cssi/SciSciGPT-SciSciNet huggingface dataset:
Uncovering microglial pathways driving sex-specific neurobiological effects in stress and depression

Abstract Women suffer from major depressive disorder (MDD) more often than men and report greater MDD symptom severity. Mounting evidence suggests that sex differences in MDD may be driven, in part, by sex-specific neurobiological mechanisms. Chronic stress is a significant risk factor in MDD, and preclinical rodent models show differential patterns of stress-induced neural remodeling and cognitive-behavioral dysfunction in males and females. For instance, chronic stress leads to synapse loss in the medial prefrontal cortex in male rodents yet has either no effect on- or increases-synapse number in females. Recent reports have implicated microglia, the immune cells of the brain, in MDD, and findings demonstrate sex-specific microglial signatures in both preclinical stress models and MDD patients. Given that microglia can remodel neural architecture, modulate synaptic transmission, and affect subsequent changes in behavior, it is plausible that microglial pathways contribute to differential stress effects on neuroplasticity and function in males and females. As such, this review examines the evidence for sex-specific microglia-neuron interactions in preclinical stress models and in patients with MDD. Discoveries highlighted herein demonstrate divergent microglial contributions in males and females and suggest that future studies investigating stress-linked disorders should be guided by sex-dependent neurobiological and behavioral findings. Examining these pathways represents a clear avenue toward both a richer understanding of brain, behavior, and immunity, and innovative psychoneuroimmunology-based applications in personalized medicine.
Molecular Dynamics of The Early Stages of High Temperature Corrosion

We performed molecular dynamics simulations of the high-temperature oxidation of metal alloys composed of Al, Cr, and Fe and compared their behavior with that of pure Fe. The metal alloy elements (Al and Cr) segregated to the surface during oxidation, producing a lower stress gradient at the metal/environment interface compared to pure Fe. We have found that the lowered stress gradients produced in the alloy material appear to play a key role in the development of corrosion. Interfaces with lower stress gradients have reduced rates of ${\mathrm{H}}_{2}\mathrm{O}$ adsorption, especially for the ferritic (bcc) alloys. The diffusivity of oxygen and hydrogen drops more rapidly for the interfaces with reduced stress gradients. The stress gradient is also diminished when the gas pressure is increased, indicating that the Fe-Cr-Al alloy system is more resistant to oxidation than pure Fe at higher pressures. Therefore, we conclude that the lower stress gradients at the alloy/environment interface reduce the stress concentration and can slow down the rate of the initial oxide scale growth. We also compared bcc and fcc alloys with pure Fe based on our three evaluation criteria (peak stress, stress gradient, and summation of stress in the oxide scale). We found that the alloys have lower values under the three criteria compared to pure Fe. The bcc alloy has the best score under a water rich environment and the fcc alloy is proven to be better for peak stress and summation of stress in the oxide scale under an oxygen rich environment. For surface segregation to occur, we find that a minimum content of Al or Cr in the near-surface region must be achieved. We also learned that the role of Al is more important than that of Cr in terms of corrosion resistant behavior at relatively higher temperatures for the Fe-Cr-Al ternary alloys.
Ferroelectrics: The positives of going negative

Negative pressure in ferroelectric nanowires has been achieved by exploiting a phase transformation between crystal structures with differing densities, leading to substantial property enhancement.
Alloantigen System L Affects the Outcome of Rous Sarcomas

This study was designed to examine the alloantigen system L effects on Rous sarcomas in three B complex genotypes. The parental stock was 50% Modified Wisconsin Line 3 × White Leghorn Line NIU 4 and 50% inbred Line 6.15-5. Pedigree matings of two B2B5 L1L2 sires to five B2B5 L1L2 dams per sire produced experimental chicks segregating for B and L genotypes. Chicks were inoculated with 20 pock-forming units (pfu) of Rous sarcoma virus (RSV) at 6 weeks of age. Tumors were scored six times over 10 weeks postinoculation after which the tumor scores were used to assign a tumor profile index (TPI) to each chicken. Tumor growth over time and TPl were evaluated by repeated-measures analysis of variance and analysis of variance, respectively. Six trials were conducted with a total of 151 chickens. The major histocompatibility (B) complex affected the responses as the B2B2 and B2B5 genotypes had significantly lower tumor growth over time and TPl than the B5B5 genotype. Separate analyses revealed no significant L sys...
Violations of the Classical Assumptions

In this chapter, we relax the assumptions made in Chapter 3 one by one and study the effect of that on the OLS estimator. In case the OLS estimator is no longer a viable estimator, we derive an alternative estimator and propose some tests that will allow us to check whether this assumption is violated.
Twelve Patients: A Book Review

Twelve Patients weaves the stories of twelve patients to tell the geopolitical stories of Americans, both those born here and elsewhere.Â At the epicenter of immigration, New York City and Bellevue Hospital serves as a testament to public health in America over the past century.Â It mirrors the challenges new immigrants have, by documenting their health challenges. Â Amidst these case studies, Dr. Eric Manheimer offers geopolitical commentary on mental health in America, Latin American geopolitical issues, palliative care, and international infectious disease.Â Â He is a clinical professor of medicine at the New York University School of Medicine, and served as the medical director at Bellevue Hospital for fourteen years.Â Fifteen years of handwritten journals of thoughts, incidents, ideas, case studies and conversations culminated into these twelve chapters, focusing on twelve patients.
Technology and the Writing Skills of Students with Learning Disabilities

