cssi/SciSciGPT-SciSciNet huggingface dataset:
Phosphorylation of the Cryptochrome 1 C-terminal Tail Regulates Circadian Period Length *

The Cryptochrome (CRY) proteins are critical components of the mammalian circadian clock and act to rhythmically repress the activity of the transcriptional activators CLOCK and BMAL1 at the heart of the clock mechanism. The CRY proteins are part of a large repressive complex, the components of which are not completely known. Using mass spectroscopy, we identified the catalytic subunit of DNA-dependent protein kinase as a CRY-interacting protein and found that loss or inhibition of this kinase results in circadian rhythms with abnormally long periods. We then identified serine 588 in the C-terminal tail of mouse CRY1 as a potential DNA-PK phosphorylation site but surprisingly found that the phosphomimetic mutation S588D also results in long period rhythms, similar to the loss of DNA-PK. Consistent with this, we found that phosphorylation of this site is increased in cells lacking DNA-PK, suggesting that DNA-PK negatively regulates the phosphorylation of this site most likely through indirect means. Furthermore, we found that phosphorylation of this site increases the stability of the CRY1 protein and prevents FBXL3-mediated degradation. The phosphorylation of this site is robustly rhythmic in mouse liver nuclei, peaking in the middle of the circadian day at a time when CRY1 levels are declining. Therefore, these data suggest a new role for the C-terminal tail of CRY1 in which phosphorylation rhythmically regulates CRY1 stability and contributes to the proper circadian period length.
Experimental study of the flow of liquid He 4 through very small channels: Finite-size effects near T λ

The flow of liquid $^{4}\mathrm{He}$ through the very small cylindrical channels present in Nuclepore filters has been studied. Filters with channel diameters in the range 100-3300 \AA{} have been utilized, with emphasis on the behavior in the vicinity of the superfluid transition. As observed by many previous workers, we find that the onset of superfluid flow of the $^{4}\mathrm{He}$ in the channels occurs at a temperature, ${T}_{\ensuremath{\lambda}s}$, which is below the transition temperature of bulk $^{4}\mathrm{He}$. Our results for the variation of ${T}_{\ensuremath{\lambda}s}$ with channel size are in good quantitative agreement with the current theory.
Population structure of Rhagoletis pomonella, the apple maggot fly

Rhagoletis pomonella, the apple maggot fly, is the best-known member of the R. pomonella species complex. Rhagoletis pomonella has attracted interest because of its economic importance and because it has been a central focus of debate over sympatric speciation via host race formation. Based on electrophoretic data for 17 allozyme loci, the population structure of the ancestral hawthorn race of R. pomonella is characterized by: (i) strong geographical differentiation across eastern North America (FST = 0.148), (ii) pronounced latitudinal clines in allele frequencies at three loci, Aat-2, Dia-2 and Had, and (iii) very strong linkage disequilibrium involving two of these loci, Dia-2 and Aat-2, which are closely linked. The 10-fold greater level of population differentiation in R. pomonella compared with its close relative R. mendax may be related to its greater flexibility in life history timing.
Graduate medical education faces housestaff stress: institutional dynamics and group process.

The authors describe their efforts and experiences in presenting information on housestaff stress, dysfunction, and psychiatric morbidity to a committee of residency educators in their medical center. A complex group process emerged, which is discussed in the context of institutional background and “dynamics,” the physician-psychiatrist relationship, and faculty role conflicts.
Pathogenesis of transthyretin amyloidosis

Current dogma for transthyretin (TTR) pathogenesis is that mutations in TTR alter its structure such that the tetramer becomes unstable and prone to release of monomer which then becomes the putative building block of the fibril. This hypothesis is supported by thermodynamic data showing decreased stability of mutant TTR tetrameric proteins and accelerated fibril formation under acidic conditions in vitro. There are, however, a number of questions that are not readily answered by this simplistic model of a very complex disease. Worrisome questions still to be answered include: 1. If the monomer is the precursor of the fibril, why do fibril deposits contain large amounts of wild-type TTR and not just variant? 2. If destabilized tetramers can form fibrils in vitro, why do we consistently find partial proteolysis of fibril subunit proteins? If enzymatic proteolysis is a required step in fibril formation, are the findings of in vitro fibril formation relevant to the true pathogenesis? 3. With some TTR mutations (e.g. 122ΔVal), it would appear that very little TTR is present in the blood (probably due to degradation prior to hepatic secretion). Enough mutant TTR circulates to the heart and nerves to cause pathology but, if the mutant only serves to initiate fibril deposition, why are not the deposits mainly wild-type TTR?4. Since mutated TTR is present from birth, why is TTR amyloidosis of such delayed onset? What is the role of aging factors?5. Do the variations in biochemical analyses of heart and nerve versus choroid and leptomeningeal fibrils tell us something about pathogenesis? These are questions we need to address. Do not expect quick and easy answers. Hopefully, they will generate thought and discussion.
Optimizing photon fluence measurements for the accurate determination of detective quantum efficiency

