cssi/SciSciGPT-SciSciNet huggingface dataset:
Probing Cytochrome c Folding Transitions upon Phototriggered Environmental Perturbations Using Time-Resolved X-ray Scattering.

Direct tracking of protein structural dynamics during folding–unfolding processes is important for understanding the roles of hierarchic structural factors in the formation of functional proteins. Using cytochrome c (cyt c) as a platform, we investigated its structural dynamics during folding processes triggered by local environmental changes (i.e., pH or heme iron center oxidation/spin/ligation states) with time-resolved X-ray solution scattering measurements. Starting from partially unfolded cyt c, a sudden pH drop initiated by light excitation of a photoacid caused a structural contraction in microseconds, followed by active site restructuring and unfolding in milliseconds. In contrast, the reduction of iron in the heme via photoinduced electron transfer did not affect conformational stability at short timescales (<1 ms), despite active site coordination geometry changes. These results demonstrate how different environmental perturbations can change the nature of interaction between the active site and...
Conclusions The Future: Relations between the EU and MERCOSUR

Rightly or wrongly, the countries of MERCOSUR have seen the European Union (EU) as their example or model. In turn, the EU has, from its earliest days, encouraged the integration process among these countries. In fact, probably unknown to many experts, the EU, using a financial grant from the European Parliament (which has been recently renewed), has, for some years now, been training MERCOSUR administrators.
Biomodulation: An integrated approach to access and manipulate biological information

The concept of altering host/tumor responsiveness (surveillance) as a specific tool in the management of neoplastic disease has been the subject of both basic science and clinical studies for many years. One of the first practical applications of this approach was described by Von Leyden and Blumenthal in 1902. In this study autologous tumor cells were injected into a patient as part of an intervention protocol. In 1908 Paul Ehrlich predicted the existence of a host immuno-dependent protective mechanism. Burnet formalized this concept in 1970. The first element of Burnet’s proposal is the existence of unstable cellular clones with neoplastic potential. These clones are a normal part of mammalian existence and are important in the maintenance of surveillance mechanisms. The second element is the proposal that the host immune system is designed to hold these clones in stasis. These two inter-related elements laid the conceptual groundwork for the theory that the “induction” of the immune system could be beneficial in cases where the normal stasis mechanisms have failed and a neoplasm has expressed. Thus, from its inception these two elements were given equal weight. The first is termed by us immuno-regulatory, with the implication of recognition and regulation [both proliferative and differentiative] components. The second is termed immuno-defensive, with its implication of effector functions involved in lytic actions. In recent years these separate concepts have been apparently collapsed into the search for enhanced specificity in immune-defensive functions. Thus the modern day applications of Burnet’s concept have evolved and the field of Biological Response Modifiers [BRMs] was created.
Perspective from grad school: Unconsciously done

Implicit, or unconscious, bias is getting a lot of press. As scientists, we often consider ourselves as experts at placing our biases aside and simply being objective. However, in the world of publishing—you know, the way we gauge our success and value—we as the science, technology, engineering, and mathematics (STEM) community have done very little to prevent bias from affecting the outcome of scientific work. The review process is single blind: Reviewers know the names of the authors of a given submission and the institutions they represent. This doesn’t sound too bad, except the whole point about implicit biases is that we don’t realize they’re affecting our judgments of others. This means that bias can exclude authors according to their gender, perceived ethnicity or nationality, or institution without reviewers even realizing it. My first paper was published recently. After nearly a year of submitting, revising, and submitting to different journals,
Risk of Hematoma From Aspirin or Clopidogrel Owing to Lumbar Puncture.

Neurologists are worried about bleeding and complications from lumbar punctures in patients who use antiplatelet agents, such as aspirin and clopidogrel. We evaluated the bleeding risks of performing lumbar punctures in patients who are using or have recently used antiplatelet agents by retrospective review of lumbar punctures performed at the Johns Hopkins Hospital between 2004 and 2018 in patients who were actively using or recently used aspirin or clopidogrel, or both. Patients were stratified into time groups based on when the lumbar puncture was done relative to the time the antiplatelet drug was discontinued: 4 weeks. We recorded red blood cell counts for the earliest and latest spinal fluid collections to determine the risk of traumatic bleeding; we also noted any complications. Antiplatelet medication use within 1 week of lumbar puncture was associated with a 3% incidence of bloody tap and 4% incidence of traumatic tap that cleared. In the group of patients who waited for a lumbar puncture at least 4 weeks after discontinuation of antiplatelet drug, there was a 5% incidence of bloody or traumatic tap. There was no difference in rates of bleeding between aspirin versus aspirin plus clopidogrel. The rate of hematoma complications was highest in the group of patients on aspirin at the time of the procedure (0.7%). Aspirin or clopidogrel, or both, did not meaningfully increase hemorrhagic complications in patients undergoing lumbar punctures, regardless of when the antiplatelet drug was discontinued relative to the time of the procedure.
Can we predict histological outcome of distinctive cohorts of patients with glandular cell abnormalities on ThinPrep Papanicolaou testing based on human papillomavirus status, age, and associated squamous abnormalities?

