cssi/SciSciGPT-SciSciNet huggingface dataset:
Estimation and inference of a cointegrated regression in panel data: a Monte Carlo study

SYNOPTIC ABSTRACTThis paper studies the finite sample properties of the least squares dummy variable (LSDV) estimator and t-statistic in a cointegrated regression in panel data. Through Monte Carlo studies we find that both the LSDV estimator and the t-statistic have a small amount of bias, and the t-statistic diverges as the cross-sectional dimension increases. We also find that the bias-corrected LSDV estimator and the bias-corrected t-statistic do not reduce the magnitude of the bias problem.
Forkhead Box Protein O1 Negatively Regulates Skeletal Myocyte Differentiation through Degradation of Mammalian Target of Rapamycin Pathway Components

The forkhead transcription factor forkhead box protein O1 (FoxO1), a downstream target of phosphatidylinositol 3-kinase/Akt signaling, has been reported to suppress skeletal myocyte differentiation, but the mechanism by which FoxO1 regulates myogenesis is not fully understood. We have previously demonstrated that a nutrient-sensing mammalian target of rapamycin (mTOR) pathway controls the autocrine production of IGF-II and the subsequent phosphatidylinositol 3-kinase/Akt signaling downstream of IGF-II in myogenesis. Here we report a regulatory loop connecting FoxO1 to the mTOR pathway. Inducible activation of a FoxO1 active mutant in the C2C12 mouse myoblasts blocks myogenic differentiation at an early stage and meanwhile leads to proteasome-dependent degradation of a specific subset of components in the mTOR signaling network, including mTOR, raptor, tuberous sclerosis complex 2, and S6 protein kinase 1. This function of FoxO1 requires new protein synthesis, consistent with the idea that a transcriptional target of FoxO1 may be responsible for the degradation of mTOR. We further show that active FoxO1 inhibits IGF-II expression at the transcriptional activation level, through the modulation of mTOR protein levels. Moreover, the addition of exogenous IGF-II fully rescues myocyte differentiation from FoxO inhibition. Taken together, we propose that the mTOR-IGF-II pathway is a major mediator of FoxO's inhibitory function in skeletal myogenesis.
Novel Luciferase-Based Reporter System to Monitor Activation of ErbB2/Her2/neu Pathway Noninvasively During Radiotherapy

Purpose To develop a split-luciferase–based reporter system that allows for noninvasive monitoring of activation of the Her2/neu pathway in vivo in a quantitative and sensitive manner. Methods and Materials Fusion proteins of the ErbB2/Her2/neu receptor to the N-terminal fragment of luciferase and of its downstream binding partner Shc to the C-terminal fragment of luciferase have been engineered owing to the rationale that on activation and binding of the Her2 receptor molecule to Shc, luciferase function will be reconstituted. Thus, the resulting bioluminescence signals can serve as a surrogate measure of receptor activation. Results We have shown that our reporter systems functions well in vitro in breast cancer cells and in vivo in xenograft tumors. In particular, the activities of Her2/neu in xenograft tumors could be monitored serially for an extended period after radiotherapy. Conclusions We believe that the novel ErbB2/Her2/neu reporter we have presented is a powerful tool to study the biology of the Her2-neu pathway in vitro and in vivo . It should also facilitate the development and rapid evaluation of new Her2/neu-targeted therapeutic agents.
901-51 Three Dimensional Reconstruction Using a New Dual Axis Multiplane Transesophageal Echo Probe: Calculation of Left Ventricular Volume

The purpose of this study is to validate LV volume measurements using a newtransesophageal echo (TEE) probe for 3 dimensional (3D) imaging which allows multiple intersecting “fan-like” scans of the...
Obstructive sleep apnea and asthma: associations and treatment implications

Obstructive sleep apnea (OSA) and asthma are highly prevalent respiratory disorders and are frequently co-morbid. Risk factors common to the two diseases include obesity, rhinitis, and gastroesophageal reflux (GER). Observational and experimental evidence implicates airways and systemic inflammation, neuromechanical effects of recurrent upper airway collapse, and asthma-controlling medications (corticosteroids) as additional explanatory factors. Therefore, undiagnosed or inadequately treated OSA may adversely affect control of asthma and vice versa. It is important for clinicians to be vigilant and specifically address weight-control, nasal obstruction, and GER in these populations. Utilizing validated screening instruments to affirm high risk of co-morbid OSA or asthma in persistently symptomatic patients will allow clinicians to cost-effectively test and treat appropriate patients, potentially improving outcomes. While non-invasive ventilation in acute asthma improves outcomes, the role of chronic continuous positive airway pressure (CPAP; the first-line treatment for OSA) in improving long-term asthma control is not known. Future research should focus on the impact of optimal CPAP therapy and adherence on asthma symptoms and outcomes.
Diverse According to Whom? Racial Group Membership and Concerns about Discrimination Shape Diversity Judgments

