cssi/SciSciGPT-SciSciNet huggingface dataset:
A diverse stochastic search algorithm for combination therapeutics.

Background. Design of drug combination cocktails to maximize sensitivity for individual patients presents a challenge in terms of minimizing the number of experiments to attain the desired objective. The enormous number of possible drug combinations constrains exhaustive experimentation approaches, and personal variations in genetic diseases restrict the use of prior knowledge in optimization. Results. We present a stochastic search algorithm that consisted of a parallel experimentation phase followed by a combination of focused and diversified sequential search. We evaluated our approach on seven synthetic examples; four of them were evaluated twice with different parameters, and two biological examples of bacterial and lung cancer cell inhibition response to combination drugs. The performance of our approach as compared to recently proposed adaptive reference update approach was superior for all the examples considered, achieving an average of 45% reduction in the number of experimental iterations. Conclusions. As the results illustrate, the proposed diverse stochastic search algorithm can produce optimized combinations in relatively smaller number of iterative steps. This approach can be combined with available knowledge on the genetic makeup of the patient to design optimal selection of drug cocktails.
Some additional potassium-argon ages of hawaiian rocks: The Maui volcanic complex of Molokai, Maui, Lanai and Kahoolawe

Abstract Potassium-argon (K-Ar) ages have been determined for rocks from the group of volcanoes vicinal to Maui, Hawaii, in an effort to fill gaps left by previous dating work. Ages for tholeiitic samples from the main shield-building stage of the volcanoes varied in sequence from 0.83 m.y. for Haleakala to 1.84 m.y. for West Molokai volcano. Some differ significantly from ages reported previously. For the volcanoes studied, ages agree with the general Hawaiian trend of volcanoes becoming progressively older to the northwest (Fig. 1B). New determinations of K-Ar ages were made for the late-stage, alkalic volcanism on Kahoolawe (1.03 m.y.), and for the later post-erosional phases at Kalaupapa, Molokai (1.24 m.y.) and from a vent of the Lahaina Series on West Maui (1.30 m.y.). These last two, when compared with the dates of the main shield-building stages of the respective volcanoes, show that very extensive erosion of these Hawaiian volcanoes has taken place in the surprisingly short period of a few hundred thousand years. This is substantiated by evidence of similar rapid erosion on the islands of Oahu and Hawaii.
Cytological demonstration of chloroplast DNA behavior during gametogenesis and zygote formation in Chlamydomonas reinhardtii.

We used the flourescent dye DAPI to visualize nucleoids of chloroplast DNA and follow their behavior through sexual reproduction by counting nucleoids in fixed cells at various stages. Nucleoid number varied greatly among cells at each stage. The mean number of nucleoids per cell was similar in mt+ and mt− vegetative cells, and declined similarly during gametogenesis. Longer periods of nitrogen starvation reduced the mean nucleoid number further. Mean nucleoid number declined again in mating pairs, and continued to drop in zygotes up to the latest stage that can be examined (24-h zygotes). The oldest zygotes had means of about 2 to 3 nucleoids in different experiments, significantly fewer than in the mt+ gametes (usually 4 to 5). The quantitative data on nucleoid number, mating efficiency, and germination efficiency allowed us to show that the decrease in nucleoid number is not limited to gametes that do not mate, or to zygotes that do not germinate. These data are consistant with earlier biochemical studies showing loss of chloroplast DNA during gametogenesis in both mating types, and with the degradation of paternal chloroplast DNA detected biochemically and (in non-quantitative studies) by DAPI staining. There may also be some fusion of nucleoids, although if it occurs it is not complete by 24 h of zygote maturation.
Tacrolimus Enhances the Immunosuppressive Effect of Cyclophosphamide But Not That of Leflunomide or Mycophenolate mofetil in a Model of Discordant Liver Xenotransplantation

Leflunomide (LEF), which suppresses both T and B cells, prolongs survival of heart xenografts in the concordant hamster to rat animal model.1 However, xenotransplantation across discordant barriers is the most likely approach to solve the problem of organ shortage. By perfusing guinea pig livers with University of Wisconsin solution containing sodium nitroprusside, we have solved the problem of poor reperfusion of this organ when transplanted into rats.2 Accordingly, we tested the effect of LEF alone or in combination with tacrolimus (FK) on survival of guinea pig to rat liver xenografts. Results were compared with those obtained following the use of cyclophosphamide (CyP) and mycophenolate mofetil (MMF).
Homogeneous Time-Resolved Fluorescence Quenching Assay (TruPoint) for Nucleic Acid Detection

