cssi/SciSciGPT-SciSciNet huggingface dataset:
Innovative use of a bacterial enzyme involved in sialic acid degradation to initiate sialic acid biosynthesis in glycoengineered insect cells.

The baculovirus/insect cell system is widely used for recombinant protein production, but it is suboptimal for recombinant glycoprotein production because it does not provide sialylation, which is an essential feature of many glycoprotein biologics. This problem has been addressed by metabolic engineering, which has extended endogenous insect cell N-glycosylation pathways and enabled glycoprotein sialylation by baculovirus/insect cell systems. However, further improvement is needed because even the most extensively engineered baculovirus/insect cell systems require media supplementation with N-acetylmannosamine, an expensive sialic acid precursor, for efficient recombinant glycoprotein sialylation. Our solution to this problem focused on E. coli N-acetylglucosamine-6-phosphate 2′-epimerase (GNPE), which normally functions in bacterial sialic acid degradation. Considering that insect cells have the product, but not the substrate for this enzyme, we hypothesized that GNPE might drive the reverse reaction in these cells, thereby initiating sialic acid biosynthesis in the absence of media supplementation. We tested this hypothesis by isolating transgenic insect cells expressing E. coli GNPE together with a suite of mammalian genes needed for N-glycoprotein sialylation. Various assays showed that these cells efficiently produced sialic acid, CMP-sialic acid, and sialylated recombinant N-glycoproteins even in growth media without N-acetylmannosamine. Thus, this study demonstrated that a eukaryotic recombinant protein production platform can be glycoengineered with a bacterial gene, that a bacterial enzyme which normally functions in sialic acid degradation can be used to initiate sialic acid biosynthesis, and that insect cells expressing this enzyme can produce sialylated N-glycoproteins without N-acetylmannosamine supplementation, which will reduce production costs in glycoengineered baculovirus/insect cell systems.
Hit-and-run mixes fast

It is shown that the “hit-and-run” algorithm for sampling from a convex body K (introduced by R.L. Smith) mixes in time O*(n2R2/r2), where R and r are the radii of the inscribed and circumscribed balls of K. Thus after appropriate preprocessing, hit-and-run produces an approximately uniformly distributed sample point in time O*(n3), which matches the best known bound for other sampling algorithms. We show that the bound is best possible in terms of R,r and n.
The Glutamate Effect on DNA Binding by Pol I DNA Polymerases: Osmotic Stress and the Effective Reversal of Salt Linkage

Abstract The significant enhancing effect of glutamate on DNA binding by Escherichia coli nucleic acid binding proteins has been extensively documented. Glutamate has also often been observed to reduce the apparent linked ion release (Δ n ions ) upon DNA binding. In this study, it is shown that the Klenow and Klentaq large fragments of the Type I DNA polymerases from E. coli and Thermus aquaticus both display enhanced DNA binding affinity in the presence of glutamate versus chloride. Across the relatively narrow salt concentration ranges often used to obtain salt linkage data, Klenow displays an apparently decreased Δ n ions in the presence of Kglutamate, while Klentaq appears not to display an anion-specific effect on Δ n ions . Osmotic stress experiments reveal that DNA binding by Klenow and Klentaq is associated with the release of ∼ 500 to 600 waters in the presence of KCl. For both proteins, replacing chloride with glutamate results in a 70% reduction in the osmotic-stress-measured hydration change associated with DNA binding (to ∼ 150–200 waters released), suggesting that glutamate plays a significant osmotic role. Measurements of the salt–DNA binding linkages were extended up to 2.5 M Kglutamate to further examine this osmotic effect of glutamate, and it is observed that a reversal of the salt linkage occurs above 800 mM for both Klenow and Klentaq. Salt-addition titrations confirm that an increase of [Kglutamate] beyond 1 M results in rebinding of salt-displaced polymerase to DNA. These data represent a rare documentation of a reversed ion linkage for a protein–DNA interaction (i.e., enhanced binding as salt concentration increases). Nonlinear linkage analysis indicates that this unusual behavior can be quantitatively accounted for by a shifting balance of ionic and osmotic effects as [Kglutamate] is increased. These results are predicted to be general for protein–DNA interactions in glutamate salts.
Outpatient pediatric blood cultures: time to positivity.