Our goal was to evaluate the error contributed by photon fluence measurements to the detective quantum efficiency (DQE) of an x-ray imaging system. The investigation consisted of separate error analyses for the exposure and spectrum measurements that determine the photon fluence. Methods were developed for each to determine the number of measurements required to achieve an acceptable error. A new method for calculating the magnification factor in the exposure measurements was presented and compared to the existing method. The new method not only produces much lower error at small source-to-image distances (SIDs) such as clinical systems, but is also independent of SID. The exposure and spectra results were combined to determine the photon fluence error contribution to the DQE of 4%. The error in this study is small because the measurements resulted from precisely controlled experimental procedures designed to minimize the error. However, these procedures are difficult to follow in clinical environments, and application of this method on clinical systems could therefore provide important insight into error reduction. This investigation was focused on the error in the photon fluence contribution to the DQE, but the error analysis method can easily be extended to a wide range of applications.
Contribution of unmyelinated afferent excitation to sympathetic reflexes.

Abstract In this study of autonomic response to peripheral nerve afferent fiber excitation it was found that: (1) Stimulation of sural or saphenous A- and C-fibers together produced a reflex discharge followed by a silent period and a secondary late C-fiber reflex discharge in lumbar segment white rami and in the renal nerve. (2) By use of stimuli subthreshold for C-fibers and use of anodal block of A-fibers it was possible to stimulate A- and C-fibers independently. It was found that the C-fiber stimulation was responsible for the secondary reflex and increased overall efferent fiber activity. A rise in blood pressure was thus induced. A-fiber stimulation produced an earlier response and subsequent silent period. Following A-fiber stimulation the silent periods so reduced overall sympathetic discharge that depressor reactions occurred. (3) Deafferentation of baroreceptors abolished the normally occurring pulsatile surges in efferent discharge which tended to obscure the silent period following mixed fiber and A-fiber stimulation. The silent period and depressor reaction became more evident on A-fiber stimulation. Excitation of C-fibers was clearly seen to produce no silent period and only the C-fiber reflex of relative long latency. (4) Because of the latencies of response and presence of a silent period the responses recorded in this work were considered to be mediated through the medulla and not segmental spinal reactions. It was concluded that the A-fibers activate both a central excitatory and inhibitory system but the C-fibers only the excitatory complex.
Genotype-guided dosing of warfarin.

Vitamin K antagonists (VKAs)2 have been used to treat thromboembolic disease for over 60 years, and they continue to be the most commonly prescribed anticoagulants worldwide. However, VKAs such as warfarin have a narrow therapeutic index, and the mean daily dose of warfarin varies widely from patient to patient. Underdosing can leave patients undertreated for their thromboembolic diseases; overdosing can result in bleeding. As such, patients are forced to undergo frequent blood testing, and dose adjustments are made on the basis of the resulting international normalized ratio (INR) values. To achieve a therapeutic INR, which is defined as a value between 2.0 and 3.0 for conditions such as atrial fibrillation and venous thromboembolism, the daily dosing of warfarin can range over 20-fold, from <1 to over 20 mg (1). The variability in warfarin dosing depends on several factors, including demographics, the environment, and genetics. Specifically, variants in the genes that encode an enzyme responsible for the metabolism of warfarin [cytochrome P450, family 2, subfamily C, polypeptide 9 ( CYP2C9 )3] and the molecular target of warfarin [vitamin K epoxide reductase complex, subunit 1 ( VKORC1 )] influence warfarin dosing. The Food and Drug Administration has noted these findings, and the warfarin label recommends that if a patient's genotype is known, then this information should be considered when initiating therapy. Nonetheless, debate continues about the utility of routine genetic testing in this setting, a topic that has been addressed by several studies, including the EUropean Pharmacogenetics of AntiCoagulant Therapy (EU-PACT) and Clarification of Optimal Anticoagulation through Genetics (COAG) trials (2, 3). The EU-PACT trial enrolled 455 patients initiating warfarin treatment, of whom approximately 72% had atrial fibrillation and 28% venous thromboembolism. In this open-label study, patients were randomized to either warfarin dosing based on an algorithm that included …
Mass replication of multifunctional surface by nanoimprint of high aspect ratio tapered nanostructures

Tapered nanostructures with high aspect ratio were fabricated using high-throughput nanoimprint process. The replicated nanostructures have axially increasing effective refractive index, which enhances the optical transmission over a wide range of wavelengths and incident angles.
Editorial: The mail, the mail, the never-ending mail

The mail in whatever form is a relentless constant in the life of any journal editor. The U.S. mail delivers six days a week plus special deliveries on occasion. Other special delivery vans seem to be in and out of my driveway on a regular basis. And then there is e-mail (that I don’t have) and fax mail (that I do have), not to mention phone mail, of course.
Does receipt of public benefits reduce material hardship in low-income families with children?

