cssi/SciSciGPT-SciSciNet huggingface dataset:
Novel biomarkers to assess in utero effects of maternal opioid use: First steps toward understanding short- and long-term neurodevelopmental sequelae.

Maternal opioid use disorder is common, resulting in significant neonatal morbidity and cost. Currently, it is not possible to predict which opioid-exposed newborns will require pharmacotherapy for neonatal abstinence syndrome. Further, little is known regarding the effects of maternal opioid use disorder on the developing human brain. We hypothesized that novel methodologies utilizing fetal central nervous system-derived extracellular vesicles isolated from maternal blood can address these gaps in knowledge. Plasma from opioid users and controls between 9 and 21 weeks was precipitated and extracellular vesicles were isolated. Mu opioid and cannabinoid receptor levels were quantified. Label-free proteomics studies and unbiased small RNA next generation sequencing was performed in paired fetal brain tissue. Maternal opioid use disorder increased mu opioid receptor protein levels in extracellular vesicles independent of opioid equivalent dose. Moreover, cannabinoid receptor levels in extracellular vesicles were upregulated with opioid exposure indicating cross talk with endocannabinoids. Maternal opioid use disorder was associated with significant changes in extracellular vesicle protein cargo and fetal brain micro RNA expression, especially in male fetuses. Many of the altered cargo molecules and micro RNAs identified are associated with adverse clinical neurodevelopmental outcomes. Our data suggest that assays relying on extracellular vesicles isolated from maternal blood extracellular vesicles may provide information regarding fetal response to opioids in the setting of maternal opioid use disorder. Prospective clinical studies are needed to evaluate the association between extracellular vesicle biomarkers, risk of neonatal abstinence syndrome and neurodevelopmental outcomes.
The forgotten front: Patron-client relationships in counterinsurgency

In this meticulously researched and well-written volume, Walter C. Ladwig III identifies a crucial oversight in the American approach to counter-insurgency (COIN) operations undertaken with partner...
1894 Measuring selection in nature

Abstract As the work of Darwin excited the community of scientists there was interest in collecting evidence of natural selection in action. Walter F. R. Weldon was one of the first to take on this task. Darwin emphasized the role of individual variation that might confer an advantage in reproduction or survival to its carrier. Weldon made measurements of the shell size of the crab Carcinus moenas among young and adult crabs (Weldon, 1894–1895). By separating out changes that might be due to growth versus changes that were due to selective loss he made one of the first attempts to measure natural selection in nature through differential survival.
CHAPTER THREE – Supply, Demand, and the Market Process

Publisher Summary This chapter focuses on supply, demand, and the market process. The rise in the price of sugars—an essential ingredient in moonshine—changed life in the laurel thickets rapidly. It takes at least 10 pounds of sugar to make a gallon of barnyard whiskey. With other inflationary factors added, moonshine that sold for $6 a gallon in the past at the still began pushing $15 a gallon. At that price, the moonshine market contracted severely, because for $15 plus retail mark-up, a customer can buy government whiskey. The price squeeze on moonshine has forced new occupations on a lot of people who were engaged, one way or another, in what might have been the largest industry in such counties as Habersham, Dawson, and Gilmer. Not all of those people whose employment depended on illegal booze were moonshiners themselves, however. For the government, one beneficial by-product of the sugar inflation and moonshine depression is an increase in arrests for firearms violations and illegal wagering.
Distrianthes exxonmobilensis (Loranthaceae), a new species in a formerly monotypic genus from Papua New Guinea

Distrianthes exxonmobilensis is described from karst environments along the PNG LNG Pipeline in southern New Guinea. It is the second species in a genus previously regarded as monotypic. The new loranth is distinguished by an inflorescence reduced to a single flower or triad, and by the geographic disjunction from previous generic localities.
The rax homeobox gene is mutated in the eyeless axolotl, Ambystoma mexicanum

Background Vertebrate eye formation requires coordinated inductive interactions between different embryonic tissue layers, first described in amphibians. A network of transcription factors and signaling molecules controls these steps, with mutations causing severe ocular, neuronal, and craniofacial defects. In eyeless mutant axolotls, eye morphogenesis arrests at the optic vesicle stage, before lens induction, and development of ventral forebrain structures is disrupted. Results We identified a 5-bp deletion in the rax (retina and anterior neural fold homeobox) gene, which was tightly linked to the recessive eyeless (e) axolotl locus in an F2 cross. This frameshift mutation, in exon 2, truncates RAX protein within the homeodomain (P154fs35X). Quantitative RNA analysis shows that mutant and wild-type rax transcripts are equally abundant in E/e embryos. Translation appears to initiate from dual start codons, via leaky ribosome scanning, a conserved feature among gnathostome RAX proteins. Previous data show rax is expressed in the optic vesicle and diencephalon, deeply conserved among metazoans, and required for eye formation in other species. Conclusion The eyeless axolotl mutation is a null allele in the rax homeobox gene, with primary defects in neural ectoderm, including the retinal and hypothalamic primordia.
In older patients with NSTE-ACS, clopidogrel safely reduced bleeding compared with ticagrelor at 1 year.

