cssi/SciSciGPT-SciSciNet huggingface dataset:
Sorbinil suppresses glomerular prostaglandin production in the streptozotocin diabetic rat.

Abstract Previous studies have suggested a link between hyperfiltration and enhanced polyol pathway activity in the streptozotocin diabetic rat. In the present study we examined the relationship between glomerular sorbitol content, a measure of polyol pathway activity and glomerular filtration rate (GFR), as a function of plasma glucose and time after induction of diabetes. GFR is increased by 1 to 2 weeks in the untreated streptozotocin diabetic rat but falls to values equal to or below control by 2 months. Treatment of diabetic rats with a low dose of insulin to achieve moderate hyperglycemia results in the maintenance of elevated GFR for 2 months. Glomerular sorbitol content in the 1- to 2-week diabetic rats was not significantly different from values in glomeruli from control rats at 1 to 2 weeks but was 11-fold higher than control by 2 months in the untreated diabetic rat. Treatment of diabetic rats with insulin to achieve moderate hyperglycemia resulted in values for glomerular sorbitol content that were not different from control. Thus, elevated GFR was not associated with elevated glomerular sorbitol content in the 1- to 2-week diabetic rat and was dissociated from elevated glomerular sorbitol content in the 2-month diabetic rat. Treatment of 1- to 2-week diabetic rats with sorbinil prevented the rise in GFR observed at this time despite the fact that sorbitol content of glomeruli was not elevated. These results suggested that sorbinil was reducing GFR in the diabetic rat by a mechanism other than aldose-reductase inhibition. The synthesis of vasodilatory prostaglandins by isolated glomeruli and the activity of phospholipase A 2 in the particulate cell fraction of glomerular homogenates is higher in 1- to 2-week diabetic rats compared with controls, a finding that may contribute to the elevated GFR in these rats. Treatment of 1- to 2-week diabetic rats with sorbinil prevented the increase in glomerular prostaglandin production and phospholipase A 2 activity of the particulate cell fraction. Sorbinil had no effect on these parameters in control rats. Moreover, sorbinil had no effect on prostaglandin synthesis or phospholipase A 2 activity when added in vitro. The results confirm the observation that sorbinil treatment reduces GFR in the 1- to 2-week diabetic rat but suggest that this action of sorbinil may be mediated by a reduction in glomerular synthesis of vasodilatory prostaglandins rather than by suppression of aldose-reductase activity. However, the role of prostaglandins in the mediation of hyperfiltration remains to be fully delineated, and factors other than prostaglandins may be involved in the reduction of GFR induced by sorbinil.
PALLIATIVE RADIATION THERAPY IN PATIENTS WITH CANCER OF THE COLON AND RECTUM.

Radiation therapy given expertly and in moderate tumor-dose courses is recommended for the control of symptoms in patients with nonresectable cancer of the colon and rectum. In this review of 165 patients undergoing palliative radiation therapy, more than 50 percent had definite symptomatic and objective response. Over 80 percent of patients with localized disease, particularly intrapelvic, received significant palliation.
Phage Lambda Mutants Deficient in rII Exclusion

The lambda gene responsible for rIIexclusion is distinct from other lambda genes and lies between the N and CI genes on the genetic map.
Analysis of temperature-dependent birefringence of a polarization-maintaining photonic crystal fiber

We have analyzed the temperature-dependent birefringence of a polarization-maintaining photonic crystal fiber. The temperature-coefficient of birefringence, dB/dT, for a commercially available polarization-maintaining photonic crystal fiber was found to be approximately −2.0×10−9 K−1. This is 35 times smaller than that of a standard polarization-maintaining fiber, which was approximately −7.0×10−8 K−1. Based on numerical analysis of the fiber structures, we determined that the temperature-dependence of the birefringence of the polarization-maintaining photonic crystal fiber is mainly due to a combination of temperature-dependent structure and index change. Due to thermal expansion of the silica, the photonic crystal structure of the fiber deforms, resulting in the shifting of the photonic band gap, which results in the birefringence change. Temperature-dependent refractive index change of the silica also causes a shift in the photonic band gap and thus a birefringence change. The numerically calculated dB/dT of the photonic crystal fiber was found to be approximately (−4±2)×10−9 K−1, and is in excellent agreement with the experimental results.
A Fluorogenic, Small Molecule Reporter for Mammalian Phospholipase C Isozymes

Phospholipase C isozymes (PLCs) catalyze the conversion of the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP(2)) into two second messengers, inositol 1,4,5-trisphosphate and diacylglycerol. This family of enzymes are key signaling proteins that regulate the physiological responses of many extracellular stimuli such as hormones, neurotransmitters, and growth factors. Aberrant regulation of PLCs has been implicated in various diseases including cancer and Alzheimer's disease. How, when, and where PLCs are activated under different cellular contexts are still largely unknown. We have developed a fluorogenic PLC reporter, WH-15, that can be cleaved in a cascade reaction to generate fluorescent 6-aminoquinoline. When applied in enzymatic assays with either pure PLCs or cell lysates, this reporter displays more than a 20-fold fluorescence enhancement in response to PLC activity. Under assay conditions, WH-15 has comparable K(m) and V(max) with the endogenous PIP(2). This novel reporter will likely find broad applications that vary from imaging PLC activity in live cells to high-throughput screening of PLC inhibitors.
The Way We See It: Surgeons' Perceptions of Perioperative Events

