cssi/SciSciGPT-SciSciNet huggingface dataset:
AML-399: A Pan-BET Degrader Shows Broad Pre-Clinical Activity in a Large Acute Myeloid Leukemia Cohort

Bromodomain and Extra Terminal (BET) proteins are ubiquitously expressed epigenetic “readers” that play a major role in regulating expression of oncogenic genes such as c-Myc. BET protein family are crucial for acute myeloid leukemia (AML) maintenance, and expression of BRD4 is a poor prognostic indicator in AML. We have developed novel and a highly potent proteolysis-targeting, chimera (PROTAC)-based pan-BET degrader, QCA570, that depletes BET. This BET-degrader is derived from a new class of inhibitor, HYD276. We tested QCA570 in a panel of 104 primary AML samples in ex-vivo cultures. Leukemia stem cells (LSCs) were enriched by positive selection with CD34 antibody. Cells were plated in LSC conducive medium containing growth factors and drugs for 72 hrs, and cell death and apoptosis induction was measured by flow cytometry for DAPI-Annexin V binding. Primary AML cells were obtained from newly diagnosed AML (N=89) or relapse/refractory AML (N=15). The median IC50 for BET-degrader was 120 pM, and only 13 samples had an IC50 >1 nM. In contrast, the median IC50 for the inhibitor HYD276 was 30,000 fold higher at 3.5 μM. An IC50 of greater than 10 μM HYD276 was considered as resistant to the BET inhibitor. BET inhibitor-resistant LSCs were found to be sensitive to the degrader QCA570, irrespective of mutation status and chromosomal aberrations, suggesting that there are additional mechanisms of action of the degrader as compared to the inhibitor. The AML cells were heterogeneous for the expression of mutant FLT-3 (36%), NPM1 (22%), IDH1/2 (16%), CEBP-alpha (2%), DNMT3A (2%), and other mutations (10%). Based on classical karyotype, 30% of them had a normal karyotype, and 55% had abnormal karyotype. The degradation of BRD4 and repression of c-MYC was confirmed by immunoblotting after a 4-hr exposure of LSCs to the degrader. Moreover, treatment of normal CD34-positive hematopoietic cells in an apoptosis assay and colony formation assays suggests lack of toxicity to normal hematopoiesis. Evaluation of this new class of drugs in patient-derived xenografts is ongoing. In conclusion, QCA570 represents a highly potent and efficacious pan-BET-BRD degrader undergoing extensive pre-clinical evaluation for the treatment of acute leukemias.
Clinical course of venous thromboembolism following abdominally based microsurgical breast reconstruction: A case series

Summary Background Venous thromboembolism (VTE) is a potentially devastating complication following abdominally based microsurgical breast reconstruction, with a reported incidence of 0.08–4%. The authors aim to describe disease presentation and clinical course following VTE diagnosis in patients within their practice. Methods A retrospective chart review identified patients who underwent microsurgical breast reconstruction from January 2007 through December 2018. Patients with VTE diagnosed within 90 days of surgery were included. Demographics, co-morbidities, signs and symptoms, and characteristics of oncologic, surgical, and post-operative care were analyzed. Results Seven hundred one patients underwent microsurgical breast reconstruction. Eleven patients with pulmonary embolism (PE) and four with deep vein thrombosis (DVT) were identified, resulting in VTE incidence of 2.1% (0.57% DVT, 1.6% PE). Patients were on average 51 years old and had an average body mass index (BMI) of 31.7 kg/m2. Two had a history of VTE, and none had a known hypercoagulable disorder. Using the 2005 Caprini model, all were high risk and seven were highest risk. Among those with PE, the most common symptom was shortness of breath, and the most common signs were desaturation or supplemental oxygen requirements. VTE was diagnosed on average 14.2 days post-operatively (range 2–52 days). Conclusion VTE is an infrequent complication following abdominally based microsurgical breast reconstruction. We recommend a high index of suspicion in women reporting shortness of breath or having desaturation, especially in those with high BMI, high Caprini scores, post-operative complications, or early return to the operating room.
Scope of practice boundary violation in occupational therapy: An online survey of practitioners' perceptions in India