People often treat diversity as an objective feature of situations that everyone perceives similarly. The current research shows, however, that disagreement often exists over whether a group is diverse. We argue that diversity judgments diverge because they are social perceptions that reflect, in part, individuals’ motivations and experiences, including concerns about how a group would treat them. Therefore, whether a group includes in-group members should affect how diverse a group appears because the inclusion or apparent exclusion of in-group members signals whether perceivers can expect to be accepted and treated fairly. Supporting our claims, three experiments demonstrate that racial minority group members perceive more diversity when groups included racial in-group members rather than members of other racial minority groups. Moreover, important differences exist between Asian Americans and African Americans, which underscore the need for more research to explore uniqueness rather than commonalities ...
160 EFFECT OF cAMP MODULATORS ON IN VITRO MATURATION OF BOVINE OOCYTES

The efficiency of in vitro production (IVP) has remained low due to an inadequate in vitro maturation (IVM) system. Thus far, the most promising methods of improving IVM utilise cAMP modulators to slow the maturation process by keeping cAMP high. This experiment compares standard IVM to an extended IVM as previously described by Albuz (2010 Hum. Reprod. 25, 2999–3011). The extended IVM consists of a 2-h pre-IVM phase with FSK (an adenylate cyclase activator) and 3-isobutyl-1-methylxanthine [IBMX, a nonspecific phosphodiesterase (PDE) inhibitor], followed by a 31-h IVM phase with cilostamide (a PDE3 inhibitor). 3-Isobutyl-1-methylxanthine inhibits all PDE in both the oocyte and CC, whereas cilostamide inhibits PDE3 only in the oocyte, allowing a gradual reversal of inhibition. Bovine oocytes (n = 363) were obtained by transvaginal ultrasound-guided aspiration of both Brahman and Angus cattle over 4 collection days. Oocytes from each cow were divided into 2 groups. The first group was placed in standard 23-h IVM medium composed of TCM-199 supplemented with 10% fetal bovine serum, sodium pyruvate, penicillin and streptomycin, glutamine, and FSH, and cultured in 5% CO2 at 39°C. A subset of oocytes was removed from maturation at 8, 13, 18, and 23 h. The second group was placed into a pre-IVM medium of HEPES-TALP supplemented with 100 μM FSK and 500 μM IBMX for 2 h at 39°C, and then moved into standard maturation medium supplemented with 20 μM cilostamide for 31 h (5% CO2, 39°C). Oocytes were sampled at 8, 13, 18, 23, 28, and 33 h. Oocytes were stained with 1% orcein and nuclear status was examined for each sample time (Table 1). Data were analysed using a chi-squared test. At 8 h, there was a significant difference (P < 0.001) between GV stage of IVM and extended IVM (7.1 v. 73.2%), and between metaphase I (MI) stage IVM and extended IVM (76.2 v. 4.9%). At the 23-h time sample, there was a significant difference between metaphase II (MII) IVM and MII extended IVM (78.9 v. 30.6%; P < 0.001). There was also a significant difference between MII oocytes at 23 h IVM and MII oocytes at 33 h extended IVM (78.9 v. 33.3%; P < 0.001). These results are consistent with the hypothesis that cAMP modulators slow the nuclear maturation process. However, results also suggest that the inhibitory effect of the cAMP modulators is not completely reversible. Oocytes appear to arrest at MI by 23-h extended IVM and do not progress to MII at the same rate as standard IVM. Table 1.Nuclear status of bovine oocytes after standard IVM and extended IVM with cAMP modulators
Why Teach Literature

Author's Summary— A wider appeal can be made by stressing literature less exclusively and the whole field of foreign culture more sharply.)
Visualization of UV-induced Replication Intermediates in E. coli using Two-dimensional Agarose-gel Analysis

Inaccurate replication in the presence of DNA damage is responsible for the majority of cellular rearrangements and mutagenesis observed in all cell types and is widely believed to be directly associated with the development of cancer in humans. DNA damage, such as that induced by UV irradiation, severely impairs the ability of replication to duplicate the genomic template accurately. A number of gene products have been identified that are required when replication encounters DNA lesions in the template. However, a remaining challenge has been to determine how these proteins process lesions during replication in vivo. Using Escherichia coli as a model system, we describe a procedure in which two-dimensional agarose-gel analysis can be used to identify the structural intermediates that arise on replicating plasmids in vivo following UV-induced DNA damage. This procedure has been used to demonstrate that replication forks blocked by UV-induced damage undergo a transient reversal that is stabilized by RecA and several gene products associated with the RecF pathway. The technique demonstrates that these replication intermediates are maintained until a time that correlates with the removal of the lesions by nucleotide excision repair and replication resumes.
Deadly Love: Mothers, Whores, and Other Demonic Females in Japanese Theatre