Abstract Objectives: The objective of this study was to examine gynecologic (GYN) surgeons' perceptions of perioperative events and their severity. Secondarily, differences in perceptions between surgeons performing elective and nonelective surgery were compared. Design: Fifty-seven perioperative scenarios associated with GYN surgery were created. The scenarios were grouped into 16 broader categories (e.g., vascular injury, neuropathy). Scenarios were electronically distributed to GYN surgeons from geographically diverse areas, and surgeons classified each scenario as either a complication or a routine perioperative event. Surgeons rated complication severity using both a numerical rating scale (1–100) and the Clavien–Dindo scale (I–V). Study participants were divided into two groups based on whether they performed elective or nonelective surgeries. Materials and Methods: PASW® version 18 was used to calculate means, standard deviations, intraclass correlation coefficients (ICC), and coefficients of varia...
‘Towards the New Authoritarianism’: Giving Section 2 Powers to the Police

In this paper, the author traces the historical evolution of the use of methods by the police and the executive to undermine the protective effects of the right to silence. He argues that the introduction of greater protections for accused persons in the provisions of the Police and Criminal Evidence Act 1984 has resulted in an increase in costs of the administration of summary jurisdiction with the commensurate reduction in the numbers of persons being convicted. Hence political initiatives are being undertaken to find an effective way to remove the effects of the right to silence, contained in these protections. He examines the effects of the so‐called s. 2 powers to compel answers to questions, possessed by the Serious Fraud Office (SFO). The paper ends by examining the proposals in the recent Report of the Royal Commission on Criminal Justice and argues that the recommendation to extend the exercise of s. 2 powers to the police is merely another step towards the introduction of an increasingly authoritarian regime of criminal justice.
Optimum sampling in spatial-temporally correlated wireless sensor networks

The optimum sampling in the one- and two-dimensional (1-D and 2-D) wireless sensor networks (WSNs) with spatial-temporally correlated data is studied in this article. The impacts of the node density in the space domain, the sampling rate in the time domain, and the space-time data correlation on the network performance are investigated asymptotically by considering a large network with infinite area but finite node density and finite temporal sampling rate, under the constraint of fixed power per unit area. The impact of space-time sampling on network performances is investigated in two cases. The first case studies the estimations of the space-time samples collected by the sensors, and the samples are discrete in both the space and time domains. The second case estimates an arbitrary data point on the space-time hyperplane by interpolating the discrete samples collected by the sensors. Optimum space-time sampling is obtained by minimizing the mean square error distortion at the network fusion center. The interactions among the various network parameters, such as spatial node density, temporal sampling rate, measurement noise, channel fading, and their impacts on the system performance are quantitatively identified with analytical and numerical studies.
Treatment of depression for patients with multiple sclerosis in neurology clinics.

The objective of this study was to examine the adequacy of antidepressant pharmacotherapy in a sample of patients with multiple sclerosis (MS) treated by neurologists.Methods MS patients under the care of neurologists were recruited from a large health maintenance organization. Major depressive disorder (MDD) was diagnosed using a structured telephone interview. Antidepressant treatment data were obtained from the HMO pharmacy database.Results Study participants included 260 patients with MS treated by 35 neurologists. A total of 67 (25.8%) patients met the criteria for MDD. Among the patients with MDD, 65.6% received no antidepressant medication, 4.7% received subthreshold doses from their neurologists, 26.6% received doses at threshold, and 3.1% received doses exceeding threshold.Discussion Depression was undertreated by the neurologists treating this sample of patients with comorbid MS and MDD. Potential solutions are discussed.
Beam loss studies in high-intensity heavy-ion linacs

A low beam-loss budget is an essential requirement for high-intensity machines and represents one of their major design challenges. In a high-intensity heavy-ion machine, losses are required to be below 1 W/m for hands-onmaintenance. The driver linac of the Rare Isotope Accelerator (RIA) is designed to accelerate beams of any ion to energies from 400 MeV per nucleon for uranium up to 950 MeV for protons with a beam power of up to 400 kW. The high intensity of the heaviest ions is achieved by acceleration of multiple-charge-state beams, which requires a careful beam dynamics optimization to minimize effective emittance growth and beam halo formation. For beam loss simulation purposes, large number of particles must be tracked through the linac. Therefore the computer code TRACK [1] has been parallelized. Calculations are being performed on the JAZZ cluster [2] recently inaugurated at ANL. This paper discusses how this powerful tool is being used for simulations for the RIA project to help decide on the highperformance and cost-effective design of the driver linac.
Some Basic Concepts from Population Genetics

The study of allele frequencies and how they vary over time and over geographic regions has led to many discoveries concerning evolutionary history, migration, gene flow, and the correlation between allele frequencies and disease rates across populations. This chapter covers only a few concepts from population genetics, emphasizing those most relevant to gene mapping: allele frequency estimation, population substructure, Hardy-Weinberg Equilibrium (HWE) and Disequilibrium (HWD), which are frequently used in the analysis of genetic data. Other concepts, e.g., Linkage Disequilibrium and Linkage Equilibrium, will be introduced in later chapters as the need arises.
Saddam Hussein and the Impartiality Deficit in International Criminal Justice

