cssi/SciSciGPT-SciSciNet huggingface dataset:
Analysis of Native-Like Proteins and Protein Complexes Using Cation to Anion Proton Transfer Reactions (CAPTR)

Mass spectra of native-like protein complexes often exhibit narrow charge-state distributions, broad peaks, and contributions from multiple, coexisting species. These factors can make it challenging to interpret those spectra, particularly for mixtures with significant heterogeneity. Here we demonstrate the use of ion/ion proton transfer reactions to reduce the charge states of m/z-selected, native-like ions of proteins and protein complexes, a technique that we refer to as cation to anion proton transfer reactions (CAPTR). We then demonstrate that CAPTR can increase the accuracy of charge state assignments and the resolution of interfering species in native mass spectrometry. The CAPTR product ion spectra for pyruvate kinase exhibit ~30 peaks and enable unambiguous determination of the charge state of each peak, whereas the corresponding precursor spectra exhibit ~6 peaks and the assigned charge states have an uncertainty of ±3%. 15+ bovine serum albumin and 21+ yeast enolase dimer both appear near m/z 4450 and are completely unresolved in a mixture. After a single CAPTR event, the resulting product ions are baseline resolved. The separation of the product ions increases dramatically after each subsequent CAPTR event; 12 events resulted in a 3000-fold improvement in separation relative to the precursor ions. Finally, we introduce a framework for interpreting and predicting the figures of merit for CAPTR experiments. More generally, these results suggest that CAPTR strongly complements other mass spectrometry tools for analyzing proteins and protein complexes, particularly those in mixtures. Graphical Abstract ᅟ.
The 'Other' Credit Report: What You Don't Know Can Hurt You

Nearly 90% of financial institutions use ChexSystems or similar account screening reports in their account opening process, yet they are under no duty to disclose this to consumers until an account is denied due to information contained in the report. For those consumers denied accounts, it is too late. They had no idea information was being collected on their checking account usage, much less that it could be used to deny them an account in the future, and are subsequently forced to go outside the mainstream and use expensive alternatives like check cashing services and money orders to conduct their everyday financial business. Increased consumer awareness of these reports is necessary so that consumers better understand the impact poor account management may have on their future usage of traditional banking services. This article examines these reports, the impact on consumers when they can’t open a new account based on information contained in such reports, and how changes in overdraft practices have encouraged poor account management, which in turn may have resulted in even more negative reports. The article also examines how the Fair Credit Reporting Act (“FCRA”) applies to account screening reports and whether new overdraft practices technically result in loans, triggering additional disclosure. The article concludes with recommendations, discussing how the reporting system could be improved and how consumers could be better informed and protected.
Case 2: Back Pain and Difficulty Ambulating in a 4-year-old Girl.

1. Christina R. MacRosty, DO* 2. Derrick L. Goubeaux, DO* 3. Youmna Mousattat, MD* 1. *West Virginia University Charleston Division/Charleston Area Medical Center, Charleston, WV. A 4-year-old girl presents to the emergency department with a 2-week history of worsening back pain focused around a dimple located in the middle of her back. She has experienced progressive difficulty in ambulating over the same time period, and today she cannot stand or walk without assistance. There is no history of trauma, loss of bowel or bladder control, or urinary retention, but she does have a history of chronic constipation. On physical examination, her temperature is 37.1°C (98.8°F), blood pressure is 120/72 mm Hg, heart rate is 113 beats/min, and respiratory rate is 22 breaths/min. She has a dimple over the T9 spinous process surrounded by mild erythema. She has exacerbated (4+) patellar and Achilles reflexes. The upper extremity reflexes are 2+ bilaterally. Babinski sign is demonstrated bilaterally. Muscle strength is 3/5 in her lower extremities and 5/5 in her upper extremities. She cannot stand without support and can only take two steps before stating that her legs are tired. Sensations to touch and pain are intact throughout the lower and upper extremities. The rest of the physical examination findings are normal. Laboratory evaluation shows normal complete metabolic panel and complete blood cell count. Erythrocyte sedimentation rate is 9 mm/hr and C-reactive protein measures less than 2.9 mg/L (27.62 nmol/L). Magnetic resonance imaging (MRI) of the thoracic spine …
Patient-reported pain with initial intracavernosal injection.

ABSTRACT Introduction Despite the efficacy of intracavernosal injections, one of the greatest impediments to injection therapy is the negative reaction of men to the thought of a needle inserted into the penis. Aim To determine the severity of pain associated with the initial intracavernosal self-injections for erectile dysfunction (both pain associated with the needle insertion and the medications). Methods This is a descriptive study of self-reported pain associated with intracavernosal self-injections in 65 men with erectile dysfunction. Pain was assessed immediately after needle insertion and again approximately 10–20 minutes postinjection, utilizing a verbal 0–10 pain scale. Main Outcome Measures A verbal 0–10 pain rating scale was used to assess pain both for injection pain and medication pain. Results For needle insertion, the mean pain rating was 0.80 (standard deviation [SD] = 0.81), with 40% reporting no pain at all. Of the 39 patients who reported pain, the mean pain rating was 1.33 (SD = 0.61). For the medication itself, the mean pain rating was 0.92 (SD = 1.5), with more than half (64.6%) reporting no pain. For those experiencing pain from the medication (N = 23), the mean pain rating was 2.6 (SD = 1.27, range 0.5–5.0). Significantly more patients with radical prostatectomy experienced pain from the medication than other men (51.9% vs. 23.7%, P = 0.02). Conclusion The majority of patients experienced little or no pain from either the needle insertion or the medication. Even for men who experienced pain, the severity was relatively low. This study provides information to help diminish fears about injection pain for patients considering penile injections. In addition, this study suggests that medication pain is more common in men postradical prostatectomy, so that it may be advisable to start with lower dosages of prostaglandin alone or in combination with other vasoactive medications for these patients. Albaugh J, and Ferrans CE. Patient-reported pain with initial intracavernosal injection. J Sex Med 2009;6:513–519.
Berkeley 17: The Oldest Open Cluster?