Co‐existing with the traditional Japanese view of woman as docile, self‐sacrificing, and nurturing is an equally ancient image of woman as powerful shamaness, terrifying demon, sexual enchantress, or suffocating mother. Misogynistic and gynophobic tendencies in traditional and contemporary Japanese culture represent to certain male artists an authentic, pre‐Buddhist, pre‐Shinto Japanese soul. Fear of female sexuality and female power is traced in selected works of Shuji Terayama, Juro Kara, Tadashi Suzuki and Shogo Ohta. These contemporary Japanese male playwrights derive themes, images and characters from the rich traditions of Japanese classical literature, folk culture, Western mythology, and personal experience. They share a preference for psycho‐sexual fantasies which are often disturbingly sado‐masochistic in their depiction of women.
The danger signal adenosine induces persistence of chlamydial infection through stimulation of A2b receptors

Infections with intracellular bacteria such as chlamydiae affect the majority of the world population. Infected tissue inflammation and granuloma formation help contain the short-term expansion of the invading pathogen, leading also to local tissue damage and hypoxia. However, the effects of key aspects of damaged inflamed tissues and hypoxia on continued infection with intracellular bacteria remain unknown. We find that development of Chlamydia trachomatis is reversibly retarded by prolonged exposure of infected cells to extracellular adenosine, a hallmark of hypoxia and advanced inflammation. In epithelial cells, this effect was mediated by the A2b adenosine receptor, unique in the adenosine receptor family for having a hypoxia-inducible factor (HIF1-α) binding site at its promoter region, and was dependent on an increase in the intracellular cAMP levels, but was independent of cAMP-dependent protein kinase (PKA). Further study of adenosine receptor signaling during intracellular bacterial infection could lead to breakthroughs in our understanding of persistent infections with these ubiquitous pathogens.
Modeling lateral control in driving studies

In driving studies based on simulators and instrumented vehicles, specific models are needed to capture key aspects of driving data such as lateral control. We propose a model that uses weighted polynomial projections to predict each data point from the previous three time points, and accommodates the attempts of the drivers to re-center the vehicle before crossing the borders of the traffic lane. Our model also allows the possibility that average position within the lane may vary from driver to driver. We demonstrate how to fit the model using standard statistical procedures available in software packages such as SAS. We used a fixed-base driving simulator to obtain data from 67 drivers with Alzheimer's disease and 128 elderly drivers without dementia. Using these data, we estimated the subject-specific parameters of our model, and we compared the two groups with respect to these parameters. We found that the parameters based on our model were able to distinguish between the groups in an interpretable manner. Hence, this model may be a useful tool to define outcome measures for observational and interventional driving studies.
Reactions to Victims of Crime: Sympathy, Defensive Attribution, and the Just World.

Two studies were conducted that explored observers' perceptions of the responsibility of a victim for her involvement in a premeditated crime. Male and female college students listened to tapes of a purported victim describing, a crime (either a rape or a mugging). Severity of crime was manipulated by having some of the crimes described as unsuccessful attempts and others as successful ones. There was a general tendency toward what we have called a sympathetic reaction pattern, that is, for victims to be assigned less responsibility the more severe the crime. This effect was strongest among those individuals who believed they had a low probability of encountering a fate similar to that of the victim. Those individuals who believed they had a high probability of encountering a fate similar to the victim's tended to make defensive attributions.
Rubble around Jupiter

NASA's Jet Propulsion Laboratory has announced that Amalthea, a 270-km-long, potato-shaped inner moon of Jupiter, “apparently is a loosely packed pile of rubble,” with empty space where the rubble does not fit well together. This is among the new findings about the moon announced by JPL astronomer John Anderson and his colleagues on 9 December at the AGU Fall Meeting in San Francisco.
The role of vaccination coverage, individual behaviors, and the public health response in the control of measles epidemics: An agent-based simulation for California

Measles cases continue to occur among susceptible individuals despite the elimination of endemic measles transmission in the United States. Clustering of disease susceptibility can threaten herd immunity and impact the likelihood of disease outbreaks in a highly vaccinated population. Previous studies have examined the role of contact tracing to control infectious diseases among clustered populations, but have not explicitly modeled the public health response using an agent-based model.
Women of the South and the Art of Carlo Levi

It was Levi's search for the “indistinto originario” (Paura della liberta 19), the primordial magma where darkness and light are still fused, that attracted him to the land of interior Lucania; an area where instinct and reason, magic and science, nature and spirit were still one. And it perhaps was the same search that attracted him later on to the islands of Sicily and Sardinia. But Lucania was to remain the most congenial place to Levi's needs. In this essay I have a twofold purpose: to examine one aspect of this “indistinto originario,” the feminine, and Levi's complex relation with woman, but also to compare the Lucanian with the Sicilian female in order to show how Levi's perception of the feminine is more in tune with the former. For this purpose I discuss Verga's character Gna Pina (la Lupa) and Levi's witch Giulia Venere. Finally I try to demonstrate that such “indistinto originario” can be better expressed through shapes and colors, that is, in painting, than through words.
Accomplishing the Visions for Professional Development of Teachers Advocated in the National Science Education Standards