Background: Occupational therapy (OT) practice in India is yet to be regulated at the national level. This presents a significant challenge to the OT community in India as it would be difficult for them to defend themselves if other professionals violate the scope of practice (SOP) boundaries. Objectives: The aim is to explore the views of occupational therapists (OTs) related to the issue of SOP boundary violation in OT practice in India. Study Design: An online survey research design was chosen to conduct this study. A 10-item electronic survey (9 with response options and one open ended) was developed based on the research question. Methods: An online survey link generated through SurveyMonkey was E-mailed to 760 OTs in India, identified through convenient sampling. The survey link was also shared on four WhatsApp Messenger groups (TNAIOTA Official Group, OTist Group, Clinic OT, and IPOTPDG1) with many Indian OTs (snowball sampling). Data were collected from January 29, to February 29, 2020. Results: The number of responses received was 126. One hundred and nine (87%) respondents believed that other professionals encroach OT's SOP boundaries knowingly or unknowingly. This belief is strong among all OTs across the nation, regardless of gender and practice experience. Conclusions: Many OTs in India believe that individuals belonging to other professions step into the domain of OT knowingly or unknowingly. Enacting an OT practice legislation, establishing a regulatory body at the national level and increasing them at state levels, endorsing an official SOP document, educating stakeholders, and engaging in awareness promotion initiatives would help mitigate the issue to a great extent. Ongoing and strategic efforts by the OT community in India are warranted.
Capturing the Experiences and Challenges of Emerging Adults in College During the COVID-19 Pandemic.

Emerging adulthood (ages 18-30 years) coincides with "aging out" of pediatric care. As a result, combined internal medicine and pediatrics (Med-Peds) providers are tasked with promoting the health and well-being of this population during and post-coronavirus disease 2019 (COVID-19). In order to inform the response efforts, we aimed to capture emerging adults' COVID-19 experiences and challenges during a two-week period of the pandemic in June 2020. We administered items from the California Health Interview Survey and an open-ended qualitative item via Qualtrics to 242 diverse emerging adults enrolled in a large US public university (mean age = 20.10, SD = 1.26). More than 90% of all students reported that they or their families or close friends experienced difficulties coping with the stressors and challenges presented by COVID-19. Almost half experienced financial difficulties and more than three-fourths experienced household disruptions during the pandemic. Qualitative findings underscored that these challenges were compounded by mental health and broader social issues. Recommendations for Med-Peds providers are provided to promote emerging adulthood health during and post-pandemic.
USE OF FLOATING SOLAR COLLECTORS IN PROCESSING ICEBERG WATER

Presented at First International Conference and Workshops on Iceberg Utilization for Fresh Water Production, Weather Modification and Other Applications, Iowa State University, Ames, Iowa, October 2-6, 1977.
Evidence for One Leucyl Transfer Ribonucleic Acid Synthetase with Specificity for Leucine Transfer Ribonucleic Acids with Different Coding Characteristics

Abstract Leucyl transfer ribonucleic acid synthetase (EC 6.1.1.4, l-leucine:tRNA ligase (AMP)) has been purified from Escherichia coli and is free of other aminoacyl-tRNA synthetases, tRNA-methylating enzymes, and CpCpA-adding enzymes. Several criteria suggest that there is one synthetase with specificity for two forms of leucine-specific tRNA which can be separated by countercurrent distribution:purification studies, the mixed substrate method, and, most conclusively, an enzyme-dependent leucine exchange from countercurrent distribution fractions tRNAileu to tRNAiileu. Leucine exchange from tRNAileu to tRNAiileu occurs in the presence of AMP, magnesium chloride, 12C-leucine, and synthetase. This exchange can best be explained by an AMP-dependent reaction in which leucine is transferred from one kind of tRNA molecule to the other through a leucyl-adenylate-synthetase complex. This exchange implies the existence of a single leucyl-tRNA synthetase which acylates the multiple forms of leucine-tRNA in E. coli.
BACTERIAL DISSIMILATION OF l-FUCOSE AND l-RHAMNOSE

Eagon, R. G. (University of Georgia, Athens). Bacterial dissimilation of l-fucose and l-rhamnose. J. Bacteriol. 82:548-550. 1961.-Of 33 microorganisms screened for the ability to utilize the methylpentoses, l-fucose and l-rhamnose, 18 species utilized one or both methylpentoses. The majority of the bacterial species capable of utilizing these methylpentoses did so by isomerization of the methylpentoses to the corresponding ketoses followed by phosphorylation of the ketoses. However, the existence of a second pathway is suggested by results obtained from Sarcina lutea, Bacillus megaterium, Gaffkya tetragena, and Rhizobium leguminosarum.
Polarization-strain coupling in the mixed ferroelectric KTa1-xNbxO3.

