cssi/SciSciGPT-SciSciNet huggingface dataset:
Booster: An Accelerator for Gradient Boosting Decision Trees.

We propose Booster, a novel accelerator for gradient boosting trees based on the unique characteristics of gradient boosting models. We observe that the dominant steps of gradient boosting training (accounting for 90-98% of training time) involve simple, fine-grained, independent operations on small-footprint data structures (e.g., accumulate and compare values in the structures). Unfortunately, existing multicores and GPUs are unable to harness this parallelism because they do not support massively-parallel data structure accesses that are irregular and data-dependent. By employing a scalable sea-of-small-SRAMs approach and an SRAM bandwidth-preserving mapping of data record fields to the SRAMs, Booster achieves significantly more parallelism (e.g., 3200-way parallelism) than multicores and GPU. In addition, Booster employs a redundant data representation that significantly lowers the memory bandwidth demand. Our simulations reveal that Booster achieves 11.4x speedup and 6.4x speedup over an ideal 32-core multicore and an ideal GPU, respectively. Based on ASIC synthesis of FPGA-validated RTL using 45 nm technology, we estimate a Booster chip to occupy 60 mm^2 of area and dissipate 23 W when operating at 1-GHz clock speed.
The Red Blood Cell Storage Lesion: A Controversy of Biology Versus Randomized Controlled Trials

Randomized controlled trials (RCTs) are reporting no difference in mortality when older v. fresher blood is transfused, yet the biology of red cell aging (storage lesions) in the blood bank shows multiple effects. The contrast of cellular biologic changes of cells removed from circulation, then stored versus outcome research is important. The difference in conclusions from these research avenues drives practice. Many physicians may be confused in light of a Cleveland Clinic retrospective study that created controversy over outcomes, after older blood was transfused. That paper sparked public hearings held by the U.S. Food and Drug Administration (FDA). Widely disparate results exist regarding the biology of aged stored blood, retrospective outcome data, and RCTs. This review poses the question of whether the RCTs to date have been designed with hypotheses based upon the findings of the biology. The RCTs have not utilized non-inferiority design- what is required for proving a negative. Therefore, it remains unclear, if claims, being made today, that age of stored blood does not make a difference are scientifically valid. In the end, much work is yet to be done. Furthermore, no RCTs have been conducted comparing the use of stored blood (any age) to the use of best practices in patient blood management to avoid transfusion altogether, but that is a different question.
Assessing sustainability factors for rural sanitation coverage in Kenya, Zambia, Nepal, and Bhutan: A qualitative case study analysis

Abstract BACKGROUND Few countries are likely to achieve universal sanitation within the next decade as sustaining sanitation coverage remains a critical challenge. The purpose of this study is to investigate factors that may have supported or hindered sustainability of sanitation coverage 1-2 years after the completion of an integrated, area-wide sanitation program in four countries. METHODS Between 2014 and 2018, the SSH4A approach was implemented in 15 countries in Africa and Asia, four of which are included in this qualitative study. We conducted focus group discussions and interviews with beneficiaries, implementors, and decision-makers to identify sustainability factors and used household survey data to characterize sub-national sanitation coverage throughout implementation, and 1-2 years after. RESULTS Our data revealed behavioral, contextual, and service delivery factors that were related to the sustainability of sanitation improvements. Service delivery factors included follow-up hygiene promotion, access to materials (e.g., plastic, cement), local government commitment post-implementation, functioning monitoring systems, uptake of the supply chain by private sector, capacity for innovation. Contextual and behavioral factors included poverty, soil type, road networks, social cohesion, desire for improved latrines, maintenance and cleaning, and knowledge of sanitation benefits. DISCUSSION The presence or absence of sustainability factors identified through this research may have implications on where certain programmatic approaches will work, and where adaptations may be required. Through comparing sustainability factors with sub-national slippage rates, we were able to illustrate how local service delivery systems may respond to barriers (e.g., poverty, lack of affordable sanitation options, changes in population density) and enablers (e.g., sufficient resource allocation, passionate leadership, social cohesion). Understanding the programmatic and contextual factors that either drive or hinder long-term sanitation coverage may allow for greater program impact through adapting implementation based on existing challenges in service delivery and context.
Metabolomic analysis of diverse mice reveals hepatic arginase-1 as source of plasma arginase in Plasmodium chabaudi infection

