cssi/SciSciGPT-SciSciNet huggingface dataset:
Genomic DNA recombination with cell-penetrating peptide-tagged cre protein in mouse skeletal and cardiac muscle

The Cre-loxP recombination system has been used to promote DNA recombination both in vitro and in vivo. For in vivo delivery, Cre expression is commonly achieved through the use of tissue/cell type-specific promoters, viral infection, or drug inducible transcription and protein translocation to promote targeted DNA excision. The development of cell permeable (or penetrating) peptide tagged proteins has facilitated the delivery of Cre recombinase protein into cells in culture, organotypic slide culture, or in living animals. In this report, we generated bacterially expressed, his-tagged Cre protein with either a cardiac targeting peptide or an antennapedia peptide at the C-terminus and demonstrated efficient uptake and recombination in both cell culture and mice. To facilitate delivery to cardiac and skeletal muscle, we mixed proteins with pluronic F-127 hydrogel and delivered Cre protein into reporter Rosa26mTmG mouse skeletal muscle or Rosa26LacZ cardiac muscle via ultrasound guided injection. Activation of reporter gene expression indicated that these Cre proteins were enzymatically active. Recombination events were detected only in the vicinity of injection areas. In conclusion, we have developed a method to deliver enzymatically active Cre protein locally to skeletal muscle and cardiac muscle that may be adapted for use with other proteins.
Developing a Drama Management Architecture for Interactive Fiction Games

A growing research community is working towards employing drama management components in interactive story-based games. These components gently guide the story towards a narrative arc that improves the player's experience. In this paper we present our Drama Management architecture for real-time interactive story games that has been connected to a real graphical interactive story based on the Anchorhead game. We also report on the natural language understanding system that has been incorporated in the system and report on a user study with an implementation of our DM architecture.
Influence of androgen on the development of sexual behavior in rats: I. Time of administration and masculine copulatory responses, penile reflexes, and androgen receptors in females

Abstract The objective of the present study was to investigate the effect of the time of administration of androgen, during the neonatal period, on the development of masculine copulatory behavior in female rats. In addition, the influence of androgen, administered neonatally, on the development of penile reflexes and cytoplasmic androgen receptor levels in the hypothalamic-preoptic area (HPOA) was examined. Female rats were injected with 0.5 mg testosterone propionate (TP) at either 1, 8, or 24 hr after birth and again 24 hr after the first injection. Fifty percent of the females treated with TP at 1 and 8 hr after birth displayed the ejaculatory response when tested in adulthood. In contrast, 93 and 87.5% of oil-treated males and females, respectively, which were androgenized at 24 hr after birth exhibited this response. The results indicate that a considerable amount of masculinization occurs postnatally in the rat. However, none of the androgenized females displayed any penile reflexes even when tested following the display of an ejaculatory response. HPOA androgen receptor levels were somewhat higher in the oil-treated females than in males but were not correlated with the ability to exhibit ejaculation patterns.
Cyclic spectral analysis for signal detection and modulation recognition

The principles and some basic applications of cyclic spectral analysis are reviewed, and receiver operating characteristics with respect to cyclic feature detection for a simulated PSK signal in variable broadband noise and narrowband interference are presented. The authors discuss a generalization of the single-cycle detector, known as a cyclic spectrum analyzer, and its applicability to the problems of signal classification and modulation recognition. They briefly discuss another generalization of the cycle detector that results in simultaneous detection and time-difference-of-arrival estimation for two-antenna reception. >
Circadian rhythmicity in dopamine content of mammalian retina: role of the photoreceptors.

Dopamine, the predominant retinal catecholamine, is a neurotransmitter and neuromodulator known to regulate light-adaptive retinal processes. Because dopamine influences several rhythmic events in the retina it is also a candidate for a retinal circadian signal. Using high performance liquid chromatography (HPLC), we have tested whether dopamine and its breakdown products are rhythmic in Royal College of Surgeons (RCS) rats with normal and dystrophic retinas. In both normal and mutant animals entrained to a 12-h light/12-h dark cycle, we found robust daily rhythms of dopamine and its two major metabolites. To address circadian rhythmicity of dopamine content, rats were entrained to light/dark cycles and released into constant darkness, using the circadian rhythm of wheel-running activity as a marker of each individual's circadian phase. Circadian rhythms of dopamine and metabolite content persisted in both wild type and retinally degenerate animals held for two weeks in constant darkness. Our results demonstrate for the first time clear circadian rhythms of dopamine content and turnover in a free-running mammal, and suggest that rods and cones are not required for dopamine rhythmicity .
Livestock Models in Translational Medicine