The peculiar polar properties of ${\mathrm{KTa}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{Nb}}_{\mathit{x}}$${\mathrm{O}}_{3}$ (KTN) are determined by the presence of electric dipoles associated with randomly distributed Nb off-center ions. Because the latter also possess an elastic quadrupole, they should permit a coupling between electric polarization and strain. In order to investigate this coupling, we have carried out an ultrasonic study of KTN for different Nb concentrations. The elastic constants ${\mathit{C}}_{11}$ and ${\mathit{C}}_{44}$ and the corresponding attenuations have been measured in the presence of dc bias electric fields of varying strengths. These fields were also applied in different directions relative to the acoustic polarization of the ultrasonic waves. The present ultrasonic results confirm the formation of polar nanoregions at ${\mathit{T}}^{\mathrm{*}}$\ensuremath{\simeq}${\mathit{T}}_{\mathit{c}}$+20 K, marking the transition to a strong-coupling regime. They can be described by a microscopic model in which the primary polarization fluctuations are associated with the collective reorientations of the Nb off-center ions within a polar nanoregion. These fluctuations and their coupling to the sound waves can be enhanced or depressed by a dc bias electric field. An ${\mathit{E}}^{2}$ dependence of the elastic constant indicates the electrostrictive nature of the coupling.
Smart Skins: Could they be the ultimate sensing tool? Today\uFFFDs industry and personal medical care both strongly demand accurate, reliable, robust, lo

Today’s industry and personal medical care both strongly demand accurate, reliable, robust, low-power, and low-cost methods to sense changes in the environment and the condition of the body. This is where the concept of smart skin comes in. Smart skins can monitor changes in environmental parameters, such as temperature, strain, and the presence of ambient gas, and communicate. The smart skin concept can also be extended to that of wearable electronic devices for continuous monitoring and reporting of critical biosignals. There are a lot of challenges for the state of the art of smart skin, such as expensive fabrication methods, a lack of flexibility and mobility, and the large area fabrication method.
Protein kinase C-dependent prostaglandin production mediates angiotensin II-induced atrial-natriuretic peptide release

The respective roles of protein kinase C (PKC) and endogenous prostaglandin formation in angiotensin II (Ang II)-induced myocardial secretion of atrial natriuretic peptide (ANP) was studied in cultured, spontaneously beating, neonatal-rat cardiomyocytes. Incubation of cardiomyocytes with 0.1 microM Ang II led to a rapid but transient increase in particulate-bound PKC activity, a response accompanied by marked increases in cellular 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) generation and ANP secretion. A role for PKC in Ang II-induced 6-oxo-PGF1 alpha formation and ANP secretion was apparent, insofar as both responses were suppressed in the presence of the PKC inhibitors staurosporine (1 microM) and CGP 41251 (1 microM), as well as in cells in which PKC had been previously down-regulated by pretreatment with phorbol diester. Furthermore, Ang II-induced 6-oxo-PGF1 alpha production was found to be strongly correlated with Ang II-induced ANP release (r = 0.87, P < 0.001, n = 6), indicating a role for prostacyclin (PGI2) in Ang II-induced ANP secretion in these cells. This hypothesis was confirmed by finding that both Ang II-induced 6-oxo-PGF1 alpha production and ANP release were abolished in the presence of the respective phospholipase A2 and cyclo-oxygenase inhibitors quinacrine (10 microM) and indomethacin (10 microM), whereas exogenously applied PGI2 (1 microM) and prostaglandin E2 (0.1 microM) mimicked Ang II-induced ANP secretion in this system. Taken together, these results suggest that Ang II induces ANP secretion in spontaneously beating rat cardiomyocytes via a PKC-dependent autocrine pathway involving a cyclo-oxygenase product and a yet-to-be-identified myocardial prostanoid receptor.
Experimental and Numerical Studies of Cold Inflow at the Exit of Buoyant Channel Flows

Experimental and numerical studies of the separation of a smooth attached buoyant flow from the inner wall of a duct, as the duct discharges into a quiescent environment, are reported. The associated penetration of neutrally buoyant ambient fluid into the duct is called cold inflow. The experimental study was carried out for air flows over ranges of Reynolds and Froude numbers, based on duct radius, of Re = 2,400 to 3,300 and Fr = 0.68 to 2.69. The experiments provide information on the onset and extent of cold inflow in a turbulent flow regime. Spatial profiles of fluctuating temperature reveal a wedge-shaped cold inflow region at the wall near the exit when Fr is decreased below a critical value. The numerical study examines the influence of Re and Fr on the structure of the cold inflow phenomenon at moderate Reynolds numbers (Re = 200 to 500 and Fr = 1 to 5). Steady-state, two-dimensional, laminar flow solutions reveal a region of downward-flowing cold air near the wall of the duct which leads to premature separation of the wall boundary layer. The separated boundary layer merges into the buoyant jet above the duct exit.
Bioavailability of Components of Resin-Based Materials Which Are Applied To Teeth

