cssi/SciSciGPT-SciSciNet huggingface dataset:
Speech and language intervention in bilinguals

Increasingly, speech and language pathologists (SLPs) around the world are faced with the unique set of issues presented by their bilingual clients. Some professional associations in different countries have presented recommendations when assessing and treating bilingual populations. In children, most of the studies have focused on intervention for language and phonology/ articulation impairments and very few focus on stuttering. In general, studies of language intervention tend to agree that intervention in the first language (L1) either increase performance on L2 or does not hinder it. In bilingual adults, monolingual versus bilingual intervention is especially relevant in cases of aphasia; dysarthria in bilinguals has been barely approached. Most studies of cross-linguistic effects in bilingual aphasics have focused on lexical retrieval training. It has been noted that even though a majority of studies have disclosed a cross-linguistic generalization from one language to the other, some methodological weaknesses are evident. It is concluded that even though speech and language intervention in bilinguals represents a most important clinical area in speech language pathology, much more research using larger samples and controlling for potentially confounding variables is evidently required.
Using hepatocytes produced from human ES and iPS cells to model hepatic involvement in serum lipid homeostasis

H play a central and crucial role for the production and elimination of serum cholesterol and lipid homeostasis and their proper function is of key importance for cardiovascular health. In particular, hepatocytes produce large amounts of endogenously-synthesized cholesterol, which is secreted into circulating blood in the form of apolipoprotein particles. Cholesterol-secreting hepatocytes are also clinically-relevant cells targeted by statin treatment in vivo. At present, the study of cholesterol homeostasis is largely restricted to the use of animal models and immortalized cell lines that fail to recapitulate many key aspects of normal human hepatocyte function. Hepatocyte-like cells (HLCs) derived from human embryonic and induced pluripotent stem cells (hESCs and hiPSCs) can potentially provide a cell culture model for the study of cholesterol homeostasis, dyslipidemias, and the action of pharmaceuticals important for cardiovascular health. This seminar will present research showing that differentiated cells resembling hepatocytes can be readily produced from hESCs and hiPSCs. The resulting HLCs exhibit many features of human hepatocytes in vivo, to include acivities related to serum lipid homeostasis. Overall, the research shows that HLCs derived from human pluripotent cells provide a robust cell culture system for the investigation of the hepatic contribution to cholesterol homeostasis at both cellular and molecular levels
Skeletal cell YAP and TAZ redundantly promote bone development by regulation of collagen I expression and organization

The functions of the transcriptional co-activators YAP and TAZ in bone are controversial. Each has been observed to either promote or inhibit osteogenesis in vitro, while their roles in bone development are unknown. Here we report that combinatorial YAP/TAZ deletion from skeletal cells in mice caused osteogenesis imperfecta with severity dependent on targeted cell lineage and allele dosage. Osteocyte-conditional deletion impaired bone accrual and matrix collagen, while allele dosage-dependent deletion from all osteogenic lineage cells caused spontaneous fractures, with neonatal lethality only in dual homozygous knockouts. We identified putative target genes whose mutation in humans causes osteogenesis imperfecta and which contain promoter-proximate binding domains for the YAP/TAZ co-effector, TEAD4. Two candidates, Col1a1 and SerpinH1, exhibited reduced expression upon either YAP/TAZ deletion or YAP/TAZ-TEAD inhibition by verteporfin. Together, these data demonstrate that YAP and TAZ redundantly promote bone matrix development and implicate YAP/TAZ-mediated transcriptional regulation of collagen in osteogenesis imperfecta.
Subtle physiological and morphological differences explain ecological success of sympatric congeners

Sympatric congeners with similar physiological and morphological characteristics may appear to overlap in niche space but respond to environmental change in different ways leading to population decline of one species while the other remains stable. Understanding why sympatric congeners vary in their ecological success can be challenging, but is particularly necessary given the magnitude of human-induced environmental change among ecosystems. We propose that identifying a complex of subtle, interacting characters among congeners may be more effective in elucidating both historical coexistence and divergent ecological success in contemporary habitats compared to identifying just one apparent limiting similarity between species. Using this subtle difference hypothesis, we examined how metabolic rate associated with habitat use and internal and external morphology collectively influenced the ecological success of a common and a rare sturgeon species that differ dramatically in their conservation status due to environmental change. Multivariate analyses of gut morphology (e.g., intestine length) combined with respirometry on sand and gravel habitats were incorporated into a bioenergetics model to compare how the fishes responded to habitat change and food quality. Energetic tradeoffs induced by habitat type and underlying morphological differences led to different predicted growth rates. Compared with the more prevalent species, the rare and endangered fish needed to seek different habitats with less energetic costs and switch to foraging at a higher trophic level to persist. Our results corresponded to observed differences in ecological success between these species in the wild. Thus, subtle physiological and morphological differences may lead to dramatic differences in ecological success in contemporary habitats for species that are very similar ecologically.
How Our Views Have Evolved: Historical Perspectives

