cssi/SciSciGPT-SciSciNet huggingface dataset:
The surgical oncology clinical trial landscape: A cross-sectional analysis of ClinicalTrials.gov from 2008-2020.

1561Background: Surgical interventions are studied less often than medical or radiation interventions in oncology clinical trials. We characterized surgical oncology trials registered on ClinicalTr...
Where There's Smoke, There's a Joint: Passive Smoking and Rheumatoid Arthritis.

Among the established risk factors associated with developing rheumatoid arthritis (RA), smoking remains one of the leading environmental exposures associated with disease onset. One meta-analysis of ten studies found that the risk of developing RA increased by 26% among those who smoked 1-10 pack-years, and nearly doubled among those with more than 20 pack-years, compared to never smokers[1]. Studies that closely examine smoking and development of RA continue to be important, as it is a modifiable risk factor that can significantly reduce the burden of disease in the population.
Study protocol for a two-center test of a nurse-implemented chronotherapeutic restoring bundle in critically ill children: RESTORE Resilience (R2).

Abstract Often, pediatric intensive care environments are not conducive to healing the sick. Critically ill children experience disruptions in their circadian rhythms, which can contribute to delayed recovery and poor outcomes. We aim to test the hypothesis that children managed via RESTORE Resilience (R2), a nurse-implemented chronotherapeutic bundle, will experience restorative circadian rhythms compared to children receiving usual care. In this two-phased, prospective cohort study, two separate pediatric intensive care units in the United Sates will enroll a total of 20 baseline subjects followed by 40 intervention subjects, 6 months to less than 18 years of age, requiring invasive mechanical ventilation. During the intervention phase, we will implement the R2 bundle, which includes: (1) a focused effort to replicate the child's pre-hospitalization daily routine, (2) cycled day-night lighting and sound modulation, (3) minimal yet effective sedation (RESTORE), (4) nighttime fasting with bolus enteral daytime feedings, (5) early progressive mobility (PICU Up!), (6) continuity in nursing care, and (7) parent diaries. Our primary outcome is circadian activity ratio post-extubation. We hypothesize that children receiving R2 will experience restored circadian rhythms as evidenced by decreased nighttime activity while in the PICU. Our exploratory outcomes include salivary melatonin levels; electroencephalogram (EEG) slow-wave activity; R2 feasibility, adherence, and system barriers; levels of patient comfort; exposure to sedative medications; time to physiological stability; and parent perception of being well cared for. This paper describes the design, rationale, and implementation of R2. Clinicaltrials.gov identifier NCT04695392.
Multifunctional Fructose 1,6-Bisphosphate Aldolase as a Therapeutic Target

Fructose 1,6-bisphosphate aldolase is a ubiquitous cytosolic enzyme that catalyzes the fourth step of glycolysis. Aldolases are classified into three groups: Class-I, Class-IA, and Class-II; all classes share similar structural features but low amino acid identity. Apart from their conserved role in carbohydrate metabolism, aldolases have been reported to perform numerous non-enzymatic functions. Here we review the myriad "moonlighting" functions of this classical enzyme, many of which are centered on its ability to bind to an array of partner proteins that impact cellular scaffolding, signaling, transcription, and motility. In addition to the cytosolic location, aldolase has been found the extracellular surface of several pathogenic bacteria, fungi, protozoans, and metazoans. In the extracellular space, the enzyme has been reported to perform virulence-enhancing moonlighting functions e.g., plasminogen binding, host cell adhesion, and immunomodulation. Aldolase's importance has made it both a drug target and vaccine candidate. In this review, we note the several inhibitors that have been synthesized with high specificity for the aldolases of pathogens and cancer cells and have been shown to inhibit classical enzyme activity and moonlighting functions. We also review the many trials in which recombinant aldolases have been used as vaccine targets against a wide variety of pathogenic organisms including bacteria, fungi, and metazoan parasites. Most of such trials generated significant protection from challenge infection, correlated with antigen-specific cellular and humoral immune responses. We argue that refinement of aldolase antigen preparations and expansion of immunization trials should be encouraged to promote the advancement of promising, protective aldolase vaccines.
Intradiscal Delivery of Anabolic Growth Factors and a Metalloproteinase Inhibitor in a Rabbit Acute Lumbar Disc Injury Model.