BACKGROUND The cytology diagnosis of glandular cell abnormalities (GCAs) is diagnostically challenging, causing inadequate reproducibility. Histological outcome of GCA on cytology varies from benign to malignant diseases. The goal of this study is to evaluate histological outcome and identify distinctive cohorts of patients with GCA based on human papillomavirus (HPV) status, age, and associated squamous abnormality to stratify the patient into high risk for squamous/glandular lesions. METHODS From 2012 to 2017, out of 162 088 ThinPrep Papanicolaou tests performed, 998 (0.61%) were reported as GCAs. Histologic follow-up was available in 638 cases and 429 had concurrent HPV results. RESULTS The overall rate of high-risk human papillomavirus (hrHPV)-positivity (hrHPV+) was 33.6% (144/429 cases). Among the hrHPV+ cases, 18.1% had cervical intraepithelial neoplasia 2/3 (CIN2/3), 3.5% squamous cell carcinoma (SCC), 3.5% cervical adenocarcinoma in situ (AIS)/adenocarcinoma (ADC), and 2.8% endometrial carcinoma. Among hrHPV- cases, 1.4% had CIN2/3, 1.1% AIS/ADC, and 17.5% endometrial carcinoma. The high-grade cervical lesions (CIN2/3/AIS/ADC) were significantly higher in women with hrHPV+ and associated squamous abnormalities compared to hrHPV- and no squamous abnormality in all age groups except patients >65 years. Endometrial carcinoma was most commonly present in women >65 years especially with HPV- and no associated squamous abnormalities. CONCLUSIONS HPV testing is useful for predicting the risk of high-grade cervical neoplasia in women with GCA especially with associated squamous abnormalities on cytology. The endometrial carcinoma is more frequent in hrHPV- older women. The combination of cytology with knowledge of associated squamous abnormality, hrHPV status, and age can significantly aid in stratifying the patient into high risk for glandular/squamous lesions which facilitates appropriate management of these patients.
Three-Dimensional Histologic, Immunohistochemical, and Multiplex Immunofluorescence Analyses of Dynamic Vessel Co-Option of Spread Through Air Spaces in Lung Adenocarcinoma

Abstract Introduction Spread through air spaces (STAS) is a method of invasion in lung adenocarcinoma and is associated with tumor recurrence and poor survival. The spatial orientation of STAS cells in the lung alveolar parenchyma is not known. The aim of this study was to use high-resolution and high-quality three-dimensional (3D) reconstruction of images from immunohistochemical (IHC) and multiplex immunofluorescence (IF) experiments to understand the spatial architecture of tumor cell clusters by STAS in the lung parenchyma. Methods Four lung adenocarcinomas, three micropapillary-predominant and one solid predominant adenocarcinoma subtypes, were investigated. A 3D reconstruction image was created from formalin-fixed, paraffin-embedded blocks. A total of 350 serial sections were obtained and subjected to hematoxylin and eosin (100 slides), IHC (200 slides), and multiplex IF staining (50 slides) with the following antibodies: cluster of differentiation 31, collagen type IV, thyroid transcription factor-1, and E-cadherin. Whole slide images were reconstructed into 3D images for evaluation. Results Serial 3D image analysis by hematoxylin and eosin, IHC, and IF staining revealed that the micropapillary clusters and solid nests of STAS are focally attached to the alveolar walls, away from the main tumor. Conclusions Our 3D reconstructions found that STAS tumor cells can attach to the alveolar walls rather than appearing free floating, as seen on the two-dimensional sections. This suggests that the tumor cells detach from the main tumor, migrate through air spaces, and reattach to the alveolar walls through vessel co-option, allowing them to survive and grow. This may explain the higher recurrence rate and worse survival of patients with STAS-positive tumors who undergo limited resection than those who undergo lobectomy.
Content learning opportunities, computer-based instruction, and students’ mathematics and science achievement

Employing data from TIMSS 2011, this study investigated the association among middle school students’ in-class computer use, content learning opportunities, and mathematics and science achievement....
The Fyn-Stat5 cascade is required for Fcγ receptor-mediated mast cell function.

Mast cells, well established effectors in allergic disease, can be activated by numerous stimuli. We previously found that the Fyn-Stat5B pathway is critical for FceRI-stimulated mast cell function. Because IgG receptors employ similar signaling pathways, we investigated Fyn-Stat5B function downstream of FcγR. We report that FcγR elicits Fyn-dependent Stat5B tyrosine phosphorylation in mast cells. As we previously found for Fyn kinase, Stat5B is indispensable for IgG-mediated mast cell cytokine expression and secretion. However, Stat5B KO macrophages responded normally to FcγR signaling, indicating a lineage-restricted role for Stat5B. This was consistent in vivo, since passive FcγR activation induced anaphylaxis in a macrophage-dominated response even when Stat5B was deleted. We further investigated this lineage restriction using the K/BxN model of inflammatory arthritis. This model exhibits a rapid and transient mast cell-dependent joint inflammation followed days later by a macrophage- and neutrophil-dependent response. Consistent with our hypothesis, Fyn or Stat5B deficiency did not protect mice from late joint swelling, but greatly reduced the early mast cell-dependent response. This was associated with decreased joint and plasma histamine. We conclude that Fyn-Stat5B is a linage-restricted pathway critical for IgG-mediated mast cell responses.
Spinal Cord Injury in Myelomeningocele: Prospects for Therapy