Faint magnitude BVI CCD photometry of the central region of the old open cluster Berkeley 17 (Be 17) has been undertaken to investigate the claim that it is the oldest open cluster yet discovered (Phelps, Janes, & Montgomery). This study reveals Be 17 to have a metallicity -0.30 ≤ [Fe/H] ≤ 0.00; a reddening 0.52 ≤ E(B-V) ≤ 0.68 or 0.61 ≤ E(V-I) ≤ 0.71; a distance modulus, (m - M)0 = 12.15 ± 0.10, corresponding to a distance of 2.7 ± 0.1 kpc; a diameter of ~10 pc; a minimum mass of 400 M☉; and an age of 10-13 Gyr. With an adopted age of 12+ 1−2 Gyr, these results suggest that Be 17 is indeed the oldest open cluster yet discovered. The inferred old age for Be 17 indicates that the cluster is an important one for studies of the differences between open and globular clusters, the transition from the halo/thick disk to the thin disk of the Galaxy, and even for establishing the minimum age of the universe.
Vasa vasorum of the heart.

Abstract The anatomy of vasa vasorum of coronary arteries, veins, and lymphatics, and of vasa of cardiac nerves in swine and man was described. Intramural vasculature and hemorrhages in coronary arteries were prominent in man in the presence of atherosclerosis and hypertension but were not observed in nonatherosclerotic pigs. Communications between the blood vascular system and lymphatics occurred in hearts of young pigs but were not observed in the human hearts studied. The clinical correlations of the study were inconclusive but suggested possibilities for further investigation. Other similarities and differences of the cardiac microcirculation in the two species and their possible significance were discussed.
E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells†‡

The conversion of early stage tumors into invasive malignancies with an aggressive phenotype has been associated with the irreversible loss of E-cadherin expression. The loss of E-cadherin expression in human tumors, including breast cancer, has been attributed to promoter CpG island hypermethylation and direct inhibition by transcriptional repressors. Recent evidence demonstrates that up-regulation of E-cadherin by microRNA-200b (miR-200b) and miR-200c through direct targeting of transcriptional repressors of E-cadherin, ZEB1, and ZEB2, inhibits epithelial-to-mesenchymal transition (EMT), a crucial process in the tumor progression. We demonstrate that microRNA miR-200 family-mediated transcriptional up-regulation of E-cadherin in mesenchymal MDA-MB-231 and BT-549 cells is associated directly with translational repression of ZEB1 and indirectly with increased acetylation of histone H3 at the E-cadherin promoter. The increase in histone H3 acetylation may be attributed to the disruption of repressive complexes between ZEB1 and histone deacetylases and to the inhibition of SIRT1, a class III histone deacetylase. These events inhibit EMT and reactivate a less aggressive epithelial phenotype in cancer cells. Additionally, disruption of ZEB1-histone deacetylase repressor complexes and down-regulation of SIRT1 histone deacetylase up-regulate proapoptotic genes in the p53 apoptotic pathway resulting in the increased sensitivity of cancer cells to the chemotherapeutic agent doxorubicin.
Experimental Study on the Influence of Foam Porosity and Pore Size on the Melting of Phase Change Materials

Experimental study was carried out to study the phase changeheat transfer within a composite of phase changematerial (PCM) infiltrated high thermal conductivityfoam. An experimental setup was built to measure the temperature profiles and capture the melting evolution of the PCM inside aluminumfoams.Aluminumfoams were used as the porous material, and low melting temperature paraffin wax was used as the PCM. It was observed from the results that the system parameters of the wax/foam composite had a significant influence on its heat transfer behavior. By using higher porosity aluminumfoam, the steady-state temperature was reached faster as compared to the foams with lower porosity. Similarly for the bigger pore size foams the steady state was attained faster as compared to the smaller pore size foams. This was due to the greater effect of convection in both the higher porosity and bigger pore size foams. However, for the lower porosity foams the heater temperature was comparatively lower than the higher porosity foams due to greater heat conduction through the foammaterial. Therefore, an optimal value should be selected for the foam porosity and pore size such that the effects of both conduction and convection heat transfers can be completely utilized to have a greater and improved thermal performance for the wax/aluminum foamcomposite.
Practical limits of optical enhancement by metal nanoparticles