ABSTRACT Background The purpose of our study was to examine the effect of controlled delivery of TGF-β3, BMP-4, and TIMP-2 with a biocompatible biopolymer, chitosan, on an acutely injured intervertebral disc (IVD) in a rabbit model. Methods After conducting an in vitro analysis of the chondrogenic capacity of the biomolecule cocktail use (ie, TGF-β3, BMP-4, and TIMP-2) and confirming stem cell viability in chitosan hydrogel, 15 New Zealand white rabbits underwent a lateral approach of the L1 to L4 IVDs. In each rabbit, the L2 to L3 IVD was left pristine, whereas the L1 to L2 and the L3 to L4 IVDs in each rabbit underwent nucleotomy via a 25-G needle, and the animal was subsequently randomized to no further treatment (defect only), chitosan alone, Chitosan + TGF-β3 + BMP-4, or chitosan + TGF-β3 + BMP-4 + TIMP-2. At 6 weeks after injury and intervention, the rabbits were killed and spines harvested to undergo quantitative T2 magnetic resonance imaging (MRI) and subsequent histologic analysis. Results In the in vitro analysis, cells treated with experimental media containing TGF-β3, BMP-4, and TIMP-2 exhibited staining indicative of GAG production and began to exhibit a chondrocytic morphology. Quantitative T2 MRI mapping demonstrates that discs treated with chitosan, chitosan containing TGF-β3 and BMP-4, or chitosan containing TGF-β3, BMP-4, and TIMP-2 had consistently higher T2 relaxation times compared with defect-only discs. When the T2 relaxation times of each treatment group and defect-only discs were normalized to the healthy control disc, it was found that the T2 relaxation time of discs treated with chitosan containing TGF-β3 and BMP-4 and discs treated with chitosan containing TGF-β3, BMP-4, and TIMP-2 were significantly greater compared with defect-only discs (P = .048 and P = .013, respectively). Histologically, animals that received chitosan only, or chitosan with TGF-β3 and BMP-4, showed a significantly higher intensity of Safranin-O staining (P = .016 and P = .02, respectively) compared with control discs, whereas the difference in staining intensity in animals that received chitosan loaded with TGF-β3, BMP-4, and TIMP-2 failed to achieve significance (P = .161). Conclusions A combination of chitosan, TGF-β3, and BMP-4 was effective at promoting regeneration in an acute disc injury rabbit model, whereas TIMP-2 did not have a significant effect.
Pain control for laparoscopic colectomy: an analysis of the incidence and utility of epidural analgesia compared to conventional analgesia.

The aim of this study was to compare short-term outcomes between epidural analgesia and conventional intravenous analgesia for patients undergoing laparoscopic colectomy. This paper uses a large national database to add a current perspective on trends in analgesia and the outcomes associated with two analgesia options. Our evidence augments the opinions of recent randomized controlled trials. The University HealthSystem Consortium, an alliance of more than 300 academic and affiliate institutions, was reviewed for the time period of October 2008 through September 2014. International Classification of Disease 9th Clinical Modification codes for laparoscopic colectomy and epidural catheter placement were used. A total of 29,429 patients met our criteria and underwent laparoscopic colectomy during the study period. One hundred and ten (0.374 %) patients had an epidural catheter placed for analgesia. Baseline patient demographics were similar for the epidural and conventional analgesia groups. Total charges were significantly higher in the epidural group ($52,998 vs. $39,277; p < 0.001). Median length of stay was longer in the epidural group (6 vs. 5 days; p < 0.001). There was no statistical difference between the epidural and conventional analgesia groups in death (0 vs. 0.03 %; p = 0.999), urinary tract infection (0 vs. 0.1 %; p = 0.999), ileus (11.8 vs. 13.6 %; p = 0.582), or readmission rate (9.1 vs. 9.3 %; p = 0.942). Compared to conventional analgesic techniques, epidural analgesia does not reduce the rate of postoperative ileus, and it is associated with increased cost and increased length of stay. Based on our data, routine use of epidural analgesia for laparoscopic colectomy cannot be justified.
Infrared and Raman spectra of heterocyclic compounds—III: The infrared studies and normal vibrations of 2,2'-bipyridine

Abstract The infrared spectra of 2,2'-bipyridine and 2,2'-bipyridine-d8 were obtained from 4000 to 40 cm−1. The absorption bands of these compounds were assigned by a comparison of their spectra to each other as well as to the structurally similar molecules: pyridine, 2-substituted pyridines and biphenyl. Normal Coordinate Analysis (NCA) were performed on 2,2'-bipyridine and its deutero analogue as complete twenty body problems with C2h symmetry. A Urey-Bradley Force Field (UBFF) containing a resonance potential was employed yielding the in-plane and out-of-plane force constants and vibrational descriptions for these molecules.
The Stereochemistry of bicyclo[3.2.1]octane—XVI : Allylic reactivity of bicyclo[3.2.1]octene-2; reduction with metal hydrides

Abstract The reductive debromination of exo-1-methyl-3,4-dibromobicyclo[3.2.1]octene-2 and its allylic isomer with LAH and LAD was shown to take place by an SN2′ mechanism. Moreover, it was established that the entering deuteride and leaving bromide ions were cis to each other.
Learning automata based multipath multicasting in cognitive radio networks

Cognitive radio networks (CRNs) have emerged as a promising solution to the problem of spectrum under utilization and artificial radio spectrum scarcity. The paradigm of dynamic spectrum access allows a secondary network comprising of secondary users (SUs) to coexist with a primary network comprising of licensed primary users (PUs) subject to the condition that SUs do not cause any interference to the primary network. Since it is necessary for SUs to avoid any interference to the primary network, PU activity precludes attempts of SUs to access the licensed spectrum and forces frequent channel switching for SUs. This dynamic nature of CRNs, coupled with the possibility that an SU may not share a common channel with all its neighbors, makes the task of multicast routing especially challenging. In this work, we have proposed a novel multipath on-demand multicast routing protocol for CRNs. The approach of multipath routing, although commonly used in unicast routing, has not been explored for multicasting earlier. Motivated by the fact that CRNs have highly dynamic conditions, whose parameters are often unknown, the multicast routing problem is modeled in the reinforcement learning based framework of learning automata. Simulation results demonstrate that the approach of multipath multicasting is feasible, with our proposed protocol showing a superior performance to a baseline state-of-the-art CRN multicasting protocol.
Magnetic Field Strength Measurements in Two Types of Region