This issue of the ILAR Journal focuses on livestock models in translational medicine. Livestock models of selected human diseases present important advantages as compared with rodent models for translating fundamental breakthroughs in biology to useful preventatives and therapeutics for humans. Livestock reflect the complexity of applying medical advances in an outbred species. In many cases, the pathogenesis of infectious, metabolic, genetic, and neoplastic diseases in livestock species more closely resembles that in humans than does the pathogenesis of rodent models. Livestock models also provide the advantage of similar organ size and function and the ability to serially sample an animal throughout the study period. Research using livestock models for human disease often benefits not only human health but animal health and food production as well. This issue of the ILAR Journal presents information on translational research using livestock models in two broad areas: microbiology and infectious disease (transmissible spongiform encephalopathies, mycobacterial infections, influenza A virus infection, vaccine development and testing, the human microbiota) and metabolic, neoplastic, and genetic disorders (stem cell therapy, male germ line cell biology, pulmonary adenocarcinoma, muscular dystrophy, wound healing). In addition, there is a manuscript devoted to Institutional Animal Care and Use Committees' responsibilities for reviewing research using livestock models. Conducting translational research using livestock models requires special facilities and researchers with expertise in livestock. There are many institutions in the world with experienced researchers and facilities designed for livestock research; primarily associated with colleges of agriculture and veterinary medicine or government laboratories.
Estimates of the Relations between Eulerian and Lagrangian Scales in Large Reynolds Number Turbulence

Abstract With Eulerian and Lagrangian spectra approximated by their “inertial subrange” forms between appropriate wave number and frequency limits, it is found that the Lagrangian integral time scale is roughly equal to the Eulerian integral length scale divided by the root-mean-square velocity. The corresponding estimate for the “microscale” ratio shows fair agreement with the large Reynolds number form of Heisen-berg's result. A similar approach to Eulerian time scales gives values approximately equal to the Lagrangian scales.
Vertical Disturbance of Sediments by Horseshoe Crabs (Limulus polyphemus) During Their Spawning Season

Biological and physical reworking of sediments can profoundly affect the structure and functioning of benthic communities. The depth of the disturbance is an important factor that controls the types of organisms that can exist within the sediments. Large numbers of horseshoe crabs,Limulus polyphemus, spawn each spring on the sandy shores of Delaware Bay beaches. We have used this abundance peak to provide an estimate of the depth of sediment disruption caused by this species on an intertidal flat adjoining a major spawning beach. Vertical columns of marked sediment were placed in three locations of an intertidal flat. Some columns were protected with cages while others remained unprotected. Analysis of variance of the depth of disruption of the marked sediment indicated that different areas of the intertidal zone were disrupted to different depths. Caged marked sediment was disturbed to an average depth of 3.2 cm while unprotected sediment was disturbed to a mean depth of 11.1 cm. Deepest mixing occurred in a trough between sandwave crests and averaged 17.7 cm deep. These mixing depths are greater than the 1.2 cm deep disturbance produced by nonstorm wave action in the study area.
Growth dynamics of sputter deposition.

A Comment on the Letter by R. P. U. Karunasiri, R. Bruinsma, and J. Rudnick, Phys. Rev. Lett. 62, 788 (1989).
Determination of the dissociation constant and limiting equivalent conductance of a weak electrolyte from conductance measurements on the weak electrolyte

Abstract A method is described for computing the dissociation constant and equivalent conductance at infinite dilution, A o , for a weak electrolyte from as few as two conductance measurements at different concentrations. The iterative procedure applied to acetic acid data yielded a dissociation constant of 1.80 X 10- 5 and an average value (n = 4) of A o of 389.5 compared with an expected value of 390.7.
Photoacoustic imaging of functional domains in primary motor cortex in rhesus macaques

Functional detection in primate brains has particular advantages because of the similarity between non-human primate brain and human brain and the potential for relevance to a wide range of conditions such as stroke and Parkinson's disease. In this research, we used photoacoustic imaging (PAI) technique to detect functional changes in primary motor cortex of awake rhesus monkeys. We observed strong increases in photoacoustic signal amplitude during both passive and active forelimb movement, which indicates an increase in total hemoglobin concentration resulting from activation of primary motor cortex. Further, with PAI approach, we were able to obtain depthresolved functional information from primary motor cortex. The results show that PAI can reliably detect primary motor cortex activation associated with forelimb movement in rhesus macaques with a minimal-invasive approach.
On the computation of ro-vibrational energy levels of triatomic molecules

Abstract We describe a new code for computing ro-vibrational energy levels for general triatomic molecules. The numerical implementation is discussed in detail and sample results are given for the water molecule. The method is capable of very high accuracy with little difficulty.
On Ideology: Second Thoughts

theory is gray; green the tree of life. —Octavio Paz (298) “Whither ideology?” is an intriguing question, to which my immediate response is: Nowhere! Has its moment passed, at least in relation to ...
Thermodynamics of the quasi-epitaxial flavin assembly around various-chirality carbon nanotubes.

Establishing methods to accurately assess and model the binding strength of surfactants around a given-chirality single-walled carbon nanotube (SWNT) are crucial for selective enrichment, targeted functionalization, and spectrally sharp nanodevices. Unlike surfactant exchange, which is subject to interferences from the second surfactant, we herein introduce a thermal dissociation method based on reversible H+/O2 doping to determine SWNT/surfactant thermodynamic stability values with greater fidelity. Thermodynamic values were reproduced using molecular mechanics augmented by ab initio calculations in order to better assess π–π interactions. This afforded detailed quantification of the flavin binding strength in terms of π–π stacking (55–58%), with the remaining portion roughly split 3:1 between electrostatic plus van der Waals flavin mononucleotide (FMN) interdigitation and H-bonding interactions, respectively. Quasi-epitaxial π–π alignment between the near-armchair FMN helix and the underlying nanotube l...
Perspectives of dental students and faculty about evidence-based dental practice.

