMS effects on executive function increase as age advances; 2) to examine the potential of rTMS to remediate executive function in older depressed patients; and 3) to assess the relationship between the executive function and mood benefits from rTMS in depression. Methods Randomized or matched-groups, blind, sham-controlled studies (12 studies, 347 participants) on excitatory rTMS applied to left DLPFC in depression were reviewed. Results A series of meta-regressions found no evidence of greater rTMS effects on executive functions as age advances. Similarly, meta-analyses showed no significant rTMS effects on executive functions in older depressed individuals. However, meta-regression analyses showed that the size of the executive function benefits from rTMS in depression are positively related to the effect size of mood symptom reduction. Despite its correlational nature, this finding is consistent with the idea that improvement in executive function may play a critical role in depression recovery. Conclusions The authors consider these findings preliminary because of the modest number of available studies. Based on a qualitative review, the authors describe methodologic modifications that may increase rTMS efficacy for both executive functions and mood in late-life depression.
Metal–Organic Framework Encapsulation for the Preservation and Photothermal Enhancement of Enzyme Activity

Interfacing biomolecules with functional materials is a key strategy toward achieving externally-triggered biological function. The rational integration of functional proteins, such as enzymes, with plasmonic nanostructures that exhibit unique optical properties such as photothermal effect provides a means to externally control the enzyme activity. However, due to the labile nature of enzymes, the photothermal effect of plasmonic nanostructures is mostly utilized for the enhancement of the biocatalytic activity of thermophilic enzymes. In order to extend and utilize the photothermal effect to a broader class of enzymes, a means to stabilize the immobilized active protein is essential. Inspired by biomineralization for the encapsulation of soft tissue within protective exteriors in nature, metal-organic framework is utilized to stabilize the enzyme. This strategy provides an effective route to enhance and externally modulate the biocatalytic activity of enzymes bound to functional nanostructures over a broad range of operating environments that are otherwise hostile to the biomolecules.
White lies: a racial history of the (post)truth

ABSTRACTIn the aftermath of the 2016 election of President Trump, a veritable cottage industry of opinion pieces, blogs, and articles emerged overnight, most of which seemed to agree that only the ...
Glucocorticoid receptors and behavior: implications for the stress response.

Stress-induced release of glucocorticoids is one of two modes of operation of the pituitary-adrenal axis, the other being the diurnal variation of glucocorticoid levels. Both operating modes are, of course, driven by CNS release of the releasing factor, CRH, in combination with other modulators such as vasopressin and oxytocin (Vale, this volume; Plotsky, this volume; (1)). However, stress-induced release is due to environmental and experiential factors such as heat, cold, anxiety, trauma and exertion, and it results in high levels of glucocorticoids in the blood. On the other hand, diurnal variation in pituitary-adrenal function is based upon an endogenous oscillator (2), although both the light-dark cycle and the anticipation of food entrain the rhythm (3, 4).
Muscle adaptations to hindlimb suspension in mature and old Fischer 344 rats

Stump, Craig S., Charles M. Tipton, and Erik J. Henriksen.Muscle adaptations to hindlimb suspension in mature and old Fischer 344 rats. J. Appl. Physiol.82(6): 1875–1881, 1997.—We examined skeletal...
Unpacking the Effect of Parental Monitoring on Early Adolescent Problem Behavior Mediation by Parental Knowledge and Moderation by Parent–Youth Warmth

This study explores the monitoring process longitudinally among a sample of rural early adolescents and addresses two research questions (1) Does maternal knowledge mediate the relationship between three aspects of the parental monitoring process and adolescent problem behavior: active parent monitoring efforts, youth disclosure, and parental supervision? (2) Are these meditational pathways moderated by the affective quality of the parent-child relationship? Parent efforts to monitor youth and youth disclosure in the Fall of Grade 6 predicted substance use and delinquency in Grade 8. These relations were mediated by increases in maternal knowledge assessed in the Spring of Grade 6, suggesting that the protective effects of these constructs are partially indirect. Supervision was not significantly related to maternal knowledge or problem behavior. Parent efforts to monitor were more strongly related to maternal knowledge in families with high levels of positive affect than in families with low levels of positive affect.
Putting the person in person-centered care: stakeholder experiences in pediatric traumatic brain injury

Purpose This pilot study sought to describe the perspectives and experiences of survivors of pediatric traumatic brain injury (pTBI), their caregivers, and the medical professionals who serve them. Methods Thirteen people participated in semi-structured interviews: five survivors of pTBI, their primary caregivers, and three medical professionals who work with persons who have sustained pTBI. The study involved a prospective, qualitative, participatory action research model with convenience sampling. All interviews were transcribed and thematic analysis identified central concepts within and between groups. Additionally, the Consolidated Criteria for Reporting Qualitative Research (COREG) were applied. Results This study found that survivors of pTBI and their caregivers commonly noted later developing issues, social challenges, and difficulty in post-rehabilitation transitions. In addition, both caregivers and medical professionals reported the need for improved follow-up with survivors, evidence-based research, and medical and therapy providers with specific training on pTBI. Conclusions The perspectives provided by key stakeholders in this pilot study identify common themes that should be central to driving innovation in rehabilitation research and clinical care.
Stereotactic Radiosurgery for Intracranial Arteriovenous Malformations

