cssi/SciSciGPT-SciSciNet huggingface dataset:
Classics in Chemical Neuroscience: Fluoxetine (Prozac)

Fluoxetine (Prozac) was the first major breakthrough for the treatment of depression since the introduction of tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) nearly 30 years earlier. It was the first selective serotonin reuptake inhibitor (SSRI) approved by the United States Food and Drug Administration, offering superior efficacy and reduced side effects relative to TCAs and MAOIs. Though a debate remains regarding the exact mechanism by which the clinical efficacy of fluoxetine is manifested, the importance of fluoxetine and related SSRIs to the field is unquestionable. The trade name Prozac has permeated popular culture, helping to raise awareness of depression and to diminish the prevalence of long-standing stigmas associated with this illness. In this Review, we will showcase the history and importance of fluoxetine to neuroscience in general, as well as for the treatment of depression, and review the synthesis, pharmacology, drug metabolism, and adverse effects of fluoxetine.
A Case Study in Malware Research Ethics Education: When Teaching Bad is Good

There is a growing interest in the research of malware in the context of cyber-security. In this paper I will present a case study that will outline the curriculum used to teach malware ethics within the context of a computer science course that teaches students malware programing techniques. Issues from computer and information ethics that apply most closely to ethical malware research will be highlighted. The topics discussed in the course will be outlined and assessment techniques will be discussed.
Venture Capitalists’ Confidence, Asymmetric Information, and Liquidity Events

Abstract Venture capitalists, in assessing and advising their portfolio firms and seeking viable exit strategies for them through discussions with investment bankers and corporate acquisitors, develop early and sophisticated insight in high potential new ventures and alternative liquidity events for them. Given this early and unique perspective that VCs have of their portfolio firms and potential liquidity events, in this paper, relying on an information asymmetries perspective, we examine whether changes in venture capitalists’ confidence, as informed by VCs’ unique informational advantage, may precede changes in the volume of liquidity events (IPOs and M&As) of venture-backed firms. To explore this notion, we conducted quarterly surveys of VCs for 3.5 years with regard to their confidence in the future high-growth entrepreneurial environment and compared our results with archival data of the volume of IPOs and M&As of venture-backed firms over the same period. We find, in fact, that changes in VC confid...
Effects of preservation on dry- and ash-free dry weight biomass of some common aquatic macro-invertebrates

The effect of preservation methods on dry weight (DW) and ash-free dry weight (AFDW) of Radix peregra (Gastropoda), Asellus aquaticus (Isopoda), Erpobdella octoculata (Hirudinea) and Glyptotendipes sp. (Chironomidae) was studied. Ethanol, formaldehyde, and Bouin were used as preservative. In case of preservation of macro-invertebrates in ethanol substancial changes in DW and AFDW biomass were observed. In the four different taxa the loss in DW varied between 7.2–21.9% after a 3 month preservation period in 70% ethanol. A comparatively small range in AFDW loss (16.2–19.7%) was found. Changes in DW and AFDW biomass during preservation were significantly affected by the duration of the preservation, by temperature, light conditions and the volume of the preservative. The changes in AFDW were also significantly affected by the concentration of the preservatives. Preservation in 10% formaldehyde did not cause significant changes in DW and AFDW biomass.
Endocrine assessment of relative reproductive age in normal eumenorrheic younger and older women across multiple cycles.

Abstract Objective The aim of this study was to better characterize the ranges and intercycle variability for day 3 follicle-stimulating hormone, estradiol, and inhibin B levels in normal eumenorrheic women. Study design Healthy eumenorrheic volunteers were recruited, of whom 27 women were 20 to 25 years old (peak reproductive age) and 36 women were 40 to 45 years old (study population). Blood samples were obtained on day 3 of two consecutive menstrual cycles. In some women, an additional blood sample on day 3 was obtained within 1 year. Results In normal women aged 20 to 25 years versus women aged 40 to 45 years, the day 3 follicle-stimulating hormone geometric mean is 5.6 IU/L (95% CI, 3.3-9.5 IU/L) versus 9.6 IU/L (95% CI, 3.8-23.8 IU/L), the day 3 estradiol geometric mean is 44.0 pg/mL (95% CI, 20.4-95.0 pg/mL) versus 52.4 pg/mL (95% CI, 22.4-122.8 pg/mL), and the day 3 inhibin B geometric mean is 100.4 pg/mL (95% CI, 51.7-195.0 pg/mL) versus 52.4 pg/mL (95% CI, 9.5-289.3 pg/mL). Furthermore, 22% of women in the older age group have a normal day 3 follicle-stimulating hormone and estradiol level in one cycle but an elevated value in a consecutive cycle ( P =.008). Conclusion In women of peak reproductive age, the upper limit of day 3 follicle-stimulating hormone and estradiol levels are 9.5 IU/L and 95.0 pg/mL, respectively, and the lower limit of day 3 inhibin B level is 51.7 pg/mL. If the initial day 3 follicle-stimulating hormone and estradiol levels in an older woman are normal, then a second measurement in a subsequent cycle should be obtained before counseling this woman regarding her reproductive potential.
Orientational effects on atomic photoelectric cross sections and their relevance to photoelectron spectra from single crystals

Abstract We have examined the dependence of the photoelectric cross section from individual atomic orbitals and from groups of orbitals adapted to crystal symmetries in order to ascertain the relevance of this effect to the photoelectron spectra arising from single crystals.
Vitreous hemorrhage in patients with high-risk retinopathy of prematurity.