We develop a simple yet rigorous theory of the enhancement of optical absorption and emission by molecules placed in the vicinity of metal nanoparticles. Both enhancement effects exhibit strong dependence on the nanoparticle size. Using the example of Ag nanospheres embedded in GaN, we show that strong enhancement can be obtained only for those quantum dots, atoms, or molecules that are originally inefficient in absorbing as well as in emitting optical energy. We then discuss practical limits of enhancement.
Reported multivitamin consumption and the occurrence of multiple congenital anomalies

The purpose of this case-control study was to determine whether multivitamin use is associated with the occurrence of multiple congenital anomalies (MCA). MCA case-infants were infants with two or more major birth defects affecting at least two different organ systems, with no recognized chromosome abnormality or single gene disorder. Control-infants were a random sample of live births with no major birth defects from the same population (metropolitan Atlanta) and time period (1993-1997) as the case-infants. Exposure to multivitamins, cereals, and supplements was ascertained from a maternal telephone interview and classified based on folic acid content. We compared women who used multivitamins three or more times per week with women who were not exposed to vitamins/cereals/supplements during the periconceptional period (3 months before pregnancy through the first trimester), adjusting for maternal age, education, race/ethnicity, first degree family history of a major birth defect, pre-pregnancy maternal body mass index, gravidity, and first trimester alcohol use and cigarette smoking. Periconceptional multivitamin use was associated with MCA among all infants (adjusted odds ratio [aOR]=2.4, 95% confidence interval [CI] 0.9-6.7), and especially when analysis was limited to those with no family history of major defects (aOR=4.0, 95% CI 1.3-12.8). MCA-infants with urinary obstructive defects were more common among multivitamin-exposed infants than among unexposed infants, but this defect did not occur within a consistent pattern of defects. While these findings provide some support for one previous study, the interpretation remains unclear given the proven protective effect of multivitamins containing folic acid on isolated neural tube defects and possibly other types of defects.
"Typhoid Mary" strikes again. The social and the scientific in the making of modern public health.

La politique developpee contre la fievre typhoide au debut du XX e siecle a New York etait humaine et non sociale
On the phonetic structure of a large hidden Markov model

It is shown that the structure of a large ergodic hidden Markov model (HMM) can be decomposed into a set of substructures representing the English phonemes. The large HMM, which is trained using a standard forward-backward algorithm, is shown to be organized in a way that reflects the phonetic nature of speech. It is shown that the states of the HMM can be classified in terms of a set of broad phonetic classes and that the spectra associated with the states are related to each state's use in the phonetic models. The phonetic models are shown to have internal structures reflecting the acoustic nature of the individual phonemes. The large HMMs used in this study are trained using the continuous speech multi-speaker TIMIT database employing a continuous observation density training algorithm. On a subset of the database, with 80 male speakers used for training and a separate set of 24 speakers reserved for testing, the phonetic recognition system achieved a 52% recognition rate with 14% insertions. >
Ipilimumab-Induced Pneumonitis: A Case Report

Objective:To report a case of ipilimumab-induced pneumonitis in a patient with metastatic melanoma.Case Summary:A 74-year-old woman with metastatic melanoma presented to the emergency department with progressive shortness of breath and dyspnea of 1 week's duration following her third cycle of ipilimumab. Upon presentation, she was hypoxic, with oxygen saturation of 66% on room air. After stabilization, she was transferred to the inpatient unit where she was placed on broad-spectrum antibiotics (intravenous vancomycin, piperacillin/tazobactam, oral ciprofloxacin, and oral trimethoprim/sulfamethoxazole) and a high-dose corticosteroid (intravenous methylprednisolone 30 mg every 6 hours). Bronchoscopy was negative for infection, and results of blood, urine, and respiratory cultures were negative. Antibiotics were eventually stopped and the patient responded to a high-dose corticosteroid for probable ipilimumab-induced pneumonitis.Discussion:Ipilimumab is a recombinant, human monoclonal antibody that was appro...
Medial septal lesions and the frustration effect.

Abstract Rats with medial septal lesions and sham operates were run in a straight runway. After running stabilized, food was omitted on selected trials and the running speed on the following trial was observed for a frustration effect (FE). The septals exhibited a significantly greater increase in speed on this trial than controls. This enhanced FE in septals is at variance with predictions from frustration theory considering the greater resistance to extinction in septals and suggests a dissociation between the immediate and conditionable effects of frustration in such animals.
Continuous-wave ultrasound and neoplastic transformation in vitro

Abstract C3H/10T1/2 cells in suspension were assayed using an initiation-promotion protocol for neoplastic transformation induced by continuous-wave ultrasound. Cells were insonated at 1.765 MHz for 40 min. Two ultrasonic intensities were used: 1.3 and 2.6 W/cm2 spatial average. The first intensity was found to be noncytotoxic; the second resulted in immediate lysis of 20% of the cells, followed by the clonogenic survival of 64% of the remaining cells. Ultrasound was delivered alone or in combination with X-rays (2 Gy, 240 kVp given before ultrasound), and/or 12-O-tetradecanoyl-phorbol-13-acetate (TPA, 0.1 μg/ml post-irradiation). Under all treatment conditions, there was no effect of ultrasound on transformation at the 95% confidence level.
The Proteins in Pemphigus Vulgaris1

In a previous paper of this series (1) it was shown that in the advanced stage of pemphigus vulgaris acutus the amount of serum albumin, as measured by electrophoresis, is markedly reduced, often to values as low as one-fourth of the normal value. The reason for the marked hypoalbuminemia was seen in the considerable loss of protein through the denuded skin surfaces. While all protein fractions are lost (2), the globulins are regenerated in adequate amounts; on the other hand, the albumin apparently cannot be regenerated at the rate at which it is lost.
Understanding Coach-Based Professional Development in Reading First: How do Coaches Spend Their Time and How do Teachers Perceive Coaches' Work?