Infections disrupt host metabolism, but the factors that dictate the nature and magnitude of metabolic change are incompletely characterized. To determine how host metabolism changes in relation to disease severity in murine malaria, we performed plasma metabolomics on eight Plasmodium chabaudi-infected mouse strains with diverse disease phenotypes. We identified plasma metabolic biomarkers for both the nature and severity of different malarial pathologies. A subset of metabolic changes, including plasma arginine depletion, match the plasma metabolomes of human malaria patients, suggesting new connections between pathology and metabolism in human malaria. In our malarial mice, liver damage, which releases hepatic arginase-1 (Arg1) into circulation, correlated with plasma arginine depletion. We confirmed that hepatic Arg1 was the primary source of increased plasma arginase activity in our model, which motivates further investigation of liver damage in human malaria patients. More broadly, our approach shows how leveraging phenotypic diversity can identify and validate relationships between metabolism and the pathophysiology of infectious disease. IMPORTANCE Malaria is a severe and sometimes fatal infectious disease endemic to tropical and subtropical regions. Effective vaccines against malaria-causing Plasmodium parasites remain elusive, and malaria treatments often fail to prevent severe disease. Small molecules that target host metabolism have recently emerged as candidates for therapeutics in malaria and other diseases. However, our limited understanding of how metabolites affect pathophysiology limits our ability to develop new metabolite therapies. By providing a rich data set of metabolite-pathology correlations and by validating one of those correlations, our work is an important step toward harnessing metabolism to mitigate disease. Specifically, we showed that liver damage in P. chabaudi-infected mice releases hepatic arginase-1 into circulation, where it may deplete plasma arginine, a candidate malaria therapeutic that mitigates vascular stress. Our data suggest that liver damage may confound efforts to increase levels of arginine in human malaria patients.
Uncertain Waters: Participatory groundwater modelling in Chicago's suburbs

Abstract Groundwater exists in underground aquifers and is largely hidden and intangible to water users. As such, groundwater models are one of the main vehicles through which groundwater is made legible. They are critical for water supply planning purposes. However, models are imperfect representations of limited data and contain much uncertainty, posing challenges for the water supply planning process. In this paper, we draw on a case from the Greater Chicago area to examine efforts by the authors and the Illinois State Water Survey to engage with local water managers to develop future water supply scenarios. Much of this area has been dependent upon the Cambrian-Ordovician Aquifer System for over 150 years. Over this period, water levels have declined by over 300 m and aquifers are expected to be unviable by 2030. Here we advance the growing field of participatory groundwater modelling (PGM) to identify forms of uncertainty and their influence on understandings of water supply and risk perceptions of depletion. Conceptually, we draw on the idea of models as world builders, where uncertainties are elucidated through knowledge production in the act of model building, while model development is simultaneously influenced by expectations, beliefs, and ambiguity surrounding those using the models. Through planning meetings and focus group discussions between groundwater modelers and water supply stakeholders, we identify four forms of interconnected uncertainty that hinder planning efforts: 1) hydrogeologic uncertainty, 2) modelling uncertainty; 3) water demand uncertainty; and 4) urban planning uncertainty. We describe our PGM efforts to reduce uncertainty and find stakeholder perceptions are as important as model uncertainties in water management decisions. Participatory modelling is effective in reducing and clarifying these four forms of uncertainty, particularly applied to short-term management decisions in a rapidly changing system. We conclude that future participatory modelling efforts need to focus on reducing communication barriers between scientists and local users.
Legal standards for evaluation research: A reply to Smith

Abstract Smith (1981), asserting that not all evaluative studies require the same degree of evidence for decision-making, suggests a legal paradigm for determining how much certainty is necessary for informed decision-making. Specifically, he argues for the use of three levels of certainty, i.e., suggestive, preponderant, or conclusive evidence, modeled after the legal standards of proof. Unfortunately, such an approach is untenable for several reasons. Smith's suggestion that decision-makers adopt legal terminology, for example, is really a recommendation of form rather than substance and, furthermore, his analogy from the law to the evaluation context is based upon a misunderstanding of the trial process. These and other problems with Smith's suggestions are discussed.
Efficient monitoring and display of thread state in Java

How many times have you asked yourself the question "what is my program doing now?" JIVE is a system that tries to answer this question. It provides insights into the execution of Java programs. It does so with minimal overhead so it can be used on arbitrary systems at any time. A large portion of the complexity of Java systems comes from the behavior and interaction of multiple threads. Thus, JIVE concentrates in part on showing what the various threads are doing. This paper describes how JIVE does this. It first describes our original approach, which simply monitored the state of each thread, displaying the time spent in each state on an interval basis. We then describe how we extended this framework to provide additional detailed information on state changes and on thread interactions. The core of this paper describes the problems that arose here, their solutions, and the resultant visualizations.
CATERPILLAR 3400 SERIES ENGINES

A new family of heavy duty diesel engines, the 3400 Series, has been developed by Caterpillar Tractor Co. The family includes Inline 6 cylinder, V-8 and V-12 engines covering the 270-750 horsepower range. Stringent program objectives were established in the areas of durability, reliability, commonality, flexibility and serviceability within defined limits of cost and weight. Design, development and manufacturing planning were closely coordinated to ensure economical manufacturing with high volume tooling. This paper deals with the design, development and certain aspects of engine applications. /GMRL/
Rank Order Correlation

Rank order correlation is often used when researchers want to consider only the ordinal aspects of their data. This might be considered when researchers believe their data represent only ordinal aspects of the measurement constructs. There may also be statistical reasons, as when a researcher does not want to assume normality or believes that monotonicity as opposed to strict linearity is plausible. Keywords: correlation; nonparametric methods; rank order correlation; statistics
An efficient all-fiber VOA with 30 kHz bandwidth and 10 mW drive power based on acousto-optic coupling on cladding etched single-mode fiber

We demonstrate a novel all-fiber ultra broadband VOA based on acousto-optic mode coupling in SM fiber with a dynamic range of 18 dB, PDL of 0.5 dB, bandwidth of 30 kHz and power consumption of 10 mW.
The short-term use of erythropoetin-stimulating agents: impact on the biochemical recurrence of prostate cancer.