Abstract Objective The study aimed at evaluating attitudes and perceptions of dental students and faculty toward evidence-based practice, integration of technology and social media, general practitioners' and specialists' scope of practice, and dental practice rewards and disadvantages. Methods A survey instrument was designed with 10 statements rated on a five-point Likert scale (strongly agree to strongly disagree) and an optional comment section. The survey instrument was delivered through SurveyMonkey, whereby 401 students and 182 faculty members from ten U.S. dental schools participated (16% estimated response rate). Null hypotheses regarding the equality between the responses of the two groups were statistically tested using Mann–Whitney U test. Statistical significance was set at .05. Results Evidence-based practice is positively perceived by both groups, but with significantly higher support by faculty than students ( P = 0.002). Both groups agreed that technological advancements are advantageous ( P = 0.95), but do not constitute good dentistry and cannot mask poor clinical skills. Students showed higher support for social media than faculty ( P = 0.000). Both groups perceived group practices positively. Faculty members showed higher agreement than students toward limitation of dental specialists' practices to their specialties ( P = 0.000). Both groups are aware of practice disadvantages, such as increased litigation, health risks, and detriment to the dentist's posture. However, they both perceive dental practice positively despite all these challenges. Conclusions Students and faculty share generally comparable perspectives toward dental practice. They are both in agreement with evidence-based practice and adoption of technology. They both acknowledge practice limitations.
The impact of loan prepayment risk and deposit withdrawal risk on the optimal intermediation margin

Abstract Numerous studies have analyzed how a bank's intermediation margin varies with respect to such factors as credit quality, funding risk, bank capital, deposit insurance and other factors. However, these studies ignore the potential that loans tend to prepay if interest rates decline and deposits tend to be withdrawn if interest rates rise. Taking this very fundamental fact into account, we derive optimal loan rates and deposit rates when the bank is subject to loan prepayments and deposit withdrawals. Among other things, we find that greater volatility of interest rates tends to increase the margin. The strength of the correlation between the level of interest rates and the propensity to prepay loans (withdraw deposits) also plays an interesting role.
Identification of the Components Controlling Inactivation of Voltage-Gated Ca2+ Channels

Ca(2+)-dependent inactivation (CDI) of L-type voltage-gated Ca(2+) channels limits Ca(2+) entry into neurons, thereby regulating numerous cellular events. Here we present the isolation and purification of the Ca(2+)-sensor complex, consisting of calmodulin (CaM) and part of the channel's pore-forming alpha(1C) subunit, and demonstrate the Ca(2+)-dependent conformational shift that underlies inactivation. Dominant-negative CaM mutants that prevent CDI block the sensor's Ca(2+)-dependent conformational change. We show how Ile1654 in the CaM binding IQ motif of alpha(1C) forms the link between the Ca(2+) sensor and the downstream inactivation machinery, using the alpha(1C) EF hand motif as a signal transducer to activate the putative pore-occluder, the alpha(1C) I-II intracellular linker.
Antenatal diagnosis of metabolic disorders.

SUMMARY Reliable techniques for the antenatal diagnosis of many inherited metabolic disorders have recently been developed. There is little doubt that the list of disorders detectable in utero will continue to expand rapidly with our knowledge of the biochemical basis of inherited disease. New antenatal diagnostic methods will be developed and existing procedures will become safer, more accurate and more readily available. These changes will undoubtedly be accompanied by new developments in the antenatal diagnosis of other types of disorders, including chromosomal abnormalities and congenital malformations as discussed in other chapters in this issue. Such developments in the prevention of genetic disease will enable us to offer additional options to our patients and families affected with these often devastating disorders.
Hydrogen permeability of multiphase V–Ti–Ni metallic membranes

Development of advanced hydrogen separation membranes in support of hydrogen production processes such as coal gasification and as front end gas purifiers for fuel cell based system is paramount to the successful implementation of a national hydrogen economy. Current generation metallic hydrogen separation membranes are based on Pd-alloys. Although the technology has proven successful, at issue is the high cost of palladium. Evaluation of non-noble metal based dense metallic separation membranes is currently receiving national and international attention. The focal point of the reported work was to evaluate a Group 5A-Ta, Nb, V-based alloy with respect to microstructural features and hydrogen permeability. Electrochemical hydrogen permeation testing of the V-Ti-Ni alloy is reported herein and compared to pure Pd measurements recorded as part of this same study. The V-Ti-Ni was demonstrated to have a steady state hydrogen permeation rate an order of magnitude higher than the pure Pd material in testing conducted at 22 C.
An Irradiation-Altered Bone Marrow Microenvironment Impacts Anabolic Actions of PTH