Abstract Purpose To investigate outcomes in premature infants with high-risk retinopathy of prematurity and secondary vitreous hemorrhage. Design Retrospective chart review. Methods Patients were selected from a database of infants undergoing retinopathy of prematurity screening from September 1997 to November 1999. Infants with high-risk retinopathy of prematurity (zone I or posterior zone II threshold disease) with and without vitreous hemorrhage were compared. Main outcome measures Final stage of retinopathy of prematurity and short-term structural outcome were assessed. Visual acuity and refraction were measured when possible. Results Twenty-two eyes of 11 patients (group 1) had high-risk (posterior zone II or zone I threshold) retinopathy of prematurity without vitreous hemorrhage. Group 1 patients had a 91% favorable short-term structural outcome. Eight eyes of five infants developed vitreous hemorrhage with high-risk retinopathy of prematurity (group 2). Group 2 patients had only a 12.5% favorable short-term structural outcome. Seven of eight (87.5%) progressed to stage IVa or IVb retinopathy of prematurity. Six eyes underwent vitreoretinal surgery after a median duration of hemorrhage of 36 ± 29 days (4–70 days). Three eyes developed stage V detachments and three progressed to phthisical degeneration. Final visual acuity was no light perception in three eyes. Conclusion Vitreous hemorrhage, in association with advanced retinopathy of prematurity, is a poor prognostic sign.
Anisotropic two-dimensional scattering. II. Finite depth and refractive index effects

A helium-neon laser beam was incident normal to the surface of a finite-depth scattering medium, and the radiant energy emerging normally form the liquid surface was measured as a function of the radial distance from the laser beam. The scattering centers used were high-quality spherical polystyrene particles of 0.261-micron diameter. It is found that the anisotropic nondimensional intensity distribution depends on the asymmetry factor g and, even though the range tested is small, (1-g) appears to be a correlation parameter in anisotropic backscattering from a medium of finite depth. The particle carriers produce very similar results, thus suggesting that the backscattering intensity is insensitive to the index of refraction of the particle carrier. 10 references.
Cells and cytokines in the pathogenesis of MAIDS, a retrovirus-induced immunodeficiency syndrome of mice

MAIDS is a retrovirus-induced immunodeficiency syndrome of mice that develops as a consequence of multiple interactions between T and B cells. The disease develops in response to infection with a defective virus encoding a Pr60gag protein that is myristylated and binds to cell membranes. T cells, B cells, and macrophages are all targets for infection by the defective virus, and some direct effects of infection have been demonstrated for T cells in the absence of other cell types. It is not known if the defective virus has direct effects on B cells and macrophages. It is clear, however, that an unusually vigorous response of the immune system to the inciting virus elicits deregulated expression of numerous cytokines. This response is antigen driven, as it does not develop in mice lacking MHC class II molecules, but the nature of the antigenic molecule is not known. Other T cell-B cell interactions of major importance to induction of disease include those mediated by ligation of CD40/CD40L and CD11a/CD54. It would appear that a significant component of the abnormal response is due to stimulation of T cells through the TCR in the absence of efficient co-stimulation, resulting in generalized anergy. The pattern of cytokine expression in MAIDS-susceptible mice — high IL-4, IL-10, and IFN-γ and low IL2 — is consistent with this model. By further increasing IFN-γ expression through treatment of mice with IL-12, it is possible to inhibit induction of disease and to reverse many manifestation of established disease. Disease inhibition by IL-12 can be ascribed in part to effects in limiting expression of the etiological virus. IL-12 may prove to be an effective treatment for other retrovirus infections with similar immunopathogenesis.
Defective Glomerulogenesis in the Absence of Laminin α5 Demonstrates a Developmental Role for the Kidney Glomerular Basement Membrane

Abstract Laminins are major components of all basement membranes. They are a diverse group of α/β/γ heterotrimers formed from five α, three β, and three γ chains. Laminin α5 is a widely expressed chain found in many embryonic and adult basement membranes. During embryogenesis, α5 has a role in disparate developmental processes, including neural tube closure, digit septation, and placentation. Here, we analyzed kidney development in Lama5 mutant embryos and found a striking defect in glomerulogenesis associated with an abnormal glomerular basement membrane (GBM). This correlates with failure of the developmental switch in laminin α chain deposition in which α5 replaces α1 in the GBM at the capillary loop stage of glomerulogenesis. In the absence of a normal GBM, glomerular epithelial cells were in disarray, and endothelial and mesangial cells were extruded from within the constricting glomerulus, leading to a complete absence of vascularized glomeruli. In addition, a minority of Lama5 mutant mice lacked one or both kidneys, indicating that laminin α5 is also important in earlier kidney development. Our results demonstrate a dual role for laminin α5 in kidney development, illustrate a novel defect in glomerulogenesis, and indicate a heretofore unappreciated developmental role for the GBM in influencing the behavior of epithelial and endothelial cells.
A Multi-Institutional Comparison of Pediatric Appendicitis Outcomes Between Teaching and Nonteaching Hospitals