AbstractA year-long study was conducted involving 5 fifth-grade students with learning disabilities with written language deficits from a parochial elementary school in the midwestern United States using a specially designed computer program as a writing tool to assist them in a weekly based writing curriculum. The study showed positive effects on the participating students’ writing behaviors and their written products.
A Polemic for Bayesian Statistics

In the early part of the 20th century, forefathers of current statistical methodology were largely Bayesians. However, by the mid-1930’s the Bayesian method fell into disfavor for many, and frequentist statistics became popular. Seventy years later the frequentist method continues to dominate. My purpose here is to compare the Bayesian and frequentist approaches. I argue for Bayesian statistics claiming the following: 1) Bayesian methods solve a wider variety of problems; and 2) It is sometimes difficult to interpret frequentist results.
Information Literacy and Blind and Visually Impaired Students

In the summer of 2007, as part of the City University of New York PeopleTech Summer Institute held at Baruch College, the author taught a class in information literacy to a group of blind and visually impaired students, using assistive technology to access the resources of the college library. Despite considerable preparation and experience, teaching the class presented unexpected difficulties, detailed in this paper. Rapid advances in information literacy technology present unusual challenges for the average student—challenges that are magnified when the intermediate assistive technology is itself not easy to master. The author explores the pertinent literature.
Adverse neurologic events associated with voriconazole use in 3 cats.

Background: Voriconazole has a broader spectrum of activity in comparison to fluconazole, itraconazole, and amphotericin B. Little documentation regarding appropriate dosing, efficacy, or adverse effects exists for cats. Neurologic adverse effects have been reported as a result of administration in other species. Hypothesis: Voriconazole administration resulted in neurologic abnormalities in 3 cats. Animals: Three cats that received voriconazole. Methods: Observational study of adverse effects associated with voriconazole administration. Results: All 3 cats had ataxia, which in 2 cats progressed to paraplegia of the rear limbs. Two of the cats had visual abnormalities including mydriasis, decreased to absent pupillary light responses, and decreased menace response. Arrhythmia and hypokalemia were noted in 2 separate cats. Conclusions and Clinical Importance: Voriconazole has potential neurologic adverse effects in cats. Additional information regarding pharmacokinetics of the drug in this species must be gathered to help determine how it can be dosed most effectively with minimal adverse effects.
Rock and roll polishing: a process for optical surface polishing

We describe and present experimental results of a nonconventional process that can be used for the polishing of optical surfaces. In particular, we present data regarding polishing uniformity, removal rate, surface microroughness, and subsurface damage.
An Enduring, Evolving Separation of Powers

This Article sets forth the theory of an enduring, evolving separation of powers, one that checks and balances state power in whatever form that power happens to take. It shows how this constitutional commitment was first renewed and refashioned in the 1930s and 1940s, wherein the construction of a secondary regime of administrative checks and balances triangulated regulatory power among politically appointed agency leaders, an independent civil service, and a vibrant and pluralistic civil society. And it supplies the legal precedent, corrective blueprint, and normative imperative for subsequent generations (including ours) to reaffirm that commitment whenever new threats to limited, rivalrous government arise. This commitment to an enduring, evolving separation of powers helps explain our past and our present — and it readies us for the future. First, reframing the administrative state through the lens of an enduring, evolving separation of powers provides a more seamless connection to the Founding. The twentieth-century shift to administrative governance toppled the Framers’ tripartite constitutional regime. But the subsequent construction of an administrative separation of powers represented an act of constitutional restoration, anchoring the modern administrative state firmly within the constitutional tradition of employing rivalrous, heterogeneous institutional counterweights to promote democratic accountability and compliance with the rule of law. Second, this reframing resolves seemingly intractable normative and jurisprudential struggles in contemporary administrative law, harmonizing today’s leading (but conflicting) theories and doctrines of public administration. And, third, this reframing prepares us for life in the post-administrative state, a reality that is already beckoning. Increasingly the forces of privatization are consolidating state and commercial power in ways that compromise administrative separation of powers. Understanding privatization not as a sui generis phenomenon but instead simply as the latest, perhaps greatest, threat to an enduring, evolving separation of powers enables us to employ the grammar and doctrinal imperatives of constitutional separation of powers to insist that privatization’s proponents take on the responsibility for reestablishing limited and rivalrous governance amid the dynamic turn to the market — or else abandon the enterprise altogether.
Helical x-ray differential phase contrast computed tomography

Helical computed tomography revolutionized the field of x-ray computed tomography two decades ago. The simultaneous translation of an image object with a standard computed tomography acquisition allows for fast volumetric scan for long image objects. X-ray phase sensitive imaging methods have been studied over the past few decades to provide new contrast mechanisms for imaging an object. A Talbot-Lau grating interferometer based differential phase contrast imaging method has recently demonstrated its potential for implementation in clinical and industrial applications. In this work, the principles of helical computed tomography are extended to differential phase contrast imaging to produce volumetric reconstructions based on fan-beam data. The method demonstrates the potential for helical differential phase contrast CT to scan long objects with relatively small detector coverage in the axial direction.
Lymphocyte adherence in multiple sclerosis: role of the cytoskeleton and prostaglandin E.