Objective. Using a continuously monitoring blood culture system, we determined the time to positivity of blood cultures performed on immunocompetent infants and children who were not receiving antibiotics at the time of culture. Study Design. This study was conducted prospectively using blood cultures taken in the emergency department and outpatient clinics of an urban pediatric teaching hospital from February 1, 1993, through December 31, 1996. Cultures were excluded if obtained from patients receiving antibiotics, patients with a central line, patients with prosthetic devices, or those being followed by the oncology division. Our measures included: 1) recording the time to positive culture obtained by using a continuously monitoring blood culture instrument, 2) patient information derived from the hospital computer system concerning antibiotic use and the presence of indwelling central venous catheters and prosthetic devices, and 3) a chart review of 10% of patients from whom positive cultures were obtained. Results. During the 47-month study period, 10 200 single bottle blood cultures were obtained, 711 (6.97%) of which became positive. Patients ranged in age from Conclusion. Because 87% of all cultures containing pathogens were detected within the first 24 hours of incubation, this study can assist emergency department, clinic, and primary care clinicians when making critical decisions concerning patients on whom blood cultures were obtained. Data on time to positivity of blood cultures can be used in conjunction with clinical status to support clinicians in making patient management decisions. Use of short stay (≤24 hours) or extended care units requiring less patient supervision may be easier to justify when a continuously monitoring blood culture instrument is used in the microbiology laboratory.bacteremia, sepsis.
Preference for long-term care arrangement and its correlates for older Korean Americans.

Objective: Care preference is important for both client’s satisfaction and quality of life in long-term care. This study examines preference for long-term care arrangement and its correlates for older Korean Americans. Methods: Data on two disability scenarios of hip fracture and stroke from a cross-section survey of 144 older Korean Americans were used to examine preferred care arrangement in terms of caregiver and care location, using multinomial logistic regression. Results: Respondents expressed stronger preferences for “all informal” or “mixed” care arrangement for hip fracture scenario, but they preferred “all formal” care arrangement in the stroke scenario. Traditional value significantly decreased the odds of choosing “all formal” or “mixed” over “all informal” care arrangement. But Medicaid coverage andan independent decision-making style increased the odds of choosing “all formal” instead of “all informal” care arrangement. Discussion: This study discusses the need for assessment of care prefere...
Speech-gesture mimicry in performance: an actor → audience, author → actor, audience → actor triangle

In this paper, I put forth the idea that a process in the production of speech can also be found, on an entirely different scale, in theatrical and film performance. Not simply that actors speak, but the semiotics of language, as a dynamic system, also appear, on their own, in the semiotics of theater. It forms a kind of “triangle” of gesture mimicry: actor → audience, audience → actor, and author → actor. Each leg has its own realization. Many reactions take place and are part of the performance triangle. The actor to audience portion is similar to what gesture coders do – spontaneously mimic the gesture and speech of a subject on video made even decades before. The author to actor leg is more surprising. Carefully written ‘scanable’ prose contains gesture-like imagery. Part of writing is building in gesture, not describing it but placing it as a pattern on which the written text is orchestrated. Actors can recover the author’s built-in gestures. Finally, the audience to actor leg arises when the actor m...
THE EFFECTS OF THE NEW 65 MILE-PER-HOUR SPEED LIMIT ON RURAL HIGHWAY FATALITIES: A STATE-BY-STATE ANALYSIS

This paper examines the effects of the new 65 mile-per-hour (mph) speed limit on U.S. rural highway fatality counts. Separate analyses are conducted for each of the 40 states that had adopted the new (higher) limit by mid-1988. Using monthly Fatal Accident Reporting System (FARS) data from January 1976 through November 1988, time-series regression equations--including policy variables, seasonal variables, and surrogate exposure variables--are estimated for each state. The results suggest that the new laws have increased fatalities on both rural interstate and rural noninterstate highways in most states, but also that these effects differ substantially across the states. For rural interstate fatalities the estimates suggest a median (among the 40 states) effect of the increased speed limit of roughly 15% more fatalities; the median estimates for rural noninterstates suggest a 5% increase in fatalities due to the increased speed limits. Estimates such as those reported here should be revised as more information becomes available.
Unusual patterns of keratin expression in the overlying epidermis of patients with dermatofibromas biochemical alterations in the epidermis as a consequence of dermal tumors

Dermatofibromas are frequently associated with acanthosis of the overlying epidermis. Using monospecific antisera and cRNA probes, we have examined the pattern of expression of keratin and keratin in mRNA in the affected epidermis of patients with these dermal tumors. Our studies reveal several abnormalities in keratin expression within the thickened areas of overlying epidermis. In two of 15 patients, we detected K6 and K16, keratins which are frequently associated with epidermal diseases of hyperproliferation [1,2] but are not present in normal epidermis. In both cases, K6 and K16 were found in suprabasal layers, similar to that seen for psoriasis and squamous cell carcinomas [2]. Expression of K6 and K16 in skin samples from patients with dermatofibromas seemed to be dependent upon how near was the tumor to the overlying epidermis, and possibly upon the degree of cellularity within the tumor mass. A second aberration in keratin expression, and one which did not appear to be linked to K6/K16 expression, was the altered expression of the basal epidermal keratin K14. Expression of this keratin and its mRNA was variable, often extending into multiple suprabasal layers and including both basal-like and squamous-like cells. In contrast to the expression of K6/K16, aberrant expression of K14 was a relatively frequent event, occurring in > 70% of the dermatofibroma skin samples examined. These observations provide the first biochemical evidence in support of previous morphologic studies, indicating that alterations in epidermal differentiation can occur as a consequence of dermal skin tumors.
What’s new in cardiac surgery