The Reading First (RF) program placed emphasis on professional development as a means of improving early elementary reading instruction. For many states literacy coaching was an important component of the professional development provided for teachers. The purpose of this article is to examine coaching in the early years of Michigan's RF program, which placed considerable emphasis on literacy coaching. We investigate the professional training and knowledge of Michigan's RF coaches, the structure and substance of coach/teacher interactions, and teachers' perceptions of factors that influence the effectiveness of the coach. Results suggest the promise of literacy coaching as a means of supporting teachers' professional growth; further study is needed to determine the particular roles of literacy coaches that bring about improvements in reading instruction.
The use of tiletamine–zolazepam–ketamine–xylazine anesthesia for feral cat sterilization

Trap-neuter-return programs have become a popular nonlethal alternative for the control of feral cat populations. The anesthetic used is an integral component of these programs. This study evaluated the use of tiletamine–zolazepam–ketamine–xylazine (TKX) as an IM anesthetic combination for large-scale feral cat sterilization surgery. Between July 1996 and August 2000, a total of 7502 cats entered large-scale feral cat clinics operating at the Colleges of Veterinary Medicine at North Carolina State University and the University of Florida. Up to 12 surgeries were performed simultaneously and up to 200 cats were sterilized in a single day. Cats were not weighed prior to anesthetic injection owing to their feral nature, so the initial anesthetic dose was based on estimated body weight. Tiletamine–zolazepam–ketamine–xylazine was administered IM while cats remained in their traps. Each milliliter of TKX contained 50 mg tiletamine, 50 mg zolazepam, 80 mg ketamine, and 20 mg xylazine. The cats were monitored by observation and palpation for mucous membrane color, heart rate, and respiratory rate, but these values were not recorded. Fluids were not routinely administered but were given subcutaneously in cases of dehydration or excessive blood loss. Yohimbine (0.5 mg) was administered IV at the end of the procedure, and cats were returned to their traps to recover. Cat signalment, drug use, and mortality data were analyzed retrospectively (July 1996–December 1999) and prospectively (December 1999–August 2000). Of those cats with complete drug records, more than 75% received a single dose of TKX with a mean total dose of 0.27 ± 0.09 mL. The overall mortality rate was one in 289 cats (0.347%) and the death rate owing to unknown causes (potential anesthetic deaths) was one in 469 cats (0.213%). These results suggest that the use of TKX for large-scale feral cat sterilization clinics has several benefits, including small volume of administration, predictable anesthetic quality and duration, low cost, and low mortality in feral cats.
Food hoarding in the Mongolian gerbil (Meriones unguiculatus): Effects of food deprivation

One to two weeks of 22.5 hr of food deprivation per day substantially increased hoarding behavior in the Mongolian gerbil (Meriones unguiculatus). Food deprivation also depressed body fat, pelt, uterine, and seminal vesicle weight. Deprivation did not affect ventral gland size or testes weight. A reconciliation is made of the paradoxical differences between deprivation-induced and natural hoarding by viewing both as a component of weight regulatory behavior. In both types of hoarding the animal appears motivated by challenges to his body weight integrity.
Celebrating 60th Anniversary of TBME [Special issue editorial]

In this special issue, celebrating TBME's 60th anniversary, we have invited 20 leading groups in biomedical engineering research to contribute review articles. Each article reviews state of the art and trends in an area of biomedical engineering research in which the authors have made important original contributions. Due to limited space, it is not our intention to cover all areas of biomedical engineering research in this special issue, but instead to provide coverage of major subfields within the discipline of biomedical engineering, including biomedical imaging, neuroengineering, cardiovascular engineering, cellular and tissue engineering, biomedical sensors and instrumentation, biomedical signal processing, medical robotics, bioinformatics, and computational biology. These review articles are witness to the development of the field of biomedical engineering, and also reflect the role that TBME has played in advancing the field of biomedical engineering over the past 60 years.
Changing Patterns of Infant Mortality and Maternal Fertility among Pumé Foragers and Horticulturalists

National census data show that the modern demographic transition—the recent trend toward declining mortality and fertility—is well underway in most countries. A different picture emerges when data from small-scale societies in unindustrialized parts of the world are considered. Many of these small-scale societies are also adapting to rapid changes in their subsistence economies. In this article, we examine the relationship between the pace of acculturation, infant mortality, and fertility levels among Pum ´ e foragers and horticulturalists, two related groups of native South Americans. During the earliest stages of acculturation, Pum ´ e horticulturalists experience not only a rapid drop in infant mortality but also a rise in birth rates. An anthropological view of demographic transitions provides important insight into how small-scale societies are affected by exposure to the labor market economy and has practical applications to effective development initiatives and public health policies. (Keywords: infant mortality, fertility, foragers, South American Indians, Pum ´ e)
Expression and Adorno's Avant-Garde: The Composer in Doktor Faustus