We report the first measurements of interstellar magnetic fields using Zeeman splitting of the 21-cm line seen in emission, made with the Hat Creek 85-foot telescope. We have five measurements in two different types of region.
Upper mantle tomographic Vp and Vs images of the Rocky Mountains in Wyoming, Colorado and New Mexico: Evidence for a thick heterogeneous chemical lithosphere

Upper mantle tomographic body wave images from the CD-ROM deployment reveal two major lithospheric anomalies across two primary structural boundaries in the southern Rocky Mountains: a ∼200 km deep high velocity north-dipping Cheyenne slab beneath the Archean-Proterozoic Cheyenne belt, and a 100 km deep low velocity Jemez body beneath the Proterozoic-Proterozoic Jemez suture. The Cheyenne slab is most likely a slab fragment accreted against the Archean Wyoming during the Proterozoic arc collision processes. This interpretation suggests that the ancient slab's thermal signature has been diffused away and non-thermal explanations for the high velocity slab are required. Tomographic modeling of possible chemical and anisotropic velocity variations associated with the slab shows that our isotropic velocity images can be explained via non-thermal models. In addition, the de-correlation of the P- and S-velocity images and the CD-ROM shear-wave splitting modeling are consistent with a dipping slab. The Jemez body plausibly results from the combination of low-solidus materials in the suture lithosphere and the late Cenozoic regional heating of the lithosphere. The 100 km deep lithospheric layering and the uniform shear-wave splitting measurements support our contention that the Jemez body is a lithospheric anomaly. A third low velocity structure extends beneath the middle Rio Grande Rift to 300 km depth. This anomaly may manifest a thermal upwelling that could increase heat flow into the lithosphere. Our results suggest that lithospheric heterogeneities related to fossil accretionary processes have been preserved in the Precambrian sutures, and are preferentially affecting the subsequent tectonism in this region.
On the Evolutionary Pathways Resulting in C4 Photosynthesis and Crassulacean Acid Metabolism (CAM)

Publisher Summary This chapter describes C 3 –C 4 intermediate photosynthesis and crassulacean acid metabolism (CAM)-like function in an evolutionary framework that can be used to evaluate some possible paths that may have been taken during the evolution of fully-expressed C 4 photosynthesis and CAM. In the case of C 4 photosynthesis, it is proposed that the initial evolutionary stages were driven by selection for reduced photorespiration rates and the influence of such reduction on the net CO 2 assimilation rate. The assimilation of respired CO 2 during the night, with assimilation of atmospheric CO 2 during the day (known as CAM-cycling) is proposed as a precursor to the evolution of fully-expressed CAM in some species. Thus, C 4 photosynthesis and CAM may have both originated from mechanisms that improved the plant's carbon balance by assimilating internally generated CO 2 . The adaptive significance of CAM-cycling is thought to be water conservation, a role that is consistent with the adaptive significance of fully expressed CAM. CAM-cycling may have evolved from the organic-acid metabolism associated with ion uptake in plants (particularly in the guard cells of stomata), or from the organic-acid metabolism characteristic of aquatic plants.
Marketing or strategy? Defining the best approach to expand the anesthesiology workforce in Israel

There is a chronic shortage of anesthesiologists in Israel. The study by Cohen et al. suggests that a marketing campaign may be one method of addressing this shortage. This commentary argues for a more comprehensive strategy based on the US experience. This would not only involve marketing as suggested by Cohen et al. but would also involve a fundamental change in the Israel anesthesia care model, as well as providing substantial financial incentives to young physicians. We believe that a combination of these approaches will help to alleviate the shortage of anesthesia providers in Israel. Creating a new class of physician extenders, namely, anesthesiologist assistants, would also provide an employment pathway for the skilled medical technicians trained by the Israel Defense Forces, and other non-physicians with an interest in anesthesiology.
Stretched water is more reactive

Molecular vibrations can play an important role in determining the outcome of chemical reactions. In his Perspective, Schatz highlights the studies by Strazisar et al. and Zhang et al., who provide conclusive evidence for the dominant role of the hydroxl stretch in the reaction of water with atomic hydrogen. Such effects may in future be exploited to steer reagents to a favored product.
Crystal structure of the C‐terminal domain of mouse TLR9

Toll-like receptors (TLRs) are important pattern recognition receptors that function in innate immunity. Elucidating the structure and signaling mechanisms of TLR9, a sensor of foreign and endogenous DNA, is essential for understanding its key role in immunity against microbial pathogens as well as in autoimmunity. Abundant evidence suggests that the TLR9-CTD (C-terminal domain) by itself is capable of DNA binding and signaling. The crystal structure of unliganded mouse TLR9-CTD is presented. TLR9-CTD exhibits one unique feature, a cluster of stacked aromatic and arginine side chains on its concave face. Overall, its structure is most related to the TLR8-CTD, suggesting a similar mode of ligand binding and signaling.
Numerical calculation of classical bremsstrahlung

