cssi/SciSciGPT-SciSciNet huggingface dataset:
Treatment of Multiple Sclerosis: A Review

Multiple sclerosis (MS) is an autoimmune demyelinating and neurodegenerative disease of the central nervous system, and the leading cause of nontraumatic neurological disability in young adults. Effective management requires a multifaceted approach to control acute attacks, manage progressive worsening, and remediate bothersome or disabling symptoms associated with this illness. Remarkable advances in treatment of all forms of MS, and especially for relapsing disease, have favorably changed the long-term outlook for many patients. There also has been a conceptual shift in understanding the immune pathology of MS, away from a purely T-cell-mediated model to recognition that B cells have a key role in pathogenesis. The emergence of higher-efficacy drugs requiring less frequent administration have made these preferred options in terms of tolerability and adherence. Many experts now recommend use of these as first-line treatment for many patients with early disease, before permanent disability is evident.
Med23 Regulates Sox9 Expression during Craniofacial Development.

The etiology and pathogenesis of craniofacial birth defects are multifactorial and include both genetic and environmental factors. Despite the identification of numerous genes associated with congenital craniofacial anomalies, our understanding of their etiology remains incomplete, and many affected individuals have an unknown genetic diagnosis. Here, we show that conditional loss of a Mediator complex subunit protein, Med23 in mouse neural crest cells (Med23fx/fx;Wnt1-Cre), results in micrognathia, glossoptosis, and cleft palate, mimicking the phenotype of Pierre Robin sequence. Sox9 messenger RNA and protein levels are both upregulated in neural crest cell-derived mesenchyme surrounding Meckel's cartilage and in the palatal shelves in Med23fx/fx;Wnt1-Cre mutant embryos compared to controls. Consistent with these observations, we demonstrate that Med23 binds to the promoter region of Sox9 and represses Sox9 expression in vitro. Interestingly, Sox9 binding to β-catenin is enhanced in Med23fx/fx;Wnt1-Cre mutant embryos, which, together with downregulation of Col2a1 and Wnt signaling target genes, results in decreased proliferation and altered jaw skeletal differentiation and cleft palate. Altogether, our data support a cell-autonomous requirement for Med23 in neural crest cells, potentially linking the global transcription machinery through Med23 to the etiology and pathogenesis of craniofacial anomalies such as micrognathia and cleft palate.
Better clinical outcomes in hospitalized COVID-19 minority patients with accompanying gastrointestinal symptoms.

Abstract Background and aims The novel coronavirus (SARS-CoV-2) is highly contagious pathogen that primarily causes respiratory illnesses. Howerver, multiple gastrointestinal (GI) symptoms have been reported in Coronavirus Disease of 2019 (COVID-19). We conducted a retrospective cohort study of inpatients with COVID-19 at the George Washington University Hospital (GWUH) to assess the prevalence of GI symptoms and their association with clinical outcomes. Methods We reviewed the charts of 401 adults admitted to GWUH with positive SARS-CoV-2 tests from February 24 to May 21, 2020, ultimately including 382 inpatients. Results 87% of our cohort was African American or Latinx. 59% of patients reported at least one GI symptom, with diarrhea being the most common (29%). Patients with GI symptoms were slightly younger (58 +/- 15.8 vs. 65 +/- 16.9, p = 0.0005), have higher body mass index (31.5 +/- Standard Deviation of 8.7 vs. 28 +/- 8.2, p = 0.0001), and more likely to be Latinx (34 vs. 27, p = 0.01). Patients who presented with abdominal pain, nausea, vomiting, or diarrhea had significantly lower rates of death during hospitalization compared to those who did not present those symptoms (Odds Ratio 0.48, 95% Confidence Interval 0.28–0.8, p = 0.004). Conclusions Our study suggests that GI symptoms portend a less-severe clinical course of COVID-19 which may reflect a different disease phenotype and lower overall immune response. Additional research should focus on more robust symptom reporting and longer follow-up.
Environmental health research needed to inform strategies, policies, and measures to manage the risks of anthropogenic climate change

Anthropogenic climate change is affecting population health and wellbeing worldwide. The two main policy options to prepare for and manage these risks are adaptation and mitigation; significantly increased investments in each are urgently needed. However, medical research councils worldwide have provided minuscule amounts of funding for environmental health research to provide timely and useful insights on effectively protecting vulnerable populations and regions, for building climate-resilient health systems, and for promoting health system-related greenhouse gas emission reductions in a changing climate.
Feasibility and Preliminary Efficacy of an Internet-Delivered Intervention for Insomnia in Individuals with Mild Cognitive Impairment.