Myelomeningocele (MMC) is the most common congenital defect of the central nervous system and results in devastating and lifelong disability. In MMC, the initial failure of neural tube closure early in gestation is followed by a progressive prenatal injury to the exposed spinal cord, which contributes to the deterioration of neurological function in fetuses. Prenatal strategies to control the spinal cord injury offer an appealing therapeutic approach to improve neurological function, although the definitive pathophysiological mechanisms of injury remain to be fully elucidated. A better understanding of these mechanisms at the cellular and molecular level is of paramount importance for the development of targeted prenatal MMC therapies to minimize or eliminate the effects of the injury and improve neurological function. In this review article, we discuss the pathological development of MMC with a focus on in utero injury to the exposed spinal cord. We emphasize the need for a better understanding of the causative factors in MMC spinal cord injury, pathophysiological alterations associated with the injury, and cellular and molecular mechanisms by which these alterations are induced.
The Power of Signaling and its Intrinsic Connection to the Price of Anarchy.

A basic lesson from game theory is that strategic behavior often renders the equilibrium outcome inefficient. The recent literature of information design -- a.k.a. signaling or persuasion -- looks to improve equilibria by providing carefully-tuned information to players in order to influence their actions. Most previous studies have focused on the question of designing optimal signaling schemes. This work departs from previous research by considering a descriptive question and looks to quantitatively characterize the power of signaling (PoS), i.e., how much a signaling designer can improve her objective of the equilibrium outcome. We consider four signaling schemes with increasing power: full information, optimal public signaling, optimal private signaling and optimal ex-ante private signaling. Our main result is a clean and tight characterization of the additional power each signaling scheme has over its immediate predecessor above in the broad classes of cost-minimization and payoff-maximization games where: (1) all players minimize non-negative cost functions or maximize non-negative payoff functions; (2) the signaling designer (naturally) optimizes the sum of players' utilities. We prove that the additional power of signaling -- defined as the worst-case ratio between the equilibrium objectives of two consecutive signaling schemes in the above list -- is bounded precisely by the well-studied notion of the price of anarchy of the corresponding games. Moreover, we show that all these bounds are tight.
Implementation Science and Quality Improvement

Quality improvement (QI), which seeks to achieve measurable changes in processes of care and outcomes, and implementation science, which studies the incorporation of evidence into practice, use specific tools, methods, frameworks, and study designs to achieve their goals within a local setting. This chapter: (1) introduces theories, frameworks, and models used in QI and implementation research; (2) describes QI and implementation strategies; (3) reviews the strengths and limitations of different research designs; (4) describes the role of context in QI and implementation; (5) discusses issues in measurement; (6) discusses opportunities for publication and funding, and (7) provides a list of resources for additional information and training. Although QI and implementation efforts are not always performed under the auspices of research, there is significant opportunity within these fields for scientific inquiry and for advancing the science of patient safety to improve the quality of care.
CVD Processes and Equipment

This chapter discusses the chemical vapor deposition (CVD) processes. The factors controlling a CVD process are the thermodynamic, mass transport, and kinetic considerations, and also the chemistry of the reaction, the processing parameters of temperature, pressure, and chemical activity. The various CVD processes comprise the thermal CVD, laser and photo CVD, and plasma CVD. The difference between these processes is the method of applying the energy required for the CVD reaction to take place. The heating methods used in thermal CVD include various types of reactors such as the hot-wall reactors, cold-wall reactors, atmospheric and low-pressure reactors, and ultra-high vacuum reactors. The chapter discusses two methods based on photon activation, which are the laser and photo CVD. Laser CVD occurs as a result of the thermal energy from the laser coming in contact with and heating an absorbing substrate. The wavelength of the laser is such that little or no energy is absorbed by the gas molecules, while in photo CVD the chemical reaction is activated by the action of photons of the ultraviolet (UV) radiation, which have sufficient energy to break the chemical bonds in the reactant molecules.
Increasing Learning: Classroom Assessment Techniques in the Online Classroom.