PTH stimulates bone formation and increases hematopoietic stem cells through mechanisms as yet uncertain. The purpose of this study was to identify mechanisms by which PTH links actions on cells of hematopoietic origin with osteoblast-mediated bone formation. C57B6 mice (10 d) were nonlethally irradiated and then administered PTH for 5–20 d. Irradiation reduced bone marrow cellularity with retention of cells lining trabeculae. PTH anabolic activity was greater in irradiated vs. nonirradiated mice, which could not be accounted for by altered osteoblasts directly or osteoclasts but instead via an altered bone marrow microenvironment. Irradiation increased fibroblast growth factor 2, TGFβ, and IL-6 mRNA levels in the bone marrow in vivo. Irradiation decreased B220 cell numbers, whereas the percent of Lin−Sca-1+c-kit+ (LSK), CD11b+, CD68+, CD41+, Lin−CD29+Sca-1+ cells, and proliferating CD45−Nestin+ cells was increased. Megakaryocyte numbers were reduced with irradiation and located more closely to trabecular...
Kentsin: Tetrapeptide from hamster embryos produces naloxone-sensitive effects without binding to opioid receptors ☆

The opioid nature of kentsin (Thr-Pro-Arg-Lys) and its ability to alter pain perception and intestinal transit were examined. Kentsin (30,000 nM) did not inhibit electrically stimulated contractions of the guinea pig ileum (GPI) or mouse vas deferens (MVD), nor did it cause a rightward displacement of the inhibitory concentration-response curves of the mu-selective opioid agonist PL017 in the GPI or the delta-selective agonist DPDPE in the MVD. Kentsin (10,000 nM) did not displace [3H] naloxone from rat brain homogenates. These results indicate that kentsin lacks opioid agonist and mu and delta opioid antagonist properties and does not bind to opioid receptors. In vivo, kentsin produced dose-dependent analgesia in both the hotplate and abdominal stretch tests when administered intracerebroventricularly (ICV) and intrathecally but not intravenously. The central analgesic effect of kentsin was partially antagonized by the opioid antagonist naloxone. Kentsin inhibited intestinal transit in a dose-dependent manner after ICV administration only. The intestinal antitransit effect of kentsin was not blocked by pretreatment with naloxone. These results suggest that kentsin acts centrally to produce both opioid and non-opioid effects. Further, the opioid-mediated analgesic effects of kentsin involve mechanisms other than direct interaction with opioid receptors.
Effects of selective spinal cord lesions on the spinal motor evoked potential (MEP) in the rat

Abstract The effects of selective spinal cord lesions on the motor evoked potential (MEP) in 21 rats were investigated. No significant change in peak amplitude was observed following lesions of the pyramidal tract. There was a significant decrease in peaks 1 and 2 with ventral funiculi lesions. All 4 peaks of the MEP were significantly reduced following lesions of the lateral funiculus. The most marked decrease in peak amplitude followed lateral funiculi lesions that involved the lateral grey of the spinal cord. In one animal where the lesion was confined to the grey matter in the cord there was a marked decrease in all peaks of the MEP. In 3 additional animals interruption of the descending tracts of the spinal cord via bilateral hemisections of the spinal cord failed to completely abolish the MEP. Increases in peak latency were also noted following spinal lesions. In some animals the increase in latency occurred in the absence of significant peak amplitude changes. The findings in this study refute the previously held position that the MEP in the rat arises from pyramidal tract activation. The role of the reticulospinal and propriospinal tracts in the generation and propagation of the MEP are discussed.
Breakage prior to entry of donor DNA in Pneumococcus transformation.

Abstract Products of the binding and uptake of high molecular weight [ 3 H]DNA by competent cells of Diplococcus pneumoniae were examined. Bound DNA, still sensitive to DNAase, could be released by NaOH or by guanidine · HCl and then examined. Double-strand breaks were found in it. The strand length distribution of this DNA was not distinguishable from that of the DNA found inside the cells at the same time, and was that expected for insertion of new breaks outside the cell at a median spacing of 2.8 · 10 6 daltons/strand. Conversion of donor label to a DNAase-resistant state was accompanied by production of an equal weight of acid-soluble donor fragments in the extracellular medium. These results suggest that double-strand breaks precede entry, that the strand segments thus produced enter without further breakage, and that the complement of each entering segment probably is degraded with release of the products outside the cell.
Physical properties of four polymorphic forms of sulfanilamide I: Densities, refractive indexes, and X-ray diffraction measurements

Densities, refractive indexes, and X-ray crystallographic data are tabulated for four crystalline forms of sulfanilamide. These data suggest that three of the forms have very similar structures.
Optical rotatory dispersion of amylose films