BACKGROUND Approximately 50%of older adults with cognitive impairment suffer from insomnia. When untreated, pre-existing cognitive problems may be exacerbated and potentially contribute to further cognitive decline. One promising approach to maintain cognitive health is to improve sleep quantity and quality. OBJECTIVE To determine feasibility, acceptability, and preliminary efficacy of Sleep Health Using the Internet for Older Adult Sufferers of Insomnia and Sleeplessness (SHUTi OASIS), an Internet-delivered cognitive behavioral therapy for insomnia (CBT-I) program in older adults with mild cognitive impairment (MCI). METHODS Older adults with MCI and insomnia were recruited from hospital-based memory and sleep disorders clinics and enrolled in a single-arm pilot study. Participants completed the six cores of SHUTi OASIS, over nine weeks with two-week baseline and post-assessments using self-reported sleep diaries. Feasibility and acceptability were informed by usage statistics and qualitative interviews; preliminary efficacy was informed by patient-generated sleep data. RESULTS Twelve participants enrolled and, on average, were 75.8 years of age. Ten participants completed the study and logged in most days. Most participants reported a positive overall experience, and interviews revealed successful and independent program management and completion. There were significant changes on all baseline to post-assessment sleep measures, including clinically meaningful improvements on the Insomnia Severity Index (13.5 to 8.3, p 0.05). CONCLUSION This study supports that older adults with cognitive impairment can independently complete CBT-I via the Internet and achieve clinical sleep improvements.
A Cell-Free Antigen Processing System Reveals Factors Critical for HIV-1 Epitope Dominance and Informs Vaccine Design

Distinct CD4+T cell epitopes have been associated with spontaneous control of HIV-1 replication, but analysis of antigen-dependent factors that influence epitope selection is lacking. To examine these factors, we used a cell-free antigen processing system that incorporates soluble HLA-DR (DR1), HLA-DM (DM), and cathepsins along with full-length protein antigens for epitope identification by LC-MS/MS. HIV-1 Gag, Pol, Env, Vif, Nef, Tat, and Rev were examined using this system. We identified 35 novel epitopes, including glycopeptides. Epitopes from smaller HIV-1 proteins with crystal structures mapped to regions of low protein stability and higher solvent accessibility. HIV-1 antigens associated with limited CD4+T cell responses were processed efficiently, while some protective epitopes were inefficiently processed. 66% of epitopes obtained from cell-free processing induced memory CD4+T cell responses in HIV-1+ donors, including 10 of 19 novel epitopes. Thus, an in vitro processing system can identify novel HIV-1 epitopes and reveal factors influencing epitope dominance.
The Biological Disposition of Drugs and Inorganic Toxins

This chapter is a discussion of how some foreign substances get into the body, how they become distributed, what their effects are, and how they are eliminated from the body. Lead is the exemplar in the biological discussion, but the biological concepts can be applied to many other substances. The mathematical discussion focuses on lead poisoning and on pharmaceuticals. Lead can be eaten, inhaled, or absorbed through the skin; it is then distributed to other tissues by the blood. Some of it is then removed from the body by excretion and defecation. Any lead that is retained in the body can have unpleasant biological consequences—anemia and mental retardation, for instance. These processes can be understood only at the levels of organ systems and of the tissues that make up those organs. Thus this chapter includes discussions of the lungs, the digestive tract, the skin, blood, the circulatory system, bones, and the kidneys, all of which are involved in the effects of lead on humans.
Regions and regionalism in the United States

Preface - PART 1 REGIONAL DIFFERENCES - The Significance of Regions - The Elements of Regional Differences in the US - The Historic Basis of Present Regional Differences in the United States - One America? - PART 2 THE CONCERNS OF REGIONALISM - 'Frostbelt' V. 'Sunbelt': A Particular Case - Regions and Resources in the late Twentieth Century - Changes in the Urban-Industrial Economy - Regionalism as a Basis for Planning - Conclusions - Notes - Bibliography - Index
Affinity Labeling of Steroid Binding Sites SYNTHESIS OF 16α-BROMOACETOXYPROGESTERONE AND ITS USE FOR AFFINITY LABELING OF 20β-HYDROXYSTEROID DEHYDROGENASE

Abstract To extend the use of affinity labeling for the characterization of macromolecular steroid binding sites, we have synthesized 16α-bromoacetoxyprogesterone and studied its reactions with various amino acids and 20β-hydroxysteroid dehydrogenase from Streptomyces hydrogenans. This compound alkylates cysteine, histidine, methionine, lysine, and β-mercaptoethanol under physiological conditions. Progesterone derivatives containing 16α-bromoacetoxy, 16α-chloroacetoxy, and 16α-acetoxy substituents are substrates of 20β-hydroxysteroid dehydrogenase with apparent Km values of 1.45 x 10-4, 0.11 x 10-4, and 1.25 x 10-4 m, respectively. Under similar conditions progesterone and cortisone have respective values of 3.95 x 10-6 and 5.1 x 10-5 m. Of the three progesterone esters employed, only 16α-bromoacetoxyprogesterone inactivates the enzyme. It does so in a time-dependent, irreversible manner. When 16α-bromoacetoxyprogesterone is present in 100-fold molar excess, the rate of inactivation follows pseudo-first order kinetics with t½ = 3 hours. Progesterone, cortisone, NAD+, and NADH slow the rate of enzyme inactivation. Excess β-mercaptoethanol stops it but does not restore enzyme activity. Tritiated 16α-bromoacetoxyprogesterone, prepared by condensation of 16α-hydroxyprogesterone with [2-3H]bromoacetic acid in the presence of dicyclohexylcarbodiimide, was used to radiolabel the enzyme-active site during inactivation. The amount of radioactivity incorporated during 30, 50, and 80% enzyme inactivation, indicated that in all cases 2 moles of steroid are bound per mole of enzyme. Amino acid analysis of the hydrolysates of 50 and 80% inactivated enzyme revealed that most of the radioactive material (70% of total counts per min) corresponded to known 1,3-dicarboxymethylhistidine. Further, the radioactivity in this enzyme hydrolysate cocrystallizes with authentic 1,3-dicarboxymethylhistidine. These observations are compatible with a mechanism whereby the progesterone moiety of 16α-bromoacetoxyprogesterone delivers the alkylating group to the active site of 20β-hydroxysteroid dehydrogenase, where it reacts with a histidine residue at that site. They provide the first direct evidence for the presence of this amino acid at a dehydrogenase catalytic site. Furthermore, this supports the view that histidine probably participates in dehydrogenation. Finally, 16α-bromoacetoxyprogesterone is offered as a compound which may be used to characterize certain steroid binding sites of high affinity present in receptor proteins of target organs.
Present and past glaciation threshold in the Cascade Range, Washington, U.S.A.: topographic and climatic controls and paleoclimatic implications