Laboratories performing genetic screening studies need simplified methods that allow automation for nucleic acid analysis. Ideally, a method should have as few handling steps as possible and allow the use of a closed-tube assay format to reduce the risk of PCR contamination. Different homogeneous assay chemistries have been exploited to integrate amplification and detection to allow simple nucleic acid analysis with minimal post-PCR handling (1)(2)(3)(4)(5). Double-stranded DNA probes consisting of a 5′-terminus-labeled fluorescent strand and a complementary strand labeled on the 3′ terminus with a quencher have been exploited in homogeneous hybridization (2)(6)(7). Fluorescence signal is generated when the fluorophore strand hybridizes with the target. When the quencher strand hybridizes with the fluorophore strand, the signal from the fluorophore is quenched. Morrison et al. (6) used probes consisting of strands of equal length and a competitive hybridization technology, whereas others have exploited probes consisting of strands with different lengths for detection of PCR products (2)(7). The use of stable and fluorescent lanthanide chelates has enabled the development of homogeneous assay technologies based on time resolution (8). Time-resolved fluorescence-quenching assays (TR-FQAs), based on energy transfer from a lanthanide chelate to a nonfluorescent quencher, have been applied in various assays of hydrolyzing enzymes (9)(10) and are commercialized as TruPoint™. The first homogeneous PCR assays with lanthanide-labeled probes used an environmentally sensitive terbium chelate, the fluorescence intensity of which changes on probe hybridization (3)(11). Subsequently, the technology was further improved by use of additional quencher probes (12). Recently, a combination of quenching and competitive hybridization has been applied for end-point detection of PCR products (13). The aim of the present study was to compare two homogeneous PCR assay approaches based on a …
Germanium geochemistry in the Southern California Borderlands

Abstract Concentrations of Ge(OH) 4 (denoted as Ge i , or inorganic germanium) and Si(OH) 4 were measured in water column and pore water samples from San Pedro and San Nicolas Basins in the Southern California Borderlands. There is a characteristic linear relationship between Ge i and Si in the water column which implies that the distributions of germanium and silica are controlled by similar processes. In contrast, the pore water chemistry of germanium appears to differ from that of silica, particularly in the reducing, organic-rich sediments of San Pedro Basin. Silica concentrations in San Pedro Basin pore water asymptotically increase to 480 μM at 35–40 cm depth. Ge i concentrations in the topmost 2 cm of pore water from San Pedro Basin are an order of magnitude greater than bottom water concentrations. Below 2 cm, Ge i concentrations decrease exponentially with a half-distance of about 8 cm. Cycling of ferric oxyhydroxides at a redox boundary is the most likely cause of the Ge i enrichment in San Pedro Basin pore water, while authigenic pyrite formation with the concomitant inclusion of germanium is a probable, but undocumented, cause of the downcore decrease in Ge i . Pore water Ge i and silica concentrations in sediments of San Nicolas Basin are generally greater than bottom water concentrations but vary irregularly with depth, probably due to irrigation.
Asymmetric Catalytic Reductive Coupling of 1,3‐Enynes and Aromatic Aldehydes

Nickel-catalyzed reductive coupling reactions of 1,3-enynes and aromatic aldehydes efficiently afford conjugated dienols in excellent regioselectivity and modest enantioselectivity when conducted in the presence of catalytic amounts of a monodentate, P-chiral ferrocenyl phosphine ligand. 1-(Trimethylsilyl)-substituted enynes are shown to be effective coupling partners in these reactions, and the dienol products thus formed readily undergo protiodesilylation under mild conditions.
Guest Editors' introduction to the special section on statistical and computational issues in inverse problems

In the words of D D Jackson, the data of real-world inverse problems tend to be inaccurate, insufficient and inconsistent (1972 Geophys. J. R. Astron. Soc. 28 97‐110). In view of these features, the characterization of solution uncertainty is an essential aspect of the study of inverse problems. The development of computational technology, in particular of multiscale and adaptive methods and robust optimization algorithms, has combined with advances in statistical methods in recent years to create unprecedented opportunities to understand and explore the role of uncertainty in inversion. Following this introductory article, the special section contains 16 papers describing recent statistical and computational advances in a variety of inverse problem settings.
Left ventricular diastolic dysfunction as a predictor of the first diagnosed nonvalvular atrial fibrillation in 840 elderly men and women

Abstract Objectives The objective of this study was to determine whether diastolic dysfunction is associated with increased risk of nonvalvular atrial fibrillation (NVAF) in older adults with no history of atrial arrhythmia. Background Few data exist regarding the relationship between diastolic function and NVAF. Methods The clinical and echocardiographic characteristics of patients age ≥65 years who had an echocardiogram performed between 1990 and 1998 were reviewed. Exclusion criteria were history of atrial arrhythmia, stroke, valvular or congenital heart disease, or pacemaker implantation. Patients were followed up in their medical records to the last clinical visit or death for documentation of first AF. Results Of 840 patients (39% men; mean [± SD] age, 75 ± 7 years), 80 (9.5%) developed NVAF over a mean (± SD) follow-up of 4.1 ± 2.7 years. Abnormal relaxation, pseudonormal, and restrictive left ventricular diastolic filling were associated with hazard ratios of 3.33 (95% confidence interval [CI], 1.5 to 7.4; p = 0.003), 4.84 (95% CI, 2.05 to 11.4; p Conclusions The presence and severity of diastolic dysfunction are independently predictive of first documented NVAF in the elderly.
Population pharmacokinetic modeling of ephedrine, norephedrine and caffeine in healthy subjects

