cssi/SciSciGPT-SciSciNet huggingface dataset:
Long-Term Prognostic Significance of Primary Gleason Pattern in Patients With Gleason Score 7 Prostate Cancer: Impact on Prostate Cancer Specific Survival

Purpose: We determined the long-term clinical significance of primary Gleason pattern in patients with Gleason score 7 prostate cancer.Materials and Methods: We reviewed the records of all patients who underwent bilateral pelvic lymph node dissection and radical retropubic prostatectomy for Gleason score 7 prostate cancer at our institution. All patients who underwent adjuvant hormonal or radiation therapy were excluded from analysis. Patients were monitored for biochemical failure, that is PSA progression, systemic recurrence and cancer specific survival.Results: We identified 1,688 patients who met admission criteria, of whom 1,256 (74.4%) had primary Gleason pattern 3 and 432 (25.6%) had primary Gleason pattern 4. Median followup was 6.9 years. At 10 years primary Gleason pattern 3 was associated with increased biochemical recurrence-free survival (48% vs 38%, p <0.001), lower systemic recurrence (8% vs 15%, p <0.001) and higher cancer specific survival (97% vs 93%, p = 0.013) for Gleason primary grade...
Acoustic evidence of aberrant velocities in stutterers' fluent speech.

Movement rates of formant frequencies and the extents of articulatory change were spectrographically analyzed in the fluent (VCV) utterances of 20 stutterers and nonstutterers. The velocities of articulator movement throughout the first vowel and velocities into the second, vowel were not significantly different for the two groups. These mean rates of movement, although nonsignificant, were slower in stutterers and slightly more variable, and the extent of articulator movement was comparable. These results do not support the contentions that stutterers use coarticulatory movements that are too rapid or that stutterers have a poorer competence for rapid coordination of speech movements. The rationales of rate-control treatment methods to slow coarticulatory movements in stutterers need to be reexamined.
A novel mutation of the luteinizing hormone receptor gene causing male gonadotropin-independent precocious puberty.

Familial male-limited precocious puberty (FMPP) is an autosomal dominant gonadotropin-independent disorder. Affected males generally develop signs of precocious puberty in early childhood. They typically show Leydig cell hyperplasia and increased testosterone production typical for their age, whereas circulating LH concentrations remain prepubertal. Several dominant point mutations of the LH receptor gene were identified in pedigrees with familial male-limited precocious puberty and were shown to cosegregate with the disease. Here we report a novel heterozygote point mutation in the LH receptor gene of a Brazilian boy with gonadotropin-independent precocious puberty. This mutation substitutes alanine 568 with valine at the carboxyterminus of the third cytosolic loop of the LH receptor. The unoccupied mutant receptors confer constitutive activation of adenyl cyclase activity when expressed in COS-7 cells, resulting in 4-fold higher cAMP concentrations over baseline compared with cells expressing an equival...
A security and robustness performance analysis of localization algorithms to signal strength attacks

Recently, it has been noted that localization algorithms that use signal strength are susceptible to noncryptographic attacks, which consequently threatens their viability for sensor applications. In this work, we examine several localization algorithms and evaluate their robustness to attacks where an adversary attenuates or amplifies the signal strength at one or more landmarks. We study both point-based and area-based methods that employ received signal strength for localization, and propose several performance metrics that quantify the estimator's precision, bias, and error, including Holder metrics, which quantify the variability in position space for a given variability in signal strength space. We then conduct a trace-driven evaluation of a set of representative algorithms, where we measured their performance as we applied attacks on real data from two different buildings. We found the median error degraded gracefully, with a linear response as a function of the attack strength. We also found that area-based algorithms experienced a decrease and a spatial-shift in the returned area under attack, implying that precision increases though bias is introduced for these schemes. Additionally, we observed similar values for the average Holder metric across most of the algorithms, thereby providing strong experimental evidence that nearly all the algorithms have similar average responses to signal strength attacks with the exception of the Bayesian Networks algorithm.
Modification of liver mitochondrial lipids and of adenine nucleotide translocase and oxidative phosphorylation by cold adaptation

Abstract The decrease in respiration rate following thyroidectomy is preceded by changes in the lipid composition of the mitochondrial membrane (Hoch, F.L., Subramanian, C., Dhopeshwarkar, G.A. and Mead, J.F. (1981) Lipids 16, 328–334) and in concert, changes in the kinetic parameters of the adenine nucleotide translocase (Mak, I.T., Shrago, E. and Elson, C.E. (1981) Fed. Proc. 40, 398). To demonstrate that physiological adaptation also involves this sequence of events, rats were housed at 8°C for 3–4 weeks. Cold adaptation resulted in a modest (5%) increase in the unsaturation index for the mitochondrial fatty acids comprised of a significant increase in arachidonic acid and a reciprocal decrease in linoleic acid. Phospholipid analysis indicated that cold adaptation increased the mitochondrial phosphatidylethanolamine and reciprocally decreased the phosphatidylcholine content. Concomitantly, cold adaptation resulted in 25–30% increases in rat liver mitochondrial respiratory activities without changing the respiratory control or ADP/O ratios. The kinetic parameters of the adenine nucleotide translocase were determined by the back-exchange method (Pfaff, E. and Klingenberg, M. (1968) Eur. J. Biochem. 6, 66–79). At 0–4 and 10°C, the V max and K m of the cold-adapted rat liver adenine nucleotide translocase were not distinguishable from the control values. The K i values determined by Dixon plot studies for atractylate and palmitoyl-CoA were also comparable between the two groups. However, at 25 and 37°C, cold-adapted rat liver adenine nucleotide translocase exhibited a 20% increase in V max and a 20% decrease in K m for external ADP. The results suggest that one adaption to a cold environment involves hormone-mediated changes in the lipid composition in the mitochondrial membranes which in turn modulate the adenine nucleotide translocase and subsequent respiratory activities.
Generalized Quasilinearization and Semilinear Elliptic Boundary Value Problems

