cssi/SciSciGPT-SciSciNet huggingface dataset:
Enantioselective radical process for synthesis of chiral indolines by metalloradical alkylation of diverse C(sp3)–H bonds

A new C-C bond formation strategy based on enantioselective radical alkylation of C(sp3)-H bonds via Co(ii)-based metalloradical catalysis has been demonstrated for stereoselective synthesis of chiral indolines. The Co(ii)-based system enables activation of aryldiazomethanes as radical precursors at room temperature for enantioselective intramolecular radical alkylation of broad types of C-H bonds, constructing 2-substituted indolines in high yields with excellent enantioselectivities. In addition to chemoselectivity and regioselectivity, this Co(ii)-catalyzed alkylation features tolerance to functional groups and compatibility with heteroaryl substrates. Detailed mechanistic studies provide insight into the underlying stepwise radical pathway.
Security analysis of an IoT system used for indoor localization in healthcare facilities

In today's world, the rapid advancement of technology allows us to find new solutions to old problems in critical areas, namely patient and staff tracking in healthcare facilities. The medical staff within these facilities are in an environment where they depend on immediately knowing the location of a patient or other medical staff. McAllister et al. [1] proposed a solution named LoCATE (Localization of Health Center Assets Through an IoT Environment) which uses existing technology to track all patients and medical staff in near real time. LoCATE makes use of the current wireless networks (e.g., WiFi) within a healthcare facility by using edge node technology as its tracking solution. It can locate an object within three to five feet of its calculated position. The ubiquity of WiFi infrastructure in healthcare facilities makes it an attractive option to use, as the backbone for a patient and staff tracking system. However, Internet of Things (IoT) devices and edge nodes create security holes in networks and leak data to the open world. This paper aims to analyze what security holes and data leaks LoCATE creates in a healthcare facility. In this paper, we show the dangers of using simple and default passwords, the need to physically secure edge nodes, and the importance of securing data before transmission. We exploit the system's weak security measures by forging edge node data, gaining unauthorized access, performing denial of service attack, and launching other attacks. We analyze the successfulness of these attacks to offer mitigation techniques for future devices located in other critical areas similar to the healthcare facilities.
Multiple Subpial Cortical Transections for the Control of Intractable Epilepsy in Exquisite Cortex

In 5 cases suffering from intractable seizures and ictal onset in exquisite (primary somatosensory or language related) cortex, surgical therapy has been done consisting wholly or in part of multiple subpial transections.
Effect of Group B Streptococcal Meningitis on Retinal and Choroidal Blood Flow in Newborn Pigs

Purpose. To assess the effect of group B streptococcal (GBS) meningitis on retinal blood flow (RetBF) and choroidal blood flow (ChBF) autoregulation in sedated newborn piglets (1 to 5 days of age). Methods. Fourteen study animals injected with 0.5 ml heat-killed GBS (10 9 ) were compared to 10 control animals injected with 0.5 ml saline. The site of injection for both groups was the cerebral lateral ventricles. RetBF and ChBF were measured by radioactive microspheres ( l4l Ce, 51 Cr, 113 Sn, 85 Sr, 95 Nb, 46 Sc) over a mean arterial blood pressure (MABP) range of 20 to 150 mm Hg. Hypertension and hypotension were induced 2 hours apart in random sequence on each animal by inflating balloon-tipped catheters placed at the descending aorta and the aortic root, respectively. RetBF and ChBF were measured 15 minutes before and after injection of GBS or saline (baseline) and during hypotension or hypertension. Results. Fifth-order polynomial regression analyses of RetBF and ChBF (ml/100 g per minute) versus MABP showed that in control animals, blood flows were constant at MABP of 60 to 110 mm Hg for RetBF and was pressure passive above and below these ranges. However, no autoregulation was observed for ChBF throughout the MABP range. In contrast, RetBF of GBS-treated animals increased with increasing blood pressure throughout range of MABP studied, and absence of autoregulation was maintained in the choroid. Vascular resistance (mm Hg/ml per minute/100 g) increased as MABP was raised to maintain constant flow and was correlated linearly with MABP at 60 to 110 mm Hg (r = 0.6682, P = 0.0003) in RetBF of control animals but not in GBS-treated animals (r = -0.291, P = NS). Vascular resistance did not change with MABP for ChBF of control animals (r = -0.264, P = NS) but decreased as MABP was raised in GBS-treated animals (r = -0.548, P < 0.0001). GBS did not alter oxygen delivery, which varied directly with MABP in control animals (RetBF : r = 0.74, P < 0.001 ; ChBF : r = 0.68, P < 0.001) and in GBS-treated animals (RetBF : r = 0.55, P < 0.001 ; ChBF : r = 0.68, P < 0.001). Conclusion. Group B streptococcal meningitis significantly impairs eye blood flow autoregulation and may contribute to increased risk of retinal damage in infants with meningitis. Invest
ERK activation by the alpha1-adrenergic receptor agonist phenylephrine in human aortic smooth muscle (AoSMC) cells