Objectives The combination of ephedrine (E) and caffeine (C) is used in herbal products for weight loss and athletic enhancement. We developed a population pharmacokinetics model (PPKM) describing E, C and the E metabolite norephedrine (NE). Methods The PPKM was developed using NONMEM based on the simultaneous modeling on plasma samples gathered from two clinical trials. Single-doses of pharmaceutical (pharm) C and E, herbal E + C and pharm E + C were given; 24 subjects contributed to a total of 379 E, 352 NE and 421 C concentrations. Results A one-compartment model with 1st order absorption described the E and C data. The rate of conversion of E to NE was non-linear and modeled according to: dNE/dt=V max E/(Km+E) − KeNE. (See Table) We detected a 34% increase in relative bioavailability (F=1.5) after the herbal vs. the pharmaceutical E administration (F=1). Simultaneous administration of C reduced E rate of absorption by 41%. Conclusions We successfully described the PK of E, and NE, the association of E with formulation and its interactions with C administration. A saturable process is involved in the metabolism of E to NE. The PK of E were different (increased apparent bioavailability) for the herbal supplement compared to the pharmaceutical one. Concomitant ingestion of C reduces E absorption rate. Clinical Pharmacology & Therapeutics (2004) 75, P39–P39; doi: 10.1016/j.clpt.2003.11.147 Table 1. Parameters Epharm CV% C CV% Parameters NE CV% Ke (L/min) 1.95−3 10 Vmax (μg/min) 1.92−4 10 CL (L/min) 0.069 16 Km (μg/L) 5.1 43 Vd (L) 315 18 38.6 20 Ke (1/min) 0.036 45 Ka (1/min) 0.033 63 0.064 50
Low Stress, High Reflectivity Thin Films for MEMS Mirrors

Au/Cr and Au/Ti films were deposited on Si (100) substrates using DC planar magnetron sputtering to assess residual stress in high reflectivity coatings. The dependence of stress on argon sputter pressure, component materials, and film thickness is discussed. Stress evolution as a function of thickness for individual Cr, Ti and Au films is also investigated to identify high-stress components of these two-layer coatings. Near-zero stress Au/Ti films were achieved with a particular set of sputtering parameters. Using the same process conditions, films were deposited onto pre-released MEMS mirrors having a number of different shapes and sizes. Optical interferometry demonstrates minimal change in the bow of 500, 250, and 125 µm diameter mirrors, consistent with a λ/40 flatness (λ = 1319 nm).
L-carnitine for anemia in hemodialysis patients: a last resort.

In this issue of the Clinical Journal of the American Society of Nephrology , Mercadal and colleagues address whether the biologically active form of carnitine, L - carnitine (LC), offers an adjuvant erythropoietic effect to patients with newly diagnosed ESRD undergoing maintenance hemodialysis ([1
Is rest or exercise hypertension a cause of a false-positive exercise test?

Study objectives To determine if a history ofhypertension or an exaggerated rise in exercise systolic BP isassociated with a false-positive exercise ECG. Design, setting, and patients Retrospective analysis of the associationsbetween exercise-induced ST-segment depression and a history ofhypertension, exercise systolic BP, and several other clinical andexercise test variables. Among 20,097 patients referred for exercisetomographic thallium imaging in a nuclear cardiology laboratory at atertiary care center, 1,873 patients met inclusion criteria for thisstudy, which included no history of myocardial infarction or coronaryartery revascularization, a normal resting ECG, and normal exercisethallium images. Results False-positive ST-segmentdepression occurred in 20% of the population. A history ofhypertension was actually associated with a lower likelihood of ST-segment depression (odds ratio, 0.70; 95% confidence interval[CI], 0.55 to 0.89; p = 0.004). A higher peak exercise systolic BPwas associated with a higher likelihood of ST-segment depression (oddsratio, 1.08 for each 10-mm Hg increase in systolic BP; 95% CI, 1.03 to1.14; p R 2 = 0.2%). For every 20-mm Hg increase inpeak exercise systolic BP, the percentage of patients with ST-segmentdepression increased by only 3%. Conclusions Inpatients with normal resting ECGs, we conclude the following: (1) ahistory of hypertension is not a cause of a false-positive exercisetest, and (2) higher exercise systolic BP is a significant but weakpredictor of ST-segment depression.
Measurement of the point spread function in the ocean

A new instrument to measure the point spread function (PSF) in the ocean is described. This instrument uses a CCD solid state camera to measure the angular radiance field due to a pulsed Lambertian source. In this way the PSF can be measured easily at sea, when precise alignments over ranges >10 m cannot be maintained. With the large dynamic range of the camera system, the PSF can be measured over short ranges (10 m), and the variation of the PSF with depth, or range, can be investigated.
Acute ST-Elevation Myocardial Infarction in Patients Hospitalized for Noncardiac Conditions