We have carried out numerical calculations for the classical bremsstrahlung spectrum, angular distribution, and polarization resulting from electrons scattering in screened atomic potentials. The calculations utilize the classical theory of electromagnetic radiation from moving charges together with the classical mechanics of energy-loss-free orbits of charged particles in such potentials. The trajectories of incident electrons in the given central potential are calculated numerically, and the doubly differential bremsstrahlung cross section is obtained by taking the Fourier transform of the acceleration of the dipole moment of the projectile and integrating the radiation over the impact parameters of the beam. Results have been obtained for several neutral atoms for electron energies from 1 eV to 500 keV, using self-consistent Dirac-Slater atomic potentials. Comparisons with quantum-mechanical partial-wave results for the spectrum show that, as in the point Coulomb case, the classical method is generally good for screened potentials for low incident electron energies. The classical method therefore can be useful in low-energy situations for which the usual Elwert-Born form-factor method is not satisfactory. We have also obtained and examined the angular distributions of classical bremsstrahlung. Screening reduces the value of the asymmetry parameter which characterizes the angular distribution of dipole radiation. The difference ofmore » screened results from the point Coulomb results increases with decreasing incident electron energy. At very low energy the value of the asymmetry parameter oscillates with energy, and this also leads to oscillations in the degree of polarization.« less
Implications of device timing variability on full chip timing

As process technologies continue to scale, the magnitude of within-die device parameter variations is expected to increase and may lead to significant timing variability. This talk presents a quantitative evaluation of how low level device timing variations impact the timing at the functional block level. We evaluate two types of timing variations: random and systematic variations. The study introduces random and systematic timing variations to several functional blocks in Intel® Core™ Duo microprocessor design database and measures the resulting timing margins. The primary conclusion of this research is that as a result of combining two probability distributions (the distribution of the random variation and the distribution of path timing margins) functional block timing margins degrade non-linearly with increasing variability
Cilia and Flagella Revealed: From Flagellar Assembly in Chlamydomonas to Human Obesity Disorders

The recent identification in Chlamydomonas of the intraflagellar transport machinery that assembles cilia and flagella has triggered a renaissance of interest in these organelles that transcends studies on their well-characterized ability to move. New studies on several fronts have revealed that the machinery for flagellar assembly/disassembly is regulated by homologs of mitotic proteins, that cilia play essential roles in sensory transduction, and that mutations in cilia/basal body proteins are responsible for cilia-related human disorders from polycystic kidney disease to a syndrome associated with obesity, hypertension, and diabetes.
Three-dimensional target recognition via sonar: a neural network model

A neural network was trained to recognize two three-dimensional shapes independent of orientation, based on echoes of ultrasonic pulses similar to those used by an echolocating bat, Eptesicus fuscus. Following supervised learning, the network was required to generalize and recognize echoes from the shapes at novel orientations. The representation of the echo was manipulated to explore how information about target shape may be encoded in sonar echoes. Three types of input representations were used: time domain (waveform and cross-correlation), frequency domain (power spectrum), and time frequency (spectrogram). The probability of correctly recognizing the novel echoes by chance was only 25%. The network using the spectrogram representation recognized 90% of the echoes from novel orientations. The bat Eptesicus fuscus uses a multiple echolocation cry, and we explored the relative contribution of low and high frequencies for carrying information about target shape. We presented the network with low-pass and high-pass filtered spectrogram representations, preserving sound energy in frequency bands roughly corresponding to either the first or the second harmonic of the bat's echolocation sounds. The network was able to recognize 90% and 95% of the novel echoes using only the first or only the second harmonic, respectively. We continued by examining whether the network could perform the task using only time domain or only frequency domain information. When presented with a time waveform representation, the network was unable to perform the task. Similar results were obtained with other time domain representations, the cross-correlations between the emitted sound and its returning echo. However, when using only frequency domain information, the network was able to recognize 70% of the echoes from novel orientations. Again, we explored the relative contribution of the frequency bands corresponding to the first and second harmonics used by the bat Eptesicus fuscus. We found that the network was able to recognize 70% of the novel echoes using the first harmonic, and only 55 % of the novel echoes using the second harmonic. The results are discussed in light of studies on echolocation of bats and models of sonar processing.
Receptor crosstalk: Communication through cell signaling pathways

The response of cells to extracellular stimuli is mediated in part by a number of intracellular signal transduction pathways. The frequent lack of a one-to-one correlation between receptor activation and intracellular responses, such as predictable nuclear transcription events, is perplexing. This lack of correlation, however, suggests that various signaling pathways intersect and crosstalk to modify and influence the biological outcome of a specific extracellular signal. In this review, the basic pathways and aspects of signal transduction are laid out, and known sites of crosstalk are discussed. A clearer understanding of receptor and cell signaling pathways and levels of crosstalk should provide insight into the paradoxes that underlie both imprecision and predictability in signal transduction.
Evoked potential and behavioral outcomes for experimental autoimmune encephalomyelitis in Lewis rats