The adaptive process of vascular remodeling causes structural alteration in blood vessels via proliferation, differentiation and migration of vascular smooth muscle cells (VSMCs) within the vessel ...
A sulphate metabolizing centre in Euglena mitochondria

Abstract We have previously shown that a sulphate activating system is present on the outside of the inner mitochondrial membrane of Euglena gracilis Klebs. var. bacillaris Cori, but efforts to couple this system to ATP produced from oxidative phosphorylation were unsuccessful. In the present work we show that the concentration of Pi ordinarily used to support oxidative phosphorylation in these mitochondria (10 mM) inhibits sulphate activation completely; by reducing the concentration of Pi 10-fold, both processes proceeded normally. Sulphate activation under these conditions is inhibited nearly completely by the uncouplers of oxidative phosphorylation dinitrophenol (0.1 mM) and carbonyl cyanide m-chlorophenylhydrazone (CCCP) (0.2 microM). Sulphate reduction to form free cysteine, most of which appears outside the organelle, and in the cysteine of mitochondrial protein can be demonstrated in the same preparations, is membrane-bound and is inhibited by chloramphenicol (100 micrograms/ml), NaN3 (5 mM), KCN (100 microM); dinitrophenol (0.1 mM) or CCCP (0.2 microM). Digitonin fractionation of the mitochondria into mitoplasts, outer membranes and an intermembrane fraction show that reduction of 35SO4(2-) to form free cysteine and cysteine of protein is located on the mitoplasts; adenosine 5'-phosphosulphate sulphotransferase, the first enzyme of sulphate reduction, is found in the same location. Sulphate activation is highly enriched in the mitochondrial fraction of Euglena; the small amount found in the chloroplast fraction can be attributed to mitochondrial contamination. Thus, in Euglena, sulphate activation and reduction are contained in a sulphate metabolizing centre on the outside of the mitochondrial inner membrane; this centre appears to supply the mitochondrion and the rest of the cell with the products of sulphate activation as well as with reduced sulphur in the form of cysteine. Mitochondria from wild-type Euglena cells and from W10BSmL, a mutant lacking plastids completely, appear to be similar in the properties studied.
A Connection Between the Observed Best Prediction and the Fence Model Selection Method

Following our presentation at the Platinum Jubilee on “Observed Best Prediction (OBP) for Small Area Counts”, we discuss a connection between OBP and predictive model selection using the fence methods.
A Review of the Most Commonly Used Methods for Sample Collection in Environmental Surveillance of Poliovirus

We performed a review of the environmental surveillance methods commonly used to collect and concentrate poliovirus (PV) from water samples. We compared the sampling approaches (trap vs grab), the process methods (precipitation vs filtration), and the various tools and chemical reagents used to separate PV from other viruses and pathogens in water samples (microporous glass, pads, polyethylene glycol [PEG]/dextran, PEG/sodium chloride, NanoCeram/ViroCap, and ester membranes). The advantages and disadvantages of each method are considered, and the geographical areas where they are currently used are discussed. Several methods have demonstrated the ability to concentrate and recover PVs from environmental samples. The details of the particular sampling conditions and locations should be considered carefully in method selection.
Hypothalamic Neurons that Regulate Feeding Can Influence Sleep/Wake States Based on Homeostatic Need

Summary Eating and sleeping represent two mutually exclusive behaviors that satisfy distinct homeostatic needs. Because an animal cannot eat and sleep at the same time, brain systems that regulate energy homeostasis are likely to influence sleep/wake behavior. Indeed, previous studies indicate that animals adjust sleep cycles around periods of food need and availability. Furthermore, hormones that affect energy homeostasis also affect sleep/wake states: the orexigenic hormone ghrelin promotes wakefulness, and the anorexigenic hormones leptin and insulin increase the duration of slow-wave sleep. However, whether neural populations that regulate feeding can influence sleep/wake states is unknown. The hypothalamic arcuate nucleus contains two neuronal populations that exert opposing effects on energy homeostasis: agouti-related protein (AgRP)-expressing neurons detect caloric need and orchestrate food-seeking behavior, whereas activity in pro-opiomelanocortin (POMC)-expressing neurons induces satiety. We tested the hypotheses that AgRP neurons affect sleep homeostasis by promoting states of wakefulness, whereas POMC neurons promote states of sleep. Indeed, optogenetic or chemogenetic stimulation of AgRP neurons in mice promoted wakefulness while decreasing the quantity and integrity of sleep. Inhibition of AgRP neurons rescued sleep integrity in food-deprived mice, highlighting the physiological importance of AgRP neuron activity for the suppression of sleep by hunger. Conversely, stimulation of POMC neurons promoted sleep states and decreased sleep fragmentation in food-deprived mice. Interestingly, we also found that sleep deprivation attenuated the effects of AgRP neuron activity on food intake and wakefulness. These results indicate that homeostatic feeding neurons can hierarchically affect behavioral outcomes, depending on homeostatic need.
Dynamic nuclear polarization via the cross effect and thermal mixing: A. The role of triple spin flips