Abstract There is a direct correlation between the structure of amylose in the solid state, as determined by X-ray diffraction, and the conformation of amylose in solution. The specific rotations of amylose films showing a methyl sulfoxide complex (V Me 2 SO ), amorphous, or alkali-amylose structure are the same as those of amylose in corresponding solutions of methyl sulfoxide, 0.5 m potassium chloride, or 0.1–0.5 m potassium hydroxide. The rotation of amylose films that give a B-type of X-ray pattern is higher than that of either amylose V or amorphous films; this higher rotation is attributed to the presence of intermolecular hydrogen-bonds between adjacent amylose chains in the B structure. It is also shown that rotatory dispersion data, alone, cannot be used to establish the conformation of amylose in solution, since the parameter λ c in the Drude equation is insensitive to changes in structure; that is, amylose V Me 2 SO , V, and water-soaked B films all have a λ c of 150 nm. Consideration of X-ray, optical rotation, and published viscosity data leads to the conclusion that there is a continuous transition from a stiff, tightly coiled helix in methyl sulfoxide to a flexible coil in neutral, aqueous solution.
Reconstructing the range expansion and subsequent invasion of introduced European green crab along the west coast of the United States

The European green crab, Carcinus maenas, was first documented in San Francisco Bay in 1989, and has since spread north along the west coast of North America. The spread of this invasion has not been a smooth expansion, which has raised questions about the underlying causes of variation in recruitment. We modeled larval development and transport along the West Coast by employing an individual-based model that incorporated oceanographic model output of water temperature and ocean currents at fine spatial and temporal scales. The distance that larvae were advected depended primarily on the timing of larval release. However, the effect of seasonal ocean currents varied across latitude and years. Our results imply that the furthest northern transport from California occurs when larvae are released from Humboldt Bay during the fall of an El Nino year, making this a particularly risky time for invasion to Oregon and Washington estuaries. To precisely predict future spread and potential impacts of green crab, we recommend further empirical research to determine the precise timing of larval release and seasonal abundance of green crab larvae from North American west coast populations.
Analysis of Neuromuscular Control in Young and Older Individuals During Lateral Stepping

Older adults can develop neuromuscular deficiencies. We tested the hypothesis that these deficiencies could be reflected in altered neuromuscular control during normal daily tasks. Hence, we compared the ability to modulate ground reaction force (GRF) during lateral stepping (LS) from different step heights between younger and older adults. Kinetic data was obtained from younger (23-33 yrs, n=5) and older (57-65 yrs, n=5) male and female subjects. They stood on top of two 4-inch/8-inch high platforms. Each platform was placed on separate force plates. The subjects were instructed to step down laterally using their non-dominant leg and then step up to the original position. GRF and joint-angle kinematics of both limbs were recorded for the two-step heights. The time (% total) to achieve maximum amount of force (as % body weight) exerted was calculated using data from the average of three LS trials per subject. It was significantly different between males (32.75±1.57) and females (35.75±1.28) (p=0.012) or between young (33.479±1.43) and old (35.021±1.43) (p=0.018) using a three way repeated measures ANOVA comparing step height (4 inch, 8 inch), gender (male, female), and age (young, old.) According to the data, neuromuscular control of the LS task is affected by age and gender.
Coordination dynamics of trajectory formation

The present study aims to understand the neurally based coordination dynamics (multistability, loss of stability, transitions, etc.) of trajectory formation in a simple task. Six subjects produced two spatial patterns of coordination in the xy plane by alternating the abduction-adduction and flexion-extension motions of their right index finger. Each pattern was characterized by a unique temporal ratio between the x and y directions of motion: (1) a figure zero, a 1?1 temporal pattern; and (2) a figure eight, a 2?1 temporal pattern. The patterns were produced rhythmically and movement frequency was scaled across ten frequency plateaus, with ten cycles of motion per step. As movement frequency increased, switching from a figure eight to a figure zero was observed at critical cycling frequencies. The switch from pattern (2) to pattern (1) was identified in the spatial trajectory and power spectra of x(t) and y(t). En route to the transition, enhancement of fluctuations was observed in the Fourier amplitudes of x(t) and y(t), specifically at f 0 (the metronome frequency) and 2f 0 (the first harmonic off 0). Interestingly, there was no difference in the spatial variability of the two patterns. Overall, the data demonstrate that spatial patterns of coordination can be characterized in terms of the temporal relationship between the spatial components of the trajectory itself. We discuss the experimental findings in relation to other end-point planning and multijoint control strategies, as well as the much more general problem of temporal synchronization in many interlimb and intralimb coordination tasks.
A young patient with polyarthralgia and hearing loss: a case report of Muenke syndrome

There are few reports of the typical radiographic findings in the hands and feet of patients with Muenke syndrome. We present a case report of a young girl with Muenke syndrome, whose diagnosis was made following the observation of coalitions and coned epiphyses on hand radiographs.
An unusual cause of small bowel obstruction.

Gastroenterol Question: A 42year-old man presented with nausea, vomiting, abdominal pain, and distention over the previous 4 days. His past medical history was significant for 2 episodes of unprovoked pulmonary embolism 6 and 4 years before admission. Despite recommendations for lifelong anticoagulation, he discontinued taking the medication 15.0 and partial thromboplastin time was 90 seconds (normal, 26–36). Prothrombin and partial thromboplastin times corrected with mixing studies ruling out the presence of circulating inhibitors. Factor activity levels for factors II, VII, IX, and X (15%, 3%, 11%, and 13%, respectively) were very low. Computed tomography (CT) of the abdomen with contrast was performed (Figure A). He also underwent upper endoscopy, which demonstrated circumferential edema and biopsies were obtained for histopathologic examination (Figure B; HE low-power original magnification). What is the most likely diagnosis? Look on page 286 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.
Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer.