The method of generalized quasilinearization is extended to semilinear elliptic problems employing both the classical and variational approaches. The results discussed are very general and include several special cases of interest.
Impact of ULF oscillations in solar wind dynamic pressure on the outer radiation belt electrons

[1] This work addresses radial transport of outer radiation belt electrons due to ULF disturbances of geomagnetic field. A new approach to calculating inductive electric field is developed and implemented using a dynamical model of the storm-time geomagnetic field. The approach is used to analyze the effects associated with solar wind dynamic pressure (Pdyn). It is found that Pdyn produces large-scale electric fields with maximum intensity at noon and midnight local time. Derived fields are used in test particle calculations of relativistic electron dynamics. The results show that even moderate oscillations of Pdyn typical for quiet-time magnetosphere can result in rapid electron scattering across the drift shells, which identifies Pdyn as one of the primary mechanisms of radial transport in the belt. Calculations show that electron motion is inconsistent with radial diffusion, and hence a more detailed description is required for accurate predictions of electron fluxes in the belt.
Thermochemical Etching Reveals Domain Structure in Magnetite.

Single crystals of magnetite were prepared for study of the magnetic domain structure by etching in a molten mixture of boron oxide and lead oxide. The domain pattern on a (110) surface shows 71°, 109°, and 180° Bloch walls. The intensity of remanent magnetization is much less than the saturation value.
The effects of texture and grain morphology on the fracture toughness and fatigue crack growth resistance of nanocrystalline platinum films

Abstract The fracture toughness and fatigue crack growth resistance of nanocrystalline materials are significantly affected by the thickness of the specimen. In this work we relate the mechanical properties of nanocrystalline platinum films to their texture and grain morphology. Tensile, creep and fatigue testing of annealed, ∼1 μm films resulted in mechanical properties similar to the as-received films (yield strength of ∼1.2 GPa, fracture toughness ∼17.8 MPa √m, and a fatigue crack growth power law exponent of ∼4.2). However, the breakdown of the initially columnar grain morphology had a marked effect on the transition point from an intergranular to transgranular fatigue cracking mode. Finite element modeling suggests that cyclic (fatigue) grain coarsening and the transition from inter- to transgranular cracking modes are a result of the relative importance of dislocation slip accommodation on in-plane and through-thickness oriented slip directions.
Impact of histological subtype on long-term outcomes of neuroendocrine carcinoma of the breast

Although rare, neuroendocrine carcinoma of the breast (NECB) is becoming an increasingly recognized entity. The current literature is limited to case reports and small series and therefore a comprehensive population-based analysis was conducted to investigate the clinicopathologic features and long-term outcomes associated with NECB. We included all patients in the SEER Database from 2003 to 2010 with a diagnosis of NECB. The 2012 WHO classification system was used to categorize patients based on histopathologic diagnosis: well-differentiated neuroendocrine tumors, small/oat cell or poorly differentiated neuroendocrine tumors, adenocarcinoma with neuroendocrine features (ANF), large cell neuroendocrine and carcinoid tumors. Survival analysis was performed for disease specific (DSS) and overall (OS) survival. Of the 284 cases identified, 52.1% were classified as well-differentiated, 25.7% small cell, 14.8% ANF, 4.9% large cell, and 2.5% carcinoid. In general, patients presented with advanced disease: 36.2% had positive lymph node metastases and 20.4% presented with systemic metastases. Five-year DSS rates for stage I-IV NECB were 88.1, 67.8, 60.5, and 12.4%, respectively, while five-year OS rates were 77.9, 57.3, 52.9, and 8.9%, respectively. DSS and OS were significantly different for well-differentiated neuroendocrine tumors and ANFs compared to small cell and carcinoid tumors. On univariate Cox proportional hazards regression, small cell carcinoma was significantly associated with worse DSS (OR 1.97, 95% CI 1.05-3.67) and OS (OR 2.66, 95% CI 1.49-4.72) compared to other neuroendocrine tumors. NECB is associated with advanced stage disease at presentation and an unfavorable prognosis for stage II-IV disease and small cell, large cell, and carcinoid histologic subtypes.
Hospital mortality in acute myocardial infarction in the era of reperfusion therapy (the Myocardial Infarction Triage and Intervention Project)

Abstract This study was conducted in 19 hospitals in the metropolitan Seattle area and included 6,270 unselected patients who had acute myocardial infarction (AMI) between January 1988 and April 1991. Hospital mortality was determined and related to patient demographic and clinical characteristics, the use of reperfusion therapies, and to complications after AML Thrombolytic therapy or direct coronary angioplasty
Biomethanation of Minnesota reed sedge peat