In dynamic nuclear polarization (DNP) via the cross effect (CE) and thermal mixing (TM) a microwave field first reduces the polarization of some electron spins, so the electron spin system deviates from thermal equilibrium with the lattice. Next, the mutual interactions combine with their interaction with the nuclear spins to transform this deviation into nuclear spin polarization. Two approaches were introduced to describe the latter process. The fluctuating field approach considers the electron spins to fluctuate between their up and down states due to their mutual interactions. This results in a classical fluctuating field at the position of the nuclear spins, and the component of this field at the NMR frequency induces flips of the nuclear spins. The scrambled states approach considers the electron and nuclear spin states to be mixed by the hyperfine and super-hyperfine interaction. Next the mutual interaction between the electron spins induces transitions between these mixed states and thus flips nuclear spins. Some authors considered the fluctuating field approach and the scrambled states approach to be just two equivalent methods to describe exactly the same process. Other authors considered the two approaches to describe two separate processes, the former exchanging electron interaction energy, the latter transferring differences of electron spin polarization to the nuclear spins. The present work introduces a generalized approach that first calculates the mixing of electron spin states exactly. Next it considers the hyperfine or super-hyperfine interaction to induce transitions involving these mixed states and the nuclear spin states. It is found that the scrambled states approach and the fluctuating field approach are neither fully equivalent, nor completely independent processes, but rather represent two distinct limits of a single process. The former corresponding to very weak mutual interactions between electron spins and the latter to very strong mutual interactions. It extends the treatment to the whole range of mutual interactions and shows that this single process simultaneously exchanges electron Zeeman energy and electron interaction energy with the nuclear spins. Expressions for these two flows as a function of the strength of the mutual interaction are derived.
Optimization techniques for time-critical cyber-physical systems

Cyber-Physical Systems (CPS) are often deployed in critical applications subject to strict timing constraints. To guarantee their timing correctness, much of the effort has been dedicated to the development of validation and verification methods for CPS (e.g., timing and schedulability analysis). As CPS becomes increasingly complex, there is an urgent need for efficient optimization techniques that can handle large-scale systems. This has been challenging as timing and schedulability analysis are often too difficult and inefficient to use in optimization framework such as mathematical programming. Existing practice mostly relies on ad-hoc heuristics which suffer from sub-optimal solution quality and limited applicability. In this paper, we discuss new directions for developing optimization algorithms for time-critical CPS that address the above issues. We present a number of previous studies and show that the proposed approaches have the potential to significantly improve on scalability while guaranteeing solution quality. Still, there are large grounds to be covered, which calls for participation from the research community.
Functionalization of iron oxide nanoparticles with small molecules and the impact on reactive oxygen species generation for potential cancer therapy

Abstract Iron oxide nanoparticles (IONPs) and their cytotoxicity via reactive oxygen species (ROS) generation have attracted much attention in the last several years. Recent studies show that alternating magnetic field (AMF) exposure can enhance the production of ROS by IONPs, and these ROS have potential use in therapeutic applications. The aim of this research was to develop iron oxide nanoparticles-based platforms with small molecule coatings and to study impact of the coating on the surface reactivity of the particles. Iron oxide nanoparticles were synthesized by a co-precipitation process and coated with citric acid, sodium phosphate, amino-silane, or dopamine. Physicochemical properties of the particles including hydrodynamic size, amount of coating, and AMF heating ability were investigated. Surface reactivity via ROS generation by the particles was evaluated using a methylene blue decolorization assay with hydrogen peroxide and various AMF exposures. It was demonstrated that in general small molecule coatings decreased surface reactivity of IONPs by inhibiting ROS generation compared to uncoated IONPs. These results indicated that small molecules inhibit the ability to use enhancement of ROS generation, and this is important to consider in the design of these systems for cancer therapy and other therapeutic applications.
Vanadium-Substituted Tunnel Structured Silver Hollandite (Ag1.2VxMn8-xO16): Impact on Morphology and Electrochemistry.