A reliable outcome measurement is needed to assess the effects of experimental lesions in the rat spinal cord as well as to assess the benefits of therapies designed to modulate them. The Basso, Beattie, and Bresnahan (BBB) behavioral scores can be indicative of the functionality in motor pathways. However, since lesions are often induced in the more accessible dorsal parts associated with the sensory pathways, the BBB scores may not be ideal measure of the disability. We propose somatosensory evoked potential (SEP) as a complementary measure to assess the integrity of sensory pathways. We used the focal experimental autoimmune encephalomyelitis (EAE) model, in which focal demyelinating lesions were induced by injecting cytokine-ethidium bromide into dorsal white matter after MOG-IFA immunization. Both the SEP and BBB measures reflected injury; however, the SEP was uniformly and consistently altered after the injury whereas the BBB varied widely. The results suggest that the SEP measures are more sensitive and reliable markers of focal spinal cord demyelination compared to the behavioral measures like the BBB score.
Scintillation Process in CsI(Tl). II. Emission Spectra and the Possible Role of Self-Trapped Holes

The luminescence emission spectra of CsI(Tl) crystals containing varying amounts of Tl have been measured upon excitation by gamma rays, protons, and alphas. The principal features include a broad Tl emission band centered near 5500 \AA{} and a narrower band centered near 3300 \AA{} which is characteristic of the host crystal. This 3300-\AA{} band is analogous to near-ultraviolet emission bands observed in NaI and KI. It is found for CsI(Tl) that the intensity of the 3300-\AA{} band relative to the Tl band is greatest upon excitation by radiation of high $\frac{\mathrm{dE}}{\mathrm{dx}}$. It is suggested that the 3300-\AA{} band arises from the recombination of free electrons with self-trapped holes. Evidence from other investigations supporting this hypothesis is summarized.
Endometrial carcinoma presenting with ascites

Three examples of endometrial carcinoma presenting with ascites are reported. The patients were in the eighth decade, had no vaginal bleeding, and were considered to have ovarian cancer preoperatively. Laparotomy revealed gross omental tumor and normal appearing ovaries. The endometrial cancers were grossly undetected and were uniformly noninvasive of the myometrium. They projected into the uterine cavity, two in polyps, and one covering a submucous leiomyoma. The fallopian tubes were the most likely route of spread to the abdominal cavity.
Inhibitors of β-Site Amyloid Precursor Protein Cleaving Enzyme (BACE1): Identification of (S)-7-(2-Fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (AMG-8718)

We have previously shown that the aminooxazoline xanthene scaffold can generate potent and orally efficacious BACE1 inhibitors although certain of these compounds exhibited potential hERG liabilities. In this article, we describe 4-aza substitution on the xanthene core as a means to increase BACE1 potency while reducing hERG binding affinity. Further optimization of the P3 and P2′ side chains resulted in the identification of 42 (AMG-8718), a compound with a balanced profile of BACE1 potency, hERG binding affinity, and Pgp recognition. This compound produced robust and sustained reductions of CSF and brain Aβ levels in a rat pharmacodynamic model and exhibited significantly reduced potential for QTc elongation in a cardiovascular safety model.
Distribution of soluble proteins within spinal motoneurons: a quantitative two-dimensional electrophoretic analysis.

: Soluble protein fractions obtained from bovine lumbar spinal motoneuron cell bodies, ventral gray matter, and ventral and dorsal roots were analyzed by two-dimensional gel electrophoresis. Each extract was separated into Coomassie blue-stained patterns of up to 350 polypeptides ranging in isoelectric point from pH 4 to 8 and in molecular weight from 10,000 to 200,000. Visual inspection of the protein pattern of the isolated cell bodies showed it to be substantially different from those of ventral gray matter and the spinal roots, while the patterns obtained from ventral and dorsal roots were indistinguishable. Computer-assisted densitometry of the major soluble proteins from spinal roots showed no quantitative difference between the predominant proteins in ventral and dorsal root extracts. Differences of 10-fold or more were common when the major proteins of the isolated perikarya were compared with those of the other fractions. Since most of the soluble proteins extracted from ventral and dorsal roots were probably derived from the axoplasm of motor and sensory nerves, respectively, these results are interpreted to mean that large differences exist in the distribution of individual soluble proteins between the cell body and axon of spinal motoneurons, while the major soluble proteins of spinal motor and sensory axons are highly similar.
Structure and tectonic history of the Eastern Panama basin