Isoglacihypses depicting the configuration of the glaciation threshold (= “glaciation limit”) in Washington broadly parallel the crest of the Cascade Range and curve around the west and south flanks of the Olympic Mountains. In both uplands the glaciation threshold rises inland (eastward) with a mean gradient of 10-12 m/km. However, the gradient in the Cascades is more variable (7-25 m/km) due to five east-trending troughs in the glaciation threshold surface that coincide with topographic depressions along the range crest and that apparently result from greater eastward penetration of moist maritime air. Mean accumulation-season precipitation correlates strongly (r2 = 0.86) with altitude of the glaciation threshold in the North Cascade Range, but the correlation of glaciation threshold with altitude of the July freezing isotherm, determined from the calculated July lapse rate within the mountains, is much weaker (r2 = 0.40). Multiple regression analysis relating independent climatic variables that affect the height of the glaciation threshold indicates that 90.4% of variance is explained by accumulation-season precipitation and estimated mean annual temperature at the glaciation threshold. The glaciation threshold during the greatest ice advance of the last (Fraser) glaciation in the southern North Cascade Range (c. 18 000-22 000 years B.P.) was 900 ± 100 m below that of the present. Depression of the glaciation threshold by this amount most likely resulted from a change in accumulation-season precipitation of no more than 30% from present values and a decrease in mean ablation-season temperature of 5-5 ± 1.5 deg.
Synthesis of 13C-labeled derivatives of cysteine for magnetic resonance imaging studies of drug uptake and conversion to glutathione in rat brain

Effects of neurodegeneration have been linked to inefficient detoxification of free radicals due to lowered concentrations of antioxidants, especially glutathione, in the brain. In the biosynthesis of glutathione, cysteine concentration is generally the limiting factor. Glutathione and cysteine administrations are not effective treatments for neurodegeneration because glutathione inefficiently crosses cell membranes and cysteine is neurotoxic at high concentrations. Prodrugs of glutathione and cysteine may have more favorable uptake and/or toxicity profiles. Three such prodrugs were synthesized with a 13C-label such that in vivo uptake of each and conversion to glutathione in the brain could be monitored by magnetic resonance imaging. L-[3-13C]-Cysteine was treated with sodium acetate trihydrate and acetic anhydride to give 2(R)-N-acetyl-[3-13C]-cysteine ([13C]-NAC; 96%). Addition of triphosgene to L-[3-13C]-cysteine provided 4(R)-[5-13C]-2-oxothiazolidine-4-carboxylic acid ([13C]-OTZ; 65%). A four-step pathway was used to synthesize ethyl γ-L-glutamyl-[3-13C]-L-cysteinate ([13C]-GCEE). L-[3-13C]-Cysteine was esterified (100% yield) and then cyclized with acetaldehyde to give ethyl 2(R,S)-methyl-[5-13C]-thiazolidine-4(R)-carboxylate (73%) as a mixture of two diastereomers (65:35). The thiazolidine was silylated (bis(trimethylsilyl)trifluoroacetamide) and reacted with N-phthaloyl-L-glutamic anhydride. Treatment with hydrazine afforded ethyl N-[γ-4′(S)-glutamyl]-2(R,S)-methyl-[5-13C]-thiazolidine-4(R)-carboxylate (48%; 73:27 mixture of diastereomers). This was converted to the desired product, [13C]-GCEE (49%), using mercury (II) acetate and hydrogen sulfide.
What do we (not) know about how paracetamol (acetaminophen) works

SUMMARY What is known and background: Although paracetamol (acetaminophen), N-(4-Hydroxyphenyl)acetamide, is one of the world’s most widely used analgesics, the mechanism by which it produces its analgesic effect is largely unknown. This lack is relevant because: (i) optimal pain treatment matches the analgesic mechanism to the (patho)physiology of the pain and (ii) modern drug discovery relies on an appropriate screening assay. Objective: To review the clinical profile and preclinical studies of paracetamol as means of gaining insight into its mechanism of analgesic action. Methods: A literature search was conducted of clinical and preclinical literature and the information obtained was organized and reviewed from the perspective of its contribution to an understanding of the mechanism of analgesic action of paracetamol. Results: Paracetamol’s broad spectrum of analgesic and other pharmacological actions is presented, along with its multiple postulated mechanism(s) of action. No one mechanism has been definitively shown to account for its analgesic activity. What is new and conclusion: Further research is needed to uncover the mechanism of analgesic action of paracetamol. The lack of this knowledge affects optimal clinical use and impedes drug discovery efforts.
Hematopoietic growth factors for the treatment of severe chronic neutropenia.