A series of tunnel structured V-substituted silver hollandite (Ag1.2VxMn8-xO16, x = 0-1.4) samples is prepared and characterized through a combination of synchrotron X-ray diffraction (XRD), synchrotron X-ray absorption spectroscopy (XAS), laboratory Raman spectroscopy, and electron microscopy measurements. The oxidation states of the individual transition metals are characterized using V and Mn K-edge XAS data indicating the vanadium centers exist as V5+, and the Mn oxidation state decreases with increased V substitution to balance the charge. Scanning transmission electron microscopy of reduced materials shows reduction-displacement of silver metal at high levels of lithiation. In lithium batteries, the V-substituted tunneled manganese oxide materials reveal previously unseen reversible nonaqueous Ag electrochemistry and exhibit up to 2.5× higher Li storage capacity relative to their unsubstituted counterparts. The highest capacity was observed for the Ag1.2(V0.8Mn7.2)O16·0.8H2O material with an intermediate level of V substitution, likely due to a combination of the atomic composition, the morphology of the particle, and the homogeneous distribution of the active material within the electrode structure where factors over multiple length scales contribute to the electrochemistry.
Intractable Pulmonary Hypertension in a Late Preterm Neonate: Alveolar Capillary Dysplasia, a Lethal Disease

Alveolar Capillary Dysplasia with Misalignment of the Pulmonary Veins (ACDMPV) is a rare disorder, with only approximately 200 cases reported to date. The most common presentation of ACDMPV is hypoxic respiratory failure, a condition commonly encountered in preterm neonates. However, the clinical course of the hypoxic respiratory failure and unremitting pulmonary hypertension contrasts dramatically from the usual course of persistent pulmonary hypertension of the neonate (PPHN) in late preterm infants. A 35 4/7 week male infant was born via spontaneous vaginal delivery after routine resuscitation with APGARS of 8 and …
Somatic CAG expansion in Huntington's disease is dependent on the MLH3 endonuclease domain, which can be excluded via splice redirection

Somatic expansion of the CAG repeat tract that causes Huntington's disease (HD) is thought to contribute to the rate of disease pathogenesis. Therefore, factors influencing repeat expansion are potential therapeutic targets. Genes in the DNA mismatch repair pathway are critical drivers of somatic expansion in HD mouse models. Here, we have tested, using genetic and pharmacological approaches, the role of the endonuclease domain of the mismatch repair protein MLH3 in somatic CAG expansion in HD mice and patient cells. A point mutation in the MLH3 endonuclease domain completely eliminated CAG expansion in the brain and peripheral tissues of a HD knock-in mouse model (HttQ111). To test whether the MLH3 endonuclease could be manipulated pharmacologically, we delivered splice switching oligonucleotides in mice to redirect Mlh3 splicing to exclude the endonuclease domain. Splice redirection to an isoform lacking the endonuclease domain was associated with reduced CAG expansion. Finally, CAG expansion in HD patient-derived primary fibroblasts was also significantly reduced by redirecting MLH3 splicing to the endogenous endonuclease domain-lacking isoform. These data indicate the potential of targeting the MLH3 endonuclease domain to slow somatic CAG repeat expansion in HD, a therapeutic strategy that may be applicable across multiple repeat expansion disorders.
Pharmacologic Interventions for Fracture Risk Reduction in the Oldest Old: What Is the Evidence?

With an increasingly older population, the proportion of patients 85 years or older seeking interventions to protect their musculoskeletal health is growing. Osteoporosis in the geriatric population presents unique diagnostic and therapeutic challenges. Multimorbidity, frailty, falls, polypharmacy, and other neurobehavioral factors influence our approach to fracture prevention in this population. The vast majority of the evidence from clinical trials establish pharmacologic fracture efficacy in postmenopausal women. The evidence is scarce for the oldest old men and women, a population also at risk for adverse events and mortality. Most studies show continued efficacy of pharmacologic interventions in this age group, although they are largely limited by small sample sizes. We herein review the available evidence of pharmacologic interventions for fracture risk reduction in this population and explore the emerging senotherapeutic interventions in the pipeline. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Achebe’s weakest link: an analysis

Chinua Achebe, author of Things Fall Apart, states in an interview that Joseph Conrad ensconces racism in his adjective-ridden writing style. More than that, Achebe even states that Conrad intentionally tries to confuse his readers so that they do not detect his racism. Arguments of intention are dangerous, especially when the author that is subjected to one is deceased. They cannot defend themselves. In order to see if Achebe’s claim of hidden racism in Heart of Darkness i s true or not, I have read two other works by Conrad, The Secret Sharer and The Shadow Line: A Confession, and compared their writing. Using more analyses of Conrad’s works, I discover that Conrad is not too confusing for his readers; most people understand him. However, I notice that Heart of Darkness is written in a more confusing style. Adding Conrad’s philosophy and reviewing it with Nietzsche’s philosophy, we see that Conrad doesn’t seem like someone who would try to be racist and then hide it. The argument of intention would also seem to have an air of arrogance, as it appears Achebe thinks other readers are unable to comprehend Conrad’s text the way he can, or at least without his guidance. In conclusion, I surmise that arguments of intention are dangerous and that no one should make them because they are largely insupportable. If anything, an argument of intention has all the qualities of prejudice and once investigated, seems just as absurd as arguments for racism.
Visual cortex development in the ferret. I. Genesis and migration of visual cortical neurons.