The National Science Education Standards include suggested visions for changing staff development programs for preparing new teachers and working with inservice teachers. Analyzing the visions for the most successful programs precedes the identification of programs that best match the NSES visions. The National Science Teachers Association is publishing a new monograph that identifies 16 model programs that approach the visions while also providing actual evidence of the successes experienced. This manuscript is an attempt to provide a setting and a rationale for the national search and for informing science teacher educators in the features of the best programs nominated after a 4-year search. Instead of only describing science teacher education programs for new and inservice teachers, actual evidence establishing their validity is offered. Perhaps the examples will be more useful if the framework and procedures used in their selections are shared with Association for Science Teacher Education members.
Relating a Social Influence Model to the Role of Acculturation in Substance Use Among Latino Adolescents1

This study examined determinants of substance use derived from the theory of planned behavior as influenced by acculturation. Latino adolescents (n= 448) completed measures of attitudes, subjective norms, perceived behavioral control, intentions toward substance use, and 2 acculturation components. The degree to which Latino adolescents were exposed to as well as use Spanish was unrelated to determinants of future substance use, whereas the degree to which they interact with non-Latino peers exerted a protective effect regarding future substance use. However, both acculturation components influenced the extent social influence determinants predicted future substance use. Intervention strategies may need to consider acculturation in order to effectively direct resources toward those psychosocial determinants of substance use of greatest relevance to Latino populations.
S. F. Platonov, P. N. Miliukov and the Theory of “Two Schools” in Russian Historiography

[This article uses the correspondence between Sergei Platonov and Pavel Miliukov to show that, before 1900, there was no clear delineation between Russian historical writing in St. Petersburg and Moscow. The theory of the “two schools,” one in St. Petersburg and its rival in Moscow, was an early twentieth century “invention,” retrospectively applied to the late nineteenth century., This article uses the correspondence between Sergei Platonov and Pavel Miliukov to show that, before 1900, there was no clear delineation between Russian historical writing in St. Petersburg and Moscow. The theory of the “two schools,” one in St. Petersburg and its rival in Moscow, was an early twentieth century “invention,” retrospectively applied to the late nineteenth century.]
Hungry pigeons make suboptimal choices, less hungry pigeons do not

Hungry animals will often choose suboptimally by being attracted to reliable signals for food that occur infrequently (they gamble) over less reliable signals for food that occur more often. That is, pigeons prefer an option that 50 % of the time provides them with a reliable signal for the appearance of food but 50 % of the time provides them with a reliable signal for the absence of food (overall 50 % reinforcement) over an alternative that always provides them with a signal for the appearance of food 75 % of the time (overall 75 % reinforcement). The pigeons appear to choose impulsively for the possibility of obtaining the reliable signal for reinforcement. There is evidence that greater hunger is associated with greater impulsivity. We tested the hypothesis that if the pigeons were less hungry, they would be less impulsive and, thus, would choose more optimally (i.e., on the basis of the overall probability of reinforcement). We found that hungry pigeons choose the 50 % reinforcement alternative suboptimally but less hungry pigeons prefer the more optimal 75 % reinforcement. Paradoxically, pigeons that needed the food more received less of it. These findings have implications for how level of motivation may also affect human suboptimal choice (e.g., purchase of lottery tickets and playing slot machines).
Intel design for manufacturing and evolution of design rules

The difficult issues in continuing Moore's law with the lack of improvement in lithography resolution are well known. 1, 2, 3 Design rules have to change and DFM methodology has to continue to improve to enable Moore's law scaling. This paper will discuss our approach to DFM though co-optimization across design and process. The poly layer is used to show how rules have changed to meet patterning requirements and how co-optimization has been used to define the poly design rules. With the introduction and ramp of several products on our 45nm technology, we have shown our ability to meet the goals of Moore's law scaling at high yields in volume manufacturing on a two year cycle.
Decreased initiation factor activity in mouse L cells treated with interferon.

INHIBITION of virus-directed protein synthesising events in extracts of cells treated with interferon has been reported1–3. Inhibition of translation of viral mRNAs has been associated with a protein bound to ribosomes of cells treated with interferon4,5. This inhibition may involve the initiation or elongation steps in protein synthesis6,7. Recently, initiation factors for protein synthesis have been isolated from a variety of eukaryotic cells, and it has been established that the initiation factors interact with non-formylated methionyl initiator RNA (Met-tRNAf) and GTP to form a ternary complex8,9. The experiments presented here show that the activity of initiation factor(s) to form a ternary complex may be impaired or altered in mouse L cells treated with homologous interferon. In preliminary experiments with the initiation factor preparation it was confirmed that the formation of a ternary complex (Met-tRNAf–elF‐GTP) required GTP for maximal formation (within 2 min at 37 C) and the amount of complex formed was directly proportional to the concentration of initiation factor (Fig. 1). ATP did not substitute for GTP and Mg2+ inhibited its formation (data not shown).
Spectral selectivity in compressive spectral imaging based on grayscale coded apertures

Compressive Spectral Imaging (CSI) is a signal acquisition technique that captures a spatial map of the spectral variation of a scene. Recently, a new optical imaging architecture called Coded Aperture Snapshot Spectral Imaging (CASSI) has emerged. The CASSI emulates the role of a spectrometer insomuch that it captures spectral information but uses coded apertures to take 2D compressed measurements from a 3D scene. Subsequently, an optimization algorithm is used to recover the full 3D spectral image from the measurements. However, in some applications is required to recover just a few selected set of spectral information. Then, compressive spectral selectivity aims to recover a specific set of spectral bands of interest. This work extends the capabilities of CASSI by replacing the traditional block-unblock coded apertures for a grayscale valued coded aperture. Further, the structures of the gray scale-valued coded apertures are designed such that a specific set of selected bands is reconstructed with high quality. A forward model and its corresponding reconstruction method are presented allowing to recover the desired bands, exclusively. Simulations are performed obtaining reconstructions exhibiting PSNRs of up to 30 dB.
Sex-Role Stereotypes: Issues of Attitudinal Changes.