Abstract Human peripheral blood lymphocytes from patients with multiple sclerosis (MS) form significantly greater numbers of rosettes with virus infected cells than healthy controls. Because increased lymphocyte adherence in MS may be important to the disease process, we have investigated the mechanisms governing lymphocyte adherence in healthy control volunteers. We have previously shown that prostaglandins E1, E2 (PGE2), and dibutyryl cyclic AMP (db cAMP) and colchicine increase control lymphocyte adherence in healthy control volunteers. Colchicine treatment enhances PGE synthesis in control cells. We now report that colchicine (10−5 + 10−7 M) treatment of mononuclear cells does not enhance PGE synthesis in cells from patients with multiple sclerosis. Colchicine treatment did not affect MS lymphocyte adherence.
Endopeptidase 24.15 inhibition and opioid antinociception.

Whereas endopeptidase 24.11 cleaves the Gly-Phe bond in both Met- and Leu-enkephalin, endopeptidase 24.15 rapidly converts dynorphin A1-8, alpha and beta-neoendorphin into Leu-enkephalin, and Met-enkephalin-Arg6-Gly7-Leu8 (MERGL) into Met-enkephalin. Inhibitors of both endopeptidase 24.11 and endopeptidase 24.15 each produce antinociception, and inhibitors of endopeptidase 24.11 increase the magnitude of enkephalin antinociception. The present study compared the central antinociceptive effect of an inhibitor of endopeptidase 24.15, N-[1-(R-S)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate (cFP-AAF-pAB) with one of endopeptidase 24.11 N-[1-(RS)-carboxy-3-phenylpropyl]-Phe-p-aminobenzoate (cFP-F-pAB) upon central opioid antinociception induced by MERGL, metenkephalin and dynorphin A1-8. cFP-AAF-pAB, but not cFP-F-pAB increased MERGL antinociception on the tail-flick and jump tests. In contrast, cFP-F-pAB, but not cFP-AAF-pAB increased met-enkephalin antinociception. Whereas central dynorphin A1-8 failed to induce antinociception itself, co-administration of cFP-AAF-pAB and dynorphin A1-8 increased nociceptive thresholds. This effect was not accompanied by motor dysfunction, but was blocked by systemic pretreatment with naloxone or central pretreatment with naltrexone or nor-binaltorphamine, but not beta-funaltrexamine. These data indicate that endopeptidase 24.15 may be responsible for the degradation of specific opioid peptides (e.g., MERGL, dynorphin), and that this process may prevent the full expression of their antinociceptive properties.
Factors Contributing to Negative Parathyroid Localization: An Analysis of 1000 patients

Background Localizing studies are the key for determining the optimal surgical strategy in patients with primary hyperparathyroidism (HP). Most of the data in the literature are retrospective in nature and from analysis on a per patient basis. This is a prospective study looking at the characteristics of the patient and the gland that determine the likelihood of an abnormal parathyroid to be detected by ultrasonography (US) and sestamibi scan (MIBI). Methods This is a prospective analysis of 1000 consecutive patients with HP who underwent parathyroidectomy at a tertiary care center. The study group included HP with single gland disease (63%), double adenoma (15%), as well as hyperplasia (15%), familial HP (2%), and secondary/tertiary HP (6%). All patients underwent surgeon-performed neck US followed by MIBI scan. Univariate logistic regression and multivariate analyses were performed on pre- and intraoperative variables. Results A total of 1845 abnormal glands were analyzed. Overall, US was superior to MIBI for the detection of abnormal glands in all subgroups. On multivariate analysis, body mass index (BMI), gland size, and gland volume were the statistically significant independent factors predicting detection by both US and MIBI in primary HP. The sensitivity of US was better for single gland disease than for multigland disease in primary HP, but the sensitivity of MIBI was similar in both groups. For a given size, hyperplastic glands in primary HP imaged less well with US and MIBI than in familial or secondary/tertiary HP. Conclusion This prospective study demonstrates that BMI and gland size independently predict accurate detection of abnormal parathyroid glands by US and MIBI in sporadic primary HP. Understanding the factors that affect the accuracy of parathyroid localization tests will allow the surgeon to develop a successful surgical strategy in a given patient.
On topological spaces of orders

We study the space of linear orders on a given set X, denoted by Op(X), endowed with the topology of pointwise convergence. We show, in particular, that if |X|=ω1 or |X|=ω0 then Op(X) is homeomorphic to 2ω1 and 2ω0, respectively.
Postnatal Caregiver Cocaine Use, Not In Utero Cocaine Exposure Alone, Is a Marker for Language Problems in Children at School Age

Postnatal Caregiver Cocaine Use, Not In Utero Cocaine Exposure Alone, Is a Marker for Language Problems in Children at School Age
Evolution of gnathostome prodynorphin and proenkephalin: Characterization of a shark proenkephalin and prodynorphin cDNAs

