cssi/SciSciGPT-SciSciNet huggingface dataset:
Globin mRNA in Ffsriend cells: its structure, function and synthesis

Accumulation of haemoglobin in induced MEL cells begins with the activation of transcription of the globin genes. Though much has been learned of cellular events affecting expression of the globin genes, e.g., from noninducible variants of MEL cells and cell fusion between MEL cells and other cell types, there is at present no in vitro system available that would permit more detailed study of the molecular events leading to transcription of the globin genes. Presumably, with the availability of cloned chromosomal genes such systems will soon be found. The products of transcription detected in induced MEL cells are 15 S and 11 S species which are precursor forms of beta- and alpha-globin mRNA, respectively. An unmodified primary transcript has not been detected. The 15 S species possesses a fully methylated 'cap' 1 structure the 5' end and poly(A) at the 3' end. Conceivably, there could be cleaving or splicing events preceding the 'capping' and polyadenylation, but all these reactions must occur extremely rapidly, since with a t 1/2 approx. 2 min a large proportion of the 15 S beta-globin RNA must be newly synthesised. It also contains the two intervening sequences found in the chromosomal genes. Selective processing occurs since from pulse and pulse-chase experiments most if not all of the 15 S beta-globin RNA is processed to mature 10 S beta-globin RNA very rapidly, whereas less than 10% of newly synthesised nuclear RNA (HnRNA) leaves the nucleus, the remainder being hydrolysed in the nucleus with a t 1/2 approx. 20 min. Perhaps rapid processing permits efficient transport to the cytoplasm. Further processing occurs in steps; apparently the large intervening sequence is removed first followed by the small intervening sequence. These steps do not appear to be rate limiting events and these sequences have not been detected separately from the 15 S beta-globin RNA. Such results and the wide divergency of intervening sequences, suggest that the intervening sequences per se play no essential function in the cell, though their presence in the nuclear transcript appears to necessary for processing to the mRNA. The selective processing accounts for more increase of the globin RNA in MEL cells, and further accumulation occurs by virtue of the stability of globin mRNA (t 1/2 approx. 17 h) compared with the bulk of poly(A)-RNA (t 1/2 approx. 3 h). It would appear, however, that specific destabilization of a class of stable mRNA (t 1/2 approx. 35 h) is necessary to allow globin mRNA to asccount for 90% of the mRNA population in reticulocytes.
Ammonia-induced upregulation of peripheral-type benzodiazepine receptors in cultured astrocytes labeled with [3H]PK 11195

Abstract Evidence suggests that peripheral-type benzodiazepine receptors (PBRs) may play a role in hepatic encephalopathy (HE), a condition associated with increased levels of ammonia in brain. In the present study, the regulation of [ 3 H]PK 11195-binding to PBRs in cultured rat astrocytes that had been previously exposed to NH 4 Cl was investigated. 24 h treatment of 21–28-day-old cultures with 2, 5 or 10 mM NH 4 Cl resulted in 25 ± 3, 48 ± 3 and 42 ± 4% increase in the number of [ 3 H]PK 11195-binding sites, respectively. No further change in [ 3 H]PK 11195-binding was observed after exposure of astrocytes to 5 mM NH 4 Cl for 48 or 72 h. Ammonia treatment did not cause any significant alteration in the affinity of [ 3 H]PK 11195 for PBRs. The present study demonstrates the susceptibility of the PK 11195-binding site of PBRs in cultured astrocytes to ammonia and suggests that increase in brain ammonia concentration causes a supersensitivity of PBRs.
Studies on pig liver microsomes I. Enzymic and pigment composition of different microsomal fractions.

Abstract 1. 1. A possible seasonal effect in pig liver microsomes is described. 2. 2. A crude fractionation of microsomes into light and bulk fractions is described. Examination in the electron microscope indicates that these contain predominantly smooth-surfaced and rough-surfaced microsomes, respectively. 3. 3. Chemical analysis and observation of the behavior of the microsomes on digestion and solubilization indicate that the smooth- and rough-surfaced microsomes are biochemically distinct, with the smooth-surfaced ones being rich in cytochrome b 5 whereas the rough-surfaced ones are rich in noncytochrome heme and contain a tan pigment. 4. 4. Properties of some microsomal components, including a CO-binding pigment and a soluble yellow pigment, have been described. 5. 5. The binding of hemoglobin to microsomes is described. 6. 6. The effects of low pH and solubilizing agents on microsomes are described. 7. 7. The properties of a microsomal substance (designated “acceptor”) which is reduced by cytochrome b 5 are described, and its origins and importance are discussed.
Old Wine into New Bottles: Responses to New Approaches in Library Education