w n the spring of 2003, cardiac surgery celebrated the 50 nniversary of the first successful use of a heart-lung achine by John H Gibbon Jr to perform safe operaions inside the opened heart. Since that first successful losure of an atrial septal defect, exponential progress has ontinued to the present day. Continuing improvements n cardiopulmonary bypass itself, the operative proceures that it enabled, and many other technologies were ot even imaginable at that time. The major developments in cardiac surgery are conentrated in those areas that most cardiac surgeons deal ith every day: treatment of coronary artery disease CAD), congenital heart disease, valvular disease, translantation, and mechanical assist. In addition, there are articularly new and important developments in the rea of surgical treatment of arrhythmias, thoracic aortic isease, and the application of robotic innovations for inimally invasive approaches. Finally, a number of imortant changes in thoracic surgical education have ocurred this past year. All of these topics will be the subect of this article, which should be considered a snapshot in time” of the journey initiated 50 years ago y Dr Gibbon.
Critical test of geminate recombination in liquid argon

Recombination and impurity attachment in liquid argon have been separated using a gridded ionization detector with adjustable cathode to grid distance. Recombination effects with an electron source and an $\ensuremath{\alpha}$ source were studied in the range 0.07 to 10 kV/cm. In contradiction to other recent results, our data do not support geminate recombination theory.
Financial fragility: Issues and policy implications

This article addresses the question of how financial institutions, contracting forms, and government financial policies affect the degree of macroeconomic volatility. Models that posit such relationships are sometimes referred to as models of “financial fragility.” These models explore ways in which the financial system can add to the volatility of economic activity by defining sources of financial “shocks” and financial “propagators” of other shocks. Financial shocks are defined as disturbances to the real economy that originate in financial markets. Financial propagation refers to the ways in which financial contracts, markets, and intermediaries can serve to aggravate shocks that originate elsewhere. Economists have not always been receptive to the idea that financial arrangements matter for business cycles. From the standpoint of traditional neoclassical general equilibrium theory, financial arrangements (which include financial contracting, the actions of financial intermediaries, and government policies toward the financial sector) typically are viewed as epiphenomenal—simply as a set of mechanisms for executing ArrowDebreu contingent claims to allocate resources optimally. Mainstream macroeconomists and finance specialists of the 1960s seemed to agree.1 Corporation financial decisions were neutral according to Modigliani and Miller (1958), with the addition of minor caveats to take account of physical bankruptcy costs and tax incentives; and firms all faced identical costs of funds adjusted for systematic risk factors according to the capital asset pricing model. Thus, there was no call to object to the standard IS-LM macroeconomic framework’s assumption that all firms effectively faced the same cost of funds (summarized by “the” interest rate) and that this cost equaled the marginal product of capital.
Possible prevention of hungry bone syndrome following parathyroidectomy by preoperative use of pamidronate.

73-year-old female was admitted to our institution after laboratory results during an outpatient follow-up visit for a longstanding hyperparathyroidism revealed a serum calcium concentration of 14.5 mg/dL. She was diagnosed with primary hyperparathyroidism 8 years prior to current presentation. Throughout this time her serum calcium and intact PTH (iPTH) concentrations ranged from 10.2 to 15.0 mg/dL and 56.2 to 2000 pg/mL, respectively. She repeatedly refused parathyroidectomy and was treated with cinacalcet, 30 mg twice a day, for 2 months prior to admission without clear-cut improvement. Her relevant medications also included alendronate during the previous 6 years.
Nipple attachment and survival in neonatal olfactory bulbectomized rats.

Abstract Seven-day-old rat pups were olfactory bulbectomized, cortical lesioned, or sham lesioned, tested for nipple attachment 24 hr after surgery, then housed with their dam and weighed daily for the next 7 days. On the basis of histological findings the bulbectomized animals were divided into two subgroups: Those with removal of all olfactory bulb tissue (n=9) and those in which some cellular elements remained in the lesioned area (n=7). There were no differences between sham and cortical lesioned groups for nipple attachment behavior or weight gain. The completely bulbectomized pups did not show nipple attachment, lost weight each day, became moribund and had to be sacrificed by the fifth postoperative day. Deficits in incompletely bulbectomized pups were somewhat less severe and each of these survived and maintained or gained weight in the latter part of the test period. These results suggest that suckling may be critically dependent upon olfaction in 8 day or older pups and that significant savings in this behavior may be mediated by small remanants of olfactory bulb tissue.
Time reversal of broadband microwave signals

The optically assisted time reversal of broadband microwave signals is demonstrated. Time reversal is obtained by imposing a wideband optical chirp onto the microwave signal followed by optical dispersion.
Long-Term Multivitamin Supplementation and Cognitive Function in Men: A Randomized Trial

Background Despite widespread use of multivitamin supplements, their effect on cognitive health – a critical issue with aging – remains inconclusive. To date, there have been no long-term clinical trials to study multivitamin use and cognitive decline in older persons.
Deep hypothermia and circulatory arrest: effect on cerebrospinal fluid electrolytes in newborn lambs.