Menstruation has been treated as everything from an ordinary event to evidence of a “curse.” Menstruating women have been treated as unclean, shunned, exiled, or ridiculed. It was well known that the touch of a menstruating woman would cause baking bread to fall, flowers to wilt, and brass to tarnish. During her period, a Muslim woman is not allowed inside a Mosque and cannot pray or fast during Ramadan. Even the Bible notes that whenever a woman has her menstrual period, she and those who touch her are “ceremonially unclean” for up to 7 days (Leviticus 15:19–33). This is their lot to deal with, preferably well away from the eyes of a male-dominated society. (The word “taboo” itself comes from the Polynesian word tapua which means “menstruation.”) When strong opiate analgesics failed to control the pain of menstrual cramps, it was easier to attribute the disability to being “all in the head” than to admit to a lack of understanding about the underlying pathophysiology. Ironically, some of these vary myths have led to today’s understanding of dysmenorrhea and menorrhagia and have made it possible for us to talk about prevention rather than relief. Indeed, the success of moving from symptoms to pathophysiology, from amelioration to prevention in dysmenorrhea, paved the way for similar efforts in conditions ranging from interstitial cystitis to migraine headaches. Understanding that journey provides valuable perspectives when we deal with patients who still suffer from these conditions.
Vector competence of selected North American Anopheles and Culex mosquitoes for Zika virus

Zika virus (ZIKV) is a vector-borne flavivirus that has caused recent outbreaks associated with serious disease in infants and newborns in the Americas. Aedes mosquitoes are the primary vectors for ZIKV, but little is known about the diversity of mosquitoes that can transmit ZIKV in North America. We chose three abundant North American mosquito species (Anopheles freeborni, Anopheles quadrimaculatus, and Culex tarsalis) and one known vector species (Aedes aegypti), fed them blood meals supplemented with a recent outbreak ZIKV strain, and tested bodies, legs, and saliva for infectious ZIKV. ZIKV was able to infect, disseminate, and be transmitted by Aedes aegypti. However, Anopheles freeborni, Anopheles quadrimaculatus, and Culex tarsalis were unable to be infected. We conclude that these species are unlikely to be involved in ZIKV transmission in North America. However, we should continue to examine the ability for other mosquito species to potentially act as ZIKV vectors in North America.
Psychopathology and Coping in Survivors of Intimate Partner Violence: Associations with Race and Abuse Severity

The present study examined how race and abuse severity independently and interactively predicted psychopathology and coping in a sample of 206 African-American and White survivors of intimate partn...
Investigation of the Line Frequency for Demand-Side Primary Frequency Control Using Behind-the-Meter Home Batteries

The aim of this work lies in investigating the grid frequency in the application of demand-side primary frequency control (PFC) with battery energy storage systems (BESS). In such an application, batteries participate in the PFC serving as energy buffer between their associated loads and the grid, and they are charged and discharged following the grid frequency conditions. The investigation focuses on the effect of PFC on the utilization of the battery in terms of its number of cycles. This includes studying the effects of the frequency dead-band on the battery charge/ discharge durations and the effects of droop settings on the charge/ discharge current rates. A case study of a 0.468 kWh battery pack is used to study the battery utilization under the reliability standards of PFC in the four interconnections of the North American grid. One-year line frequency data of the power system practically measured at Little Rock-AR is used in the analysis.
Commentary on Part I

During the nineteenth century, the study of algebra moved into the secondary school curriculum as colleges and universities began to require it for admission (Kilpatrick and Iszak 2008). Coming after an extensive treatment of arithmetic in the elementary grades, school algebra was commonly introduced formally as a generalization of that arithmetic, with an emphasis on symbol manipulation and equation solving. Given the well-established status of algebra in the secondary curriculum, mathematics educators today confront the question of, in the words of Subramaniam and Banerjee, how “to manage the transition from arithmetic to symbolic algebra.”
Rotterdam CT Score Can Detect Differences between Pediatric and Adult TBI (P06.241)

OBJECTIVE: To determine if radiographic differences can be measured using the Rotterdam CT Score between adult and pediatric traumatic brain injury (TBI). BACKGROUND: Traumatic brain injury (TBI) represents one of the leading causes of hospitalization and death among pediatric patients. Admission computerized tomography(CT) scans play an important role in classifying and treating TBI, but little is known about the differences between CT findings in adult and pediatric populations. DESIGN/METHODS: This is a retrospective analysis of TBI registry data from 1,206 consecutive non-penetrating TBI patients treated at a Level 1 adult and pediatric trauma center from August 2008 to January 2011. RESULTS: The distribution of gender, race, and GCS were not significantly different between adult and pediatric populations. The distribution of CT findings, however, was significantly different. Pediatric TBI patients were more likely to have skull fractures (OR 3.21, p CONCLUSIONS: We found significant differences in CT scan findings in pediatric versus adult TBI, despite the fact that both groups were statistically similar with regard to clinical severity of injury as measured by the GCS score. These differences may be due to anatomical characteristics, biomechanics of injury, and/or differences in injury mechanisms between pediatric and adult patients. The unique characteristics of pediatric TBI warrant consideration when designing clinical trial design, or predicting functional outcome using prognostic models developed from adult TBI data. Disclosure: Dr. Sarkar has nothing to disclose. Dr. Zwienenberg-Lee has nothing to disclose. Dr. Muizelaar has nothing to disclose. Dr. Shahlaie has nothing to disclose.
Self-organized dynamics and the transition to turbulence of confined active nematics