AbstractLibrary schools historically have paid little attention to paradigm shifts in society. They have been slow to change their curricula in meaningful ways, and their leaders have not paid enough attention to forces from the external social environment. The limited theoretical foundation for librarianship leaves librarians without a clear sense of future direction. Five themes related to improving library education were proposed and discussed at the Feather River Institute held in May 1997. 1. Librarians lack a strong sense of identity.2. The profession of librarianship lacks an adequate body of underlying theory.3. Library schools and the library profession have been weak in regulating themselves.4. Library schools have been slow to respond to technological changes.5. The time is ripe for major changes in the curricula of library schools.
Adaptive medical information delivery combining user, task and situation models

Medical information delivery for users with different levels of expertise will be required for the manned mission to Mars due to limited potential for communication with Earth. The Mars Medical Assistant (MMA) uses a combination of user, situation, and task models to create virtual hypertext structures by piecing together medical “information components.” Information components are chosen based on the semantic content and the cognitive characteristics of the component's media type. The medical assistant currently supports three tasks: 1) describing medical procedures, 2) aiding diagnosis, and 3) providing information on health concerns. Conflicting suggestions from the three models need to be resolved. Tradeoffs in the model representations and conflict resolution strategies are being explored in the context of MMA.
Search and market for lemons

Abstract This paper provides an explanation, not found in the literature, for the origin of quality dispersion in product markets. The consumer's pure experience case of sequential search is modeled and the model is closed by explaining the firm's optimal decision making problem. Then the necessary and sufficient conditions for a non-degenerate distribution of quality are established. It is also shown that if a non-degenerate equilibrium distribution of quality does exist then it is an unstable equilibrium. The only stable equilibrium distribution is the degenerate lemon distribution. Therefore the model provides added support for Akerlof's argument that lemons tend to drive out good quality.
Different experiences, different effects: a longitudinal study of learning a computer program in a network environment

Students' previous computer experience has been widely considered an important factor affecting subsequent computer performance. However, little research has been done to examine the contributions of different types of computer experience to computer performance at different time points. The present study compared the effects of four types of computer experience on 30 graduate students' learning of a statistical program over one semester. Among the four types of computer experience, students' earlier experience of using computer network systems was found to affect their initial performance of learning the statistics program, but the experience of using statistical programs, the experience of email programs, and the length of using computers did not. These findings suggest complex relationships between students' computer experience and their computer performance and have implications for both learning and teaching computer programs and understanding the transfer of learning.
Estimation of parameters of linear homogeneous stochastic differential equations

Abstract In this paper we investigate the problem of parametric estimation for multidimensional linear autonomous homogeneous stochastic differential equations. We prove the Local Asymptotical Normality (LAN) property, find the Maximum Likelihood Estimator (MLE), and prove an asymptotical efficiency of MLE for bounded loss functions, when the observation time tends to infinity.
Low Molecular Weight Opioid Peptide Esters Could be Developed as a New Class of Analgesics.

Low molecular weight opioid peptide esters (OPE) could become a class of analgesics with different side effect profiles than current opiates. OPE may have sufficient plasma stability to cross the blood brain barrier (BBB), undergo ester hydrolysis and produce analgesia. OPE of dipeptides, tyr-pro and tyr-gly conjugated to ethanol have a structure similar to the anesthestic agent, etomidate. Based upon the analgesic activity of dipeptide opioids, Lipinski’s criteria, and permeability of select GABA esters to cross the BBB, opioid peptides (OP) conjugated to ethanol, cholesterol or 3-glucose are lead recommendations. Preliminary animal data suggests that tyr-pro-ethyl ester crosses the BBB and unexpectedly produces hyperalgesia. Currently, there are no approved OP analgesics available for clinical use. Clinical trials of good manufacturing practice OP administered to patients suffering from chronic pain with indwelling intrathecal pumps could resolve the issue that OP may be superior to opiates and may redirect research.
Reply to Mark Elam

My essay on the empty black box seems to have hit some raw nerves. I am grateful to Mark Elam for taking time to respond and I appreciate the passion in his words. Unfortunately, he seems more interested in applying ideological decals and passing peremptory judgments than in addressing any of the issues I posed. Presenting himself in the graceful image of a "good liberal ironist," Elam shoots some rather illiberal, nonironic shots at "fear and loathing," "predilection for cruelty," and such like. Oh my. It looks as though Baudelaire is wearing his Godzilla costume today. Mr. Elam correctly notes that I urge scholars to take a position on the larger questions about technology and the human condition. I am convinced that important questions about moral and political life are answered within the artificial forms and processes of our technological world. For that reason it is incumbent upon a writer not only to describe, analyze, and interpret but also to let people know what he or she makes of these technologically embodied ways of living. This should not be the focus of every moment of scholarship and intellectual exchange. But, surely, at the end of the day, our readers and our students should know where we stand on such broad issues as the promise of "technological development" or on what we would advise on particular consequential social and technical patterns. Elam mistakenly supposes that I insist on rooting positions of this kind in "truth." Wrong decal. As a matter of fact, my view is that both evaluations of technology and the cultivation of lasting virtues that concern technological choice must emerge from dialogue within real communities in particular situations. As regards technological decision making, I believe that the challenge is not that of how to impose universal standards of judgment clarified by "liberal metaphysics," but how to expand the social and political spaces where ordinary citizens can play a role in making choices early on about technologies that will affect them (as argued in Winner 1992). From that point of view there is a great deal to be learned from social histories and sociological studies, including those written in a constructivist
Impact of subdomain D1 of the short form S1b of the human prolactin receptor on its inhibitory action on the function of the long form of the receptor induced by prolactin.