Abstract The high moisture content of peat, the occurrence in peat of large concentrations of fermentable organics of plant origin, the use of hydraulic peat mining techniques, and the possibility of recycling digested peat residue to the peat bogs are factors that support the position that biological gasification methods can be effectively utilized. Chemical characterization work indicated that peat is rich in organic matter, has all the essential elements needed for biological gasification, and should, in theory, be digestible. However, the chemical analyses also point to three possible impediments to vigorous digestion of peat: (1) The presence in peat of large concentrations of cellulose, hemicellulose, lignin, and other complex substances of low biodegradabilities; (2) The nonavailability of such essential elements as nitrogen, phosphorus, etc., that are mostly organically bound; and (3) The toxicities arising because of nitrates and other inhibitors. The work reported here consisted of exploratory digestion runs designed to study the effects of such factors as digestion mode, inoculum source, temperature, loading, detention time, feed particle size, and chemical pretreatment on peat digester gas yield, production rate, and gas quality. Work with Minnesota Reed Sedge Peat showed that it could be digested in both batch and continuous modes with or without external nutrient additions. A thermophilic temperature of 55°C effected higher gas yields than other mesophilic or thermophilic test temperatures. A thermophilic (55°C) methane yield of 0.14 std m 3 /kg (2.2 SCF/lb) VS (volatile solids) added was obtained with raw as-received peat during batch digestion for about 86 days, compared with a methane yield of 0.11 std m 3 /kg (1.7 SCF/lb) VS added observed during semicontinuous thermophilic (55°C digestion at a 60-day detention time and 0.80 kg VS/m 3 -day (0.05 lb VS/ft 3 -day) loading. Subsequent batch digestion showed that particle size reduction and acid or alkali treatment could cause a three fold increase in methane production over that obtained with raw untreated peat. This suggests that a methane yield of up to 0.31 std m 3 /kg (5 SCF/lb) VS added — which is about 60% of the maximum theoretical yield — may be obtained by optimizing the digestion and feed pretreatment conditions.
ELECTRICAL VARIATIONS DUE TO MECHANICAL TRANSMISSION OF STIMULI.

Mechanical stimulation of Nitella often produces responses resembling propagated negative variations but traveling faster and going past a killed spot. They appear to result from a mechanical disturbance traveling along the cell and stimulating each spot it touches (i.e. the stimulus itself travels). They are called mechanical variations to distinguish them from propagated negative variations. A mechanical disturbance may cause an irreversible change (death wave), but in traveling along the cell it may lose intensity and then produce only a reversible response (mechanical variation) which may eventually change to a propagated negative variation. The all or none law does not apply to incomplete mechanical variations, for the response varies with the strength of the stimulus.
A FORTRAN 77 program for determining the minimum significant increase of the multiple correlation coefficient

A FORTRAN 77 program is presented which computes the minimum multiple correlation coefficient needed for significance when another predictor is added, and the Wherry (1940) and Olkin and Pratt (1958) corrections for shrinkage.
Recent trends in adolescent substance use, primary care screening, and updates in treatment options

Purpose of reviewTo provide a brief overview on trends in common substances of abuse in adolescents, a summary of tools to evaluate adolescent substance abuse in an outpatient setting, and an update of outpatient and inpatient treatment options.Recent findingsRecent national data suggest an overall
Atypical Down Syndrome phenotype with translocation Trisomy 21

Down Syndrome (DS) is the most common chromosomal aneuploidy. Ninety-five percent of DS cases are due to free Trisomy while 3-4% are due to an unbalanced translocation. Generally, there are no phenotypic differences between these two causes of DS. We report an infant with Trisomy 21 due to 21q 21q translocation, who presented with an atypical DS phenotype. The proband was an AGA 36-week gestation infant born by SVD to a 35y.o. G2P2AB1 woman following two normal prenatal ultrasounds and a normal MSAFP. Pregnancy, labor and delivery were uncomplicated. At 2.5 months, exam revealed ht at 10-25th %, wt and HC at <5th%, mild facial asymmetry, high mildly deviated nasal bridge, downslanting palpebral fissures, absent Brushfield spots, moderate micrognathia, left ptosis, low set ears with overfolded superior helices, right Bell's palsy, left torticollis. Other findings were dermatoglyphics: right WRWAU, left ARUUU, tapered fingers with positional clenching of fist, sacral dimple and neurological abnormalities of hypertonia and arching of the back. Vision, hearing and echocardiogram were normal. By diagnostic criteria published in the J. of Peds. (1982), she did not meet the diagnosis of DS. Chromosome analysis by two laboratories at band level KI 550 revealed: 46,XX, +21, der (21; 21)(q10; q10). Both parents had normal karyotypes. FISH analysis utilizing the TUPLE; LSI 13,21 probe confirmed the Trisomy 21 translocation. At 8 months, she has continued hypertonia and developmental delay with functioning at 5-6 months. Our patient with Trisomy 21 due to translocation does not have the characteristic phenotype of DS. In 1977, Avramopoulos et al (1997) reported a patient with full standard Trisomy 21, who also had atypical phenotypes for DS. Possible etiologies for these findings may include: 1) small molecular deletion of the critical region of chromosome 21, 2) disruption of a gene by gene- gene interaction or 3) mosaicism in other cell lines. Further molecular research studies are planned.
Reactivity of monocyclic aromatic compounds under hydrothermal conditions