We study how confinement transforms the chaotic dynamics of bulk microtubule-based active nematics into regular spatiotemporal patterns. For weak confinements in disks, multiple continuously nucleating and annihilating topological defects self-organize into persistent circular flows of either handedness. Increasing confinement strength leads to the emergence of distinct dynamics, in which the slow periodic nucleation of topological defects at the boundary is superimposed onto a fast procession of a pair of defects. A defect pair migrates toward the confinement core over multiple rotation cycles, while the associated nematic director field evolves from a distinct double spiral toward a nearly circularly symmetric configuration. The collapse of the defect orbits is punctuated by another boundary-localized nucleation event, that sets up long-term doubly periodic dynamics. Comparing experimental data to a theoretical model of an active nematic reveals that theory captures the fast procession of a pair of [Formula: see text] defects, but not the slow spiral transformation nor the periodic nucleation of defect pairs. Theory also fails to predict the emergence of circular flows in the weak confinement regime. The developed confinement methods are generalized to more complex geometries, providing a robust microfluidic platform for rationally engineering 2D autonomous flows.
Compensable transactions

The concept of a compensable transaction has been embodied in modern business workflow languages like BPEL. This article uses the concept of a box-structured Petri net to formalise the definition of a compensable transaction. The standard definitions of structured program connectives are extended to construct longer-running transactions out of shorter fine-grain ones. Floyd-type assertions on the arcs of the net specify the intended properties of the transaction and of its component programs. The correctness of the whole transaction can therefore be proved by local reasoning.
Case Files® Collection on AccessMedicine™

AbstractThe Case Files® Collection on AccessMedicine™ from McGraw-Hill Education provides the complete collection of basic science, clinical medicine, and postgraduate level cases from 23 Case Files® series books in an interactive format. This collection helps users at a variety of levels learn and apply basic science and clinical medicine concepts through the utilization of realistic patient cases to sharpen critical thinking skills and aid in exam preparation. Users can take advantage of personalized functionality to view cases completed and in progress, save favorite items, and create alerts. The collection also allows faculty to include content from clinical cases in their digital curricula.
Atezolizumab potentiates Tcell-mediated cytotoxicity and coordinates with FAK to suppress cell invasion and motility in PD-L1+ triple negative breast cancer cells

Immune check point inhibitors targeting programmed cell death protein-1 (PD-1) and its ligand (PD-L1) have shown clinical success in treatment of human malignancies. Triple negative breast cancer (TNBC), which is primarily characterized by high heterogeneity and presence of tumor infiltrating lymphocytes, remains therapeutic challenge due to unavailability of approved targeted therapy. Therapeutic potential of immune check point inhibitors for TNBC patients is under active clinical investigation. In this study, we show that FDA-approved anti-PD-L1 antibody, atezolizumab (ATE), potentiates T cell-mediated cytotoxicity and apoptosis of TNBC cells that express higher levels of PD-L1, but does not have significant effect on TNBC cells expressing low levels of PD-L1. PD-L1 knockdown further confirmed that ability of ATE to promote T cell-induced cytotoxicity is PD-L1 expression dependent. Combination of ATE with PD-L1 upregulating agents, such as HDAC, proteasomal, and lysosomal inhibitors, further augmented cytotoxic activity of T cells toward TNBC cells. Based on analysis of breast cancer tissue samples deposited in The Cancer Genome Atlas (TCGA), we found a positive correlation between PD-L1 and focal adhesion kinase (FAK) mRNA expression in PD-L1-positive (PD-L1+) TNBC, suggesting a functional association of FAK and immune checkpoints. We further demonstrate that ATE dramatically downregulates phosphorylation status of FAK, an important regulator of cell invasion and migration, and significantly enhances FAK inhibitor mediated inhibition of cell motility and invasion of PD-L1+ TNBC cells independent of T cells. Taken together, our data suggest that ATE shows promising anti-tumor activity in PD-L1+ TNBC via both T cell-dependent and -independent mechanisms.
Carnosine Supplementation Mitigates the Deleterious Effects of Particulate Matter Exposure in Mice

Background Exposure to fine airborne particulate matter (PM 2.5) induces quantitative and qualitative defects in bone marrow–derived endothelial progenitor cells of mice, and similar outcomes in hu...
Activity-Based Sensing for Site-Specific Proteomic Analysis of Cysteine Oxidation.

