cssi/SciSciGPT-SciSciNet huggingface dataset:
A dose–schedule finding design for phase I–II clinical trials

Dose-finding methods aiming at identifying an optimal dose of a treatment with a given schedule may be at a risk of misidentifying the best treatment for patients. In this article we propose a phase I/II clinical trial design to find the optimal dose-schedule combination. We define schedule as the method and timing of administration of a given total dose in a treatment cycle. We propose a Bayesian dynamic model for the joint effects of dose and schedule. The proposed model allows us to borrow strength across dose-schedule combinations without making overly restrictive assumptions on the ordering pattern of the schedule effects. We develop a dose-schedule-finding algorithm to sequentially allocate patients to a desirable dose-schedule combination, and select an optimal combination at the end of the trial. We apply the proposed design to a phase I/II clinical trial of a γ-secretase inhibitor in patients with refractory metastatic or locally advanced solid tumours, and examine the operating characteristics of the design through simulations.
A few changes in wild-type picornavirus genome lead to immunosuppression (VIR8P.1068)

Viruses, such as human immunodeficiency virus and poliovirus, use a variety of mechanisms to suppress the immune response and evade clearance by the host. Therefore, investigating how a few changes in the viral genome of a non-lethal virus can lead to an alteration in disease, from survivable to immunosuppression and death, would provide valuable information into viral pathogenesis. Here we investigate a picornavirus, the Theiler’s murine encephalomyelitis virus (TMEV), in its natural host, the mouse. C57BL/6 mice infected intracerebrally (i.c.) with the DA strain of TMEV develop acute encephalitis; mice survive the acute disease and clear the virus. A mutant of the DA strain of TMEV was inadvertently created, called H101, which encodes a point mutation (T101I) in VP1. Additional sequencing showed several nucleotide substitutions in the 5’ untranslated region as well as additional amino acid substitutions in the capsid protein coding region, suggesting that there are a number of perturbations in the viral genome. C57BL/6 mice infected with the H101 mutant via a peripheral route [intraperitoneal (i.p.)] become immunosuppressed through specific depletion of T cells. For C57BL/6 mice infected with the H101 mutant virus by either the i.c. or i.p. route, the immunosuppression is profound. This study provides experimental evidence that infection by a virus having just a few changes in the viral genome can now result in profound immunosuppression due to T cell depletion.
Challenges in Fabrication of Polymer Nanocomposites (PNCs)

As is the case for conventional composites, the key to the performance of polymer nanocomposites is the quality of dispersion of the nano-reinforcement and the interfacial interaction between the matrix and the reinforcement phase. Optimization of these properties requires various special and complicated treatments, which are not always easy to determine. The aim of this paper is to give some examples of the application of different approaches to both thermoset and thermoplastic polymer nanocomposites, fabricated by different means, such as solution, melt-processing, and in-situ polymerization.
Conversion from gastric bypass to sleeve gastrectomy for complications of gastric bypass

Abstract Background Complications after gastric bypass (RYGB) are well documented. Reversal of RYGB is indicated in select cases but can lead to weight gain. Conversion from RYGB to sleeve gastrectomy (SG) has been proposed for correction of complications of RYGB without associated weight gain. However, little is known about outcomes after this procedure. Objectives To examine outcomes after conversion from RYGB to SG. Setting University hospital. Methods A retrospective study of patients who underwent RYGB to SG conversion was undertaken. Results Twelve patients underwent RYGB to SG conversion for refractory marginal ulceration, stricture, dumping, gastrogastric fistula, hypoglycemia, and failed weight loss. No deaths occurred. Four patients experienced 7 major complications, including portal vein thrombosis, bleeding, pancreatic leak, pulmonary embolus, seroma, anastomotic leak, and stricture. Two required reoperation, and 6 were readmitted within 30 days. Four required nasoenteric feeding postoperatively because of prolonged nausea. The complication of RYGB resolved in 11 of 12 patients. At 14.7 months, change in body mass index for all patients was a decrease of 2.2 kg/m 2 . In 5 patients with morbid obesity at conversion, the change in body mass index was a decrease of 6.4 kg/m 2 at 19 months. Conclusions Laparoscopic conversion from RYGB to SG is successful in resolving certain complications of RYGB and does not result in short-term weight gain. However, conversion has a high rate of major complications as well as a high rate of readmission and need for supplemental nutrition. Although conversion to SG may be appropriate in carefully-selected patients, other options for patients with severe chronic complications after RYGB should be considered.
Challenges in obtaining reliable measurements of point rainfall

[1] Extensive data recorded from storm systems passing over the well-instrumented 21.4 km2 Goodwin Creek watershed in northern Mississippi are used to highlight uncertainties associated with the measurement of surface rainfall, focusing on data quality control, gauge calibration, out-of-level gauge orifices, and wind effects on rain gauge catch. Assessment of the wind effect on gauge catch is central to the presented analyses, including an in-depth evaluation of a recent technique for estimating the rainfall undercatch by means of wind and raindrop size information. Our findings emphasize that quantification of the wind effect on rain gauge catch is difficult because of uncertainties associated with measuring rainfall, drop size distribution, and the wind at gauge rim height. On the basis of our evaluation the sophisticated wind effect correction technique that makes use of raindrop size and wind information is much less effective than traditional methods based on rainfall rate and wind observations alone.
On the history and future of cosmic planet formation