Analyses of prodynorphin and proenkephalin cDNAs cloned from the central nervous system of the shark, Heterodontus portusjacksoni, provided additional evidence that these two opioid precursor-coding genes were most likely directly derived from a common ancestral gene. The two cDNAs could be aligned by inserting only seven gaps. The prodynorphin cDNA encodes five opioid sequences which could be aligned to opioid positions B through F in the proenkephalin cDNA. The sequence identity within the opioid positions was 59% at the amino acid level. Shark α-neo-endorphin, dynorphin A, and dynorphin B have amino acid motifs in common with shark met-enkephalin-8, and shark proenkephalin opioid positions E and F, respectively, which have not been observed in other gnathostome prodynorphin and proenkephalin precursor sequences. Shark prodynorphin encodes both kappa (α-neo-endorphin, dynorphin A, and dynorphin B) and delta (met-enkephalin and leu-enkephalin) opioid sequences. Mixed function prodynorphin precursors (encoding both enkephalins and dynorphins) are also found in representatives of the teleost fishes, lungfishes, and amphibians. It appears that only mammals evolved a prodynorphin precursor that exclusively encodes kappa opioid agonists (dynorphins).
Asymmetric synthesis of (+)-indatraline using rhodium-catalyzed C–H activation

Abstract The potent monoamine reuptake inhibitor (+)-indatraline, 1 , was prepared in greater than 98% ee employing a highly enantioselective carbenoid C–H insertion reaction into 1,4-cyclohexadiene catalyzed by the chiral rhodium complex, Rh2(S-DOSP)4.
Inhibition of ERK attenuates autophagy and potentiates tumour necrosis factor-α-induced cell death in MCF-7 cells

The role of autophagy in cell death is under considerable debate. The process of autophagy has been shown to lead to either cell survival or cell death depending on cell type and stimulus. In the present study, we determined the contribution of ERK1/2 signalling to autophagy and cell death induced by tumour necrosis factor-α (TNF) in MCF-7 breast cancer cells. Treatment of MCF-7 cells with TNF caused a time-dependent increase in ERK1/2 activity. There was an induction of autophagy and cleavage of caspase-7, -8, -9 and PARP. Pharmacological inhibition of ERK1/2 phosphorylation with U0126 or PD98059 resulted in a decrease in TNF-induced autophagy that was accompanied by an increase in cleavage of caspase-7, -8, -9 and PARP Furthermore, inhibition of ERK1/2 signalling resulted in decreased clonogenic capacity of MCF-7 cells. These data suggest that TNF-induces autophagy through ERK1/2 and that inhibition of autophagy increases cellular sensitivity to TNF.
Predicting properties and minimizing residual stress in quenched steel parts

Quenching refers to the process of rapidly cooling metal parts from the austenitizing or solution treating temperature, typically in the range of 845 to 870°C (1550 to 1600°F) for carbon and low alloy steels, for the purpose of forming martensite. Several factors determine whether a particular part can be successfully hardened, including the type, molecular weight, and thermal characteristics of the quenchant, the quenchant use conditions (such as velocity, temperature, and polymer concentration, etc.), section thickness of the part, and the transformation characteristics of the specific alloy being quenched. Successful hardening usually means achieving the required hardness, strength, or toughness while minimizing residual stress, distortion, and the possibility of cracking. Heat removal from parts during quenching can be described in terms of the effective interface heat transfer coefficient. A quenchant must impart a sufficiently high interface heat transfer coefficient to produce a cooling rate that will minimize transformation of austenite to ferrite or pearlite and yield the desired amount of martensite. A quench factorQ has been devised that interrelates quenching variables and transformation kinetics of steel to provide a single number indicating the extent to which a part can be hardened at various locations within the part. The quenchant and the quenchant operating conditions should be selected to provide the proper quench factor while minimizing thermal gradients that can cause distortion or cracking. Cooling curves, interface heat transfer coefficients, quench factors, and thermal gradients produced by a variety of quenchants are presented.
When Clients Are Untruthful: Implications for the Therapeutic Alliance, Case Conceptualization, and Intervention.

Therapists endeavor to be genuine and trustworthy with clients, thus facilitating the establishment and maintenance of a positive therapeutic relationship. Unfortunately, clients sometimes knowingly give false or misleading information, maintain counter therapeutic hidden agendas, and deliberately obscure clinically relevant facts. Such factors likely will obstruct the process of case conceptualization, strain the therapeutic relationship, and result in disagreements about proper interventions. We discuss some of the telltale signs of clients’ untruthfulness, and suggest ways in such cases for therapists to draw upon clients’ behaviors in session to construct useful case formulations. Additionally, we describe a number of interventions that increase the chances of pursuing healthy, appropriate, therapeutic goals, irrespective of clients’ degree of sincerity.
Development of the Radiometer Atmospheric CubeSat Experiment payload

The Jet Propulsion Laboratory (JPL) is developing the Radiometer Atmospheric CubeSat Experiment (RACE), which consists of a water vapor radiometer integrated on a 3 U CubeSat platform. RACE will measure 2 channels off the 183 GHz water vapor line, and will be used to validate new low noise amplifier technology and internal calibration methodology. RACE will advance the technology readiness level (TRL) of the 183 GHz receiver subsystem from TRL 4 to TRL 6 and a CubeSat 183 GHz radiometer system from TRL 4 to TRL 7.
Palmitoylethanolamide regulates development of intestinal radiation injury in a mast cell-dependent manner.