Abstract Using data from the Survey of Income and Program Participation (1996 and 2001 panels), we determined that experiencing four types of material hardships (inadequate housing, inability to meet basic expenses, unmet medical/dental need, and food insufficiency) was common in low-income families with children. These hardships existed even though 85% of the families received at least one public benefit during the previous year. Receipt of public benefits also was related to an increased risk of experiencing all four types of material hardships. Finally, we attempted to adjust for one type of selection bias by considering families' need and their failure to access public benefits or additional benefits. We found that families reporting a need and failing to access public benefits for a variety of reasons, or to access additional benefits regardless of the number of benefits received, were more likely to experience material hardship compared with families receiving public benefits and reporting no need. These findings suggest that public benefits are insufficient to fully alleviate material hardship, and barriers to accessing public benefits may be one reason. If these families were able to access benefits that meet basic needs, receipt of public benefits might reduce material hardship.
High-speed Si MSM photodetector and VCSEL for optoelectronic interconnects

We report the fabrication and processing of thin film MSM silicon photo-detector and thin film VCSEL for optoelectronic interconnects. These two components, together with polyimide wave-guide can be used in constructing the high sped, low power, low cost optical interconnection system. Such a system will provide the fast board level data transmission. The DC and AC characteristics of thin film silicon MSM photo-detector, and the I-V and L-I characteristics of thin film VCSEL are measured.
Skin problems from marine echinoderms

Marine echinoderms include more than 6000 species of sea stars, sea urchins, sand dollars, heart urchins, and sea cucumbers. Several sea urchins, a sea star, and sea cucumbers have been found responsible for human injury. Thermolabile toxins are reputed to be responsible. Immersion in hot water provides pain relief and promotes resolution of symptoms.
Edge‐coloring of multigraphs: Recoloring technique

New upper and lower bounds for the chromatic index of a finite muitigraph are obtained. A complete description is given of multigraphs satisfying χ′ > 1/8(9ρ + 6) where χ′ and ρ denote the chromatic index and the maximum vertex degree of a multigraph. Some new and old conjectures are discussed.
Accuracy of CT-based measurements of glenoid version for total shoulder arthroplasty

Background/Hypothesis The arthritic glenoid is typically in retroversion and restoration to neutral version is recommended. While a method for measurement of glenoid version using axial computed tomography (CT) has been reported and has been widely accepted, its accuracy and reproducibility has not been established. Methods In 33 patients scheduled for shoulder arthroplasty, glenoid version and maximum wear of the glenoid articular surface were measured with respect to the scapular body axis on 2-dimensional- (2D) CT slices as well as on 3-dimensional- (3D) reconstructed models of the same CT slices. Results Clinical CT scans were axially aligned with the patient's torso but were almost never perpendicular to the scapular body. The average absolute error in version measured on the 2D-CT slice passing through the tip of the coracoid was 5.1° (range, 0 - 16°, P Conclusion Error in measuring version and depth of maximum wear can substantially affect the determination of the degree of correction necessary in arthritic glenoids. Accurately measuring glenoid version and locating the direction of maximum wear requires a full 3D-CT reconstruction and analysis.
Selection experiments for body composition in mice and rats: A review☆

Abstract Selection studies for body composition traits that used mice and rats as a model for livestock have been reviewed. Average realized heritability is higher for fat traits (0.49) than for lean traits (0.37), but there is considerable overlap. Selection for lean weight traits produced positive realized genetic correlations in growth, feed intake, gross feed efficiency and lean body mass, but body fat and protein percentages were not modified significantly at age of selection. Selection for fat percentage caused positive genetic correlations in growth, feed intake, feed efficiency and body fat, a negative response in body protein percentage and no response in lean body mass. An inexpensive and non-invasive method of measuring body composition is needed to improve the technical efficiency of selection. Future research should compare genetic variation in body composition at different ages. Desired gains and restricted selection index methods should be applied to modify body composition and growth. Hormones known to affect body composition and growth may be considered as additional selection criteria. Use of transgenic animals carrying genes coding for growth-promoting hormones, combined with artificial selection, offer additional strategies for changing body composition.
Evidence for superoxide generation by NADPH-cytochrome c reductase of rat liver microsomes.

Abstract Rat liver microsomes are capable of catalyzing an NADPH-dependent oxidation of epinephrine to adrenochrome that is inhibited by superoxide dismutase. Activity is greater and more sensitive to inhibition by superoxide dismutase at pH 8.5 than pH 7.7. The epinephrine oxidation activity copurifies with NADPH-cytochrome c reductase.
Biomechanical evaluation of lifting tasks: a microcomputer-based model

Abstract This paper discusses a static and dynamic biomechanical evaluation of sagittal lifting activities via a microcomputer model. The input to the developed model includes operator's anthropometric data, and sex. The model provides the reactive forces and torques at the various joints of the body expressed in both British and metric systems. Also, the model shows the calculated compressive force on the spine at the fifth lumber/first sacral joint (L5/S1), and both kinematic and kinetic informations are displayed. The model has a menu of five options: (1) to analyze stress imposed on the L5/S1 during a dynamic activity; (2) to determine maximum weight to be allowed during a dynamic motion; (3) to check stress on the spine (L5/S1) for specified static postures; (4) to determine maximum weight to be allowed for a static posture; or (5) to stimulate the lifting action and determine critical postures while performing lifting tasks based on static biochemical analysis.
MATERNAL ANEMIA AND POSTPARTUM WEIGHT CHANGE ASSOCIATED WITH DECREASED MATERNAL-INFANT INTERACTION IN A RURAL KENYAN POPULATION