We combine constraints on galaxy formation histories with planet formation models, yielding the Earth-like and giant planet formation histories of the Milky Way and the Universe as a whole. In the Hubble volume (10 13 Mpc 3 ), we expect there to be ∼10 20 Earth-like and ∼10 20 giant planets; our own galaxy is expected to host ∼10 9 and ∼10 10 Earth-like and giant planets, respectively. Proposed metallicity thresholds for planet formation do not significantly affect these numbers. However, the metallicity dependence for giant planets results in later typical formation times and larger host galaxies than for Earth-like planets. The Solar system formed at the median age for existing giant planets in the Milky Way, and consistent with past estimates, formed after 80percent of Earth-like planets. However, if existing gas within virialized dark matter haloes continues to collapse and form stars and planets, the Universe will form over 10 times more planets than currently exist. We show that this would imply at least a 92percent chance that we are not the only civilization the Universe will ever have, independent of arguments involving the Drake equation.
Corrosion inhibition of mild steel by an imidazolium ionic liquid compound: the effect of pH and surface pre-corrosion

The corrosion inhibition performance of 1-decyl-3-methylimidazolium chloride (DMICL) on mild steel was investigated in a carbon dioxide-saturated NaCl solution at pH 3.8 and 6.8. Electrochemical and surface analysis techniques were used to characterize the corrosion process in blank and inhibiting solutions. Open circuit potential, polarization curves and impedance spectroscopy were recorded to analyze the inhibition behavior of DMICL for specimens with a well-polished surface and a pre-corroded surface. Scanning electron microscopy images showed that the specimen surfaces were well protected from uniform corrosion in the inhibition solution. The energy dispersive spectroscopy and X-ray photoelectron spectroscopy data indicated the presence of specific elements following a dissolution mechanism under different pH conditions. The electrochemical fitting data facilitated calculations of inhibition efficiency and accounted for the interfacial changes.
Depression and Help Seeking Among Mexican–Americans: The Mediating Role of Familism

Increased depression symptomatology results in a reduced willingness to seek help from family. Focusing on Mexican–Americans, the current study hypothesized that the a reduction in favorable perceptions of familial relations could be partially to blame for limited help seeking among people with depression. Data were collected from 84 Mexican–Americans. Measures assessed depression symptomatology, familism, perceptions of help seeking from family, and demographics. As predicted: (1) depression symptomatology was negatively associated with perceptions of help seeking from family; (2) familism was positively associated with perceptions of help seeking from family; and, (3) depression symptomatology was negatively associated with familism. Further, familism partially mediated the relationship between depression symptomatology and help seeking comfort, as well as between depression symptomatology and the perceived utility of familial help seeking. The results indicate a reduction in familistic values may be partially responsible for reduced help seeking among Mexican–Americans with depression.
On a stability theorem for nonlinear systems with slowly varying inputs

Recently, M. Kelemen (IEEE Trans. Automat. Contr., vol.AC-31, 766-768, Aug. 1986) presented a stability result that deals with the response of a nonlinear system to slowly varying input signals. In this work a proof is given, under a weaker hypothesis on the input signal, by constructing a Lyapunov function that is standard in the control literature. This proof may be more accessible than the other approaches. For completeness, brief proofs of some intermediate results that are regarded as well known are included. A simple example is given to show that this approach can yield explicit bounds in certain situations of interest. >
Differential phonatory characteristics of four women with amyotrophic lateral sclerosis.

Summary Patients with specific neural subsystem involvement are often reported to present with particular perceptual characteristics of voice. This has been true for diseases such as amyotrophic lateral sclerosis (ALS), a progressive disease in which mixed neurologic signs are present. This article reports acoustic data on the phonatory performance of four women diagnosed with ALS who had initial bulbar signs and progressive phonatory deterioration. The data presented here demonstrate that the phonatory characteristics of women with ALS are not uniform, but in fact may vary greatly from patient to patient.
Conformational studies utilizing asymmetric torsional frequencies

Abstract The utility of asymmetric torsional frequencies, obtained from low frequency infrared and/or Raman spectra of the gas phase, for conformational studies is presented. Vibrational spectroscopy may well be the most generally applicable method to be used in the study of the conformations of certain types of small molecules with few substituents because infrared and Raman spectra can be recorded in all phases, and variable temperature experiments can also be conducted. Additionally, gas phase band contours in both the infrared and Raman spectra, along with Raman depolarization data, provide considerable structural information and lend confidence to conclusions arrived at from vibrational studies. The theory and experimental difficulties involved in the determination of potential functions governing internal rotation is presented, and illustrated by a few examples.
Sequence of I-E genes from autoimmune New Zealand white mice.