Systematic study of current sex-role beliefs has been aided by the development of the Sex Role Stereotype Questionnaire. This inquiry explored the assumption that the sex-role stereotypes of school counselors, tested seven years after the development of the questionnaire, would differ substantially from the norming samples. The data analysis revealed that the majority (three-quarters) of the behavioral characteristics viewed as stereotypic by the original samples were not seen by male and female school counselors or by either the male or female counselor independently as differentiating men and women.
Rapid liquid chromatography–tandem mass spectrometry-based method for the analysis of alcohol ethoxylates and alkylphenol ethoxylates in environmental samples

A sensitive and selective method for the determination of alcohol ethoxylates (AEOs) and alkylphenol ethoxylates (APEOs) using solid-phase extraction (SPE) and LC-MS/MS was developed and applied to the analysis of water samples. All AEO and APEO homologues, a total of 152 analytes, were analyzed within a run time of 11min, and the MS allowed for the detection of ethoxymers containing 2-20 ethoxy units (nEO=2-20). The limits of detection (LOD) were as low as 0.1pg injected, which generally increased as nEO increased (e.g., as high as 300pg for nEO=20). Additionally, the responses of the various ethoxymers varied by orders of magnitude, with ethoxymers with nEO=3-5 being the most sensitive and those with nEO>15 producing the least response in the MS. Absolute extraction recoveries of the analytes ranged from 37% to 69% in ultrapure water (RSD≤20%), with the recovery depending on the length of the alkyl chain. Abiotic stability studies were performed, and C14-18 ethoxylates showed significant degrees of degradation. Water samples from the Colorado River were then analyzed for AEOs and APEOs, with absolute extraction recoveries ranging from 33% to 45% (RSD≤12%). The predominant species observed in most samples were the octylphenol (OP) and nonylphenol (NP) ethoxylates, which contained total concentrations that were greater than 100ng/L APEOs in a couple samples. Other AEO homologues were identified in the river water samples, including C13, C15, C16, and C18 ethoxylates, but these compounds were generally present at much lower levels (i.e., <50ng/L total concentration).
Chemotherapy induced DNA damage response: Convergence of drugs and pathways

Chemotherapeutics target rapidly dividing cancer cells by directly or indirectly inducing DNA damage. Upon recognizing DNA damage, cells initiate a variety of signaling pathways collectively referred to as the DNA damage response (DDR). Interestingly, the pathways used to elicit this response are as varied as the types of DNA damage induced. However, the activation of these various pathways has similar results including DNA repair, suppression of global general translation, cell cycle arrest and, ultimately, either cell survival or cell death. This review will focus on a series of chemotherapy-induced DNA lesions and highlight recent advances in our understanding of the DDR, the DNA repair pathways it activates and the cellular consequences of these converging pathways.
Zonal Embedded Grids for Numerical Simulations of Wall-Bounded Turbulent Flows

A B-spline based numerical method on a zonal embedded grid has been developed. The method is aimed at reducing the computational requirements for large eddy simulations (LES) and direct numerical simulations (DNS) of wall-bounded turbulent flows. The objective is to reduce the number of grid points required to resolve the near-wall eddies without placing a large number of grid points in the outer layers. DNS and LES calculations of a turbulent channel flow were performed on a grid with a zone near the wall that was refined in all three directions. The results from the zonal grid calculations show good agreement with previously published numerical and experimental results obtained for the same flow conditions. The zonal grid calculations required only a fraction of the CPU time required for the single zone grid calculation with the same near-wall grid density. In addition, the memory requirements for the zonal grid calculations are significantly reduced.
Use of FDG-PET in differentiating benign from malignant compression fractures.

Objective The objective was to evaluate the use of fluorodeoxyglucose positron emission tomography (FDG-PET) in differentiating benign from malignant compression fractures.
The effect of inhibitor binding on the structural stability and cooperativity of the HIV-1 protease.