Severe chronic neutropenia (SCN) is a rare but important cause of recurrent fevers, oropharyngeal ulcerations and severe infections. In three forms of SCN, i.e., congenital neutropenia (Kostmann's syndrome and related syndromes), idiopathic neutropenia (both childhood and adult), and cyclic neutropenia, it is now established that long-term treatment with the hematopoietic growth factor, recombinant human granulocyte colony stimulating factor (rHuG-CSF or Filgrastim), can elevate blood neutrophil counts to the normal range in most patients, with a concomitant reduction in infection-related events including fever, oral ulcerations, antibiotic use and symptoms of inflammation. Treatment with this growth factor causes an increase in the number and maturity of marrow cells of the neutrophilic series; other cell lines are largely unaffected. Marrow stimulation and expansion are reflected by the occurrence of bone pain early in therapy, as well as some increase in spleen size in most cases. Adverse effects of therapy are infrequent in both children and adults, and long-term treatment with daily or every-other-day s.c. injections of rHuG-CSF are well accepted. Because of the risk that some patients with chronic neutropenia may have or develop myelodysplasia and/or leukemia, careful pretreatment evaluations (blood, bone marrow and cytogenetics) and long-term observations are extremely important. An international registry for patients with SCN has been established to maintain records and further investigate these conditions.
Step Bunching, Chemical Ordering, and Diffusivity in Si1−yCy Heteroepitaxy

The growth of Si1−yCy on Si(001) and Si(118) surfaces is investigated experimentally and theoretically. A step instability is found on (118) surfaces leading to step bunching, under low C-concentrations. This behavior is explained by increased diffusivity of Si dimers in the vicinity of carbon. Self adjusting step bunches are found in kinetic Monte Carlo simulations with ordering of the carbon along nearly (001) planes. Experimental parameters (i.e., temperature, flux rate, and tilt angle of the substrate), which are controllable experimentally, can be used to adjust the length scale of the step bunching.
Bidirectional replication from an internal origin in a linear streptomyces plasmid

Commonly, linear replicons that have protein covalently attached to 5' DNA termini replicate by protein-primed, strand-displacing, continuous synthesis of full-length strands. The synthesis of DNA in pSLA2, a 17-kilobase linear plasmid of Streptomyces rochei containing 5' terminal protein, occurs bidirectionally from an internally located replication origin. The replication intermediates are linear duplex molecules that have recessed (approximately 280 nucleotides) 5' ends rather than full-length single strands. The 3' over-hangs may serve as templates for the non-displacing synthesis of the lagging strand terminus primed by the covalently attached 5' DNA binding protein.
Interpretation of the Phase Shifts in Pion-Nucleon Scattering

Wigner has shown that there is a lower limit on the derivative of the scattering phase shift with respect to energy, the limit being expressed in terms of the range of the interaction. Orear has pointed out that this condition is not satisfied by the pion-nucleon $S$-wave phase shifts given by Bethe and de Hoffmann for energies near 200 Mev. Orear's alternate solution, satisfying Wigner's criterion, fits the data equally well. The use of the Wigner condition for pion-nucleon scattering is somewhat questionable because the concept of interaction radius is not well defined. It is shown here that a similar condition may be obtained without the use of this concept. Orear's argument is strengthened on this basis. A simple interpretation of the $S$-wave phase shifts is given in terms of an $I=\frac{1}{2}$ resonance at very high energy, the only parameter being the ratio of level width to resonance energy. A simple two-parameter interpretation of the $P$-wave phase is also presented.
Synthesis of isotopically labeled puromycin derivatives for kinetic isotope effect analysis of ribosome catalyzed peptide bond formation

Abstract The mechanism by which the ribosome catalyze peptide bond formation remains controversial. Here we describe the synthesis of dinucleotides that can be used in kinetic isotope effect experiments to assess the transition state of ribosome catalyzed peptide bond formation. These substrates are the isotopically labeled dinucleotide cytidylyl-(3′-5′)-3′-amino-3′-deoxy-3′- l -phenylalanyl-N6,N6-dimethyladenosine (Cm6ANPhe-NH2) and cytidylyl-(3′-5′)-3′-amino-3′-deoxy-3′-( l -2-hydroxy-3-phenylpropionyl)-N6,N6-dimethyladenosine (Cm6ANPhe-OH). These substrates are active in peptide bond formation and can be used to measure kinetic isotope effects in ribosome catalyzed protein synthesis.
Polysaccharides in ulcerative colitis and normal human rectum compared by stains of biopsy specimens.