ConspectusOxidative post-translational modifications (OxiPTMs) of cysteine residues are the molecular foundation of thiol-based redox regulation that modulates physiological events such as cell pro...
ASSOCIATION OF DIABETES MELLITUS WITH POOR OUTCOMES IN PATIENTS WITH INFECTIVE ENDOCARDITIS

While studies have demonstrated an increased risk for infective endocarditis (IE) in patients with diabetes mellitus (DM), it is unclear if the coexistence of DM and IE portends a higher risk of cardiovascular outcomes. We reviewed the records of 11,955 patients from the National Inpatient Sample (
ldquo Silent rdquo Acute Native Valve Leaflet Avulsion during Transcatheter Aortic Valve Replacement

It is estimated that more than of the population above the age of suffer from significant aortic stenosis Transcatheter aortic valve replacement TAVR is increasing being utilized in the treatment of surgically high risk or inoperable patients with severe symptomatic aortic stenosis and has been shown to increase survival With the unavoidable operator learning curve unexpected adverse events are likely to be encountered These should be promptly recognized and the appropriate management strategy instituted Feared complications include annulus rupture ldquo frozen leaflet coronary occlusion embolization of the prosthetic device Cerebrovascular accidents as well as complications related to the vascular access site However other uncommon events may occur that also have the potential to be catastrophic We describe a case of acute native leaflet avulsion during a TAVR procedure Fortunately this was of no significant hemodynamic importance and the patient was successfully managed conservative
The Unseen Picture: Issues with Health Care, Discrimination, Police and Safety, and Housing Experienced by Native American Populations in Rural America

PURPOSE Despite increased national attention to improving rural health, rural Native American populations face unique problems that are often unseen in aggregate research on the rural United States. The objective of this study was to examine rural Native Americans' experiences with serious problems across domains important to health, using rural Whites as a comparison group. METHODS Using 2 probability-based national telephone surveys (2017 and 2019), we examined rural Native American adults' reported problems in health care, discrimination, police and safety, and housing. We then compared Native American-White differences in reported problems across domains. FINDINGS Among rural Native American adults, 33% reported recent problems accessing health care when they needed it, 28% reported they or family members recently experienced major problems paying for medical bills, and 28% reported recent problems with health care quality. Several Native American-White differences were reported, including experiencing racial violence (34% vs 5%, P < .001), discrimination in health care (19% vs 3%, P = .003), unfair police treatment (27% vs 5%, P = .002), and major housing problems (48% vs 26%, P < .001). CONCLUSIONS Rural Native American adults report ongoing and widespread problems with health care, discrimination, the police, safety, and housing. These findings support many national policy recommendations to improve federal funding and oversight for programs serving Native American populations living in rural areas.
Unraveling the Mysteries of PAX8 in Reproductive Tract Cancers.

Paired Box 8 (PAX8) is a lineage-specific transcription factor that has essential roles during embryogenesis and tumorigenesis. The importance of PAX8 in the development of the reproductive system is highlighted by abnormalities observed upon the loss or mutation of this PAX family member. In cancer, PAX8 expression is deregulated in a key set of neoplasms, including those arising from the Mullerian ducts. The roles of PAX8 in oncogenesis are diverse and include epigenetic remodeling, stimulation of proliferation, inhibition of apoptosis, and regulation of angiogenesis. PAX8 can interact with different protein partners during cancer progression and may exhibit significant function-altering alternative splicing. Moreover, expression of PAX8 in cancer can also serve as biomarker for diagnostic and prognostic purposes. In this review, we focus on the roles of PAX8 in cancers of the reproductive system. Understanding the diverse mechanisms of action of PAX8 in development and oncogenesis may identify new vulnerabilities in malignancies that currently lack effective therapies.
Otolaryngology Resident Wellness, Training, and Education in the Early Phase of the COVID-19 Pandemic.

Objective:To determine changes in the residency experience early in the COVID-19 pandemic and evaluate wellness measures among otolaryngology residents.Methods:A web-based survey was administered t...
The Italian Catholic God Does Not Sit Well with American Critics

I promessi sposiholds a central place in Italian literature as its first great historical novel. It is hailed for having contributed significantly to the systematization of the Italian language in the prose medium. Outside of Italy, however, and particularly in America, I promessi sposiis little read. In general, it does not command the same respect as other comparable big nineteenth-century novels nor has it solicited much commentary in the English-speaking world. It is not featured, for example, in the principal American anthologies dealing with the genre. This paper examines why I promessi sposireceives so little attention in the US. What is it about the novel that does not suit American tastes? This paper makes the case thatI promessi sposi’sreligious thematic hinders its popularity. I begin by considering the role religion plays in American literary studies as a scholarly topic of inquiry. I then discuss the religious dimensions of I promessi sposi. Finally, I will investigate how the Catholic message of Manzoni’s novel may have affected its reception both at home and in the US. I will also touch upon the role of anti-Catholic and anti-Italian nativism still prevalent in American society.
Intuitive Hedonism

The hoary philosophical tradition of hedonism – the view that pleasure is the basic ethical or normative value – suggests that it is at least reasonably and roughly intuitive. But philosophers no longer treat hedonism that way. For the most part, they think that they know it to be obviously false on intuitive grounds, much more obviously false on such grounds than familiar competitors. I argue that this consensus is wrong. I defend the intuitive cogency of hedonism relative to the dominant desire-based and objectivist conceptions of well-being and the good. I argue that hedonism is still a contender, and indeed that our current understanding of commonsense intuition on balance supports it.
Division of labor between the pore-1 loops of the D1 and D2 AAA+ rings coordinates substrate selectivity of the ClpAP protease.