Background Mast cells and neuroimmune interactions regulate the severity of intestinal radiation mucositis, a dose-limiting toxicity during radiation therapy of abdominal malignancies.
Characteristics of the mate recognition factor in the rotifer Brachionus plicatilis

Abstract 1. 1. Brachionus plicatilis males attempted to mate with live and freeze-killed females with equal probability. 2. 2. Heating females to 100°C gradually destroyed the mate recognition factor (MRF) and reduced the probability of male copulation. 3. 3. Exposure of freeze-killed females to the general proteases, proteinase K and pronase E, degraded the MRF. 4. 4. The specific proteases trypsin and carboxypeptidase A did not significantly degrade the MRF, but chymotrypsin caused a linear decline of MRF activity over 60 min. 5. 5. Of eight glycohydrolases tested, only β-amylase significantly degraded the MRF. 6. 6. Because of its heat lability and susceptibility to protease and glycohydrolase degradation, the B. plicatilis MRF is most likely to be a glycoprotein.
Dermal ischemia in the burn wound

Abstract Rats receiving full-thickness burns were studied by postmortem angiography of the burn wound. Immediately postburn, the circulation was found to be patent and unchanged from unburned controls. Vascular compromise was found to be progressive over 24 hr, with the first evidence of disruption between 2 and 4 hr postburn. Animals were then given heparin postburn with no change in the pathologic process. However, when animals were pretreated with heparin, the vascular integrity was spared up to 72 hr postburn. The authors speculate that some tissues in the burn wound are not irreversibly destroyed at the time of injury but die later as a result of an ongoing pathologic process. They further speculate that there is a prepathologic period during which this process may be reversed or prevented by pharmacologic manipulation. The prepathologic period may last up to 4 hr postburn.
Exploring the building energy impacts of green roof design decisions-a modeling study of buildings in four distinct climates

This study explores the complex and interacting physical mechanisms that lead to building energy use implications of green roof design decisions. The EnergyPlus building energy simulation program, ...
Kinetic Isotope Effects for Nonadiabatic Proton Transfer Reactions in a Polar Environment. 2. Comparison with an Electronically Diabatic Description

Kinetic isotope effects (KIEs) for proton transfer (PT) in a polar environment in the nonadiabatic, i.e., tunneling, regime was presented in the preceding paper (Kiefer, P. M.; Hynes, J. T, J. Phys. Chem. A 2004, 108, 0000). The present paper extends this work by comparing the electronically adiabatic (EAd) view of tunneling PT reactions of that paper with electronically diabatic (EDi) tunneling PT descriptions. Compared to the EAd PT description, the electronically diabatic character inherent in EDi PT produces smaller rate constants, larger KIE magnitudes with a smaller variation with reaction asymmetry, and a smaller activation energy difference EAD − EAH. Specifically, the EDi PT picture is characterized by a “nonadiabatic coupling” element that is smaller and less sensitive to both H-bond motion and proton vibrational excitation than those for EAd PT.
Development of the chick columella: immunohistochemical studies with anti-collagen monoclonal antibodies

Developmentally regulated changes in the extracellular matrices of the columella have been immunohistochemically analyzed with anti-collagen, type-specific monoclonal antibodies. In the 12-day chick embryo, the ossicle is entirely cartilagenous. By using immunohistochemical methods, we found that the 12-day columella contains type II collagen within the cartilagenous matrix and type I collagen in the surrounding perichondrium, but no type X collagen. Previous studies have shown that type X collagen is specific for hypertrophic cartilage (i.e., the site of future marrow cavity formation and ossification). By 16 days, hypertrophic cartilage is evident, type X collagen is present, and ossification has started medially adjacent to the oval window. These results both confirm and extend those of other chick endochondral bones that have been studied. Thus, the columella can serve as a model system for analysis of ossicular development and the associated temporal and spatial changes which occur within its extracellular matrices.
Relative Rearrangements Of Synaptotagmin3 C2A And C2B Domains Are Influenced ay Calcium, Lipids And SNARE Proteins

Synaptotagmins are able to bind negatively charged lipids in Ca2+ dependent manner and act as Ca2+ sensors. Together with SNARE and additional auxiliary proteins synaptotagmins coordinate Ca2+ triggered vesicle exocytosis, although the exact mechanism remains unclear. Synaptotagmins are transmembrane proteins comprised of a short intralumenal/extracellular sequence, single transmembrane helix, long unstructured linker followed by two cytoplasmic domains, called C2A and C2B, which are separated by a short flexible linker. The reports of the intramolecular interactions between C2A and C2B domains in solution are inconsistent. In order to determine relative rearrangements of C2A and C2B domains in the presence of synaptotagmin ligands, lipids, SNARE proteins and SNARE complex, single molecule fluorescence resonance energy transfer (sm FRET) was used. C2A and C2B domains were each labeled with a single fluorophore, tethered to the surface and conformational dynamics monitored using smFRET. Results suggest that the relative rearrangement of Synaptotagmin III C2A and C2B domains in the presence and absence of calcium is dynamic and influenced by interactions with liposomes, SNARE proteins, and SNARE complex.
TERATOGENIC AGENTS AND CONGENITAL MALFORMATIONS.