Objective In this era of heightened emphasis on patient outcomes, it is important to document the effect of residents acting as the surgeon for a surgical procedure. This study compares the outcomes of appendicitis between teaching and nonteaching institutions. Design A retrospective review from 1998 to 2007 was performed. The study outcomes were postoperative morbidity and length of hospitalization (LOH). Data were analyzed using Wilcoxon rank-sum test and χ 2 analysis. Setting Two teaching institutions (each with its own General Surgery residency program) were compared with 10 nonteaching institutions. Results A total of 1472 patients were treated at the teaching institutions (mean age=9.8 years, male=63%), and 6431 patients were treated at the nonteaching institutions (mean age=10.8 years, male=62%). The perforated appendicitis rate was 37% at the teaching institutions and 30% at the nonteaching institutions (p Conclusions Postoperative morbidity was similar in children with nonperforated appendicitis and lower in children with perforated appendicitis at teaching institutions. LOH was similar between teaching and nonteaching institutions. Overall, the presence of surgical trainees had no adverse impact on the quality of care for children with appendicitis.
Comparison of pulmonary endothelial cell and fibroblast proliferation using time-lapse cinematographic analysis

Abstract Time-lapse cinematography was used to study and compare the proliferation and migration activity of pulmonary endothelial cells and fibroblasts, two cell types with very different structural and functional properties. Endothelial cells were found to have a mere rapid growth rate than fibroblasts. Contributing to the shorter population doubling time of the endothelial cells were lower interdivision times and a tendency for these cells to remain in division cycle with successive generations of growth. Striking differences between endothelial cells and fibroblasts were seen in migration behaviour. Endothelial cells had lower migration rates and tended to remain within a restricted growth area, whereas fibroblasts migrated freely throughout the growth area.
Public policy and the quality of life: How relevant is economics? Public policy and the quality of life: Market incentives versus government planning Randall G. Holcombe greenwood press, 1995, 190 pp.

This article summarizes and critiques Holcombe's arguments on the influence of private ownership and markets on the quality of life. Holcombe summarizes the free market-oriented literature and provides interesting anecdotes in arguing that markets are superior to public policies and more cost-effective in pursuing social goals such as health care, environmental protection, and housing. This critique argues that Holcombe's approach is much too narrow in that it reduces the quality of life to commercial value, cost minimization, and property rights. Economic analysis can become more relevant to the public discourse by recognizing that social values are broader than cost minimization and efficiency. Public sensibilities on equity, justice, equal opportunity, and human dignity shape the sociocultural context for evaluating the impact of public policy on the quality of life. Ideas are offered for enhancing the relevance of economics to policy discussions on the quality of life.
Starting a Nutrition Support Team Short-Term Pain for Long-Term Gain

This article relates the collective wisdom of five nutrition support professionals who share their experience in starting a nutrition support team. These professionals describe how to navigate the administrative— and political—waters, which are often murky and filled with obstacles. In addition, a hospital administrator discloses what CEO types look for when clinicians propose starting up a nutrition support team in their institutions. The upshot: In this rapidly changing environment, nutrition support professionals would do well to hone their political skills and use them to persuade their administrators that nutrition support is indeed a cost-effective therapy that benefits patients—and that it is best delivered in an interdisciplinary approach.
Laparoendoscopic single site (LESS) cholecystectomy.

The journey from conventional “open” operations to truly “minimally invasive” operations naturally includes progression from operations involving multiple trocars and multiple incisions to operations involving access through the umbilicus alone. Laparoscopic operations through the umbilicus alone, laparoendoscopic single site surgery (LESS), offer improved cosmesis and hopes for less pain and improved recovery. This study was undertaken to evaluate our initial experience with LESS cholecystectomy and to compare our initial experience to concurrent outcomes with more conventional multiport, multi-incision laparoscopic cholecystectomy. All patients referred for cholecystectomy over a 6-month period were offered LESS. Outcomes, including blood loss, operative time, complications, and length of stay were recorded. Outcomes with our first LESS cholecystectomies were compared to an uncontrolled group of concurrent patients undergoing multiport, multi-incision laparoscopic cholecystectomy at the same hospital by the same surgeon. Twenty-nine patients of median age 50 years undergoing LESS cholecystectomy from November 2007 until May 2008 were compared to 29* patients, median age 48 years, undergoing standard multiport, multiple-incision laparoscopic cholecystectomy over the same time period. Median operative time for patients undergoing LESS cholecystectomy was 72 min and was not different from that of patients undergoing multiport, multi-incision laparoscopic cholecystectomy (p = 0.81). Median length of hospital stay was 1.0 day for patients undergoing LESS cholecystectomy and was not different from patients undergoing standard laparoscopic cholecystectomy (p = 0.46). Operative estimated blood loss was less than 100 cc for all patients. No patients undergoing attempted LESS cholecystectomy had conversions to “open” operations; two patients had an additional trocar(s) placed distant from the umbilicus to aid in exposure. Three patients undergoing LESS cholecystectomy had complications: two were troubled by pain control and another had urinary retention. LESS cholecystectomy is a safe and effective alternative to standard laparoscopic cholecystectomy. It can be undertaken without the expense of added operative time and provides patients with minimal, if any, apparent scarring. We believe LESS cholecystectomy will be driven by consumer demand, and therefore, laparoscopic surgeons will need to become proficient with LESS procedures.
Arc: an OAI service provider for cross-archive searching