Abstract Cerebrospinal fluid (CSF) Na, K, and acid-base changes were studied in 13 new-born lambs anesthetized with α-chloralose (60 mg/kg) or diethylether during 90 min of normothermic (37 °C) or hypothermic (20 °C) circulatory arrest. CSF K concentration increased linearly from 3.1 to 23.2 meq/liter during 90 min of normothermic circulatory arrest. During hypothermic circulatory arrest, animals anesthetized with α-chloralose exhibited an exponential increase in CSF K concentration from 3.1 to 13.6 meq/liter and animals anesthetized with diethylether had an exponential increase in CSF K concentration from 3.3 to 12.7 meq/liter. The rate of increase in CSF K concentration in hypothermic and normothermic animals between 60 and 90 min of circulatory arrest was the same. CSF Na concentration decreased slightly in both hypothermic and normothermic animals, with a greater decrease in the normothermic group. Although CSF pH and bicarbonate were significantly decreased during normothermia as well as hypothermia, both CSF pH and bicarbonate showed greater decreases during normothermia. Mean pH values after 90 min of circulatory arrest were 6.34, 6.87, and 6.77, respectively, in the normothermic, α-chloralose-hypothermic, and diethylether-hypothermic groups; corresponding values for bicarbonate were 7.7, 13.8, and 12.2 meq/liter. CSF pCO2 increased linearly from 40.2 to 190.0 Torr during 90 min of normothermic circulatory arrest, from 28.6 to 92 Torr in the ether-hypothermic group, and from 28 to 81 Torr in the α-chloralose-hypothermic group.
Settlement and distribution of colony-founding queens of the arboreal ant, Crematogaster ashmeadi, in a longleaf pine forest

Crematogaster ashmeadi is the dominant arboreal ant occurring on longleaf pines in the Apalachicola National Forest of northern Florida. Newly-mated C. ashmeadi queens preferentially founded colonies in abandoned beetle galleries in the dead branches of longleaf pine saplings. There was a positive association between the frequency of queens in trees, several size-related tree characteristics and the amount of insect boring activity in dead branches. The dispersion of newly-mated queens among trees was clumped, suggesting that these queens selected founding sites according to their suitability for colony founding, and that these favorable characteristics were clumped among saplings. The occurrence of founding nests was not related to the prior presence of other ants on the tree. Survival of incipient colonies during the first year was low (7.6 %), and their dispersion was not different from random. One possible explanation for this change in dispersion over the year is aggressive interference competition between incipient colonies, although random mortality cannot be discounted. Overall, the distribution of young C. ashmeadi colonies in longleaf pine saplings was probably determined by several factors including: the distribution of saplings, the distribution of suitable founding sites within these saplings, and aggressive interactions among incipient colonies, conspecifics and heterospecifics. C. ashmeadi probably gains dominance through a combination of early colonization and aggressive interference competition.
Glutathione and mercapturic acid conjugations in the metabolism of naphthalene and 1-naphthyl N-methylcarbamate (carbaryl).

The formation of glutathione (GSH) conjugate in the detoxification of [1-14C]-naphthalene and [naphthyl-14C]-carbaryl was investigated using rat liver homogenate. The mercapturic acid conjugate in rats was also investigated by collection of urine after intraperitoneal injection of 14C substrates. The formation of water-soluble metabolites in vitro from naphthalene was dependent on the amount of glutathione added, but this was not seen in carbaryl metabolism. In vitro, the metabolism of [1-14C]-naphthalene produced 50% GSH conjugates in the incubation mixture, whereas in vivo the metabolism of this compound produced 65% mercapturic acid conjugate in the urine. There was no evidence of GSH or mercapturic acid conjugate in the metabolism of [naphthyl-14C]-carbaryl in vitro and in vivo. This conclusion was made by comparing the nature and chemical characteristics of GSH and mercapturic acid conjugates formed in [1-14C]-naphthalene metabolism. With the aid of the specific enzyme (e.g. beta-glucuronidase and sulfatase) and acid hydrolysis, the water-soluble metabolites of [naphthyl-14C]-carbaryl were tentatively recognized as glucuronide or sulfate conjugated mainly with 5,6-dihydro-5,6-dihydroxycarbaryl or N-hydroxy-methyl carbaryl and their hydrolytic products. This data demonstrated that the substituent group on the naphthalene molecule may affect the significance of GSH conjugation.
Computing the Soft Error Rate of a Combinational Logic Circuit Using Parameterized Descriptors