Autoimmune New Zealand white (NZW) mice contribute to (New Zealand black × New Zealand white)F1 mice 1 or more major histocompatibility complex-linked genes that strongly correlate with susceptibility to murine lupus. The NZW class II major histocompatibility complex genes, I-Eα and I-Eβ, were cloned and sequenced and found to differ from normal B10.PL (H-2u) mice by 3 amino acids in the first domain of the I-Eβ subunit. Of these differences, the arginine at position 72 of NZW mice could be an important disease determinant since it lies in a predicted antigen-binding cleft.
Modulation of protein kinase C and diverse cell functions by sphingosine--a pharmacologically interesting compound linking sphingolipids and signal transduction.

Sphingosine, the backbone moiety of sphingomyelin, gangliosides and other complex sphingolipids, is a potent inhibitor of protein kinase C in vitro and of cellular events dependent on this enzyme. The systems that have been found, thus far, to be affected by spingosine encompass various components of host defense system, including the activation of platelets, neutrophils and natural killer cells; the cytolytic activity of pathogens and expression of viral genes; cell growth and differentiation is several cell types, including leukemic and neuronal cells; insulin stimulated hexose transport and metabolism in adipocytes; ion-transport systems in various models; the response of neuronal cells to excitatory compounds; and receptor densitization. While sphingosine has appeared to be a relatively potent and specific inhibitor of protein kinase C in the systems studied, recent findings with the epidermal growth factor receptor indicate that it may serve as a pleotrophic modulator of celll functions. New strategies for the design of phrmacologically active agents should arise from further studies of the action of long-chain (sphingoid) bases. Furthermore, since free sphingosine is a natural constituent of cells and the levels can be modulated by phorbol esters and other factors, a cycle of complex sphingolipid hydrolysis and resynthesis to regulate the amount of free sphingosine may constitute one mechanism of action of these compounds.
Transformation of Montmorillonite to Kaolinite during Weathering

Extensive deposits of kaolinite in Florida are formed by transformation of montmorillonite during low-temperature supergene weathering. The transformation occurs by intracrystalline leaching of interlayer cations and tetrahedral silica layers. Interposition of stripped layers within montmorillonite creates a regular 1:1 mixedlayered montmorillonite-kaolinite, a new clay structure. Kaolin-like layers are nourished by lateral epitaxy, as the iron-rich montmorillonite decomposes. Hexagonal outgrowths of new kaolinite develop at the edges of montmorillonite flakes and nucleate new vertical growth. Kaolinitic sands impregnated with goethite are ultimately formed, and the released silica enriches groundwater and forms secondary chert.
Effects of 131I thyroid irradiation damage, thyroxine, and thiocyanate on radioiodine metabolism in dairy cows.

Abstract This investigation utilized seven pairs of identical-twin cows and two nonpaired cows. Thyroid-damaged cows yielded 53% as much milk containing almost twice as much of a radioiodine dose as their normal controls. Other parameters of iodine metabolism as percentages of the control were: ratio of milk radioiodine to plasma nonbound radioiodine, 227; 72-hr thyroid uptake, 17; plasma-bound iodine, 30; and plasma radioiodine half time, 130. Daily subcutaneous injections to cows with thyroid damage of 5 mg thyroxine increased milk yield 24%, heart rate 29%, and plasma-bound iodine 500%, and resulted in reductions of 29% in milk radioiodine, 46% in milk radioiodine to plasma nonbound iodine ratio, and 40% in plasma half life. These changes were partially maintaind by feeding 80 mg thyroxine daily. Feeding 10 g/day sodium thiocyanate in addition to injected thyroxine caused further reductions of 72% in milk radioiodine, 73% in milk radioiodine to plasma nonbound radioiodine ratio, and 45% in plasma half life. Thiocyanate alone had no effect on milk yield but decreased milk radioiodine 66%, milk radioiodine to plasma nonbound radioiodine ratio 77%, plasma half life 17% and thyroid uptake 80% in thyroid-damaged cows, and 58, 62, 38, and 87%, respectively, in normal cows. These results indicate an inverse relationship between circulating thyroxine levels and radioiodine secretion into milk. Thiocyanate produces a greater or over-riding effect on milk radioiodine concentrations.
Strategic Upstream and Downstream Considerations for Effective Global Performance Management

In the context of balancing the dynamic tensions of duality and competing forces of convergence and divergence in global business management, this article examines various important company headquarters ‘upstream’ and local country unit ‘downstream’ processes and activities that must work in sync to build global synergies and effectively implement company strategy. Upstream processes and activities of global performance management considered here include strategic performance management integration and coordination, workforce internal alignment, knowledge management, and organizational learning. Downstream considerations include responsiveness to local conditions, sensitivity to cross cultural differences, establishment of the performance management relationship, and comprehensive training efforts.
Cardiac-directed expression of adenylyl cyclase reverses electrical remodeling in cardiomyopathy.