Background Major advances have been made in the treatment of ST-elevation myocardial infarction (STEMI) in outpatients. In contrast, little is known about outcomes in STEMI that occur in patients hospitalized for a noncardiac condition. Methods and Results This was a retrospective, single-center study of inpatient STEMIs from January 1, 2007, to July 31, 2011. Forty-eight cases were confirmed to be inpatient STEMIs of a total of 139 410 adult discharges. These patients were older and more often female and had higher rates of chronic kidney disease and prior cerebrovascular events compared with 227 patients with outpatient STEMIs treated during the same period. Onset of inpatient STEMI was heralded most frequently by a change in clinical status (60%) and less commonly by patient complaints (33%) or changes on telemetry. Coronary angiography and percutaneous coronary intervention were performed in 71% and 56% of patients, respectively. The median time to obtain ECG (41 [10, 600] versus 5 [2, 10] minutes; P <0.001), ECG to angiography time (91 [26, 209] versus 35 [25, 46] minutes; P <0.001) and ECG to first device activation (FDA) (129 [65, 25] versus 60 [47, 76] minutes; P <0.001) were longer for inpatient versus outpatient STEMI. Survival to discharge was lower for inpatient STEMI (60% versus 96%; P <0.001), and this difference persisted after adjusting for potential confounders. Conclusions Patients who develop a STEMI while hospitalized for a noncardiac condition are older and more often female, have more comorbidities, have longer ECG-to-FDA times, and are less likely to survive than patients with an outpatient STEMI.
Effect of atmospheric water vapor on modification of stable isotopes in near-surface snow on ice sheets

South Pole are used to simulate the d 18 O of near-surface snow as it evolves in time. The sensitivity of d 18 O of near-surface snow to wind speed, surface temperature, and accumulation rate is tested through model experiments. A steady wind of 5–10 m s �1 results in annual mean d 18 O enrichment of 3–7%. Enrichment of the heavy isotope occurs predominantly in buried winter snow layers during summer. However, in many simulations, there is a slight depletion of d 18 O summer layers that occurs as atmospheric water vapor is deposited within the snow during winter. Postdepositional modification of water stable isotopes in near-surface snow also depends on the snow accumulation rate; high accumulation rates quickly advect snow layers away from the influence of the atmosphere, preventing significant modification. Low accumulation rates (e.g., at Vostok and Dome C) allow significant postdepositional modification because the near-surface snow is exposed to forced ventilation for several annual cycles. Postdepositional modification during the Last Glacial Maximum (LGM) at Summit, Greenland is estimated to be greater than the present-day postdepositional modification. Therefore the temperature difference for LGM may be larger than that previously inferred from the d 18 O record. However, because of the compensating effects of lower temperatures and smaller accumulation during the LGM in Antarctica, the postdepositional enrichment in East Antarctica may be approximately the same for LGM as for the modern climate.
Tips on Tuning Each Device: Technical Pearls

Although the basic technique is relatively similar among the currently available left ventricular assist devices (LVAD), there are many subtle potential technical pitfalls for each device that could result in grave adverse events. In this article, the technical perils of the principal implantation technique and LVAD-related concomitant surgical procedures as well as of the implantation technique specific to currently available implantable LVADs, including HeartMate XVE, HeartMate II, HeartWare, and DuraHeart, are described.
Structural comparison and consumer choice

Psychological research has demonstrated important parallels between the structural alignment process involved in judgments of similarity and the processes that are involved in analogical reasoning. Gradually, this work on comparisons was applied to consumer choice. In this paper, we review the influence of structural alignment on choices among a set of options. Then, we discuss extensions of this work to comparative advertising and to the role of analogy in marketing communication. Finally, we discuss important extensions to structural alignment suggested by this work such as the key role that affect plays in comparisons made during the choice process.
Why the Psychological Experience of Respect Matters in Group Life: An Integrative Account

The psychological experience of respect has implications for the nature and quality of group life and for the individual's psychological and physical well-being. However, the manner in which respect has been studied and defined has frequently differed among researchers, making it difficult to connect the various findings. Whereas some researchers have focused on the implications of respectful treatment from group members (e.g., authorities, peers), others have focused on individuals’ perceptions of how they are generally evaluated by the group. We present the dual pathway model of respect in which these various lines of research are integrated within a single framework. Organized around two basic social motives – the need for status and the need to belong – the model describes two pathways (status evaluation and liking) through which respect from the group shapes social engagement, self-esteem, and health. These evaluative dimensions are informed by interactions with group authorities and peers and differentially predict social psychological outcomes.
A Study of Cyclone Mesoscale Structure with Emphasis on a Large-Amplitude Inertia–Gravity Wave

Abstract An analysis is presented of prominent mesoscale structure in a moderately intense cyclone with emphasis on a long-lived, large-amplitude inertia–gravity wave (IGW) that moved through the northeastern United States on 4 January 1994. Available National Weather Service WSR-88D Doppler radar and wind profiler observations are employed to illustrate the rich, time-dependent, three-dimensional structure of the IGW. As the IGW amplified [peak crest-to-trough pressure falls exceeded 13 hPa (30 min)−1], it also accelerated away from the cyclone, reaching a peak forward speed of 35–40 m s−1 across eastern New England. The IGW was one of three prominent mesoscale features associated with the cyclone, the others being a weak offshore precursor warm-frontal wave and an onshore band of heavy snow (“snow bomb”) in which peak hourly snowfalls of 10–15 cm were observed. None of these three prominent mesoscale features were well forecast by existing operational prediction models, particularly with regard to preci...
Empirical price modeling for sponsored search