Chemical components of many materials used in dental practice can move into the local biophase, where they can have beneficial or adverse effects. The strongest indirect evidence that components of resin-based materials used in dentistry can move into the biophase are the many reports of allergic dermatitis in dental personnel. Direct measurement of component release has shown that triethylene glycol dimethacrylate (TEGDMA), hydroxyethyl methacrylate (HEMA), and, in the case of some orthodontic cements, bis-glycidyl methacrylate and benzoyl peroxide can move into an aqueous medium from a range of resin-based materials which are applied to teeth as part of oral care. In the case of resin composite restorations, HEMA and TEGDMA are available in microgram quantities via the salivary surface in the minutes and hours after clinical placement and via dentin and pulp in the hours and days after placement. Fortunately, moderate thickness of dentin protects pulp tissue against local toxicity. There are no data whi...
Photophysics of Reduced Silicon Tetraphenylporphyrin

The contrasting photophysical properties of two silicon (IV) tetraphenylporphyrins, Si(TPP)(py)2 and Si(TPP)Cl2, have been investigated using static absorption and fluorescence spectroscopy and ultrafast transient absorption measurements. The parent Si(TPP)Cl2, in which the porphyrin macrocycle has its normal 2− oxidation state, has a fluorescence yield of 0.027, and a lifetime of 1.8 ns for the lowest excited singlet state. In marked contrast, the reduced, anti-aromatic complex Si(TPP)(py)2, with the macrocycle in the 4− oxidation state, has an extremely low fluorescence yield (≤0.0004) and a 750-fold shorter excited-state lifetime (2.4 ps) in the same solvent (pyridine). The rapid deactivation of photoexcited Si(TPP)(py)2 to the ground state is likely associated with its ruffled structure and the presence of low-energy excited states in its electronic manifold.
in-law relationships in the American kinship system: the impact of divorce and remarriage

This paper reports on the impact marital changes are having on American middle-class kinship systems. Using concepts and theories long used in other cultural contexts, the analysis will focus on the cultural domain, the definitions and meanings of kinship, and how these change with the restructuring of the family following marital changes. The analysis illustrates that the American kinship system is mutable and flexible as its members accommodate to the realities of marital change. The findings suggest that this flexibility is delimited, however, because the key issue in family and kinship reorganization following divorce centers on access to the children of divorce. To retain a connection to these children, individuals redefine relationships and initiate strategies by which they navigate through a complex network of relatives by blood, marriage and divorce. The analysis focuses on the grandparents and their roles in these emerging kinship systems, because grandparents are at particular risk of having their access to grandchildren blocked when their children divorce. The means they use to retain access to their grandchildren are described in order to illustrate how the sense of blood relatedness continues through generations. These strategies, I propose, are not idiosyncratic but have identifiable dialectical patterns that can help us develop new models of contemporary American kinship systems.
A computational parameter study for the three-dimensional shock–bubble interaction

The morphology and time-dependent integral properties of the multifluid compressible flow resulting from the shock–bubble interaction in a gas environment are investigated using a series of three-dimensional multifluid-Eulerian simulations. The bubble consists of a spherical gas volume of radius 2.54 cm (128 grid points), which is accelerated by a planar shock wave. Fourteen scenarios are considered: four gas pairings, including Atwood numbers −0.8 0.2, three-dimensional (non-axisymmetric) effects become particularly significant in the total enstrophy at late times. A new model for the total velocity circulation is proposed, also based on properties derived from one-dimensional gasdynamics, which compares favourably with circulation data obtained from calculations, relative to existing models. The action of nonlinear-acoustic effects and primary and secondary vorticity production is depicted in sequenced visualizations of the density and vorticity fields, which indicate the significance of both secondary vorticity generation and turbulent effects, particularly for M > 2 and A > 0.2. Movies are available with the online version of the paper.
Representation in Pictorialism and Connectionism

Pictorialism is the thesis that mental images represent in the manner of pictures. Connectionism, or “parallel distributed processing,” as it is sometimes called, is a much more general thesis about the mind. Central to this thesis are the following claims: the mind is a huge structure of simple units linked together in a uniform, largely parallel network; units interact by exciting or inhibiting activity in one another; information processing takes place through the interactions between units; mental representations are typically patterns of activation involving many units.1 On the face of it, then, pictorialism and connectionism have little in common. Under the surface, however, there are certain similarities. Both views introduce concepts of representation which are not easy to grasp. Both views, although couched in information processing terms, have a definite physiological flavor. Admittedly, in the case of pictorialism, this flavor is not immediately discernible. But, it comes to the fore, as we shall see later, once the pictorialist thesis is fully stated. And both views seem opposed to the dominant idea in cognitive psychology over the past twenty-five years that the exercise of our cognitive capacities always involves the computational manipulation of linguistic or quasi-linguistic representations.
CHANGES IN THE SELF-CONCEPT OF UNWED MOTHERS.