Abstract Adenylyl cyclase (AC) is an effector molecule in β-adrenergic receptor signaling, catalyzing conversion of ATP to cAMP. Agents that increase intracellular levels of cAMP have been used previously to treat clinical heart failure. Recently, Roth et al. have shown that long-term cardiac-directed expression of ACVI, a dominant AC isoform in mammalian cardiac myocytes, increases survival and abrogates myocardial hypertrophy in transgenic (TG) mice with Gαq-associated cardiomyopathy. Indeed, it has been proposed that increasing the cardiac content of ACVI is fundamentally different than other strategies used to increase cAMP function. However, one important but unexplored issue is its effects on electrical remodeling. Electrophysiological properties of Gαq mice have been characterized. Similar to other models of cardiac hypertrophy and failure, cardiac myocytes isolated from Gαq mice show prolonged action potential with reduced transient outward K+ current (Ito) and inward rectifier K+ current (IK1) density compare to wild-type (WT) animals. We directly examined the electrical remodeling of cardiac-directed ACVI over-expression in Gαq mice using ECG recordings and whole-cell patch-clamp recordings. Four groups of animals were used: WT (double negative), ACVI, Gαq and double positive TG mice (Gαq/ACVI). Cardiac-directed expression of ACVI results in the reversal of adverse electrical remodeling in the Gαq mice and is associated with significant improvement in the delay of cardiac repolarization and arrhythmias. Specifically, there is a normalization of Ito, IK1 and action potential duration in Gαq/ACVI compared to Gαq mice. In summary, our data provide evidence that increased cardiac ACVI content has a salutary effect in cardiomyopathy and cardiac electrical remodeling.
Biomechanical Benefits of Crosslink Augmentation in Spinal Discs

This study involved an investigation into the effect of non-toxic crosslink augmentation on spinal discs on disc durability and joint stability. Non-destructive indentation techniques were developed to quantify annulus fibrosis material property degradation resulting from non-traumatic cyclic fatigue. Joint stability was assessed using two different natural zone measures. A non-toxic crosslinking reagent formulation reduced fatigue-induced viscoelastic relaxation by two- to three-fold compared to controls. The same treatment was found to produce a four-fold reduction of instability scores. Stabilization was observed to be greater in the more mechanically unstable discs.Copyright © 2003 by ASME
Optimized encoder design algorithm for joint compression and recognition

Sensor data, such as SAR and FLIR images, are commonly transmitted from aircraft or satellites to airborne or ground stations for target detection and recognition processing. ATR algorithms are typically run at remote locations because they are very complex computationally, and require powerful computer resources. Rarely is unlimited channel bandwidth available for transmission. Thus one must also contend with delay-cost-quality tradeoff issues, which are often addressed by compressing data prior to transmission. Overall performance is largely restricted by the computational power of the on-board processor, since this limits the complexity and quality of the compression, which in turn affects the speed of transmission. Given some fixed level of computational power available for compression and transmission on board the aircraft, a useful technological improvement would be to have some level of on-board detection/recognition capability so that immediate action could be taken as appropriate. Toward this end, we introduce a method of joint compression and recognition for potential implementation on sensor-equipped aircraft. The algorithm is formulated to provide a level of immediate classification as a by-product of the compression, which in turn would provide the pilot with potential target information instantly.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Bright and Water-Soluble Near IR-Emitting CdSe/CdTe/ZnSe Type-II/Type-I Nanocrystals, Tuning the Efficiency and Stability by Growth

Highly photoluminescent CdSe/CdTe/ZnSe type-II/type-I composite nanocrystals, both dot- and peanut-shaped, were prepared via the modified successive ionic layer adsorption and reaction (SILAR) techniques, straight SILAR for peanut-shaped ones and SILAR coupled with thermal-cycling (SILAR-TC) for dot-shaped ones. The CdSe/CdTe type-II heterojunction offered the nanocrystals with near-infrared emission and the CdTe/ZnSe type-I heterojunction helped to confine the photogenerated charges away from the ligands and solution environment. This structural feature makes the photoluminescence quantum yield of the CdSe/CdTe/ZnSe core/shell/shell type-II/type-I dots that have a uniformly grown ZnSe shell retain as high as 60% after replacing the original amine ligands with mercaptopropionic acid (MPA). Conversely, the emission of the corresponding CdSe/CdTe core/shell dots (CdSe/CdTe/ZnSe composite peanuts) was completely (almost completely) quenched by the same ligand treatment. The emission properties of the MPA-coa...
Cilostazol Has Beneficial Effects in Treatment of Intermittent Claudication Results From a Multicenter, Randomized, Prospective, Double-blind Trial

Background—Cilostazol is a new phosphodiesterase inhibitor that suppresses platelet aggregation and also acts as a direct arterial vasodilator. This prospective, randomized, placebo-controlled, parallel-group clinical trial evaluated the efficacy of cilostazol for treatment of stable, moderately severe intermittent claudication. Methods and Results—Study inclusion criteria included age ≥40 years, initial claudication distance (ICD) on treadmill (12.5% incline, 3.2 km/h) between 30 and 200 m, and confirmation of diagnosis of chronic lower-extremity arterial occlusive disease. After stabilization and single-blind placebo lead-in, 81 subjects (62 male, 19 female) from 3 centers were randomized unequally (2:1) to 12 weeks of treatment with cilostazol 100 mg PO BID or placebo. Primary outcome measures included ICD and maximum distance walked (absolute claudication distance, or ACD). Secondary outcome measures included ankle pressures, subjective assessments of benefit by patients and physicians, and safety. Tr...
Renal function in Macaca speciosa