The usefulness of the many on-line journals and scientific digital lib raries that exist today is limited by the lack of a service that can federate them through a unified interface. The Open Archive Initiative (OAI) is one major effort to address technical interoperability among distributed archives. The objective of OAI is to develop a framework to facilitate the discovery of content in distributed archives. In this paper, we describe our experience and lessons learned in building Arc, the first federated searching service based on the OAI protocol. Arc harvests metadata from several OAI compliant archives, normalizes them, and stores them in a search service based on a relational database (MySQL or Oracle). At present we have over 165K metadata records from 16 data providers from various domains.
Software Use in Psychometric Research

Research on psychometric methods is heavily dependent on software. The quality, availability, and documentation of such software are critical to the advancement of the field. In 2000, an ad hoc committee of NCME recommended that NCME adopt policies that promote greater availability and better documentation of software. This article follows the ad hoc committee's report by examining the use of software in four top-tiered journals in recent years. The results indicated that the most frequently cited programs were those written by the articles' authors. The documentation and availability for these programs are often not clear, particularly for software used for simulations. The use of proprietary software was not widespread in the four journals, but there is still room for concern in the future. This article recommends that NCME form a permanent committee to address software issues.
A focus on the September 1985 Michoacan earthquakes

The severity of damage to Mexico City as a result of the 19 September 1985 Michoacan earthquake was unusual given the city's distance (350 km) from the zone of seismic energy release. To explain the damage many authors have suggested that unusual source or transmission path characteristics contributed to enhanced ground motion in Mexico City. The purpose of this paper is to present a summary of results obtained from data recorded during the earthquake related to possible anomalous source characteristics.
THERMAL INITIATION OF VINYL POLYMERIZATION BY CERIC SOLUTIONS

Acid solutions of ceric perchlorate, nitrate, and sulfate initiated vinyl polymerization in the dark, via a normal free-radical mechanism.
Infrared overtone spectroscopy of adsorbed hydrogen in MOF-5

Abstract Overtone spectroscopy is used to observe the rovibrational spectra of the hydrogen isotopologues H2, HD, and D2 adsorbed in the metal–organic framework known as MOF-5. It is shown that the overtone spectrum facilitates the identification of hydrogen modes which are obscured in the fundamental region by the presence of MOF-5 features. Further, the overtone spectrum of H2 at the primary adsorption site is greatly enhanced relative to other sites, and thus ambiguities about feature assignment can be avoided. The frequency (wavenumber) of the overtone modes are in good agreement with a Buckingham perturbative model while the relative intensity of the Q 2 (0) pure vibrational mode is found to be anomalously large, most likely arising through mode coupling to the MOF-5 framework.
Neural evidence reveals the rapid effects of reward history on selective attention

Selective attention is often framed as being primarily driven by two factors: task-relevance and physical salience. However, factors like selection and reward history, which are neither currently task-relevant nor physically salient, can reliably and persistently influence visual selective attention. The current study investigated the nature of the persistent effects of irrelevant, physically non-salient, reward-associated features. These features affected one of the earliest reliable neural indicators of visual selective attention in humans, the P1 event-related potential, measured one week after the reward associations were learned. However, the effects of reward history were moderated by current task demands. The modulation of visually evoked activity supports the hypothesis that reward history influences the innate salience of reward associated features, such that even when no longer relevant, nor physically salient, these features have a rapid, persistent, and robust effect on early visual selective attention.
Reactions of Tungsten(VI) Dialkyl Complexes with tBuNC: Synthesis and Characterization of New Square Pyramidal and Trigonal Bipyramidal Tungsten(VI) Complexes

The complexes [(TMS)2pda](NPh)WR2 ((TMS)2pda = o-(Me3SiN)2C6H4}2-; R = CH3 (1), CH2CMe3 (4)) react with tBuNC to form the octahedral monoadducts [(TMS)2pda](NPh)WR2(CNtBu) (1a and 4a). 1a is observed only at low temperature, while 4a can be isolated. Both 1a and 4a react with tBuNC to form the corresponding trigonal bipyramidal bis(η2-imino-acyl) species [(TMS)2pda](NPh)W[η2-(tBu)NCR]2 (R = CH3 (2), CH2CMe3 (5)), which have been isolated and characterized. Compound 2 isomerizes upon heating to the square pyramidal metallacycle [(TMS)2pda](NPh)W[(tBu)NC(CH3)C(CH3)N(tBu)] (3), which has been isolated as a red solid. X-ray crystal structures have been obtained for compounds 2 and 3. Crystals of 2 are orthorhombic, space group P212121, with a = 9.1175(3) A, b = 17.9587(5) A, c = 20.9435(6) A, and Z = 4. Compound 2 has trigonal bipyramidal geometry with the imido N and one amido N in axial positions. Crystals of 3 are monoclinic, space group C2/c, with a = 35.1302(9) A, b = 12.6459(2) A, c = 16.2386(6) A, β = ...
Light-scattering properties of a woven shade-screen material used for daylighting and solar heat-gain control