Five full-time online mathematics instructors participated in a study to test the impact of using discussion forums as a space for formative assessments. Mean student posting activity and student quiz scores for sections in which the instructors used formative assessments were compared with previous sections in which formative assessments were not used. The research indicates that online discussion forums can be an important part of the learning process. Specifically, a certain type of formative assessment, known as classroom assessment techniques (Cross and Angelo 1988), may actually elicit more discussion forum conversation from students and positively impact student quiz scores.
Conformational analysis—CXVII

Abstract The conformation of methyl ethyl disulfide was investigated by molecular mechanics calculations using a recently developed force field for sulfur-containing alkanes. The results indicate that in the gas phase the molecule exists predominantly in two conformations, both with the CSSC dihedral angle gauche (84°), and the SSCC dihedral angle either gauche (72°) or trans (179°), and the methyl protons staggered. Ab initio molecular orbital calculations using an STO-3G basis set were employed to corroborate that these two conformations are of roughly equal stability, and that the next most stable conformation (by 0.6 kcal/mole) has the SSCC dihedral angle gauche (295°) with the terminal methyls proximal. In contrast to earlier CNDO/2 (spd) predictions, the SSCC cis conformer is the least stable, and no sizable attractive S⋯HC nonbonded interactions are discerned. Reasons for this are traced to a failure of the CNDO/2 method, which is especially serious when d orbitals are included in the basis set (spd) and the rigid rotor approximation is used. The present results are found to be consistent with recent electron diffraction, IR, Raman spectroscopic and X-ray diffraction data. The conformation of diethyl disulfide was also investigated by molecular mechanics calculations, and again gauche and trans SSCC arrangements are predicted to be preferred.
Nutritional evaluation of gynecologic cancer patients during initial diagnosis of their disease

Ninety-seven gynecologic cancer patients received a thorough nutritional assessment during the initial evaluation of their disease. Patients with Stages III and IV ovarian cancer were shown to have severe protein-calorie malnutrition (p less than 0.01) unrelated to any gastrointestinal obstruction or laparotomies. Patients with other types of gynecologic cancers at all stages demonstrated nearly normal nutritional assessment parameters, with the exception of recent weight loss. Nutritional assessment and active nutritional intervention therapy are suggested especially for patients with advanced ovarian cancer.
Tertiary or Mesozoic komatiites from Gorgona Island, Colombia: Field relations and geochemistry

An exceptional occurrence of ultramafic lavas within the volcanic member of the Mesozoic (or younger) Gorgona Igneous Complex represents the first known komatiites of post-Precambrian age. Gorgona komatiites are virtually unaltered and display typical spinifex textures, with 7–10 cm long plates of olivine (Fo 88 to 91) surrounded by acicular aluminous augite, subordinate plagioclase (An 56 to 78), basaltic glass, and two spinel phases. The MgO contents of the komatiites range from 15 to 22 wt.%. Sr and Nd isotopic compositions are indicative of depletion of incompatible elements in the mantle source region, as is the case for “normal” mid-ocean ridge basalts. The komatiites are low in total REE abundances and extremely depleted in LREE. They represent primary melts generated by high degree of partial melting of the mantle. Eruption temperatures are estimated at 1,450° to 1,500° C.
Comparing Judicial Selection Systems in Common Law Democracies: Creating a Framework for Comparison

How does our current system of selecting judges compare to judicial selection systems in other countries? This research provides a framework for categorizing and analyzing the systems of judicial selection in countries similar to the United States. This framework accommodates and organizes a number of different institutional actors and arrangements. Additionally, this paper addresses a variety of other relevant characteristics of judicial selection systems, including professional qualifications and mandatory retirement ages. In all, countries seeking to fill judicial positions similar to that of a US Supreme Court justice have decided to do this in many different ways. This paper identifies the key players and variables common to these systems, providing researchers with a common vocabulary that allows for equivalence of measures among disparate systems.
Is there a need for an alternative in the era of novel anticoagulants

With the development of the new direct oral anticoagulants, many of the unmet needs of the vitamin K antagonists were fulfilled, such as the absence of dietary interactions, few drug interactions, predictable effects and no need for monitoring. However, growing experience with the direct oral anticoagulants indicates there is still room for improvement. Developing antithrombotic agents that optimize their antithrombotic effect while producing little or no risk of bleeding is a long sought after goal. This and other enhanced attributes of candidate drugs are on the horizon.
Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: V. Aminoglycosides

Summary Intravenous (IV) anti-pseudomonal aminoglycosides (i.e., amikacin and tobramycin) have been shown to be tolerable and effective in the treatment of acute pulmonary exacerbations (APEs) in both pediatric and adult patients with cystic fibrosis. The aim of this review is to provide an evidence-based summary of pharmacokinetic/pharmacodynamic, tolerability, and efficacy studies utilizing IV amikacin, gentamicin, and tobramycin in the treatment of APE and to highlight areas where further investigation is needed. The Cystic Fibrosis Foundation Pulmonary Guidelines recommend that once-daily administration of aminoglycosides is preferred over three times per day in the treatment of an APE. The literature supports dosing ranges for amikacin and tobramycin of 30–35 and 7–15 mg/kg/day, respectively, given once daily, with subsequent doses determined by therapeutic drug concentration monitoring. The literature does not support the routine use of gentamicin in the treatment of APE due to a lack of studies showing efficacy and evidence indicating an increased risk of nephrotoxicity. Further studies are needed to determine the optimal dosing strategy of amikacin in the treatment of an APE, and to further identify risk factors and determinants that influence the development of P. aeruginosa resistance with once-daily administration of tobramycin. Pediatr Pulmonol. 2013; 48:1047–1061. © 2013 Wiley Periodicals, Inc.
Numerical Simulation of Unsteady Blood Flow through Capillary Networks