Abstract 1. 1. Clearances of creatinine, inulin and para-aminmohippurate as well as diluting ability and response to hypertonic saline infusion were measured in Macaca speciosa. 2. 2. Clearance values obtained are similar to those reported in other small primate species and similar to values in humans. 3. 3. Diluting ability is comparable to that in man. 4. 4. This species alters sodium excretion in response to hypertonic saline infusion by changes in tubular reabsorption, rather by changing glomerular filtration rate.
Surgery for obesity in older women

The global epidemic of obesity continues to grow, with over 1.7 billion people worldwide classified as obese (body mass index; BMI ≥ 30 kg/m2). Of special concern is the population of older women, since women are more obese than men and gain weight early during menopause. Obesity with co-morbidities is the leading threat to women's health and longevity. Specific female co-morbidities, such as reproductive failure, urinary stress incontinence and disproportionate prevalence of serious diseases such as diabetes, cardiovascular disease and cardiopulmonary failure in addition to breast cancer and gynaecologic malignancies, reduce the fitness benefits grandmothers provide to the species by ensuring reproductive success of their children and health and survival of grandchildren. In fact, female life-expectancy is decreasing in industrialized nations. Non-surgical treatment for obesity itself is ineffective; currently there is not enough evidence to recommend weight loss medications for routine use in the elderl...
Acute Myoperidarditis with Focal ECG Findings Mimicking Acute Myocardial Infarction

Abstract Background: Although history, physical examination, laboratory data points, and electrocardiogram (ECG) are helpful, distinguishing among pericarditis, myopericarditis, and myocardial infarction can be difficult. Objectives: This case, which presents as pericarditis with concomitant myocarditis (myopericarditis), illustrates the four evolving ECG stages of pericarditis and highlights some of the potential difficulties in differentiating between myopericarditis and acute myocardial infarction. Case Report: We present the case of a previously healthy 15-year-old boy who presented to the Emergency Department (ED) from his family physician's office for chest pain and presumed pericarditis. The patient's initial ECG showed infero-lateral ST-segment elevation, and his troponin T was elevated at 1.54 ng/mL (ref.
Preliminary Observations of 1–16 Hz Natural Background Infrasound and Signals from Apollo 14 and Aircraft

Summary Infrasound with frequencies of 1–16 Hz, detected by an array of four thermistor flow-meter microphones in Sterling Forest, New York, was observed to have a continuous background with peak energy distributed near 16 Hz in frequency, with amplitudes of about 1 dyn cm-2, and arriving from the south-west and south-east at slightly above the speed of sound in air at ground level. The same array of microphones detected 5 dyn cm-2 signals from the Apollo 14. The earlier part of the 10-min signal arrived from the first stage re-entry, the later from the launch site vicinity. It is shown that aircraft beyond the visible and audible range can be detected and tracked by monitoring the infrasound emitted throughout most of the 1–16 Hz frequency band.
AN INTERVIEW WITH COSTAS AZARIADIS

Costas Azariadis was born in Athens, Greece, in 1943. He attended the National Technical University in Athens and received a degree in chemical engineering in 1969. He then attended Carnegie Mellon University, receiving an MBA in 1971 and his Ph.D. in 1975. His doctoral dissertation was advised by Edward Prescott and Robert Lucas. Azariadis's first academic appointment was as an assistant professor at Brown University between 1973 and 1977, after which he moved to the University of Pennsylvania. In 1992, he moved to UCLA. In addition, Azariadis spent two semesters at Hebrew University and Princeton and has held briefer visiting positions all over the world.
CN(X 2Σ) fine structure populations formed in the photofragmentation of BrCN as a function of wavelength

Abstract The relative population of the fine structure components of BrCN have been measured as a function of the photolysis wave-length from 210 to 260 nm. The form of the fine structure difference function changes as the wavelength changes. At longer wavelengths there are oscillations in the fine structure difference function but at shorter wavelengths it is relatively flat but biased toward the F 1 component. These observations are interpreted in terms of a predominance of one or the other spin states of the Br atom.
Double origin of the pericellular baskets of the pyramidal cells of the human motor cortex: a Golgi study.

Abstract The structure, intracortical distribution and orientation of a special type of basket-forming afferent fiber from the motor cortex of a 2.5-day-old infant is presented. The existence of these fibers confirm original observations made by Cajal concerning the origin of the pericellular baskets of the human motor cortex. It is concluded from this study that the pericellular baskets formed around the bodies of the giant pyramidal neurons of layer V (and possibly of lower layer III) of the human motor cortex have a double origin from intrinsic and extrinsic sources. The intrinsic component of these pericellular baskets is furnished by a special type of stellate interneuron previously described and named the cortical basket cell. The extrinsic component is furnished by the basket-forming afferent fibers described in this communication. Both of these subsystems are similarly distributed and oriented within narrow vertical planes perpendicular to the long axis of the precentral gyrus of the motor cortex. The dimensions of the planes determined by the intracortical distribution of these two subsystems are also similar. It is suggested that there is a close anatomical and possible functional interrelationship between these two subsystems of the motor cortex. Although the origin of these basket-forming afferent fibers is unknown it is postulated that they may originate in the projective neurons of the nucleus ventralis lateralis of the thalamus and that they may be part of the cerebello-thalamo-cortical pathway.
Pathology and biology associated with the fragile FHIT gene and gene product