We present a characterization of empirical price data from sponsored search auctions. We show that simple models drawing bid values independently from a fixed distribution can be tuned to match empirical data on average, but still fail to account for deviations observed in individual auctions. Hypothesizing that these deviations are due to strategic bidding, we define measures of "jamming" behavior and show that actual auctions exhibit significantly more jamming than predicted by such models. Correspondingly, removing the jamming bids from observed auction data yields a much closer fit. We demonstrate that this characterization is a revealing tool for analysis, using model parameter values and measures of jamming to summarize the effects of query modifers on a set of keyword auctions.
Limitations on contrast sensitivity and dynamic range imposed by human-eye response characteristics, film-density, and radiographic viewing conditions

Models for characterizing the signal-to-noise ratio for radiographic imaging systems typically ignore the human interface. In this work, images of a calibrated mammographic step wedge and a very low contrast paper step wedge were made with mammography film-screen systems and with direct x-ray exposures. Large and small density differences between adjacent steps were thus obtained over a wide range of film optical densities. Experienced viewers determined large-area threshold contrast sensitivity as a function of film density and viewbox luminance at constant low ambient illuminance with masking to exclude transmission of bright viewbox light through any area other than that portion of the step-wedge image being examined. Then, at high and low levels of viewbox luminance, threshold contrast sensitivity was determined at four different levels of ambient illuminance ranging from lower to higher than levels ordinarily used in clinical practice. threshold contrast sensitivity with and without masking was determined for viewing on a typical radiographic viewbox at a constant luminance level. The resulting data give strong qualitative support to the conclusion that viewing conditions (viewbox luminance, masking, and ambient illuminance) typically used in clinical practice are insufficient for optimum detection of the diagnostic information that can be recorded and displayed with modern mammography film-screen systems.
The neural correlates of speech motor sequence learning

Speech is perhaps the most sophisticated example of a species-wide movement capability in the animal kingdom, requiring split-second sequencing of approximately 100 muscles in the respiratory, laryngeal, and oral movement systems. Despite the unique role speech plays in human interaction and the debilitating impact of its disruption, little is known about the neural mechanisms underlying speech motor learning. Here, we studied the behavioral and neural correlates of learning new speech motor sequences. Participants repeatedly produced novel, meaningless syllables comprising illegal consonant clusters e.g., GVAZF over 2 days of practice. Following practice, participants produced the sequences with fewer errors and shorter durations, indicative of motor learning. Using fMRI, we compared brain activity during production of the learned illegal sequences and novel illegal sequences. Greater activity was noted during production of novel sequences in brain regions linked to non-speech motor sequence learning, including the BG and pre-SMA. Activity during novel sequence production was also greater in brain regions associated with learning and maintaining speech motor programs, including lateral premotor cortex, frontal operculum, and posterior superior temporal cortex. Measures of learning success correlated positively with activity in left frontal operculum and white matter integrity under left posterior superior temporal sulcus. These findings indicate speech motor sequence learning relies not only on brain areas involved generally in motor sequencing learning but also those associated with feedback-based speech motor learning. Furthermore, learning success is modulated by the integrity of structural connectivity between these motor and sensory brain regions.
Relationship between dental development and skeletal growth in modern humans and its implications for interpreting ontogeny in fossil hominins

Dental development and skeletal growth are central aspects used by anthropologists when investigating the ontogeny of a population or species. The interrelatedness of the two phenomena is often assumed to be high, but the nature of their relationship is obscured by the fact that they are both highly dependent upon chronological age. The exact relationship between the tempo of dental development and skeletal growth is unclear even in modern humans, which limits the ability to extrapolate to archaeological or fossil forms. It is clear that the influence of chronological age on these two aspects of ontogeny must be accounted for before examining their relationship to one another. This study tests whether dental development and skeletal growth are conditionally independent given age using known-age modern human skeletal samples and proportional odds logistic regression. The results suggest that dental development and skeletal growth are moderately correlated and thus not conditionally independent given age. That is, individuals that are dentally advanced relative to their peers also tend to be skeletally advanced. However, this relationship is moderate at best, so dental development does not appear to be a highly reliable proxy for skeletal growth, or vice versa, in modern humans. These findings have implications for the reconstruction of ontogeny and life history of fossil hominin taxa, since the pace of dental development is often used as a life history proxy. Implications of this study suggest that the proposed accelerated dental development in Pleistocene hominins was not necessarily accompanied by faster skeletal growth. Am J Phys Anthropol, 2013. © 2012 Wiley Periodicals, Inc.
Commentary to 'persistent renin-angiotensin system activation after anti-reflux surgery and its management'.