Soft errors have emerged as an important reliability challenge for nanoscale very large scale integration designs. In this paper, we present a fast and efficient soft error rate (SER) analysis methodology for combinational circuits. We first present a novel parametric waveform model based on the Weibull function to represent particle strikes at individual nodes in the circuit. We then describe the construction of the descriptor object that efficiently captures the correlation between the transient waveforms and their associated rate distribution functions. The proposed algorithm consists of operations to inject, propagate, and merge these descriptors while traversing forward along the gates in a circuit. The parameterized waveforms enable an efficient static approach to calculate the SER of a circuit. We exercise the proposed approach on a wide variety of combinational circuits and observe that our algorithm has linear runtime with the size of the circuit. The runtimes for soft error estimation were observed to be in the order of about 1 s, compared to several minutes or even hours for previously proposed methods
Detecting concept mentions in biomedical text using hidden Markov model: multiple concept types at once or one at a time?

Background Identifying phrases that refer to particular concept types is a critical step in extracting information from documents. Provided with annotated documents as training data, supervised machine learning can automate this process. When building a machine learning model for this task, the model may be built to detect all types simultaneously (all-types-at-once) or it may be built for one or a few selected types at a time (one-type- or a-few-types-at-a-time). It is of interest to investigate which strategy yields better detection performance.
Systematic Review of Structural and Functional Neuroimaging Findings in Children and Adults with CKD

CKD has been linked with cognitive deficits and affective disorders in multiple studies. Analysis of structural and functional neuroimaging in adults and children with kidney disease may provide additional important insights into the pathobiology of this relationship. This paper comprehensively reviews neuroimaging studies in both children and adults. Major databases (PsychLit, MEDLINE, WorldCat, ArticleFirst, PubMed, Ovid MEDLINE) were searched using consistent search terms, and studies published between 1975 and 2012 were included if their samples focused on CKD as the primary disease process. Exclusion criteria included case reports, chapters, and review articles. This systematic process yielded 43 studies for inclusion (30 in adults, 13 in children). Findings from this review identified several clear trends: (1) presence of cerebral atrophy and cerebral density changes in patients with CKD; (2) cerebral vascular disease, including deep white matter hyperintensities, white matter lesions, cerebral microbleeds, silent cerebral infarction, and cortical infarction, in patients with CKD; and (3) similarities in regional cerebral blood flow between patients with CKD and those with affective disorders. These findings document the importance of neuroimaging procedures in understanding the effect of CKD on brain structure, function, and associated behaviors. Results provide a developmental linkage between childhood and adulthood, with respect to the effect of CKD on brain functioning across the lifespan, with strong implications for a cerebrovascular mechanism contributing to this developmental linkage. Use of neuroimaging methods to corroborate manifest neuropsychological deficits or perhaps to indicate preventive actions may prove useful to individuals with CKD.
Long-gap esophageal atresia: experience with Kato's instrumental anastomosis, with cervicothoracic procedure and primary anastomosis, and with retrosternal colonic interposition.

The best esophagus is the esophagus which consists of tissue prepared for its function in the site assigned for it. The way to achieve this in long-gap esophageal atresia was shown by Fritz Rehbein, who developed the thread method and later the olive-thread adaptive technique. Further development led to instrumental insertion of the thread. Kato and Hollmann built a specially designed instrument for this purpose in our experimental laboratory (Kato et al. 1980). The instrument consists of a frame and two hollow bows which can be adjusted so that their tips exactly touch one another (Fig.1). The anesthetized infant is positioned with overstretched head. Then the upper bow is led through the oral cavity to the upper pouch, the lower bow via a gastrostoma to the lower pouch (Fig. 2). When the frame is adjusted it is tested by X-ray to see whether both bows are in exactly opposite positions. Then a strong wire is brought into the lumen of the lower bow, bridging the gap and exiting with a thread attached via the lumen of the upper bow. Bougienage can now be started or, in case of a long gap, stretching dilatation using Rehbein’s olive technique.
Growing a pattern language (for security)

Researchers and practitioners have been successfully documenting software patterns for over two decades. But the next step--building pattern languages--has proven much more difficult. This paper describes an approach for building a large pattern language for security: an approach that can be used to create pattern languages for other software domains. We describe the mechanism of growing this pattern language: how we cataloged the security patterns from books, papers and pattern collections written by all security experts over the last 15 years, how we classified the patterns to help developers find the appropriate ones, and how we identified and described the relationships between patterns in the language. To our best knowledge, this is the largest pattern language in software. But the most significant contribution of this paper is the story behind how the pattern language is grown; it illustrates the steps that can be adapted to create and grow pattern languages for other domains.
Novel Assay Reveals Multiple Pathways Regulating Stress-Induced Accumulations of Inorganic Polyphosphate in Escherichia coli