New marine geophysical data allow the preparation of revised bathymetric and magnetic anomaly charts of the Panama Basin and demonstrate that the eastern part of the basin, between the fracture zone at long 83°W and the Colombian continental margin, was formed by highly asymmetric sea-floor spreading along the boundary of the Nazca and Cocos plates 27 to 8 m.y. B.P. Lineated magnetic anomalies recording this history are oriented approximately east-west. The oldest set of north-flank anomalies overlaps in age with those adjacent to the Grijalva scarp, south of the western Panama Basin, where they are oriented 065°. Younger anomalies (5C to 5) in the eastern basin are approximately parallel to anomalies of this age identified on the Carnegie platform and the flanks of the Costa Rica rift. The eastern basin now contains a pattern of fossil spreading centers (including the Malpelo rift) and transform faults (including the Yaquina graben) that were abandoned 8 m.y. B.P. by a shift in plate boundaries that transferred a large section of the Cocos plate to the Nazca plate. Cessation of Nazca-Cocos spreading east of long 83°W was heralded by a 3-m.y. deceleration of spreading on the eastern segments, which created rough topography and axial rift valleys typical of slow-spreading ridges. Westward jumping of the Nazca-Cocos-Caribbean triple junction rejuvenated the northern segment of the fracture zone at long 83°W, causing uplift of the adjacent Coiba Ridge. Recently, active transform faulting has jumped farther west, from the foot of the Coiba Ridge to the Panama fracture zone. Apart from changes in plate boundaries, the main event in the tectonic evolution of the region was initiation about 22 to 20 m.y. B.P. of the hot spot that created the Malpelo, Cocos, and Carnegie Ridges. Precursors of effusive ridge-building volcanism included major fracturing of the oceanic crust to the north of the present Malpelo Ridge. Both processes hamper identification of magnetic anomalies in the vicinity of the ridges. Our interpretation of the tectonic history is also incomplete in the easternmost parts of the basin, where data are insufficient; this impairs our interpretation of the adjacent continental geology in terms of changing interaction between oceanic and continental plates. The geologic history of the Isthmus of Panama is compatible with our application of the plate-tectonic model.
Replicating adenovirus vector prime/protein boost strategies for HIV vaccine development.

Background: In recent years the HIV vaccine field introduced a number of promising vaccine candidates into human clinical trials. Objective: To briefly discuss the advances made in vaccine development and HIV pathogenesis and give an overview of the body of work our lab has generated in multiple animal models on replication-competent Adenovirus recombinant vaccines. Methods: Emphasis is placed on comparative examination of vaccine components, routes of immunization and challenge models using replicating Adenovirus vectors. Results/conclusion: The findings make the case that replicating Adenovirus vectors are superior in priming multiple arms of the immune system, and in conjunction with protein boosting, have resulted in dramatic protective efficacy leading to their advancement to Phase I trials. Implications of the recent halting of the Merck Ad5-HIV Phase IIb clinical trial of our vaccine approach and other vectored vaccines are discussed.
Physics of protein–DNA interactions: mechanisms of facilitated target search

One of the most critical aspects of protein–DNA interactions is the ability of protein molecules to quickly find and recognize specific target sequences on DNA. Experimental measurements indicate that the corresponding association rates to few specific sites among large number of non-specific sites are typically large. For some proteins they might be even larger than maximal allowed three-dimensional diffusion rates. Although significant progress in understanding protein search and recognition of targets on DNA has been achieved, detailed mechanisms of these processes are still strongly debated. Here we present a critical review of current theoretical approaches and some experimental observations in this area. Specifically, the role of lowering dimensionality, non-specific interactions, diffusion along the DNA molecules, protein and target sites concentrations, and electrostatic effects are critically analyzed. Possible future directions and outstanding problems are also presented and discussed.
Formation of IIAB iron meteorites

Abstract Group IIAB is the third largest group of iron meteorites and the second largest group that formed by fractional crystallization; many of these irons formed from the P-rich portion of a magma consisting of two-immiscible liquids. We report neutron-activation data for 78 IIAB irons. These confirm earlier studies showing that the group has the largest known range in Ir concentrations (a factor of 4000) and that slopes are steeply negative on plots of Ir vs. Au or As (or Ni). High negative slopes imply relatively high distribution coefficients for Ir, Au, and As (but, with rare exceptions, remaining less than unity for the latter). IIAB appears to have had the highest S contents of any magmatic group of iron meteorites, consistent with its high contents of other volatile siderophiles, particularly Ga and Ge. Large fractions of trapped melt were present in the IIAB irons with the highest Au and As and lowest Ir contents. As a result, when these irons crystallized, the DAu and DAs values can, with moderate accuracy, be estimated to have been roughly 0.53 and 0.46, respectively. These low values imply that the initial nonmetal (S + P) content of the magma was much lower than 170 mg/g, as estimated in earlier studies; our estimate is 75 mg/g. Our results are consistent with an initial P/S ratio of 0.25, similar to the ratio estimated for other magmatic groups. There is little doubt that incompatible S-rich and P-rich metallic liquids were involved during the formation of group IIAB. After 20% crystallization of our assumed starting composition the two-liquid boundary is encountered (at 72 mg/g S and 18 mg/g P). Initially the volume of S-rich liquid is very small, but continued crystallization increased the volume of this phase and decreased its P/S ratio while increasing this ratio in the P-rich liquid. Most crystallization of the IIAB magma would have occurred in the lower, P-rich portion of the core. However, metal was still a liquidus phase at the top of the core and, because both the immiscible liquids would have convected, they may have approached equilibrium throughout the very limited crystallization of the magma recorded in group IIAB. All IIAB irons contain trapped melt, and this melt will have had very different compositions depending on whether the liquid is S-rich (at the outer solid/liquid interface) or P-rich (at the inner interface). The P/S ratio in the melt trapped in the Santa Luzia iron is about 0.6 g/g, consistent with our modeling of Ir–Au and Ir–As trends implying that Santa Luzia formed in the lower, P-rich portion of the core after about 48% crystallization of the magma. Because the liquids were in equilibrium, the point at which immiscibility first occurred is not recorded by a dramatic change in the trends on element–Au diagrams; the main compositional effect is recorded in the P/S ratio of the trapped melt. The high-Au (>0.8 μg/g) irons for which large sections are available all contain skeletal schreibersite implying a relatively high (>0.3 g/g) P/S ratio; none of these irons could have crystallized from the S-rich upper layer of the core.
An optically-pumped rubidium 87 magnetometer for offshore magnetic surveys