A numerical method is implemented for computing unsteady blood flow through a branching capillary network. The evolution of the discharge hematocrit along each capillary segment is computed by integrating in time a one-dimensional convection equation using a finite-difference method. The convection velocity is determined by the local and instantaneous effective capillary blood viscosity, while the tube to discharge hematocrit ratio is deduced from available correlations. Boundary conditions for the discharge hematocrit at divergent bifurcations arise from the partitioning law proposed by Klitzman and Johnson involving a dimensionless exponent, q≥1. When q=1, the cells are partitioned in proportion to the flow rate; as q tends to infinity, the cells are channeled into the branch with the highest flow rate. Simulations are performed for a tree-like, perfectly symmetric or randomly perturbed capillary network with m generations. When the tree involves more than a few generations, a supercritical Hopf bifurcation occurs at a critical value of q, yielding spontaneous self-sustained oscillations in the absence of external forcing. A phase diagram in the m–q plane is presented to establish conditions for unsteady flow, and the effect of various geometrical and physical parameters is examined. For a given network tree order, m, oscillations can be induced for a sufficiently high value of q by increasing the apparent intrinsic viscosity, decreasing the ratio of the vessel diameter from one generation to the next, or by decreasing the diameter of the terminal vessels. With other parameters fixed, oscillations are inhibited by increasing m. The results of the continuum model are in excellent agreement with the predictions of a discrete model where the motion of individual cells is followed from inlet to outlet.
Regulation of arachidonate-induced platelet aggregation by the lipoxygenase product, 12-hydroperoxyeicosatetraenoic acid

The lipoxygenase product, 12-hydroperoxyeicosatetraenoic acid (12-HPETE) was biosynthesized, purified and incubated with washed human platelet. It inhibited arachidonic acid, azo-prostaglandin H2 or U-46619-induced aggregation and secretion in a concentration-dependent fashion (IC50 = 2-3 microM). Collagen-induced aggregation and secretion were also inhibited (IC50 = 6 microM). 12-HPETE inhibited malondialdehyde and thromboxane B2 formation in platelets stimulated with arachidonic acid or thrombin. While thrombin-induced aggregation was unaffected by 50 microM 12-HPETE, thrombin-induced secretion was inhibited. Inhibiton of secretion by 12-HPETE was observed in platelets from untreated as well as aspirin-treated donors, indicating that 12-HPETE inhibits secretion independently of its ability to inhibit prostaglandin formation. Aggregation of washed human platelets by arachidonic acid yielded a bell-shaped concentration-response curve. Diminished aggregation at higher concentrations was associated with an increase in the ratio of lipoxygenase products to thromboxane B2. The data suggest that 12-HPETE formation may regulate platelet aggregation and secretion and that its primary effect, at low concentrations, is inhibition of endoperoxide-induced responses. At higher concentrations 12-HPETE also inhibits arachidonic acid metabolism. Thus, the combined inhibitory effects on endoperoxide-induced aggregation and thromboxane formation would explain the diminished aggregation observed in response to high concentrations of arachidonic acid.
Characterization of Human Expired Air: A Promising Investigative and Diagnostic Technique

Expired air samples have been collected from a carefully selected population of normal healthy human subjects under controlled experimental conditions. The samples were concentrated and analyzed by quantitative, reproducible and sensitive techniques which resulted in well-defined composite compositional and occurrence profiles of the organic constituents present in normal expired air. The composite profiles provide valuable baseline information upon which suitable correlation studies may be advanced toward the use of human expired air for diagnostic purposes.
Effect of Proteolytic Bacteria in the Natural Fermentation of Corn to Increase its Nutritive Value

There was no significant difference in % relative nutritive value, lysine or tryptophan levels between natural lactic fermentations of Costa Rican corn meal fermented with tap water of pH 7.2 and 5.3 However, the fermented values were all significantly (P<0.05) higher than nonfermented values. Most of the increase in % relative nutritive value occurred in the first 48 hr. Free essential amino acids increased and the amino acid balance changed during typical fermentations. Proteolytic bacteria decreased after 3 days of the fermentation and declined to a few cells per ml by the 4th day. Proteolysis decreased by the second day of natural lactic fermentation.
Angry Thoughts and Daily Emotion Logs: Validity of the Angry Cognitions Scale

The Angry Cognitions Scale (ACS; Martin and Dahlen in J Ration Emot Cogn Behav Therapy 25:155–173, 2007) was designed to measure six cognitive processes related to anger: misattributing causation, overgeneralizing, catastrophizing, demandingness, inflammatory labeling, and adaptive processes. Preliminary evidence on the reliability of the ACS has been positive, demonstrating that the ACS is correlated with the experience and expression of anger, anger consequences, hostile thoughts, and responses to provocation (Martin and Dahlen in J Ration Emot Cogn Behav Therapy 25:155–173, 2007; J Ration Emot Cogn Behav Therapy, 29:65–76, 2011). This previous research, however, has suffered from limitations associated with demand characteristics and the reliance on retrospective data. The current study sought to address these limitations by using daily emotion logs. Results showed that the ACS predicted the daily experience of anger and anger related consequences, contributing to the literature on the ACS as a valuable measure of anger-related cognitions.
Treat‐to‐target trials: uses, interpretation and review of concepts