The production of ferret visual cortical neurons was studied using 3H- thymidine autoradiography. The genesis of cortical neurons begins on or slightly before embryonic day 20 (E20) of the 41 d gestational period, continues postnatally until 2 weeks after birth (P14), and follows an inside-out radial gradient with neurons for the deeper cortical layers being generated before those for the superficial layers. Layer I neurons are generated both early (E20-E30) and late (P1-P14) in the period of cortical neurogenesis and, thus, provide at least a partial exception to the inside-out gradient of cortical neurogenesis. Tangential gradients of cortical neurogenesis extend across areas 17 and 18 in both the anterior-to-posterior and lateral-to-medial directions. Neither of these gradients bears a meaningful relationship to the cortical representation of the visual field. Most infragranular and granular layer neurons are generated prenatally, while most supragranular layer neurons are produced postnatally. Neurons destined for a given layer are produced over a period of several days, and the neurons generated on any given day contribute to the formation of 2 or more cortical layers. In general, prenatally generated neurons complete their migration in 1 week or less, while most postnatally generated neurons require approximately 2 weeks to complete their migration.
The Primary Structure of the Clostridium thermosaccharolyticum Ferredoxin, a Heat-stable Ferredoxin

Abstract The amino acid sequence of Clostridium thermosaccharolyticum ferredoxin was determined to be:[see PDF for sequence]. Compared to the heat-stable ferredoxin from Clostridium tartarivorum, only two differences in the sequence were noted. Glutamine-31 and glutamine-44 in C. tartarivorum ferredoxin were replaced by glutamic acid in the C. thermosaccharolyticum ferredoxin. These changes increase the heat stability of the ferredoxin, since the C. thermosaccharolyticum ferredoxin is the most heat stable of all the ferredoxins isolated thus far. The structure of the heat-stable ferredoxin is discussed and compared with the three-dimensional structure of the Micrococcus aerogenes ferredoxin, a non-heat-stable ferredoxin which has just been completed (Adman, E. T., Sieker, L. C., and Jensen, L. H. (1973) J. Biol. Chem. 248, 3987–3996).
Two-population dynamics in a growing network model

We introduce a growing network evolution model with nodal attributes. The model describes the interactions between potentially violent V and non-violent N agents who have different affinities in establishing connections within their own population versus between the populations. The model is able to generate all stable triads observed in real social systems. In the framework of rate equations theory, we employ the mean-field approximation to derive analytical expressions of the degree distribution and the local clustering coefficient for each type of nodes. Analytical derivations agree well with numerical simulation results. The assortativity of the potentially violent network qualitatively resembles the connectivity pattern in terrorist networks that was recently reported. The assortativity of the network driven by aggression shows clearly different behavior than the assortativity of the networks with connections of non-aggressive nature in agreement with recent empirical results of an online social system. 2011 Elsevier B.V. All rights reserved.
Effects of epidermal growth factor on acid secretion from guinea pig gastric mucosa: in vitro analysis.

Epidermal growth factor (EGF) has been tested on guinea pig gastric mucosa mounted in Ussing chambers to investigate the suitability of using in vitro methods for examining EGF's effects on acid secretion. Epidermal growth factor reduced the rate of histamine-induced acid secretion to near basal levels when applied to the serosal gastric surface at nanomolar concentrations. Inhibitory effects were evident 10-15 min after EGF treatment and were maximal by 40 min. Cyclic adenosine monophosphate-induced secretion was also reduced by EGF, although the effect occurred more slowly than in histamine-treated tissues. Epidermal growth factor increased transmucosal resistance in histaminetreated, but not cyclic adenosine monophosphatetreated mucosa; potential difference was unaffected. Nerve growth factor had no effect when tested in the in vitro system. The EGF binding protein was found to enhance slightly the inhibitory activity of EGF on acid secretion. When applied to the luminal (mucosal) gastric surface, EGF inhibited secretion marginally but only at micromolar concentrations. These results indicate that EGF acts directly upon cells within the gastric mucosa, and is most effective when applied to the serosal gastric surface. They further suggest that in vitro preparations of intact gastric mucosa can be used for analyzing the inhibitory effects of EGF on gastric acid secretion.
Swine hepatitis E virus: cross-species infection and risk in xenotransplantation.