This article examines - in light of what here is called an impartiality deficit critique - the tribunal that is now scheduled to begin trial of deposed Iraqi President Saddam Hussein and his associates on October 19, 2005. The term is derived from democracy deficit, the label by which multilateral institutions are faulted for lack of accountability mechanisms common in modern constitutional states. Critics have extended that latter notion to a centerpiece of the international criminal justice project, the permanent International Criminal Court that began operations in 2002. In contrast, the impartiality deficit critique assumes the propriety of establishing international criminal justice mechanisms. In the hope of improving the quality of those mechanisms, it exposes instances in which defendants were denied any component of this injunction of the International Covenant on Civil and Political Rights: In the determination of any criminal charge against him, ... everyone shall be entitled to a fair and public hearing by a competent, independent and impartial tribunal established by law. Within this analysis, one might examine several tribunals to see whether they meet a single fairness criterion, such as the duty of judges to act without bias; alternatively, one might assess a single tribunal in light of several criteria. This article opts for the latter course, applying the impartiality deficit critique to the Iraqi High Criminal Court, which stands poised to try persons charged with responsibility for torture, killings, and other crimes of repression over a thirty-five-year period. The article first lays out key concerns of the impartiality deficit critique and then evaluates the Court in light of them. It shows that initial implementation occurred in a manner so devoid of basic guarantees that there seemed little likelihood that the accused would receive either the appearance or reality of a fair trial.
Influence of Temperature and Material Deposit on Material Removal Uniformity during Optical Pad Polishing

The effects of temperature and material deposit on workpiece material removal spatial uniformity during optical pad polishing are described. Round and square-fused silica workpieces (25–265 mm in size) were polished on a polyurethane pad using ceria slurry under various conditions. Using a nonrotated workpiece on a rotating lap, elevated temperatures (as measured by IR imaging), due to frictional heating at the workpiece–lap interface, were observed having a largely radial symmetric profile (relative to the lap center) on both the workpiece and lap with a peak temperature corresponding to the workpiece center. A 3D steady-state thermal model of the polishing process, which accounts for the frictional heating and effective heat transfer from various surfaces, quantitatively describes the observed thermal profiles. The temperature spatial uniformity, which affects the material removal spatial uniformity, can be significantly improved using a rotated workpiece and a specially designed compensating septum during polishing. Next, using a rotating workpiece and lap, the workpiece surface develops two types of mid-range structure: (1) fine ripples (sub-mm scale length) that run circumferentially with respect to the lap, which have been attributed to microscopic islands of slurry on the lap leading to radial material removal nonuniformities; and (2) a center depression (cm scale length) which has been attributed to nonlinear slurry & glass products buildup at a specific radial lap location. A polishing simulator model (called Surface Figure or SurF), which accounts for workpiece wear, pad wear, and now deposition on the pad, correctly simulates the preferential material deposit on the pad and the center depression structure developed on the workpiece. Strategies, such as time averaging through kinematics and diamond conditioning, for preventing both these nonuniformities are demonstrated.
Transportation of phytopathogenic fungi by the bark beetle Ips sexdentatus boerner and associated mites

The bark beetle Ips sexdentatus carries several types of conidiospores and ascopores in the pronotal punctures located around the setae on the sides of the pronotum. For swarming beetles, some of the spores seem to be germinating. Nine species of mites were phoretic on swarming Ips sexdentatus in France. Hypophoretic on these mites were 16 morphologically distinct types of fungal ascopores and conidia, but lesser kinds of spore types were seen on the beetles. Although the spores seemed to stick anywhere on the mites, masses of spores were concentrated in punctures on the sides of the beetle pronota. Ascospores of Ophiostoma brunneo-ciliatum were the most common ascospores both on the mites and the beetle, but ascospores of the potentially pathogenic O. minus were present on five mite species. Resume Mode de transport de champignons phytopathogenes associes au Scolyte Ips sexdentatus Boerner et a ses acariens phoretiques Le Scolyte Ips sexdentatus peut le plus souvent transporter divers types de conidiospores et d'ascospores dans les depressions cuticulaires entourant les soies des faces laterales du pronotum. Chez plusieurs esaimants, certaines spores etaient en phase de germination. 9 especes d'Acariens phoretiques ont ete localisees sur des I. sexdentatus essaimants. Seize types d'ascospores et de conidies morphologiquement differentes leur sont associees. Bien que ces spores semblent pouvoir se coller n'importe ou sur l'Acarien, les masses principales sont localisees dans les depressions cuticulaires laterales du pronotum. Les ascospores d'Ophiostoma brunneo-ciliatum paraissent les plus frequentes tant sur le Scolyte que sur les Acariens et celles des champignons potentiellement pathogenes Ophiostoma minus sont fixees sur 5 especes d'Acariens. Le Scolyte Ips sexdentatus peut le plus souvent transporter divers types de conidiospores et d'ascopores dans les depressions entourant les voies des faces laterales du pronotum. Zusammenfassung Zur Ubertragung phytopathogener Pilze durch den Borkenkafer Ips sexdentatus Boerner und durch assoziierte Milben Ips sexdentatus tragt mehrere Konidio- und Ascosporen verschiedener Pilze in der Punktierung des Pronotums, die an der seitlichen Pronotumbeborstung lokalisiert ist. Bei schwarmenden Kafern scheinen einige Sporen auszukeimen. Auf schwarmenden I. sexdentatus konnten in Frankreich 9 phoretische Milbenarten festgestellt werden. Auf diesen Milben konnten die Asco- und Konidiosporen von 16 morphologisch verschiedenen, hyperphoretischen Pilzen festgestellt werden; auf den Kafern selbst wurden jedoch weniger Sporen gefunden. Obwohl die Sporen offensichtlich uberall auf den Milben vorhanden sind, waren bei den Kafern grosere Sporenmengen in der Punktierung des seitlichen Pronotums vorhanden. Die Ascosporen von Ophiostoma brunneo-ciliatum waren die haufigsten Ascosporen, sowohl bei den Kafern als auch bei den Milben. Dagegen konnten die Ascosporen des potentiell pathogenen Pilzes O. minus an 5 Milbenarten festgestellt werden.
Association of Smoking, Sleep Apnea, and Plasma Alkalosis With Nocturnal Ventricular Arrhythmias in Men With Systolic Heart Failure