Summary Changes in the self-concept of 25 unwed mothers over the period of time from entering a home for unwed mothers at the beginning of the third trimester to shortly after parturition, and the relationship between the mother's self-concept and descriptions of her by staff members at the home, were assessed by administering twice a revision of the Interpersonal Check List with six instructional sets (e.g., “I am now …,” “Most teen-age girls are …,” etc.). The results indicate that, upon admission to the home, the subjects viewed themselves as differing greatly in interpersonal behavior from their conception of what they and their parents would have liked them to be, and as differing especially from their conception of what most other teen-age girls are. A week after parturition, however, the subjects saw themselves as being significantly more like other teen-age girls and more like what they and their parents would like them to be. The relationships between the staff members' descriptions of the subjec...
Brain potentials reflect violations of gender stereotypes

Event-related brain potentials (ERPs) were recorded while 14 males and 14 females read sentences containing a reflexive pronoun that referred to a definitionally or stereotypically male or female antecedent noun. Pronouns that disagreed with the gender definition or gender stereotype of the antecedent elicited a large-amplitude positive wave. Violations of gender definitions elicited a larger positive wave than did violations of gender stereotypes. Furthermore, the positive wave elicited by stereotype violations persisted even when subjects judged these sentences to be acceptable. Finally, female subjects exhibited larger positivities than did male subjects, regardless of whether the gender mismatch involved a definitional or stereotypical antecedent. These results are taken to indicate that ERPs are sensitive to violations of gender-based occupational stereotypes and that the ERP response to stereotype violations is similar to the P600 effect elicited by a variety of syntactic anomalies.
The role of the study section in the NIH peer review system

This paper describes the NIH grants review system, which is designed to evaluate a grant proposal for both technical merit and programmatic interest. In particular, it discusses the initial review for scientific and technical merit, using as example the Computer Study Section, which reviews applications in computer science, physiological modeling, and statistics. Criteria for evaluation include: knowledge of the state of the field, relevance to scientific innovation, commitment by the investigator, strength of association between theoretician and practitioner, methodology, human factors, and experience.
Pharmacogenetics in drug discovery and development: a translational perspective

The ability to predict a patient's drug response on the basis of their genetic information is expected to decrease attrition during the development of new, innovative drugs, and reduce adverse events by being able to predict individual patients at risk. Most pharmacogenetic investigations have focused on drug-metabolism genes or candidate genes that are thought to be involved in specific diseases. However, robust new genetic tools now enable researchers to carry out multi-candidate gene-association and genome-wide studies for target discovery and drug development. Despite the expanding role of pharmacogenetics in industry, however, there is a paucity of published data. New forms of effective and efficient collaboration between industry and academia that may enhance the systematic collection of pharmacogenetic data are necessary to establish genetic profiles related to drug response, confirm pharmacogenetic associations and expedite the development of new drugs and diagnostic tests.
PACE4: a subtilisin-like endoprotease prevalent in the anterior pituitary and regulated by thyroid status.

Low stringency screening of a rat hypothalamic complementary DNA library for additional members of the subtilisin-like prohormone convertase (PC) family identified rat PACE4, which is 90% identical to human PACE4 in amino acid sequence, with much lower similarity to rat PC1, PC2, furin, PC4, or PC6. The rat PACE4 sequence has the Asp-His-Ser catalytic site triad, an Arg-Gly-Asp potential integrin binding site, and three potential sites for N-linked glycosylation. Rat PACE4 has a long COOH-terminal region, which is very rich in Cys residues (15%). The unique signal sequence of rat PACE4 mediates translocation across microsomal membranes during in vitro translation and secretion of PACE4 from stably transfected fibroblast cells. Rat PACE4 has a tissue and cell line distribution unlike any reported PC, including human PACE4, with high expression in the anterior pituitary and readily detectable expression in several brain regions, the atrium, and the ventricle; negligible PACE4 messenger RNA (mRNA) is detecte...
An evaluation of nalidixic acid film as a UV-A radiation dosimeter.

Nalidixic Acid (NA)* incorporated into a polyvinyl chloride film has recently been proposed as a UV-A radiation dosimeter. A trial, in which two different batches of NA film were exposed to both solar simulating and monochromatic 330 nm radiation is described. With both batches of film a linear relationship was observed between the UV-A fluence derived from the NA film and the fiuence determined with conventional electronic radiometric equipment. There was, however, considerable batch variation in response to UV-A radiation. Corrections may be made for batch differences. If the batch response can be standardized, our results would support the use of NA film as a simple routine method of measuring UV-A radiation.
Pitfalls in the display of color Doppler jet areas: combined variability due to Doppler angle, frame rate, and scanning direction.

