cssi/SciSciGPT-SciSciNet huggingface dataset:
Hypoglossal Cranial Nerve Palsy: Unusual Microvascular Complication (P6.011)

Objective: Hypoglossal nerve palsy without evidence of grave underlying pathology or surgical interventions is infrequent in literature. We report a unilateral hypoglossal nerve palsy developed in the setting of microvascular infarct, which may have been categorized idiopathic. Here we investigate a 76-year-old lady with hyperlipidemia admitted with lateral neck pain and development of dyarthria with a profound tongue deviation likely from microvascular infarct given the time course, pain preceding motor symptoms and recovery. Awareness of the possibility of ischemic microvascular causes in cranial nerves may be key to appropriate treatment and recovery. Background: Reported causes of isolated hypoglossal nerve palsy include metastasis, nasopharyngeal carcinoma, skull base fracture, blunt head trauma, carotid dissection, Chiari malformation, medial medullary infarcts and rarely infectious mononucleosis. Many idiopathic cases in younger individuals have been observed to resolve spontaneously and present with a specific pattern of pain preceding motor symptoms, which may clue into the microvascular nature of etiology. Design/Methods: N/A Results: The evidence for the microvascular nature of this patient’s isolated hypoglossal injury can be found in several key aspects of this patient’s risk factors, presentation and clinical course. Specifically, the patient had major vascular risk factors that significantly increased the likelihood of a presumed microvascular etiology as in other idiopathic cranial nerve palsies, such as isolated third, fourth and sixth cranial nerve palsies. Ischemia of particular segments of the nerve cause inflammation of the sheath, which affects trigeminal-innervated territories and explain the pain experienced by our patient. Conclusions: Isolated hypoglossal nerve injury in a setting free of trauma, malignancy or other underlying anatomical pathology is rare. The etiology of nerve injury in our patient is postulated to be microvascular ischemia given clear vasculopathic risk factors, structural location and association pain. Attention to these factors may allow for wider recognition of such cases and optimal care. Disclosure: Dr. Chilakamarri has nothing to disclose. Dr Bhattacharyya has nothing to disclose.
Photochemical conversion of a cytidine derivative to a thymidine analog via [2+2]-cycloaddition

Epigenetic information is encoded in the mammalian genome in the form of cytosines methylated at the 5 position. Cytosine methylation has multiple biological effects, but our understanding of these effects has lagged because extant methods for mapping methylation sites genome-wide have severe shortcomings. For instance, the gold standard bisulfite sequencing approach suffers from the use of harsh reaction conditions resulting in DNA cleavage and incomplete conversion of unmethylated cytosine to uracil. We report here on a new photochemical method in which a DNA (cytosine-5)-methyltransferase can be used to covalently attach reactive functionalities which upon irradiation at ∼350 nm initiate photoinduced intramolecular reactions that convert modified C to T analogues. We synthesized a model compound, a cinnamyl ether-containing cytidine derivative, and demonstrated its conversion to a thymidine analogue using mild conditions and a DNA-compatible wavelength (∼350 nm), enabled by the use of a triplet sensitizer, thioxanthone. Transfer of a cinnamyl ether or comparable reactive functionality from an AdoMet analog to cytosine followed by the use of this photoconversion method would require only small amounts of DNA and allow complete methylation profiling on both long and short read sequencing platforms.
Crowdsourcing in HCI Research

By recruiting large numbers of people online to perform small tasks, researchers can perform important assessments that are hard to obtain otherwise, at a very reasonable cost and speed. These tasks include assessing quality, reading characters that OCR readers can’t decipher, labeling photographs, and even answering questions in a survey. Care must be taken in using crowdsourcing, however, because some people “game” the system or simply misunderstand the task. However, there are techniques to minimize or detect questionable data.
A sequential multinomial selection procedure with elimination

We discuss a multinomial procedure for selecting the best of a number of competing systems or alternatives. The new procedure is an augmentation of the Bechhofer and Kulkarni (1984) (BK) sequential indifference-zone procedure for selecting the most probable multinomial cell; the augmentation eliminates noncompetitive events from further consideration as sampling progresses. The advantages of this procedure over the BK procedure are highlighted with specific attention given to the reduction in the expected number of total samples required. We present Monte Carlo simulation results to illustrate the performance of the cell elimination augmentation.
Diagnostic Imaging for Pediatric Appendicitis

Children with suspected appendicitis may be diagnosed based on history and physical examination, but often require imaging, including ultrasonography (U/S), computed tomography (CT), magnetic resonance imaging (MRI), or a sequential combination. Modality choice is multifactorial, with characteristics of the patient, family, facility, provider, method, and technique influencing imaging decisions. All three modalities exhibit strong test characteristics (sensitivity and specificity) and have a role in the diagnostic armamentarium for evaluating pediatric abdominal pain. The purpose of this chapter is to review the strengths and weakness of each modality, describe adjunct methods to improve their utility, and discuss the controversies surrounding imaging choice.
Black Skin, White Faces: Dead Presidents and the African-American Vietnam Veteran