Background Excess sudden death due to ventricular tachyarrhythmias remains a major mode of mortality in patients with systolic heart failure. The aim of this study was to determine the association of nocturnal ventricular arrhythmias in patients with low ejection fraction heart failure. We incorporated a large number of known pathophysiologic triggers to identify potential targets for therapy to reduce the persistently high incidence of sudden death in this population despite contemporary treatment. Methods Eighty-six ambulatory male patients with stable low (≤ 45%) ejection fraction heart failure underwent full-night attendant polysomnography and simultaneous Holter recordings. Patients were divided into groups according to the presence or absence of couplets (paired premature ventricular excitations) and ventricular tachycardia (VT) (at least three consecutive premature ventricular excitations) during sleep. Results In multiple regression analysis, four variables (current smoking status, increased number of arousals, plasma alkalinity, and old age) were associated with VT and two variables (apnea-hypopnea index and low right ventricular ejection fraction) were associated with couplets during sleep. Conclusions We speculate that cessation of smoking, effective treatment of sleep apnea, and plasma alkalosis could collectively decrease the incidence of nocturnal ventricular tachyarrhythmias and the consequent risk of sudden death, which remains high despite the use of β blockades.
Wireless passive sensor development for harsh environment applications

Three researchers at University of Central Florida from electrical engineering, materials science, and mechanical engineering teamed together to develop high-temperature (> 1000°C) sensors for various harsh environment applications such as combustion turbines. In this paper, we will provide an overview of the recent progress in the development of sensing materials, sensor fabrication methods, and wireless sensing techniques.
Molecular mechanisms of platelet-tumor cell adhesion under flow

The ability of tumor cells to interact with platelets constitutes an indispensable determinant in the success of metastatic spread. This study was undertaken to investigate the sequence of molecular events mediating human colon (LS174T) carcinoma cell adhesion to surface adherent platelets under flow. A two-step process of tumor cell recruitment has been elucidated, involving LS174T tethering mediated primarily by platelet P-selectin, and subsequent arrest via platelet /spl alpha//sub IIb//spl beta//sub 3/. This cascade of events depicts an efficacious process for colon carcinoma arrest at sites of vascular injury.
Poultry progress in Nigeria.

(1967). Poultry Progress in Nigeria. World's Poultry Science Journal: Vol. 23, No. 3, pp. 234-236.
Engaging Freshmen Through Advisor Seminars

A little more than a decade ago, MIT initiated a program of Freshman Advisor Seminars (FAS) in response to the need for improved academic advising and intellectual diversity in the freshman year. FAS build on a “very small group” learning model by bringing eight advisees together with an advisor (normally a faculty member) and an upperclass associate advisor for a weekly, informal seminar on one of a wide variety of leader-chosen topics. FAS have become the dominant mode of first year advising at MIT, with approximately 90% of the freshman class enrolled in 135 different seminars during the 1996-97 Academic Year. This paper introduces the MIT FAS program, sets forth its origins and its goals, and presents a case study of its implementation within one MIT academic department. Some lessons learned are extracted from the study.
Potassic Diagenesis of Cambrian Sandstones and Precambrian Granitic Basement in UPH-3 Deep Hole, Upper Mississippi Valley, U.S.A.