Summary1. The lysozyme substrate contained in Micrococcus lysodeikticus is stained by the Hotchkiss or McManus technic after fixation and sectioning by the same procedure utilized for tissue. After fixation and sectioning, the substrate remains susceptible to lysis by lysozyme. Egg albumin, as used in application of sections to slides, does not lyse the lysozyme substrate.2. Biopsy specimens of rectal mucosa from normal persons and patients with active ulcerative colitis after various methods of fixation show no consistent difference in reaction to the Hotchkiss or McManus stain.3. In vitro application of lysozyme and hyaluronidase to human rectal tissue of normal individuals and patients with ulcerative colitis does not alter the reaction of the tissue to the Hotchkiss or McManus stain.
Reproducibility of coronary lumen, plaque, and vessel wall reconstruction and of endothelial shear stress measurements in vivo in humans.

The purpose of this study was to assess the reproducibility of an in vivo methodology to reconstruct the lumen, plaque, and external elastic membrane (EEM) of coronary arteries and estimate endothelial shear stress (ESS). Ten coronary arteries without significant stenoses (five native and five stented arteries) were investigated. The 3D lumen and EEM boundaries of each coronary artery were determined by fusing end-diastolic intravascular ultrasound images with biplane coronary angiograms. Coronary flow was measured. Computational fluid dynamics was used to calculate local ESS. Complete data acquisition was then repeated. Analysis was performed on each data set in a blinded manner. The intertest correlation coefficients for all arteries for the two measurements of lumen radius, EEM radius, plaque thickness, and ESS were r = 0.96, 0.96, 0.94, 0.91, respectively (all P values < 0.0001). The 3D anatomy and ESS of human coronary arteries can be reproducibly estimated in vivo. This methodology provides a tool to examine the effect of ESS on atherogenesis, remodeling, and restenosis; the contribution of arterial remodeling and plaque growth to changes in the lumen; and the impact of new therapies.
Framework for architecture-independent run-time reconfigurable applications

Configurable Computing Machines (CCMs) have emerged as a technology with the computational benefits of custom ASICs as well as the flexibility and reconfigurability of general-purpose microprocessors. Significant effort from the research community has focused on techniques to move this reconfigurability from a rapid application development tool to a run-time tool. This requires the ability to change the hardware design while the application is executing and is known as Run-Time Reconfiguration (RTR). Widespread acceptance of run-time reconfigurable custom computing depends upon the existence of high-level automated design tools. Such tools must reduce the designers effort to port applications between different platforms as the architecture, hardware, and software evolves. A Java implementation of a high-level application framework, called Janus, is presented here. In this environment, developers create Java classes that describe the structural behavior of an application. The framework allows hardware and software modules to be freely mixed and interchanged. A compilation phase of the development process analyzes the structure of the application and adapts it to the target platform. Janus is capable of structuring the run-time behavior of an application to take advantage of the memory and computational resources available.
A new water-based liquid scintillator and potential applications

In this paper we describe a new type of scintillating liquid based on water. We describe the concept, preparation, and properties of this liquid, and how it could be used for a very large, but economical detector. The applications of such a detector range from fundamental physics such as nucleon decay and neutrino physics to physics with broader application such as neutron detection. We briefly describe the scientific requirements of these applications, and how they can be satisfied by the new material.
Control of heteroepitaxial stacking by substrate miscut

We report studies of fcc epitaxial crystals, grown on Nb(110), in which the Nb surface offers a template for selection between the two alternative stackings, {ital ABCA}{hor_ellipsis} and {ital ACBA}{hor_ellipsis} of the fcc close-packed planes. The Nb templates were grown epitaxially about 500 {Angstrom} thick on sapphire (11{bar 2}0), and the fcc material studied was Cu{sub 3}Au. From symmetry it is not possible for the perfect bcc (110) surface to cause any such selection, which is here attributed instead to vicinal miscut: the logarithm of the stacking ratio must be even in miscut along [001] and odd in miscut along [1{bar 1}0]. We find that the measured selectivity is small for miscuts less than about 0.5{degree}, but approaches a factor 10{sup 3} for miscuts along [1{bar 1}0] greater than about 1{degree}. A mechanism for the selection process is discussed in terms of fingered mesostructures that grow on Nb(110) in this regime, as observed first by Zhou, Bonham, and Flynn. {copyright} {ital 1998} {ital The American Physical Society}
Intercalated discs as a cause for discontinuous propagation in cardiac muscle: A theoretical simulation

A theoretical model of a cardiac muscle fiber (strand) based on core conductor principles and which includes a periodic intercalated disc structure has been developed. The model allows for examination of the mechanism of electrical propagation in cardiac muscle on a microscopic cell-to-cell level. The results of the model simulations demonstrate the discontinuous nature of electrical propagation in cardiac muscle and the inability of classical continuous cable theory to adequately describe propagation phenomena in cardiac muscle.
Future Directions for Research on the Development of Relational and Physical Peer Victimization

After several decades of research on peer victimization and associated constructs the field is poised to make a number of important discoveries and advances. More specifically, the study of peer victimization subtypes has rapidly increased since the seminal work of Crick and Grotpeter (1996) on relational and physical victimization. The current state of the field is briefly reviewed, and recommendations for future directions are provided to advance our literature. Critical future directions are discussed and include (a) broaden the range of adjustment outcomes and examine differential pathways associated with physical and relational peer victimization; (b) study peer victimization subtypes at multiple levels of influence including psychophysiological and gene–environment interactions; (c) study physical and relational victimization outside of friendships and links with other close relationship systems; (d) examine the role of culture on peer victimization subtypes; (e) focus on context including but not l...
Effective storage of granulocytes collected by centrifugation leukapheresis from donors stimulated with granulocyte–colony-stimulating factor