Shade-screens are widely used in commercial buildings as a way to limit the amount of direct sunlight that can disturb people in the building. The shade screens also reduce the solar heat-gain through glazing the system. Modern energy and daylighting analysis software such as EnergyPlus and Radiance require complete scattering properties of the scattering materials in the system. In this paper a shade screen used in the LBNL daylighting testbed is characterized using a photogoniometer and a normal angle of incidence integrating sphere. The data is used to create a complete bi-directional scattering distribution function (BSDF) that can be used in simulation programs. The resulting BSDF is compared to a model BADFs, both directly and by calculating the solar heat-gain coefficient for a dual pane system using Window 6.
Metabolism of benthic octopods (Cephalopoda) as a function of habitat depth and oxygen concentration

The oxygen consumption rates and activities of key metabolic enzymes were measured and analyzed as a function of habitat depth for several species of benthic octopod (Cephalopoda: Octopoda) including a recently described hydrothermal vent endemic species. Oxygen consumption rates and citrate synthase activity, an indicator of aerobic metabolic potential, did not vary significantly with increasing habitat depth. Anaerobic metabolic potential, as evidenced by octopine dehydrogenase activity, declined significantly with increasing habitat depth. It is suggested that burst swimming abilities, and hence glycolytic potential, are not strongly selected for in the deep-sea, where visual predator-prey interactions are reduced because of light-limitation. Oxygen consumption rates for Octopus californicus and O. bimaculoides were analyzed as a function of oxygen partial pressure as well. O. californicus, which lives in the hypoxic Santa Barbara basin at 500 m depth, was able to regulate its oxygen consumption to the limit of detectable oxygen partial pressures. O. bimaculoides, an intertidal species, had a minimum critical oxygen partial pressure of 16 mmHg. It is also shown that oxygen consumption rates and oxygen consumption regulation are strongly affected by individual experiment duration (either handling stress or food deprivation). O. californicus appears to be much more strongly affected by experiment duration than is O. bimaculoides.
Chronic Alcohol Self‐Administration in Monkeys Shows Long‐Term Quantity/Frequency Categorical Stability

Background The current criteria for alcohol use disorders (AUDs) do not include consumption (quantity/frequency) measures of alcohol intake, in part due to the difficulty of these measures in humans. Animal models of ethanol (EtOH) self-administration have been fundamental in advancing our understanding of the neurobiological basis of AUD and can address quantity/frequency measures with accurate measurements over prolonged periods of time. The nonhuman primate model of voluntary oral alcohol self-administration has documented both binge drinking and drinking to dependence and can be used to test the stability of consumption measures over time. Methods Here, an extensive set of alcohol intakes (g/kg/d) was analyzed from a large multi-cohort population of Rhesus (Macaca mulatta) monkeys (n = 31). Daily EtOH intake was uniformly distributed over chronic (12 months) access for all animals. Results Underlying this distribution of intakes were subpopulations of monkeys that exhibited distinctive clustering of drinking patterns, allowing us to categorically define very heavy drinking (VHD), heavy drinking (HD), binge drinking (BD), and low drinking (LD). These categories were stable across the 12 months assessed by the protocol, but exhibited fluctuations when examined at shorter intervals. Conclusions The establishment of persistent drinking categories based on quantity/frequency suggests that consumption variables can be used to track long-term changes in behavioral, molecular, or physiochemical mechanisms related to our understanding of diagnosis, prevention, intervention, and treatment efficacies.
Dissection of the energetic coupling across the Src SH2 domain-tyrosyl phosphopeptide interface.

Abstract Src Homology (SH2) domains play critical roles in signaling pathways by binding to phosphotyrosine (pTyr)-containing sequences, thereby recruiting SH2 domain-containing proteins to tyrosine-phosphorylated sites on receptor molecules. Investigations of the peptide binding specificity of the SH2 domain of the Src kinase (Src SH2 domain) have defined the EEI motif C-terminal to the phosphotyrosine as the preferential binding sequence. A subsequent study that probed the importance of eight specificity-determining residues of the Src SH2 domain found two residues which when mutated to Ala had significant effects on binding: TyrβD5 and LysβD3. The mutation of LysβD3 to Ala was particularly intriguing, since a Glu to Ala mutation at the first (+1) position of the EEI motif (the residue interacting with LysβD3) did not significantly affect binding. Hence, the interaction between LysβD3 and +1 Glu is energetically coupled. This study is focused on the dissection of the energetic coupling observed across the SH2 domain-phosphopeptide interface at and around the +1 position of the peptide. It was found that three residues of the SH2 domain, LysβD3, AspβC8 and AspCD2 (altogether forming the so-called +1 binding region) contribute to the selection of Glu at the +1 position of the ligand. A double (AspβC8Ala, AspCD2Ala) mutant does not exhibit energetic coupling between LysβD3 and +1 Glu, and binds to the pYEEI sequence 0.3 kcal/mol tighter than the wild-type Src SH2 domain. These results suggest that LysβD3 in the double mutant is now free to interact with the +1 Glu and that the role of LysβD3 in the wild-type is to neutralize the acidic patch formed by AspβC8 and AspCD2 rather than specifically select for a Glu at the +1 position as it had been hypothesized previously. A triple mutant (LysβD3Ala, AspβC8Ala, AspCD2Ala) has reduced binding affinity compared to the double (AspβC8Ala, AspCD2Ala) mutant, yet binds the pYEEI peptide as well as the wild-type Src SH2 domain. The structural basis for such high affinity interaction was investigated crystallographically by determining the structure of the triple (LysβD3Ala, AspβC8Ala, AspCD2Ala) mutant bound to the octapeptide PQpYEEIPI (where pY indicates a phosphotyrosine). This structure reveals for the first time contacts between the SH2 domain and the −1 and −2 positions of the peptide (i.e. the two residues N-terminal to pY). Thus, unexpectedly, mutations in the +1 binding region affect binding of other regions of the peptide. Such additional contacts may account for the high affinity interaction of the triple mutant for the pYEEI-containing peptide.
Natural-source d-α-tocopheryl acetate inhibits oxidant stress and modulates atopic asthma in humans in vivo.