SOURCE CITATION Gimbel M, Qaderdan K, Willemsen L, et al. Clopidogrel versus ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation acute coronary syndrome (POPular AGE): the randomised, open-label, non-inferiority trial. Lancet. 2020;395:1374-81. 32334703.
Cross-Disciplinary Analysis in Global Tension, 2010–2020

In language, contrast developed between internal language and spoken language. Studies of emotions advanced at the level of individual organisms, including animals, and in human groups. Comparisons of the learning of humans and primates revealed both parallels and specific human distinctions. Work in philosophy and economics showed how explicit groups, formed by agreement among individuals, could function differently from uncommitted individuals, leading to a theory of social institutions. Various approaches to social evolution are shown to rely on differing time frames. The conclusion summarizes contemporary study in human evolution at six scales of biological, cultural, and social analysis. The growth in multidisciplinary research and writing suggests that one may expect clarification of more of the questions in human evolution, along with collaboration that may bring some answers (126).
1Phytoestrogens and bone

Abstract Practically all plant foods contain small amounts of the diverse phytoestrogen moleculesthat have the potential to improve health. Phytoestrogens, especially the soy-derived isoflavones, are receiving great scrutiny as food supplements for the purposes of both enhancing the health of tissues and preventing several common diseases, such as cardiovascular diseases, cancers of reproductive tissues and osteoporosis. Investigations of isoflavones, in particular, have recently become more prominent because of their oestrogenic activities. These actions may be as either partial oestrogen agonists or antioestrogens (inhibitors of natural oestrogen activity). For example, the isoflavones of soy, mainly genistein and daidzein, have been shown by at least three different laboratories to conserve bone in ovariectomized rodent models, and they probably have similar conservatory effects in higher mammalian species. Nevertheless, the only positive effects of phytoestrogens on bone observed so far in post-menopausal women have been small and limited to the lumbar vertebrae. Additional information on human studies currently in progress is needed before the efficacy of these preparations in human subjects is known.
Effect of first-line biologic initiation on glucocorticoid exposure in children hospitalized with new-onset systemic juvenile idiopathic arthritis: emulation of a pragmatic trial using observational data.

BACKGROUND Glucocorticoid exposure is a significant driver of morbidity in children with systemic juvenile idiopathic arthritis (sJIA). We determined the effect of early initiation of biologic therapy (IL-1 or IL-6 inhibition) on glucocorticoid exposure in hospitalized patients with new-onset sJIA. METHODS We emulated a pragmatic sequence of trials ("pseudo-trials") of biologic initiation in children (≤ 18 years) hospitalized with new-onset sJIA utilizing retrospective data from an administrative database from 52 tertiary care children's hospitals from 2008 to 2019. Eligibility window, treatment assignment and start of follow-up between biologic and non-biologic study arms were aligned for each pseudo-trial. Patients in the source population could meet eligibility criteria at several timepoints. Mixed-effects logistic regression was used to determine the effect of biologic initiation on in-hospital glucocorticoid exposure. RESULTS Four hundred sixty-eight children met eligibility criteria, of which 19% received biologic therapy without preceding or concomitant initiation of immunomodulatory medications. This proportion significantly increased over time during the study period (p < 0.01). 1451 trial subjects were included across 4 pseudo-trials with 71 assigned to the biologic arm and 1380 assigned to the non-biologic arm. After adjustment, there was a trend toward decreased odds of glucocorticoid initiation in the biologic arm compared to the non-biologic arm (OR 0.39, 95% CI [0.13, 1.15]). CONCLUSION Biologic initiation in children hospitalized with new-onset sJIA significantly increased over time and may be associated with reduced glucocorticoid exposure. The increasing use of first-line biologic therapy may lead to clinically relevant reductions in treatment-related adverse effects of glucocorticoid-reliant therapeutic approaches.
Confronting Late Work in the Student-Centered Classroom

This Quick Fix describes the author’s use of a single-use “Life Happens Waiver” as a modification of an otherwise typical late work policy. The strategy is intended to empower students, to establis...
In Search of Patents: A tool for real-time search of the United States Patent and Trademark Office data at scale

Use of patent data by academics is widespread, especially in scholarship related to innovation and technology management. However, even with increased online access to patent databases, patent searches at scale are still challenging. We present Patentopia, a simple online tool extracting information from the PatentsView portal linked to the United States Patent and Trademark Office. In this note, we describe the tool's operation, use cases, and envisioned usage.
TH-EF-BRD-03: Demonstration of a Concurrent Monte Carlo Dose Calculation and Fluence Optimization Platform with Low Memory Footprint