Monocyclic aromatic compounds (MAC) represent a significant fraction of the total organic carbon in many geologic environments such as hydrothermal systems and petroleum reservoirs, yet the factors that control their abundance in these environments remain highly uncertain. In order to evaluate whether aqueous reactions involving MAC have a significant impact on their occurrence, laboratory experiments were conducted to observe the reactivity of several simple MAC under hydrothermal conditions that included the presence of mineral redox buffers. Aqueous solutions of individual MAC were heated at 300 to 330°C and 350 bar in flexible gold reaction vessels with titanium fittings. Toluene in aqueous solution was found to gradually decompose during heating to form primarily benzene plus CO2, indicating the decomposition proceeded by an oxidative decarboxylation pathway. The rate of this reaction was enhanced by the presence of dissolved sulfur compounds and relatively oxidizing conditions, suggesting that intermediate oxidation state sulfur compounds (such as thiosulfate or polythionates) could play a role in promoting the reaction by facilitating the transfer of electrons among reactants. Benzoic acid decomposed rapidly to benzene plus CO2, suggesting that formation of benzoic acid is the rate-limiting step in the overall conversion of toluene to benzene. Both benzene and phenol were found to be essentially unreactive. An assessment of the reaction products was performed to evaluate whether reactions among MAC attained metastable thermodynamic equilibrium. The results of this assessment, however, were equivocal, with some observations suggesting approach to thermodynamic equilibrium while other data indicate that criteria to demonstrate equilibrium were not met. The laboratory results demonstrate that aqueous reactions can play a role in controlling the abundance of aromatic compounds in geologic environments.
Müller-Lyer illusion and the structure-strategy dichotomy

The relative contributions of structural and strategic factors involved in the Muller-Lyer illusion were examined as a function of training procedure. Estimates of structural and strategic factors were procedure specific, and greater correction of inaccurate strategic factors was observed for subjects trained with feedback than for those trained with visual-inspection or control procedures. No additive effects of combining feedback with visual inspection were observed.
Monoclonal antibodies potentially useful for diagnosis of squamous cell oral carcinoma

Five murine monoclonal antibodies (MoAbs) (F1/A, F1/B, F1/C, F1/D, and F1/E) were produced that react with different antigenic determinants on the cell surface of human oral squamous cell carcinomas. They each immunoprecipitate a complex containing three polypeptides with molecular weights 38, 80, and 180 kD on SDS polyacrylamide gel electrophoresis under reducing conditions. These monoclonal antibodies were used in immunohistochemical analysis to study frozen tissue sections of surgical specimens from the floor of the mouth. Antibodies F1/A and F1/B: 1) detected virtually all malignant cells in 13/14 cases of high-grade squamous cell oral carcinomas; 2) reacted weakly with nonneoplastic cells in oral biopsies showing severe dysplasia; and 3) did not react with normal stratified squamous epithelium. In comparison, antibodies F1/C, F1/D, and F1/E reacted only with approximately 50% of oral carcinomas, but not with cells in dysplastic oral lesions. These MoAbs were able to sensitize squamous tumor cells to killing by antibody-dependent cellular cytotoxicity (ADCC) cells and complement-mediated cytolysis. Our data suggest that these antibodies may be potentially useful for diagnosis and perhaps treatment of squamous cell oral carcinoma.
Scaling Pharmacodynamics from In Vitro and Preclinical Animal Studies to Humans

An important feature of mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) models is the identification of drug- and system-specific factors that determine the intensity and time-course of pharmacological effects. This provides an opportunity to integrate information obtained from in vitro bioassays and preclinical pharmacological studies in animals to anticipate the clinical and adverse responses to drugs in humans. The fact that contemporary PK/PD modeling continues to evolve and seeks to emulate systems level properties should provide enhanced capabilities to scale-up pharmacodynamic data. Critical steps in drug discovery and development, such as lead compound and first in human dose selection, may become more efficient with the implementation and further refinement of translational PK/PD modeling. In this review, we highlight fundamental principles in pharmacodynamics and the basic expectations for in vitro bioassays and traditional allometric scaling in PK/PD modeling. Discussion of PK/PD modeling efforts for recombinant human erythropoietin is also included as a case study showing the potential for advanced systems analysis to facilitate extrapolations and improve understanding of inter-species differences in drug responses.
Challenges in Identifying Native Hawaiians and Pacific Islanders in Population-Based Cancer Registries in the U.S.