ABSTRACT The Mt. Simon Sandstone (Cambrian) in core from Hole UPH-3 in northwestern Illinois contains three distinct diagenetic zones. A zone with K-feldspar overgrowths characterizes the upper 51 m of Mt. Simon Sandstone. An intermediate, underlying sericite zone is about 126 m thick, and a lowermost feldspar zone is about 87 m thick. Authigenic K-feldspar in the Mt. Simon Sandstone occurs in several modes: overgrowths, rhombs, penetration-twinned crystals, chert-like aggregates surrounded by coarser K-feldspar, mosaics of anhedral to euhedral crystals, and as replacements of microcline. Sericite (I/S) occurs as pore-filling aggregates of minute flakes. Quartz overgrowths are common throughout these three diagenetic zones. K-feldspar was the first to form, closely followed by quartz, then by ericite, and lastly, possibly by a second addition of quartz overgrowth. The upper 6.1 m of Precambrian granite gneiss basement exhibits similar potassic alteration to the overlying Mt. Simon Sandstone. The uppermost 2.5 m of the basement rock is a probable weathering profile in which pedogenic clays were replaced by sericite (I/S) and chlorite. Sericite in the basement rock was likely formed during the same episode as in the Mt. Simon Sandstone, based on 18O values. Authigenic K-feldspar occurs as pore-fillings, overgrowths, replacements of microcline, and intergrown with phyllosilicate. Below the profile it partially replaces plagioclase. Similar potassic alteration of the Mt. Simon Sandstone of UPH-3 occurs in cores of both UPH-1 and 2, indicating a lateral extent of about 7 km. A K/Ar date of 394.6 ± 6 Ma was obtained from authigenic K-feldspar of the basal Mt. Simon Sandstone. This Early Devonian age is within the range of ages from authigenic K-feldspar in Ordovician tuffs of the Upper Mississippi Valley, suggesting that the K-feldspar is the product of a single, regional diagenetic event. K/Ar dates of 271.3 ± 4.6 Ma, 254.4 ± 4.6 Ma, and 214.1 ± 4.6 Ma were obtained from authigenic sericite of the Mt. Simon Sandstone. The Devonian age for the K-feldspar and Permian ages for the sericite are nearly coeval with times of uplift of the Findlay and Pascola Arches respectively. These diagenet c episodes are attributed to regional migration of basinal brines caused by groundwater recharge on these uplifted arches. Potassium for both the K-feldspar and sericite possibly came from the Michigan and Illinois basins, respectively. Devonian and Permian dates for potassic diagenesis possibly coincide with two episodes of Pb-leaching of basement rocks at 400 Ma and 260 Ma. Thus the potassic fluids may have leached Pb and Zn from Precambrian basement, particulary paleosols, and then formed Upper Mississippi Valley Pb-Zn deposits.
Interaction of MutS and Vsr: Some Dominant-Negative mutS Mutations That Disable Methyladenine-Directed Mismatch Repair Are Active in Very-Short-Patch Repair

In Escherichia coli and related bacteria, the very-short-patch (VSP) repair pathway uses an endonuclease, Vsr, to correct T · G mismatches that result from the deamination of 5-methylcytosines in DNA to C · G. The products of mutS and mutL, which are required for adenine methylation-directed mismatch repair (MMR), enhance VSP repair. Multicopy plasmids carrying mutS alleles that are dominant negative for MMR were tested for their effects on VSP repair. Some mutS mutations (class I) did not lower VSP repair in a mutS+ background, and most class I mutations increased VSP repair in mutS cells more than plasmids containing mutS+. Other plasmid-borne mutS mutations (class II) and mutS+ decreased VSP repair in the mutS+ background. Thus, MutS protein lacking functions required for MMR can still participate in VSP repair, and our results are consistent with a model in which MutS binds transiently to the mispair and then translocates away from the mispair to create a specialized structure that enhances the binding of Vsr.
Olfaction and the Brain. Olfaction, Taste, and Cognition. C. Rouby, B. Schaal, D. Doubois, R. Gervais, and A. Holley (Eds.). 2002. Cambridge, UK: Cambridge University Press. 462 pp., $95.00.

This 27-chapter volume arose from a symposium held in Lyon, France, in June of 1999, that sought to integrate information from academic scientific studies of olfaction, largely psychological in nature, with knowledge derived from the perfume industry. It is dedicated to the French perfumer Edmond Roudnitska, known for creating such classic fragrances as “Femme” (1944, Rochas), “Diorama” (1948, Dior), L'Eau” (1951, Hermes), “Diorissimo” (1956, Dior), “Eau Savage” (1966, Dior), and “Diorella” (1972, Dior), and addresses such topics as odor classification, odor memory, odor conditioning, and the plasticity of chemosensation.
Patterns of Growth and Size-Localized Competition in the New York State Life Insurance Industry, 1860–1985

Les AA. etudient le developpement des assurances sur la vie aux Etats-Unis et plus particulierement dans l'Etat de New York entre 1860 et 1985. Ils testent la loi de Gibrat qui affirme que la croissance d'une organisation depend de sa taille. Ils montrent que ce principe ne s'applique pas dans ce cas precis. Les taux de croissance ont davantage tendance a decliner proportionellement a la taille. L'inertie des structures organisationnelles semblent reduire les possibilites de developpement des compagnies d'assurance. La competition entre compagnies de meme taille a un effet reducteur sur leur croissance
Individual differences in adult human sleep and wakefulness: Leitmotif for a research agenda.

This paper reviews the literature on interindividual variability in human sleep parameters, sleepiness, responses to sleep deprivation, and manifestations of sleep disorders. Variability among individuals in sleep/wake biology and behavior is pervasive. The magnitude of such individual differences is often considerable and comparable to the effect sizes of many experimental and clinical interventions. Evidence is accu- mulating that certain aspects of sleep/wake-related variability—such as sleep duration, daytime sleepiness, and vulnerability to the effects of sleep loss—involve trait characteristics in healthy populations and among sleep-disordered patients. Establishing the trait-specific nature of variabil- ity in sleep/wake parameters is a prerequisite for elucidating the corre- sponding neurophysiologic and/or genetic mechanisms. At present, it remains largely unknown what underlies or predicts sleep/wake-related traits, what relationships these traits may have to each other, and what functional significance may be associated with specific traits. Scientific studies addressing these issues are warranted, as understanding the basis of trait variability may yield new insights into sleep/wake regulation and sleep pathology. Understanding individual differences in sleep and wakefulness may also have provocative but important implications for health economics and clinical care, as well as for safety, productivity, and general well-being. This paper gives suggestions for a research agenda focusing on individual differences in sleep research and sleep medicine.
Treatment response in the PIVENS trial is associated with decreased hedgehog pathway activity