Kathleen McClancy focuses on the marginalized perspective of the African-American Vietnam veteran in both war films and scholarship. She argues that the film Dead Presidents (1995) reverses the typical Vietnam movie plot, both restoring and contextualizing the experiences of Blacks and veterans in American more generally. In this way, the film reminds Americans of the often-repressed black struggle and offers a revolutionary framework for violence and “gangsta” culture. It also, however, displays how American cultural memory tends to maintain structural inequality via the marginalization of minorities. To address this, McClancy calls on scholars to continue to focus on marginal war films so as not to further silence minority voices.
RAF autoinhibition and 14-3-3 proteins promote paradoxical activation

Abstract RAF kinase inhibitors can actually increase RAF kinase signaling. This process, which is commonly referred to as “paradoxical activation” (PA), is incompletely understood. RAF kinases are regulated by autoinhibitory conformational changes, and the role of these conformational changes in PA is unclear. Our mathematical investigations find that PA can result from a dynamical equilibrium between autoinhibited and non-autoinhibited forms of RAF, along with the RAF inhibitor stabilizing the non-autoinhibited form. We also investigate whether PA is influenced by 14-3-3 proteins, which can both stabilize RAF autoinhibition and RAF dimerization. Using both computational and experimental methods we demonstrate that 14-3-3 proteins potentiate PA. Third generation RAF inhibitors normally display minimal to no PA. Our mathematical modeling led us to hypothesize that increased 14-3-3 expression should also amplify PA for these agents. Subsequent experiments support our hypothesis and show that 14-3-3 overexpression increases PA in these third generation RAF inhibitors, effectively “breaking” these “paradox breakers” and pan-RAF inhibitors. We have therefore created and experimentally validated a robust mechanism for PA based solely on equilibrium dynamics of canonical interactions in RAF signaling.
The Bromodomains of the mammalian SWI/SNF (mSWI/SNF) ATPases Brahma (BRM) and Brahma Related Gene 1 (BRG1) promote chromatin interaction and are critical for skeletal muscle differentiation

Skeletal muscle differentiation induces changes in the epigenome of myoblasts as they proceed towards a myogenic phenotype. mSWI/SNF chromatin remodeling enzymes coordinate with lineage-determining transcription factors and are key regulators of differentiation. Three mSWI/SNF proteins, the mutually exclusive ATPases, BRG1 and BRM, and the BAF180 protein (Polybromo1, PBRM1) contain bromodomains belonging to the same structural subfamily. Bromodomains bind to acetylated lysines on histone N-terminal tails and on other proteins. Pharmacological inhibition of mSWI/SNF bromodomain function using the selective inhibitor PFI-3 reduced differentiation, decreased expression of myogenic genes, and increased the expression of cell cycle-related genes and the number of cells that remained in the cell cycle. Knockdown of BAF180 had no effect on differentiation, suggesting that only the BRG1 and BRM bromodomains contributed to differentiation. Comparison with existing gene expression data from myoblasts subjected to knockdown of BRG1 or BRM showed that bromodomain function was required for a subset of BRG1- and BRM-dependent gene expression. ChIP analysis revealed decreased BRG1 and BRM binding to target gene promoters, indicating that the BRG1 and BRM bromodomains promote chromatin binding. Thus mSWI/SNF ATPase bromodomains contribute to cell cycle exit, to skeletal muscle-specific gene expression, and to stable promoter binding by the mSWI/SNF ATPases.
Book Review: Myles Mcgregor-Lowndes and Bob Wyatt (Eds.), Regulating Charities: The Inside Story, New York: Routledge (2017)

REGULATING CHARITIES: THE INSIDE STORY is a fascinating amalgam that is part history, part chronology, and part storytelling about recent changes in how five historically connected common law countries approach regulating their charitable sectors. These countries are England and Wales, the United States, Canada, New Zealand and Australia, with each country’s evolutions being covered distinctively in at least two chapters. Chapter authors include those who have served as principle executives of their country’s primary regulatory body, members and chairs of government oversight commissions, a legislator, and leaders and practitioners from within the respective charitable sectors, including one with a decidedly state-level orientation. Many authors cross several categories, and some cut across multiple jurisdictions having served as advisors to others or substantive participants in international gatherings of charitable sector regulators. The book decidedly eschews a coordinated effort or commanded approach and successfully avoids merely comparing and contrasting among jurisdictions. Instead, the editors allow the chapter authors to communicate their perspectives on and experiences with the recent changes in the manner they believe will be most useful. In the process, the reader can draw their own comparisons, especially across the several key themes that organically emerge: the influence of political power, challenges balancing regulator independence vis a vis government and the sector, views of permissible proactive engagement by charitable sector entities in policy activity, and the effects in some countries of increasingly blurring lines with other sectors -- government and business. With this combination and approach, REGULATING CHARITIES satisfies certain curiosities, stokes others, and ignites new ones, perhaps especially in allowing the reader to decipher for him or herself just how much of the approaches taken by any given jurisdiction may or may not be readily transferrable to others. The book succeeds in demonstrating that appropriately regulating the charitable sector is challenging and that adapting from another jurisdiction(s) is not as easy nor as obvious as it might appear on the surface.
Sociology’s inescapable past:

Why does sociology teaching uniquely require study of its classics? The answer, it is suggested, lies in the indeterminacy of the idea of what is social—what constitutes and exemplifies it, at diff...
Implications of changing cropping pattern to low water demand plants due to climate change: evidence from Iran

In this research, 17 implications of changing cropping patterns (CP) to low water demand plants (LWDPs) were identified. Then, the experts were asked to determine the standard (optimal) level of each implication. In addition, the farmers were to determine the extent that each of these implications was implemented in the region under the study. Further, the status of each of the implications was evaluated both horizontally and vertically. In the horizontal mode, the level of implementation for each implication was compared to its standard level, while the ranking of the implementation level of the implications was evaluated with their standard level rank in the vertical mode. The results showed that the implementation level for all implications was lower than the standard level, and the difference means were significant in all of the 17 cases. Also, it has been found that the three implications, viz. (i) giving production input in the form of subsidy to farmers, (ii) making easier credit and facilities, and (iii) the use of local leaders and successful farmers to extend the cultivation of LWDPs, are the most important implications in changing the CP to LWDPs. The implementation priorities for these implications are 15, 12, and 1, respectively. The results indicated that none of the above implications have yet been met to change the CP in Iran.
Biosynthesis of Oligogalactosyl Side Chains of the Cell Envelope Glycoprotein of Cryptococcus laurentii

Abstract A particulate enzyme preparation from the fungus imperfectus Cryptococcus laurentii var. flavescens (NNRL Y-1401) catalyzes the transfer of galactosyl residues from UDP-[14C]-galactose to an endogenous acceptor. The radioactive reaction product is particle-bound, but is solubilized by pronase treatment. The solubilized radioactive material migrates as a single peak on a column of Sepharose 4-B, indicating that the galactosyl residues are transferred to an endogenous polymeric acceptor of high molecular weight. After elution from Sepharose 4B the material was found to contain 70% carbohydrate and 30% protein. The monosaccharides released after acid hydrolysis are mannose, galactose, and xylose, galactose being the only radioactive monosaccharide constituent. The radioactive reaction product is retained on DEAE-cellulose, from which over 80% of it is eluted with 0.5 m NaCl together with endogenous carbohydrate and protein. After treatment with NaOH-NaBH4, the radioactive material no longer binds to DEAE-cellulose. Subsequent gel filtration on Sephadex G-25 results in a symmetrical radioactive peak of approximately 2000 molecular weight, suggesting liberation of a dodecasaccharide chain. Treatment with NaOH-NaB3H4 followed by complete acid hydrolysis allows the isolation of tritium-labeled alanine and α-aminobutyric acid, indicating that carbohydrate side chains are linked through seryl and threonyl residues to protein. The major radioactive disaccharides isolated after partial acid hydrolysis are 6-O-α-[14C]galactosyl-O-[14C]galactose and O-β-[14C]-galactosyl-O-mannose. The data suggest addition of multiple galactosyl residues to an endogenous glycoprotein acceptor: the first galactosyl residue is linked to a mannosyl residue forming a β linkage; subsequently additional galactosyl residues are transferred sequentially forming linear chains containing 6-O-α-galactosyl-O-galactosyl linkages.
Cholesterol at the Endoplasmic Reticulum: Roles of the Sigma-1 Receptor Chaperone and Implications thereof in Human Diseases

Despite substantial data elucidating the roles of cholesterol in lipid rafts at the plasma membrane, the roles of cholesterol and related lipids in lipid raft microdomains at the level of subcellular membrane, such as the endoplasmic reticulum (ER) membrane, remain less understood. Growing evidence, however, begins to unveil the importance of cholesterol and lipids on the lipid raft at the ER membrane. A few ER proteins including the sigma-1 receptor chaperone were identified at lipid raft-like microdomains of the ER membrane. The sigma-1 receptor, which is highly expressed at a subdomain of ER membrane directly apposing mitochondria and known as the mitochondria-associated ER membrane or MAM, has been shown to associate with steroids as well as cholesterol. The sigma-1 receptor has been implicated in ER lipid metabolisms/transports, lipid raft reconstitution at the plasma membrane, trophic factor signalling, cellular differentiation, and cellular protection against β-amyloid-induced neurotoxicity. Recent studies on sigma-1 receptor chaperones and other ER proteins clearly suggest that cholesterol, in concert with those ER proteins, may regulate several important functions of the ER including folding, degradation, compartmentalization, and segregation of ER proteins, and the biosynthesis of sphingolipids.
On the Lift and Circulation of Airfoils in Some Unsteady-Flow Problems

RIEF REPORTS of investigations in the aeronautical sciences and discussions of papers published in the JOURNAL are presented in this special department. The publication will be completed as soon as possible after receipt of the material. The Editorial Committee does not hold itself responsible for the opinions expressed by the correspondents. Contributions should not exceed 800 words in length. B
Lipid mediators and their metabolism in the nucleous: implications for Alzheimer's disease