Treat-to-target trial designs compare investigational insulins with a standard insulin. Treat-to-target trials force-titrate insulin dosages to achieve a prespecified treatment goal. With comparable glycaemic control, comparisons of safety endpoints such as hypoglycaemia can be made to establish the risk-benefit profile of the new insulin. Glargine versus NPH showed comparable A1C reductions; however, A1C <7% without associated nocturnal hypoglycaemia was reached in more patients on glargine and overall hypoglycaemia was lower. Detemir versus glargine showed non-inferiority between the groups; however, with less weight gain and more injection site reactions with detemir. Detemir/aspart versus glargine/aspart showed non-inferiority between the treatments, however, with less weight gain in the detemir group but comparable risk of hypoglycaemia. Degludec in combination with aspart versus glargine/aspart showed comparable A1C reductions. However, degludec-treated patients had less overall hypoglycaemia and less nocturnal hypoglycaemia. Because insulin titrations are guided by goal attainment with each treatment, treat-to-target trials enable clinicians to determine differences in non-glycaemic treatment effects, such as rates of hypoglycaemia and weight gain, at the same level of glycaemic control.
Toxicity and the smoke problem

Abstract The production and toxicological effects of selected, major fire gases are reviewed. These gases include carbon monoxide, hydrogen cyanide, carbon dioxide, irritants and oxygen depletion, among others. The measurement of the toxicity of smoke is discussed relative to the parameters which need to be measured, in addition to some selected, existing test methods. These test methods are reviewed relative to their relevance to “real” fires, utility and appropriateness as standard tests.
New genetic and physicochemical data on structure of dinoflagellate chromosomes.

THE majority of free-living dinoflagellates differ from other eukaryotes in possessing high chromosome numbers1, large amounts of DNA2 per cell, uniform chromosome size and in their apparent lack of histone proteins3. One of their most interesting properties which they share along with the euglenids4 is the condensed state of their chromosomes throughout the cell cycle5.
The Role and Influence of American Medical Missionaries in the Modern Hygiene Movement in Canton, 1835–1935

The American medical missionary movement in the 19th and 20th centuries in South China was one of the important movements to influence the country. This movement had an impact on hygiene modernization in China generally and in Canton particularly. The American doctors in Canton not only criticized the Chinese for lacking modern concepts of bodily cleanliness and fitness, but also participated in campaigns against contagious disease. Both American doctors and the Cantonese government took part in the hygiene and health management of Cantonese residents. This article focuses on how the American medical missionaries encouraged the Cantonese to change their unhygienic habits and to improve the unsanitary environment of Canton, conducted vaccination work, fought the plague, treated opium addicts and lepers, and promoted rural hygiene and health work. This article also studies how the Cantonese elites, encouraged by Americans and impressed by Western preventive medicines and measures to some degree, advocated s...
The increased financial burden of further proposed orthopaedic resident work-hour reductions.

Background: Increased funding for graduate medical education was not provided during implementation of the eighty-hour work week. Many teaching hospitals responded to decreased work hours by hiring physician extenders to maintain continuity of care. Recent proposals have included a further decrease in work hours to a total of fifty-six hours. The goal of this study was to determine the direct cost related to a further reduction in orthopaedic-resident work hours. Methods: A survey was delivered to 152 residency programs to determine the number of full-time equivalent (FTE) physician extenders hired after implementation of the eighty-hour work-week restriction. Thirty-six programs responded (twenty-nine university-based programs and seven community-based programs), encompassing 1021 residents. Previous published data were used to determine the change in resident work hours with implementation of the eighty-hour regulation. A ratio between change in full-time equivalent staff per resident and number of reduced hours was used to determine the cost of the proposed further decrease. Results: After implementation of the eighty-hour work week, the average reduction among orthopaedic residents was approximately five work hours per week. One hundred and forty-three physician extenders (equal to 142 full-time equivalent units) were hired to meet compliance at a frequency-weighted average cost of $96,000 per full-time equivalent unit. A further reduction to fifty-six hours would increase the cost by $64,000 per resident. With approximately 3200 orthopaedic residents nationwide, sensitivity analyses (based on models of eighty and seventy-three-hour work weeks) demonstrate that the increased cost would be between $147 million and $208 million per fiscal year. For each hourly decrease in weekly work hours, the cost is $8 million to $12 million over the course of a fiscal year. Conclusions: Mandated reductions in resident work hours are a costly proposition, without a clear decrease in adverse events. The federal government should consider these data prior to initiating unfunded work-hour mandates, as further reductions in resident work hours may make resident education financially unsustainable.
Effects of alcohol consumption on the prevention and alleviation of stress-reactions