Abstract Background Long-form (LF) homodimers of the human prolactin receptor (PRLR) mediate prolactin's diverse actions. Short form S1b inhibits the LF function through heterodimerization. Reduced S1b/LF-ratio in breast cancer could contribute to tumor development/progression. Current work defines the structural and functional relevance of the D1 domain of S1b on its inhibitory function on prolactin-induced LF function. Methods Studies were conducted using mutagenesis, promoter/signaling analyses, bioluminescence resonance energy transfer (BRET) and molecular modeling approaches. Results Mutation of E69 in D1 S1b or adjacent residues at the receptor surface near to the binding pocket (S) causes loss of its inhibitory effect while mutations away from this region (A) or in the D2 domain display inhibitory action as the wild-type. All S1b mutants preserved prolactin-induced Jak2 activation. BRET reveals an increased affinity in D1 mutated S1b (S) homodimers in transfected cells stably expressing LF. In contrast, affinity in S1b homodimers with either D1 (A) or D2 mutations remained unchanged. This favors LF mediated signaling induced by prolactin. Molecular dynamics simulations show that mutations (S) elicit major conformational changes that propagate downward to the D1/D2 interface and change their relative orientation in the dimers. Conclusions These findings demonstrate the essential role of D1 on the S1b structure and its inhibitory action on prolactin-induced LF-mediated function. General significance Major changes in receptor conformation and dimerization affinity are triggered by single mutations in critical regions of D1. Our structure–function/simulation studies provide a basis for modeling and design of small molecules to enhance inhibition of LF activation for potential use in breast cancer treatment.
Diagnostic Fiberoptic Bronchoscopy: Techniques and Results of Biopsy in 600 Patients

Six hundred patients underwent diagnostic flexible fiberoptic bronchoscopy (FFB). The two diseases most frequently encountered were bronchogenic carcinoma in 330 patients (55 percent) and bacterial infection in 94 (16 percent). A positive cytology on biopsy material was obtained in 279 of 330 patients (85 percent) with primary lung cancer. Fluoroscopy was a valuable aid in diagnosing bronchogenic carcinoma, since 42 percent of the tumors were not visible endoscopically and required fluoroscopic control for placement of the biopsy instrument. Of the 55 patients with hemoptysis and negative chest x-ray films, nine (16 percent) had flberoptically visible endobronchial carcinomas! In addition, two patients with carcinoma of the larynx and one with carcinoma of the nasopharynx were discovered. Transbronchial biopsy (TBB) in 68 patients with diffuse and localized disease achieved an overall 69 percent diagnostic success, including a correct diagnosis in each of four patients with Pneumocystis carinii pneumonia. Brush biopsy provided additional valuable laboratory data in bacterial, mycobacterial and cytomegalovirus infections but had a poor yield in Pneumocystis infections. Complications as a result of forceps biopsy were minimal, except for brisk bleeding in six patients.
Status of glomerular proteoglycans in aminonucleoside nephrosis

Status of glomerular proteoglycans in aminonucleoside nephrosis. Status of glomerular proteoglycans (PGs) in puromycin aminonucleoside nephrosis was investigated. Rats were made nephrotic and sacrificed 0, 7, 14, and 21 days later. Maximal proteinuric response was observed between 7 and 14 days. Prior to sacrifice, they received injections of conjugated or unconjugated anti-heparan–sulfate–proteoglycan antibody, directed against its core protein (M r = 18,000). Their kidneys were processed for direct and indirect immunofluorescence, immunoperoxidase, tannic–acid staining, and tissue autoradiography (ARG). By tannic–acid staining, antibody binding sites identical to the anionic sites described previously were discovered. No qualitative differences were observed by these immunohistochemical techniques. Quantitative tissue ARG did not reveal any statistical differences in the binding of antibody between the control and nephrotic groups. For de novo biosynthetic studies, rats were sacrificed on day 10. Their kidneys were utilized for labeling of basement membrane PGs by employing [ 35 S]-sulfate as the precursor product. Tissue ARG, as well as biochemical studies, were performed on the radiolabeled glomeruli. PGs were extracted with 4 M GuCl and characterized by Sepharose CL-6B and DEAE-Sephacel chromatography. There was an overall increase in the total incorporated radioactivities in the glomerular and media fractions. No differences were observed in the macro-molecular size characteristics of intact PGs and glycosaminoglycan chains of either glomerular or media fractions. However, an increase in the charge–density characteristics was observed in PGs of the nephrotic group. By tissue ARG, an increase in the grain densities over the basement membrane and mesangial matrices of the glomerulus was noted. These data indicate that the intact PGs, their chains and core protein do not undergo significant biochemical alterations; however, de novo synthesized PGs have higher charge–density characteristics which may be related to a higher degree of sulfation that occurs during the course of aminonucleoside nephrosis.
Efficient culture of CD8+ T cells from the islets of NOD mice and their use for the study of autoreactive specificities