The effects of the peptide inhibitor acetyl pepstatin on the structural stability of the HIV-1 protease have been measured by high sensitivity calorimetric techniques. At 25°C and pH 3.6, acetyl pepstatin binds to HIV-1 protease with an affinity of 1.6 × 107 M-1 and an enthalpy of 7.3 ± 0.5 kcal/mol, indicating that binding is not favored enthalpically and that the favorable Gibbs energy originates from a large positive entropy. Since the binding of acetyl pepstatin is associated with a negative change in heat capacity (−450 cal/K⋅mol) the association reaction becomes enthalpically favored at temperatures higher than 40°C. The presence of the inhibitor stabilizes the dimeric structure of the protease in a fashion that can be quantitatively described by a set of thermodynamic linkage equations. The combination of titration and differential scanning calorimetry provides an accurate way of determining binding constants for high affinity inhibitors that cannot be determined by titration calorimetry alone. A structure-based thermodynamic analysis of the binding process indicates that the stabilization effect is not distributed uniformly throughout the protease molecule. The binding of the inhibitor selectively stabilizes those conformational states in which the binding site is formed, triggering a redistribution of the state probabilities in the ensemble of conformations populated under native conditions. As a result, the stability constants for individual residues do not exhibit the same change in magnitude upon inhibitor binding. Residues in certain areas of the protein are affected significantly whereas residues in other areas are not affected at all. In particular, inhibitor binding has a significant effect on those regions that define the binding site, especially the flap region which becomes structurally stable as a result of the additional binding free energy. The induced stabilization propagates to regions not in direct contact with the inhibitor, particularly to the strand between residues Pro9 and Ala22 and the helix between Arg87 and Gly94. On the other hand, the stability of the strand between Asp60 and Leu76 is not significantly affected by inhibitor binding. The structural distribution of binding effects define cooperative pathways within the protease molecule. Proteins 1999;36:147–156. © 1999 Wiley-Liss, Inc.
Nervenkitt: notes on the history of the concept of neuroglia.

The evolution of concepts concerning the identity and the functions of neuroglia is traced. Some of the main ideas in the works of Virchow, Deiters, Golgi, Lenhossek, Lugaro, Ramon y Cajal, del Rio-Hortega, Achucarro, Penfield, and others are highlighted.
Obsolete and Irreversible: Technology, Local Economic Development, and the Environment

While “economic development” projects have long been proposed and supported by local growth machine elites, technological change has affected the social desirability of large projects in three ways. First, large development projects—we examine water transportation—have grown in size, meaning that backers often seek public funding. With increased size and the need for external funding, many years or decades can elapse by the time a project can be conceived, politically supported, funded, and built. Second, during that time, the technology of the industrial sector in question may have changed radically—to the point that the project can be obsolete, or rapidly nearing obsolescence, by the time it is actually completed. Third, the massive size of the project may also mean that even if the project is obsolete as well as environmentally harmful, we may find ourselves unable to undo it or the environmental damage that it has caused.
Limits to food intake by the Prairie Vole: effects of time for digestion

Summary 1 Prairie Voles (Microtus ochrogaster Wagner) are among the smallest vegetation-feeding mammalian herbivores, and thus show a high ratio of energetic expenditure to energy content of ingested food that may lead to digestive bottlenecks. By varying the periodicity of 3 h of food availability, it was found that energy assimilation in Prairie Voles is not limited by the time required to consume food, but by the time required to digest and absorb food. 2 Three hours is all the time that is necessary for a Prairie Vole to consume the food needed for 1 day. Although voles offered food in one 3-h block per 24 h increased dry matter digestibility, they could not consume enough food to maintain body mass. However, when offered 3 h of food availability but divided into six 30-min periods evenly spaced throughout 24 h Prairie Voles reached a level of food intake similar to that of control voles fed ad libitum and stabilized body mass similar to controls. 3 It is suggested that a vole’s stomach capacity limits intake for each feeding bout, regardless of how empty the following chambers are after any period of food restriction and the rate of stomach emptying may dictate the feeding bout periodicity. The amount of stomach contents (1·1–1·4 g) found in voles held under similar conditions to those in our experiments closely resembles the amount of food consumed (0·78–1·4 g) during each of the six 30-min periods of feeding. 4 The bottleneck limits intake of food and keeps feeding bouts spaced. The time required for digestion may be the cause for a vole’s observed 2–4 h ultradian activity rhythm. Evidence is given that spacing between activity periods may be adjusted to the metabolic demands of the species.
Elimination of speckle and target orientation requirements in millimeter-wave active imaging by modulated multimode mixing illumination.

Active imaging can provide significantly larger signal margins in the millimeter-wave spectral region than passive imaging, especially indoors—an important application for which there is no cold sky illumination. However, coherent effects, such as speckle, negate much of this advantage by destroying image clarity and target recognition. Moreover, active imaging demonstrations often use strategically chosen target orientations to optimally reflect power from the active illuminator back to the imaging receiver. In this paper we will discuss and show experimental results for a new active imaging approach that largely eliminates coherent effects and the need for optimized target orientation. The work described uses a synthesized harmonic multiplier chain to drive a 5 W extended interaction klystron at 218.4 GHz, a mechanical mode mixer to illuminate and modulate many modes, and a heterodyne receiver coupled into a 60 cm scanning mirror. Large signal margins were obtained in this ∼50 m range work, showing paths to imaging at ∼1 km, imaging with considerably less powerful illuminators, and the use of focal plane arrays.
The barriers in protein folding