A major impediment to understanding the biological roles of inorganic polyphosphate (polyP) has been the lack of sensitive definitive methods to extract and quantitate cellular polyP. We show that polyP recovered in extracts from cells lysed with guanidinium isothiocynate can be bound to silicate glass and quantitatively measured by a two-enzyme assay: polyP is first converted to ATP by polyP kinase, and the ATP is hydrolyzed by luciferase to generate light. This nonradioactive method can detect picomolar amounts of phosphate residues in polyP per milligram of extracted protein. A simplified procedure for preparing polyP synthesized by polyP kinase is also described. Using the new assay, we found that bacteria subjected to nutritional or osmotic stress in a rich medium or to nitrogen exhaustion had large and dynamic accumulations of polyP. By contrast, carbon exhaustion, changes in pH, temperature upshifts, and oxidative stress had no effect on polyP levels. Analysis of Escherichia coli mutants revealed that polyP accumulation depends on several regulatory genes, glnD (NtrC), rpoS, relA, and phoB.
When is excision necessary for atypical lobular hyperplasia and lobular carcinoma in situ

SUMMARY This management perspective briefly covers the histology and molecular features of lobular in situ neoplasia and provides an in-depth discussion of the need for surgical excision if lobular in situ neoplasia is diagnosed on core-needle biopsy. The management of lobular in situ neoplasia found on core-needle biopsy has been an area of recent study with varying results. Emerging data suggest that low-risk patients with a limited extent of isolated classic lobular in situ neoplasia found on core-needle biopsy may not require subsequent surgical excision. However, high-risk patients, those with extensive lobular in situ neoplasia, or other high-risk lesions noted on core-needle biopsy likely benefit from surgical excision. Most authors recommend surgical excision when pleomorphic lobular carcinoma in situ is found on core-needle biopsy due to its higher association with invasive carcinoma. However, the natural history of this more recently described variant of lobular carcinoma in situ is not fully de...
Comments on the Ricardi letter

Summary form only given, as follows. The G-AP Editor comments on only one item in the above-named letter [ibid, vol 14, no 4, Dec 1972, page 9], namely No. 3, where Mr. Ricardi suggests that we might require authors of political letters to have, say, 100 members co-sign or condone the letter. He would not consider this to be very practical and he seriously doubts if it would ever be necessary. As editor of the G-AP newsletter, he has repeatedly asked for letters or comments from the members. I is now editing his fourth issue and the letters received so far have been very, very few. He Sincerely welcome others. Even though they are political, if they are pertinent and of general interest to G-AP members, he would want to publish them.
Cover Picture: Total Synthesis and Absolute Configuration of the Bisanthraquinone Antibiotic BE-43472B (Angew. Chem. Int. Ed. 19/2009)

A cascade sequence featuring a Diels–Alder reaction, a lactolization, and an SN(Ar)-type substitution forms the core of the bisanthraquinone antibiotic BE-43472B in its first total synthesis, which K. C. Nicolaou et al. describe in their Communication on page 3444 ff. The background of the cover picture is a photograph of Ecteinascidia turbinata (courtesy of John Easley Photography), the marine source of the streptomyces strain producing this antibiotic. A cascade sequence featuring a Diels–Alder reaction, a lactolization, and an SN(Ar)-type substitution forms the core of the bisanthraquinone antibiotic BE-43472B in its first total synthesis, which K. C. Nicolaou et al. describe in their Communication on page 3444 ff. The background of the cover picture is a photograph of Ecteinascidia turbinata (courtesy of John Easley Photography), the marine source of the streptomyces strain producing this antibiotic.
SHYNESS SITUATIONS: PERSPECTIVES OF A DIVERSE SAMPLE OF SHY FEMALES

To determine whether shyness-eliciting situations identified by college students would generalize to a mote diverse sample, data were gathered from 187 shy females (14 to 58 yr. of age) who responded to a popular magazine's article about shyness. Coding of responses about shyness situations gave a set of categories highly congruent with previous research involving students. Engaging in conversations and encountering strangers or unfamiliar surroundings seem particularly problematic situations for shy people.
Is There a Cognate Advantage for Typically Developing Spanish-Speaking English-Language Learners?

Purpose Cross-linguistic cognates are words that share form and meaning in two languages (e.g., helicopter–helicoptero); translation equivalents are words that share meaning but not form (e.g., ho...
Results, Rhetoric, and Randomized Trials: The Case of Donepezil

Whether donepezil provides meaningful benefit to patients with Alzheimer's disease (AD) is controversial, but drug sales annually total billions of dollars. A review of data from published randomized clinical trials (RCTs) found rhetorical patterns that may encourage use of this drug. To create a reproducible observation, the sentences occurring at five specific text sites in all 18 RCTs of donepezil for AD were tabulated, as were study design, sources of financial support, and outcomes that could be compared between trials. Rhetoric in the 13 vendor-supported trials (15 publications) was strongly positive. Three early trials used the motif “efficacious (or effective) … treating … symptoms” four times. “Well-tolerated and efficacious” or an equivalent motif appeared 11 times in five RCTs. Nine RCTs referred 15 times to previously proven effectiveness. Seven trials encourage off-label use, for “early” cognitive impairment, severe dementia in advance of the Food and Drug Administration labeling change, or behavioral symptoms. These rhetorical motifs and themes appeared only in the vendor-supported trials. Trials without vendor support described the drug's effects as “small” or absent; two emphasized the need for better treatments. RCT results were highly consistent in all trials; the small differences do not explain differences in rhetoric. At these text sites in the primary research literature on donepezil for AD, uniformly positive rhetoric is present in all vendor-supported RCTs. Reference to the limited benefit of donepezil is confined to RCTs without vendor support. Data in the trials are highly consistent. This observation generates the hypothesis that rhetoric in vendor-supported published RCTs may promote vendors' products.
Short Day Lengths Delay Reproductive Aging