During progression to type 1 diabetes (T1D), the pancreatic islets of humans and of the widely studied mouse model of T1D, the nonobese diabetic (NOD) mouse, are infiltrated by cells of the immune system. Here we report that infiltrated mouse islets (“translucent islets”) can be identified visually. We demonstrate the use of an efficient method for the isolation and culture of the islet-infiltrating cells of NOD mice, which results in a high percentage of CD8+ T cells after seven days, with minimal manipulation. We show that islet-infiltrating cells exit the islets soon after they are placed in culture and can be used in flow cytometric experiments several hours later. Importantly, we demonstrate that the cultured cells are antigen-responsive and that specificities present at the beginning of the culture are generally still present on day seven. In addition, some reactivities are undetected without culture, supporting the validity of the seven-day expansion period. This technique greatly facilitates investigations of the CD8+ T cell reactivities that play a pivotal role in the demise of pancreatic beta cells leading to the development of T1D.
The great sea-ice dwindle

Record minima in Arctic summer sea ice have been trumping each other. Marika Holland reflects on the likely fate of the northern sea ice cap.
Increased plasma arginine vasopressin levels in patients with congestive heart failure.

The antidiuretic hormone arginine vasopressin could contribute to both the vasoconstriction and impaired water handling frequently found in patients with congestive heart failure. In order to determine basal levels for vasopressin in this condition, plasma vasopressin was measured by radioimmunoassay in a group of 31 patients with advanced congestive heart failure. At the same time, plasma norepinephrine, plasma renin activity and numerous hemodynamic variables were also measured. In a subgroup of patients, the response of vasopressin to hemodynamic changes induced by nitroprusside infusion and to inhibition of the renin-angiotensin system with captopril was studied. The basal vasopressin levels in the patients were compared with those obtained from 51 comparably aged normal subjects. The mean vasopressin level (± standard error of the mean) in the patients was 9.5 ± 0.89 pg/ml as compared with 4.7 ± 0.66 (probability [p] Thus, vasopressin levels measured under steady state conditions are usuallv increased in patients with congestive heart failure. The increase is not dependent on reduced cardiac index. There appears to be an abnormality in the relation between vasopressin and serum sodium in some persons and vasopressin does not respond to acute hemodynamic changes with or without the inhibition of the renin-angiotensin system. The mechanisms causing increased vasopressin levels and their biologic importance in congestive heart failure remain to be defined.
Chain decompositions and independent trees in 4-connected graphs

This work was motivated by the study of a multitree approach to reliability in distributed networks and by the study of non-separating paths and cycles in highly connected graphs. We first give a result on "non-separating chains" in 4-connected graphs. This result is then used to obtain a "non-separating chain decomposition" of a 4-connected graph G, and an O(vV(G)v2vE(G)v) algorithm for constructing such a decomposition. As an application of this decomposition, we show how to produce four "independent spanning trees" in a 4-connected graph in O(vV(G)v3) time.
Microvilli and blebs as sources of reserve surface membrane during cell spreading

Abstract The increase in surface area that occurs as cells spread from the rounded to the flattened state has been examined in synchronized BHK 21 cells in the scanning electron microscope. Rounded cells, whether in mitosis or dissociated and freshly seeded in culture, are covered with a mixture of folds, blebs, and microvilli. As cells spread, these protuberances disappear, first in the flattening marginal region and progressively submarginally until the entire cell surface is virtually smooth. The estimated surface area of rounded post-mitotic daughter cells, taking microvilli into account, is close to that of fully spread cells 4 h after mitosis. Likewise, rounded early mitotic mother cells, which are also covered with microvilli, have approximately the same surface as fully spread cells just prior to mitosis. These findings suggest that cells possess a membrane reserve in their microvilli and other protuberances which can be utilized for spreading and initiating cell locomotion.
The Development and Implementation of a Pediatric Radiology Web Site

Over the past decade there has been rapid growth in the technology for the pediatric radiology population. This expansion has brought about an increased need for pediatric nurses in the radiology area. The care of these children can be complex and challenging. Nurses at Children's Hospital, Boston felt a need to share pediatric radiology information worldwide. In April 2005, Children's Hospital, Boston pioneered a pediatric radiology Web site to provide an international forum for sharing and networking regarding pediatric radiology issues and sedation strategies. This poster will highlight the development of this Web site and how it has been used to date.
Incidence of lung nodules found in patients undergoing lung volume reduction.