Associations between maternal nutritional factors including energy intake, body mass index, postpartum weight change, and anemia status and maternal-infant interactions were examined in 124 mother-infant pairs from a marginally malnourished, rural Kenyan population. Anemic mothers spent less time holding and caring for their infants than nonanemic mothers. Mothers who retained their pregnancy weight gain or were able to gain weight postpartum spent more time looking at their infants than mothers who lost weight postpartum. Maternal food intake per se was not associated with patterns of infant interaction. Lower birth weight infants were held more, cared for more, and looked at face-to-face more by their mothers. Older sisters tended to be more involved in infant interactions with higher birth weight infants.
Hidden Markov modeling of speech using Toeplitz covariance matrices

Abstract Hidden Markov modeling of speech waveforms using structured covariance matrices is studied and applied to recognition of clean and noisy speech signals. This technique allows for easier model adaptation in additive noise than does cepstral modeling of speech. Waveform modeling using autoregressive (AR) structured covariances has been extensively studied and applied previously. However, other covariance structures are possible and here we consider waveform modeling using Toeplitz and circulant structured covariances. We detail maximum likelihood (ML) hidden Markov model training and recognition routines using these matrices, and ML speech gain estimation routines. We show equivalence of asymptotic probabilities of recognition error, under certain conditions, using Toeplitz and circulant matrices to using AR matrices. In experimental results on isolated digits in clean conditions, the Toeplitz covariance structure provides higher performance than the AR structure and has performance similar to that reported in the literature of a cepstral system on the same database. In additive Gaussian noise, we demonstrate superior performance to both the cepstral system and the AR system.
Synthesis of Butene−Ethylene and Hexene−Butene−Ethylene Copolymers from Ethylene via Tandem Action of Well-Defined Homogeneous Catalysts

Recent progress in the chemistry of well-defined organometallic catalysts has made a significant impact in the manufacture of polyolefins. An ever-growing menu of metal-ligand combinations exists to control the activity, copolymerization aptitude, and stereoselectivity of the catalytic site. The authors recently reported the use of tandem catalysis to produce branched chain polyethylene from a single feedstock of ethylene. Mixtures of (C{sub 5}H{sub 5}B-OEt){sub 2}ZrCl{sub 2} (1) and [({eta}{sup 5}-C{sub 5}Me{sub 4})SiMe{sub 2}({eta}{sup 1}-NCMe{sub 3})]TiCl{sub 2} (2) produce branched polyethylene from ethylene when activated with methylaluminoxane (MAO). In this process, 1/MAO produces linear 1-alkenes which insert into the growing polyethylene chain at the 2/MAO site. In this paper the authors report how such a tandem catalysis system can be created for the synthesis of poly(ethylene-co-1-butene) or polyethylene with ethyl and butyl branches.
Role of aggrecan in growth plate development: Use of genetically altered mouse models

understood. Tetraspanin 18 (Tspan18) is a member of the tetraspanin family of transmembrane proteins that have been implicated in cell signaling, motility and adhesion. Tspan18 is abundantly and specifically expressed in chick premigratory neural crest, but is downregulated when neural crest cells begin to migrate, suggesting that Tspan18 may negatively regulate neural crest migration. Interestingly, mRNA and protein levels of the known neural crest EMT regulator Cadherin6B (Cad6B) decrease following Tspan18 knock-down, while neural crest migration is inconsistently enhanced. In contrast, Tspan18 overexpression impedes neural crest migration, which preliminary results suggest is due in part to Cad6B stabilization. Consistent with the fact that the neural crest transcription factor FoxD3 regulates neural crest cell–cell adhesion and promotes migration, FoxD3 represses Tspan18 expression. Taken together, these data suggest that Tspan18, as a readout of FoxD3, plays an important role in restricting neural crest migration by affecting levels of Cad6B. Experiments are in progress to identify proteins that interact with Tspan18 to gain insight into how dynamic interactions at the neural crest cell surface impact migration, and may provide clues to the mechanisms of EMT during metastasis. Supported by NIH F31 GM087951 and a U of MN Grant in Aid.
Identification of the structural motif responsible for trimeric assembly of the C-terminal regulatory domains of polycystin channels PKD2L1 and PKD2