Lack of disaggregated data for Native Hawaiians and Pacific Islanders (NHPIs) in the U.S. has resulted in severe gaps in understanding health disparities and unique health needs of NHPIs. Telephone interviews were conducted with 272 cancer patients identified by a population-based cancer registry. The self-reported NHPIs status was compared with that identified by the registry. Sensitivity, Specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) were calculated. Alternative NHPIs identification methods were explored. The registry had acceptable sensitivity (89%), specificity (96%) and NPV (99%), but low PPV (62%) in identifying NHPIs. Using additional information on surname and birthplace from the registry improved the identification of NHPIs, but either increased the false positive or decreased the counts of true NHPIs cases. Improved data collection methods and practices in identifying NHPIs in population-based cancer registries are needed and caution in interpreting cancer data for NHPIs is warranted.
Harmonic-oscillator model of the spin of the ω-meson

A harmonic-oscillator model of the ω-meson is analysed to account for the known fact that the ω-meson has spin one. Possibilities of generalizing the theory to relativistic resonances are briefly considered.
CMOS integrated circuit reliability

Abstract This paper summarizes recently published data on CMOS integrated circuit failure rates, and provides information on the effects of voltage, temperature, device complexity, and packaging on CMOS failure rates. Other factors which can affect failure rate are also indicated, including designs, materials, processes, in-process controls, screening tests, and product maturity. Data on failure rates of NMOS and PMOS integrated circuits are provided to enable comparison with CMOS data. It is concluded that available data do not indicate any consistent reliability difference for CMOS versus NMOS or PMOS integrated circuits. Because of the many advantages of CMOS integrated circuit technology, continued increase in usage of CMOS circuits has been forecast, accompanied by further increases in CMOS integrated circuit reliability.
Sedimentary cycling and environmental change in the Late Proterozoic: Evidence from stable and radiogenic isotopes

We report C, Sr, and O isotopic as well as selected major and trace element data from Late Proterozoic (ca. 540–900 Ma) marine carbonates in three widely separated basins. The isotopic and elemental data are used to evaluate effects of post-depositional alteration of 87Sr86Sr and δ13C. Using our present best estimates for unaltered samples, we construct a new δ13C-curve for 500–850 Ma marine carbonates using data in this paper and from literature sources. δ13C values are high (+4 to +8%) during most of the late Riphean (ca. 600–900 Ma) with brief negative excursions likely associated with glacial periods. Similarly, in the Vendian δ13C falls sharply (from late Riphean highs) to < −3% around the Varanger glaciation (ca. 600 Ma), and then returns to high values (+4 to +2%) remaining until the Precambrian-Cambrian boundary where the curve drops to a value of about − 1% in Lower Cambrian carbonates. Coupling of the Sr and C isotopic data is used to develop a simple model for evaluating organic carbon (Corg) burial in Late Proterozoic oceans. These calculations indicate that Corg burial rates were lower than present-day values during much of the late Riphean, at the same time that erosion rates were low. Excess O2 produced by the burial of Corg was likely balanced by oxidation of reduced hydrothermal fluids and weathering reactions. Near the time of the Varanger glaciation, Corg burial rates dropped but quickly recovered and reached a maximum (a factor of 2–4 greater than present day) in Vendian sediments. High Corg burial rates were probably driven by high sedimentation rates, and possibly high productivity. The high Corg burial rate likely gave rise to a large flux of O2; high values of δ34S in Late Proterozoic marine sulfates suggest that this O2 flux was not balanced by increased sulfate formation. Further, the Sr-isotopic record indicates that excess O2 was not balanced by oxidation of submarine hydrothermal fluids. Increased oxidative weathering was probably an important sink for O2; nonetheless, we conclude that a significant and rapid increase in atmospheric O2 occurred in the Vendian. These results have important implications for environmental changes during the first appearance of an Ediacaran metazoan fauna.
Voice-Band Data Modem Performance Over Companded Delta Modulation Channels

This paper reports upon the results of tests of the transmission of data over single- and multiple-hop companded delta modulation (DM) systems. The DM coder-decoder (CODEC) was optimized for voice transmission. Modem bit error rate (BER) achievable over the range of 1200-9600 bits/s is presented. A comparison with the performance of pulse code modulation (PCM) is included. The comparison indicates that the two systems are comparable for error-free digital lines but favors the DM system for lines with errors.
Interactions with Actin Monomers, Actin Filaments, and Arp2/3 Complex Define the Roles of WASP Family Proteins and Cortactin in Coordinately Regulating Branched Actin Networks

Arp2/3 complex is an important actin filament nucleator that creates branched actin filament networks required for formation of lamellipodia and endocytic actin structures. Cellular assembly of branched actin networks frequently requires multiple Arp2/3 complex activators, called nucleation promoting factors (NPFs). We recently presented a mechanism by which cortactin, a weak NPF, can displace a more potent NPF, N-WASP, from nascent branch junctions to synergistically accelerate nucleation. The distinct roles of these NPFs in branching nucleation are surprising given their similarities. We biochemically dissected these two classes of NPFs to determine how their Arp2/3 complex and actin interacting segments modulate their influences on branched actin networks. We find that the Arp2/3 complex-interacting N-terminal acidic sequence (NtA) of cortactin has structural features distinct from WASP acidic regions (A) that are required for synergy between the two NPFs. Our mutational analysis shows that differences between NtA and A do not explain the weak intrinsic NPF activity of cortactin, but instead that cortactin is a weak NPF because it cannot recruit actin monomers to Arp2/3 complex. We use TIRF microscopy to show that cortactin bundles branched actin filaments using actin filament binding repeats within a single cortactin molecule, but that N-WASP antagonizes cortactin-mediated bundling. Finally, we demonstrate that multiple WASP family proteins synergistically activate Arp2/3 complex and determine the biochemical requirements in WASP proteins for synergy. Our data indicate that synergy between WASP proteins and cortactin may play a general role in assembling diverse actin-based structures, including lamellipodia, podosomes, and endocytic actin networks.
Whose Science Do You Believe? Explaining Trust in Sources of Scientific Information About the Environment