The authors present compelling work on a controversial topic: the pathogenesis of renal damage in patients with VUR. The authors propose that renal scarring in patients with VUR is mediated through RAS activation. They report a temporary decline in plasma renin activity following reflux surgery with further improvement in renal function which was maintained with the addition of an ACE-I. The authors recommend ACE-I ‘soon’ after surgery to prevent further renal injury but only have data for patients on medical therapy in the late postoperative period. Should one be surprised that following ACE-I administration an improvement in several renal parameters was seen knowing the renal protective effects of ACE-I in patients with renal dysfunction? Given the high preponderance of boys in the study group and the degree of renal dysfunction found during
The vertebral level of origin of spinal nerves in the rat

Abstract Several dissections were performed to determine the level of spinal cord termination and the vertebral level at which the dorsal and ventral roots of spinal nerves C1-S4 emerged from the spinal cord in the rat. These levels of emergence were then compared to the level of exit from the vertebral canal. The dissections demonstrated that the effect of differential growth between spinal cord and vertebral column begins in the lower cervical region and becomes progressively more pronounced throughout thoracic and lumbar levels. The disparity between the vertebral level of emergence of spinal roots from the spinal cord and their level of exit via intervertebral foramina was found to be considerably larger than was previously reported by Greene ('68). It was further noted that the spinal cord terminated at the level of the intervertebral disc between the third and fourth lumbar vertebrae, not between the fourth and fifth lumbar vertebrae as reported by Greene ('68).
Isolation of Cardiac Muscle Mitochondria: An Update

In cardiac muscle cells, mitochondria occupy about 40% of the total volume (Page and McCallister, 1973) and provide about 90% of the ATP required under normal aerobic conditions (Neely and Morgan, 1974). In addition to being the major source of ATP, mitochondria contain distinct Ca2+ influx and efflux systems (Carafoli, 1979), the role of which in cell function is still incompletely understood. The structure and function of mitochondria are known to be damaged in such disease conditions as myocardial ischemia (Jennings and Ganote, 1974; Rouslin, 1983; Rouslin and Millard, 1980, 1981; Sordahl and Stewart, 1980; Wood et al., 1979; Nagao et al., 1980) and heart failure (Lindenmayer et al., 1968, 1970, 1971; Lochner et al., 1968; Meerson et al., 1964; Rouslin et al., 1979; Schwartz and Lee, 1962; Wollenberger et al., 1963). A major thrust of research in this area has been the elucidation of mechanisms and factors responsible for mitochondrial damage and the design of pharmacological interventions to prevent cellular injury. In most of these studies, it is necessary to study the structure and function of mitochondria in vitro after isolation and purification.
Intelligent data analysis of human genetic data

The last two decades have witnessed impressive developments in the technology of genotyping and sequencing. Thousands of human DNA samples have been genotyped at increasing densities or sequenced in full using next generation DNA sequencing technology. The challenge is now to equip computational scientists with the right tools to go beyond mining genetic data to discover small gold nuggets and build models that can decipher the mechanism linking genotypes to phenotypes and can be used to identify subjects at risk for disease. We will discuss different approaches to model genetic data, and emphasize the need of blending a deep understanding of study design, with statistical modeling techniques and intelligent data approaches to make analysis feasible and results interpretable and useful.
Who receives a medical evaluation for infertility in the United States

Objective To investigate characteristics of receiving a medical evaluation for infertility among infertile women. Design Prospective cohort. Setting Academic institution. Patient(s) A total of 7,422 women who reported incident infertility between 1989 and 2009 in the Nurses' Health Study II. Intervention(s) None. Main Outcome Measure(s) Report of receiving a medical evaluation for infertility. Result(s) Approximately 65% of women who reported infertility had a medical evaluation for infertility. Infertile women who were parous (relative risk [RR] = 0.81, 95% confidence interval [CI] 0.78–0.84), older, current smokers (RR = 0.89, 95% CI 0.83–0.96), or who had a higher body mass index (BMI) were less likely to report receiving a medical infertility evaluation. Infertile women who exercised frequently, took multivitamins (RR = 1.03, 95% CI 1.00–1.07), lived in states with comprehensive insurance coverage (RR = 1.09, 95% CI 1.00–1.19), had a high household income, or who had a recent physical examination (RR = 1.15, 95% CI 1.06–1.24) were more likely to report receiving a medical infertility evaluation. Conclusion(s) These findings highlight demographic, lifestyle, and access barriers to receiving medical infertility care. Historically, the discussion of barriers to infertility care has centered on financial access, geographic access, and socioeconomic status. Our findings build off literature by supporting previously reported associations and showcasing the importance of demographic and lifestyle factors in accessing care.
The Role of n-Alkane Solvent Carbon Number on the Gelation of Long-Chained n-Alkanes in Solution

Crystallization and subsequent gelation of n-alkanes in subsea oil pipelines is an issue of great economic importance to the petroleum industry. To develop better wax remediation strategies, it is of interest to gain a better understanding of how n-alkanes crystallize in gel in solution. In this work, the role of the solvent on gelation properties was explored. Model oil solutions containing one or two long-chain n-alkanes (carbon numbers of 28, 32, and 36) solutes were dissolved at varying wax fractions in short-chain n-alkanes (carbon numbers of 7, 10, 12, and 16). The cloud points, gel points, and pour points were measured for these solutions. Results showed that all of the cloud points could be condensed into one relationship using only the mole fraction of the least-soluble solute, a result of the solutions all following ideal solution theory. Rheometric results were consistent for samples where the solvent was decane or dodecane. However, hexadecane samples provided results that were much different,...
Independent Selection of Multiple Mechanisms for Pyrethroid Resistance in Guatemalan Anopheles albimanus (Diptera: Culicidae)