Study Type – Harm (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Erythropoletin-stimulating agents (ESAs) have been widely prescribed for treating anaemia secondary to advanced maligancies with the objective of reducing the need for red blood cell transfusions and improving the quality of life. However, the risk/benefit of ESAs has recently been questioned and metaanalyses showing that these agents are associated with an increased risk of mortality when chronically administered to patients with advanced/metastatic cancers. In this study we examined the impact of short-term preoperative utilization of ESAs on biochemical recurrence – free survival rates after open radical retropubic prostatectomy (ORRP). OBJECTIVE • To examine the impact of short-term preoperative utilization of erythropoietin-stimulating agents (ESAs) on biochemical recurrence (BCR)-free survival rates after open radical retropubic prostatectomy (ORRP) in light of the fact that the risk/benefit of ESAs has recently been questioned by the Food and Drug Administration (FDA) after reports showing a decreased survival. PATIENTS AND METHODS • From 2000 to 2008, 1567 patients underwent ORRP and 97.5% of these signed informed consent to participate in the New York University Prospective and Longitudinal Outcomes Study. • Of the remaining 1528 patients, 1317 (86%) received preoperative ESA (group 1) and 211 (14%) did not (group 2). • Patients were also classified as having low-, intermediate- or high-risk disease based on D’Amico risk categories. • Kaplan–Meier survival curves and Cox’s proportional hazard models were used to estimate BCR-free survival by ESA treatment. RESULTS • A significant difference was observed for BCR-free survival between the low- and intermediate/high-risk groups. • There were no statistically significant differences between groups 1 and 2 for BCR-free survival in the entire study populations and within risk groups. • In addition, Cox regression models showed no statistically significant differences in BCR-free survival according to preoperative ESA administration in the entire cohort as well as among the low- and intermediate/high-risk groups. CONCLUSIONS • The short-term use of ESAs as a preoperative blood management strategy for patients undergoing ORRP has no clinically relevant adverse effects on the biology of prostate cancer. • The present study supports the use of these agents before the procedure in patients undergoing surgery for localized disease.
Protein factors that bind to the murine 2′,5′-oligoadenylate synthetase ME-12 gene 5′ upstream regulatory region.

The murine 2',5'-oligoadenylate synthetase ME-12 gene regulatory region AB forms six complexes with protein factors in murine BALB/c 3T3 cells as demonstrated by the mobility shift electrophoresis assay under the reaction conditions used. The complexes, designated C1-C6 in order of their decreasing electrophoretic mobility, showed three distinctive specificities with regulatory region AB, element A, and element B as probes or competing DNA: 1) C1 is region AB-specific (this complex did not form with either element A or B used alone or as a mixture); 2) C5 formed both with element A and element B; 3) C2, C3, C4, and C6 formed with element B, but not A. The protein factors that give rise to these complexes show differential DNA binding activities in various buffer solutions at different pH values. The C4-forming protein factor is the interferon (IFN)-alpha/beta-stimulated response factor (ISRF) which shows element B specificity. It preexists in the cytoplasm. ISRF appears to be complexed to an inhibitor (ISRFI) in the cytoplasm and to dissociate from the inhibitor and to translocate into the nucleus upon treatment of cells with IFN-alpha/beta. We propose that IFN-alpha/beta treatment of BALB/c 3T3 can trigger at least two events: 1) loosening of a tight inhibitor-ISRF complex with the release of free ISRF; this may be mediated via phosphorylation of ISRF or ISRFI; 2) translocation of ISRF into the nucleus and binding to the enhancer element B, which results in the activation of 2',5'-oligoadenylate synthetase gene expression.
Therapeutic Approaches for Clostridium difficile Infections

Metronidazole and vancomycin remain the front-line therapies for most Clostridium difficile infections (CDI). However, recurrent CDI occurs in ∼25% of patients, causing significant morbidity and mortality and healthcare costs. For this population, traditional antibiotic therapies fail and new treatment options are greatly needed. The US Food and Drug Administration recently approved fidaxomicin for CDI treatment. This narrow-spectrum antibiotic preserves the normal gut microbiota and shows promise as a treatment for severe and recurrent CDI. Monoclonal antibodies and vaccines directed against toxin are currently in clinical trials and represent alternative, non-antibiotic therapies. Less traditional therapeutic interventions include bacteriotherapy with non-toxigenic C. difficile and fecal transplant. This commentary will provide an overview of current and forthcoming CDI therapies. Curr. Protoc. Microbiol. 30:9A.3.1-9A.3.9. © 2013 by John Wiley & Sons, Inc. Keywords: colitis; antibiotics; diarrhea; vaccine
Cesarean section: A 15-year review of changing incidence, indications, and risks