Background. The risk of lung cancer is increased with cigarette smoking and obstructive lung disease. Patients having a lung volume reduction operation represent a high-risk population for cancer. Methods. Between March 1994 and December 1996, 281 patients underwent a lung volume reduction operation. All had severe obstructive lung disease with hyperinflation. The incidence of lung nodules and their management were addressed. Results. Of the 281 patients, 39.5% had at least one lung nodule identified. Fifty-two nodules had typical benign calcification patterns. Of the remaining nodules, 78 were resected and 20 were followed up. Seventeen nodules resected were cancerous, of which 13 were primary lung cancers. Of the resected nodules there were 28 nodules not identified by the preoperative radiologic evaluation. Conclusions. Nodules are frequently seen in patients undergoing lung volume reduction operations. The overall incidence of cancer was 6.4%, with several only identified in the pathologic examination. Survival at short follow-up has been excellent for those with primary lung cancer. Nodules seen in this group of patients should be aggressively diagnosed and managed.
EXPLORING THE KAPPA CONUNDRUM : THE ROLE OF RECYCLING IN THE LEAD ISOTOPE EVOLUTION OF THE MANTLE

It has long been known that the measured kappa (232Th/238U, or κ) of mid-ocean ridge basalts (MORB) and, by inference, the upper mantle, is much lower than the time-integrated κ recorded by Pb isotope ratios (κPb). We examine models that can reconcile this kappa conundrum by in situ decay of U and Th in the upper mantle. Monte Carlo simulations reveal a restricted range of permissible `in situ' paths of MORB mantle evolution. These solutions require a roughly constant 232Th/238U ratio during early Earth history, followed by a period of steadily decreasing 232Th/238U from the end of the Archean to the present. These model criteria make good geological sense in terms of post-Archean recycling of crustal uranium back into the mantle. Preferential recycling of uranium, relative to thorium, can result from the high aqueous mobility of uranium in the oxidising environment at the Earth's surface. Soluble uranium is transported from continents to the altered oceanic crust and ultimately, by subduction, back into the mantle. In contrast, insoluble thorium remains in the weathered continental residue. This process is only likely to have become important after the marked increase in atmospheric oxygen fugacity at ∼2.2 Ga which led to a change in the predominant surface oxidation state of uranium. The uranium fluxes required in this Post-Archean Uranium Recycling (PURE) model are compatible with estimates derived from present-day fluxes of `excess' continental uranium returned to the mantle by subduction, integrated over some 2 Ga. Further modelling of Earth evolution in the context of differentiation into crust, depleted mantle and recycled plume reservoirs demonstrates the viability of this scenario in explaining modern-day lead isotopic signatures of both MORB and `HIMU' ocean island basalts. We emphasise that resolution of the kappa conundrum does not require a steady state upper mantle with its lead isotope ratios buffered by entrainment of material from another, deeper reservoir.
Mnemonics: Enhancing the Math Performance of Students with Learning Difficulties

Provides examples of acronym mnemonics that have been used successfully to improve the math performance of students with learning disabilities
STEREOELECTRONIC PROPERTIES OF PHOTOSYNTHETIC AND RELATED SYSTEMS—VII. AB INITIO QUANTUM MECHANICAL CHARACTERIZATION OF THE ELECTRONIC STRUCTURE AND SPECTRA OF CHLOROPHYLLIDE a AND BACTERIOCHLOROPHYLLIDE a CATION RADICALS

—Ab initio configuration interaction wavefunctions and energies are reported for 29 doublet states and three quartet states of the cation radicals of ethyl chlorophyllide a (Et-Chl a+) and ethyl bacteriochlorophyllide a (Et-BChl a+). In Et-Chl a.+ I the lowest excited doublet state D1 is estimated to lie 5220 cm-1 above the ground state D0, with a negligibly small D1 D0 transition probability. The lowest quartet state, Q1, is estimated to lie 7980 cm-1 above D1. The absorption spectrum up to 20,000cm-1 is shown to consist primarily of numerous low-intensity ‘background’ transitions, with transitions to D5 and D11 accounting for the observed peaks at 12,200cm-1 and 17,500cm-1, respectively. The large intense band at 25,000cm-1 is due primarily to transitions to D22 and D23, with numerous lower-intensity transitions to neighboring states. In Et-BChl a.+ D1 is estimated to lie 7112 cm-1 above D0, and Q, is approximately 5725 cm-1 above D. A pair of states, D3 and D5, account for the absorption at 11,000 cm-1, while another pair of states, D13 and D14, are associated with the broad, weak absorption near 20,000 cm-1. The two prominent intense peaks at 23,700 cm-1 and 27,700 cm-1 are assigned to D23 and D28, respectively, while the shoulder located at 25,500cm-1 is attributed to transitions to D24 and D26. As in Et-Chl at, numerous background transitions are found throughout the spectrum. The π spin density distribution in D0 of both molecules is similar, with spin density found predominantly on the α-carbon atoms. In both systems, approximately 65% of the π spin density in D1 is found on the methine carbon atoms, with the remainder found largely on the nitrogen atoms.
Aerobic and anaerobic metabolism of paired male lizards (Anolis carolinensis).