An optically pumped rubidium 87 vapor magnetometer is described which measures the earth's magnetic field to one part in 3frac{1}{2} million. The sensitivity is about .01 gamma in the earth's field of 52,000 \lambda (0.52 oersteds). Rubidium 87 is preferred to rubidium 85 because the nuclear spin is 3/2 rather than 5/2. Thus the magnetometer described can "lock on" to a single hyperfine absorption line and not show orientation effects common in self-oscillating rubidium 85 magnetometers. Two magnetometers are used in offshore surveys, one fixed and one towed behind a vessel. The record of the fixed stations is subtracted from the moving station record thereby eliminating the time variations of H. Space variations are interpreted in terms of subsurface structures. In particular, negative magnetic anomalies may indicate salt domes usually having oil around their perimeters.
Stimulation of Uridine, Leucine, and Sulfate Incorporation into Rat Cartilage Macromolecules by Adenosine 3′,5′-Monophosphate*

Conflicting findings on the ability of cAMP analogs or phophodiesterase inhibitors to stimulate precursor incorporation into macromolecules of rat cartilage have been reported. Therefore, the effects of these compounds on the incorporation of uridine into RNA, leucine into proteins, and sulfate into proteoglycans have been reexamined in cartilage from normal and hypophysectomized rats. When cartilage was incubated for 24 h in a medium with the test agents and then pulsed for 2 h in the basal medium containing labeled precursors, both monobutyryl cAMP (BucAMP) and methylisobutylxanthine (MIX) enhanced the ability of the tissue to incorporate precursors into macromolecules. The effect of BucAMP was significant in most cases at a concentration of 30 microM, optimal at concentrations of 100-300 microM, and diminished at a concentration of 1000 microM. Similar stimulation was produced by dibutyrul cAMP [(Bu)2cAMP] or 8-dimethylamino cAMP, but monobutyryl cGMP was ineffective. MIX in a concentration of 20 microM increased precursor incorporation in most cases, and a concentration of 100 microM was optimal; at a concentration of 500 microM, MIX had no significant effect on leucine or sulfate incorporation. When cartilage from hypophysectomized rats was incubated in a medium with the test agents for 4-6 h and the labeled precursors were added for the last 2 h, BucAMP did not increase incorporation of any of the precursors. MIX was also ineffective, even though tissue cAMP levels were increased. However, precursor incorporation was increased by exposure to partially purified rat somatomedin for the same periods. The degree of stimulation of sulfate incorporation induced by either BucAMP or MIX was proportional to the time of exposure to these agents. Preincubation of cartilage in basal medium alone for 22 h or longer increased basal sulfate incorporation, but caused only a slight enhancement of the action of BucAMP. The addition of synthetic bovine PTH-(1-34) (1 microM) to the incubation medium increased sulfate incorporation into hypophysectomized rat cartilage by 24 h, and this effect was potentiated by MIX (10 microM). No stimulation was detectable by 6 h, even with MIX in the medium. PTH-(1-34) increased the cartilage cAMP level, and this effect was also potentiated by MIX. In the presence of MIX, PTH-(1-34) increased the level of cAMP within 30 min, while the rat somatomedin preparation had no effect on the cAMP level during 60 min of incubation. The level of cartilage cGMP was not raised by either PTH or somatomedin.(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of Electromagnetic Parameters on the Process of Low Frequency Electromagnetic Hot-Top Casting of Aluminium Alloy

During the low frequency electromagnetic casting process, the electromagnetic parameter plays an important role among the casting parameters. In this work, effects of electromagnetic parameters on the electromagnetic field and body force are analyzed by constructing a two-dimensional finite element model and using ANSYS software which is a kind of commercial FEM analysis software. The results show that the current frequency mainly influences the distribution of electromagnetic body force, the current intensity determines the intensity of electromagnetic body force, and the current frequency and intensity should be matched during the low frequency electromagnetic casting process.
Dramatic beach and nearshore morphological changes due to extreme flooding at a wave-dominated river mouth