More than 12 years and >800 scientific publications after the discovery of the first gene at a chromosome fragile site, the FHIT gene at FRA3B, there are still questions to pursue concerning the selective advantage conferred to cells by loss of expression of FHIT, the most frequent target of allele deletion in precancerous lesions and cancers. These questions are considered in light of recent investigations of genetic and epigenetic alterations to the locus and in a retrospective consideration of biological roles of the Fhit protein discovered through functional studies.
Vapor pressure deficit calculations and their effect on the combination equation

Abstract Of the several models used to calculate potential evapotranspiration (PET), many researchers use the combination method because of its theoretical basis. This model can be affected by random errors in the input parameters (net radiation, air temperature, wind speed, and daily average vapor pressure deficit, ▿) and sensitivity analyses have described the impact of these errors. However, a more subtle non-random error may be introduced in PET estimates by changing the form by which the ▿ term is specified. At least 12 different ways to present ▿ have been published; the primary differences among them are the measured humidity parameter and the algebra used to compute ▿. The effect of all applicable published computational methods on monthly and seasonal PET values for a range of locations differing in evaporative demand was examined in this study. Related methods of computing ▿ resulted in little difference between PET values. The range of summer PET means obtained from the extreme methods was 8–17% of the best estimate method over all locations. Although this range approximates the expected accuracy of the combination method, it must be stressed that the net effect of the systematic and random errors may constitute a bias and, therefore, should be evaluated as such. Apparently innocuous computational differences can significantly affect PET results and, therefore, degrade confidence in the resulting values.
An experimental study of eight current arterial prostheses

Abstract Eight currently used arterial prostheses with differing constructions and materials were implanted in the descending thoracic aorta of mongrel dogs. The prostheses were Gore-Tex (polytetrafluoroethylene), DeBakey Woven, Cooley Woven, Meadox Woven Double Velour, Cooley Knitted Double Velour, Microvel, Vasculour II, and Bionit II. Five series of these eight prostheses were serially implanted in heparinized subjects. During the 40 implantations, attention was focused on three major characteristics: preclotting efficiency, surgical handling characteristics, and healing. Gore-Tex is impervious to blood. The DeBakey and Cooley woven grafts are nearly so. The remaining prostheses required preclotting. The Meadox Woven Double Velour became impervious after two preclotting steps, the Cooley Knitted Double Velour and the Bionit II required three, and the Vasculour II and the Microvel required four. The surgical handling characteristics of the knitted prostheses clearly surpassed those of the DeBakey and Cooley woven and Gore-Tex prostheses. Although the Meadox Woven Double Velour prosthesis had better conformability than the nonveloured woven, the tendency of its cut edge to fray was more pronounced. Healing was much more advanced in the knitted and woven prostheses than in the Gore-Tex. (J VASC SURG 1986;4:33-41.)
Perceptual influences on Fitts' law

The linear relationship between movement time (MT) and index of difficulty (ID) for Fitts' type tasks has proven ubiquitous over the last 50+ years. A reciprocal aiming task (IDs 3, 4.5, 6) was used to determine if an enlarged visual display (visual angle 5.1 degrees , 7.4 degrees , or 13.3 degrees) would alter this relationship. With ID = 6, a condition typically associated with discrete action control, the largest visual display (13.3 degrees) allowed the motor system to exploit features of cyclical action control, e.g., shorter dwell times, more harmonic motion, less time decelerating the limb. The large visual display resulted in a quadratic relationship between MT and ID. For the IDs of 3 and 4.5, the visual displays did not alter the underlying control processes. The results are discussed in terms of the preference of the motor system to assemble movements from harmonic basis functions when salient visual information is provided.
Optical emissions from weld arcs and their effects on the performance of welding robot vision systems

The design and operation of one-pass arc welding robot vision systems are greatly complicated by the presence of the bright weld arc and the harsh welding environment. In this paper we present absolute intensity measurements of weld arc spectra at visible and near-IR wavelengths using Ar–O2 shield gas with solid wire and CO2 shield gas with flux-core wire. These measurements reveal the existence of many strong emission lines in the weld arc spectrum. The intense arc interference can be avoided by appropriately choosing the operating wavelength and by using a narrowband interference filter to prevent most of the arc radiation from reaching the detector of the vision system camera.
The diagnostic utility of D2-40 for malignant mesothelioma versus pulmonary carcinoma with pleural involvement.