Abstract purpose: To determine the long-term impact of medical and surgical treatment of well differentiated papillary and follicular thyroid cancer. methods: Patients with papillary and follicular cancer (n = 1,355) treated either in U.S. Air Force or Ohio State University hospitals over the past 40 years were prospectively followed by questionnaire or personal examination to determine treatment outcomes. Outcomes were analyzed by Kaplan-Meier survival curves and Cox proportional-hazard regression model. results: Median follow-up was 15.7 years; 42% (568) of the patients were followed for 20 years and 14% (185) for 30 years. After 30 years, the survival rate was 76%, the recurrence rate was 30%, and the cancer death rate was 8%. Recurrences were most frequent at the extremes of age ( 59 years). Cancer mortality rates were lowest in patients younger than 40 years and increased with each subsequent decade of life. Thirty-year cancer mortality rates were greatest in follicular cancer patients, who were more likely to have adverse prognostic factors: older age, larger tumors, more mediastinal node involvement, and distant metastases. When patients with distant metasteses at diagnosis were excluded, follicular and papillary cancer mortality rates were similar (10% versus 6%, P not significant [NS]). In a Cox regression model that excluded patients who presented with distant metastases, the likelihood of cancer death was (1) increased by age ≥40 years, tumor size ≥1.5 cm, local tumor invasion, regional lymph-node metastases, and delay in therapy ≥12 months; (2) reduced by female sex, surgery more extensive than lobectomy, and 131 I plus thyroid hormone therapy; and (3) unaffected by tumor histologic type. Following 131 I therapy given only to ablate normal thyroid gland remnants, the recurrence rate was less than one third the rate after thyroid hormone therapy alone ( P 131 I has died of thyroid cancer. Low 131 I doses (29 to 50 mCi) were as effective as high doses (51 to 200 mCi) in controlling tumor recurrence (7% versus 9%, P = NS ). Following 131 I therapy, whether given for thyroid remnant ablation or cancer therapy, recurrence and the likelihood of cancer death were reduced by at least half, despite the existence of more adverse prognostic factors in patients given 131 I. At 30 years, the cumulative cancer mortality rate following 131 I therapy, regardless of the reason for its use, was one third that in patients not so treated ( P = 0.03). conclusion: Over the long term, for tumors ≥1.5 cm that are not initially metastatic to distant sites, near-total thyroidectomy followed by 131 I plus thyroid hormone therapy confers a distinct outcome advantage. This therapy reduces tumor recurrence and mortality sufficiently to offset the augmented risks incurred by delayed therapy, age ≥40 at the time of diagnosis, and tumors that are much larger than 1.5 cm, multicentric, locally invasive, or regionally metastatic.
Imaging S1P1 Activation In Vivo

Sphingosine-1-phosphate receptor 1 (S1P1) is a G protein-coupled receptor that is activated by the sphingolipid ligand sphingosine-1-phosphate (S1P). S1P1 is widely expressed across tissues and, when activated, has broad functions in the immune, vascular and nervous systems. In several diseases in which inflammation plays a critical role, S1P1 activation has been found to be involved in pathogenesis. However, the details of S1P1 activation in vivo under different physiologic conditions are not well understood. Here we describe how a new in vivo methodology to identify S1P1 activation has helped increase understanding of the manner in which this signaling molecule functions both in homeostasis and during inflammation.
Intergenerational transmission of attachment for infants raised in a prison nursery.

Within a larger intervention study, attachment was assessed with the Strange Situation Procedure for 30 infants who co-resided with their mothers in a prison nursery. Sixty percent of infants were ...
Independence of dysplastic nevi from total nevi in determining risk for nonfamilial melanoma

Abstract In the determination of risk for melanoma, relatively little is known about the possible independence of two important predictors, total nevi and clinically dysplastic nevi. From a study conducted in Sydney, Australia [see J. J. Nordlund et al., Cancer Res. 45 , 1855–1861 (1985)], 246 cases of melanoma (excluding 7% of targeted patients with a history of melanoma in a first-degree relative) were compared with 134 nonmelanoma controls. Participants had been examined by a dermatologist and an oncologist. Logistic regression analysis was used and included an age-sex interaction term in computing all estimates of relative risk in this report. Relative risk for melanoma in those with 16+ total nevi was significantly elevated at 1.8 but declined to a statistically nonsignificant level of 1.2 (95% confidence limit (CL): 0.7, 2.0) after adjustment for dysplastic nevi. In contrast, relative risk for melanoma in those with any dysplastic nevi was 7.6 (95% CL: 3.6, 16.0) but was maintained at a similarly elevated and statistically significant level of 7.7 (95% CL: 3.5, 17.1) after adjustment for total nevi. These patterns were even more evident in the younger half of the study population. The analyses suggest that much of the association between TN and nonfamilial melanoma is explained by the presence of dysplastic nevi and, conversely, they imply that dysplastic nevi represent a clinically distinct, qualitative disorder rather than simply a quantitative disorder wherein dysplastic nevi stem merely from an increase in total nevi. The dysplastic nevus syndrome accounts for 32% of all nonfamilial melanomas.
Progesterone receptor expression is a marker for early stage breast cancer: implications for progesterone receptor as a therapeutic tool and target.