Background Donor stimulation with granulocyte-colony-stimulating factor (G-CSF) has increased the number of neutrophils (PMNs) that can be collected for granulocyte transfusion therapy. Clinical utility, however, has been limited by the inability to store functional PMNs ex vivo. This study was conducted to determine whether granulocyte products from G-CSF-stimulated donors could be effectively stored at reduced temperature (22 degrees C vs. 10 degrees C) with maintenance of functional properties in vitro and in vivo. Study design and methods Nine normal subjects received G-CSF (600 microg subcutaneously) 12 hours before centrifugation leukapheresis. Granulocyte products were divided and stored for 24 and 48 hours under four conditions: 1) 22 degrees C; 2) 22 degrees C, with supplemental G-CSF (100 ng/mL); 3) 10 degrees C; and 4) 10 degrees C, with supplemental G-CSF. Functional PMN activity during ex vivo storage was assessed in vitro and in vivo by the skin-window technique for granulocytes stored at 10 degrees C for 24 hours. Results Surface expression of CD11b/CD18, CD14, CD16, CD32, and CD64 was maintained during 48-hour storage at reduced temperature. Inducible respiratory burst activity, bactericidal activity, and fungicidal activity were preserved during storage for 48-hour storage at 10 degrees C. Proinflammatory cytokine production was decreased in product stored at 10 degrees C. Supplemental G-CSF ex vivo did not substantially improve functional activity during storage. After storage at 10 degrees C for 24 hours, in vitro chemotactic potential was maintained, and transfused granulocytes retained capacity to circulate and migrate appropriately in vivo. Conclusions Granulocyte product collected by centrifugation leukapheresis from G-CSF-stimulated donors can be effectively stored at subphysiologic temperature for 24 hours with preservation of functional activity. Storage at 10 degrees C appears to be slightly superior to storage at 22 degrees C.
SINGLE-CRYSTAL 27AL NMR OF ANDALUSITE AND CALCULATED ELECTRIC FIELD GRADIENTS : THE FIRST COMPLETE NMR ASSIGNMENT FOR A 5-COORDINATE ALUMINUM SITE

Andalusite, Al2SiO5, contains 5- and 6-coordinate aluminum sites, and is a preeminent model for 27Al NMR spectroscopy. We describe a combined NMR, crystallography, and theory project: single-crystal 27Al NMR spectra at 298 K, the crystal structure of andalusite at 115 K, and electric field gradient calculations. The low-symmetry 5-coordinate site is a stiff test of the computational methods. In addition, the chemical shift tensor is measured for the 5-coordinate site. The small body of 27Al NMR data, especially for rare 5-coordinate sites, inspires the calculation of NMR parameters. We explore the accuracy of two approaches for 27Al EFG calculations: first, ab initio molecular orbital calculations of small clusters embedded in an array of point charges; second, full-potential linearized augmented plane wave density functional calculations of the crystal. The agreement between the experimental EFG orientation and that from the full-crystal density functional theory is remarkably close, differing by only ...
Faith and the Suspension of the Ethical in Fear and Trembling

This paper concerns Kierkegaard's notion of a teleological suspension of the ethical, which is presented by his pseudonym Johannes de Silentio in Fear and Trembling in connection with the biblical narrative of Abraham's sacrifice of Isaac. Against prevailing readings, I argue that Abraham's suspension of the ethical (as de Silentio interprets it) does not consist in his violating the ethical in order to satisfy a higher normative requirement (such as the duty to obey God). Rather, it consists in his preparedness to violate an overriding ethical norm, even where he does not believe that there is some competing requirement that such a violation will satisfy - indeed, even where he believes that he has no reason to commit the violation and conclusive reason not to. Abraham's faith, as expressed in the teleological suspension, consists not in his willingness to obey God or his recognition that God's authority overrides that of the ethical; it consists in his trustful confidence that what seems certain - that ...
Interactive Effects of Achievement Orientation and Teaching Style on Academic Achievement.

This study examines the hypothesis that the interaction between a student's achievement orientation and the teaching style to which he is exposed differentially affects both the amount o f learning that takes place and the degree of expressed satisfaction w ith the scholastic environment One hundred students, selected because of their extreme scores on the Achievement-via-Conformance and Achievement-via-Independence scales of the California Psychological Inventory, were assigned to introductory psychology sections taught in either a conforming or an independent manner. An analysis o f their scores on a final examination consisting o f multiple-choice items and essay questions, as well as their ratings of teacher effectiveness and course evaluation, indicated a clear interaction effect. Students taught in a manner consonant w ith their achievement orientation obtained significantly higher means on the multiple-choice items, on factual knowledge ratings of their essay answers, and on their ratings o f teacher effectiveness and course evaluation, than their peers who were taught in a dissonant manner.
The current use of estrogens for growth-suppressant therapy in adolescent girls.