Caloric restriction and hormone treatment delay reproductive senescence in female mammals, but a natural model of decelerated reproductive aging does not presently exist. In addition to describing such a model, this study shows that an abiotic signal (photoperiod) can induce physiological changes that slow senescence. Relative to animals born in April, rodents born in September delay their first reproductive effort by up to 7 mo, at which age reduced fertility is expected. We tested the hypothesis that the shorter day lengths experienced by late-born Siberian hamsters ameliorate the reproductive decline associated with advancing age. Short-day females (10L:14D) achieved puberty at a much later age than long-day animals (14L:10D) and had twice as many ovarian primordial follicles. At 10 mo of age, 86% of females previously maintained in short day lengths produced litters, compared with 58% of their long day counterparts. Changes in pineal gland production of melatonin appear to mediate the effects of day length on reproductive aging; only 30% of pinealectomized females housed in short days produced litters. Exposure to short days induces substantial decreases in voluntary food intake and body mass, reduced ovarian estradiol secretion, and enhanced production of melatonin. One or more of these changes may account for the protective effect of short day lengths on female reproduction. In delaying reproductive senescence, the decrease in day length after the summer solstice is of presumed adaptive significance for offspring born late in the breeding season that first breed at an advanced chronological age.
An explanation of the interpandemic antigenic mutability of influenza viruses.

The unique and extreme antigenic changes of human influenza A viruses associated with pandemics have been postulated to originate in animal reservoirs, perhaps through genetic recombination of human and animal viruses. The lesser interpandemic antigenic mutations of the virus are also unique and unexplained. It is proposed that autorecombination within the infected host can salvage the mutations occurring in noninfective virus particles for ultimate incorporation into infective virions, thus creating an extended mutational pool. Selection of antigenic mutants would then be favored within individuals possessing antibodies specific for the original infecting virus.
FIRE AND POPULATION DYNAMICS OF WOODY PLANTS IN A NEOTROPICAL SAVANNA: MATRIX MODEL PROJECTIONS

Human activity has resulted in high fire frequency in many moist tropical savannas. To simulate the effects of increased fire frequency on woody plants of the cerrado savannas of Brazil, I constructed matrix population models for five species, including a subshrub, two shrubs, and two trees, using four years of demographic data. The models projected that four of the five species will decline under frequent burning but will increase in abundance under infrequent burning. For these four, fire intervals of 2-9 yr are required for long-term persistence, depending on the species. The fifth species, a shrub, was virtually unaffected by burning. Similar data for three herbaceous species were obtained from literature sources. Among the eight species, there was a negative relationship between population growth under annual burning and population growth under unburned conditions. Woody plant species performed best under low fire frequency, and herbaceous species performed best under high fire frequency. Three of the study species propagate vegetatively by producing root suckers. Fire stim- ulates vegetative propagation in all three species but reduces sexual reproduction. Elasticity analysis revealed that vegetative propagation is more important than sexual reproduction for population maintenance of these three species, and that vegetative propagation is rel- atively more important under frequent burning. However, stasis and progression were always much more important than either mode of reproduction, with stasis making the largest contribution to population growth. Analyses of life history response experiments were performed to determine what de- mographic variables contributed most to the population decline under frequent burning. The effect of fire on sexual reproduction contributed little to the overall effect of fire on population growth, particularly for clonal species. Fire-induced mortality also had little
Low yield of transthoracic echocardiography for cardiac source of embolism.

Abstract To test the hypothesis that the yield for a cardiac source of embolism is very low using transthoracic echocardiography, we reviewed the echocardiographic reports of 1,010 consecutive patients with cerebrovascular accidents who had undergone echocardiography to rule out a cardiac source of embolism; risk factor information was also available in 493 patients. We also used 325 controls who had undergone echocardiography for other reasons during the same period. Each report was examined for the presence of predefined findings depending on their propensity for causing cerebrovascular accidents via an embolic process. The prevalence of a highly probable source of embolism was low in cases (
Short Paper: Asynchronous programming with Tarragon