Differentiating malignant mesothelioma (MM) from pulmonary carcinoma in pleural fluid cytology can be challenging. Recent studies have suggested that D2-40, a novel lymphatic marker, may be a useful marker for mesothelial differentiation in surgical specimens. However, there are no available data regarding its utility in effusion cytology specimens. We investigated the utility of D2-40 in pleural fluid cytology in differentiating MM from pulmonary carcinomas. Twenty cases of pleural effusion smears of surgically confirmed MM with their corresponding cell blocks were retrieved from the database of the hospital computer system. We also included 10 cases of metastatic pulmonary adenocarcinoma (PA) and 10 cases metastatic pulmonary squamous cell carcinoma (PSCC) involving the pleural fluid. Cell blocks were formalin-fixed, paraffin embedded, and immunostained for TTF1, p63, calretinin, CK5/6, WT-1, and D2-40. Cases were scored as negative ( 5% moderate/strong positivity). The positive rates for TTF1, p63, calretinin, CK5/6, WT-1, and D2-40 were as follows: MM (0/20), (0/20), (17/20), (18/20), (19/20), (17/20), for PA (8/10), (0/10), (3/10), (0/10), (0/10), (0/10), and for PSCC (1/10), (10/10), (6/10), (10/10), (0/15), (0/10). The staining pattern for D2-40 was characterized by thick membranous staining. Diffuse cytoplasmic staining by D2-40 was seen in 2 cases of pulmonary carcinoma, counted as negative. Our study showed that in differentiating MM from PA, CK5/6, WT-1, and D2-40 have high specificity and sensitivity for MM. Although calretinin is a sensitive IHC marker for MM, it is not specific since it stained 30% of PA. Conversely, to differentiate between MM and PSCC, p63 and WT-1 are the best available markers. We recommend a panel of CK5/6, p63, D2-40, and WT-1 to differentiate MM from pulmonary carcinomas in effusion cytology specimens.
Origin of neutrino mass

Abstract I discuss briefly why the neutrino mass has been, is, and will be interesting as a probe to physics at very high energy scales as well as early cosmology.
Mechanism of neurotensin depolarization of rabbit colonic smooth muscle.

Abstract The aims of this study were (1) to measure the effect of neurotensin on the membrane potential of circular muscle of the distal colon of the rabbit and (2) to determine the mechanism by which neurotensin affects the membrane potential of this tissue. The membrane potential was measured with microelectrodes placed intracellularly and the double sucrose gap. Neurotensin (10 −11 M to 10 −7 M) dose-dependently decreased the membrane potential. The maximum decrease in membrane potential occurred with 10 −9 M neurotensin. The ED 50 of neurotensin depolarization of the membrane potential was 0.87 ± 0.33 × 10 −10 M. The frequency of the slow waves was unchanged after neurotensin. The voltage response to a constant current pulse decreased as the concentration of neurotensin increased. The amplitude of the voltage response after a 0.6 μA current pulse decreased by 6 ± 0.5 mV after neurotensin (10 −7 M) compared to the Krebs control ( P + ] 0 to 0–23 mM did not affect the decrease in membrane potential after neurotensin. However, perfusion with a test solution containing no added Ca 2+ or verapamil (10 −5 M) inhibited neurotensin depolarization of the tissue. Evidence was found that neurotensin depolarizes colonic circular smooth muscle, and the decrease in membrane potential is associated with an increase in conductance which is dependent on influx of Ca 2+ .
Observations on the Binding of Four Anti-carbohydrate Monoclonal Antibodies to Their Homologous Ligands

The binding of four monoclonal immunoglobulins, two with specificity for beta(1-->6)-linked D-galactopyranans (IgA X24 and IgA J539) and two with specificity for the chain terminus of alpha(1-->6)-linked d-glucopyranans (IgA W3129 and IgA 16.4.12E), was measured with a number of their homologous oligosaccharide ligands at different temperatures. The results show a linear relationship between lnKa and 1/T, where Ka is the affinity constant and T is the absolute temperature. The unitary free energy of binding, DeltaGu, is virtually independent of T, and the DeltaSu is small when compared with DeltaGu. The enthalpy changes derived from van't Hoff plots are large and negative, indicating an exothermic binding effect, whereas the entropy changes are small and negative, indicating minor overall hydrophobic contributions. Measurements of the free energies of binding, in low and high salt buffers, of methyl beta-d-galactopyranoside and the methyl glycoside of beta(1-->6)-D-galactopyranotetraose with anti-galactan IgA X24 indicate that the monosaccharide has no hydrophobic interaction with the highest affinity subsite of IgA, whereas the tetraoside might have a modest hydrophobic interaction with the three other hapten-binding subsites of IgA. The standard entropy change of binding of the two groups (galactosyl and glucosyl) of oligosaccharides to the two respective sets (anti-galactan and anti-dextran) of antibodies shows a distinct, differing correlation with the hapten chain length within each set. This correlation agrees with the type of association previously established between the antibodies and either the interior determinants of the antigen (in the case of the anti-galactans) or the chain terminus (in the case of the anti-dextrans).
Polymer–Drug Interacted Systems in the Physicochemical Design of Pharmaceutical Dosage Forms I: Drug Salts with PVM/MA and with a PVM/MA Hemi-Ester

The applicability of a polymer-drug interacted system in the physicochemical design of pharmaceutical dosage forms has been investigated. Salts of poly(methyl vinyl ether/maleic anhydride) and methapyrilene base were prepared. In vitro release patterns were determined by an equilibrium dialysis procedure. Dialytic release rates of the polymer-drug salt in solution demonstrated no appreciable difference in drug availability with respect to the free drug or its hydrochloride salt. In vitro dissolution rates of the polymer-drug salt in solid form showed similar results. Polymer-drug salts formed with the 1,12-dihydroxyoctadecane hemi-ester of poly-(methyl vinyl ether/maleic anhydride) exhibited prolongation of the release of the drug from granular and tableted forms in vitro.
Neurotrophins and their receptors: signaling trios in complex biological systems.