Polycystin 2-type cation channels PKD2 and PKD2L1 interact with polycystin 1-type proteins PKD1 and PKD1L3 respectively, to form receptor-cation-channel complexes. The PKD2L1-PKD1L3 complex perceives sour taste, whereas disruption of the PKD2-PKD1 complex, responsible for mechanosensation, leads to development of ADPKD (autosomal-dominant polycystic kidney disease). Besides modulating channel activity and related signalling events, the CRDs (C-terminal regulatory domains) of PKD2 and PKD2L1 play a central role in channel oligomerization. The present study investigates the aggregation state of purified full-length PKD2L1-CRD as well as truncations of CRDs from PKD2 channels. Far- and near-UV CD spectroscopy show that the full-length PKD2L1 CRD (PKD2L1-198) and the truncated PKD2 CRD (PKD2-244) are alpha-helical with no beta-sheet, the alpha-helix content agrees with sequence-based predictions, and some of its aromatic residues are in an asymmetric environment created at least by partially structured regions. Additionally, the CRD truncations exhibit an expected biochemical function by binding Ca2+ in a physiologically relevant range with Kd values of 2.8 muM for PKD2-244 and 0.51 muM for PKD2L1-198. Complimentary biophysical and biochemical techniques establish that truncations of the PKD2 and PKD2L1 CRDs are elongated molecules that assemble as trimers, and the trimeric aggregation state is independent of Ca2+ binding. Finally, we show that a common coiled-coil motif is sufficient and necessary to drive oligomerization of the PKD2 and PKD2L1 CRD truncations under study. Despite the moderate sequence identity (39%) between CRDs of PKD2 and PKD2L1, they both form trimers, implying that trimeric organization of CRDs may be true of all polycystin channels.
Effect of point defects on the decay of the longitudinal optical mode

Abstract The longitudinal optical mode at the zone center often has the highest frequency in the phonon spectrum, so that its phonons cannot be scattered elastically into other modes. Their decay rate Γ is enhanced by defects above the intrinsic anharmonic rate Γ ah by the combined action of anharmonic processes and defects such as point defects. This can occur by a second-order process. The phonon is scattered first into a neighboring mode. This intermediate state is followed by anharmonic decay. The intrinsic anharmonic decay rate Γ ah is almost independent of the intermediate state mode, so that Γ ah can be factored out of the second-order decay rate. An expression of the overall decay rate is obtained. A different result can be obtained by convoluting the point defect scattering over the anharmonic line width. This procedure was used numerically for isotopic mixtures of Ge and Si. An algebraic expression for the convolution is given here. These different approaches are compared to each other and compared to the observed line broadening in the isotopic mixtures. The second-order theory is also applied to line broadening due to Si solutes and their associated Al vacancies in aluminum nitride.
influence of UV-B radiation on polyamines, lipid peroxidation and membrane lipids in cucumber

Sensitive (Poinsett) and insensitive (Ashley) cultivars of cucumber (Cucumis sativus) were grown for four weeks from planting in unshaded greenhouses at 0 or 12.2 kJ m−2 day−1 of biologically effective ultraviolet-B (UY-BBE) radiation. The latter irradiance corresponded to a decrease in stratospheric ozone of ca 20% for clear sky conditions at Beitsville, MD on 21 June. The diamine putrescine and the polyamine spermidine accumulated in cotyledon and leaf tissues in response to UV-B radiation in both cultivars, but levels were not correlated with sensitivity to UV-B. Lipid peroxidation, as quantified by measurement of malondialdehyde (MDA), was increased by UV-B exposure. Significant cultivar differences were observed, with increases in lipid peroxidation in both cotyledons and leaves being correlated with UV-B sensitivity. Determination of membrane lipid composition indicated slight decreases in the unsaturated/saturated fatty acid ratios as a result of UV-B exposure. In general, Poinsett had a lower unsaturated/saturated ratio of fatty acids than did Ashley. These results indicate that membrane lipids may be a target of UV-B damage and that differences in the UV-B susceptibility of these two cultivars may involve differences in lipid metabolism. Polyamine accumulation in response to UV-B radiation stress is consistent with similar responses to other environmental stressors.
Vitamin K-dependent carboxylation in the developing rat: evidence for a similar mechanism of action of warfarin in fetal and adult livers.

Vitamin K-Dependent Carboxylation in the Developing Rat: Evidence for a Similar Mechanism of Action of Warfarin in Fetal and Adult Livers
Residential Mobility, Personality, and Subjective and Physical Well-Being An Analysis of Cortisol Secretion

Frequent residential moves in childhood may be stressful. Because introverts find making new friends in a new town more difficult than extraverts, the authors predicted that residential moves would...
Temperature and strain-rate effects on deformation mechanisms in irradiated stainless steel

Analysis of the deformation microstructures in ion-irradiated stainless steel shows twinning to be the predominant deformation mode at room temperature. Dislocation channelling also occurs under slow strain rate conditions. Stresses required for twinning were calculated by the model of Venables and are compatible with observed yield stresses in neutron-irradiated material if loops are the principal twin source. Computation of the expected radiation hardening from the defect structure, based on a simple model, is consistent with yield strengths measured on neutron-irradiated steels. Lower yield stresses and greater thermal energy at 288°C lessen the probability of twinning and dislocation channeling becomes the primary deformation mode at the higher temperature. However, preliminary results show that some twinning does occur in the irradiated stainless steel even at the higher temperature when higher strain rates are used.
Extreme scale computing: Modeling the impact of system noise in multicore clustered systems