Lipid mediators are important endogenous regulators derived from enzymatic degradation of glycerophospholipids, sphingolipids, and cholesterol by phospholipases, sphingomyelinases, and cytochrome P450 hydroxylases, respectively. In neural cells, lipid mediators are associated with proliferation, differentiation, oxidative stress, inflammation, and apoptosis. A major group of lipid mediators, which originates from the enzymatic oxidation of arachidonic acid, is called eicosanoids (i.e., prostaglandins, leukotrienes, thromboxanes, and lipoxins). The corresponding lipid mediators of docosahexaenoic acid metabolism are named as docosanoids. They include resolvins, protectins (neuroprotectins), and maresins. Docosanoids produce antioxidant, anti-inflammatory, and antiapoptotic effects in brain tissue. Other glycerophospholipid-derived lipid mediators are platelet activating factor, lysophosphatidic acid, and endocannabinoids. Degradation of sphingolipids also results in the generation of sphingolipid-derived lipid mediators, such as ceramide, ceramide 1-phosphate, sphingosine, and sphingosine 1-phosphate. These mediators are involved in differentiation, growth, cell migration, and apoptosis. Similarly, cholesterol-derived lipid mediators, hydroxycholesterol, produce apoptosis. Abnormal metabolism of lipid mediators may be closely associated with pathogenesis of Alzheimer's disease.
Effect of the beta6 Glu replaced by Val mutation on the optical activity of hemoglobin S and of its beta subunits.

The carbomonoxy derivatives of hemoglobin A and S showed a different optical activity in the Soret region of the spectrum as measured by circular dichroism. Different optical activity was also measured in the carbomonoxy derivatives of the beta subunits of hemoglobin A and S, the respective deoxy derivatives showed different circular dichroism spectra only in the presence of inositol hexaphosphate. Sedimentation velocity experiments showed that the differences in optical activity are not due to a different state of aggregation of the subunits. Modification of the tertiary structure of the beta subunits seems to be responsible for the phenomenon. Speculation based on the work of Hsu and Woody (Hsu, M.C., and Woody, R.W. (1971) J. Am. Chem. Soc. 93, 3515-3525) suggests the involvement of the beta15 tryptophan in the conformational changes produced by the beta6 Glu-Val mutation in hemoglobin S.
Sex-linked hydrocephalus. Report of two families, with chromosomal study of two cases.

Two families, each containing more than one hydrocephalic male member, have been reported. Chromosomal analysis has been normal in one member of each family. Reports of 11 families have been found in the literature with multiple male hydrocephalic members and without affected female members. From an analysis of these families it seems likely that there is a sex-linked factor in the heredity of one form of hydrocephalus.
Severe Hyperandrogenemia and Insulin Resistance in a 12-Year-Old Girl

Abstract Background Signs of androgen excess are common complaints of adolescents and young adults. Rapid onset/progression of hyperandrogenism or virilization should prompt further investigation to exclude an androgen-secreting tumor. Case We report the case of an obese young adolescent girl who presented with hirsutism, deepened voice, oligomenorrhea, marked acanthosis nigricans, and rapidly increasing testosterone and insulin levels. Imaging studies were negative for both ovarian and adrenal masses. She was successfully treated with continuous combined oral contraceptives. Investigation, treatment, and outcome are reviewed. Summary and Conclusion This case demonstrates that patients with PCOS may present with a testosterone > 200 ng/dL and that severe hyperinsulinemia can be associated with rapid progression of hyperandrogenism.
Design of Triple Helix Forming C-Glycoside Molecules

The modeling, synthesis, and characterization of oligomers containing 2-aminoquinazolin-5-yl 2‘-deoxynucleotide residues are reported. The 2-aminoquinazoline residues sequence specifically bind via Hoogsteen base pairing as a third strand in the center of the major groove at T:A base pair Watson−Crick duplex sequences. Evidence for the formation of a sequence specific three-stranded structure is based on thermal denaturation UV−vis and fluorescence studies. The novel 2-aminoquinazoline C-nucleotide is a component of a system designed to overcome the homopurine requirement for triple helix structures.
Stereoselective Synthesis of the Decahydrofluorene Core of the Hirsutellones.

A stereoselective synthesis of the decahydrofluorene core of the hirsutellones was accomplished in eight steps and in 43% overall yield. The key step of the synthesis is the highly stereoselective intramolecular Diels–Alder cyclization of the siloxacyclopentene-constrained tetraene 1.
Novel polarization control scheme for spectral surface plasmon resonance sensors

Abstract An analysis of polarization phenomena occurring at surface plasmon resonance is carried out. Based on the results of the analysis, a novel polarization control scheme for spectral surface plasmon resonance (SPR) sensors based on attenuated total reflection method is proposed which allows observing SPR as a peak in the spectrum of the reflected light. The implementation of this polarization control scheme leads to an SPR sensor based on the measurement of the wavelength at which the light intensity maximum occurs which may be more easy to monitor than the position of an SPR dip. This polarization control scheme is of particular interest for the development of multichannel spectral SPR sensors in which mutually spectrally shifted sensing channels are simultaneously monitored by a spectrum analyzer.
Heteromeric mixing of connexins: compatibility of partners and functional consequences.