The neurotrophins, a class of four related growth factors, utilize a dual receptor system consisting of Trk receptor tyrosine kinases and the structurally unrelated p75NTR to modulate diverse and sometimes opposing biological actions. The identification of novel ligands for p75NTR, unconventional mechanisms for Trk activation and unique signaling intermediates further underscores the complex nature of neurotrophin: receptor interactions, as well as their functions within and outside of the nervous systems. This review summarizes recent surprises of how ligand-receptor pairing may affect diverse developmental events, regulate response to injury and extend their influence on memory and learning.
Is crossbreeding the answer to questions of dairy breed utilization

The current interest in crossbreeding in the commercial dairy industry, even though it is quite limited, raises questions of breed utilization. Fewer than 5% of US dairy cattle are other than purebred or grade Holsteins. The large advantage of Holsteins for additive genetic merit for lactation milk yield is apparently responsible for this trend. Why, then, this interest in crossbreeding? The economic importance of traits such as reproduction, health, and survival in dairy production systems is likely the basis for the interest in crossbreeding, even though these traits are secondary to milk yield. Several US studies and a Canadian study confirmed that while several crossbred groups were equivalent to Holsteins for lactation milk yield, none were superior. Two crossbred groups in the Canadian study had lifetime yields, milk value, and net returns equivalent to Holsteins. In the New Zealand study, Friesian-Jersey reciprocal crossbreds were predicted to exceed Friesians in first-lactation fat yield. Crossbred performance is dictated by a combination of additive and nonadditive genetic effects. Evidence exists for direct, maternal, heterosis, and cytoplasmic maternal effects. Heterosis of 15 to 20% for lifetime traits was found in two studies. Results from previous crossbreeding studies have something to recommend for inclusion of Holstein, Ayrshire, Brown Swiss, and Jersey breeds in a crossbreeding scheme. However, multiple-generation lifetime performance on an array of purebreds and crossbreds under US condition does not exist. Full unique identification of individual animals, including breed composition, would permit the use of DHIA data to estimate additive and nonadditive genetic parameters for the traits recorded therein. Survival data from birth and health data would need to be fully recorded to provide complete data on lifetime performance. Self-propagation of crossbred replacements is mandatory if any crossbreeding system is to be successful. Based on current empirical data, a two-breed rotational crossing system appears to be the most viable system to maximize economic merit. The theoretical advantages of a three-breed rotational crossing system are clear, but the data to recommend the third breed and this system in practice are limited. Full-scale long-term breeding experiments or analysis of field data paired with a comprehensive modeling of alternative breed utilization strategies for US conditions are recommended.
Design of a low leakage ESD clamp for high voltage supply in 65nm CMOS technology

System on Chip (SOC) designs in 65nm and beyond CMOS processes have the need to support higher voltage power supply domains in addition to the more traditional core and I/O voltages. In this work a new supply clamp architecture is proposed which ensures a reliable low leakage performance at the Higher supply voltages (5.0V for 65nm). The clamp's turn-on characteristics spans the full duration of the actual ESD events making it fully capable to effectively protect the sensitive devices in the 5V core circuit. The low leakage aspect of the supply clamp is demonstrated with the help of high temperature measurements.
Unattended ground sensor system architecture for reduced information dissemination timeline

In a multi-layered command structure, information from unattended ground sensor systems has typically been transferred from the observation area to the highest level of command. The information is analyzed from many such regions and disseminated to the appropriate forward operating base as intelligence or action orders. Some missions, like the detection and interdiction of Time Critical Targets, may be hampered by the current data dissemination timeline. Therefore alternate, faster methods of providing actionable intelligence into theater are required for these missions. This paper discusses alternative architectures that reduce the information dissemination time line from the sensor fields through the command center and back down to the quick reactionary forces.
Functional insight into development of positive allosteric modulators of AMPA receptors.

Positive allosteric modulators of α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) ionotropic glutamate receptors facilitate synaptic plasticity and contribute essentially to learning and memory, properties which make AMPA receptors targets for drug discovery and development. One region at which several different classes of positive allosteric modulators bind lies at the dimer interface between the ligand-binding core of the second, membrane-proximal, extracellular domain of AMPA receptors. This solvent-accessible binding pocket has been the target of drug discovery efforts, leading to the recent delineation of five “subsites” which differentially allow access to modulator moieties, and for which distinct modulator affinities and apparent efficacies are attributed. Here we use the voltage-clamp technique in conjunction with rapid drug application to study the effects of mutants lining subsites “A” and “B” of the allosteric modulator pocket to assess affinity and efficacy of allosteric modulation by cyclothiazide, CX614, CMPDA and CMPDB. A novel analysis of the decay of current produced by the onset of desensitization has allowed us to estimate both affinity and efficacy from single concentrations of modulator. Such an approach may be useful for effective high throughput screening of new target compounds.