System noise or Jitter is the activity of hardware, firmware, operating system, runtime system, and management software events. It is shown to disproportionately impact application performance in current generation large-scale clustered systems running general-purpose operating systems (GPOS). Jitter mitigation techniques such as co-scheduling jitter events across operating systems improve application performance but their effectiveness on future petascale systems is unknown. To understand if existing co-scheduling solutions enable scalable petascale performance, we construct two complementary jitter models based on detailed analysis of system noise from the nodes of a large-scale system running a GPOS. We validate these two models using experimental data from a system consisting of 128 GPOS instances with 4096 CPUs. Based on our models, we project a minimum slowdown of 2.1%, 5.9%, and 11.5% for applications executing on a similar one petaflop system running 1024 GPOS instances and having global synchronization operations once every 1000 msec, 100 msec, and 10 msec, respectively. Our projections indicate that additional system noise mitigation techniques are required to contain the impact of jitter on multi-petaflop systems, especially for tightly synchronized applications.
Channel Selection in EEG-based Prediction of Shoulder/Elbow Movement Intentions involving Stroke Patients: A Computational Approach

Brain computer interface (BCI) has gained a lot of attention recently, as a means to detect individuals' intents using brain signals such as electroencephalographic (EEG) for control of machines. In order to achieve the possible use of BCI in stroke rehabilitation, computational intelligent algorithms are important for reliable separation of shoulder versus elbow movement intentions. Efforts have been made on developing data processing and classification algorithm for such task. Differently, this paper investigates the optimal use of electrodes and signal channels, which is formulated as a data-driven feature selection problem. 163 EEG electrodes are used to collect scalp recordings to predict shoulder abduction and elbow flexion intentions in healthy and stroke subjects. We combine the support vector channel selection with a time-frequency synthesized classification algorithm and examine the performances of using different subsets of channel inputs. Preliminary results show that 1) a reduced number of electrodes can be used to achieve the same or better performance than using the full set of signal channels; 2) besides the fact that the accuracy on able-bodied subjects is expectedly higher than the stroke subject, the stroke subject tends to need more electrodes to achieve the best performance; 3) visualization of spatial distribution of channel rankings shows reasonable connection with functional motor cortex areas
Discriminative Motif Finding for Predicting Protein Subcellular Localization

Many methods have been described to predict the subcellular location of proteins from sequence information. However, most of these methods either rely on global sequence properties or use a set of known protein targeting motifs to predict protein localization. Here, we develop and test a novel method that identifies potential targeting motifs using a discriminative approach based on hidden Markov models (discriminative HMMs). These models search for motifs that are present in a compartment but absent in other, nearby, compartments by utilizing an hierarchical structure that mimics the protein sorting mechanism. We show that both discriminative motif finding and the hierarchical structure improve localization prediction on a benchmark data set of yeast proteins. The motifs identified can be mapped to known targeting motifs and they are more conserved than the average protein sequence. Using our motif-based predictions, we can identify potential annotation errors in public databases for the location of some of the proteins. A software implementation and the data set described in this paper are available from http://murphylab.web.cmu.edu/software/2009_TCBB_motif/.
Novel mutations in the respiratory syncytial virus G gene identified in viral isolates from a girl with severe combined immune deficiency treated with intravenous immune globulin

Background: Respiratory syncytial virus (RSV) can cause prolonged infections in individuals with compromised immunity. Objectives: To investigate whether RSV evolves during prolonged infection in an immunocompromised host. Study design: We sequenced the envalope glycoprotein genes of RSV obtained at three time points during a 59-day period from a 4-year-old female with severe combined immune deficiency (SCID) treated with intravenous immunoglobulin (IVIG). Results: Sporadic silent mutations were found in the SH, G and F genes among three RSV samples collected at days 0, 19 and 59. Premature stop codons at amino acid positions 257 and 278 were present in the RSV G glycoprotein gene sequenced from each time point. None of the 48 RSV G sequences available on GenBank or any of 50 genetically diverse clinical isolates of RSV contained these mutations. These premature stop codon mutations occurred at the same positions of the G glycoprotein gene as those described in in vitro monoclonal-antibody resistant mutants reported elsewhere. Conclusion: Our patient was most likely infected with a single RSV strain that did not mutate during the study period. This strain contains unique mutations that may have previously evolved in this individual who had prolonged infection and was treated with monthly IVIG.
Replication of Chimeric Human Immunodeficiency Virus Type 1 (HIV-1) Containing HIV-2 Integrase (IN): Naturally Selected Mutations in IN Augment DNA Synthesis

The human immunodeficiency virus type 1 (HIV-1) integrase (IN) protein augments the initiation of reverse transcription. Chimeric HIV-1 containing HIV-2 IN (SG3IN2) is severely impaired in virus infectivity and DNA synthesis. To analyze the nature of this defect, we infected T cells with the chimeric SG3IN2 virus and by continuous passage in cell culture selected for virus with improved replication properties. Viruses from two different time points were chosen for further analysis, an early culture-adapted virus (CF-65) that exhibited an intermediate level of infectivity, and a later-passaged virus (CF-131) that was significantly more infectious. Sequence analysis of multiple clones derived from the CF-65 virus culture demonstrated a diversity of mutations in the reverse transcriptase (RT) and a common V204I IN mutation. Analysis of clones derived from the CF-131 virus indicated the selection of two additional IN mutations, Q96H and K127E, and a fixed V179I RT mutation. By cloning RT and/or IN sequences back into the original SG3IN2 chimeric virus, we demonstrated that mutations in both RT and IN contributed to the improvement in viral fitness. The effect of the HIV-2IN(IN2) mutations on virus DNA synthesis was analyzed by packaging IN2 mutants into HIV-1 as Vpr-IN2 fusion proteins. This analysis revealed that the Q96H, K127E and V204I mutations increased the infectivity of the chimeric virus by augmenting the initiation of viral cDNA synthesis in infected cells. The Q96H and K127E mutations are present in adjacent helical structures on the surface of the IN protein and together account for most of the increase observed in DNA synthesis. Our findings provide evidence that the IN protein augments the initiation of reverse transcription through specific interactions with other viral components comprising the initiation complex. Moreover, they implicate specific regions on the surface of IN that may help to elucidate mechanisms by which the HIV-1 IN protein augments the initiation of HIV-1 reverse transcription in vivo.
Halophilic 20S Proteasomes of the Archaeon Haloferax volcanii: Purification, Characterization, and Gene Sequence Analysis