Purpose: To enable a treatment planning solution that utilizes voxel-specific penalties requires optimizing over a large solution space both quickly and accurately. Although challenging, such methods will enhance the clinical impact of adaptive (online and offline) and biologically guided radiotherapy. Monte Carlo calculations generally provide improved accuracy over deterministic methods, but with increased computation time. Instead, we present a low memory footprint direct Monte Carlo optimization platform that optimizes the fluence concurrently during the MC dose calculation. This reduces the wasted computation time spent on minimally contributing beamlets, and makes the combined optimization and dose calculation tasks both fast and accurate even over a large mathematical space. Methods: The Monte Carlo code Geant4 v9.6 was used to create the Fluence Adjusted Scaled Transport Monte Carlo (FASTMC) platform. The FASTMC platform minimizes clinical cost objectives during the dose calculation using multiple co-planar sources of arbitrary gantry angle and SID, for rotational or fixed beams. Beamlet particle histories are transported in iterative steps; cost is evaluated after each iteration, with beamlet intensity and dose profile incremented such that the cost is decreased. A Greedy Heuristic algorithm is employed that circumvents the necessity of a dose coefficient matrix, resulting in a memory footprint scaling that is independent of the patient CT resolution, and allows for intelligently biased selection, and calculation of beamlets based on costs in prior iterations. Results: A multi-field coplanar prostate plan was generated during the MC dose calculation, resulting in an optimized dose profile that is calculated concurrently with the optimized fluence. All clinical constraints for the target and OARs were met for this plan. Conclusion: This study demonstrated the feasibility of optimizing an incident fluence map using voxel-specific penalties during Monte Carlo dose calculations as a means of treatment planning tailored to emerging radiation therapy delivery paradigms. This work is partially based upon an idea conceived by Varian Medical Systems. This work is partially supported by the NIH Training Grant 2T32CA009206-36A1.
EXCRETORY NITROGEN METABOLISM AND GLUCONEOGENESIS DURING DEVELOPMENT OF HIGHER VERTEBRATES

ABSTRACT The concept of nitrogen “excretion” by mammalian and avian embryos is examined in light of contemporary knowledge of hepatic metabolism. The origin of “waste” nitrogen and the hepatic pathways for its conversion to either urea or uric acid for excretion are described. The probable evolution of these pathways among the higher tetrapod vertebrates and the impact of the selective advantage of uricoteley on the radiation of the archosaurs are considered. The intimate connection of hepatic gluconeogenesis with nitrogenous end product formation in birds and mammals is examined. Finally, the development of the capacities for gluconeogenesis and for either ureogenesis or urieogenesis in the perinate is discussed relative to the problem of development in a cleidoic egg.
Autoregulation of Eukaryotic Transcription Factors

The structures of several promoters regulating the expression of eukaryotic transcription factors have in recent years been examined. In many cases there is good evidence for autoregulation, in which a given factor binds to its own promoter and either activates or represses transcription. Autoregulation occurs in all eukaryotes and is an important component in controlling expression of basal, cell cycle specific, inducible response and cell type-specific factors. The basal factors are autoregulatory, being strictly necessary for their own expression, and as such must be epigenetically inherited. Autoregulation of stimulus response factors typically serves to amplify cellular signals transiently and also to attenuate the response whether or not a given inducer remains. Cell cycle-specific transcription factors are positively and negatively autoregulatory, but this frequently depends on interlocking circuits among family members. Autoregulation of cell type-specific factors results in a form of cellular memory that can contribute, or define, a determined state. Autoregulation of transcription factors provides a simple circuitry, useful in many cellular circumstances, that does not require the involvement of additional factors, which, in turn, would need to be subject to another hierarchy of regulation. Autoregulation additionally can provide a direct means to sense and control the cellular conce]ntration of a given factor. However, autoregulatory loops are often dependent on cellular pathways that create the circumstances under which autoregulation occurs.
Membranous cytochrome c oxidase: A freeze-fracture electron microscopic analysis

Abstract Suspensions of membranous cytochrome c oxidase prepared from beef heart mitochondria by Triton extraction were ultra-rapidly cooled (in excess of 10,000 deg.C/s) and analyzed using freeze-fracture and freeze-fracture-etch techniques. The preparations contained non-crystalline and crystalline vesicles as isolated vesicles, vesicles inside other vesicles and stacks of vesicles. In non-crystalline vesicles the particles (about 100 A diameter) are probably formed by the deviation of hydrophobic fracture planes of the membranes around the large transmembrane enzymes. The intramembrane particles thus formed are compared to particles (about 80 A diameter) in a vesicle reconstituted from purified enzyme and lipid. Crystalline membranous cytochrome c oxidase vesicles display an unusual fracture pattern in which adjacent crystalline surfaces are separated from each other and from the surrounding ice by fracture steps that are approximately the thickness of a single membrane (100 to 120 A). In addition adjacent crystalline fracture surfaces have similar low-relief textures, both of which differ significantly from the hydrophobic surfaces normally exposed in membrane fractures. This fracture morphology is interpreted in terms of fractures along hydrophilic surfaces of the membranes. Images of etched crystalline vesicles provide support for this interpretation because etching exposes no new surfaces. It is concluded that the crystalline lattices are derived from the portions of enzymes that protrude from the membrane bilayers and that the interdigitation of the enzymes on the inside surfaces of the vesicles or between vesicles determines the appearance of the crystalline surfaces. The arrangement of the tails of the y-shaped molecules on the cytoplasmic sides of the crystalline membranes can be visualized in micrographs directly and in reconstructions of filtered images. The more complex pattern of arms protruding on the matrix side is obscured by the unidirectional shadowing. Fragmentation of the crystalline membranes during fracturing is indicated by particles sometimes present at the edges of fractured membranes and by deep, irregular pits observed in crystalline surfaces. Particles resting on some crystalline surfaces may be fragments of crystalline membranes removed during fracturing. In other crystalline membranes non-protein is removed during fracturing, leaving globular particles embedded in the lattice, which measure about 118 A diameter. Comparing these particles to the 3-dimensional arrangement of protein described in the accompanying paper (Frey et al. , 1982) suggests that such particles are composed of 2 dimers paired along the a -axis. Intramembrane and fragmentation particles of similar size may also have this protein composition.
A cellular protein phosphorylated by the avian sarcoma virus transforming gene product is associated with ribonucleoprotein particles.