Cx43 is widely expressed in many different cell types, and many of these cells also express other connexins. If these connexins are capable of mixing, the functional properties of channels containing heteromeric connexons may substantially influence intercellular communication between such cells. We used biochemical strategies (sedimentation through sucrose gradients, co-immunoprecipitation, or co-purification by Ni-NTA chromatography) to examine heteromeric mixing of Cx43 with other connexins (including Cx26, Cx37, Cx40, Cx45, and Cx56) in transfected cells. These analyses showed that all of the tested connexins except Cx26 formed heteromeric connexons with Cx43. We used the double whole-cell patch-camp technique to analyze the electrophysiological properties of gap junction channels in pairs of co-expressing cells. Cx37 and Cx45 made a large variety of functional heteromeric combinations with Cx43 based on detection of many different single channel conductances. Most of the channel event sizes observed ...
Kinetics of Drug Action in Disease States XXXII: Effect of Experimental Hypertension on the Pharmacodynamics of Phenobarbital in Rats

The purpose of this investigation was to determine the effect of experimental hypertension on the concentrations of phenobarbital required to produce a defined hypnotic effect (loss of righting reflex) in adult, female Lewis rats. Hypertension was induced with deoxycorticosterone acetate (DOCA), administered by im injection (first experiment) or by pellet implant (second experiment), and 1 % NaCl in the drinking water. There were two control groups: one that received im injections of water or a drug-free pellet implant plus 1 % NaCl in the drinking water, the other that received water injections or drug-free pellet implants and no NaCl in the drinking water. These treatments were carried out for 3 months and resulted in appreciable elevation of blood pressure and increased heart weight in the DOCA + NaCl-treated (but not in the NaCl alone) rats. All animals then received an infusion of phenobarbital until onset of loss of righting reflex. The concentrations of phenobarbital in the serum, serum water, brain, and CSF of the hypertensive rats at the pharmacologic endpoint did not differ significantly from corresponding concentrations in the control groups (except for a marginal difference of the drug concentration in serum water between the DOCA pellet group and the drug-free pellet control group). It is concluded that DOCA-induced hypertension has no apparent effect on the sensitivity of the central nervous system to the hypnotic action of a barbiturate in female rats.
Availability of methods for suicide and suicide rates.

Summary.-Correlations between suicidal and accidental deaths by similar methods over states and over age groups were positive, suggesting chat accidental death rates may indirectly measure the availability of methods for suicide. Lester (1989) suggested that accidental death rates could be used as measures of the availability of a method for suicide, and he reported that the accidental death rate in the states of America from poisons, gases, and firearms were positively associated, respectively, with the suicide rate from poisons, gases, and firearms. Further data to test this idea come from Baker, O'Neill, and Karpf (1984) who presented suicidal and accidental rates for each continental state of the USA from 1977 through 1979 and for each of 10 age groups within the population. Pearson correlations over the continental states between the accidental and suicidal death rates were significant for firearms-explosives (r = 0.53, twotailed p < .001), solids-liquids (r = 0.43, p < .01), and motor vehicle exhaust (r = 0.40, p< .01) but not for jumping-falls from buildings and structures (r = 0.13) or submersion-nonboating drowning (r = - 0.15). Pearson correlations over the 10 age groups were less supportive. For the methods listed above, the Pearson correlations were, in order, - 0.70 (p< .05), 0.48, 0.87 (p = .001), - 0.51, and - 0.28. The results, then, indicate support for Lester's suggestion, but only for correlations over regions.
L-gulonolactone oxidase is present in the invertebrate, Limulus polyphemus

L-Gulonolactone oxidase (EC 1.1.3.8) which catalyzes oxidation of L-gulonolactone to L-ascorbic acid was detected in tissues ofLimulus polyphemus.
Seizure measurement in clinical trials

The traditional endpoint in clinical trials of antiepileptic drugs has been based on counting complex partial seizures. Other aspects of seizures such as severity and precipitating factors also should be considered. A review of scales developed to assess multiple aspects of seizures is used to define additional aspects of seizures that could be measured in clinical trials. Three scales (VA Seizures Frequency and Severity Scale, Liverpool Seizure Severity Scale, and National Hospital Seizure Severity Scale) are compared for 15 aspects of seizure assessment. Nontraditional methods of seizure assessment might provide valuable data that could differentiate among treatments.
The Role of Genomics in the Neonatal ICU

Results of both the Human Genome and International HapMap Projects have provided the technology and resources necessary to enable fundamental advances through the study of DNA sequence variation in almost all fields of medicine, including neonatology. Genome-wide association studies are now practical, and the first of these studies are appearing in the literature. This article provides the reader with an overview of the issues in technology and study design relating to genome-wide association studies and summarizes the current state of association studies in neonatal ICU populations with a brief review of the relevant literature. Future recommendations for genomic association studies in neonatal ICU populations are also provided.
17O NMR Investigation of Aryl Isocyanates: Electronic and Steric Effects

Abstract The natural abundance 170 nmr spectra of seventeen aryl isocyanates are reported. Electronic effects of substituents are consistent with previously investigated carbonyl containing functional groups; however, the steric effects of ortho-alky 1 groups give results which are opposite to those noted for other systems.
Kupffer cell activation by lipopolysaccharide in rats: Role for lipopolysaccharide binding protein and toll-like receptor 4