T H E recent thalidomide tragedy has focused worldwide medical concern on the problem of human teratology and renewed the interest in environmentally induced malformations which was generated over twenty years ago by the recognition of the rubella malformation syndrome. Until 30 years ago, with the exception of fetal irradiation, human malformations were considered to be almost entirely genetically determined. Though laboratory experience had demonstrated that a variety of agents could affect development in lower animals, it was confidently believed that, in the mammal, the placenta served as an effective defensive barrier protecting the fetus from teratogenic insult. The era of active investigation of mammalian teratology began with the observation in swine by Hale, 1 and later in
Chromatographic Analysis of Phospholipids during Monocyte Maturation

Abstract Whether ether phospholipids are intrinsic to cell membranes or are acquired concomitantly with capacity for motion is unknown. Plasmalogen content was assessed in the human monocyte-macrophage-like cell line U937 that can be induced with dimethylsulfoxide (1.3%) to synchronously differentiate from poorly motile immature leukocytic cells to briskly motile mature cells. The phosphatidylethanolamine (PE) content of immature cells was 180 ± 10 μg/108 cells for U937 cells. Alkaline hydrolysis of PE resulted in 50% lyso-PE and 50% free fatty acid. Treatment of lyso-PE with acid and phospholipase A2 demonstrated that PE is 1-(0-1'-aklenyl), 2-acyl PE. This was confirmed by infrared and proton nuclear magnetic resonance ('H-NMR) spectroscopy. The phosphatidylcholine (PC) content of immature cells was 235 ± 5 μg/108 cells. In contrast to PE< 100% of PC was diacyl homologues. Following differentiation to mature motile cells, the plasmalogen content of PE and PE significantly increased. The content of PC an...
A new two-color Fab labeling method for autoantigen protein microarrays

Antigen microarrays hold great promise for profiling the humoral immune response in the settings of autoimmunity, allergy and cancer. This approach involves immobilizing antigens on a slide surface and then exposing the array to biological fluids containing immunoglobulins. Although these arrays have proven extremely useful as research tools, they suffer from several sources of variability. To address these issues, we have developed a new two-color Fab labeling method that allows two samples to be applied simultaneously to the same array. This straightforward labeling approach improves reproducibility and reliably detects changes in autoantibody concentrations. Using this technique we profiled serum from a mouse model of systemic lupus erythematosus (SLE) and detected both expected and previously unrecognized reactivities. The improved labeling and detection method described here overcomes several problems that have hindered antigen microarrays and should facilitate translation to the clinical setting.
Terminology model discovery using natural language processing and visualization techniques

Medical terminologies are important for unambiguous encoding and exchange of clinical information. The traditional manual method of developing terminology models is time-consuming and limited in the number of phrases that a human developer can examine. In this paper, we present an automated method for developing medical terminology models based on natural language processing (NLP) and information visualization techniques. Surgical pathology reports were selected as the testing corpus for developing a pathology procedure terminology model. The use of a general NLP processor for the medical domain, MedLEE, provides an automated method for acquiring semantic structures from a free text corpus and sheds light on a new high-throughput method of medical terminology model development. The use of an information visualization technique supports the summarization and visualization of the large quantity of semantic structures generated from medical documents. We believe that a general method based on NLP and information visualization will facilitate the modeling of medical terminologies.
The influence of neural retina and lens on lens regeneration from dorsal iris implants in Triturus viridescens larvae.

Abstract In order to study the role of the neural retina and lens on lens regeneration from the iris, sectors of mid-dorsal iris from larval Triturus viridescens donors were implanted into the following sites in larval hosts of the same species: (a) dorsal fin, (b) anterior chamber of the eye, host lens present, (c) vitreous chamber of the eye, host lens absent, and (d) vitreous chamber of the eye, host lens present. In these locations, the implanted iris was subject to the influence of (a) neither neural retina nor lens, (b) probably only lens. (c) neural retina only, or (d) neural retina and lens together. Lens regeneration failed to take place in the anterior chamber or dorsal fin, thus showing the necessity of the neural retinal stimulus. Lens regeneration occurred from implants into the vitreous chamber not only in the absence of the host lens, but also in its presence. However, both the frequency of lens regeneration and the size and growth rate of the regenerates were decreased when the implant was located between the neural retina and host lens, therefore being subject to the influence of both tissues together. It was suggested that the inhibitory action of the host lens on iris implants in this location could be (1) mechanical, by displacing the implant more deeply into the vitreous chamber or (2) chemical, by competing with the lens developing from the implant for the neural retinal factor or through the production of a specific inhibitor for the homologous tissue.
Pineal response to light: mediation by the accessory optic system in the monkey.