Abstract We determined the association of estrogen receptor (ER) and progesterone receptor (PR) expression in invasive breast cancer with stage at diagnosis. Univariate analyses indicated that although ER and PR expression were inversely associated with grade ( P P P = 0.03) and not ER expression (OR, 1.04; CI, 0.94–1.16; P = 0.45) was inversely associated with stage. PR and not ER expression is a marker for early stage breast cancer.
Breaking symmetry in myxobacteria.

O.A.I. was supported by a Howard Hughes predoctoral fellowship. G.O. was supported by National Science Foundation grant DMS-9972826 and National Institutes of Health grant GM59875-02. D.K. was supported by National Institutes of Health Grant GM23441. The authors thank Albert Goldbeter for pointing out the feedback necessary to produce the FrzE oscillations. This model will be discussed in detail elsewhere. The authors thank David Zusman and David Astling for valuable conversations concerning the biochemical circuit in Figure 3A.
Cellular and molecular mechanisms of renal fibrosis

Renal fibrosis, particularly tubulointerstitial fibrosis, is the common final outcome of almost all progressive chronic kidney diseases. Renal fibrosis is also a reliable predictor of prognosis and a major determinant of renal insufficiency. Irrespective of the initial causes, renal fibrogenesis is a dynamic and converging process that consists of four overlapping phases: priming, activation, execution and progression. Nonresolving inflammation after a sustained injury sets up the fibrogenic stage (priming) and triggers the activation and expansion of matrix-producing cells from multiple sources through diverse mechanisms, including activation of interstitial fibroblasts and pericytes, phenotypic conversion of tubular epithelial and endothelial cells and recruitment of circulating fibrocytes. Upon activation, matrix-producing cells assemble a multicomponent, integrin-associated protein complex that integrates input from various fibrogenic signals and orchestrates the production of matrix components and their extracellular assembly. Multiple cellular and molecular events, such as tubular atrophy, microvascular rarefaction and tissue hypoxia, promote scar formation and ensure a vicious progression to end-stage kidney failure. This Review outlines our current understanding of the cellular and molecular mechanisms of renal fibrosis, which could offer novel insights into the development of new therapeutic strategies.
Molecular cloning of a partial cDNA of the interleukin-2 receptor-β in normal mouse brain: in situ localization in the hippocampus and expression by neuroblastoma cells

Abstract While interleukin-2 (IL-2) has been shown to produce a variety of effects in the CNS and has recently been implicated as an endogenous brain neurokine, little is known about the molecular biology of IL-2 receptors in normal brain. The present investigation provides the first evidence that mRNA for IL-2 receptor-β (IL-2Rβ), an essential subunit for signal transduction by peripheral immune cells, is expressed in normal murine forebrain. Using polymerase chain reaction (PCR) cloning, a partial cDNA (349 bp) corresponding to the extracellular domain was cloned and found to have the identical sequence as the lymphocyte IL-2Rβ. IL-2Rβ mRNA expression was confirmed by a ribonuclease protection assay, and using in situ hybridization histochemistry, IL-2Rβ mRNA was localized in the hippocampus where an intense signal was present over the neuron-rich granule cells of the dentate gyrus and Ammon's horn. Moreover, cDNA clones obtained from two murine neuroblastoma cell lines exhibited the same sequence as IL-2Rβ cDNA from normal brain. IL-2Rβ gene expression was also detected in the frontal cortex and striatum using PCR. Further in sity hybridization studies will be important to extent this intial observation to determine the brain regional localization and cell-specific anatomy of IL-2Rβ mRNA in the CNS.
Cloud particle effects on laminar flow and instrumentation for their measurement aboard a NASA LFC aircraft

Fuel costs account now for approximately 60 percent of the direct operating costs of airlines and future commercial transport will utilize advanced technologies for saving fuel on the basis of drag reduction. Laminar flow control (LFC) represents such an advanced technology. A new laminar flow wing on a reconfigured WB-66 aircraft was tested in the X-21 flight program. The tests confirmed that extensive laminar flow could be achieved at subsonic transport cruise conditions. Factors affecting adversely the maintenance of laminar flow were found to be related to ice particles encountered during the penetration of cirrus clouds or haze. The present investigation is concerned with the effect of ice particles on LFC, taking into account the results obtained in the Leading Edge Flight Test (LEFT) being conducted by NASA. Attention is given to ice particle measurements in the LEFT program.
A simple model for phosphorus uptake kinetics of wheat seedlings

Abstract A simple model to compare and predict phosphorus (P) uptake behavior of plants may be useful to agronomists. A predictive equation based on Michaelis‐Menten kinetics was developed for this purpose. Kinetic parameters for use in the model were determined in an experiment using two cultivars of winter wheat grown for 21 days in 14 soil treatments, including seven P levels, each in fumigated and unfumigated soil. In another experiment, the same wheat cultivars were grown for 7, 14, or 21 days at one soil P level in both fumigated and unfiimigated soil. Using parameter values developed in the first experiment with multiple P levels and one time period, the model closely (R2=0.966, P<0.001) predicted P uptake in the second experiment with one P level over multiple time periods. The model could be a useful agronomic tool because of its simplicity and because no data need be collected from artificial growing conditions.
Incremented alkyl derivatives enhance collision induced glycosidic bond cleavage in mass spectrometry of disaccharides.