Abstract Alcohol's Stress-Response-Dampening (SRD) effect has been the subject of much research, but little has been done to examine the effects of drinking alcohol after experiencing a stressor (Stress-Response-Recovery: SRR). In this study, 65 male and 65 female moderate or heavy drinking undergraduates were randomly assigned (with equal numbers of each sex per group) to 1 of 13 groups. Six experimental conditions were used to compare alcohol's SRD and SRR effects with two doses (moderate: .75 ml/kg; low: .33 ml/kg) and a placebo, and seven control conditions were used to measure the effects of the stressor (uncontrollable aversive noise) and the alcohol doses alone on the dependent measures. The major dependent variable was escape learning in a human shuttle box. In the SRD conditions, subjects who drank a moderate dose of alcohol learned to escape faster than those drinking the low dose or placebo. However, in the SRR conditions, subjects in the placebo group did not show escape learning deficits, in contrast to the impaired performance of subjects in the two alcohol groups. These results suggest a complex alcohol-stress relationship in which timing, dose, and expectations about alcohol lead to differential SRD and SRR effects.
Amino-acids, Aliphatic and Aromatic Hydrocarbons in the Murchison Meteorite

Type III carbonaceous chondrite Murchison meteorite, obtaining amino acids, aliphatic and aromatic hydrocarbons from specimen
Hydrology in a California oak woodland watershed: a 17-year study

The western foothills of the Sierra-Nevada are some of the most rapidly developing lands in California. Use of these lands includes vineyards, retirement and family home construction, livestock grazing, and fuelwood harvesting. These many uses require varying levels of woodland conversion and oak tree removal that alters the nutrient cycling, wildlife habitat and hydrology of these watersheds. There is little long-term hydrologic data to help determine the impact of these land use changes on water yield or quality. To fill this gap, precipitation and stream flow data were collected for 17 years in a 103 ha California oak woodland watershed, from which oaks were removed from 14% of the land area. These data were combined with measured potential evapotranspiration (PET) to develop a simple water balance and to investigate changes in water yield from oak removal. Hydrologic data included continuous stage height records from a three-foot Parshall flume and a one-foot 908 V-notch weir. Rainfall measurements were made using a tipping bucket rain gage. Average annual rainfall, runoff, and estimated evapotranspiration (ET) for the 17 years were 708, 344, and 364 mm, respectively. In this Mediterranean climate, ET is less dependent upon rainfall than is runoff because the majority of precipitation coincides with the period of lowest PET. Mean annual baseflow depth was 24 mm ranging between 15 and 40 mm. Depth of baseflow was more strongly associated with the annual rainfall than with rainfall from previous years, indicating that changes in soil moisture storage approaches zero on an annual time-scale. Effective depth for watershed soils was calculated to be 217 mm. Potential soil water storage between bedrock and the top of the clay-rich subsoil (Bt Horizon) was 52 mm. This quantity accounts for summer ET and stream baseflow. A weakly significant difference between the pre- and post-harvest mean monthly effective rainfall was observed, indicating that oak removal, from 1984 to 1986, had little influence on watershed hydrology. Peak monthly effective rainfall corresponded to peak monthly runoff. The threshold of response to significantly increase water yield from oak harvesting is greater than 14% of a watershed area for the Sierra-Nevada foothills oak woodlands. q 2000 Elsevier Science B.V. All rights reserved.
Band structure, density waves and symmetries of aperiodic crystals

There are three types of invariants in crystals. The first two, corresponding to electronic degeneracies, are well known, but the third is novel, realized in incommensurate crystals of non-minimal rank. Since the first two invariants have consequences in band structure, it is natural to look there for the third type as well. Rather than developing an atomic or tiling model with the third type of symmetry, we introduce a tight-binding approach based on a density-wave pattern, which is easy to generate from the Rokhsar–Wright–Mermin phase functions.
Ventral medullary neuronal responses to peripheral chemoreceptor stimulation

Abstract Recent findings suggest that carotid chemoreceptor input into the ventral medullary surface intermediate area during hypoxia is inhibitory (Gozal et al. , (1994) Neurosci. Lett. 178, 73–76. However, systemic hypoxia is a complex stimulus, and effects of carotid chemoreceptor stimulation per se on intermediate ventral medullary surface neuronal activity are difficult to isolate. Therefore, we studied neural activation of the intermediate ventral medullary surface during peripheral chemoreceptor stimulation by intravenous sodium cyanide using optical procedures in seven pentobarbital-anesthetized cats. Control recordings were also acquired in the suprasylvian cortex of three cats. Images of reflected 660 nm light were collected at 1/s with a charge-coupled device camera, triggered by the cardiac R wave, after 0.0, 0.5, 2, 5, 10, 20 and 40 μg/kg i.v. sodium cyanide administration before and following carotid sinus denervation. Sodium cyanide doses >5 μg/kg significantly increased ventilation, an effect which was eliminated following carotid sinus denervation. A pronounced, dose-dependent activity decrease within the intermediate ventral medullary surface occurred within seconds of sodium cyanide administration, with subsequent return to baseline. Carotid sinus denervation eliminated rapid-onset neural responses to all sodium cyanide doses. However, at the 40 μg/kg dose, a smaller, slower onset (25 s), activity decrease occurred both pre- and postdenervation. In the neocortex, the sodium cyanide-induced fast responses were absent. Intravenous cyanide, acting via a carotid sinus nerve pathway, results in a dose-dependent decrease in neural activity within the intermediate ventral medullary surface of cats. High-dose sodium cyanide also appears to decrease intermediate ventral medullary surface neural activity directly.
Evidence for resonant tunneling of electrons via sodium ions in silicon dioxide