Hedgehog (Hh) ligand production by ballooned hepatocytes drives nonalcoholic steatohepatitis (NASH) progression in mice. The NIDDK-sponsored PIVENS trial (NCT00063622) showed that vitamin E (VitE) improved NASH. We investigated whether VitE treatment and improvement in NASH were associated with changes in Hh pathway activity. Immunohistochemistry (IHC) was performed on both pre- and posttreatment liver biopsies of 59 PIVENS patients randomized to VitE (n = 30) or placebo (n = 29). Sonic Hh (Shh) ligand-producing cells and Shh-responsive cells were quantified. The latter was accomplished by triple IHC for gli2+ (marker of Hh signaling), sox-9 (progenitor marker), and α-smooth muscle actin (α-SMA; myofibroblast marker). Ballooned hepatocytes were quantified by keratin 8/18 and ubiquitin (K8/18/Ub) staining. IHC results were correlated with primary clinical and histologic PIVENS data. Pretreatment clinical, histologic, and IHC parameters did not differ significantly in the two treatment groups. Regardless of treatment arm, the number of Shh+ hepatocytes correlated with K8/18/Ub foci (r2 = 0.47, P < 0.001) and aspartate aminotransferase (AST) (r2 = 0.15, P = 0.002). Treatment-related changes in the numbers of Shh+ hepatocytes correlated with changes in serum AST (partial r2 = 0.75, P < 0.0001), hepatocyte ballooning (P = 0.004), the ductular reaction (i.e., numbers of gli2+/sox9+ cells; P = 0.03 and α-SMA+ cells; P = 0.10), and fibrosis stage (P = 0.02). Treatment response was associated with a greater decrease in Shh+ hepatocytes than nonresponse (P = 0.007). The VitE group demonstrated a greater reduction in K8/18/Ub+ foci (P < 0.08) and Shh+ hepatocytes (P < 0.05) than the placebo group, effects that became more significant after correction for baseline differences and multiple linear regression analysis. Conclusion: During PIVENS, treatment response correlated with loss of Shh+ hepatocytes and improvement in Hh-regulated processes that promote NASH progression. (Hepatology 2015;61:98–107)
On the Predictability of Lagrangian Trajectories in the Ocean

The predictability of particle trajectories in oceanic flows is investigated in the context of a primitive equation, idealized, double-gyre ocean model. This study is motivated not only by the fact that this is an important conceptual problem but also by practical applications, such as searching for objects lost at sea, and ecological problems, such as the spreading of pollutants or fish larvae. The original aspect of this study is the use of Lagrangian drifter data to improve the accuracy of predicted trajectories. The prediction is performed by assimilating velocity data from the surrounding drifters into a Gauss‐Markov model for particle motion. The assimilation is carried out using a simplified Kalman filter. The performance of the prediction scheme is quantified as a function of a number of factors: 1) dynamically different flow regimes, such as interior gyre, western boundary current, and midlatitude jet regions; 2) density of drifter data used in assimilation; and 3) uncertainties in the knowledge of the mean flow field and the initial conditions. The data density is quantified by the number of data per degrees of freedom NR, defined as the number of drifters within the typical Eulerian space scale from the prediction particle. The simulations indicate that the actual World Ocean Circulation Experiment sampling (1 particle/[5 83 58 ]o rNR K 1) does not improve particle prediction, but predictions improve significantly when NR k 1. For instance, a coverage of 1 particle/ [1 83 18 ]o rNR ; O(1) is already able to reduce the errors of about one-third or one-half. If the sampling resolution is increased to 1 particle/[0.5 83 0.58] or 1 particle/[0.25 83 0.258 ]o rNR k 1, reasonably accurate predictions (rms errors of less than 50 km) can be obtained for periods ranging from one week (western boundary current and midlatitude jet regions) to three months (interior gyre region). Even when the mean flow field and initial turbulent velocities are not known accurately, the information derived from the surrounding drifter data is shown to compensate when NR . 1. Theoretical error estimates are derived that are based on the main statistical parameters of the flow field. Theoretical formulas show good agreement with the numerical results, and hence, they may serve as useful a priori estimates of Lagrangian prediction error for practical applications.
Endocrine causes of short stature

The primary clinical characteristic of shortness of stature due to endocrine deficiency is a slow rate of growth (less than 1.5 in., or 4 cm, each year). Dental and skeletal ages are delayed. Specific tests of thyroid and pituitary function must be done to document the deficiency. Replacement therapy with levothyroxine or human growth hormone, or both, should be given as indicated. Short children who do not have hormone deficiency grow about 1.5 in. (4 cm) each year but have normal skeletal and dental ages. Children with Turner syndrome, primordial or genetic short stature, or intrauterine growth retardation do not respond to levothyroxine or human growth hormone replacement therapy. Constitutional delay in sexual development is a common cause of short stature in adolescent males and must be differentiated from hypopituitarism.
Discovery of RNA splicing and genes in pieces