The Doppler color jet area depicting a regurgitant or shunt lesion may be useful in estimating its severity. However, color jet area may be affected by technical factors. We studied the combined effects of Doppler angle, frame rate, and scanning direction on the Doppler color jet area of a free jet with 10-mL injection. Results: (1) Angle effects: color flow area was 11.7 ± 2.0 cm2 at a Doppler angle of 20°, and 2.3 ± 1.2 cm2 at an angle of 60°, when other parameters were kept constant (frame rate=12 frames/sec, reverse scanning direction). (2) Frame rate effects: with other parameters kept constant (Doppler angle = 20°, reverse scanning direction), color flow area was 11.7 ± 2.0 cm2 at a rate of 12 frames/sec and 6.5 ± 1.8 cm2 at 6 frames/sec. (3) Scanning direction effects: with other parameters kept constant (Doppler angle=20°, frame rate = 9 frames/sec), color flow area was 7.3 ± 1.1 cm2 with scanning in the reverse direction, and 20.5 ± 1.6 cm2 with scanning in the forward direction. (4) Combined effects: In our in vitro studies, the maximum color flow area was 20.5 ± 1.6 cm2, and the minimum area was 1.5 ± 0.2 cm2 (nearly twelve-fold). Conclusions: Doppler color jet area correlated inversely with Doppler angle (P<0.01) and directly with frame rate (P<0.01). Color jet area was increased in the forward (following flow), compared with the reverse (against flow) scanning direction (P<0.01). These machine factors must be considered clinically in quantitating color Doppler jet area.
New insight into the structure of RNA in red clover necrotic mosaic virus and the role of divalent cations revealed by small-angle neutron scattering.

Red clover necrotic mosaic virus (RCNMV) is a 36-nm-diameter, T = 3 icosahedral plant virus with a genome that is split between two single-stranded RNA molecules of approximately 3.9 kb and 1.5 kb, as well as a 400-nucleotide degradation product. The structure of the virus capsid and its response to removing Ca2+ and Mg2+ was previously studied by cryo-electron microscopy (cryo-EM) (Sherman et al. J Virol 80:10395–10406, 2006) but the structure of the RNA was only partially resolved in that study. To better understand the organization of the RNA and conformational changes resulting from the removal of divalent cations, small-angle neutron scattering with contrast variation experiments were performed. The results expand upon the cryo-EM results by clearly showing that virtually all of the RNA is contained in a thin shell that is in contact with the interior domains of the viral capsid protein, and they provide new insight into changes in the RNA packing that result from removal of divalent cations.
Uniaxial Mechanical Strain : An In Vitro Correlate to Distraction Osteogenesis

Background Distraction osteogenesis is a valuable clinical tool; however the molecular mechanisms governing successful distraction remain unknown. We have used a uniaxial in vitro strain device to simulate the uniaxial mechanical environment of the interfragmentary distraction gap. Materials and methods Using the Flexcell system, normal human osteoblasts were subjected to different levels of cyclical uniaxial mechanical strain. Cellular morphology, proliferation, migration, and the expression of angiogenic (vascular endothelial growth factor [VEGF] and fibroblast growth factor-2 [FGF-2]) and osteogenic (osteonectin, osteopontin, and osteocalcin) proteins and extracellular matrix molecules (collagen IαII) were analyzed in response to uniaxial cyclic strain. Results Osteoblasts exposed to strain assumed a fusiform spindle-shaped morphology aligning parallel to the axis of uniaxial strain and osteoblasts exposed to strain or conditioned media had a 3-fold increase in proliferation. Osteoblast migration was maximal (5-fold) in response to 9% strain. Angiogenic cytokine, VEGF, and FGF-2, increased 32-fold and 2.6-fold ( P P P Conclusions Uniaxial cyclic strain using the Flexcell device under appropriate strain parameters provides a novel in vitro model that induces osteoblast cellular and molecular expression patterns that simulate patterns observed in the in vivo distraction gap.
Development of segments and appendages in embryos of the desert scorpion Paruroctonus mesaensis (Scorpiones: Vaejovidae).