Lipopolysaccharide (LPS) binding protein (LBP) is a key serum factor that mediates LPS activation of mononuclear cells. In the presence of LBP, 1/1,000 the concentration of LPS is sufficient to activate peripheral blood monocytes. Previous studies with Kupffer cells have shown a variable effect of serum on LPS activation of these cells and led to the conclusion that, unlike extrahepatic mononuclear cells, Kupffer cells do not respond to LPS in an LBP-dependent fashion. Because there are multiple components in serum other than LBP that might affect LPS activation, these reports with serum are difficult to interpret. To investigate the specific role of LBP in LPS activation of Kupffer cells, we produced a functional recombinant rat LBP using a baculovirus expression system, which we used to selectively examine the role of LBP's on Kupffer-cell function. Isolated Kupffer cells exposed to increasing concentrations of LPS (0, 1, 10 ng/mL) showed a dose-dependent increase in TNF-alpha production, which was augmented and accelerated by the presence of LBP. The effects of LBP on Kupffer cell activation by LPS are dependent on a functional Toll-like receptor 4 (Tlr 4) because Kupffer cells from C3H/HeJ mice failed to respond to LPS in the presence of LBP. LBP plays an important role in mediating Kupffer cell activation by LPS, and these effects are dependent on the presence of functioning Tlr 4.
Cross-validation of a system for predicting training success of Medex trainees.

Summary.--An already developed multiple-regression model for predicting success of Medex trainees in their training program mas cross-validated using a new group of Medex trainees. Six psychological test predictor variables (2 on the MMPI and 4 on the Strong) "held up" upon cross-validation. The results Lent credence to the use 04 multidimensional judgment scaling for establishment of a personnel evaluation-grading criterion measure. As promised (4), a cross-validation of the prediction model, described in that report, has been completed. They originally found that, based on multiple-regression analyses, 14 predictor variables (5 on the MMPI and 9 on the Strong), when properly weighted, would quite accurately predict success of trainees in a Medex, i.e., physician's extender, training program (our firs! Medex training project) when the criterion measure of success was based on multidimensional iudgment scaling principles (5). The MMPI (Form R) and the Strong Vocational Interest Blank, Form T399, were administered to the trainees in our second Medex training project (prior to their being selected or shortly after selection). Since a major loss, in mid-program, of some of the projects's training staff was anticipated, a mid-program obtaining of the criterion trainingsuccess measure, based on the same kind of procedures (5), was accomplished in order that the full complement of knowledgeable judges (Js) could be used (the Director and the Deputy Director, M.D.s; Project Administrator, an economist; Assistant Director for Trainee Liaison, a graduate Medex) . The Js made similarity estimations regarding pair-comparison presentations of the trainees' names (the stimuli) ; their judgmental data were subjected to a multidimensional scaling analysis [see (5) for a more technical discussion of the methodology employed, the Stone-Coles method (6), as the present investigation followed these same procedures]. From the multidimensional scaling analysis, the first and most major (largest) dimension extracted (it accounted for 39% of the judgmental variance prior to rotation and 25% following rotation) was clearly identified, by the Js involved, as a sort of "quality of trainee within the program" dimension. With this evaluation dimension as the criterion measure (dependent variable), it and the 14 predictor variables identified (4) were entered in a multiple-regression routine based on the logic of backward eliminauon, a modified version of a program described by IBM (2). This regression analysis indicated that six of the 14 predictor variables were significantly associated (in multiple-regression fashion) with the dependent variable (Rl.%asr = 37, df = 6/11, F = 5.53, p < .01); in other words, six of these predictor variables "held up" upon cross-validation. The multiple-regression equation based on these six variables is as follows: Y = (-4.34)
QUANTITATIVE HPLC ANALYSIS OF 4-[4-4-(CHLOROPHENYL)PHENYL]-4-OXO-2S-(PHENYLTHIOMETHYL) BUTANOIC ACID (BAY 12-9566), A METALLOPROTEINASE INHIBITOR, AND ITS METABOLITES IN HUMAN PLASMA

A High Performance Liquid Chromatographic (HPLC) method was developed for the analysis of Bay 12-9566 (4-[4-4-(chlorophenyl)Phenyl]-4-oxo-2S-(phenylthiomethyl) butanoic acid), a metalloproteinase inhibitor, and its three metabolites, M1 (sulfoxide), M2 (ρ-hydroxy) and M3 (reduction product) in plasma. Sample preparation involved precipitation of plasma proteins using acidified acetonitrile. A reverse phase chromatography with gradient elution, ultraviolet detection at 290 nm and internal standard were used for separation and quantitation of all analytes. The quantitation range was 0.10 μg/mL to 50 μg/mL for BAY 12-9566, and 0.10 μg/mL to 3.00 μg/mL for all three metabolites. The limit of detection for BAY 12-9566 and for all three metabolites was 0.05 μg/mL. Intra-day accuracy for BAY 12-9566 and the three metabolites ranged from 95.0 to 105.0% and precision (CV) ranged from 0.0 to 4.76%. Inter-day accuracy and precision were based on quality control samples analyzed concurrently with subject plasma sampl...
Feeding and Management of Dairy Heifers for Optimal Lifetime Productivity