Elimination of an interaction which forms in denatured cytochrome c enables the majority of the molecules to fold to the native state on a 15 ms time scale, without populating observable intermediates. These results are contrary to the current view that particular steps in protein folding, including the supposedly rate-limiting molten globule to native transition, are intrinsically slow. Instead it appears that intermediates characterized so far may be kinetically trapped by barriers that are optional rather than integral to the folding process. Major barriers may result from misorganization of the chain in the initial condensation step.
Thymic anti-tumor effectors in mice cured of lymphoma by cyclophosphamide plus TNF-α therapy: Phenotypic and functional characterization up to 20 months after initial tumor inoculation

As reported previously, cyclophosphamide plus tumor necrosis factor-α treatment of C57BL/6 mice bearing advanced EL4 lymphoma induced approx. 60% long-term (i.e., >60 days) survivors. These mice developed protective immunity, as evidenced by 1) rejection (100% survival) of EL4 tumor re-implanted on day 60 (day 0 = initial tumor implantation); and 2) development of significant levels of specific EL4 tumor cell killing activity by both splenocytes and thymocytes. Using this model, age-related changes in functionally and phenotypically definable thymocyte subsets were assessed. In thymocytes from 90 to 308 day survivors, specific immune memory was long term; both CD4+ and CD8+ cells were required for the ex vivo stimulation of lytic activity, but the specific anti-EL4 cytotoxic effector was CD4−CD8+. On day 520, the surviving mice were randomized into 2 groups. One group received a second re-challenge with EL4 tumor cells and all survived. The other group was sacrificed on day 520. Their thymocytes, exposed to X-irradiated EL4, developed anti-EL4 lytic activity and, in comparison with thymocytes of young and age-matched control mice, were markedly enriched in CD4−CD8+CD44+ cells. On day 625, thymocytes from the survivors of the day 520 re-challenge were evaluated and were found to have developed specific anti-EL4 lytic activity. Phenotypically, they had returned toward the pattern seen in age-matched control mice although CD4−CD8+CD44+ cells remained increased. These mice were ≥2 years old, the median life span of C57BL/6 mice. Thus, mice cured of tumor by an immuno-modulating regimen rejected re-implanted primary tumor and maintained specific thymic anti-tumor immune memory for life. Int. J. Cancer 76:579–586, 1998.© 1998 Wiley-Liss, Inc.
Cytostatic gene therapy for vascular proliferative disorders with a constitutively active form of the retinoblastoma gene product

Vascular smooth muscle cell (SMC) proliferation in response to injury is an important etiologic factor in vascular proliferative disorders such as atherosclerosis and restenosis after balloon angioplasty. The retinoblastoma gene product (Rb) is present in the unphosphorylated and active form in quiescent primary arterial SMCs, but is rapidly inactivated by phosphorylation in response to growth factor stimulation in vitro. A replication-defective adenovirus encoding a nonphosphorylatable, constitutively active form of Rb was constructed. Infection of cultured primary rat aortic SMCs with this virus inhibited growth factor-stimulated cell proliferation in vitro. Localized arterial infection with the virus at the time of balloon angioplasty significantly reduced SMC proliferation and neointima formation in both the rat carotid and porcine femoral artery models of restenosis. These results demonstrate the role of Rb in regulating vascular SMC proliferation and suggest a gene therapy approach for vascular proliferative disorders associated with arterial injury.
Actimeter-derived sleep and wake data and nocturnal ambulatory blood pressure estimation in subjects with stroke and transient ischaemic attack.

Background/Aims Abnormalities in nocturnal blood pressure control identified using ambulatory blood pressure monitoring are associated with adverse cardiovascular outcomes. Sleep and wake episodes during such studies are usually identified by means of sleep diaries but these may be inaccurate in stroke patients. We performed a study to determine whether sleep–wake data obtained using wrist-mounted actimeters would significantly influence the results of routinely performed nocturnal ambulatory blood pressure monitoring when compared with diary-based sleep–wake recording and fixed time-period data. Methods Actimetry was performed using a wrist-mounted device during routine ambulatory blood pressure monitoring in subjects who had suffered a transient ischaemic attack or stroke. The mean nocturnal blood pressure readings were calculated using sleep data derived from actimetry and diaries and compared for a fixed time period from 11:00 pm to 8:00 am. Results Twenty subjects (mean age 68 years, and 13 female) were studied. Patients were found to have slept for a median of six-hours (one- to eight-hours) by diary and five-hours (zero- to eight-hours) by actimeter data. Diary and actimeter data agreed in 69% of recordings. The mean sleeping systolic blood pressure was lower when calculated by actimeter data than by diary data (119·6 mmHg vs. 123·2 mmHg, P=0·049, paired t-test) but there was no significant difference in diastolic blood pressure. The mean nocturnal blood pressure calculated from 11:00 pm to 7:00 am was higher than sleeping blood pressure calculated from diary data. (mean systolic blood pressure: 127·6 mmHg vs. 123·6 mmHg, P=0·065; mean diastolic blood pressure 69·0 vs. 64·0, P=0·028). Conclusion Calculation of nocturnal and sleeping blood pressure is lower in subjects with stroke and transient ischaemic attack when objective actimeter-derived sleep/wake data are used.
Theory of single-well tests in acute fracture?wellbore systems