Abstract During 15 years (1965 through 1979), 9,718 cesarean sections were performed at Hutzel Hospital. This report concerns the indications, incidence, morbidity, and mortality. Dystocia, fetal distress, and breech presentations were the most common indications for primary cesarean section. The incidence rose from 9.8% to 16.8% during this study. Forceps deliveries dropped from 47.5% to 12.0%, and vaginal breech deliveries decreased from 86% to 35%. Spinal anesthesia was used in 90%. Cesarean section hysterectomies were performed in 128. The most common indications were carcinoma in situ of the cervix, uterine leiomyoma, and hemorrhage. Puerperal sepsis and urinary tract and wound infections were the major causes of morbidity. Perinatal mortality decreased from 40% to 29%. There were 10 maternal deaths. Sepsis was the major cause of death. At least four deaths could have been avoided if ultra-high-risk patients had not been pregnant in the first place.
Designing safer drugs based on the soft drug approach

In the general drug design process, one starts with a known bioactive molecule which is used as the lead compound and then undertakes structural moditiciltions either by the gmup or biotimctional moieties appmach in order to enhance the desired biological activity of the compound. This is most successful if one can identify the structural part responsible for the activity’. More recently, some other types of considerations were also involved in drug design, namely to improve delivery, distribution and pharmacokinetic properties of the drugs. In the general drug design process, however, little or no attention was paid to the metabolic disposition of the drugs. This is the case despite the fact that the toxicity of a number of bioactive molecules and drugs is due to their new %ructural pmperdes introduced during the design process. This means that the passible toxic metabolites or unwanted pharmacokinetic properties will generally be further enhanced when more active corn pounds are obtained. It is generally accepted that drugs, and particularly their metabolic processes, contribute to toxic processes by formation of active metaboliteP”. This phenomenon, the metabolic activation to reactive intennediates which covalendy bind to tissue macm molecules, is the initial step in the damage. The main reason that not much anention was paid to these processes is because the highly reactive metabolic intermediates cannot generally be idcntitied or observed as the excreted and identified metabolites are the end products of a long process. In order to impmve the therapeutic index for drugs. one has to be able to separate the activity and toxicity properties. Many drug designers believe that this is practically impossible and that most of the toxic side effects will parallel the increase ordecreaw in the desired pharmacological activity. One intemsting thought to avoid drug toxicity was provided by A&Ens. who suggested design of non-metabolizable drugs5. AI first sight this idea sounds really attractive as one would in this way avoid unwanted toxicity and the pharmacokia etics of the drug would b* rather simple, controlled only by renal excretion. We could call these kinds of non-metabolizable compnunds’harddrugs’. It is very unlikely, however, that one can ever succeed in designing ideal hard drugs. lt is wellknown [hat the body can attack and alter chemically quite stable suucmrcs and even if a drug was excreted 9&!25?41 unchanged. the unaccounted small potion might, and most likely would. cause toxicity by forming some reactive intermediates. It is also evident that one could achieve a complete inertness towards the metabolic process only if going to pharmacokinetic extremes. meaning drugs which arc rxtremcl?_ kdrrlphilic or extremely hydrophobic.
Membership Characteristics of the American Society of Primatologists Through 2002

Approximately once a decade, the Treasurer of the American Society of Primatologists (ASP) publishes a report on the current membership characteristics of the society. Each year, when members join the ASP they answer a series of questions designed to evaluate the composition of the society and the interests of its members. In 2002 the society had 691 members (443 full members, 222 student members, and 26 retired members). This represents only a 3.1% increase in overall membership during the past decade, and a decrease of 10.8% from 2001. Over the years, the proportion of student (32.1%) and retired (3.8%) members has grown considerably, while the proportion of full members (64.1%) has decreased correspondingly. Of 691 members, 59 were source-country primatologists who received complimentary (full or student) memberships. Women now comprise 57.7% of the membership, an increase of 5.9% over the last decade. Recent changes in the assessment and collection of annual dues have resulted in three important membership changes. First, 8.5% of current ASP members are source-country primatologists who receive complimentary memberships in the ASP and complimentary subscriptions to the American Journal of Primatology (AJP). Second, mandatory subscription to AJP for full and student members in 2000 resulted in an immediate 8.7% decrease in membership, which appears to be continuing. Third, in 2002 approximately 50% of the members opted to pay their ASP dues with a credit card and/or via the Internet. It is hoped that the current decline in membership numbers represents a temporary trend, and that this loss will be reversed by 2004. Am. J. Primatol. 61:45–52, 2003. © 2003 Wiley-Liss, Inc.
PEMPHIGUS ANTIBODIES: THEIR ROLE IN DISEASE

Transfusion of human pemphigus plasma into four monkeys failed to produce disease or lesions in spite of strong binding of antibody to the epidermal intercellular space. These experiments cast doubt on the direct role of pemphigus antibodies in the pathogenesis of this disease.
Surface modification of La0.8Sr0.2CrO3−δ–YSZ dual-phase membranes for syngas production