A 20S proteasome, composed of α1 and β subunits arranged in a barrel-shaped structure of four stacked rings, was purified from a halophilic archaeon Haloferax volcanii. The predominant peptide-hydrolyzing activity of the 600-kDa α1β-proteasome on synthetic substrates was cleavage carboxyl to hydrophobic residues (chymotrypsin-like [CL] activity) and was optimal at 2 M NaCl, pH 7.7 to 9.5, and 75°C. The α1β-proteasome also hydrolyzed insulin B-chain protein. Removal of NaCl inactivated the CL activity of the α1β-proteasome and dissociated the complex into monomers. Rapid equilibration of the monomers into buffer containing 2 M NaCl facilitated their reassociation into fully active α1β-proteasomes of 600 kDa. However, long-term incubation of the halophilic proteasome in the absence of salt resulted in hydrolysis and irreversible inactivation of the enzyme. Thus, the isolated proteasome has unusual salt requirements which distinguish it from any proteasome which has been described. Comparison of the β-subunit protein sequence with the sequence deduced from the gene revealed that a 49-residue propeptide is removed to expose a highly conserved N-terminal threonine which is proposed to serve as the catalytic nucleophile and primary proton acceptor during peptide bond hydrolysis. Consistent with this mechanism, the known proteasome inhibitors carbobenzoxyl-leucinyl-leucinyl-leucinal-H (MG132) and N-acetyl-leucinyl-leucinyl-norleucinal (calpain inhibitor I) were found to inhibit the CL activity of the H. volcanii proteasome (Ki = 0.2 and 8 μM, respectively). In addition to the genes encoding the α1 and β subunits, a gene encoding a second α-type proteasome protein (α2) was identified. All three genes coding for the proteasome subunits were mapped in the chromosome and found to be unlinked. Modification of the methods used to purify the α1β-proteasome resulted in the copurification of the α2 protein with the α1 and β subunits in nonstoichometric ratios as cylindrical particles of four stacked rings of 600 kDa with CL activity rates similar to the α1β-proteasome, suggesting that at least two separate 20S proteasomes are synthesized. This study is the first description of a prokaryote which produces two separate 20S proteasomes and suggests that there may be distinct physiological roles for the two different α subunits in this halophilic archaeon.
Understanding the recovery phase of breast reconstructions: Patient-reported outcomes correlated to the type and timing of reconstruction

Summary Introduction During preoperative discussions with breast reconstruction patients, questions often arise about what to expect during the recovery period. However, there is a paucity of data elucidating post-breast reconstruction pain, fatigue, and physical morbidity. This information is important to patient and physician understanding of reconstructive choices and the postoperative recovery process. We sought to evaluate how recovery may vary for patients based on the timing and type of reconstruction. Materials and methods Patients were recruited as part of the Mastectomy Reconstruction Outcomes Consortium (MROC) study, which is a prospective, multicentered National Institute of Health (NIH)-funded study (1RO1CA152192). Here, patients completed the Numerical Pain Rating Scale (NPRS), McGill Pain Questionnaire, and Breast-Q preoperatively, at 1 week, and 3 months postoperatively. Pain, fatigue, and upper body morbidity were evaluated by the type and timing of reconstruction. Results A total of 2013 MROC study participants had completed a 3-month follow-up, and therefore they were included for the analysis. A total of 1583 (78.6%) and 1517 patients (75.3%) completed surveys at 1 week and 3 months, respectively, post reconstruction. Across all procedure groups, fatigue and physical well-being scores did not return to preoperative levels by 3 months. At 3 months, pain measured by the NPRS differed across procedure types ( P = 0.01), with tissue expander/implant (TE/I) having more pain than direct to implant ( P P Conclusions For all reconstructive procedure groups, patients did not fully recover at 3 months post surgery. In addition, postoperative pain and upper body physical morbidity vary significantly by reconstructive procedure with patients undergoing TE/I reporting the most distress.
Perceived Correlates of Domain-Specific Physical Activity in Rural Adults in the Midwest