Abstract ClpAP, an ATP-dependent protease consisting of ClpA, a double-ring hexameric unfoldase of the AAA+ (ATPases associated with diverse cellular activities) superfamily and the ClpP peptidase, degrades damaged and unneeded proteins to support cellular proteostasis. ClpA recognizes many protein substrates directly, but it can also be regulated by an adaptor, ClpS, that modifies ClpA’s substrate profile towards N-degron substrates. Conserved tyrosines in the twelve pore-1 loops lining the central channel of the stacked D1 and D2 rings of ClpA are critical for degradation, but the roles of these residues in individual steps during direct or adaptor-mediated degradation are poorly understood. Using engineered ClpA hexamers with zero, three, or six pore-1 loop mutations in each AAA+ ring, we found that active D1 pore loops initiate productive engagement of substrates, whereas active D2 pore loops are most important for mediating the robust unfolding of stable native substrates. In complex with ClpS, active D1 pore loops are required to form a high affinity ClpA•ClpS•substrate complex, but D2 pore loops are needed to “tug on” and remodel ClpS to transfer the N-degron substrate to ClpA. Overall, we find that the pore-1 loop tyrosines in D1 are critical for direct substrate engagement, whereas ClpS-mediated substrate delivery requires unique contributions from both the D1 and D2 pore loops. In conclusion, our study illustrates how pore loop engagement, substrate capture, and powering of the unfolding/translocation steps are distributed between the two rings of ClpA, illuminating new mechanistic features that may be common to double-ring protein unfolding machines.
Effects on plant growth of inoculation of stored stripmining topsoil in North Dakota with mycorrhizal fungi contained in native soils

Stored topsoil from stripmining operations in western North Dakota was inoculated with mycorrhizal fungi contained in native prairie soil. The effects on plant mycorrhizal infection percentage, growth as shoot dry weight, and phosphorus uptake were determined. The studied topsoil piles were found to contain little or no vesicular arbuscular mycorrhizal (VAM) fungal inoculum at a depth of 120 cm. The inoculum soil was mixed into the stored soil at rates of 10% and 1%, or surface-applied at 1%. In control pots, sterilized inoculum soil was used. Corn plant (Zea mays) bioassays were used. After 30 days growth the percent VAM fungal infection of the test plants increased with both the 10% and 1% soil inocula. Phosphorus concentrations were generally increased by inoculation with 10% soil mixtures but not 1%. Shoot dry weights of the plants were not measurably different between 10% and 1% inoculation. However, when the plant growth period was increased to 60 days, all three parameters were increased over the check plants. When the inoculum was not mixed into the soil, but layered on the surface, there were no differences in any of the parameters.
A prototype user interface for a mobile electronic clinical note entry system.

Recent advances in mobile computing technologies have made electronic medical records (EMRs) on handheld devices an attractive possibility. However, data entry paradigms popular on desktop machines do not translate well to mobile devices1,2. Based on a review of the literature on mobile device usability1–4, we built a prototype user interface for mobile EMRs and held focus groups with clinician users whose feedback provided useful insight about design choices, functionality and optimal workflow integration.
Conscious software: a computational view of mind

Here we describe a software agent that implements the global workspace theory of consciousness. A clerical agent that corresponds with humans in natural language via email, CMattie composes and sends weekly seminar announcements to a mailing list she maintains. She's designed under a two tiered architecture with high-level concepts, behaviors, associations, etc., undergirded with low-level codelets that do most of the actual work. A wide variety of computational mechanisms, many taken form what is now called softcomputing, flesh out the architecture. As a computational model, CMattie provides ready answers, that, is testable hypotheses, to very many questions about human cognition. Several such are noted. There's also a discussion of the extent to which such "conscious" software agents can be expected to be conscious.
Improved generation of anti-tumor immunity by antigen dose limitation

Background The malignant cells of cutaneous T cell lymphoma (CTCL) display immunogenic peptides derived from the clonal T cell receptor (TCR) providing an attractive model for refinement of anti-tumor immunization methodology. To produce a clinically meaningful anti-tumor response, induction of cytotoxic anti-CTCL cells must be maximized while suppressive T regulatory cells (Treg) should be minimized. We have demonstrated that engulfment of apoptotic CTCL cells by dendritic cells (DC) can lead to either CD8 anti-CTCL responses or immunosuppressive Treg induction. Treg generation is favored when the number of apoptotic cells available for ingestion is high.
The Role of Angiogenesis in Neuroblastoma

Neuroblastoma (NB), a common pediatric neoplasm arising from neural crest cells, is characterized by a diversity of clinical behavior ranging from spontaneous remission to rapid tumor progression and death. Biologic and genetic factors have been identified which, to a certain extent, can predict prognosis and guide risk-based therapy. Recent research has focused on the role of angiogenesis in NB tumor biology and in determining clinical phenotype. Preclinical studies have explored the efficacy of antiangiogenic therapies as a novel treatment modality for children with NB. This review discusses the current understanding of angiogenesis in NB, the clinical implications, and future directions for antiangiogenic therapeutic strategies in NB.
Metabolite regulation of argininosuccinate synthetase in cultured human cells.