Isofemale lines were established containing either, both, or neither of the elevated esterase and oxidase resistance mechanisms conferring pyrethroid resistance in a Guatemalan strain of Anopheles albimanus (Wiedemann). Plots of esterase and oxidase levels for individual mosquitoes from these single families correlated with data obtained using oxidase and esterase synergists in bioassays run in the bottle format. Mixed populations of pyrethroid-resistant A. albimanus adult females were selected using DDT, permethrin, or malathion; and the esterase and oxidase levels of the individual progeny were plotted. These data showed that the 3 classes of insecticide selected the 2 mechanisms differently. These results are discussed in terms of the problem of multiresistance surveillance in the field, especially concerning pyrethroid insecticides and the interaction of agricultural and public health insecticide application.
Abstract 4437: HSA coated iron oxide nanoparticle as a drug delivery vehicle for cancer therapy

An on-going effort in the field of nanomedicine is to develop nanoplatforms with both imaging and therapeutic functions, the so-called “nano-theranostics”. We have previously developed a human serum albumin (HSA) coated iron oxide nanoparticle (HINP) formula and used multiple imaging modalities to validate its tumor targeting attributes. In the current study, we sought to impart doxorubicin (Dox) onto the HINPs and to assess the potential of the conjugates as theranostic agents. In a typical preparation, we found that about 0.5 mg of Dox and 1 mg of iron oxide nanoparticles (IONPs, Fe content) could be loaded into 10 mg of HSA matrices. The resulting Dox-loaded HINPs (D-HINPs) retained a tumor targeting capability, as manifested by both in vivo MRI and ex vivo immunostaining studies. For therapeutic studies, 25 4T1 tumor mice were divided into 5 groups (5 mice/group), and were treated with 1) D-HINPs (3 mg Dox/kg); 2) free Dox (3 mg Dox/kg); 3) Doxil (3 mg Dox/kg); 4) HINPs and 5) PBS. For Group 4, HINPs were injected at the same Fe concentration as in Group 1. The drugs (including controls) were given every other day for a total of 4 doses. A dramatic increase in tumor volume was found in the PBS control group. The group injected with HINPs manifested a tumor growth pattern that was similar to the PBS group and showed no weight loss throughout the treatment, indicating that the HINPs alone had neither therapeutic nor toxic effects in the studied mice. Compared with the control group, the injection of Dox led to some tumor suppression in the first week of treatment but gradually lost efficacy. D-HINPs showed a striking tumor suppression effect that was comparable to Doxil and that greatly outperformed free Dox. Such a strategy can be readily extended to load other types of small molecules, making HINP a promising theranostic nanoplatform. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4437. doi:10.1158/1538-7445.AM2011-4437
The benefits of improved covariance estimation

Recent advances in covariance estimation can improve portfolio formation strategies aimed at avoiding high risk market environments. We consider a covariance specification with information variables that include both historical firm specific variables and an ex ante measure of macro volatility (CBOE VIX). We compare the in-sample and predictive out-of-sample performance of the information instrument model relative to three alternative approaches. Out-of-sample, a risk-on, risk-off strategy that optimally weights the global minimum variance (GMV) portfolio and a riskless asset shows the information instrument model provides effective exit signals during the financial crisis and other high risk environments.
Toward Comprehensive Security

The practitioners of Pakistan’s national security policy have been guilty in the past of pursuing a partial rather than a comprehensive approach. This unidimensional and military-dominated approach to national security has been the main source of many of the flaws in the country’s foreign policy and the primary cause of its internal and external problems. Pakistan’s policy makers must adopt a comprehensive approach to the handling of national security issues placing adequate emphasis on its political, economic, diplomatic, and military dimensions. This would be made possible by creating a national security mechanism directly under the prime minister with the responsibility of obtaining inputs from relevant ministries and departments and synthesizing them into viable security policy options for consideration by the government.
Potential for Sulfoxaflor to Improve Conservation Biological Control of Aphis glycines (Hemiptera: Aphididae) in Soybean

Soybean aphid, Aphis glycines Matsumura, is one of the most important insect pests of soybean in the north central United States. Management of A. glycines currently relies on applications of broad-spectrum insecticides. However, broad-spectrum insecticides can negatively impact the natural enemies associated with aphids. Selective insecticides, on the other hand, are promising control tactics for reducing the negative impact of insecticide applications. Here, we compared the effects of sulfoxaflor (a new selective insecticide) and broad-spectrum insecticides on A. glycines and predators in a two-year field experiment. We sampled A. glycines and aphid predator populations using visual whole-plant inspection. In addition, sweep-net sampling was performed to monitor predator populations. To evaluate the toxicity of the insecticides on predator populations, laboratory bioassays were performed on Hippodamia convergens Guerin-Meneville, Orius insidiosus (Say), and Chrysoperla rufilabris (Burmeister). Field results showed that sulfoxaflor was as effective as the broad-spectrum insecticide in suppressing soybean aphid populations and was less impactful on predator populations. The laboratory bioassays showed that sulfoxaflor was moderately harmful to O. insidiosus, harmless to slightly harmful to H. convergens, and harmless to C. rufilabris These studies suggest that sulfoxaflor holds promise for improving integration of chemical and biological controls for A. glycines management.
Cefamandole kinetics in uremic patients undergoing hemodialysis