Abstract In chick embryo fibroblasts transformed by Rous sarcoma virus (RSV) the tyrosine phosphorylation of a cellular protein of 34,000 daltons mol. wt. (34 kd) is greatly enhanced; this was shown to be catalyzed by the phosphotransferase activity of RSV transforming protein pp60src. We report here that in cytoplasmic extracts of both normal and transformed cells, in the presence of magnesium ions, the majority of the 34-kd protein is associated with large structures and that a fraction of 34 kd appears to be associated with ribonucleoprotein particles (RNPs). In addition, upon u.v. light cross-linking of RNA to protein in normal or transformed cells, an anti-34 kd serum immunoprecipitates RNA fragments of apparent low sequence complexity as detected by T1 fingerprint analysis. Our results indicate that the 34-kd protein may play a role in the cell at the level of RNPs.
ID: 252: Molecular mechanism for viral RNA detection: RIG-I-like receptors

Efficient host defense against viral infection depends on proper functions of pattern recognition receptors. One such family of receptors consists of RIG-I and MDA5, well-conserved cytoplasmic helicases that detect viral RNAs during infection and activate the type I interferon (IFN) signaling pathway. My laboratory has been investigating the molecular mechanisms by which these receptors recognize viral dsRNAs and elicit the IFN response against a broad range of viruses. In this talk, I will present our discoveries on the oligomerization of these receptors during viral RNA recognition and activation of the downstream adaptor molecule, MAVS. I will also describe our recent findings on the previously unappreciated effector-like functions of these receptors that are mediated by their abilities to remodel viral RNA: protein complexes.
A medium access protocol for wireless LANs which supports isochronous and asynchronous traffic

In this paper we present a medium access control (MAC) protocol for a wireless LAN which is designed to support both isochronous (voice) and asynchronous (data) traffic. The protocol is designed for use in a frequency hopping system and uses a TDMA access protocol to support voice and a CSMA/CA access protocol to support data. A wireless LAN using this protocol can be operated as either an ad-hoc network (in which case only the data service is supported) or as a managed network under the control of a control point or base station (in which case the voice service is also supported).
Clinical hypnosis for chronic pain in adults

Reason for Withdrawal This protocol has been withdrawn due to the author team being unavailable to complete the full review. To view the published versions of this article, please click the 'Other versions' tab.
When Good Intentions Are Not Enough: Obtaining Follow-Up Data in Living Kidney Donors

The Organ Procurement Transplant Network/United Network for Organ Sharing (OPTN/UNOS) has increased the amount of data collected before and after donation and increased the duration of donor follow-up to 2 years, yet there is evidence that reporting is incomplete. We examined the frequency of missing data in the OPTN/UNOS donor follow-up registry and found that reporting rates were low, particularly for donors who may have limited access to health care. We argue that a national donor follow-up registry is essential to ensure transparency in ascertaining long-term health outcomes among all living donors and in providing assessments of quality assurance within transplant programs. We have suggested approaches to strengthen the donor follow-up registry system. These include setting clear and high standards for follow-up reporting, a system of incentives and penalties that would motivate transplant centers to comply with these standards and would encourage donors to follow-up and lifelong follow-up reporting by primary care providers. We argue that the US government must provide funding to support a donor follow-up registry that can allow for meaningful and valid conclusions, in recognition of donors' public service and to maintain trust in the system of living organ donation.
Perspective: Science and technology policy – What is at stake and why should scientists participate?

US legislators prepare and make decisions on bills that involve science and technology (S&T) policy components, but they or their staff may not have sufficient expertise to do this. Therefore, it becomes critical that scientists and engineers from academia and industry spend time in Washington, DC to constructively engage in policy decisions. R&D investment helps drive economic growth. However, US R&D investment has been on the decline, whereas investment continues to increase in some emerging and developed economies. Scientists and engineers need to be champions for R&D investment to keep the USA competitive in the global market. This perspective paper discusses: what is S&T policy, who makes laws, the federal R&D budget and the importance of sustained R&D funding, how the USA compares with the rest of the world in R&D investment and numbers of science graduates. Finally, the author discusses his experiences as an S&T fellow in Washington, DC.
The effect of metallization contact resistance on the measurement of the field effect mobility of long-channel unannealed amorphous In–Zn–O thin film transistors