Abstract Objective: To assess the current prevalence of growth-suppressant therapy using oral estrogens for tall adolescent girls among U.S. pediatric endocrinologists. Methods: A questionnaire was mailed to pediatric endocrinologists practicing in the United States, asking how many patients each clinician had recently treated for tall stature using oral estrogens, whether he/she continued to offer such treatment, reasons for offering or declining to offer it, criteria for initiating and terminating treatment, choice of estrogen, and typical doses, durations, and effects. Results: Of 411 respondents, 92 (22%) reported having treated 1–5 girls for tall stature during the preceding five years. Only 4 (1%) had treated more than 5 cases during this period. Growth-suppression treatment was currently offered by 137 respondents (33.3%). Reasons for doing so included parents' and patients' concerns about stature and the adverse social effects of unusually tall stature. Reasons for not offering such treatments were that its long-term risks are unknown, that tall stature is not a disease, and a lack of referrals. Few clinicians initiated treatment if predicted mature height was below 183 cm. Treatment was typically terminated based on evidence of epiphyseal fusion, usually within less than two years, although extended treatments were common. Frequently reported adverse effects included weight gain, nausea/vomiting, areolar or nipple pigmentation, headache, and irregular menses. Conclusions: Although treatment is less commonly initiated than in the past, many pediatric endocrinologists continue to offer oral estrogens to suppress growth for tall adolescent girls.
Do we really know the CvLPRIT in Myocardial infarction? or just stent all lesions?

Primary percutaneous coronary intervention (PCI), where available, is the clear treatment of choice for ST-segment myocardial infarction (STEMI) [(1)][1]. A major controversy is whether to only treat the culprit lesion or to also treat obstructive nonculprit lesions—and when. Many
A Conservative Isothermal Wall Boundary Condition for the Compressible Navier---Stokes Equations

We present a conservative isothermal wall boundary condition treatment for the compressible Navier-Stokes equations. The treatment is based on a manipulation of the Osher solver to predict the pressure and density at the wall, while specifying a zero boundary flux and a fixed temperature. With other solvers, a non-zero mass flux occurs through a wall boundary, which is significant at low resolutions in closed geometries. A simulation of a lid driven cavity flow with a multidomain spectral method illustrates the effect of the new boundary condition treatment.
Interview - Searching for biomarkers in Parkinson's disease

Clemens R Scherzer, MD, is Assistant Professor of Neurology at Harvard Medical School, an associate neurologist at Brigham and Women’s Hospital, Co-director of the Harvard NeuroDiscovery Center Biomarker Study (HBS) and directs the Laboratory for Neurogenomics at the Center for Neurologic Diseases. His laboratory looks at a global view of gene activity in human Parkinson’s disease to discover disease genes, drug targets and molecular biomarkers. It integrates large-scale clinical studies with genome-wide expression analysis and genetic validation in human and animal models of Parkinson’s and other neurodegenerative diseases. Scherzer received the Paul B Beeson Award of the American Federation for Aging Research and the National Institute on Aging, and a Dr George Cotzias Memorial Award for the American Parkinson’s Disease Association. He completed a neurology residency at Emory University and fellowship training in movement disorders and genomics at Massachusetts General Hospital and Harvard Medical Schoo...
Determinants and Functions of Standardized Assessment Use Among School Mental Health Clinicians: A Mixed Methods Evaluation.

The current study evaluated why and how school mental health clinicians use standardized assessment tools in their work with youth and families. Quantitative and qualitative (focus group) data were collected prior to and following a training and consultation sequence as part of a trial program to assess school clinician’s (n = 15) experiences administering standardized tools to youth on their caseloads (n = 191). Findings indicated that, although assessment use was initially somewhat low, clinicians used measures to conduct initial assessments with the bulk of their caseloads (average = 62.2 %) during the implementation period. Clinicians also reported on factors influencing their use of assessments at the client, provider, and system levels; perceived functions of assessment; student responses to assessment use; and use of additional sources of clinically-relevant information (primarily educational data) for the purposes of assessment and progress monitoring. Implications for the contextual appropriateness of standardized assessment and training in assessment tools are discussed.
Measurement and Prediction of Effective Diffusivities through Spreading and Nonspreading Oils in Unsaturated Porous Media

The difference in phase continuity between spreading and nonspreading oils at low saturations was examined by measuring the oil phase effective diffusivity. Results indicated that for the sand and water saturations studied, the spreading oil (1-octanol) remained continuous at saturations as low as approximately 0.035 (the lowest oil saturation measured), while the nonspreading oil (n-dodecane) became discontinuous at a saturation of approximately 0.055. 1-Octanol also showed higher effective diffusivities than the n-dodecane throughout the saturation range examined, indicating that the spreading oil was more highly connected. Two separate models, one for spreading and another for nonspreading oils, were used to describe the behavior of the oils in the unsaturated porous medium. Each model gave a reasonable prediction of the experimental data and was able to describe the difference in continuity between nonspreading and spreading oils.
Feedforward hysteresis compensation in trajectory control of piezoelectrically-driven nanostagers