Swine hepatitis E Virus (swine HEV), a ubiquitous agent recently discovered in pigs, is antigenically and genetically closely related to the human HEV. Swine HEV infection in pigs generally occurs at about 2-3 months of age, and about 80%-100% of the pigs in commercial farms in the USA were infected. Swine HEV infections have now been recognized in pigs in many other countries of the world. Interspecies transmission has been documented, as swine HEV infects nonhuman primates and some strains of human HEV infect pigs. Recent seroepidemiological studies showed that swine veterinarians and other pig handlers are at higher risk of HEV infection compared to normal blood donors. In addition, novel strains of human HEV recovered from hepatitis patients in the USA, Japan and Taiwan are genetically more closely related to strains of swine HEV from respective countries than to other strains of human HEV. The ubiquitous nature of the virus in pigs and the demonstrated ability of cross-species infection raise a potential concern for swine HEV infection in xenotransplantation with pig organs. This chapter discusses the recent advances in HEV research with emphases on potential zoonosis and xenozoonosis.
Learning rules by integer linear programming

In this work, an inductive machine learning algorithm called CLILP2, which uses integer linear programming to generate multiple decision rules, is applied to two types of medical data. One is concerned with heart data to recognize coronary artery stenosis from the left ventricle scintigraphic images, and the other data set represents different types of cancer, namely, breast cancer, lymphography and a primary tumor. >
Acute pancreatic graft fistula and peripancreatic fluid collection: demonstration by secretin-stimulated MRI

Peripancreatic fluid collections are among the common post pancreas transplant complications, which are mainly due to leakage from the anastomosis site to bowel and graft pancreatitis. Differentiation between these two entities is important because they are treated differently. In this case, secretin stimulated magnetic resonance cholangiopancreatography revealed gradual intraperitoneal fluid collection and accumulation of fluid in small bowel excluded leakage from the anastomosis of the pancreas to bowel and changed the management from surgery to medical treatment.
Exquisite specificity and peptide epitope recognition promiscuity, properties shared by antibodies from sharks to humans

This review considers definitions of the specificity of antibodies including the development of recent concepts of recognition polyspecificity and epitope promiscuity. Using sets of homologous and unrelated peptides derived from the sequences of immunoglobulin and T cell receptor chains we offer operational definitions of cross-reactivity by investigating correlations of either identities in amino acid sequence, or in hydrophobicity/hydrophilicity profiles with degree of binding in enzyme-linked immunosorbent assays. Polyreactivity, or polyspecificity, are terms used to denote binding of a monoclonal antibody or purified antibody preparation to large complex molecules that are structurally unrelated, such as thyroglobulin and DNA. As a first approximation, there is a linear correlation between degree of sequence identity or hydrophobicity/hydrophilicity and antigenic cross-binding. However, catastrophic interchanges of amino acids can occur where changing of one amino acid out of 16 in a synthetic peptide essentially eliminates binding to certain antibodies. An operational definition of epitope promiscuity for peptides is the case where two peptides show little or no identity in amino acid sequence but bind strongly to the same antibody as shown by either direct binding or competitive inhibition. Analysis of antibodies of humans and sharks, the two most divergent species in evolution to express antibodies and the combinatorial immune response, indicates that the capacity for both exquisite specificity and epitope recognition promiscuity are essential conserved features of individual vertebrate antibodies.
Can You Find an Automated External Defibrillator If a Life Depends on It

Every year, approximately 300 000 Americans have an out-of-hospital cardiac arrest, and survival rates are dismal—approximately 6.4%.1 Automated external defibrillators (AEDs) can restart the heart and provide life-saving audible cardiopulmonary resuscitation (CPR) instructions to aid victims. For patients with ventricular fibrillation, rapid defibrillation with CPR can improve chances of survival to more than 50%.2–4 AEDs can be easily and effectively used by untrained laypersons and are located in public places such as airports, recreation centers, banks, casinos, churches, gyms, and schools.5 Despite the life-saving potential of AEDs, they are of no value if they cannot be located and brought to the victim. Further, there is no US map of AED locations, nor do we even know where all the AEDs are located. Devices are purchased by distributors who then sell them on the Internet, in bulk, or individually. AED registration is the responsibility of the device owner, and the requirements and process differ significantly by region. The Food and Drug Administration has recently highlighted how the lack of registration data makes device recalls and surveillance for potential adverse events challenging. Additionally, this creates a barrier to the use of AEDs when they are needed. Imagine bystanders assisting the resuscitation of a victim in a public area, unaware that an AED is located less than 100 feet away inside a nearby store. They have called 911, and the local emergency medical service personnel are en route, but the emergency dispatchers do not realize that an AED is nearby. The very limited time frame for defibrillation success is certainly more likely to be achieved if those bystanders not providing CPR could be guided to a device that had been previously located and mapped. The problem is easy to understand, and the solution is easy to imagine. Indeed, …
Roles of Pt and BaO in the Sulfation of Pt/BaO/Al2O3 Lean NOx Trap Materials: Sulfur K-edge XANES and Pt LIII XAFS Studies