Electrospray ionization and collision induced dissociation on a triple quadrupole mass spectrometer were used to determine the effect of spatial crowding of incremented alkyl groups of two anomeric pairs of peralkylated (methyl to pentyl) disaccharides (maltose/cellobiose and isomaltose/gentiobiose). Protonated molecules were generated which underwent extensive fragmentation under low energy conditions. For both the 1 → 4 and 1 → 6 α and β isomers, at comparable collision energies the methyl derivative exhibited the least fragmentation followed by ethyl, propyl, butyl, and pentyl. Collision energy is converted to rotational-vibrational modes in competition with bond cleavage, as represented by the slope of product/parent ion (D/P) ratio versus offset energy. Variable rotational freedom at the glycosidic linkage with incremented alkyl groups is hypothesized to be responsible for this effect. Discrimination of anomeric configuration was also assessed for these stereoiosmeric disaccharides. A systematic study showed that an increasing discrimination was attained for the 1 → 4 isomeric pair as the size of the derivative increased from methyl to pentyl. No anomeric discrimination was attained for the 1 → 6 isomeric pair. Parent and product ion scans confirmed the consistency of fragmentation pathways among derivatives. Chem-X and MM3 molecular modeling programs were used to obtain minimum energy structures and freedom of motion volumes for the permethylated disaccharides. The modeling results correlated with the fragmentation ratios obtained in the mass spectrometer giving strong indication that the collision induced spectra are dependent on the freedom of rotational motion around the glycosidic bond.
Pareto Front Approximation Using a Hybrid Approach

Abstract A new method is proposed for approximating a Pareto front of a bound constrained biobjective optimization problem (BOP) where the evaluation of the objective functions is very expensive and/or the structure of the objective functions either cannot be exploited or not known. The method employs a hybrid optimization approach using two direct search techniques (dividing rectangles and mesh adaptive direct search). The algorithm iteratively formulates and solves several single objective optimization problems of the original BOP by using an adaptive weighting scheme, and moves closer to the true Pareto front at the end of each iteration. The method is tested on problems from the literature designed to illustrate some of the inherent difficulties in biobjective optimization such as a nonconvex or disjoint Pareto front, local Pareto front, or a nonuniform Pareto front. Finally, the algorithm is compared with a recent biobjective optimization algorithm, BiMADS, that generates an approximation of the Pareto front by solving a series of single objective formulations of the original BOP. Results show that the proposed algorithm efficiently generates a set of evenly distributed globally Pareto optimal solutions for a diverse types of problems. The accuracy and the distribution of the solutions obtained can be improved further with a relaxed budget in terms of true function evaluations.
Retrograde perfusions of the pineal region and the question of pineal vascular routes to brain and choroid plexuses

The purpose of this study was to experimentally and critically examine the possibility of vascular routes from the pineal gland to the brain in the laboratory rat. Vascular perfusions in the pineal region with India ink in heparinized saline were performed on animals of diverse ages (1 month to 2 years) during the early and middle parts of the daily period of light and immediately post-mortem. Cleared specimens were studied both before and after serial sectioning for light microscopy. Pineal microvasculature was relatively resistant to retrograde perfusion from the adjacent venous sinuses. But the choroid plexus of the suprapineal recess commonly contained perfusate from these sinuses and the pineal gland. The results define the anatomical limits of possible pineal to brain blood flow, but do not of course provide any direct evidence that such flow exists in vivo. Nevertheless, the results from the perfusions lead to the conclusion that if a direct and non-systemic vascular path carries pineal hormone to brain, the path consists of the vena cerebri magna and the choroid plexus of the suprapineal recess. This concept assumes reversibility of direction of blood flow in these vessels, an observed physiological property of at least some intracranial veins in other species.
Droop models of nutrient-plankton interaction with intratrophic predation

Droop models of nutrient-phytoplankton-zooplankton interaction with intratrophic predation of zooplankton are introduced and investigated. The models proposed in this study are open ecosystems which include both a constant and a periodic input nutrient models. A simple stochastic model mimics a randomly varying nutrient input is also presented. For the deterministic models it is shown analytically that intratrophic predation has no effect on the global asymptotic dynamics of the systems if either one of the populations has a negative growth rate. Numerical simulations are also used to investigate the effects of intratrophic predation. Unlike the deterministic models for which both populations can coexist with each other if populations' net growth rates are positive, plankton populations can become extinct if the input nutrient concentration is varied randomly.