Purpose: In response to calls for more specificity when measuring physical activity, this study examined perceived correlates of this behavior in rural adults separately by the domain in which this behavior occurs (ie, home care, work, active living, and sport). Methods: A cross-sectional survey was completed by 407 adults from 2 rural towns in the Midwest. The questionnaire assessed the perceived social and physical environment, including neighborhood characteristics, as well as barriers to being active. The Kaiser Physical Activity Survey captured domainspecific activity levels. The response rate was 25%. Multiple regression analyses were conducted to examine the associations between social and physical environment factors and domain-specific physical activity. Findings: Having a favorable attitude toward using government funds for exercise and activity-friendly neighborhood characteristic were positively associated with active living. Friends encouraging exercise was positively associated with participation in sport. Barriers were inversely associated with active living and sport. Total physical activity was positively associated with workplace incentives for exercise, favorable policy attitudes toward supporting physical education in schools and supporting the use of government funds for biking trails, and it was inversely associated with barriers. There were no factors associated with physical activity in the domains of work or home care. Conclusions: Correlates of physical activity are unique to the domain in which this behavior occurs. Programs to increase physical activity in rural adults should target policy attitudes, neighborhood characteristics, and social support from friends while also working to decrease personal barriers to exercise.
Laboratory‐measured H2SO4‐H2O‐NH3 ternary homogeneous nucleation rates: Initial observations

[1] We have measured nucleation rates of sulfuric acid-water-ammonia (H2SO4-H2O-NH3) ternary homogeneous nucleation (THN), with a fast flow nucleation reactor attached to two chemical ionization mass spectrometers (CIMSs) to measure H2SO4 and NH3 concentrations simultaneously. Under our experimental conditions with a temperature of 288 K and RH from 4–42% and initial [H2SO4] in the 108–109 cm−3 range and [NH3] from 10–50 ppbv (∼2 × 1011–1 × 1012 cm−3), the enhancement factor (EF) compared to the binary system ranges up to ∼1,000 depending on [H2SO4], [NH3] and RH; EF also exponentially increases with decreasing RH and decreasing initial [H2SO4]. The numbers of H2SO4 (9–10) and H2O molecules (6–15) in the critical clusters are reduced in the presence of NH3 [(6–8) and (4–10), respectively]; the number of NH3 molecules in the critical clusters is smaller than 2, under our experimental conditions.
Reconsidering the Impact of Jurisprudential Regimes

Objectives. Recent work on Supreme Court decision making has argued that different areas of law demonstrate the creation of jurisprudential regimes, which alter the importance of different case facts to the justices, suggesting that the justices do alter their behavior in response to changes in the law. However, the work on jurisprudential regimes has suggested that all justices, or at least all justices who participate in establishing the regime, react similarly to the regime creation. Methods. I separate out the justices who support the establishment of the regime and those who oppose the establishment of the regime to test the hypothesis that majority and dissenting justices react differently to the creation of jurisprudential regimes. Results. Both sets of justices react to the establishment of the regime, but the change in behavior of the dissenters occurs after that of the majority. Conclusions. These results suggest that the impact of jurisprudential regimes may be even more substantial than previously believed.
An analysis of time-dependent planning

This paper presents a framework for exploring issues in time-dependent planning: planning in which the time available to respond to predicted events varies, and the decision making required to formulate effective responses is complex. Our analysis of time-dependent planning suggests an approach based on a class of algorithms that we call anytime algorithms. Anytime algorithms can be interrupted at any point during computation to return a result whose utility is a function of computation time. We explore methods for solving time-dependent planning problems based on the properties of anytime algorithms.
The Molecular Biology of Cystic Fibrosis

Cystic fibrosis afflicts many children and, as the life expectancy for patients with this disease steadily increases, many adults as well. The identification and characterization of the gene responsible for this disorder provide a basis for understanding the pathophysiology of cystic fibrosis. Basic science advances are rapidly being integrated into the diagnostic and therapeutic regimens used by physicians in the care of patients with this disease.
Purposive diversification and economic performance: The multimarket firm

Large manufacturing firms typically operate in many markets. As a result, when we analyze a market's performance as a function of its structure, we need to consider the diversification of the market's sellers and their multimarket contact. The operations of the typical firm among the largest 1000 U.S. manufacturers span several lines of business. Table 1.1 provides the frequency distribution describing the number of manufacturing lines of business (LBs – an LB is a company's operations in a particular industry) for the 437 companies in the sample used in this chapter. The companies are all among the largest 1000 U.S. manufacturers and comprise the Federal Trade Commission Line of Business (FTC LB) Program sample for 1974. These large companies average a bit under eight manufacturing LBs per company. Of course, the motives for such diversification are numerous. For just a sampling of the variety of commentary through the years, consider Penrose (1959), Gort (1962), Rumelt (1974), Berry (1975), Mueller (1987), and Montgomery and Werner felt (1988). Although random discrepancies in the valuation of assets (Gort, 1969) and the risk aversion of managers (Amihud and Lev, 1981) can motivate pure conglomerate diversification, the purposive pursuit of (private) efficiencies because of complementarities across industry categories motivates “related” diversification. I shall focus on the trade-off that such diversification creates between the possibilities for technical efficiencies and for market power and then investigate the ensuing overall performance effects on static and dynamic efficiency. I shall explore the causes and effects of diversification.