Oxygen permeation fluxes were studied in Mixed Ionic and Electronic Conducting (MIEC) membranes based on composites of 40 vol% La0.8Sr0.2CrO3 (LSCr) and 60 vol% yttria-stabilized zirconia (YSZ), using ambient air and flowing CO to establish a P(O2) gradient. The ambipolar conductivity of the dense LSCr–YSZ composite was determined for membranes with dense layers that were 115 μm and 650 μm thick. Other parts of the investigation focused on how modifications to the surface on the CO side affected the fluxes. Using a porous LSCr–YSZ composite on the surface as the base case, oxygen fluxes were shown to increase dramatically upon addition of 5 wt% CeO2 as a catalyst and an additional increase was observed with 1 wt% Pt. Changes in the structure of the porous composite LSCr–YSZ surface to improve connectivity of the YSZ phase also led to large increases in the oxygen fluxes.
Exploring the binding conformations of bulkier dipeptide amide inhibitors in constitutive nitric oxide synthases

A series of L-nitroarginine-based dipeptide inhibitors are highly selective for neuronal nitric oxide synthase (nNOS) over the endothelial isoform (eNOS). Crystal structures of these dipeptides bound to both isoforms revealed two different conformations, curled in nNOS and extended in eNOS, corresponding to higher and lower binding affinity to the two isoforms, respectively. In previous studies we found that the primary reason for selectivity is that Asp597 in nNOS, which is Asn368 in eNOS, provides greater electrostatic stabilization in the inhibitor complex. While this is the case for smaller dipeptide inhibitors, electrostatic stabilization may no longer be the sole determinant for isoform selectivity with bulkier dipeptide inhibitors. Another residue farther away from the active site, Met336 in nNOS (Val106 in eNOS), is in contact with bulkier dipeptide inhibitors. Double mutants were made to exchange the D597/M336 pair in nNOS with N368/V106 in eNOS. Here we report crystal structures and inhibition constants for bulkier dipeptide inhibitors bound to nNOS and eNOS that illustrate the important role played by residues near the entry to the active site in isoform selective inhibition.
Comparison of uranium-series, radiocarbon, and amino acid data from marine molluscs, Baffin Island, Arctic Canada

Uranium-series and /sup 14/C dates and the extent of amino acid racemization are reported for 24 marine shell samples from three areas of Baffin Island, Arctic Canada. When the radiometric dates are plotted against the ratio of D-alloisoleucene:L-isoleucene in the shells, five broad age groups are recognized. The uranium-series data indicate that /sup 231/Pa is incompletely retained in most fossil shells and that /sup 230/Th is lost from some of the samples. Therefore, their apparent ages are minimum. However, a few dated samples in each group have yielded useful age results, and the minimum ages of the five groups of samples are estimated as 7,000 to 11,000, greater than or equal to70,000, greater than or equal to136,000, greater than or equal to190,000 and >300,000 yr. Calculated integrated thermal histories based on the epimerization reaction in the mollusc Hiatella arctica Linne give paleotemperature estimates of around -5/sup o/C, compared to the present mean annual air temperature of about -11/sup o/C.
Pressure-induced phase transformations in ice.

Using molecular-dynamics calculations, we show that at 80 K, ice Ih undergoes a transition to a high-density amorphous (hda) form at about 13 kbar. At higher pressures, the calculated oxygen atom radial distribution function shows strong resemblance to that of ice VIII. The most characteristic feature of hda ice, namely the peak observed around 3.5 A\r{} in the oxygen radial distribution function, is ascribed to molecules occupying interstitial-like sites. On warming of a sample of hda ice recovered at zero pressure, the structure evolves to a lower-density form. These observations are in good accord with available experimental data.
Remaking Scale: Competition and Cooperation in Prenational and Postnational Europe

The geography of Europe only two decades ago was broadly conceived as a stable hierarchy of places at different spatial scales: Eastern and Western blocs, discrete nations, subnational regions, and local and urban communities. The disruption of this “given” postwar geography in the intervening two decades and of the political, economic and cultural assumptions that went with it could barely have been predicted in the early 1970s (but see Mandel 1975, 310–42 for a prescient discussion; Rowthorn 1971; Murray 1971). Certainly the development of a “European Economic Community”, equalizing conditions of trade in several commodities between six countries beginning in the early 1950s, and the steady growth of a more fully fledged “Common Market” served notice that some disruption of the traditional economic geography (at least at the national scale) was afoot. Nonetheless, the reconstruction of Europe at all spatial scales that would follow the 1970s economic depressions in the West and the post-1989 implosion of official Communist Party rule in the East were quite unforeseeable. Thereby, the largely economic evolution of the Common Market into the European Community in the 1970s and 1980s and now into the more politically inspired European Union was bound up with a much more complex and halting entanglement of social, cultural and political as well as economic restructurings.
A portable pupilometer system for measuring pupillary size and light reflex

A new pupilometry assessment system was evaluated as an instrument for potential use in basic research and clinical studies of addictive drug use in humans. The system is portable and can be used as a peripheral device with a variety of IBM-compatible personal computers. The pupilometer electronically measures the pupil diameter with infrared sensors and has the ability to stimulate the pupil with a programmable pulse of light and to record the resultant papillary response. The present report compares the static pupil-diameter measurements obtained with this infrared pupilometer and those obtained photographically in a bench-top and in a clinical setting. The infrared pupilometer was also used to record the light reflex of the pupil in research subjects after administration of various morphine-related drugs. The results indicate that static pupil-diameter measurements made with the infrared pupilometer compare favorably with the photographic measurement. The ability of the infrared pupilometer to record the light reflex may provide an additional means of quantitatively measuring drug action.
EXP597, a nonpeptide angiotensin II receptor antagonist with high affinities for the angiotensin AT1 and AT2 receptor subtypes