Abstract The associations of physical activity, skin color, body mass difference and conspecific olfactory cues with short-term aerobic and anaerobic metabolism in paired male Anolis carolinensis were examined. Control measurements for mild laboratory manipulation (such as the movement of a metabolic chamber) yielded significant increases in the rate of oxygen consumption, but not in the lactate concentration of these animals; stronger manipulation increased both. A possible influence of conspecific olfactory cues on the metabolism of lizards introduced into empty chambers was undetected. Anoles that turned from green to brown with handling showed an increase in oxygen uptake, but an association between this color shift and total body lactate level was not detected. Elevated rates of oxygen use and glycolysis were found in pairs of males in the absence of physical activity. Lactate levels of the individuals of a pair were positively correlated with one another; the lactate concentrations of lizards placed into occupied metabolic chambers were correlated with the difference in body mass of the pair.
Dynamic performance tuning for speculative threads

In response to the emergence of multicore processors, various novel and sophisticated execution models have been introduced to fully utilize these processors. One such execution model is Thread-Level Speculation (TLS), which allows potentially dependent threads to execute speculatively in parallel. While TLS offers significant performance potential for applications that are otherwise non-parallel, extracting efficient speculative threads in the presence of complex control flow and ambiguous data dependences is a real challenge. This task is further complicated by the fact that the performance of speculative threads is often architecture-dependent, input-sensitive, and exhibits phase behaviors. Thus we propose dynamic performance tuning mechanisms that determine where and how to create speculative threads at runtime.This paper describes the design, implementation, and evaluation of hardware and software support that takes advantage of runtime performance profiles to extract efficient speculative threads. In our proposed framework, speculative threads are monitored by hardware-based performance counters and their performance impact is estimated. The creation of speculative threads is adjusted based on the estimation. This paper proposes speculative threads performance estimation techniques, that are capable of correctly determining whether speculation can improve performance for loops that corresponds to 83.8% of total loop execution time across all benchmarks. This paper also examines several dynamic performance tuning policies and finds that the best tuning policy achieves an overall speedup of 36.8%on a set of benchmarks from SPEC2000 suite, which outperforms static thread management by 9.5%.
Virus-specific Activation of a Novel Interferon Regulatory Factor, IRF-5, Results in the Induction of Distinct Interferon α Genes

Interferon regulatory factor (IRF) genes encode DNA-binding proteins that are involved in the innate immune response to infection. Two of these proteins, IRF-3 and IRF-7, serve as direct transducers of virus-mediated signaling and play critical roles in the induction of type I interferon genes. We have now shown that another factor, IRF-5, participates in the induction of interferon A (IFNA) and IFNB genes and can replace the requirement for IRF-7 in the induction of IFNA genes. We demonstrate that, despite the functional similarity, IRF-5 possesses unique characteristics and does not have a redundant role. Thus, 1) activation of IRF-5 by phosphorylation is virus-specific, and its in vivo association with the IFNA promoter can be detected only in cells infected with NDV, not Sendai virus, while both viruses activate IRF-3 and IRF-7, and 2) NDV infection of IRF-5-overexpressing cells preferentially induced the IFNA8 subtype, while IFNA1 was primarily induced in IRF-7 expressing cells. These data indicate that multiple signaling pathways induced by infection may be differentially recognized by members of the IRF family and modulate transcription of individual IFNA genes in a virus and cell type-specific manner.
Neonatal tissue injury reduces the intrinsic excitability of adult mouse superficial dorsal horn neurons

Tissue damage during the neonatal period evokes long-lasting changes in nociceptive processing within the adult spinal cord which contribute to persistent alterations in pain sensitivity. However, it remains unclear if the observed modifications in neuronal activity within the mature superficial dorsal horn (SDH) following early injury reflect shifts in the intrinsic membrane properties of these cells. Therefore, the present study was undertaken to identify the effects of neonatal surgical injury on the intrinsic excitability of both GABAergic and presumed glutamatergic neurons within lamina II of the adult SDH using in vitro patch clamp recordings from spinal cord slices prepared from glutamic acid decarboxylase-green fluorescent protein (Gad-GFP) mice. The results demonstrate that hindpaw surgical incision at postnatal day (P) 3 altered the passive membrane properties of both Gad-GFP and adjacent, non-GFP neurons in the mature SDH, as evidenced by decreased membrane resistance and more negative resting potentials in comparison to naive littermate controls. This was accompanied by a reduction in the prevalence of spontaneous activity within the GABAergic population. Both Gad-GFP and non-GFP neurons displayed a significant elevation in rheobase and decreased instantaneous firing frequency after incision, suggesting that early tissue damage lowers the intrinsic membrane excitability of adult SDH neurons. Isolation of inward-rectifying K(+) (K(ir)) currents revealed that neonatal incision significantly increased K(ir) conductance near physiological membrane potentials in GABAergic, but not glutamatergic, lamina II neurons. Overall, these findings suggest that neonatal tissue injury causes a long-term dampening of intrinsic firing across the general population of lamina II interneurons, but the underlying ionic mechanisms may be cell-type specific.
Some geological implications of average Quaternary glacial conditions