Given that trust plays a key role in the communication of scientific information about the environment to the public, this study examines what explains trust in specific sources of such information...
Neuromuscular Control of the Knee During a Resisted Single-Limb Squat Exercise

BackgroundClosed kinetic chain exercises such as single-limb squats are preferred for knee rehabilitation. A complete understanding of the neuromuscular control of the knee during the single-limb squat is essential to increase the efficiency of rehabilitation programs.HypothesisPerforming a controlled single-limb squat with resistance to knee flexion and extension will increase the coactivation of the hamstring muscle group, thus reducing the quadriceps/hamstrings ratio.Study DesignDescriptive laboratory study.MethodsA total of 15 healthy human subjects (7 women, 8 men) performed controlled single-limb squats in a custom mechanical device that provided resistance to both flexion and extension. Subjects performed the task at 3 levels of resistance, set as a percentage of body weight. Surface electromyographic recordings from 7 muscles (gluteus medius, rectus femoris, vastus medialis oblique, vastus lateralis, biceps femoris, semitendinosus, and medial gastrocnemius) were collected during the task.ResultsBi...
Elastic deformation and failure in protein filament bundles: Atomistic simulations and coarse-grained modeling

The synthetic peptide RAD16-II has shown promise in tissue engineering and drug delivery. It has been studied as a vehicle for cell delivery and controlled release of IGF-1 to repair infarcted cardiac tissue, and as a scaffold to promote capillary formation for an in vitro model of angiogenesis. The structure of RAD16-II is hierarchical, with monomers forming long β-sheets that pair together to form filaments; filaments form bundles approximately 30–60 nm in diameter; branching networks of filament bundles form macroscopic gels. We investigate the mechanics of shearing between the two β-sheets constituting one filament, and between cohered filaments of RAD16-II. This shear loading is found in filament bundle bending or in tensile loading of fibers composed of partial-length filaments. Molecular dynamics simulations show that time to failure is a stochastic function of applied shear stress, and that for a given loading time behavior is elastic for sufficiently small shear loads. We propose a coarse-grained model based on Langevin dynamics that matches molecular dynamics results and facilities extending simulations in space and time. The model treats a filament as an elastic string of particles, each having potential energy that is a periodic function of its position relative to the neighboring filament. With insight from these simulations, we discuss strategies for strengthening RAD16-II and similar materials.
Local infiltration of neuropeptide Y as a potential therapeutic agent against apoptosis and fibrosis in a swine model of hypercholesterolemia and chronic myocardial ischemia

While the angiogenic effects of Neuropeptide Y (NPY) in myocardial ischemia and hypercholesterolemia have been studied, its effects on altering oxidative stress, fibrosis and cell death are not known. We hypothesized that local infiltration of NPY in a swine model of chronic myocardial ischemia and hypercholesterolemia will induce nerve growth and cell survival, while reducing oxidative stress and fibrosis. Yorkshire mini-swine (n=15) were fed a high cholesterol diet for 5 weeks. Three weeks after surgical induction of focal myocardial ischemia, an osmotic pump was implanted, which delivered NPY (n=8, high cholesterol treated, HCT) or the vehicle (n=7, high cholesterol control, HCC) for 5 weeks. Then myocardium was harvested for analysis. Assessment of myocardial function and perfusion was made the last intervention. Immunoblotting demonstrated significantly decreased levels of MMP-9 (p=0.001) and TGF-β (p=0.05) and significantly increased levels of Ang-1 (p=0.002), MnSOD (p=0.006) and NGF (p=0.01) in HCT. Immunohistochemistry results revealed significantly decreased TUNEL staining (p=0.005) and GLUT4 translocation (p=0.004) in HCT. The functional data showed significantly improved blood flow reserve (p=0.02) and improved diastolic function -dP/dt (p=0.009) in the treated animals. Local infiltration of NPY results in positive remodeling in ischemic myocardium in the setting of hypercholesterolemia. By initiating angio and neurogenesis, NPY infiltration improves blood flow reserve and restoration of fatty acid metabolism. The associated increased cell survival and decreased fibrosis result in improved myocardial diastolic function. NPY may have a potential therapeutic role in patients with hypercholesterolemia associated coronary artery disease.
Mathematical modeling of cold-wall channel CVD reactors

Abstract A two-dimensional numerical model employing the method of finite elements is described for mass transfer-controlled chemical vapor deposition in channel reactors. This model includes all relevant transport processes occurring in the two primary dimensions, including thermal diffusion, buoyancy forces, and the diffusion of energy, mass, and momentum in the axial (flow) direction. The model represents conditions occurring in reactors with large aspect ratios (channel width/height) in the absence of longitudinal roll waves, conditions conducive to the best growth uniformity. The model was used to calculate growth rate uniformity for metalorganic chemical vapor deposition (MOCVD) growth of InP from trimethyl indium. Thermal diffusion was found to be a significant term in the mass transfer equation, decreasing growth rate by about 30% near the front of the susceptor and by lesser amounts further downstream. Growth rate was found to be insensitive to susceptor temperature but dependent on the binary diffusion coefficient and thermal diffusion factor of the reactant in the carrier gas. Use of a tilted susceptor allows for conditions to be established for which there is a region of relatively uniform growth rate. Tilt angle must be chosen to balance between high growth rate and uniformity over large area.
"Bru-u-u-uce": The simple economics of mob goods