A total of 433 Holstein heifer calves were fed two different energy amounts from 6 wk of age to breeding weight to determine the effect of early nutrition and age at first calving on lifetime performance. A control group of 182 heifers was fed according to the Beltsville growth standard. A second group of 251 heifers was accelerated in growth by providing more energy during early development. Both groups of heifers were bred at a minimum weight of 340 kg. Average ages at first calving for control and accelerated heifers were 24.6 mo and 22.2 mo with corresponding 305-d first lactation unadjusted milk production values of 6985 and 6729 kg and unadjusted milk fat yields of 222 and 216 kg. Average 305-d milk production values through subsequent lactations for control and accelerated animals, were lactation 2, 7790, 7842 kg; lactation 3, 8200, 8330 kg; lactation 4, 9481, 9134 kg; lactation 5, 9865, 9588 kg; lactation 6, 9515, 10,108; lactation 7, 9661, 10,112. Average total milk yields over five lactations were 42,321 and 41,623 kg. Percentages of cows remaining in the herd after five lactations were 19 and 18 for control and accelerated animals. Reproductive problems, mastitis, and deaths accounted for 70% of cows leaving the herd and did not differ between treatment groups.
Effects of submicrometer particulate silica addenda on the adhesion of micrometer-size particles to a polyester-composite substrate

The force needed to detach five sets of different size particles, having number-averaged diameters between 3.6 and 8.5 µm, from a composite substrate was measured using an ultracentrifuge. In addition to size variations, the asperity concentration for each size particle was adjusted by varying the silica concentration, adjusted so that the surface area concentration at each level was kept constant for the five sizes of particles. Due to the changing silica concentration and particle size, the charge per particle also varied. It was found that the detachment force appeared to be virtually independent of charge, with any correlation actually appearing slightly negative, if anything. However, the detachment force increased monotonically with increasing particle diameter and decreased monotonically with increasing silica concentration. Moreover, upon normalizing the detachment force to the particle diameter and the silica concentration to the surface area concentration of silica, it was found that the detachm...
Effect of aldosterone on ribonucleic acid polymerase activity in rat kidney cortical and medullary mitochondria.

The involvement of mitochondria in the mechanism of action of aldosterone is suggested by the ability of this hormone to alter the activity of certain mitochondrial enzymes. Since the mitochondrion is able to synthesize some of its own macromolecules, we investigated whether the mineralocorticoid effects mitochondrial RNA synthesis in isolated kidney mitochondria. Rat kidney mitochondria were purified and then separated into two populations by sucrose density gradient centrifugation; mitochondria sedimenting at 1.2 M sucrose were predominantly of medullary origin, while mitochondria sedimenting at 1.4 M sucrose were mainly from the cortex. RNA polymerase activity in medullary mitochondria was almost twice that of cortical mitochondria. The activity was characterized as α-amanitin resistant and rifampicin sensitive DNA-dependent RNA polymerase. Adrenalectomy resulted in a 40 per cent decrease in the RNA polymerase activity of cortical mitochondria 5 days later (P < 0.001), but no decrease occurred in medullary mitochondrial activity, compared to sham-operated controls. Three hr after aldosterone administration ( 2 μmg/100 g body wt, i.p.) the RNA polymerase activities of medullary and cortical mitochondria were increased 20 and 50 per cent, respectively, above the adrenalectomized values (P < 0.05, P < 0.001). Spironolactone, an antagonist of aldosterone (7 mg/100 g body wt, i.p., 30 min prior to aldosterone administration), blocked the stimulation of RNA polymerase by aldosterone (P < 0.05). Steroid hormones other than aldosterone did not produce significant enhancement of mitochondrial RNA polymerase activity. No change in RNA polymerase activity occurred after direct addition of aldosterone or spironolactone to the assay medium. The results suggest that the mechanism of mineralocorticoid action is at least in part mediated through its effects on mitochondrially synthesized proteins.
Electrical Behavior of Flexible Cables With Intermittent Faults

This paper presents a study on the effects of flexing on the electrical behavior of motor cables in application to automation and robotic systems. Focus is given to their resistance change from the pristine to the intermittent state. The samples were PVC-insulated 22 AWG wires with bare copper conductor strands. It was found that, under continual flexing, the cable resistance remained small and stable until the intermittent stage, where all the conductor strands were broken. The resistance then increased abruptly by over 40 times and became unstable. Yet, current managed to pass through the cable via the lapped strands. The phenomenon is closely related to electrical contacts under low forces and large displacements. Interestingly, with injected currents as for motor driving, an intermittent cable is "healed" with its resistance reduces drastically. Hence, the cable is still usable. Apart from resistance measurement, scanning electron microscope (SEM) and energy dispersive X-ray spectroscopy (EDX) were applied to examine the broken strands. Traces of arcing were observed signifying (1) the passage of currents across the contacting strands, as well as (2) welding at their contact interfaces.
Appreciation of Cartoons with Profanity in Captions

The present study investigated sex differences in appreciation of cartoons with three levels of profanity in the captions. 111 female and 99 male students evaluated the cartoon with mild profanity in the caption as funnier than either the non-profane or strong-profanity caption. When the cartoon caption was non-profane, there was no difference between men's and women's evaluations of funniness, but when the cartoon caption included either mild or strong profanity, men found the cartoon funnier than women.
Flexible angioscopy seems faster and more specific than arteriography.