During the 1960s and 1970s, there was a major conundrum in eukaryotic molecular biology regarding the synthesis of mRNA in animal cells. Pulse and pulse-chase radio-labeling experiments with tritiated uridine had shown that a large fraction of nuclear RNA was degraded very rapidly after synthesis, whereas only a small fraction of the initially synthesized RNA was exported from the nucleus to the cytoplasm where it functions as far more stable mRNAs (1, 2). This short-lived nuclear RNA ranged in lengths up to several tens of kilobases, much longer than most cytoplasmic mRNAs, and was referred to as heterogeneous nuclear RNA (hnRNA) (3, 4). Pulse-chase labeling yielded results consistent with hnRNA functioning as a precursor of mRNA. hnRNA is rapidly labeled, whereas label appeared in mRNAs more slowly. Also, as for mRNA, a large fraction of hnRNA was shown to be polyadenylated at its 3′ end like mRNA, consistent with the model that RNA sequences near the 3′ end of hnRNAs are retained in shorter mRNAs exported to the cytoplasm (5, 6). Also, like mRNAs, hnRNAs were found to have the 7-methyl guanine 5′–5′ phosphotriester “cap” structure at their 5′ ends, like mRNAs. Remarkably, the methyl groups in hnRNA cap structures appeared to be conserved as RNA was exported to the cytoplasm, even though, on average, hnRNA molecules in the nucleus are at least four times longer than mRNAs in the cytoplasm (7, 8). However, it was not possible to prove rigorously from the flow of radiolabel in pulse-chase labeling experiments that hnRNAs are precursors to mRNAs. There were two principal reasons for this. First, the pool of ribonucleoside triphosphates in mammalian … [↵][1]1Email: berk{at}mbi.ucla.edu. [1]: #xref-corresp-1-1
RAG-mediated DNA double-strand breaks activate a cell type–specific checkpoint to inhibit pre–B cell receptor signals

DNA double-strand breaks (DSBs) activate a canonical DNA damage response, including highly conserved cell cycle checkpoint pathways that prevent cells with DSBs from progressing through the cell cycle. In developing B cells, pre-B cell receptor (pre-BCR) signals initiate immunoglobulin light (Igl) chain gene assembly, leading to RAG-mediated DNA DSBs. The pre-BCR also promotes cell cycle entry, which could cause aberrant DSB repair and genome instability in pre-B cells. Here, we show that RAG DSBs inhibit pre-BCR signals through the ATM- and NF-κB2-dependent induction of SPIC, a hematopoietic-specific transcriptional repressor. SPIC inhibits expression of the SYK tyrosine kinase and BLNK adaptor, resulting in suppression of pre-BCR signaling. This regulatory circuit prevents the pre-BCR from inducing additional Igl chain gene rearrangements and driving pre-B cells with RAG DSBs into cycle. We propose that pre-B cells toggle between pre-BCR signals and a RAG DSB-dependent checkpoint to maintain genome stability while iteratively assembling Igl chain genes.
Islet Cell Tumors

Islet cell tumors can originate from different cell types of the islets of Langerhans. Depending on the cell type from which they originate, islet cell tumors can hypersecrete insulin, gastrin, glucagon, or vasoactive intestinal polypeptide. In this chapter, the physiological control of glucose homeostasis is discussed first as a prelude to understanding the manifold presentations of the β-cell tumor, insulinoma. This is followed by an overview of the physiological control of gastrin secretion as a background for understanding the Zollinger—Ellison syndromes. Finally, the features of the rare Verner—Morrison syndrome and glucagonoma are presented.
Requirements Development for Momentum Control Systems

This chapter addresses the subject of how to flow spacecraft agility requirements down to an array of momentum devices and provides guidelines for choosing the appropriate technology. We shall see that the design trades in selecting and sizing momentum devices span orders of magnitude in performance, complexity, and cost. Therefore, to arrive at an efficient and cost-effective design, it is important not to over-specify the momentum-system requirements.
An interdepartmental collaboration to improve preoperative glycemic control.

Background: The Centers for Disease Control and Prevention estimates that 25.8 million adults in the United States have diabetes, and these patients experience higher rates of morbidity and mortali...
A Vast New Storehouse of Transportation and Marketing Data

The monumental traffic jam on U. S. streets and highways has sparked a massive program of research in land use, economic data, and travel habits. Current inventories and projections into the future...
Therapy for ongoing graft-versus-host disease induced across the major or minor histocompatibility barrier in mice with anti-CD3F(ab')2-ricin toxin A chain immunotoxin

A new pharmacologic agent, anti-CD3F(ab')2-ricin toxin A chain (RTA), was synthesized for the purpose of targeting T cells and as a means of treating established graft-versus-host disease (GVHD). The Fc region of anti-CD3 monoclonal antibody (MoAb) was removed to prevent its ability to activate T cells. The resulting F(ab')2 fragments were conjugated to deglycosylated RTA (dgRTA), a catalytic and potent phytotoxin. The resulting immunotoxin (IT) was potent (greater than 95% inhibition) and selective in inhibiting T-cell mitogenesis in vitro. In vivo, the IT depleted 80% of T cells in mice receiving bone marrow (BM) transplants. Transplantation in an aggressive acute GVHD model using C57BL/6 donor cells and H-2 disparate B10.BR recipients resulted in an infiltration of CD3-expressing cells and a median survival time (MST) of 20 to 30 days. A 5-day course of anti-CD3F(ab')2-RTA (30 micrograms/d intraperitoneally) beginning 7 days after GVHD induction was beneficial in treating established GVHD in these mice, as evidenced by significantly prolonged survival (MST, greater than 80 days), superior mean weight values, and improved clinical appearance. Neither intact anti-CD3, unconjugated anti-CD3 F(ab')2 fragments, nor a mixture of anti-CD4 and anti-CD8 MoAbs (which are highly effective in prophylactic models) were as effective. F(ab')2 fragments made from anti-Lyt-1 (the murine homologue of human anti-CD5) linked to RTA were also not effective, despite the fact that both anti-CD3F(ab')2-RTA and anti-Lyt-1F(ab')2-RTA had similar half-lives of about 9 hours. The IT also increased MST in two aggressive models of GVHD across non-H-2 minor histocompatibility barriers, indicating that the usefulness of anti-CD3F(ab')2-dgRTA is not limited to a single-strain combination. This agent should be further investigated as an alternative to current strategies for treating steroid refractory GVHD.
Rapid Screening for the Robust Expression of Recombinant Proteins in Algal Plastids