Analyses of Quaternary landscape evolution tend to focus on events associated with culminations of glacial and interglacial ages, but for most of Quaternary time, environments were intermediate in character. Average Quaternary glacial conditions, based on assessment of the marine isotope record, approximated those near the stage 2/stage 1 transition and during substages 5b and 5d; isotope stages 3 and 4 and substages 5a-d lie within one standard deviation of the mean value. Under average glacial conditions, ice sheets lying over northern North America and Europe were much more contracted than their full-glacial counterparts, and the distribution of mountain glaciers reflected a snowline depression of some 500 m. Geomorphic processes operating under average Quaternary conditions contributed importantly to landscape evolution. Examples of landscapes that may represent such average conditions include cirques and fluvial deposits of the Pacific Northwest, the fjords and strandflat of western Norway, and atolls of the tropical oceans. By examining the geologic record from the perspective of average conditions, rather than those of climatic extremes, added insight can be gained regarding the evolution of Quaternary landscapes.
Sound source perception in anuran amphibians

Sound source perception refers to the auditory system's ability to parse incoming sensory information into coherent representations of distinct sound sources in the environment. Such abilities are no doubt key to successful communication in many taxa, but we know little about their function in animal communication systems. For anuran amphibians (frogs and toads), social and reproductive behaviors depend on a listener's ability to hear and identify sound signals amid high levels of background noise in acoustically cluttered environments. Recent neuroethological studies are revealing how frogs parse these complex acoustic scenes to identify individual calls in noisy breeding choruses. Current evidence highlights some interesting similarities and differences in how the auditory systems of frogs and other vertebrates (most notably birds and mammals) perform auditory scene analysis.
Optimal filters with heuristic 1-norm sparsity constraints

We present a design method for sparse optimal Finite Impulse Response (FIR) filters that improve the visibility of a desired stochastic signal corrupted with white Gaussian noise. We emphasize that the filters we seek are of high-order but sparse, thus significantly reducing computational complexity. An optimal FIR filter for the estimation of a desired signal corrupted with white noise can be designed by maximizing the signal-to-noise ratio (SNR) of the filter output with the constraint that the magnitude (in 2-norm) of the FIR filter coefficients are set to unity.1, 2 This optimization problem is in essence maximizing the Rayleigh quotient and is thus equivalent to finding the eigenvector with the largest eigenvalue.3 While such filters are optimal, they are rarely sparse. To ensure sparsity, one must introduce a cardinality constraint in the optimization procedure. For high order filters such constraints are computationally burdensome due to the combinatorial search space. We relax the cardinality constraint by using the 1-norm approximation of the cardinality function. This is a relaxation heuristic similar to the recent sparse filter design work of Baran, Wei, and Oppenheim.4 The advantage of this relaxation heuristic is that the solutions tend to be sparse and the optimization procedure reduces to a convex program, thus ensuring global optimality. In addition to our proposed optimization procedure for deriving sparse FIR filters, we show examples where sparse high-order filters significantly perform better than low-order filters, whereas complexity is reduced by a factor of 10.
Quasi-Steady State Principle and In Situ Real-Time Investigation of Transient Strains in 6061-T6 Al Alloy Using Neutron Diffraction

Neutron diffraction research has been limited to the "static" behavior of materials since the number of collected neutrons is insufficient to reach the adequate neutron counts in rapid changes of material state. In order to achieve the desired precision for the study of the transient material behavior, we propose an in-situ neutron-diffraction measurement method based on the quasi-steady state (QSS) phenomenon. The QSS principle was applied for the measurement of transient lattice spacing changes in a 6061-T6 aluminum alloy plate during thermo-mechanical processing.
Estimating the global prevalence of zinc deficiency: results based on zinc availability in national food supplies and the prevalence of stunting.

Background Adequate zinc nutrition is essential for adequate growth, immunocompetence and neurobehavioral development, but limited information on population zinc status hinders the expansion of interventions to control zinc deficiency. The present analyses were conducted to: (1) estimate the country-specific prevalence of inadequate zinc intake; and (2) investigate relationships between country-specific estimated prevalence of dietary zinc inadequacy and dietary patterns and stunting prevalence. Methodology and Principal Findings National food balance sheet data were obtained from the Food and Agriculture Organization of the United Nations. Country-specific estimated prevalence of inadequate zinc intake were calculated based on the estimated absorbable zinc content of the national food supply, International Zinc Nutrition Consultative Group estimated physiological requirements for absorbed zinc, and demographic data obtained from United Nations estimates. Stunting data were obtained from a recent systematic analysis based on World Health Organization growth standards. An estimated 17.3% of the world’s population is at risk of inadequate zinc intake. Country-specific estimated prevalence of inadequate zinc intake was negatively correlated with the total energy and zinc contents of the national food supply and the percent of zinc obtained from animal source foods, and positively correlated with the phytate: zinc molar ratio of the food supply. The estimated prevalence of inadequate zinc intake was correlated with the prevalence of stunting (low height-for-age) in children under five years of age (r = 0.48, P<0.001). Conclusions and Significance These results, which indicate that inadequate dietary zinc intake may be fairly common, particularly in Sub-Saharan Africa and South Asia, allow inter-country comparisons regarding the relative likelihood of zinc deficiency as a public health problem. Data from these analyses should be used to determine the need for direct biochemical and dietary assessments of population zinc status, as part of nationally representative nutritional surveys targeting countries estimated to be at high risk.
Two decades beyond BRCA1/2: Homologous recombination, hereditary cancer risk and a target for ovarian cancer therapy ☆