Thomas Mann prefaces Die Entstehung des Doktor Eaustus: Roman eines Romans (1949) with an excerpt from Goethe's Dichtung und Wahrheit. Here, Goethe contends that works having an immediate impact on their contempo rary cultures and works treating issues of national culture become ineffective as time passes. His solution: "Deshalb ist es billig, ihnen [solchen Arbeiten] einen historischen Wert zu verschaffen, indem man sich ?ber ihre Entstehung mit wohlwollenden Kennern unterh?lt" (qtd. in Mann, Entstehung 145). Initi ating a discourse about a work, Goethe says, will endow it with historical value. By beginning his account with this quotation, Mann suggests that Doktor Eaustus (1947) runs the risk of being forgotten, a risk that legitimizes the need for a novel about the genesis of his novel. Theodor W Adorno is a prominent figure in this partial autobiography of the years Mann spent writing Doktor Eaustus in Los Angeles. In fact, Die Entstehung des Doktor Eaustus makes it hard to overestimate Adorno's impor tance to Doktor Eaustus. Finding himself unable to take on his challenging project completely on his own, Mann is glad to find this other exiled intellec tual living just up the street: "Der Helfer, Ratgeber, teilnehmende Instruktor wurde gefunden, ?nach seiner ausnehmenden Beschlagenheit im Fachlichen und seinem geistigen Rang genau der Richtige" (172). Mann needs Adorno for his knowledge of music, in particular. He not only reads Adorno's books, but also meets with him regularly to discuss specific passages from Doktor Eaustus. Several of the major ideas that Adorno formulates in his Philosophie der neuen Musik, which he brought to Mann in manuscript form at this time, resurface in Mann's text. It is clear, then, that a good portion of the theoretical commen tary on music in Doktor Eaustus comes from Adorno. However, the philoso phies of music articulated in the novel often part ways with Adorno's. One especially important divergence concerns the role of the composer in modern music. Adorno claims that composers' subjective contributions are far less important than in the past. The historical development of music, he asserts, leaves little or no room for composers to make subjective decisions or to express subjective ideas. Mann's novel, in contrast, emphasizes the subjective aspect of expression, even where Adorno denies its possibility most vehe
The two components of the crystallographic transition in VO2

Abstract Two distinguishable mechanisms of the monoclinic-to-tetragonal transition in VO 2 are identified: an antiferroelectric-to-paraelectric transition at a temperature T t as well as a change from homopolar to metallic VV bonding at a temperature T t ′. In pure VO 2 at atmospheric pressure, the two transitions occur at the same temperature, T t ′ = T t = 340°K. However, a T t ′ T t may be induced by atomic substitutions; and in the intermediate temperature range the structure is orthorhombic, the antiferroelectric distortions being somewhat different in the absence of homopolar VV bonding. From energy-band considerations, the semiconductor-to-metal transition is to be associated with the transition at T t ; but below T t ′ the semiconducting energy gap should be larger and the charge-carrier mobilities should be smaller. The existence of two transition temperatures in doped VO 2 is distinguished from the claim of two transition temperatures in the Magneli phases V n O 2 n −1 . In this latter case, the appearance of two transitions reflects a two-phase region consisting of two adjoining Magneli phases.
Pharmacogenomics: New paradigms for targeted therapy based on individual response to drugs.

Targeted therapy is the “holy grail” sought to achieve efficacy and reduce toxicity in cancer treatment. It is difficult nowadays to avoid reference to the word “targeted” or “personalized” in publications describing “novel” strategies for treating cancer. During the last decade, spectacular advances in genomics have brought the realization of targeted therapy closer to the bedside in treating patients with hematologic and solid tumors. Remarkable progress based on our understanding of aberrant genes and signaling has led to novel strategies for targeted therapy, understanding efficacy in select patients, and possible mechanisms leading to development of resistance. However, the absence of durable responses, rapid development of resistance to treatment, and dose limiting toxicity continue to be major hurdles that hamper progress. The focus of this seminar in Urologic Oncology is certainly timely given the availability of drugs and pathways that can be targeted in the treatment of urologic malignancies. To accompany this article, we have 2 excellent essays that provide a comprehensive and informative review on the current status and the future of targeted therapy in bladder cancer and renal cancer. Although it is unfortunate that we do not have an essay on prostate cancer where targeted therapy has led to remarkable progress in the clinical management of metastatic disease, in this editorial, the theme of targeted therapy in prostate cancer is addressed because evolving paradigms with this disease are relevant in understanding why we have successes or failures. Although chemotherapy with classical cytotoxic drugs does not often directly address putative drug targets that govern efficacy or toxicity in therapy, targeting of specific aberrant genes/pathways with small molecule inhibitors in cancer represents a more rational approach. However, similar to chemotherapy with cytotoxic drugs, presence of a presumed target per se does not necessarily assure efficacy, and we face similar problems with several of the small molecule–targeted drugs that are active clinically in select malignancies. Moreover, in this era of targeted therapy, the age-old problem of “intrinsic” and “acquired resistance” is an issue that continues to be poorly understood. Drugs that target specific mutations can be aided with a companion test to achieve selectivity, but this luxury does not exist with aberrant signaling pathways, e.g., angio
Humphry Davy, nitrous oxide, the Pneumatic Institution, and the Royal Institution