Abstract The effect of contact resistance on the measurement of the field effect mobility of compositionally homogeneous channel indium zinc oxide (IZO)/IZO metallization thin film transistors (TFTs) is reported. The TFTs studied in this work operate in depletion mode as n-channel field effect devices with a field effect mobility calculated in the linear regime (μFE) of 20 ± 1.9 cm2/Vs and similar of 18 ± 1.3 cm2/Vs when calculated in the saturation regime (μFEsat). These values, however, significantly underestimate the channel mobility since a large part of the applied drain voltage is dropped across the source/drain contact interface. The transmission line method was employed to characterize the contact resistance and it was found that the conducting-IZO/semiconducting-IZO channel contact is highly resistive (specific contact resistance, ρC > 100 Ωcm2) and, further, this contact resistance is modulated with applied gate voltage. Accounting for the contact resistance (which is large and modulated by gate voltage), the corrected μFE is shown to be 39 ± 2.6 cm2/Vs which is consistent with Hall mobility measurements of high carrier density IZO.
Subroutines for computing minimum variance unbiased estimators of functions of the parameters in the normal and gamma distributions

In this paper subroutines are given which calculate the uniformly minimum variance unbiased estimators (UMVUE’ s) of a broad class of functions of the parameters of the normal and gamma distributions. These subroutines employ the new expressions for the UMVUE’ s given recently by Gray, Watkins, and Schucany (1973), Woodward and Gray (1975), and Gray, Schucany, and Woodward (1976). In order to employ the subroutines here the user need only be able to provide a FORTRAN function subprogram to calculate derivatives of the function, either analytically or numerically.
Projector augmented-wave method

An approach for electronic structure calculations is described that generalizes both the pseudopotential method and the linear augmented-plane-wave (LAPW) method in a natural way. The method allows high-quality first-principles molecular-dynamics calculations to be performed using the original fictitious Lagrangian approach of Car and Parrinello. Like the LAPW method it can be used to treat first-row and transition-metal elements with affordable effort and provides access to the full wave function. The augmentation procedure is generalized in that partial-wave expansions are not determined by the value and the derivative of the envelope function at some muffin-tin radius, but rather by the overlap with localized projector functions. The pseudopotential approach based on generalized separable pseudopotentials can be regained by a simple approximation.
Implicit image models in image fractal compression

Why does fractal image compression work. What properties must an image have for fractal block coders to work well. What is the implicit image model underlying fractal image compression. The behavior of fractal block coders is clear for deterministically self-similar structures. In this paper we examine the behavior of these coders on statistically self-similar structures. Specifically, we examine their behavior for fractional Brownian motion, a simple texture model. Our analysis suggests that the properties necessary for fractal block coders to work well are not so dissimilar from those required by DCT and wavelet transform based coders. Fractal block coders work well for images consisting of ensembles of locally self-similar regions together with locally stationary regions with decaying power spectra, local statistical similarity, and local isotropy. Our analysis motivates a generalization of fractal block coders that leads to substantial improvements in coding performance and also illuminates some of the fundamental limitations of current fractal compression schemes.
Kinetics of Domain Formation by Sickle Hemoglobin Polymers

We have monitored the growth of domains of sickle hemoglobin polymers by using temporally and spatially resolved light scattering and birefringence measured pseudosimultaneously on a 50-microns square area. Polymerization was induced and indefinitely maintained by photolysis of the carbonmonoxy derivative using an argon ion laser. Intensity of scattering and birefringence (measured as intensity transmitted through crossed polarizers) were measured using a silicon-intensified target vidicon interfaced to a computer. Polymer concentration, as inferred by light scattering, grew with primarily circular symmetry, with approximately 20% of the signal initially in a twofold symmetric pattern. In time the circular symmetry increased. A distinct decrease in the scattering signal developed which spread outward from the center of the domain. Birefringence lagged the scattering and initially grew in a twofold pattern, with the formation of a characteristic Maltese cross only appearing much later, and well after the scattering signal had peaked. Radial profiles of the domain scattering and birefringence were both approximately gaussian. We successfully modeled the decrease in scattering by fitting the profiles to a large gaussian from which a second smaller gaussian was subtracted. This second gaussian had the width of the birefringence gaussian. The width of the birefringence gaussian grew linearly in time, while the width of the scattering gaussian showed a notable acceleration. We conclude that domains form primarily as disordered arrays which align at later times. We explain the above observations, including the shape of the birefringence progress curves, as the result of an alignment transition which is solely due to a redistribution of monomers from short to long, and from entangled to radial, polymers. We present a theoretical justification for this process in an appendix. In a separate paper (Zhou, H. X., and F. A. Ferrone, manuscript submitted for publication) we show that the gaussian shapes and acceleration of the width naturally arise from a generalization of the double nucleation mechanism for sickle hemoglobin gelation (Ferrone, F. A., J. Hofrichter, H. Sunshine, and W. A. Eaton 1980. Biophys. J. 32:361-377; Ferrone, F. A., J. Hofrichter, and W. A. Eaton. 1985. J. Mol. Biol. 183:611-631).
A mechanistic study of the metabolism of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD) to 2,2-bis(p-chlorophenyl)acetic acid (DDA)