Almost exactly 20 years after their discovery, the BRCA1 and BRCA2 genes have become the target of the first "personalized" therapy available for patients with ovarian cancer. In December 2014, a poly(ADP-ribose) polymerase (PARP) inhibitor was granted expedited approved by the United States Food and Drug Administration for use in advanced ovarian cancer patients with germline BRCA1/2 mutations who have received three or more prior lines of chemotherapy. This review article will discuss (1) the BRCA1 and BRCA2 genes within the larger context of homologous recombination deficiency; (2) the advances in our understanding of hereditary cancer risk and the dramatic shifts that have occurred in the genetic testing landscape since the landmark 2013 Supreme Court ruling invalidating patents on BRCA1 and BRCA2 genetic testing; and (3) the clinical trials leading to the approval of olaparib, the first in human PARP inhibitor.
A randomized controlled trial to evaluate the effects of high-dose versus low-dose of arginine therapy on hepatic function tests in argininosuccinic aciduria

Abstract Objective To compare the effects of combinatorial therapy with low-dose arginine and a nitrogen scavenging agent (sodium phenylbutyrate) vs. monotherapy with high-dose arginine on liver function tests in patients with argininosuccinic aciduria (ASA). Study design Twelve patients with ASA were enrolled in a double-blind, placebo-controlled, cross-over study design. Subjects were randomized to receive either a low-dose of arginine therapy (100 mg·kg − 1 ·d − 1 ) combined with sodium phenylbutyrate (500 mg·kg − 1 ·d − 1 ) (LDA arm) or a high-dose of arginine alone (500 mg·kg − 1 ·d − 1 ) (HDA arm) for one week. At the end of one week of therapy, liver function tests were assessed and metabolite fluxes were measured using a multi-tracer stable isotope protocol. Results Plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), and measures of synthetic functions of the liver were the primary outcomes. Subjects had significantly increased levels of argininosuccinate ( P P Conclusions Administering higher doses of arginine in subjects with ASA results in increases in AST and ALT levels, especially in the subset of patients with elevated baseline aminotransferases. Hence, low-dose arginine sufficient to normalize arginine levels in plasma combined with nitrogen scavenging therapy should be considered as a therapeutic option for treatment of ASA in patients with elevations of hepatic aminotransferases.
Walk-up keyboard: an efficient low overhead interface for transient workers

A situation that traditional PC centered computing does not serve well is that of transient workers; workers who are required to move from place to place frequently, yet still be able to interact with their data. We used intra-body signaling to construct a system that allows workers to carry wearable computers and interact with them through a standard keyboard and monitor. The system has low overhead when changing terminals as the association between terminal and wearable occurs automatically when the user comes into contact with the terminal. Although the system is still under development, an initial implementation has verified that the desired functionality is obtainable.
Theorizing Federalism in Iraq

Abstract The debate regarding whether federalism can manage, prevent or resolve conflict in deeply divided societies while maintaining the territorial integrity of existing states is ongoing—both on the ground and in the theoretical literature. This paper explores one central facet of the debate about federalism through an exploration of the case of Iraq. It is argued that institutional features of federalism and realities on the ground make Iraq uniquely vulnerable to secessionist pressures. However, not all federations (and not all federalisms) are equally vulnerable to secessionist pressures. By exploring features of Iraqi federalism and the Iraqi state that will make it vulnerable to secessionist pressures, this paper provides some direction in resolving the paradox of federalism—the contradictory finding (and assertion) that federalism seems to both facilitate and prevent secessionist conflict.
A queueing network model for flexible manufacturing systems with tool management

The analytical model in this paper allows the evaluation of the performance of a flexible manufacturing system (FMS) with a tool management system. Design parameters such as the transportation time for tools to machines, as well as the number of transportation vehicles for tools, are explicitly considered. The part and the tool transportation system are modeled as two interacting closed queueing networks. The classical convolution algorithm is used to evaluate the part transportation system and mean value analysis approximation is applied to evaluate the tool transportation system. The resulting set of nonlinear equations allows then to estimate important system parameters such as the throughput of parts, the utilization of the tool transportation vehicles and the service interruptions caused by a tool supply order.