AT1 and AT2 are the two major receptor subtypes for angiotensin II that have been pharmacologically defined by using the selective ligands losartan and PD123177, respectively. EXP597 (4-[(5-(2-benzoyl)benzyloxycarbonyl-4-ethyl-2-n-propylimidazole-1- yl)methyl]-3-fluoro-2'-isoamyloxycarbonylaminosulfonyl-[1,1']-biph enyl, potassium salt) is a nonpeptide angiotensin II receptor ligand which in the rat adrenal exhibits binding affinities (IC50) of 0.5 and 0.7 nM for angiotensin AT1 and AT2 receptor subtypes, respectively. Further, EXP597 is an insurmountable angiotensin II receptor antagonist in the isolated rabbit aorta and lowers blood pressure in renal hypertensive rats with i.v. and p.o. ED30 values of 0.05 and 0.9 mg/kg, respectively.
Endoscopic repair of orbital floor fractures

A variety of surgical approaches to orbital floor fractures have been described. These approaches include the subciliary, transconjunctival, transmaxillary, endonasal, and, recently, the endoscopic transmaxillary approach. As in other surgical specialties, technological advances continue to be used for the betterment of patients with facial trauma. The treatment of orbital fractures has benefited from these advances, particularly in the endoscopic arena. Currently, most orbital floor fractures are repaired with either a transcutaneous or transconjunctival eyelid approach. The use of endoscopy can easily be added to these approaches to enhance the surgeon's visualization, particularly deep in the orbital cavity. Endoscopy also can be used in a minimally invasive, transmaxillary approach to the orbital floor that eliminates complications associated with eyelid incisions (ie external scarring, eyelid edema, ectropion, entropion, and granuloma formation). In this article, we review the technique for transmaxillary, endoscopic repair of orbital blow-out fractures.
Live attenuated influenza virus vaccines strains with temperature-sensitive defects in P3 protein and nucleoprotein

Abstract The temperature-sensitive influenza virus A/Hong Kong/68 (H3N2) ts -1[E] has been used as a prototype live attenuated influenza virus vaccine. Using recently developed techniques to map the genome of influenza viruses and to “genotype” influenza virus recombinants, the temperature-sensitive lesions in the virus were identified. These defects, responsible for the attenuation of the virus, are located in the genes for the P3 protein and the nucleoprotein and are associated with virus-specific RNA synthesis. Hong Kong/68 (H3N2) ts -1[E] virus can also serve as a donor of “attenuation characteristics” for the selection of recombinant strains which have different surface antigens and may be used as vaccine strains in the future. The temperature-sensitive mutations of Hong Kong/68 (H3N2) ts -1[E] virus were previously transferred to recombinant viruses carrying the HO hemagglutinin. The RNAs of 8 of these temperature-sensitive recombinants were analyzed. One of these viruses, R1, classified in group 1 of the Hong Kong mutant virus set was found to possess a ts defect only in the P3 protein. R8, a member of group 2 of the Hong Kong mutant virus set had a ts mutation in the nucleoprotein.
A pair of epimeric 13-hydroxy-2,3,6,7-tetramethoxy-8b,11,12,12a,13,13a-hexahydro-9H-9a-azacyclopenta[b]triphenylene-10-ones.

The structures of two compounds which are intermediates in the synthesis of phenanthroindolizidine alkaloids have been determined. (8bS,13aS,14R,14aR)-8b,9,11,12,13,13a,14,14a-Octahydro-14-hydroxy-2,3,6,7-tetramethoxydibenzo[f,h]pyrrolo[1,2-b]isoquinolin-11-one acetone solvate, C 24 H 27 NO 6 .C 3 H 6 O, (II), crystallizes in a chiral space group with one solvent molecule (acetone) present in the asymmetric unit. On the other hand, (8bS,13aS,14S,14aR)-8b,9,11,12,13,13a,14,14a-octahydro-14-hydroxy-2,3,6,7-tetramethoxydibenzo[f,h]pyrrolo[1,2-b]isoquinolin-11-one, C 24 H 27 NO 6 , (III), crystallizes in a centrosymmetric space group with two molecules in the asymmetric unit and with no solvent present. The two molecules in the asymmetric unit of (III) are structurally the same. Compounds (II) and (III) are epimers at the C atom carrying the OH group; otherwise they are very similar in structure.
Genetic monogamy across variable demographic landscapes in cooperatively breeding Florida scrub-jays