The metabolism of [1-2H]-1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD-d) and [1-2H]-1-chloro-2,2-bis(p-chlorophenyl)ethene (DDMU-d) and their corresponding non-deuterated isomers DDD and DDMU was studied in female Swiss mice over a 96-hr period. The only detected urinary metabolite of DDD-d and DDD was 2,2-bis(p-chlorophenyl)acetic acid (DDA). Animals administered DDD excreted approximately 2.4-fold more DDA than those treated with DDD-d over the total collection period. The initial (0-36 hr) linear excretion rates of DDA for DDD and DDD-d were 17.1 and 5.5 micrograms/hr respectively. DDMU- and DDMU-d-treated mice excreted significant quantities of DDA, 2,2-bis(p-chlorophenyl)ethanol (DDOH) and 2,2-bis(p-chlorophenyl)ethanol (DDCHO). The only quantitative difference between DDMU and DDMU-d was that the non-deuterated isomer afforded approximately 1.8 times more DDA over the 96-hr collection. The initial (0-36 hr) linear excretion rates of DDMU and DDMU-d were 10.7 and 6.2 micrograms/hr respectively. The qualitative and quantitative results are consistent with DDD being metabolized to DDA via enzyme-mediated hydroxylation on the C-1 side chain carbon.
The nature and mechanism of the damage induced in DNA by a protein antibiotic.

NCS, an antitumor protein, that causes DNA strand scissions both in vitro and in vivo lowers the template activity of DNA for DNA polymerase I in vitro. A correlation exists between the extent of strand scission and the degree of inhibition of the polymerase. NCS-induced strand breakage generates non-functional binding sites for the polymerase. By the use of bacterial alkaline phosphatase and exonuclease III it is shown that NCS generates gaps in the DNA that bear phosphomonoester groups at both the 3′- and 5′-ends. In the intact cell possessing the complete system for DNA repair, these lesions in the DNA are repaired to a considerable degree as indicated by the marked stimulation of dTMP incorporation into DNA induced by NCS. Experiments on the stoichiometry of the DNA cutting reaction reveal a zero order reaction with regard to DNA. Possible mechanisms for inducing the lesion described and accounting for the characteristics of the NCS-DNA interaction are discussed.
Prostaglandin F2a stimulates progesterone secretion by porcine luteal cells in vitro throughout the estrous cycle

In this study we examined the stimulatory effects of PGF2α on progesterone secretion by procine luteal cells on different days of the estrous cycle, and the effects of PGF2α, A23187 and PMA on progesterone secretion by isolated large and small luteal cells, in vitro. Corpora lutea were obtained from cycling pigs (days 6–16), collagenase dispersed and luteal cells incubated in medium 199 in the absence or presence of increasing doses of PGF2α, A23187, and PMA. Progesterone concentrations in spent media were measured by RIA. PGF2α stimulation of progesterone secretion by mixed luteal cells did not vary significantly throughout the estrous cycle. Progesterone secretion by large, but not small, luteal cells was increased (p<0.05) in a dose-dependent fashion by PGF2α. A23187 also caused a dose-dependent increase in progesterone secretion by large luteal cells but inhibited small luteal cells. Progesterone secretion by both large and small luteal cells was significantly increased by increasing doses of PMA. We conclude that the stimulatory response of luteal cells to PGF2α in vitro did not correlate with PGF2α receptor concentrations (not measured in this study), and we speculate that calcium/protein kinase C may be involved in mediating the stimulatory action of PGF2α on luteal cell progesterone secretion.
Evidence for Atmospheric Transport and Deposition of Polychlorinated Biphenyls to the Lake Tahoe Basin, California−Nevada

PCB congener concentrations in air, water, fish, and snow were determined in the Lake Tahoe basin and in the water and fish of an adjacent but more remote rural comparison lake, Marlette Lake, to examine whether atmospheric transport and deposition are primary sources of contamination to this alpine region of the Sierra Nevada Mountains. Profiles of 97 congeners analyzed by capillary GC−ECD from surface waters of Lake Tahoe and Marlette Lake were closely matched, with total dissolved PCB (t-PCB) concentrations of 0.37 ng/L in Lake Tahoe and 0.67 ng/L in Marlette Lake. Gas-phase t-PCB concentra tions measured in air samples from the Lake Tahoe basin averaged 72 pg/m3, and t-PCB (dissolved and particulate) concentrations in snow were 4.8−5.1 ng/L. Rainbow trout from Marlette Lake and lake trout from Lake Tahoe had similar distributions of congeners, with t-PCB tissue levels varying from 3 to 14 ng/g wet weight. The finding of PCBs in all sampled compartments, particularly snow and air, and the similar patte...
The International Competitiveness of the U.S. Textile Mill Products Industry: Corporate Strategies for the Future

This article reports on the strategic adjustments undertaken by the larger firms of 5 European, 3 Asian Pacific, and the U.S. textile mill products companies during the 1960s and 1970s, and examines several of the underlying reasons for the gradual decline in the U.S. industry's international competitiveness. The study's basic conclusions are that the majority of the foreign textile industries view customer markets differently than the U.S. industry; that they place different emphasis on technology, production, marketing, and strategic planning; and that they have different relationships with their governments than U.S. firms do. The implications of these findings are discussed, and corporate strategy recommendations that are designed to enhance the future international competitiveness of the U.S. industry are presented.
High pressure study of flexible fluorescent dye molecules in solid polymeric media. II: Polyester yellow 6G-LSW