Background Asthma is associated with oxidant stress and diminished antioxidant defenses. Yet, the mechanistic role of oxidant stress and antioxidant supplementation in human asthmatics remains uncertain. We determined the effect of high doses of the antioxidant natural-source d-α-tocopheryl acetate for 16 weeks on allergen-induced airway oxidant stress, inflammation, and bronchial responsiveness to methacholine and allergen in atopic asthmatics in vivo. Methods Thirty-three mild atopic asthmatics underwent bronchoscopy with baseline bronchoalveolar lavage and segmental allergen challenge. The allergen-challenged airway was lavaged 24 h later. At least 3 weeks later, patients underwent inhaled challenges with methacholine and specific allergen. Volunteers took 1500 IU of natural-source d-α-tocopheryl acetate daily for at least 16 weeks. At the end of the treatment, the two bronchoscopies and inhaled methacholine and allergen challenges were repeated. F2-isoprostanes, specific markers of oxidant stress, and selected Th1 and Th2 cytokines were analyzed in the lavage fluid. Results Following supplementation of natural-source d-α-tocopheryl acetate, plasma concentrations of α-tocopherol increased and γ-tocopherol decreased. Both baseline and allergen-induced F2-isoprostanes significantly decreased, providing biochemical evidence for an antioxidant effect. Natural-source d-α-tocopheryl acetate reduced allergen-provoked concentrations of interleukin 3 and interleukin 4 and augmented levels of interleukin 12 in bronchoalveolar lavage fluid. Natural-source d-α-tocopheryl acetate improved airway responsiveness to methacholine but did not alter airway reactivity to specific allergen. Conclusions Inhibition of oxidant stress by natural-source d-α-tocopheryl acetate modulates allergic inflammation and airway hyperresponsiveness in human atopic asthmatics in vivo. These results need to be confirmed by a randomized placebo-controlled trial.
The role of peroxidase vs. the role of tyrosinase in enzymatic conversion of tyrosine to melanin in melanocytes, mast cells and eosinophils.

Autoradiographic-histochemical observations, correlated with previous histochemical and biochemical studies in our laboratory, and with studies with isolated mammalian peroxidase, have provided evidence that mammalian peroxidase can mediate the enzymatic conversion of tyrosine to melanin, in the presence of dopa as co-factor. Our studies provided no conclusive evidence that mammalian tyrosinase has significant ability to oxidize tyrosine to melanin, although they showed that this enzyme has strong dopa oxidase activity. It is suggested that peroxidase may be the enzyme initiating melanin synthesis in vivo and that tyrosinase may utilize dopa synthesized by enzymatic activity of peroxidase. Tyrosinase may therefore function primarily as a dopa oxidase, as conceived by Bloch.
Fiber production and properties in genetically furred and furless rabbits

The objectives of this study were to describe and compare means and measures of variability of fiber characteristics and fiber production between genetically furred and furless rabbits and among classes of furless rabbits. An F1 generation of rabbits was produced by mating New Zealand White does to a rare, furless Mini Lop buck. All F1 offspring had normal coats of fur. Inter se random matings of the F1 stock (barring full-sibling matings) were made to produce the F2 generation that consisted of approximately 75% furred and 25% furless progeny. Furless animals were further subjectively classified into 3 distinct classes (1 to 3) having increasingly more fur. In yr 1, 17 furred and 20 furless rabbits (age 28 to 49 d) were randomly assigned to growing pens, and in yr 2, 17 additional furless and 9 additional furred rabbits were included to increase the size. After 6 wk, the rabbits were weighed, and a measured area of fur (approximately 20 cm2) was shorn from the left flank of each rabbit. This fiber was weighed and measured for staple length, fiber diameter, prickle factor (% of fibers > 30 microm in diameter), and fiber curvature. Fiber production per unit area of skin was calculated and fiber production per animal was estimated. In yr 2, all of the furless and 2 of the furred rabbits were shorn over their entire bodies to obtain direct measurements of total fur weight. Furless rabbits were 9% heavier (1,941 vs. 1,783 g of BW, P < 0.01) and produced approximately 90% less fiber per unit area of skin than furred rabbits (1.74 vs. 15.83 mg/cm2, P < 0.01). The fibers from furless rabbits were shorter (1.54 vs. 2.56 cm, P < 0.01) and coarser (15.8 vs. 14.5 microm diameter, P < 0.01) than those from furred rabbits and exhibited greater prickle factor (11.3 vs. 3.5%, P < 0.01) and curvature values (47.5 vs. 38.5 deg/mm, P < 0.01). Class 3 furless rabbits were heavier than rabbits of classes 1 and 2 (2,075 vs. 1,817 and 1,981 g of BW, respectively, P < 0.05). Means for actual total fiber production per animal for classes 1 to 3 were 0.64, 2.07, and 8.68 g, respectively, compared with 23.0 g for furred rabbits (P < 0.01). Although some similarities were present, several of the correlations involving fiber properties and BW were substantially different (e.g., BW vs. staple length and fiber diameter vs. weight of fiber per unit area) for furred and furless groups. These results, and those reported elsewhere from a series of experiments, support the potential for production of furless rabbits in arid and tropical environments.
Direct observation of spiropyran phosphorescence in imidazolium ionic liquids