We have studied the transcription of the argininosuccinate synthetase gene in cultured RPMI 2650 cells under conditions where the enzyme is subject to metabolite regulation and in canavanine-resistant variants (Canr1 cells) which overproduce the enzyme greater than 200-fold. When grown continuously in medium with citrulline substituted for arginine, the argininosuccinate synthetase activity of RPMI 2650 cells increases 5- to 10-fold. In these cells, expression of a transfected minigene containing the 5′-flanking region of the argininosuccinate synthetase gene was increased 20-fold by short term starvation for arginine and 10-fold by short term starvation for leucine. Levels of nuclear RNA from the first intron of the gene correlated with enzyme activity; i.e. RPMI 2650 cells cultured in arginine medium less than RPMI 2650 cells cultured in citrulline medium less than Canr1 cells. Run-off transcription experiments showed that the transcription of argininosuccinate synthetase increased in RPMI 2650 cells starved for either arginine or leucine. While expression of the minigene and the transcription rate for argininosuccinate synthetase were increased during 48 to 72 h of starvation, the endogenous enzyme activity did not increase in RPMI 2650 cells. Amino acid starvation did not affect the rate of transcription of argininosuccinate synthetase in Canr1 cells. The results indicate that the steady state levels of argininosuccinate synthetase expression in Canr1 cells and in citrulline-adapted RPMI 2650 cells are largely determined by the rate of transcription. The failure of increased transcription rate to correlate with increased enzyme activity during acute starvation for arginine or leucine may suggest the involvement of post-transcriptional regulatory mechanisms for argininosuccinate synthetase or may merely be due to amino acid deprivation. The finding that leucine starvation has effects similar to arginine starvation raises the question of whether mammalian cells have general control mechanisms which are similar to the general control of amino acid biosynthesis in Saccharomyces cerevisiae.
Studies with tRNA adenylyl(cytidylyl)transferase from Escherichia coli B: II. Regulation of AMP and CMP incorporation into tRNApCpC and tRNApC☆

Abstract Incorporation of CMP into tRNApCpC by tRNA adenylyl(cytidylyl)transferase purified 7000-fold from Escherichia coli occurs in the absence of ATP. This abnormal reaction is prevented by the presence of ATP or by short-term incubation and is, to a large extent, influenced by enzyme concentration. More than one CMP (multiple CMP) will be accepted by tRNApC in the absence of ATP but not in its presence. This may reflect a control mechanism at the cellular level whereby the integrity of the CCA terminus of the tRNA is maintained by the ATP:CTP concentration. AMP incorporation into tRNApC or pyrophosphorolyzed tRNA is incomplete if unlimited CMP incorporation is allowed to precede it. After removal of a portion of the CCA terminus of purified tRNA Phe ( E. coli ) by pyrophosphorolysis, the amino acid acceptor activity could be restored by the transferase only if both CMP and AMP incorporation occur simultaneously. Pyrophosphorolyzed purified tRNA Val ( E. coli ) was also restored to its original acceptor activity by simultaneous CMP and AMP incorporation. Both UMP and AMP are incorporated by the transferase into tRNApC.
Avaliação do estresse oxidativo e contaminação por chumbo em praticantes de tiro esportivo - DOI: 10.4025/actascihealthsci.v25i1.2300

Lead is a toxic metal used in munitions. Recent studies have shown indications of oxidative stress in mice treated with lead acetate. Our work had the goal of evaluating the possible correlation of lead and oxidative stress in human outdoor and indoor marksmen. The lead concentration was measured by atomic absorption. Oxidative stress was accessed through the reaction products with tiobarbituric acid (TBARS) and the total antioxidant capacity was appraised using Total Antioxidant Status (RANDOX ® ). The results show that 12,5% of the outdoor and 20,8% of the indoor marksmen present lead values over what is considered normal in non-exposed groups. TBARS were significantly higher for marksmen than for the control group. No statistically significant differences in the total serum antioxidant capacity were observed in individuals tested.
A Classification Problem in Medical Radioscintigraphy

While digital image processing in nuclear medicine until recently consisted in a quality improvement by various filter methods, but left the recognition and classification fully to the human inspection and experience, the proposed test is a step towards automatic pattern recognition and classification. Its practical application is still in the beginning stage, but the success with simulated images lets us assume that it will be helpful in the clinical work.
ID: 14: Immune regulation at barrier surfaces