A single intravenous 15 mg/kg dose of cefamandole was given to 6 patients in chronic renal failure before hemodialysis, and 3 were examined during an interdialysis period. Mean cefamandole clearance by hemodialysis was 24 +/- 12 ml/min; 35 +/- 15% of the dose was recovered in the dialysate. The cefamandole half-life (1 1/2) on dialysis was 4.0 +/- 0.29 hr; off dialysis it was 13.9 +/- 4.2 hr. High urine concentrations of cefamandole in these patients suggests usefulness in urinary tract infection.
Development and initial psychometric assessment of the Childhood Religious Experience Inventory – Primary Caregiver

Abstract Childhood religious experiences with primary caregivers are instrumental in the development of religiosity. However, the ways that primary caregivers influence these experiences have not been properly operationalized and measured. We addressed this limitation by developing the Childhood Religious Experiences Inventory – Primary Caregiver (CREI-PC). An act nomination procedure (Study 1, n = 201) resulted in 120 items describing specific things a primary caregiver said to, did to, or did with, a participant during their childhood. In Study 2 (n = 497), participants indicated how frequently each item occurred in their childhood. Principal Component Analysis yielded 16 items loading on four components: Assurance; Disapproval and Punishment; Social Involvement, and Encouraged Skepticism. The CREI-PC allows researchers to quantify primary caregiver influence on childhood religious experiences, enabling future investigation of whether and how these influences predict adult religiosity.
CHARSTAR: Clock Hierarchy Aware Resource Scaling in Tiled ARchitectures

High-performance architectures are over-provisioned with resources to extract the maximum achievable performance out of applications. Two sources of avoidable power dissipation are the leakage power from underutilized resources, along with clock power from the clock hierarchy that feeds these resources. Most reconfiguration mechanisms either focus solely on power gating execution resources alone or in addition, simply turn off the immediate clock tree segment which supplied the clock to those resources. These proposals neither attempt to gate further up the clock hierarchy nor do they involve the clock hierarchy in influencing the reconfiguration decisions. The primary contribution of CHARSTAR is optimizing reconfiguration mechanisms to become clock hierarchy aware. Resource gating decisions are cognizant of the power consumed by each node in the clock hierarchy and additionally, entire branches of the clock tree are greedily shut down whenever possible.The CHARSTAR design is further optimized for balanced spatio-temporal reconfiguration and also enables efficient joint control of resource and frequency scaling. The proposal is implemented by leveraging the inherent advantages of spatial architectures, utilizing a control mechanism driven by a lightweight offline trained neural predictor. CHARSTAR, when deployed on the CRIB tiled microarchitecture, improves processor energy efficiency by 20-25%, with efficiency improvements of roughly 2x in comparison to a naive power gating mechanism. Alternatively, it improves performance by 10-20% under varying power and energy constraints.
Treatment disparities in the management of epistaxis in United States emergency departments.

Objectives There is limited data on epistaxis presentation and management patterns in U.S. emergency departments (EDs). We aim to characterize patients who present to the ED with epistaxis and identify factors associated with nasal-packing use. Study Design Retrospective review of Nationwide Emergency Department Sample (NEDS) from 2009 to 2011. Methods NEDS was queried for patient visits with a primary diagnosis of epistaxis (International Classification of Diseases, Ninth Revision, Clinical Modification code 784.7). Patient demographics, comorbidities, and hospital characteristics were obtained. Predictors of nasal packing were determined by multivariable logistic regression. Results There were 1,234,267 ED visits for epistaxis. The highest proportion of patients were seen in the winter (37.2%) at nontrauma hospitals (76.9%), and were discharged home (95.5%). Fifteen percent of patients were on long-term anticoagulation, 33% had hypertension, and 0.9% had a coagulopathy. Nasal packing was utilized in 243,268 patients (19.7%). Predictors strongly associated with nasal packing included lower socioeconomic quartile (odds ratio [OR] 1.30, 95% confidence interval [CI] = 1.10–1.53), hospital located in the geographic South (OR 1.62, CI = 1.12–2.34) and Midwest (OR 1.85, P < 0.0001), and nontrauma hospital (OR 1.56, CI = 1.19–2.05). Other factors included long-term anticoagulation (OR 1.21, CI = 1.10–1.33), winter season (OR 1.20, CI = 1.12–1.23), male gender (OR 1.14, CI = 1.10–1.17), and older age (OR 1.01, CI = 1.01–1.02). Mean ED charge was greater for patients who were packed ($1,473 vs. $1,048, P < 0.0001). Conclusion Several factors, including lower socioeconomic status, geographic location, and nontrauma hospital designation, predict use of nasal packing. These results raise concerns about potential treatment disparities that may result in increased patient morbidity and costs. Level of Evidence 2C. Laryngoscope, 128:356–362, 2018