Tarragon is an actor-based programming model and library for implementing latency tolerant asynchronous event driven simulations. It is novel in its support for meta data describing run time virtualized process structures, which may be optimized as a free-standing object. We demonstrate early results with a synthetic benchmark, and observe that Tarragon can mask communication costs with ongoing computation
Optimal Multileaf Collimator Leaf Sequencing in IMRT Treatment Planning

We consider a problem dealing with the efficient delivery of intensity modulated radiation therapy (IMRT) to individual patients. IMRT treatment planning is usually performed in three phases. The first phase determines a set of beam angles through which radiation is delivered, followed by a second phase that determines an optimal radiation intensity profile (or fluence map). This intensity profile is selected to ensure that certain targets receive a required amount of dose while functional organs are spared. To deliver these intensity profiles to the patient, a third phase must decompose them into a collection of apertures and corresponding intensities. In this paper, we investigate this last problem. Formally, an intensity profile is represented as a nonnegative integer matrix; an aperture is represented as a binary matrix whose ones appear consecutively in each row. A feasible decomposition is one in which the original desired intensity profile is equal to the sum of a number of feasible binary matrices multiplied by corresponding intensity values. To most efficiently treat a patient, we wish to minimize a measure of total treatment time, which is given as a weighted sum of the number of apertures and the sum of the aperture intensities used in the decomposition. We develop the first exact algorithm capable of solving real-world problem instances to optimality within practicable computational limits, using a combination of integer programming decomposition and combinatorial search techniques. We demonstrate the efficacy of our approach on a set of 25 test instances derived from actual clinical data and on 100 randomly generated instances.
GaAs Photoconductive Semiconductor Switch Fabrication for Improved Reliability

Summary form only given. Pulsed power systems designed with many switches or many different switch trigger times are heavily dependent upon the triggering systems. Conceptual pulsed power systems for fusion and isentropic compression are being designed with hundreds to hundreds of thousands of switches. Some have to be triggered simultaneously and some will need to be programmable and staggered in time. Trigger system cost, performance, and lifetime will be driving factors in these systems. For example, designers of repetitive pulsed power systems considered for fusion are seeking switch lifetimes >107 shots. A solution that addresses the performance requirements is the use of optically triggered photoconductive semiconductor switches (PCSS), which excel at delivering low jitter, fast-rise-time pulses. Lifetimes for these devices have been demonstrated to be in the >> 106 shot range at lower currents (tens of amps), but drop to the 10~ shot range when the current per filament is hundreds of amps. To increase the switch reliability at higher current levels necessitates further investigation of device reliability and failure mechanisms. Results from lifetime studies on GaAs PCSS devices indicate that the majority of failures occur near the anode. However, switch fabrication variables can shift this failure mechanism to a short-life, cathode-limited condition. A statistical sample population of PCSS switches in a circuit designed to deliver 500V/100A, 10ns pulses is shown to have a single log-normal distribution of shot life over a range of testing temperatures and voltages. Switches for higher operating voltage (70 kV) were fabricated in multiple split lots to identify the influence of design and processing parameters on the switch lifetime. It was found that these larger-gap 70kV switches exhibit the same anode-limited lifetime as the 500V devices. This paper discuss results from the lifetime studies, including variables in the fabrication process (annealing temperature, pad-metal thickness, length of contact-metal extension beyond the pad-metal, and inclusion of a silicon nitride passivation/anti-reflection coating) that affect reliability, and provide strategies for improving shot life.
Efficiency of selenite cystine and TT enrichment broths for the detection of Salmonella.

Comparisons of selenite cystine (SC) and TT enrichment broths for detecting salmonellas were made with pure culture suspensions, with samples of naturally or artificially contaminated foods and with poultry feed. Selenite cystine recovered higher numbers of salmonellas from pure cultures and ground beef, while TT broth recovered higher numbers from pork sausage and poultry feed. Differences in the recovery of salmonellas from other food products appeared to be insignificant. The use of both SC and TT is thus recommended for maximal recovery of these organisms.
Negative regulation of calcineurin signaling by Hrr25p, a yeast homolog of casein kinase I

Calcineurin is a Ca2+/calmodulin-regulated protein phosphatase required for Saccharomyces cerevisiae to respond to a variety of environmental stresses. Calcineurin promotes cell survival during stress by dephosphorylating and activating the Zn-finger transcription factor Crz1p/Tcn1p. Using a high-throughput assay, we screened 119 yeast kinases for their ability to phosphorylate Crz1p in vitro and identified the casein kinase I homolog Hrr25p. Here we show that Hrr25p negatively regulates Crz1p activity and nuclear localization in vivo. Hrr25p binds to and phosphorylates Crz1p in vitro and in vivo. Overexpression of Hrr25p decreases Crz1p-dependent transcription and antagonizes its Ca2+-induced nuclear accumulation. In the absence of Hrr25p, activation of Crz1p by Ca2+/calcineurin is potentiated. These findings represent the first identification of a negative regulator for Crz1p, and establish a novel physiological role for Hrr25p in antagonizing calcineurin signaling.