Humphry Davy (1778-1829) has an interesting place in the history of respiratory gases because the Pneumatic Institution in which he did much of his early work signaled the end of an era of discovery. The previous 40 years had seen essentially all of the important respiratory gases described, and the Institution was formed to exploit their possible value in medical treatment. Davy himself is well known for producing nitrous oxide and demonstrating that its inhalation could cause euphoria and heightened imagination. His thinking influenced the poets Samuel Taylor Coleridge and William Wordsworth, and perhaps we can claim that our discipline colored the poetry of the Romantic Movement. Davy was also the first person to measure the residual volume of the lung. The Pneumatic Institution was the brainchild of Thomas Beddoes, who had trained in Edinburgh under Joseph Black, who discovered carbon dioxide. Later Davy moved to the Royal Institution in London formed, in part, to diffuse the knowledge of scientific discoveries to the general public. Davy was a brilliant lecturer and developed an enthusiastic following. In addition he exploited the newly described electric battery to discover several new elements. He also invented the safety lamp in response to a series of devastating explosions in coal mines. Ultimately Davy became president of the Royal Society, a remarkable honor for somebody with such humble origins. Another of his important contributions was to introduce Michael Faraday (1791-1867) to science. Faraday became one of the most illustrious British scientists of all time.
Effect of somatostatin in patients with acromegaly: suppression of growth hormone, prolactin, insulin and glucose levels.

Abstract In five patients with acromegaly, the chronic hypersecretion of growth hormone was effectively inhibited by the administration of synthetic somatostatin (intravenous bolus of 250 μg followed by a constant infusion, 500 μg per 45 minutes). The rate of growth hormone decline during the infusion was rapid, with a mean half-time of 24 minutes. After the infusion, a return of secretion to previously elevated levels was observed. These data suggest that the inhibitory action of somatostatin on growth hormone secretion is nearly complete and that the biologic action of somatostatin is brief. In addition, somatostatin induced a concomitant fall in circulating levels of insulin, glucose and prolactin and an increase in fatty free acids. No effect on levels of thyrotropin, follicle-stimulating hormone or luteinizing hormone was observed. (N Engl J Med 290:935–938, 1974)
Anti-secretory effects and pharmacokinetics of low dose ranitidine.

SUMMARY The purpose of this study was to examine the anti-secretory effect of low doses of orally administered ranitidine on meal-stimulated gastric acid secretion and assess its pharmacokinetics. The effect of 20, 40, 60 and 80 mg of ranitidine p.o. and placebo were tested on 5 separate days (Latin square, double-blind) in 15 healthy males (mean age 35 years). Gastric acid secretion was measured prior to and for 8 h following two sequential mixed liquid meals administered at 4-h intervals. Venous blood samples were obtained at frequent intervals before and following each dose for determination of plasma ranitidine concentration by high pressure liquid chromatography. Each dose of ranitidine significantly (P < 0.01) decreased the peak and cumulative 4-h acid secretory responses to the first meal (range 58–93 %), and the 60 and 80 mg doses significantly inhibited the response to the second meal by 31 and 43%, respectively. Total 8-h meal-stimulated acid outputs were decreased significantly in a dose-related manner (range 38–73%). Peak plasma ranitidine occurred approximately 1 h after dosing. Ranitidine tmax, t½ and clearances were independent of dose; however, AUC and C. were dose-related. Inhibition of acid secretion was related to plasma ranitidine concentration; the mean IC50 was 27 (± 6.4) ng/ml. We conclude that modest doses (equivalent to 7–27% of the daily therapeutic dose) of ranitidine effectively suppress meal-stimulated gastric acid secretion in a dose-related manner. If these doses are of clinical efficacy, it may be possible for substantial cost savings to occur.
A peroxidative model of human erythrocyte intracellular Ca2+ changes with in vivo cell aging: measurement by 19F-NMR spectroscopy.