The roles of barium oxide and platinum during the sulfation of Pt−BaO/Al2O3 lean NOx trap catalysts were investigated by S K edge XANES (X-ray absorption near-edge spectroscopy) and Pt LIII XAFS (X-ray absorption fine structure). All of the samples studied [Al2O3, BaO(x; x = 8 or 20 wt %)/Al2O3, Pt(2.5 wt %)/Al2O3, and Pt(2 wt %)-BaO(x; x = 8 or 20 wt %)/Al2O3] were pre-sulfated prior to the X-ray absorption measurements. It was found that barium oxide itself has the ability to directly form barium sulfate even in the absence of Pt and gas-phase oxygen. In the platinum-containing samples, the presence of Pt−O species plays an important role in the formation of sulfate species. For the case of the BaO(8)/Al2O3 sample, where the barium coverage is about 0.26 ML, both baria and alumina phases are available for sulfation. S XANES results show that barium sulfates are formed preferentially over aluminum sulfates. When oxygen is absent from the gas phase, the sulfation route that involves Pt−O is eliminated aft...
METABOLIC EFFECTS OF A SINGLE INTRAVENOUS INFUSION OF HYDROCORTISONE RELATED TO PLASMA LEVELS IN A NORMAL VERSUS AN ADRENALLY INSUFFICIENT SUBJECT

ALTHOUGH numerous studies of the metabolic effects of adrenal sterioids in man have been made, little information is available regarding the time of onset and duration of effect following their administration as a single dose to either normal subjects or patients with adrenal insufficiency. Fourman and his associates (1) reported metabolic studies following a single intramuscular injection of 30 mg. of desoxycorticosterone acetate in oil into a normal subject. This group also determined the metabolic effects of 50 mg. of hydrocortisone administered intramuscularly to a normal male in four doses over three hours (2). Others (3–5) have studied the metabolic changes induced by cortisone, corticosterone, or hydrocortisone administered by continuous intravenous infusion for periods of four to eight hours at rates of 1 mg. to 25 mg. per hour, but the duration of effect was not reported. Most metabolic experiments have involved the use of repeated injections of steroids for several days, with collection periods ...
Movement-related skin strain associated with goal-oriented lip actions

It is generally accepted that sensory input contributes to the generation of natural movements. In most motor systems, muscle spindles, tendon organs, joint receptors, and cutaneous mechanoreceptors may provide proprioceptive information. However, the perioral area of the human face lacks muscle spindles, tendon organs, and joint receptors and is therefore a model system for the study of cutaneous afferent contributions to proprioception. This investigation examined a series of skin strains associated with lower-lip movements in human subjects to determine if such strains, which serve as stimuli for cutaneous mechanoreceptors, may underlie proprioception in the face. The results suggested that strains associated with lower-lip movements were of sufficient magnitude to elicit cutaneous mechanoreceptor discharge, as shown in recent human microneurographic studies. Further, the magnitude of multiple strains was predictive of lower-lip movement endpoints. These results highlight the potential importance of cutaneous mechanoreceptors as putative proprioceptors.
Integrating HIV Prevention Activities into the HIV Medical Care Setting: A Report from the NYC HIV Centers Consortium

With the maturing of the HIV epidemic and availability of potent antiretroviral therapies in the US, priorities for HIV prevention have shifted from general population approaches to case finding, treatment, risk reduction and relapse prevention activities among those at greatest risk for acquiring or transmitting HIV infection. The challenges of this approach include ensuring access and adherence to HIV care and treatment and appropriate prevention activities to ensure adequate and sustained sexual and drug use risk reduction across diverse populations. Experience with approaches to address these issues, particularly in the context of primary care, has been limited. An agenda for future research and practice includes continued development and evaluation of interventions that can address this next generation of health care issues.
Effects of body size on agonistic encounters between male jumping spiders (Araneae: Salticidae)

. Agonistic encounters were staged between males of the jumping spider Zygoballus rufipes to study the relationship between body size (as estimated by weight) and encounter duration, intensity and outcome. Encounters terminated at one of five different levels of intensity. All encounters started at the lowest level of intensity, and most bilaterally escalated to higher levels. A small number of encounters were unilaterally escalated by the heavier male from the lowest level of intensity directly to the highest level. The associations between weight difference and encounter outcome, duration and maximum level of intensity were assessed using the likelihood ratio statistic. As weight difference decreased, more encounters than expected were won by the lighter male, more were of longer duration and more escalated bilaterally to higher levels of intensity before terminating. Within levels of weight difference, heavier males won more bilaterally-escalated encounters terminating at higher levels of intensity than expected by chance, but won fewer encounters terminating at lower levels of intensity. These results suggest that weight has a significant influence on agonistic encounter outcome, duration and maximum level of intensity, and that when weight difference is small, bilateral escalation to higher levels of intensity is necessary for males to accurately determine body size differences.
A long-lived excited state of O−3; evidence from collision-induced dissociation

Abstract Translational energy thresholds were determined for collision-induced dissociation of O − 3 formed by two alternative reactions. The different thresholds observed for these two processes, 0.96 eV and 1.80 eV respectively, suggest the existence of a long-lived (> μs) excited state or isomeric form of O − 3 .
Learning Disabilities in Children's and Adolescent Literature: How Are Characters Portrayed?.