The scanning electron microscope was used to study the changing features of scorpion embryos from the blastula through early stages in the development of appendages. The earliest scorpion fossils (Silurian period) have structures more advanced than the embryos herein, so the possibility is considered that these embryos still retain and display some features indicative of evolutionary patterns in adult pre-Silurian ancestors. The blastodisc stage is followed by a knob-like germinal center that gives rise to most of the embryo body. The germinal center elongates on the ventral surface of the spherical yolk mass. The broad cephalic lobe is first delineated from the following pedipalpal segment. The limbbuds for the pedipalps and anterior walking legs appear, as additional segments are added at a growth zone at the rear of the embryo body. Initially, in the cephalic lobe there are no limbbuds; then the cheliceral buds emerge from the posterior part of the lobe. The stomodeum appears first in the anterior half of the cephalic lobe, but an oral groove forms and the mouth is displaced posteriorly within the groove. This repositioning allows space anteriorly for invagination (semilunar grooves) of epithelium for the brain and medial eyes. The mouth is directed ventrally in all stages of this study. The widespread chelicerae are initially posterior to the mouth, but later move anterior and dorsal to it. Small limbbud bulges on mesosomal segments disappear later and never become protruding appendages. Metasomal segments are produced free from the yolk surface in a ventral flexure beneath the embryo body. The telson starts as two spherical lobes, but later elongates and tapers distally, not yet developing the sharp sting (aculeus) seen in Silurian and all subsequent scorpions. The walking legs are digitigrade, as in most fossil aquatic scorpions. Segments are delineated in the appendages; the chelicerae and pedipalps are divided distally for chela (claw) formation. Bilateral swellings (limbbuds) on the third abdominal segment become larger than the others, indicating the site of pectine formation. The early fin-like pectines are somewhat posterior in the mesosoma, suggesting ancestral swimming, maneuvering, and balancing for the elongate abdomen. The pectinal surface is initially smooth but later transverse striations increase the surface area as a possible respiratory adaptation. Pectinal teeth (present in Silurian and all subsequent scorpions) and foward movement and merging of anterior abdominal segments are not yet evident in embryos of this study. J. Morphol. 250:70–88, 2001. © 2001 Wiley-Liss, Inc.
Boundedly complete weak-Cauchy basic sequences in Banach spaces with the PCP

Abstract It is proved that every non-trivial weak-Cauchy sequence in a Banach space with the PCP ( the Point of Continuity Property ) has a boundedly complete basic subsequence . The following result, due independently to S. Bellenot and C. Finet, is then deduced as a corollary. If a Banach space X has separable dual and the PCP, then every non-trivial weak-Cauchy sequence in X has a subsequence spanning an order-one quasi-reflexive space .
Research ethics and evidence based medicine

In this paper, the author argues that the requirement to conduct randomised clinical trials to inform policy in cases where one wants to identify a cheaper alternative to known effective but expensive interventions raises an important ethical issue. This situation will eventually arise whenever there are resource constraints, and a policy decision has been made not to fund an intervention on cost effectiveness grounds. It has been thought that this is an issue only in extremely resource poor settings. This paper gives an example from the United Kingdom illustrating that this is also a problem faced by richer countries.
Laser monitoring for the CMS ECAL

The Compact Muon Solenoid (CMS) detector at the LHC is equipped with a high precision lead tungstate crystal electromagnetic calorimeter (ECAL). To ensure the stability of the calorimetric response at the level of a few per mille, every channel of the detector is monitored with a laser system. This system enables corrections for fluctuations in the detector response with high precision, in particular the expected radiation induced changes in the crystal transparency. We describe the implementation of the laser monitoring system and report results from tests on the fully equipped supermodules of the ECAL. Specifically, we discuss results concerning the dynamics of crystal transparency change from dedicated irradiation studies in test beams.
Projection as an Interpersonal Influence Tactic: The Effects of the Pot Calling the Kettle Black

In his analysis of Nazi propaganda, Ellis Freeman identified an influence tactic based on projection: accusing another person of the negative traits and behaviors that one possesses and exhibits with the goal of deflecting blame away from one’s own misdeeds and toward the accused. Although the use of projection as an influence tactic is not limited to fascist regimes and its consequences can be socially devastating, the projection tactic has not been subjected to experimental analysis. In four experiments, the authors found that projection was effective in (a) increasing the blame placed on the target of the projection and (b) decreasing the culpability of the accuser (or projectionist). These effects occurred despite (a) raising suspicions about the motives of the projectionist, (b) providing evidence that the projectionist is guilty of the deed, and (c) timing the projection so that it occurred after the misdeeds came to light.
Conversion of a 2-(N-nitroso)acetamido hexose into a five-carbon, acetylenic sugar derivative

Abstract Dinitrogen tetraoxide was used to convert 2-acetamido-1,3,4,6-tetra- O -acetyl-2-deoxy-β- D -glucopyranose ( 1 ) in high yield into the syrupy N -nitroso derivative 2 , and benzyl 2-acetamido-3,4,6-tri- O -acetyl-2-deoxy-β- D -glucopyranose ( 6 ) into the crystalline N -nitroso analog 7 . The N -nitroso derivative 2 in acetonitrile underwent photolysis by pyrex-filtered, u.v. light to regenerate the starting acetamide 1 in high yield; spontaneous decomposition of 2 afforded β- D -glucopyranose pentaacetate ( 3 ) and other products. In ethereal solution, compound 2 reacted with potassium hydroxide in isopropyl alcohol with loss of the 2-substituent and C-1, to give a C 5 acetylene, 1,2-dideoxy- D - erythro -pent-1-ynitol, isolated in high yield as its triacetate 4 and characterized by conversion into the known, crystalline 1,2-dideoxy-3- O -(3,5- dinitrobenzoyl)-4,5- O -isopropylidene- D - erythro -pent-1-ynitol ( 5 ).
Congenital stenosis of the hepatic duct at the porta hepatis in children with choledochal cyst.