Variation in ecological and demographic characteristics may alter the value of extrapair paternity (EPP) for socially monogamous species, thereby leading to variation in mating strategies among conspecific populations. Environmental factors influencing the need for parental care, and demographic factors influencing relatedness of social pairs or availability of unrelated extrapair partners, are both predicted to influence the direct and indirect benefits of EPP in cooperatively breeding birds. We examined genetic mating strategies in 3 long-term study populations of cooperatively breeding Florida scrub-jays (FSJs; Aphelocoma coerulescens) in which the value of EPP—or opportunities for it—was likely to vary: a fragmented site with a high frequency of inbreeding (potentially elevating the value of EPP as a means of increasing offspring heterozygosity); a suburban population with high rates of brood reduction (potentially elevating the value of shared parental investment); and a wildland site with a high frequency of unrelated breeders and opposite-sex auxiliaries (potentially elevating the opportunity for shared within-group parentage). Despite these differences, genetic monogamy dominated at all sites: 100% of the offspring sampled from the suburban site (144 offspring) and fragmented site (258 offspring), and 99.5% of offspring from the wildland site (367 of 369 offspring) were produced monogamously. Rare exceptions in our study populations demonstrate that, even in the FSJ, genetic monogamy is a plastic trait. The near ubiquity of genetic monogamy across 3 ecologically different study sites, however, suggests that this tendency toward monogamy is impervious to the population-level environmental and social variation that we documented. Key words: Aphelocoma coerulescens, extrapair paternity, Florida scrub-jay, genetic monogamy. [Behav Ecol]
Effect of heteroporosity on membrane rejection coefficients

Abstract Statistical heteroporosity theory is applied to the case of ultrafiltration across a membrane composed of an array of independent channels or pores. The primary question addressed is: For given values of the reflection coefficient σ, and diffusive permeability Ps, measured independently for a membrane of unknown heteroporosity, how accurately can the rejection coefficient R be predicted by using the Spiegler—Kedem expression for rejection, derived without concern for heteroporosity? For the case of applied pressure much greater than back-osmotic pressure, limits are analytically derived which show a maximum 30% relative error in R at σ → 0, and a maximum absolute error of 0.06 at σ ≅ 0.5. Experimental regions where heteroporosity effects should be largest are given explicitly. It appears that, except for these regions, the Spiegler—Kedem equation can be used to describe accurately rejection across membranes of arbitrary heteroporosity. p]For the case of appreciable solute concentration in the feedstream, a proposed test of heteroporosity consists of measurements of rejection vs. volume flux, at small and large solute concentrations. For a particular model of membrane structure called the two-pipe model it is shown that, in principle, heteroporosity can result in significant changes of rejection with concentration at a given volume flow, but for three real membranes used as examples the effects are predicted to be relatively small.
A high-resolution structure of a DNA–chromomycin–Co(II) complex determined from pseudocontact shifts in nuclear magnetic resonance

Abstract Background: The drug chromomycin-A 3 binds to the minor groove of DNA and requires a divalent metal ion for complex formation. 1 H, 31 P and 13 C pseudocontact shifts occurring in the presence of a tightly bound divalent cobalt ion in the complex between d(TTGGCCAA) 2 and chromomycin-A 3 have been used to determine the structure of the complex. The accuracy of the structure was verified by validation with nuclear Overhauser enhancements (NOEs) and J-coupling constants not used in the structure calculation. Results: The final structure was determined to 0.7 A resolution. The structure was compared with a structure obtained in an earlier study using NOEs, in order to assess the accuracy of NOEs in giving global structural information for a DNA complex. Although some basic features of the structures agreed, they differed substantially in the fine structural details and in the DNA axis curvature generated by the drug. The distortion of base-pair planarity that was observed in the NOE structure was not seen in our structure. Differences in drug orientation and hydrogen bonding also occurred. The curvature and elongation of the DNA that was obtained previously was not found to occur in our study. Conclusions: The use of pseudocontact shifts has enabled us to obtain a high-precision global structure of the chromomycin–DNA complex, which provides an accurate template on which to consider targeting minor groove binding drugs. The effect of such binding is not propagated far along the helix but is restricted to a local kink in the axis that reverts to its original direction within four base pairs.
Proton affinities of neutral molecules

Abstract Values for proton affinities (gas-phase basicities) published during the past ca. 25 years are given. Methods for determining these values are discussed.
Using a mathematical model of a weathering clast to explore the effects of curvature on weathering

Abstract For the first time, we show that rind thicknesses developed on surfaces of a clast with different values of curvature can be used to estimate the duration of clast weathering. To obtain an analytical expression for the velocity of the curvilinear weathering front on a clast of arbitrary shape, we approximate our previous multi-mineral reactive-diffusion model and explore a simplified 2-D model numerically and analytically. Our analysis documents that with increasing curvature of the weathering front, the mathematical description of weathering advance is equivalent to that derived for advection as the dominant solute transport mechanism, even for the case where transport is occurring by diffusion only. Specifically, for a curvilinear weathering front with constant curvature K
Structural and Spectroscopic Characterization of Iron(III) Dioxoporphodimethene Complexes and Their Autoreduction to an Iron(II) Complex in Pyridine.