Abstract Record flooding on the Santa Clara River of California (USA) during January 2005 injected ∼ 5 million m3 of littoral-grade sediment into the Santa Barbara Littoral Cell, approximately an order of magnitude more than both the average annual river loads and the average annual alongshore littoral transport in this portion of the cell. This event appears to be the largest sediment transport event on record for a Southern California river. Over 170 m of local shoreline (mean high water (MHW)) progradation was observed as a result of the flood, followed by 3 years of rapid local shoreline recession. During this post-flood stage, linear regression-determined shoreline change rates are up to −45 m a− 1 on the subaerial beach (MHW) and − 114 m a− 1 on the submarine delta (6 m isobath). Starting approximately 1 km downdrift of the river mouth, shoreline progradation persisted throughout the 3-year post-flood monitoring period, with rates up to + 19 m a− 1. Post-flood bathymetric surveys show nearshore (0 to 12 m depth) erosion on the delta exceeding 400 m3/m a− 1, more than an order of magnitude higher than mean seasonal cross-shore sediment transport rates in the region. Changes were not constant with depth, however; sediment accumulation and subsequent erosion on the delta were greatest at − 5 to − 8 m, and accretion in downdrift areas was greatest above –2 m. Thus, this research shows that the topographic bulge (or “wave”) of sediment exhibited both advective and diffusive changes with time, although there were significant variations in the rates of change with depth. The advection and diffusion of the shoreline position was adequately reproduced with a simple “one line” model, although these modeling techniques miss the important cross-shore variations observed in this area. This study illustrates the importance of understanding low-frequency, high volume coastal discharge events for understanding short- and long-term sediment supply, littoral transport, and beach and nearshore evolution in coastal systems adjacent to river mouths.
On the bimodal grain growth in zirconium grade 702 alloy

Abstract This study is built upon previously published work that involved bimodal grain growth in cold worked and annealed samples of zirconium 702 alloy. Similar to the earlier study, the new zirconium 702 alloy samples were rolled and bent at different percentages of cold work and then annealed at 1375 °F. While bimodal grain growth did occur in the previous samples under bending when annealed above 1275 °F, no bimodal grain growth was observed in any of the new samples. This result is attributed to the different weight percent of alloying elements in the two samples. Additionally, a recovery anneal was performed on the old samples in an effort to inhibit grain growth in the alloy system. Although the recovery anneal did not prevent bimodal grain growth, it did significantly reduce the degree to which it occurred.
Decreased Secretion and Unfolded Protein Response Up-Regulation Are Correlated With Intracellular Retention for Single-Chain Antibody Variants Produced in Yeast

Heterologous protein expression can easily overwhelm a cell's capacity to properly fold protein, initiating the unfolded protein response (UPR), and resulting in a loss of protein expression. In the current model of the unfolded protein response, the chaperone BiP modulates the activation of the UPR due to its interactions with the signaling protein Ire1p and newly synthesized proteins. In this research, 4−4−20 scFv variants were generated by rational design to alter BiP binding to newly synthesized scFv proteins or via directed evolution aimed at improved secretion. Interestingly, the predicted BiP binding ability did not correlate significantly with the unfolded protein response. However, pulse-chase analysis of scFv fate revealed that mutants with a decreased ER residence time were more highly secreted, indicating that improved protein folding was more likely the cause for improved secretion. In fact, decreased secretion correlated with increased binding by BiP, as determined by co-immune precipitation studies. This suggests that the algorithm is not useful for in vivo prediction of variants, and that in vivo screens are more effective for finding variants with improved properties.
The critique of Heideggerian hermeneutical nursing research

The critique of Heideggerian hermeneutical nursing research Within the past decade, over 25 research reports claiming to be based on Heideggerian interpretive phenomenology have been published in the nursing literature. This article reviews this research focusing on two critical issues. First, do the reports reflect a convergence of researcher understanding and participant narratives as called for by the Heideggerian tradition? Second, do Heideggerian ideas inform and enrich the studies’ findings? The review reveals wide variations with regard to how these two issues are reflected in published reports. The author recommends that Heideggerian nurse researchers (a) seek to create a new narrative literature that allows for flexible and creative presentation of interpretive findings, while demanding adherence to sound interpretive scholarship, and (b) strengthen their partnerships with philosophers and other scholars so that ideas from Heideggerian interpretive phenomenology and other sources can not only guide their methods, but enrich their findings.
The influence of substrate compensation on inter-electrode leakage and back-gating in GaAs MESFETs

Substrate leakage between electrodes and back-gating are two major non-idealities which affect device and circuit performance in GaAs integrated circuits fabricated on semi-insulating substrates. Simple analytical models and simulation results are presented to elucidate the roles of substrate compensation type, carrier densities and trap parameters in the manifestation of these effects. Chrome-doped substrates exhibit long-range negative-bias back-gating because the bias is supported across the channel-substrate junction. Undoped LEC substrates are insensitive to long-range back-gating in either direction unless holes are introduced (e.g. by radiation) or fast transients are present. Above the onset voltage for TFL conduction, both substrates exhibit strong back-gating. While p-wells tied to a voltage source reduce back-gating, floating p-wells or wells shallower than the device n+ implants can significantly worsen back-gating.
Two Cities, Five Industries: Similarities and Differences within and between Cultural Industries in New York and Los Angeles:

Recent work has pointed towards the possibility that industries are not tied to their specific urban location as much as to their linkages with particular types of infrastructure and to their socia...