THE activity of the melatonin-forming enzyme in the rat pineal gland, hydroxyindole-O-methyl-transferase (HIOMT), is high in animals kept in constant darkness and low when they are kept in constant light1. The response to light depends on the integrity of one component of the central retinal projections, the accessory optic system. Rats subjected to bilateral section of the inferior accessory optic tracts do not show a pineal HIOMT response to light although their visual behaviour is otherwise normal2,3. In contrast, animals with bilateral transection of the primary optic tracts behave as though they were blind but exhibit a normal pineal response to light2,3. There seem to be two separate functions carried out by the central retinal projections in the rat; one projection, the primary optic tracts, maintains visually guided behaviour, and the other, the accessory optic system, shares in the control of a pineal response to light.
Magnetic changes observed in a solar flare

The present investigation is concerned with an exceptionally well observed flare showing good evidence of magnetic change occurring in the impulse peak of the energy release. The presented observations confirm that a flare can produce observable, sudden, permanent changes in the photospheric magnetic field. The considered flare occurred on April 10, 1980, in Hale Region 16747 (NOAA Region 2372). The observations indicate that the flare was triggered by a small emerging magnetic bipole. The main energy release occurred in the eruption of a filament.
Sex differences in the links between attractiveness, self-esteem and the body

Abstract Two studies were conducted to determine: if the links between the body and self-perceived attractiveness and self-esteem for men and women differ. Following evolutionary and social learning theories, affective and cognitive links were hypothesized for women's attractiveness while no links were hypothesized for men's attractiveness. Additionally, affective links were expected for women's self-esteem while no links were expected for men's self-esteem. The results obtained supported these hypotheses. Findings are discussed in terms of the societal value placed on women's attractiveness and evolutionary theory.
The use of in vitro methods for assessing reproductive toxicity. Dichlorophenols

Environmental levels of dichlorophenols (DCPs) appear to be increasing. A paucity of knowledge exists concerning the impact of these agents on human health, including reproductive effects. Mice are being exposed to various DCPs to determine their toxic potential. In addition, the mouse in vitro fertilization method was used to evaluate the potential reproductive effects of a series of DCPs. This method is a preliminary reproductive screening procedure. In vitro penetration was depressed by 2,5-DCP, 3,4-DCP and 3,5-DCP. None of the agents affected sperm motility. Acridine orange fluorescent microscopy revealed that 3,4-DCP and 3,5-DCP disrupted the sperm acrosome; this could result in depressed penetration.
Should children ever donate kidneys? Views of U.S. transplant centers.

Background. Living donors provide the best outcome for children undergoing renal transplantation. Most of these donors are parents. When parents are unable to donate, siblings are often considered. But what if the siblings are also children? Should they be permitted to donate? Methods. To see how this difficult ethical question is currently handled, a survey was mailed to all U.S. renal transplant centers asking for their policies regarding kidney donation by minors (<18 years old). Results. Among the 117 responding centers that offer pediatric transplantation, the vast majority (81%) prefer living related donors for pediatric recipients. Yet, only 33% of responding centers would allow a monozygotic twin minor to donate a kidney to his or her twin, and even fewer (21%) would allow a nontwin minor to donate to a sibling. In the year before the survey, only two of these centers had actually used a child as a kidney donor. Furthermore, the great majority of responding centers (68%) require living donors to be at least 18 years old. Conclusions. These data indicate that most U.S. transplant centers are opposed to using children as living kidney donors. On the other hand, a careful analysis of this issue suggests that although donation by a minor should be uncommon, a complete ban of this practice may be unwarranted. In unusual circumstances in which no other suitable donor is available, consenting mature minors, and even rare immature minors who are highly likely to benefit from donating, may be ethically acceptable. Although there are probably no absolute wrong or right answers, the question of kidney donation by children should be readdressed.
Cost analysis of colposcopy for abnormal cytology in post-treatment surveillance for cervical cancer

Abstract Objective The aim of this study was to estimate cost and outcomes associated with colposcopy following abnormal Pap for women with a history of cervical cancer. Methods Decision models compared the costs and number of isolated local recurrences (ILR) detected using two strategies, colposcopy and no colposcopy, for women with a history of cervical cancer and low grade or high grade Pap. Clinical data for input were derived from a cohort of women with a history of cervical cancer undergoing surveillance Paps at 2 institutions. Costs were obtained using national reimbursement data. Results Five hundred fifty-six patients underwent 2900 surveillance Paps. Twenty-seven of 50 women with a low grade Pap underwent colposcopy. One of 3 recurrences in the colposcopy group was an ILR diagnosed colposcopically. Colposcopy following low grade Pap costs $354 more and resulted in a lower rate of diagnosis of ILR compared to no colposcopy (3.7% vs 8.6%). Sixty of 78 women with a high grade Pap underwent colposcopy. Three of 15 recurrences in the colposcopy group were ILR diagnosed colposcopically. Colposcopy following high grade Pap costs $623 more than no colposcopy but resulted in a higher rate of diagnosis of ILR (5% vs 0%; $7481 per additional ILR). Conclusions Colposcopy following low or high grade surveillance Pap smear adds substantial cost to the management of women with cervical cancer. Only colposcopy following a high grade Pap is associated with a higher probability that cervical cancer recurrence will be detected when salvageable. These findings support withholding colposcopy for abnormal surveillance Pap tests less than high grade.
Self-Assembling Dendrimers