Abstract Numerous changes occur with human erythrocyte aging in vivo, including an increase in free ionic intracellular calcium concentration ([Ca 2+ ]i) (N.R. Aiken et al. (1992) Biochim. Biophys. Acta 1136, 155–160). An attractive hypothesis of cell aging suggests that oxidative stress is responsible for many age-related changes. To determine whether oxidative stress leads to increased intracellular Ca 2+ concentrations, we used the fluorinated calcium probe 5,5′-difluoroBAPTA and fluorine nuclear magnetic resonance spectroscopy ( 19 F-NMR) to measure [Ca 2+ ] i following mild hydrogen peroxide (H 2 O 2 ) stress to young red cells. Cells were separated using density centrifugation, exposed to 815 μM H 2 O 2 , loaded with the calcium probe, and [Ca 2+ ] i measured. Intracellular [Ca 2+ ] increased from 62 nM (± 4, S.E.) in untreated young cells to 173 nM (± 11) in peroxide treated cohort young cells. This value approached our previously reported [Ca 2+ ] i of 221 nM (± 25) in old human erythrocytes. Pretreatment of young cells with (a) cobalt, which blocks Ca 2+ influx through calcium channels, or (b) carbon monoxide, which prevents methemoglobin formation, inhibited the peroxide-induced increase in ionic intracellular calcium. These findings are consistent with the hypothesis that oxidative stress of erythrocytes contributes to the increased [Ca 2+ ] i found in senescent cells, and that this is due to increased membrane Ca 2+ leak resulting from oxidatively induced methemoglobin-cytoskeletal protein crosslinking.
The adiabatic correction to the ring puckering potential of oxetane

Abstract The adiabatic correction to the Hartree-Fock ring puckering potential of oxetane is presented along with the adiabatic correction to potential functions of H 2 , CO, and CO 2 . The oxetane calculation allows the identification of the source of the disagreement between theory and experiment for the barrier to ring planarity.
Bowl Shapes Are Better with Buffers–Sometimes

We consider tandem queueing systems with a general arrival process and exponential service distribution. The queueing system consists of several stations with finite intermediate buffer capacity between the stations. We address the problem of determining the optimal arrangement for the stations. We find that considering the last two stations, the departure process is stochastically faster if the slower station is last. Our results are consistent with the “bowl shape” phenomenon that has been observed in serial queueing systems with zero buffer capacity.
Tm-Fiber 2 µm Laser for Laser-Induced Plasma Spectroscopy of Organic and Biological Materials

This study applies a Tm-fiber laser emitting at 2 ?m for LIBS analysis of organic samples and discusses the benefits of the use of this fiber laser for analytical applications towards biological samples.
Optical Imaging and Microscopy of the Living Brain

Techniques for capturing functional information from the living brain including high-speed multispectral optical intrinsic signal imaging (MS-OISI) and dual-beam in-vivo two-photon microscopy, and their applications to understanding brain blood flow control will be described.
Analysing the short-term reduction in streamflow pH resulting from acidic precipitation

Abstract The effects of acidic precipitation on stream chemistry were measured on an east-central Pennsylvania basin. When combined with flow and chemical mass balances, the data can help quantify hydrological source areas and their contributions to acidic storm hydrographs. For small storms on the well-buffered agricultural basin, small volumes of acidic precipitation falling directly on the stream surface react with more alkaline inflows from subsurface flow and surface runoff components to reduce streamflow pH temporarily by approximately one-half unit. During larger storms, the pH of surface runoff approaches that of precipitation, causing a relatively large acidic loading to the stream. However, this large input is buffered by a correspondingly larger subsurface flow component which results in stream pH reductions similar to those observed during the smaller events. Hydrological interpretations derived from a pH based mass balance are reinforced by a mass balance based on electrical conductivity and ...
Computation of Heat Capacities of Liquid Polymers

The liquid heat capacities at constant pressure of a series of linear polymers have been computed as the sum of vibrational, external, and conformational contributions. Most of the heat capacity of liquid macromolecules arises from vibrational motion. The external contribution is assumed to approach zero at constant volume. The conformational contribution, finally, is calculated using a fit of experimental heat capacities, as available from the ATHAS data bank, to a one-dimensional Ising-type model with two discrete, degenerate states. A stiffness and a cooperativity parameter permit the representation of the experimental data for polyethylene, polypropylene, poly(methyl methacrylate), poly(n-butyl methacrylate), and polystyrene. Agreement between computation and experiment lies within a few percent, close to the experimental precision.
Development of an Instrument for Measuring Parental Beliefs about Reading Aloud to Young Children

This study assessed the psychometric properties of an instrument designed to measure parents' beliefs about the goals and process of reading aloud to young children. 155 parents of children ages 2 to 5 years completed the Parent Reading Belief Inventory. The inventory's items formed a single factor with high scores reflecting beliefs consistent with current theories of language acquisition and emergent literacy. The inventory had acceptable internal consistency (coefficients alpha for the scales ranged from .50 to .85) and short-term test-retest reliability of .79. When parental education and income were controlled, inventory scores remained significantly correlated .36 with self-report measures of parents' own book-reading habits, .40 with children's interest in books, and .30 with children's exposure to joint book-reading activities. Scores also showed significant partial correlations with the observed frequency of parental questions (.65) and responsiveness to children's speech (.41) during book-readin...
Millimeter-Wave Dielectric Permittivity of Glasses

A dielectric study of new glass specimens is reported using free-space quasi-optical spectroscopy over a frequency range spanning from 40 GHz to 120 GHz. This wide band spectroscopy makes use of a backward wave oscillator as a high power tunable source of radiation. It enables the achievement of relatively higher output power compared to other non-contact techniques. It is more preferable for the complex permittivity measurement of highly absorbing materials due to the higher level of radiation transmission through the specimen.
The effectiveness of astronomical speckle transfer function reweighting algorithms