This paper provides a pure economic rationale for chronic excess demand for tickets to events like rock concerts. The model focuses on "mob goods", which are consumed jointly with crowd reaction, or "noise". Whereas the primary commodity is provided by the seller, the joint product is provided collectively by buyers. If propensities to make noise are inversely correlated with reservation prices and a capacity constraint applies, excess demand (queuing) is a necessary condition for profit maximization. One important implication is that anti-scalping laws may be welfare-increasing. The paper explores other applications in professional sports, restaurants, and on-stage theatre.
Drug resistance in ostertagiasis.

Abstract Benzimidazole- and levamisole-resistant Ostertagia circumcincta from sheep have been reported from several countries, but there are no reports of anthelmintic-resistant O. ostertagi in cattle, where resistance has been confirmed in controlled trials. The reasons for this may include (1) the biology of the worm, (2) avoidance of drug action by inhibition, (3) host metabolism of drugs, (4) less anthelmintic used in cattle than in sheep, (5) high costs of controlled trials, (6) lack of adequate in vitro tests to detect resistant worms and (7) lack of reporting of anthelmintic failures. Reduced efficacy of the anthelmintics levamisole and thiabendazole to adult O. ostertagi and of modern benzimidazoles to the inhibited L 4 larvae has been reported in cattle. This latter effect might, in part, represent a stage-specific expression of resistance.Although anthelmintic resistance in O. ostertagi is not known to be a problem at present, it could potentially become a serious issue.
Character Variation in Two Land Snails from the Dutch Leeward Islands: Geography, Environment and Evolution

Cerion tva (L.) and Tudora megacheilos (Potiez and Michaud) are the dominant land snails of Aruba, Bonaire and Curacao; both display the high degree of intraspecific character variation so often noted in terrestrial gastropods. This study correlates patterns of morphologic diversity with geographic and environmental distribution. Projected upon factor axes, the samples of each species fall into four groups corresponding to degrees of geographic isolation: Aruba, Bonaire, eastern and western Curacao. Factor axes represent the major trends of variation in shell size and shape. Subgrouping within geographic clusters is influenced by environmental parameters. In Cerion, for example, shells collected from volcanic rocks tend to be larger than those from limestone. In all geographic regions, these volcanic samples are distinguished by their higher projection on an axis representing increased size and concomitant changes of shape. Pulmonates usually favor limestone, but the anomaly of Cerion's smaller size is related to the unfavorable climatic conditions associated with limestone areas in the Dutch West Indies (dry, windy, and poorly vegetated). If the morphologic differences among geographic regions are similar to ecologicallyinduced variation within regions, then interregional differences are probably adaptive, and not a fortuitous result of geographic isolation, as many have claimed. Cerion is small ancd Tudora large in eastern Curacao; Tudora is small and Cerion large in western Curacao. This interregional relationship is parallelled by significant negative correlations between sizes of the two species for samples within regions. Diversity patterns did not change significantly during 16 years separating the studies of Baker and Hummelinek. Baker's data show the same distinction of four geographic areas and similar patterns of distribution within areas; significant positive correlation exists between measures made by Baker and Hummelinck on samples collected from the same localities. Fossil samples from cave phosphates do not conform to modem distributions. The basic character diversity pattem-good (presumably genetic) distinction among regions and ecologically induced variation within regions-requires a revision of Baker's classification. Separate names for the four regions are warranted, but the cumbersome nomenclature for intraregional diversity should be dropped.
Failure of sulfites to produce clinical responses in patients with systemic mastocytosis or recurrent anaphylaxis: results of a single-blind study.

Abstract Although sulfite sensitivity can precipitate asthma in a subpopulation of subjects with asthma, its role in precipitating anaphylaxis or as a nonspecific mast cell degranulator in systemic mastocytosis has not been examined. To evaluate critically the importance of sulfites in these diseases, eight patients with systemic mastocytosis and 25 patients with unexplained, recurrent anaphylaxis were challenged in a single-blind fashion; sodium bisulfite in capsules was administered in increasing doses of 1, 5, 10, 25, 50, 100, and 200 mg every 30 minutes. On separate occasions a liquid suspension of 200 mg of sodium bisulfite was administered to one patient with systemic mastocytosis and nine patients with anaphylaxis. Vital signs, pulmonary function tests, plasma histamine levels, and clinical reactions were monitored. There were no observable responses in either the mastocytosis group or in 23 of 25 patients in the anaphylaxis group. Two patients in the anaphylaxis group with initial positive challenges had similar symptoms on subsequent placebo challenge. One subject with asthma and with a history suggestive of sulfite sensitivity responded to oral challenge with 5 mg of sodium bisulfite and 100 μg of sodium bisulfite intradermally with a dramatic reduction in FEV, requiring treatment with bronchodilators. A comparison of baseline plasma histamine levels with those obtained after the sulfite challenge procedure in each category demonstrated a significant rise ( p
Choline acetyltransferase activity in mouse cerebellar cultures