• Fiberoptic angioscopy was performed with 2.5- and 3.3-mm angioscopes in 25 arteries and grafts in 19 patients. Radiologically normal and abnormal arteries and anastomotic sites were examined. All vessels and grafts were visualized and images of normal arterial wall, subclinical and obstructing atherosclerotic plaque, and suture lines were defined. Unexpected endovascular findings were noted in five patients (26%) and included large amounts of free-floating clot (one patient), atherosclerotic debris (two patients), and membranelike obstructions (two patients). Angioscopy required three to ten minutes and resulted in no complications. Experience with the flexible angioscope indicates that satisfactory visualization and specific recognition of angiographically unsuspected problems can be obtained. The flexible angioscope is faster and appears more etiologically specific than arteriography. (Arch Surg1987;122:279-282)
Separation‐Friendly Mitsunobu Reactions: A Microcosm of Recent Developments in Separation Strategies

The Mitsunobu reaction is famous for its scope and power, but infamous for its separation headaches. Typically, the target product is enticed away from the reagent-derived byproducts by careful chromatography. The use of polymer-bound Mitsunobu reagents solves only half of the problem, because polymer-bound diethyl azodicarboxylate (DEAD) and phosphine reagents cannot be employed simultaneously. This article classifies, compares, and contrasts various emerging strategies for product isolation in Mitsunobu reactions. Because so many different strategies have been used, the Mitsunobu reaction is a microcosm for the new field of strategy level separations.
Developmental impact and lesion maturation of histotripsy-mediated non-invasive tissue ablation in a fetal sheep model.

Abstract Non-invasive histotripsy therapy has previously been used to achieve precise fetal tissue ablation in a sheep model. To further assess the clinical viability of the technique, this study investigated potential effects of histotripsy therapy during the remaining gestation and its local impact on fetal development. Five ewes (six lambs) at 95–107 d of gestation were treated and allowed to complete the full gestation period of 150 d. A 1-MHz focused transducer was used to treat the fetal kidney and liver with 5-μs pulses at 500-Hz repetition rates and 10- to 16-MPa peak negative pressures; ultrasound imaging provided real-time treatment guidance. The lambs were euthanized after delivery and treated organs were harvested. Samples were examined by magnetic resonance imaging and histopathologic analysis. These data were compared with results from four other ewes (four lambs) that underwent similar treatments but were sacrificed immediately after the procedure. The sheep tolerated the treatment well, and acute lesion samples displayed well-defined ablated regions characterized by the presence of fractionated tissue and hemorrhage. All fetuses that were allowed to continue gestation survived and were delivered at full term. The lambs were healthy on delivery, with no signs of external injury. A minor indentation was observed in each of the treated kidneys with minimal presence of fibrous tissue, while no discernible signs of lesions were detected in treated livers. In a sheep model, histotripsy-mediated fetal tissue ablation caused no acute or pregnancy-related complications, supporting the potential safety and effectiveness of histotripsy therapy as a tool in fetal intervention procedures.
Fundamental mechanisms for energy dissipation at small solid sliding surfaces

Abstract Previous results by the present author on microscopic mechanisms for kinetic friction between solid surfaces which are sliding relative to each other are reviewed and explained in terms of simple models involving driven harmonic oscillators. It is then argued that there is no friction for sufficiently small anharmonic solids at sufficiently low temperatures and for sufficiently weak intersurface interaction. (In the present work, dissipationless sliding was found to occur for the position-dependent part of the force acting on an atom at the interface about equal to 3 × 10 −12 N which is comparable to the value expected for rare gas films as a microbalance.)
LOW TEMPERATURE FABRICATION OF ZNO-WHEY PROTEIN ISOLATE NANOCOMPOSITE

Abstract Nanocrystalline zinc oxide (ZnO) particles coated with whey protein isolate (WPI) were fabricated in the weak basic aqueous solution condition at near room temperature. The X-ray diffraction and transmission electron microscopy measurements confirmed the nanoscaled composite structure of ZnO–WPI. The average composite granules size was about 300 nm and the embedded ZnO nanoparticles were uniform and monodisperse with an average diameter of 65 nm.
Interferon externalization by producing cell before induction of antiviral state.

Abstract The mechanism by which poly(I · C) induces the antiviral state in human fibroblast cells was studied using antisera which were selectively reactive with the inducer [poly(I · C)], the product (human fibroblast interferon), and the fibroblast cell surface. Anti-interferon serum completely neutralized the antiviral effect of human fibroblast interferon. Furthermore, when added to the medium of the cells in which interferon synthesis had already been induced by poly(I · C), interferon antiserum prevented the intracellular antiviral state from developing. Antibodies specific to double stranded RNA inhibited the antiviral activity of poly(I · C) whether it was in solution or bound to the cells, but the same antibodies were without effect when added after the induction of the antiviral state was initiated. Treatment with serum directed against the cell surface of human fibroblasts failed to inhibit the antiviral activity of poly (I · C) or of human interferon in these cells. These results indicate that the antiviral effect of poly(I · C) is interferon mediated, and that for the development of the antiviral state, interferon has to interact with the external part of the cellular membrane of the producing cell.