Abstract Emission spectroscopy is used to investigate the photochromism of a spiropyran ester in imidazolium ionic liquids. While the spiropyran exhibits positive photochromism, the ring-opening reaction is slowed such that both fluorescence from the merocyanine form and phosphorescence from the spiro form are observed. These results illustrate the first example of spiropyran phosphorescence in ionic liquids and suggest that this system could be used to design a robust two-color emitting molecular device that depends on the state of the photochrome, where the state can be modulated by internal (the medium) and external (irradiation wavelength) factors.
Bullying, psychosocial adjustment, and academic performance in elementary school.

Background Over the past decade, concerns about bullying and its role in school violence, depression, and health concerns have grown. However, no large studies in the United States have examined the prevalence of bullying during elementary school or its association with objective measures of school attendance and achievement. Objective To determine the prevalence of bullying during elementary school and its association with school attendance, academic achievement, disciplinary actions, and self-reported feelings of sadness, safety, and belonging. Design Cross-sectional study using 2001-2002 school data. Setting Urban, West Coast public school district. Participants Three thousand five hundred thirty (91.4%) third, fourth, and fifth grade students. Main Outcome Measure Self-reported involvement in bullying. Results Twenty-two percent of children surveyed were involved in bullying either as a victim, bully, or both. Victims and bully-victims were more likely to have low achievement than bystanders (odds ratios [ORs], 0.8 [95% confidence interval (CI), 0.7-0.9] and 0.8 [95% CI, 0.6-1.0], respectively). All 3 bullying-involved groups were significantly more likely than bystanders to feel unsafe at school (victims, OR, 2.1 [95% CI, 1.1-4.2]; bullies, OR, 2.5 [95% CI, 1.5-4.1]; bully-victims, OR, 5.0 [95% CI, 1.9-13.6]). Victims and bully-victims were more likely to report feeling that they don’t belong at school (ORs, 4.1 [95% CI, 2.6-6.5] and 3.1 [95% CI, 1.3-7.2], respectively). Bullies and victims were more likely than bystanders to feel sad most days (ORs 1.5 [95% CI, 1.2-1.9] and 1.8 [95% CI, 1.2-2.8], respectively). Bullies and bully-victims were more likely to be male (ORs, 1.5 [95% CI, 1.2-1.9] and 3.0 [95% CI, 1.3-7.0], respectively). Conclusions The prevalence of frequent bullying among elementary school children is substantial. Associations between bullying involvement and school problems indicate this is a serious issue for elementary schools. The research presented herein demonstrates the need for evidence-based antibullying curricula in the elementary grades.
Neonatal-mouse infectivity of intact Cryptosporidium parvum oocysts isolated after optimized in vitro excystation

We reexamined the finding of Neumann et al. (10) that intact Cryptosporidium parvum oocysts obtained after in vitro excystation were infectious for neonatal CD-1 mice. We used both established excystation protocols and our own protocol that maximized excystation (2). Although intact oocysts isolated after any of three protocols were infectious for neonatal CD-1 mice, the infectivity of intact oocysts isolated with our optimized excystation protocol was significantly lower than the infectivity of intact oocysts isolated after established protocols or from fresh oocysts. Excystation should not be considered a valid measure of C. parvum viability, given that it is biologically implausible for oocysts to be nonviable and yet infectious.
Introduction to special issue of Physiology and Behavior: a tribute to Bart Hoebel.

► This special issue of is dedicated to Dr. Bart Hoebel. ► The articles included in it reflect the remarkable breadth of Bart's research projects. ► This Introduction summarizes each of the authors' contributions.
DYNAMIC PHENOMENA IN ORGANIC METAL (BEDT-TTF)3TA2F11

Abstract Dynamic electron spin resonance, ESR measurements suggest that this paramagnetic, layered organic metal behaves similarly to cuprate superconductors. There is a dynamic equilibrium between doublet, D and triplet, T* states near the transition temperature to superconductivity Tc= 10±3 K; antiferromagnetic, AF resonance is observed from room temperature to ≈ 150 K, in this temperature region the temperature dependence of the D Lorentzian ESR line widths obtains a first order rate constant for the disappearance of the state (k1 = 3.5 ×107 e−111/T/s) and T* ESR is not observed, it is detected only below 44 K when the lifetime of AF domains, τAF decreases below 10-10s; the onset of superconductivity is ascertained by the appearance of an energy loss at exactly H=0 near 10 K and by the magnetization oscillations observed versus H below Tc when the samples are cooled in a non-zero field H; the fourfold increase in the relaxation time τ1 for the half field T* ESR absorption near 10 ±3 K is interpreted us...
The chromo superfamily: new members, duplication of the chromo domain and possible role in delivering transcription regulators to chromatin