Employing models of microbial colonization, pathogen infection, chronic inflammation and tissue repair, research in the Artis lab is examining how mammalian host genetics and signals derived from the environment and commensal microbial communities influence innate and adaptive immune cell responses. We are employing gnotobiotic mice to examine the influence of defined commensal microbial communities on intestinal and peripheral immune cell development, function and influence on tissue homeostasis. Our recent findings indicate that commensal microbes have a significant regulatory influence on lymphocyte, innate lymphoid cell and granulocyte function associated with susceptibility to multiple infectious, inflammatory and metabolic disease processes. It is hoped that the results of these studies will advance understanding of the pathophysiology of multiple chronic inflammatory diseases, including asthma, allergy, inflammatory bowel disease and obesity, and provide a framework to test new therapeutic pathways to prevent and treat these diseases.
Substitutions in the Ω-Loop of TEM β-Lactamase Change the Substrate Profile of the Enzyme (LB140)

Serine β-lactamases are bacterial enzymes that hydrolyze β-lactam antibiotics. Mechanistically, serine β-lactamases are similar to serine proteases such as chymotrypsin. They both utilize acylation and deacylation of an active site serine in their mechanism of catalysis. TEM-1, a common plasmid-encoded serine β‐lactamase, catalyzes the hydrolysis of early penicillins and cephalosporins. Here we examine a previously identified triple mutant of TEM-1, 165-TyrTyrGly-167 (wild type165-TrpGluPro-167) with substrate specificity altered from preferential hydrolysis of ampicillin to that of ceftazidime. When compared to chymotrypsin, the Glu166Tyr substitution in the TEM-1 triple mutant is analogous to a substitution of the general base His57 in chymotrypsin that results in an enzyme that maintains function. Our findings agree with previous observations of altered substrate specificity of the triple mutant, which displays increased hydrolysis of ceftazidime. Additionally, enzyme kinetic analyses show that the hyd...
Improvement of fault tolerance in AC motor drives using a digital delta-hysteresis modulation scheme

In this paper, a novel digital delta-hysteresis regulation (DDHR) scheme is proposed that allows motor drive systems to maintain relatively accurate control of phase currents in the event of the loss of all phase current sensors. Within the scheme, line currents are reconstructed using knowledge of the DC-link current and switching states. The generation of switching signals is based upon traditional delta-hysteresis regulation (DHR). However, modifications are made to DHR to ensure the DC-link current always contains sufficient information to reconstruct phase currents. Experimental results obtained from a vector-controlled induction machine are used to show that there is a relatively small difference between the performance of the pre- and post- fault systems.
Collaboratories: doing science on the Internet

The success of many complex scientific investigations hinges on bringing the capabilities of diverse individuals from multiple institutions together with state-of-the-art instrumentation. Computer scientists working with domain specialists have made progress on several fronts to create and integrate the tools required for Internet-based scientific collaboration. However, both technical and sociological challenges remain. The tools of computer-supported cooperative work are now being applied to such collaborations. Through immersive electronic interaction, team members distributed across a widespread area can collaborate, using the newest instruments and computing resources. The paper discusses some collaboratory prototypes and considers the sociology of collaboration.
Manometric responses of human duodenum during infusion of HCl, hyperosmolar saline, bile and oleic acid

Duodenal motor activity is incompletely understood. The purpose of this study was to define the contractile patterns of the duodenum that occur in response to rate controlled injection of various solutions. In nine healthy volunteers we placed a six channel perfused catheter, and recorded pressure activity in the antrum, pylorus and duodenum. Volumes of 10 and 20 mL of 0.9% NaCl, 100 mM HCl (pH 1), 5% NaCl (1711 mOsm/kg), human bile and iso-osmolar sodium oleate were randomly injected into the duodenum at 20 ml/min, starting 15 min after phase III migratory motor complex (MMC). A 20 mL bolus of each solution caused more activity (P < 0.05) than a 10 mL bolus, but the motor pattern was similar. The control, 0.9% NaCl, produced occasional pressure waves, whereas bile and sodium oleate induced more (P < 0.05) activity which consisted of low amplitude, isolated or clusters (2-4 cycle/min) of non-propagating pressure waves that occurred at random sites. In three subjects, oleate produced isolated pyloric phasic contractions. In contrast, HCl and 5% NaCl induced high amplitude pressure waves that were seen either at a single channel or at multiple channels, occurring simultaneously. The motility index was also greater (P < 0.05) than that induced by other solutions. Additionally, within 2 min of infusion, a phase III MMC like pattern was observed in five of the nine subjects who received HCl and three of the nine who received 5% NaCl. A non-nutrient iso-osmolar solution induced occasional motor activity. HCl and hyperosmolar solutions induced more frequent and large amplitude, segmental contractions whereas lipid and bile induced fewer and smaller amplitude contractions. The volume, the pH, the osmolar and the nutrient make up of the infusate may each influence the duodenal motor responses.
Electrophoretic mobility of glucose-6-phosphate dehydrogenase in lymphocytes and granulocytes

Abstract The electrophoretic mobility of glucose-6-phosphate dehydrogenase (G-6-P D) was determined utilizing enzymes from total white blood cells as well as pure populations of polymorphonuclear leukocytes and lymphocytes. The enzyme from the cell fractions was partially purified and characterized. Although different electrophoretic mobilities were found for G-6-P D from lymphocytes and polymorphonuclear leukocytes, the physiochemical characteristics were found to be similar.
Prolactin-induced proliferation of the Nb2 T-lymphoma is associated with protein kinase-C-independent phosphorylation of stathmin.