Metal-oxide-silicon field-effect transistors (MOSFET's) were fabricated with ${\mathrm{Na}}^{+}$ ions in the gate oxide. Large peaks in the tunneling conductivity through the oxide were observed which are interpreted as resonant tunneling of electrons through localized ${\mathrm{Na}}^{+}$ impurities. It was demonstrated that the tunneling current was spatially localized. The temperature dependence of several peaks was measured and found to be consistent with a simple model for resonant tunneling through localized states. The position of the state in the direction of tunneling can be determined from the temperature dependence.
The computer as a subculture

In return for the privilege of speaking at an interdisciplinary panel, the speakers owe the audience some information to allow a guess about identity and identifications. Thus: I am an experimental psychologist with psychoanalytic training. Some years of experience in educational research have convinced me and my colleague that we need all the methodological help we can get from other behavioral sciences expecially from anthropology.
Photovoltaic technology: World Bank's attitude and activities☆

Abstract Several major problems stand in the way of the implementation of solar cells in developing countries; these are discussed first and relate to the following: (i) technology; (ii) national strategy; (iii) required capital. Next, the possible role of the World Bank is discussed. Although there is a strong commitment to the development of renewable energy sources, it is pointed out that the World Bank rates the direct solar technologies far behind biomass conversion. This results from the relatively high cost of solar cells. Nevertheless, there are several Bank-financed projects which are being carried out to enable the Bank to decide for itself the true state of the art. In view of the results obtained, it is believed that this was an appropriate course of action. It is concluded that a combination of efforts from the manufacturers and from the funding organizations is necessary if the Third World market for photovoltaics is to expand to its potential size.
Increased concentration of CTP synthetase in hepatoma 3924A: immunological evidence.

Abstract CTP synthetase (UTP:L-glutamine ligase, EC 6.3.4.2) was purified 370-fold from rapidly growing rat hepatoma 3924A. A major band was demonstrated by acrylamide gel electrophoresis which corresponded to this enzymic activity. It was estimated that the enzyme was 90% pure. Antibodies were produced in rabbit using this purified hepatoma enzyme. The specificity of the anti-serum was proved by the absence of the reaction between control serum and CTP synthetase. The amount of anti-serum required to inactivate completely the cytosolic CTP synthetase of hepatoma 3924A was 11-fold of that required for normal liver which is in good agreement with the 11-fold increase in CTP synthetase activity in this hepatoma. These results demonstrate that the liver and hepatoma 3924A CTP synthetases were immunologically similar or identical and that the markedly increased enzymic activity in hepatoma 3924A reflected an increase in the enzyme protein amount. These studies provide further evidence that in the neoplastic transformation a reprogramming of gene expression takes place which is manifested in the emergence of increased concentrations of CTP synthetase which should provide selective advantages to cancer cells by increasing the capacity for this rate-limiting step in de novo CTP biosynthesis.
Mechanistic structure—Activity studies of carcinogenic dialkylnitrosamines

Candidate molecular indicators of the relative metabolism and carcinogenic potency of a series of dialkylnitrosamines R2NNO (R = CH3, C2H5, n-C3H7, n-C4H9, or n-C5H11) were calculated using the semiempirical molecular orbital method called mndo together with geometry optimization and transition state identification. Specifically, thermodynamic and kinetic properties related to formation of putative ultimate carcinogens and indicators of the electrophilic properties of these active forms were determined. Of all the properties examined, the initial hydroxylations by cytochrome-P450 at activating (α-carbon) and inactivating (β-ω-carbon) positions appear to be the major modulators of parent compound activity as rat liver carcinogens. Neither the extent of further proposed nonenzymatic transformation of Cα-hydroxynitrosamines to alkyldiazohydroxides (RNNOH), diazonium ions [(RNN)+], or alkylcations (R+) nor the electrophilicity of these species appeared to be significant factors in differentiating parent compound carcinogenic activity.
Perinatal Mortality Associated with Intrauterine Infection Due to Pseudomonads

Pseudomonads are common causes of nosocomial infections but are rarely implicated in perinatal disease. In a retrospective autopsy study we found that 9% of all acute congenital bacterial infections were due to Pseudomonas species. Premature rupture of membranes occurred in half the cases and clinical maternal amnionitis in two-thirds. One case was apparently nosocomial in origin. No known risk factors were implicated in any other case. Seven infants were stillborn and two died within a few hours. Congenital pneumonia, funisitis, and chorioamnionitis were found at autopsy. Intrauterine infection due to the pseudomonads poses a serious problem that has not been previously recognized.