Abstract The finding of the acetylcholine synthetic enzyme, choline acetyltransferase, has been reported in mouse cerebellar cultures, and it has been used as an index of neuronal survival and maturation. These results are curious in light of immunocytochemical studies which show that this enzyme is localized within mossy fiber terminals in glomerular structures of the cerebellar cortex. Since most mossy fibers are of extracerebellar origin, a significant population of mossy fiber terminals would not be expected to be present in cerebellar cultures. The origin of this acetylcholine synthetic activity has been examined in mouse cerebellar cultures. Two groups of explants, one with and the other without incorporated dorsal pontine tissue, were cultivated. Only cultures that included pons showed well developed glomerular structures with mossy fiber rosettes. Homogenates of the cultures were assayed for their ability to synthesize acetylcholine, and the synthesis was shown to be due to choline acetyltransferase by use of the specific inhibitor, (naphthylvinyl)pyridine. Cultures lacking dorsal pontine tissue had only low levels of enzyme activity, whereas those which included pons had 20–60 times greater synthetic activity. These results indicate that the choline acetyltransferase activity arises from pontine tissue in cerebellar cultures and are consistent with mossy fibers being the source of this enzyme.
Observed Microphysical Evolution for Two East Coast Winter Storms and the Associated Snow Bands

AbstractThis paper presents the observed microphysical evolution of two coastal extratropical cyclones (19–20 December 2009 and 12 January 2011) and the associated passage of heavy snowbands in the cyclone comma head. The observations were made approximately 93 km east of New York City at Stony Brook, New York. Surface microphysical measurements of snow habit and degree of riming were taken every 15–30 min using a stereo microscope and camera, and snow depth and snow density were also recorded. A vertically pointing Ku-band radar observed the vertical evolution of reflectivity and Doppler vertical velocities. There were rapid variations in the snow habits and densities related to the changes in vertical motion and depth of saturation. At any one time, a mixture of different ice habits was observed. Certain ice habits were dominant at the surface when the maximum vertical motion aloft occurred at their favored temperature for depositional growth. Convective seeder cells above 4 km MSL resulted in relativel...
Lithium Bis(3‐trimethylsilyl‐1‐propen‐2‐yl)cuprate

[–] C12H26CuLiSi2 (MW 297.05) InChI = 1S/2C6H13Si.Cu.Li/c2*1-5-6-7(2,3)4;;/h2*1,6H2,2-4H3;; InChIKey = LHLGWIFARZRKQF-UHFFFAOYSA-N (precursor to diene used in tandem Diels–Alder reactions) Preparative Method: 2-Bromo-3-trimethylsilyl-1-propene is lithiated with n-Butyllithium in ether at −78 °C, followed by addition of 0.5 equiv Copper(I) Iodide1. Handling, Storage, and Precautions: air- and moisture-sensitive; use in a fume hood.
Taxation of Wage Income for Economic Justice

The conception of distributive justice advocated by John Rawls, most comprehensively in A Theory of Justice , appears to be the first complete principle of social choice to command wide and serious interest since the time of sum-of-satisfactions utilitarianism. This chapter discusses the implications of the Rawls' criterion for the graduated taxation of wage incomes within the context of two simple models of household earning decisions. It describes the criterion and Rawls' defense of this principle. Rawls refers to the general concept of justice as the notion of a standard by which the distribution of the burdens and benefits from cooperation by the individuals in society is to be determined. The particular conception of justice, the specific distribution criterion, argued for in Justice is what he calls the difference principle: in the just economy, the welfare of the worst-off is as large as is feasible. The principle does not imply the obliteration of all inequalities in well-being. Differences in liberty and opportunity, income, and other primary social goods are justifiable insofar as they benefit the least well-off. It is the modern-day analogue of Aquinas: everything for the greater utility of the poor.
Mass spectrometry and next-generation sequencing reveal an abundant and rapidly evolving abalone sperm protein†

Abalone, a broadcast spawning marine mollusk, is an important model for molecular interactions and positive selection in fertilization, but the focus has previously been on only two sperm proteins, lysin and sp18. We used genomic and proteomic techniques to bring new insights to this model by characterizing the testis transcriptome and sperm proteome of the Red abalone Haliotis rufescens. One pair of homologous, testis-specific proteins contains a secretion signal and is small, abundant, and associated with the acrosome. Comparative analysis revealed that homologs are extremely divergent between species, and show strong evidence for positive selection. The acrosomal localization and rapid evolution of these proteins indicates that they play an important role in fertilization, and could be involved in the species-specificity of sperm-egg interactions in abalone. Our genomic and proteomic characterization of abalone fertilization resulted in the identification of interesting, novel peptides that have eluded detection in this important model system for 20 years.
Production of " prothrombin deficiency " and response to vitamins A, D and K.

Summary1. Prothrombin deficiency has been produced in rats by feeding an adequate diet containing 20% by weight of mineral oil. 2. The subcutaneous administration of Vitamin K corrected the prothrombin deficiency; activated ergosterol definitely improved the deficiency; Vitamin A had no effect on the deficiency.