Three iron complexes of the meso-dioxo derivative of octaethylporphryin (trans-H(2)OEPO(2)) were characterized by X-ray diffraction. Green ClFe(III)(trans-OEPO(2)).1.5C(6)H(6) crystallizes in the monoclinic space group P2(1)/c with a = 13.766(3) A, b = 19.075(3) A, c = 15.217(3) A, beta = 99.87(2) degrees at 123 K with Z = 4. Refinement of 2712 reflections with F > 6.0sigma(F) and 223 parameters yielded R = 0.0624, R(w) = 0.0596. The iron complex contains a domed dioxoporphodimethene macrocyclic ligand. The observation of a five-coordinate iron(III) ion with an axial Fe-Cl distance of 2.232(2) A and in-plane Fe-N distances averaging 2.082 A is consistent with its high-spin (S = (5)/(2)) character. This monomer is readily converted to the green {Fe(III)(trans-OEPO(2))}(2)O using aqueous hydroxide. {Fe(III)(trans-OEPO(2))}(2)O crystallizes in the monoclinic space group C2/c with a = 23.541(8) A, b = 15.392(5) A, c = 18.686(8) A, and beta = 90.09(3) degrees at 294 K with Z = 8. Refinement of 3472 reflections with F > 6.0sigma(F) and 393 parameters yielded R = 0.0484, R(w) = 0.0527. The complex possesses a crystallographically imposed 2-fold symmetry axis that passes through the oxo ligand. The dioxoporphodimethene ligands within the molecule are roof-shaped and fold away from each other. The axial Fe-O distance is 1.749(1) A with longer in-plane Fe-N distances (average 2.077 A). The Fe-O-Fe angle of 165.4(2) degrees deviates significantly from linearity and is more acute than related porphyrin complexes. Pyridine solutions of either the iron(III) monomer or m-oxo dimer autoreduce over a period of days to give (py)(2)Fe(II)(trans-OEPO(2)). This red compound crystallizes in the space group P2(1) with a = 19.177(4) A, b = 20.039(4) A, c = 10.547(2) A, and beta = 100.36(3) degrees at 130 K with Z = 2. Refinement of 5090 reflections with one restraint and 984 parameters yielded R1 = 0.0684, wR2 = 0.1763. The complex crystallizes with two distinct molecules in the asymmetric unit; each molecule contains a different degree of disorder with respect to the trans meso oxygen atoms (50/50, 71/29). Each independent molecule exhibits severe ruffling of the macrocycle. The six coordinate iron(II) center is diamagnetic. The axial Fe-N(pyridine) distances average 1.98 A, and the in-plane Fe-N(pyrrole) distances average 1.95 A. A common trend observed for the dioxoporphodimethene macrocycle in all of these structures is an elongation toward the trans oxidized meso carbons. These complexes were originally prepared as cis and trans isomeric mixtures that can be enriched in the trans isomer by fractional crystallization. This is evident in their distinctive (1)H NMR spectra. In addition, these compounds are characterized by electron impact mass spectrometry and UV-visible, ESR, and infrared spectroscopies.
Complete Allogeneic Hematopoietic Chimerism Achieved by a Combined Strategy of In Utero Hematopoietic Stem Cell Transplantation and Postnatal Donor Lymphocyte Infusion

In utero hematopoietic stem cell transplantation (IUHSCTx) can achieve mixed hematopoietic chimerism and donor-specific tolerance without cytoreductive conditioning or immunosuppression. The primary limitation to the clinical application of IUHSCTx has been minimal donor cell engraftment, well below therapeutic levels for most target diseases. Donor lymphocyte infusion (DLI) has been used in postnatal circumstances of mixed chimerism as targeted immunotherapy to achieve a graft-versus-hematopoietic effect and to increase levels of donor cell engraftment. In this report we demonstrate in the murine model that a combined approach of IUHSCTx followed by postnatal DLI can convert low-level, mixed hematopoietic chimerism to complete donor chimerism across full major histocompatibility complex barriers with minimal risk for graft-versus-host disease (GVHD). Time-dated embryonic day 14 (E14) to E15 Balb/c (H-2K(d), CD45.2) fetuses underwent intraperitoneal injection of 5 x 10(6) T-cell-depleted B6 (H-2K(b), CD45.2) bone marrow cells. Chimeric recipients then received transplants at either 4 or 8 weeks of age with 1 of 3 doses (5, 15, or 30 x 10(6) cells) of donor congenic splenocytes (B6-Ly5.2/Cr, H-2K(b), CD45.1). The response to DLI was dose dependent, with conversion to complete donor peripheral blood chimerism in 100% of animals that received high-dose (30 x 10(6) cells) DLI. Only 1 of 56 animals receiving this dose succumbed to GVHD. This study directly supports the potential therapeutic strategy of prenatal tolerance induction to facilitate nontoxic postnatal cellular therapy and organ transplantation, and it has broad implications for the potential treatment of prenatally diagnosed genetic disorders.
A two-parameter model of interaction in father-son status mobility

An abstract model is developed for the relation between social distance, measured on an interval scale, and social mobility. Applied to British mobility data the model is used to analyze occupational status mobility, specifically, to analyze the pattern by which the occupational status of a son is related to the occupational status of his father. There appear to be two components to the interaction among statuses. The first component places a son near his father's absolute position, whereas the second component places a son near his father's relative position. The abstract model proposes an exact description of these two effects, and the description fits the British data. The model is substantively and methodologically close to several earlier mobility analyses, but it is shown to be more parsimonious and more accurate, and the model suggests that the actual social process underlying the mobility data may be more regular and more well-behaved than had been anticipated.