Using computer methods for detecting conserved amino acid sequence motifs, we show that the chromatin organization modifier (chromo) domain that has been previously identified in several proteins involved in transcription down-regulation is present in a much larger group of (putative) chromatin-binding proteins, some of which are positive rather than negative regulators of transcription. The most interesting new members of the chromo superfamily are Drosophila male-specific lethal (MSL-3) protein involved in the X chromosome gene dosage compensation in the males and human retinoblastoma-binding protein RBP-1. We show that the chromo domain is duplicated in several chromatin-binding proteins and use this observation to interpret recent results on chromatin binding obtained with chimeric chromo domain-containing proteins. We hypothesize that the chromo domain may be a vehicle that delivers both positive and negative transcription regulators to the sites of their action on chromatin.
Inference with path resolution and semantic graphs

A graphical representation of quantifier-free predicate calculus formulas in negation normal form and a new rule of inference that employs this representation are introduced. The new rule, path resolution, is an amalgamation of resolution and Prawitz analysis. The goal in the design of path resolution is to retain some of the advantages of both Prawitz analysis and resolution methods, and yet to avoid to some extent their disadvantages.Path resolution allows Prawitz analysis of an arbitrary subgraph of the graph representing a formula. If such a subgraph is not large enough to demonstrate a contradiction, a path resolvent of the subgraph may be generated with respect to the entire graph. This generalizes the notions of large inference present in hyperresolution, clash-resolution, NC-resolution, and UR-resolution. A class of subgraphs is described for which deletion of some of the links resolved upon preserves the spanning property.
S-Adenosylmethionine Levels in the Diagnosis of Pneumocystis carinii Pneumonia in Patients with HIV Infection

BACKGROUND: S-adenosylmethionine (AdoMet) is a key molecule involved in methylation reactions and polyamine synthesis. Pneumocystis carinii are unable to synthesize this molecule and have been shown to scavenge this metabolic intermediate from the plasma of rats during active infection. A prior study involving humans strongly suggested that low levels of plasma AdoMet are sensitive and specific indicators of acute infection. METHODS: From March 2004 through January 2006 we collected plasma AdoMet levels from patients with human immunodeficiency virus (HIV) infection and either confirmed Pneumocystis carinii pneumonia (PCP) confirmed pulmonary tuberculosis or confirmed bacterial pneumonia. We compared levels in patients with PCP with those in patients with other diseases and also monitored changes in levels during treatment of PCP. RESULTS: Initial AdoMet levels were significantly lower in patients with PCP and there was no overlap between the groups. Among patients with PCP levels of AdoMetincreased with successful treatment. CONCLUSIONS: Measurement of plasma AdoMet levels in patients with HIV infection who have pulmonary infections can identify those with PCP.
Asymmetrical protein kinase A activity establishes neutrophil cytoskeletal polarity and enables chemotaxis

Neutrophil chemotaxis requires precise spatial organization of the actin cytoskeleton and integrin activation to polarize the cell and enable migration. Protein kinase A (PKA) activity regulates integrin activation and actin cytoskeletal organization, suggesting that PKA is a key element in the mechanism regulating neutrophil chemotaxis. Our hypothesis is that asymmetrical PKA activity is critical for establishing neutrophil adhesive and cytoskeletal polarity required for migration during chemotaxis. To test this hypothesis, we first determined that global treatment with the PKA inhibitor KT5720 decreased formylated Met-Leu-Phe (fMLF)-induced migration. The ability of PKA inhibitors to reduce migration correlated with increased overall beta2 integrin cell-surface expression, affinity activation, and cellular adhesion. We next determined whether asymmetrical PKA activity was sufficient to induce migration. Exposure to gradient of the PKA inhibitors KT5720 or H-89 or a stearated, cell-permeant peptide (St-Ht31), which inhibits PKA binding to anchorage proteins, stimulated neutrophil migration in a chemotaxis chamber. Global treatment with KT5720 abolished the ability of fMLF to polarize the neutrophil actin cytoskeleton. In contrast to global treatment with KT5720, a point source of KT5720 was sufficient to polarize the actin cytoskeleton. The ability of KT5720 and St-Ht31 to stimulate migration was abolished by pretreatment with the phosphatidylinositol-3 kinase (PI-3K) inhibitors wortmannin and LY294002. These data suggest that asymmetrical PKA activity is necessary and sufficient for actin cytoskeletal polarization and migration during neutrophil chemotaxis. In addition, our data suggest PI-3K is an effector of PKA during chemotaxis.
Treatment of Hyperpigmented Photodamaged Skin

Photodamaged skin is one of the most common problems addressed by the dermatologist. It can be simplistically characterized by the visual changes of dyspigmentation, fine wrinkles, and tactile roughness [1, 2]. The hyperpigmentation aspect of photodamage is probably one of the most disconcerting to patients as healthy skin is perceived to be even-colored. The discoloration results from stimulation of the melanocytes by UV-A radiation that causes excess pigment production. While the pigment produced by the skin is photoprotective, the inability of the melanocytes to evenly generate melanin causes localized pigmented spots, known as lentigenes, and a reticulated dyspigmentation, known as melasma. This chapter will focus on the topical treatments available for hyperpigmented photodamaged skin.