Hydrogen bond-mediated self-assembly is a powerful strategy for generating large structures from smaller subunits. The synthesis of molecules containing two isophthalic acid units covalently attached to a rigid aromatic spacer is described. By normal pairing of carboxylic acids into hydrogen-bonded dimers, these molecules self-assemble in organic solvents to form either a series of linear aggregates or a cyclic hexamer. These molecules were linked to the core of a family of polyether dendrimers, which caused the hexamer to be formed preferentially. The stability of the hexamer depended on the generation number of the dendrimer. The largest of these hydrogen-bonded macromolecular assemblies is roughly disk-shaped with a 9-nanometer diameter and a 2-nanometer thickness. Its size and molecular mass (34,000 daltons) are comparable to that of small proteins.
Role of Saccharomyces Single-Stranded DNA-Binding Protein RPA in the Strand Invasion Step of Double-Strand Break Repair

The single-stranded DNA (ssDNA)-binding protein replication protein A (RPA) is essential for both DNA replication and recombination. Chromatin immunoprecipitation techniques were used to visualize the kinetics and extent of RPA binding following induction of a double-strand break (DSB) and during its repair by homologous recombination in yeast. RPA assembles at the HO endonuclease-cut MAT locus simultaneously with the appearance of the DSB, and binding spreads away from the DSB as 5′ to 3′ exonuclease activity creates more ssDNA. RPA binding precedes binding of the Rad51 recombination protein. The extent of RPA binding is greater when Rad51 is absent, supporting the idea that Rad51 displaces RPA from ssDNA. RPA plays an important role during RAD51-mediated strand invasion of the MAT ssDNA into the donor sequence HML. The replication-proficient but recombination-defective rfa1-t11 (K45E) mutation in the large subunit of RPA is normal in facilitating Rad51 filament formation on ssDNA, but is unable to achieve synapsis between MAT and HML. Thus, RPA appears to play a role in strand invasion as well as in facilitating Rad51 binding to ssDNA, possibly by stabilizing the displaced ssDNA.
Recently Enacted Programs to Address the Dropout Problem in New York State.

In New York, the state has responded to the student dropout problem, which is particularly acute in urban school districts, by enacting a number of new state aid programs to address this problem. However, because many of the program grants are awarded competitively, the benefits are not distributed equally to all school districts. There is also much duplication and overlap in terms of program purposes and activities. Dropout prevention in the schools might be better served if some of the various programs were consolidated and the funds distributed on a more equitable basis so that aid is directed to areas of greatest need and the administrative burden at both the state and local levels is reduced.
Comparative studies on the properties of the eukaryotic protein synthesis initiation factor IF-I from several sources.

Eukaryotic protein synthesis initiation factor IF-I has been purified from a variety of cells and tissues, and some of the properties of these preparations are compared. IF-I activity from all sources elutes close to the excluded volume of Sephadex G-200 columns, indicating similar, if not identical, molecular weights (350 000). There is little or no species or tissue specificity in the binding of the initiator tRNA from one source to IF-I purified from another source. The ability of all IF-I preparations to form a ternary complex with GTP and the initiator tRNA is inactivated by N-ethylmaleimide; this sulfhydryl reagent also completely inactivates the rabbit reticulocyte IF-I-mediated binding of the initiator tRNA (rabbit liver) to rabbit reticulocyte 40-S ribosomal subunits. Thus, it appears that IF-I is an obligatory and ubiquitous protein synthesis initiation factor in the cytoplasm of all eukaryotes.
Predictors of Abnormal Findings of Computed Tomography of the Head in Pediatric Patients Presenting With Seizures

Abstract Study objective: To develop a preliminary clinical decision guideline, using characteristics of ED pediatric patients presenting with seizures, that successfully predicts all abnormal results of computed tomography (CT) of the head. Methods: We assembled a retrospective case series in the ED of a tertiary care children's hospital without trauma designation. The series comprised all patients who presented between January 1, 1992, and December 31, 1994, with seizures (febrile and afebrile) who underwent head CT as part of ED evaluation. Results: Our inclusion criteria were met by 203 patients. Of these patients, who had a median age of 3.1 years, 53% were boys; 18% had been transferred from another facility; 25% had received anticonvulsant medication in the field, at the referring facility, or both; 32% had a history of seizures before the presenting episode; 6% had sustained a closed-head injury (CHI); 15% had a cerebrospinal fluid (CSF) shunt; 4% had an underlying malignancy or neurocutaneous disorder (NCT); and 30% had a documented fever. CT findings were abnormal in 25 patients (12%). CT showed evidence of hemorrhage in eight patients (32%), small focal abnormalities in four (16%), cerebral edema in three (12%), and shunt obstruction in two (8%). χ 2 Recursive-partitioning analysis revealed that CT scan results were always normal when the patient did not have an underlying high-risk condition (malignancy, NCT, recent CHI, or recent CSF shunt revision), was older than 6 months, had sustained a seizure of 15 minutes or less, and did not have a history of a new-onset focal neurologic deficit. Retrospective application of these criteria revealed that 41% of the CT scans could have been deferred. Conclusion: In this case series, the absence of defined high-risk factors predicted normal head CT findings. The deferral of emergency CT in this population should be considered. [Warden CR, Brownstein DR, Del Beccaro MA: Predictors of abnormal findings of computed tomography of the head in pediatric patients presenting with seizures. Ann Emerg Med April 1997; 29:518-523.]