Abstract We have measured the luminescence efficiency of polyester 6G-LSW (PY) as a function of pressure in several polymeric matrices. The quenching of the luminescence is largely due to twisting could be identified, one involving a malononitrile group and one a C-N-phenyl group on a side chain. From the pressure data we were able to separate these two twisting processes and to characterize them in terms of a parameter k ′ nr which is a function of the rates of crossing from the planar to the twisted conformation and the reverse process, and of the rate of thermal dissipation of energy from the twisted state.
Radiation effects of various electro-optic devices

We have measured the effects of radiation on various electro-optical devices used as communication components. The measurements were performed with 2.5 MeV electrons from the Lehigh University Van de Graaff. The performance of the devices was monitored both during irradiation and after irradiation. We report here the results of irradiation on various electro-optical devices used for optical communications. These devices include simple waveguide couplers, optical waveguide switching devices, transistors, and total amplifier systems. The 3 MeV High Voltage KN3000 Van de Graaff at Lehigh University was used for the irradiations. The machine provided beams of electrons which could be directly used or gamma rays from the electron beam bremsstrahlung. We looked for slowly changing time effects using a continuous beam as well as transient effects with a pulsed beam arrangement. We now review the results obtained with various electro-optical components.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
ATM Protein Physically and Functionally Interacts with Proliferating Cell Nuclear Antigen to Regulate DNA Synthesis

Ataxia telangiectasia (A-T) is a pleiotropic disease, with a characteristic hypersensitivity to ionizing radiation that is caused by biallelic mutations in A-T mutated (ATM), a gene encoding a protein kinase critical for the induction of cellular responses to DNA damage, particularly to DNA double strand breaks. A long known characteristic of A-T cells is their ability to synthesize DNA even in the presence of ionizing radiation-induced DNA damage, a phenomenon termed radioresistant DNA synthesis. We previously reported that ATM kinase inhibition, but not ATM protein disruption, blocks sister chromatid exchange following DNA damage. We now show that ATM kinase inhibition, but not ATM protein disruption, also inhibits DNA synthesis. Investigating a potential physical interaction of ATM with the DNA replication machinery, we found that ATM co-precipitates with proliferating cell nuclear antigen (PCNA) from cellular extracts. Using bacterially purified ATM truncation mutants and in vitro translated PCNA, we showed that the interaction is direct and mediated by the C terminus of ATM. Indeed, a 20-amino acid region close to the kinase domain is sufficient for strong binding to PCNA. This binding is specific to ATM, because the homologous regions of other PIKK members, including the closely related kinase A-T and Rad3-related (ATR), did not bind PCNA. ATM was found to bind two regions in PCNA. To examine the functional significance of the interaction between ATM and PCNA, we tested the ability of ATM to stimulate DNA synthesis by DNA polymerase δ, which is implicated in both DNA replication and DNA repair processes. ATM was observed to stimulate DNA polymerase activity in a PCNA-dependent manner.
Genetic control of cell communication in C. elegans development.

Cell communication is crucial for many aspects of growth and differentiation during the development of the nematode Caenorhabditis elegans. Two genes, glp-1 and lin-12, mediate a number of known cell–cell interactions. Genetic and molecular analyses of these two genes lead to the conclusion that they are structurally and functionally related. We summarize these studies as well as those involving the identification of other genes that interact with glp-1 and / or lin-12.
Thyroid hormone receptors : multiple forms, multiple possibilities

I. Introduction THE biological importance of the thyroid gland has been recognized for centuries (1). The realization in the late 19th century that cretinism and myxedema result from loss of thyroid function led to the discovery of T4 (2) and T3 (3) as the predominant and most potent thyroid hormones, respectively. During the ensuing decades the plasma membrane (4), synapse (5), endoplasmic reticulum (6), and mitochondria (7) have all been considered as potential cellular sites of action of the thyroid hormones. In the 1960s, however, it was noted that many of the physiological actions of T3 were preceded by nuclear RNA transcription (8, 9), and high-affinity nuclear receptors for T3 were discovered soon thereafter (10,11). The specificity of the nuclear T3 receptors (TRs) for thyroid hormone analogs closely parallels the biological potency of the compounds (12, 13), and the levels of the nuclear TRs correlate well with the developmental and tissue-specific effects of T3 in most cases (14, 15). Thus, alth...
Competitive health plans and alternative payment arrangements for physicians in the United States: public sector examples*

The Medicaid program in the United States is moving to a competitive managed care system whereby patients no longer have freedom of choice of physicians and physicians are given incentives to provide care cost effectively. The wide variety of competitive managed care programs represents attempts to introduce rationality into the relationship between consumers and providers in a community. Early evidence, based largely on preliminary data analysis indicates that competing plans which place physicians at some financial risk and also employ administrative mechanisms, are more likely to show cost savings than health plans that do not employ these methods.
Foreign body response to subcutaneous biomaterial implants in a mast cell-deficient Kitw-Sh murine model