Abstract Two methods for reweighting the astronomical speckle transfer function are compared using a combination of analysis and numerical computation. One method, long exposure subtraction, is shown to perform well only for very short wavefront correlation lengths (shorter than the correlation length expected from a real atmosphere). The other method, reference star division, is demonstrated to be effective and accurate, even when the wavefront statistics for the reference star data are substantially changed from the object data statistics. An experimental result using real telescope data is included which substantiates the analysis.
A colorimetric micromethod for determination of ammonia; the ammonia content of rat tissues and human plasma

Summary A method is described for the determination of ammonia in the presence of labile amides. The method combines rapid microdiffusion with an extremely sensitive colorimetric procedure. When applied to normal human plasma, concentrations of the order of 40 μ g. NH 3 N/100 ml. were obtained. The method was also applied to rat brain, skeletal muscle, and liver. Resting muscle was found to contain less than 1 μ mole/100 g. tissue, and liver less than 4 μ moles/100 g. Data are presented which indicate that, in the living steady state, these values are markedly reduced and approach zero.
Le Texte et le corps: la pensée dialectique de Diderot dans Le Supplément au voyage de Bougainville

By using a dialogical method in Le Supplement au voyage de Bougainville (1772), Diderot contrasts two places: the civilized European world and the primitive island of Tahiti. The dialogical structure of his work entails a questioning of the concept of libertinage through the theme of the corporeal. Indeed, the dialectical method he employs in the text unifies his vision on what the body represents. This work will demonstrate that for Diderot the body can be defined as three entities: the text, the physical, and the social. All these three categories are intertwined for him. Using them as a leitmotiv enables him to call into question the moral and social conventions of his own country.
Cytochromes a and a3: Catalytic activity and spectral shifts in situ and in solution

Abstract 1. The inhibitory and spectroscopic effects of azide on phosphorylating and non-phosphorylating systems have been studied. In non-phosphorylating particles succinate oxidase inhibition requires 10 times the concentration of azide needed to inhibit the oxidase itself. 2. Reduction of cytochrome a in non-phosphorylating particles oxidizing succinate occurs at low azide concentrations; inhibition supervenes only if sufficient azide is present to cause appreciable steady-state reduction of endogenous cytochrome c . 3. The previously reported shift in the α band of reduced cytochrome a from 605 to 600 mμ in presence of azide is now observed in all respiratory states of the mitochondrion, in Keilin-Hartree particles and in the isolated oxidase. It is concluded that this form of cytochrome a is neither a high-energy compound nor a complex with azide but the result of heme-heme interaction between reduced a and the classical oxidized a 3 -azide complex. 4. The high sensitivity of mitochondrial respiration in ADP-stimulated State 3 to azide is not accompanied by an increased sensitivity of mitochondrial oxidase activity. The changes in steady-state reduction of cytochromes c and a parallel the inhibition of respiration. Relief of inhibition by uncouplers is not explained by changes in intramitochondrial azide concentration and does not involve the disappearance of cytochrome a with an α band at 600 mμ. 5. It is suggested that the relief of azide inhibition by uncouplers is due to a change in electron-transfer pathways permitting a direct reduction of a 3 by c and short-circuiting cytochrome a . 6. The spectrum of reduced a 3 is discussed and it is indicated that this cytochrome probably has no appreciable α band at 605 mμ but instead is characterized in the visible region solely by a broad band centered at 560 mμ.
Malignant thymoma: renal metastases responding to cis-platinum.

A patient with invasive malignant thymoma and renal metastases was treated with cis-platinum, resulting in a complete response as documented by CTT and gallium scans. The association of renal metastases from thymoma is discussed.
Death by Splicing: Tumor Suppressor RBM5 Freezes Splice-Site Pairing

In a recent issue of Molecular Cell, Bonnal et al. (2008) demonstrate that the tumor suppressor gene RBM5 regulates alternative splicing of Fas pre-mRNA by interfering with splice-site pairing.
Moisture gain of spray-applied insulations and its effect on effective thermal conductivity ― Part I

The presence of free water in fibrous insulating materials can have a very det rimental effect on their thermal and physical properties. Fiberglass and cellu lose insulations were spray-applied to horizontal aluminum plates and exposed to air at relative humidities of 30, 50, and 70% and temperature differences of 20 and 27 C°. The moisture gain was determined by periodically weighing the samples, and the effect of the moisture on the heat flow and temperature distri bution was measured by heat flow sensors and thermocouples. Drying was also investigated by reducing the relative humidity to 10% once steady state had been reached. The rate of moisture gain and the total moisture gain increased with increasing relative humidity and temperature difference, and, after an initial increase, the apparent thermal conductivity would attain a quasi-steady state value that was directly proportional to the moisture gain.
The collection channel in a Wireless Sensor Network

We define the collection channel in a Wireless Sensor Network (WSN) and show how this collection channel can be used in the proofs of new types of coding theorems for WSNs. These coding theorems differ from traditional coding theorems in that they are used to describe aspects of the WSN other than source and channel codes. We also determine the capacity of the collection channel. This capacity is complementary to the transport capacity of a communication system and represents the WNS's ability to obtain information about a phenomenon that it is sensing.