Phosphorylation of stathmin, a 19-kDa protein found in many tissues, has been linked to cell differentiation and proliferation. This protein is present in lymphocytes, and both phosphorylation and expression of stathmin are regulated by lymphotropic agents. In this study an antibody specific for stathmin was used to examine phosphorylation in response to PRL. The results suggest that PRL stimulates stathmin phosphorylation in the Nb2 lymphoma and that phosphorylation correlates with PRL-induced cell proliferation. Stathmin expression does not change substantially as PRL-stimulated Nb2 cells move through the cell cycle and enter into the S-phase. Thus, stathmin phosphorylation, but not expression, is regulated by PRL. Activation of protein kinase-C (PKC) in Nb2 cells also induces phosphorylation of stathmin, but PKC does not appear to mediate phosphorylation in response to PRL. The pattern of phosphorylation in response to 12-O-tetradecanoylphorbol-13-acetate differs from that in response to PRL, and down-...
Dicaffeoyltartaric acid analogues inhibit human immunodeficiency virus type 1 (HIV-1) integrase and HIV-1 replication at nontoxic concentrations.

The human immunodeficiency virus type 1 (HIV-1) is a major health problem worldwide. In this study, 17 analogues of l-chicoric acid, a potent inhibitor of HIV integrase, were studied. Of these analogues, five submicromolar inhibitors of integrase were discovered and 13 compounds with activity against integrase at less than 10 μM were identified. Six demonstrated greater than 10-fold selectivity for HIV replication over cellular toxicity. Ten analogues inhibited HIV replication at nontoxic concentrations. Alteration of the linkages between the two bis-catechol rings, including the use of amides, mixed amide esters, cholate, and alkyl bridges, was explored. Amides were as active as esters but were more toxic in tissue culture. Alkyl and cholate bridges were significantly less potent against HIV-1 integrase in vitro and were inactive against HIV-1 replication. Two amino acid derivates and one digalloylderivative of l-chicoric acid (l-CA) showed improved selectivity over l-CA against integration in cell cultu...
Quantitative Phase Imaging with a Scanning Transmission X-Ray Microscope

We obtain quantitative phase reconstructions from differential phase contrast images obtained with a scanning transmission x-ray microscope and 2.5 keV x rays. The theoretical basis of the technique is presented along with measurements and their interpretation.
Prevention and Reduction of AD-type Pathology in PDAPP Mice Immunized with Aβ1-42

In AD certain brain structures contain a pathological density of A beta protein deposited into plaques. The effect of genetic mutations found in early onset AD patients was an overproduction of A beta 42, strongly suggesting that overproduction of A beta 42 is associated with AD. We hypothesized that an immunological response to A beta 42 might alter its turnover and metabolism. Young PDAPP transgenic mice were immunized with A beta 1-42, which essentially prevented amyloid deposition; astrocytosis was dramatically reduced and there was reduction in A beta-induced inflammatory response as well. A beta 1-42 immunization also appeared to arrest the progression of amyloidosis in older PDAPP mice. A beta immunization appears to increase clearance of amyloid plaques, and may therefore be a novel and effective approach for the treatment of AD.
Virus‐like, double‐stranded RNAs in the parasitic protozoan Cryptosporidium parvum

We have discovered and analysed two novel, linear extrachromosomal double-stranded RNAs (dsRNAs) within oocysts of major north Amercian isolates of Cryptosporidium parvum, a parasitic protozoan that infects the gastrointestinal tract of a variety of mammals, including humans. These dsRNAs were found to reside within the cytoplasm of sporozoites, and were not detected in other species of the genus. cDNAs representing both dsRNA genomes were cloned and sequenced, 1786 and 1374 nt, and each encoded one large open reading frame (ORF). The deduced protein sequence of the larger dsRNA (L-dsRNA) had homology with viral RNA-dependent RNA polymerases (RDRP), with more similarity to polymerases from fungi than those from other protozoa. The deduced protein sequence from the smaller dsRNA (S-dsRNA) had limited similarity with mitogen-activated c-June NH2 terminal protein kinases (JNK) from mammalian cells. Attempts to visually identify or purify virus-like particles associated with the dsRNAs were unsuccessful. Sensitivity of the dsRNAs to RNase A also suggests that the dsRNAs may be unencapsidated. A RDRP activity was identified in crude extracts from C. parvum sporozoites and products of RNA polymerase activity derived in vitro were similar to the dsRNAs purified directly from the parasites.