Abstract This study aims at establishing an understanding of the influence of the (fracture–wellbore) system intersection angle on various predictions made through single-well tests and developing mathematical models which can reproduce the responses of acute systems to various forms of disturbances under different conditions. The differential equation governing flow in conceptualized acute systems is derived from basic principles. Analytical solutions to this equation are reached for both transient and steady constant-flux test conditions. The potential theory is utilized to delineate the flow network and the zone of influence in acute systems during tests under initially non-uniform head conditions. The likelihood of non-linear flow regime and its influence on the observed head changes and hence the aperture (or permeability) predictions are addressed and a general formulation is introduced. An overall discussion for the proposed models also addresses the natural extension of the basic concepts to refine estimates of other well test models. Major observations of practical significance include: (a) permeability of a hydraulically effective fracture is misjudged whenever an acute system is reduced to an orthogonal or a vertical system configuration and (b) efficiency of production wells is largely affected from the angle of intersection, the fracture(s) dominating flow forms with the wellbore. © 1997 Elsevier Science B.V. All rights reserved.
Effects of preweaning injections of adrenalin on later open field behavior of rats

Wistar rats were given 0.0, 0.4, 1.2, or 3.6 mg/kg injections of epinephrine at either 2 or 10 days of age. Three weeks later their open field behavior was compared to non-injected matched littermates. No age or dosage differences were found, but all injected groups defecated less than non-treated groups.
Human embryo research and the language of moral uncertainty.

In bioethics as in the sciences, enormous discussions often concern the very small. Central to public debate over emerging reproductive and regenerative biotechnologies is the question of the moral status of the human embryo. Because news media have played a prominent role in framing the vocabulary of the debate, this study surveyed the use of language reporting on human embryo research in news articles spanning a two-year period. Terminology that devalued moral status—for example, the descriptors things, property, tissue, or experimental material —was found to outnumber fivefold those that affirmed any degree of moral status above that of inanimate cellular matter; for example, living, human life, or human being. A quarter of the articles failed to note that the embryos under discussion were human. These findings confirm that even among scientific and philosophical experts a diversity of opinion exists on society's moral obligations to nascent human life. The skewed linguistic distribution also indicates...
Human Eyeblink Classical Conditioning: Effects of Manipulating Awareness of the Stimulus Contingencies

In four groups, we either promoted or prevented awareness of the stimulus contingencies during trace or delay differential eyeblink classical conditioning. To reduce awareness of the stimulus contingencies, we asked two groups to engage in a secondary attention-demanding task during trace or delay conditioning. To promote awareness of the stimulus contingencies, we explained the relationships between the stimuli to two other groups before trace conditioning. One of these groups then engaged in the secondary task during conditioning. Following conditioning, awareness of the stimulus contingencies was assessed with a true/false questionnaire. Preventing awareness of the stimulus contingencies disrupted trace differential eyeblink conditioning but did not affect delay differential conditioning. Providing knowledge about the stimulus contingencies facilitated trace conditioning. Finally, providing knowledge about the stimulus contingencies, then having subjects engage in a distraction task, disrupted trace co...
Maternal Union Transitions and Household Food Insecurity Differences by Race and Ethnicity

The study investigates how transitions in maternal unions are related to household food insecurity among a low-income sample using pooled time series data from the Early Childhood Longitudinal Survey–Birth Cohort. Pooled time series fixed effects models indicate that transitioning into unions for White and Hispanic households is associated with reductions in household food insecurity compared with White and Hispanic households who experienced no transitions. Furthermore, transitioning into unions for Hispanic households is associated with reductions in household food insecurity status compared with Hispanic households that experienced dissolving unions. Last, results indicate that maternal union transitions are not related to household food insecurity status of Black and Other race and ethnic households. The authors discuss how the findings may be related to socioeconomic factors of race and ethnic households.
A relational framework for higher-order shape analysis

We propose the integration of a relational specification framework within a dependent type system capable of verifying complex invariants over the shapes of algebraic datatypes. Our approach is based on the observation that structural properties of such datatypes can often be naturally expressed as inductively-defined relations over the recursive structure evident in their definitions. By interpreting constructor applications (abstractly) in a relational domain, we can define expressive relational abstractions for a variety of complex data structures, whose structural and shape invariants can be automatically verified. Our specification language also allows for definitions of parametricrelations for polymorphic data types that enable highly composable specifications and naturally generalizes to higher-order polymorphic functions. We describe an algorithm that translates relational specifications into a decidable fragment of first-order logic that can be efficiently discharged by an SMT solver. We have implemented these ideas in a type checker called CATALYST that is incorporated within the MLton SML compiler. Experimental results and case studies indicate that our verification strategy is both practical and effective.