Complex structural nonlinearities of piezoelectric materials drastically degrade their performance in variety of micro- and nano-positioning applications. From the precision positioning and control perspective, the multi-path time-history dependent hysteresis phenomenon is the most concerned nonlinearity in piezoelectric actuators to be analyzed. To realize the underlying physics of this phenomenon and to develop an efficient compensation strategy, the intelligent properties of hysteresis with the effects of non-local memories are discussed. Through performing a set of experiments on a piezoelectrically-driven nanostager with high resolution capacitive position sensor, it is shown that for the precise prediction of hysteresis path, certain memory units are required to store the previous hysteresis trajectory data. Based on the experimental observations, a constitutive memory-based mathematical modeling framework is developed and trained for the precise prediction of hysteresis path for arbitrarily assigned input profiles. Using the inverse hysteresis model, a feedforward control strategy is then developed and implemented on the nanostager to compensate for the system everpresent nonlinearity. Experimental results demonstrate that the controller remarkably eliminates the nonlinear effect if memory units are sufficiently chosen for the inverse model.
On Correlating Channel Error with Bandwidth

Identification of a perspective, for presenting to junior level engineering students, of how a signal transiting an instrument channel is molested by the dynamic properties of that channel. An approximation for relating the frequency content of the signal with the channel bandwidth to achieve a specified percent error over all time is presented.
Caring for identified versus statistical lives: An evolutionary view of medical distributive justice

A central medical ethical concern is distributive justice, which may be framed as a problem in valuing identified lives versus statistical lives. Framing the issue in this way is important for two reasons. First, the growth of medical costs has been fueled and will continue to be fueled primarily by the growth of medical technology focused intensively, and often with little benefit for cost, on the care of identified lives. Second, there is some evidence that less expensive primary care, as opposed to high-tech medicine, is positively correlated with improved life expectancy, decreased infant and neonatal mortality, and fewer cases of low birth weight. However, shifting resources from high-tech medicine to primary care will be difficult because people find it psychologically painful to deny care to identified lives. People value identified lives more than statistical lives because we are influenced by certain cognitive preferences inherent to human nature. Natural selection has primed these cognitive preferences. There are no easy solutions to the profound problems facing healthcare systems. However, evolutionary insights can help us understand these problems and could productively inform attempts to promote primary care as opposed to high-tech medicine, thereby improving benefit for cost and enhancing social welfare.
Recursive utility and the rate of impatience

This paper studies the role of impatience in a model with recursively defined preferences. A method is introduced whereby the rate of impatience can be parametrically adjusted for a given aggregator. Using lattice programming and Topkis' Theorem (1978) sufficient conditions are discovered to guarantee that a reduction in the rate of impatience will lead to greater capital stocks in every period.
Evidence for the multiverse in the standard model and beyond

In any theory it is unnatural if the observed values of parameters lie very close to special values that determine the existence of complex structures necessary for observers. A naturalness probability $P$ is introduced to numerically evaluate the degree of unnaturalness. If $P$ is very small in all known theories, corresponding to a high degree of fine-tuning, then there is an observer naturalness problem. In addition to the well-known case of the cosmological constant, we argue that nuclear stability and electroweak symmetry breaking represent significant observer naturalness problems. The naturalness probability associated with nuclear stability depends on the theory of flavor, but for all known theories is conservatively estimated as ${P}_{\mathrm{nuc}}\ensuremath{\lesssim}({10}^{\ensuremath{-}3}--{10}^{\ensuremath{-}2})$, and for simple theories of electroweak symmetry breaking ${P}_{\mathrm{EWSB}}\ensuremath{\lesssim}({10}^{\ensuremath{-}2}--{10}^{\ensuremath{-}1})$. This pattern of unnaturalness in three different arenas, cosmology, nuclear physics, and electroweak symmetry breaking, provides evidence for the multiverse, since each problem may be easily solved by environmental selection. In the nuclear case the problem is largely solved even if the multiverse distribution for the relevant parameters is relatively flat. With somewhat strongly varying distributions, it is possible to understand both the close proximity to neutron stability and the values of ${m}_{e}$ and ${m}_{d}\ensuremath{-}{m}_{u}$ in terms of the electromagnetic mass difference between the proton and neutron, ${\ensuremath{\delta}}_{\mathrm{EM}}\ensuremath{\simeq}1\ifmmode\pm\else\textpm\fi{}0.5\text{ }\text{ }\mathrm{MeV}$. It is reasonable that multiverse distributions are strong functions of Lagrangian parameters, since they depend not only on the landscape of vacua, but also on the population mechanism, ``integrating out'' other parameters, and on a density of observers factor. In any theory with mass scale $M$ that is the origin of electroweak symmetry breaking, strongly varying multiverse distributions typically lead either to a little hierarchy $v/M\ensuremath{\approx}({10}^{\ensuremath{-}2}--{10}^{\ensuremath{-}1})$, or to a large hierarchy $v\ensuremath{\ll}M$. In certain multiverses, where electroweak symmetry breaking occurs only if $M$ is below some critical value, we find that a little hierarchy develops with the value of ${v}^{2}/{M}^{2}$ suppressed by an extra loop factor, as well as by the strength of the distribution. Since the correct theory of electroweak symmetry breaking is unknown, our estimate for ${P}_{\mathrm{EWSB}}$ is theoretical. The LHC will lead to a much more robust determination of ${P}_{\mathrm{EWSB}}$, and, depending on which theory is indicated by the data, the observer naturalness problem of electroweak symmetry breaking may be removed or strengthened. For each of the three arenas, the discovery of a natural theory would eliminate the evidence for the multiverse; but in the absence of such a theory, the multiverse provides a provisional understanding of the data.