Chlamydomonas reinhardtii has many advantages as a photosynthetic model organism. One of these is facile, targeted chloroplast transformation by particle bombardment. Functional recombinant proteins can be expressed to significant levels in this system, potentially outperforming higher plants in speed of scaling, cost, and space requirements. Several strategies and regulatory regions can be used for achieving transgene expression. Here we present two of those strategies: one makes use of the psbD promoter for expressing moderate levels of the recombinant protein in a photosynthetic background. The other strategy is based on the strong psbA promoter for obtaining high yields of the recombinant product in a non-photosynthetic strain. We herein describe the vectors, transformation procedures, and screening methods associated with these two strategies.
A multidisciplinary approach to improve the quality of care for patients with fragility fractures.

Background Fragility fractures have become a worldwide epidemic associated with significant morbidity and mortality. As the world population ages, the number of patients that experience these fractures is also expected to rise. A multidisciplinary team was assembled that was coordinated by the Acute Inpatient Medical Service and included orthopedic surgeons, geriatricians, anesthesiologists, cardiologists, nurses, trauma surgeons, emergency medicine physicians, physiatrists, and physical therapists. This team was formed with the expectation that geriatric fragility fracture complications, specifically hip fractures, could be reduced by identifying and implementing best practices using guidelines from the American Academy of Orthopedic Surgery and those from the International Geriatric Fracture Society.
A multidisciplinary approach to reducing alarm fatigue and cost through appropriate use of cardiac telemetry

Background Alarm fatigue (AF) is a distressing factor for staff and patients in the hospital. Using cardiac telemetry (CT) without clinical indications can create unnecessary alarms, and increase AF and cost of healthcare. We sought to reduce AF and cost associated with CT monitoring. Methods After implementing a new protocol for CT placement, data were collected on telemetry orders, alarms and bed cost for 13 weeks from 1 January 2015 through 31 March 2015. We also retrospectively collected data on the same variables for the 13 weeks prior to the intervention. A survey was administered to nurses to assess past and present perceptions of AF. Interventions included protocol creation and education for participants. Results At baseline, 77% of patients were monitored with CT. A total of 145 (31%) order discrepancies were discovered during data collection, of which 72% had no indication for CT, so CT was discontinued. The other 28% had indications, so orders were placed. A total of 8336 alarms were recorded during 4 weeks of data collection, of which 333 (4%) were classified as true actionable alarms. Postintervention data showed 67% CT assignment with 10% reduction in CT usage, with no increase in mortality (p 0.05, respectively). A 42% cost reduction was achieved after adjusting the patient status. Nurses reported 27% perceived reduction in AF. One-year follow-up revealed that 69% of patients were being monitored by CT, and the rate of order discrepancies due to lack of indication was 9%. Conclusion All hospital units may benefit from the protocols created during this study. If applied appropriately, these protocols can lead to reduced AF and cost per episode of care.
Gamified Twitter Microblogging to Support Resident Preparation for the American Board of Surgery In-Service Training Examination

Objective We sought to determine if a daily gamified microblogging project improves American Board of Surgery In-Service Training Examination (ABSITE) scores for participants. Design In July 2016, we instituted a gamified microblogging project using Twitter as the platform and modified questions from one of several available question banks. A question of the day was posted at 7-o׳clock each morning, Monday through Friday. Respondents were awarded points for speed, accuracy, and contribution to discussion topics. The moderator challenged respondents by asking additional questions and prompted them to find evidence for their claims to fuel further discussion. Since 4 months into the microblogging program, a survey was administered to all residents. Responses were collected and analyzed. After 6 months of tweeting, residents took the ABSITE examination. We compared participating residents׳ ABSITE percentile rank to those of their nonparticipating peers. We also compared residents׳ percentile rank from 2016 to those in 2017 after their participation in the microblogging project. Setting The University of Connecticut general surgery residency is an integrated program that is decentralized across 5 hospitals in the central Connecticut region, including Saint Francis Hospital and Medical Center, located in Hartford. Participants We advertised our account to the University of Connecticut general surgery residents. Out of 45 residents, 11 participated in Twitter microblogging (24.4%) and 17 responded to the questionnaire (37.8%). Results In all, 100% of the residents who were participating in Twitter reported that daily microblogging prompted them to engage in academic reading. Twitter participants significantly increased their ABSITE percentile rank from 2016 to 2017 by an average of 13.7% (±14.1%) while nonparticipants on average decreased their ABSITE percentile rank by 10.0% (±16.6) (p = 0.003). Conclusions Microblogging via Twitter with gamification is a feasible strategy to facilitate improving performance on the ABSITE, especially in a geographically distributed residency.