Cerebral arteriovenous malformations (AVMs) are vascular lesions consisting of abnormal connections between arteries and veins with no intermediate capillary network. With an annual spontaneous rupture rate of approximately 2–4%, they represent a significant source of hemorrhagic stroke and neurologic morbidity and mortality in young patients. The current treatment paradigms for AVMs include microsurgery, stereotactic radiosurgery (SRS), and embolization, all of which aim to abolish the risk of hemorrhage by obliterating the AVM nidus. Stereotactic radiosurgery is a minimally invasive and effective treatment option that is particularly suitable for small- to medium-sized AVMs located in deep or eloquent brain regions. Obliteration is achieved in 70–80% of cases, following a latency period of approximately 1–3-year posttreatment. SRS carries a unique complication profile including a sustained risk of hemorrhage during the latency period, as well as adverse radiation effects with associated neurologic deficits. AVM lesions vary widely in their natural histories and their suitability for treatment with SRS, based on characteristics such as size, location, and rupture status. For large AVMs, adjunct techniques such as endovascular embolization or volume and dose staging may be utilized to make the lesions appropriate targets for SRS. In the case of unruptured AVMs, early data from recent prospective trials have suggested that conservative medical management may result in better short-term outcomes than interventional treatment. Thus, the risks and complications associated with SRS therapy for individual AVMs must be carefully balanced against the morbidities associated with the natural history of the disease. Here we discuss the salient clinical and pathophysiologic indications for the use of SRS, review data on treatment efficacy and outcomes, and profile the major complications.
The relationship of Medicaid expansion to psychiatric comorbidity care within substance use disorder treatment programs.

Abstract Background Co-occurring mental health disorders are common among substance use disorder (SUD) patients. Medicaid expansion aimed to reduce barriers to SUD and mental health care and thereby improve treatment outcomes. Methods We estimated change in the proportion of United States SUD treatment sites offering treatment for psychiatric comorbidities following Medicaid expansion as part of implementation of the Affordable Care Act (ACA) in 2014. Using panel data from the 2013–2014, n = 660, and 2016–2017, n = 638, waves of the National Drug Abuse Treatment System Survey (NDATSS), we estimated change in the proportion of sites offering antidepressant medication, other psychiatric medication, behavioral treatment, or any combination thereof for treatment of mental health comorbidities (i.e., beyond services focused on SUD). We modeled the impact of Medicaid expansion as an interaction between year and date of Medicaid expansion. We constructed a mixed-effects linear regression model for each outcome, with the interaction variable as the main exposure, site as a random effect, and site's average duration of treatment, proportion of clients with psychiatric comorbidities, average caseload per treatment prescribing-clinician on staff, type of facility and geographic region as covariates, to estimate a difference-in-differences (D-I-D) equation. Results The adjusted D-I-D analysis indicated that the proportion of SUD treatment sites offering antidepressants for psychiatric treatment increased 10% (95% CI 1%, 18%) in the Medicaid expansion sites compared to non-expansion sites. The D-I-D for other psychiatric medications was also 10% (95% 1%, 19%). No significant changes were observed in behavioral treatment or the combination measure. The strongest association between Medicaid expansion and offering medication for mental health comorbidities was the 34% increase observed for residential treatment settings (95% CI 10%, 59%). Conclusion Availability of psychiatric medication treatment in SUD treatment settings increased following Medicaid expansion, particularly in residential SUD facilities. This policy change has facilitated integrated treatment for the substantial share of SUD treatment patients with mental health comorbidities, with the greatest benefit for patients receiving SUD treatment in residential programs.
Hail-Producing Storms on the Great Plains

Excerpted from: Great Plains Weather, by Kenneth F. Dewey. University of Nebraska Press, Lincoln. A Project of the Center for Great Plains Studies, University of Nebraska. © 2019 by the Board of Re...
Vietnamese Contingents to the Western Front, 1915–1919

The 100,000 troops that were raised in French Indochina included 19 battalions of Vietnamese, four of which were combat units that fought successfully, while others served either in direct support, often under fire or farther back in industry. Personal accounts and other records indicate the vast majority of the Vietnamese, despite claims to the contrary by anti-colonialist writers, were to varying degrees volunteers. The combat and frontline labor troops saw action on the Western front (in battles such as Verdun and Chemin-des-Dames) or in Macedonia. Some were convinced to stay beyond the armistice and make up for the French loss of manpower. When most returned home with transformed expectations, they faced poor compensation and frequent disappointment, generating a reservoir of seasoned recruits for the anti-colonial struggle.