Ninety fictional books written for children or adolescents that portrayed at least one character with a learning disability were analyzed to determine how learning disabilities and related topics were addressed. Results indicated that most of the characters with learning disabilities were dynamic, meaning they changed or grew through the course of the story line. Also, most were the main character, the story was told from their point of view, and their learning disability had a major impact on the plot. Most commonly the learning disability was in the areas of reading and written language, with the character receiving services in a resource room. The diagnostic/evaluation process was often described, but few details about instructional methods were part of the story. Both negative and positive portrayals of teachers were evident.
Iron induces degeneration of nigrostriatal neurons.

Abstract Parkinson's-diseased (PD) brains have been reported to contain increased quantities of iron within the zona compacta of the substantia nigra (SN). To test whether excess iron in the SN could cause a PD-like loss of dopaminergic neurons, various concentrations of iron were infused unilaterally within the SN of adult male rats. At 1–2 months post-infusion, examination of thionine and iron stained brain sections from animals infused with low concentration iron revealed: 1. (1) iron diffusion limited to and concentrated within the infused SN 2. (2) a selective degeneration of neurons within zona compacta of SN. Infusion of higher iron concentrations induced near complete neuronal losses in zona compacta, as well as neuronal degeneration within zona reticularis and areas immediately adjacent to the SN. Striatal dopamine and its catabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were reduced in a dose-dependent fashion, with over 80% depletions observed at the highest iron concentration infused. These data indicated that neurons within zona compacta of SN are sensitive to infusions of low iron concentrations. The data support the notion that iron in zona compacta of the SN could act as an endotoxin in the pathogenesis of PD.
Shaped-Hole Film Cooling With Pulsed Secondary Flow

The effects of the coolant jet pulsing frequency (PF), duty cycle (DC), and hole shape geometry on heat transfer coefficient and film effectiveness were investigated with a film hole located on a semicircular leading edge test model with an afterbody. Cylindrical and diffusion-shaped holes located at 21.5° from the stagnation line were investigated. An infrared thermography technique with a single transient test was used to determine both the heat transfer coefficient and film effectiveness. Spanwise averaged heat transfer coefficient and film effectiveness were computed from the local values for all test conditions under the same Reynolds number (Re) of 60,000 and density ratio (DR) of 1.11. A dimensionless Frossling number (Fr) was used to represent the heat transfer coefficient. The effects of duty cycles of 50%, 75%, and 100% (continuous coolant) on film effectiveness and heat transfer coefficient were investigated at coolant jet pulsing frequencies of 5 Hertz (Hz) and 10 Hertz. The duty cycle and pulsing frequency were controlled by the opening and closing time settings of two synchronized pulsed valves. The blowing parameters investigated included continuous coolant at the blowing ratios (M) of 0.75, 1.00, 1.50 and 2.00. The subsequent pulsed cases for a combination of pulsing frequency and duty cycle were varied from the corresponding continuous case without changing the coolant flow rate (or blowing ratio) setting for a total of 40 cases for the shaped and cylindrical film holes. The shaped hole provides higher local film effectiveness values than the classical cylindrical hole when coolant flow is steady at M = 1.00. The higher local film effectiveness for the shaped hole was also observed for pulsed cases at M = 1.50 (Meff = 1.25) and M = 2.00 (Meff = 1.07) due to wider film spreading or coverage. The pulsed coolant cases provide higher spanwise averaged film effectiveness than the continuous coolant at M = 1.50 for both hole geometries. In contrast to the film effectiveness, the spanwise averaged Frossling numbers of pulsed coolant are lower compared to the continuous coolant for both hole shapes at the same blowing ratio. Combining the effects of heat transfer coefficient and film effectiveness, one can compute a relative heat load ratio to evaluate the performance of the film cooling. The pulsed coolant cases in general perform better than continuous coolant. The shaped hole geometry provides better film cooling performance than the cylindrical hole geometry for all blowing ratios including the continuous and the pulsed coolant cases studied.Copyright © 2006 by ASME
In Vivo Aggregation of β-Amyloid Peptide Variants

Transgenic Caenorhabditis elegans animals have been engineered to express wild-type and single-amino acid variants of a long form of human beta-amyloid peptide (A beta 1-42). These animals express high levels (approximately 300 ng of A beta/mg of total protein) of apparently full-length peptide, as determined by quantitative immunoblot. Expression of wild-type A beta in these animals leads to rapid production of amyloid deposits reactive with Congo red and thioflavin S. This model system has been used to examine the effect of Leu17Pro, Leu17Val, Ala30Pro, Met35Cys, and Met35Leu substitutions on the in vivo production of amyloid deposits. We find that the Leu17Pro and Met35Cys substitutions completely block the formation of thioflavin S-reactive deposits, implicating these as key residues for in vivo amyloid formation. We have also constructed transgenic strains expressing a novel A beta variant, the single-chain dimer. Animals expressing high levels of this variant also fail to produce thioflavin S-reactive deposits.