Mast cells (MCs)_are recognized for their functional role in wound-healing and allergic and inflammatory responses – host responses that are frequently detrimental to implanted biomaterials if extended beyond acute reactivity. These tissue reactions impact especially on the performance of sensing implants such as continuous glucose monitoring (CGM) devices. Our hypothesis that effective blockade of MC activity around implants could alter the host foreign body response (FBR) and enhance the in vivo lifetime of these implantable devices motivated this study. Stem cell factor and its ligand c-KIT receptor are critically important for MC survival, differentiation and degranulation. Therefore, an MC-deficient sash mouse model was used to assess MC relationships to the in vivo performance of CGM implants. Additionally, local delivery of a tyrosine kinase inhibitor (TKI) that inhibits c-KIT activity was also used to evaluate the role of MCs in modulating the FBR. Model sensor implants comprising polyester fibers coated with a rapidly dissolving polymer coating containing drug-releasing degradable microspheres were implanted subcutaneously in sash mice for various time points, and the FBR was evaluated for chronic inflammation and fibrous capsule formation around the implants. No significant differences were observed in the foreign body capsule formation between control and drug-releasing implant groups in MC-deficient mice. However, fibrous encapsulation was significantly greater around the drug-releasing implants in sash mice compared to drug-releasing implants in wild-type (e.g. MC-competent) mice. These results provide insights into the role of MCs in the FBR, suggesting that MC deficiency provides alternative pathways for host inflammatory responses to implanted biomaterials.
Identification and Cloning of an Orphan G Protein-Coupled Receptor of the Glycoprotein Hormone Receptor Subfamily

Abstract Mining of the EST database identified a human EST that was predicted to encode a novel member of the glycoprotein hormone receptor subfamily. Based on the sequence information, the full-length coding region of this gene was isolated and sequenced. This gene, designated HG38, is predicted to encode a polypeptide of 907 amino acid residues with a putative signal peptide sequence at its very N-terminus. HG38 is most closely related to members of the glycoprotein hormone receptor subfamily with ∼35% overall identity at the protein sequence level. As with the glycoprotein hormone receptors, HG38 contains a long extracellular domain with a total of 16 leucine-rich repeats. Northern blot analysis showed that HG38 was expressed in skeletal muscle, placenta, spinal cord, and various regions of the brain. Radiation hybrid mapping placed HG38 into human chromosome 12q22-23. HG38 is most likely to be a receptor for a novel class of glycoprotein ligands.
MALE JEALOUSY AND THE SUSPECTED SOTAH TOWARD A COUNTER-READING OF NUMBERS 5:11-31

Until recently, discussions of the Sotah ritual (Numbers 5) stood at an impasse between the view that it provides wives protection from jealous husbands and the view that it mainly subordinates women. This article examines the place of writing and curses in the biblical text, highlighting its almost compulsive concern to bring certainty to uncertainty. Dynamics of body and text, writing and erasure, uncertainty and linguistic power inform the Sotah text in ways that resist univocal readings. With the full weight of priestly and legal authority brought to bear on the problem of male jealousy, there can be no doubt that the ritual enforces patriarchal controls on women’s agency. It thus instantiates the development of what Deleuze and Guattari call the ‘despotic sign’, whereby ‘[t]he mouth no longer speaks, it drinks the letter’. Yet as the law on oaths later in Numbers (ch. 30) attests, women could also exercise powerful speech, making their agency a reality in biblical times. Building on theoretical models from Irigaray and Butler, I sketch two strategies of counter-reading the Sotah text: reversal, in which the tables of suspicion are turned on the accusing husband, and parody, in which the entire ritual, like the exchange of sandals in Ruth 4, seems strange from a particular point of view.
Emotional avoidance and panicogenic responding to a biological challenge procedure

Healthy undergraduates high (n = 27) and low (n = 27) in experiential avoidance underwent twelve 20 s inhalations of 20% carbon dioxide-enriched air, while physiological (e.g., skin conductance, heart rate, EMG, and end-tidal CO2) and subjective (e.g., subjective units of distress, evaluative ratings, number and severity of panic symptoms endorsed) reactions were continuously monitored. Individuals high in experiential avoidance endorsed more panic symptoms, more severe cognitive symptoms, and more fear, panic, and uncontrollability than their less avoidant counterparts. Magnitude of autonomic response did not discriminate between groups, nor were the observed effects accounted for by other risk factors for challenge-induced panic such as anxiety sensitivity. Results are discussed in terms of the pathoplastic relation between emotional avoidance and exacerbation of unpleasant emotional responses and the view that emotional avoidance may constitute a risk factor in the development and maintenance of anxiety disorders.
A two-dimensional coupled oscillator array

Design, fabrication, and test of a two-dimensional (2-D) coupled oscillator array is described. The array consists of nine voltage-controlled oscillators in a 3/spl times/3 configuration and operates at S-band. It is demonstrated experimentally that the array can generate planar phase distributions suitable for producing a radiated beam which is agile in two dimensions via tuning of the perimeter oscillators only. This is believed to be the first implementation of such an array.