Abstract Background The intrahepatic gallstone is known as one of the complications of choledochal cyst. Stenosis of the hepatic duct may contribute to the formation of the stone. This report describes concurrent congenital stenosis of the hepatic duct identified during the primary operation of choledochal cyst. Methods Fourteen children were operated on for choledochal cyst. To identify the concurrent stenosis, cholangiography and inspection of the hepatic duct were performed during the operation. In those patients with identified membranous stenosis, the membrane was resected. In those with nonmembranous stenosis, the wide hilar hepaticojejunostomy was performed after hepatic duct plasty. Results Eleven sites of hepatic duct stenosis were identified, 8 membranous stenoses and 3 relative stenoses without membrane. The membranous stenoses were classified into 4 subtypes as follows: a small central opening, a marginal opening, 2 openings, and a bridgelike structure. At the primary surgery on choledochal cyst, those stenoses were released, and the formation of the gallstone has not been observed in 4 to 11 years in all cases.
Disposition of cryopreserved embryos by infertility patients desiring to discontinue storage

Objective To review our patients' decisions for disposition of their cryopreserved embryos and compare the findings with those reported in the scientific literature. Patients who no longer wish to store their cryopreserved embryos have three choices: discarding, donation to research, or donation to someone else for initiation of a pregnancy. Design Retrospective review of patient records from January 2002 to July 2007 to determine preferences for embryo disposition. Setting University hospital. Patient(s) Patients who elected to discontinue embryo cryostorage. Intervention(s) None. Main Outcome Measure(s) Patients' decisions regarding embryo disposition, length of storage, treatment outcome, age at oocyte retrieval, and age at time of disposition. Result(s) A total of 149 disposition requests were reviewed, with 59% donating to scientific research, 38% discarding, and 3% donating to a known or anonymous person/couple for attempted pregnancy. There was no significant difference in the choice selected between patients who achieved a pregnancy with delivery compared with those who did not. Patient age at retrieval and at the time of disposition as well as the total time in storage was not significantly different between patients electing to discard and those donating to research. Conclusion(s) Patients in our program wanting to discontinue cryostorage were more likely to request that their surplus embryos be used for scientific research.
Narrow-Line and Broadband Spectra of Iridium(III) Complexes in a Shpol'skii Matrix and an Amorphous Host

Narrow-line emission and excitation spectra of the lowest triplet state have been studied in a Shpol'skii host (n-octane) for three cyclometalated IrL2acac complexes of current practical interest. ...
A further study of adrenal function in the opossum (Didelphis virginiana).

Abstract Studies are reported on the in vitro metabolism of progesterone-4- 14 C by adrenal tissue taken from the American opossum ( Didelphis virginiana ) before and after chronic caval constriction. Comparison of paired adrenals from the same animal showed that this procedure diverted steroid metabolic pathways to produce more mineralocorticoid and less glucocorticoid but aldosterone levels were reduced in favor of deoxycorticosterone. Thoracic caval obstruction sufficient to produce a fall in mean arterial pressure caused a marked rise in aldosterone secretion in as short a period of time as 15 min, in some cases. A single injection of 1–2 μg of aldosterone caused a marked decline in urinary sodium excretion which did not appear until the second hour after administration of the steroid. The effect on potassium was variable. In these three respects the adrenal steroid metabolism and utilization in the American opossum appear to be similar to that of higher mammals.
Structure of a tyrosyl-tRNA synthetase splicing factor bound to a group I intron RNA

Life on Earth is believed to have evolved from an 'RNA world' where RNA molecules both catalysed essential chemical reactions and carried genetic information. In modern biology, proteins have become the enzymatic workhorses of the cell, while nucleic acids retain the informational role. Within cells, however, relics of the RNA world remain. One such is the mitochondrial tyrosyl-tRNA synthetase, CYT-18, from the fungus Neurospora crassa, which also binds a group I intron ribozyme and facilitates splicing. The crystal structure of this protein/ribozyme complex has now been determined. The interaction surface is different from that used by CYT-18 to bind tRNATyr in its enzymic role. Specific changes are found which do not exist in non-splicing tRNA synthetases, suggesting ways in which RNA–protein complexes could have evolved from RNA-only enzymes. The structure of truncated Neurospora crassa mitochondrial tyrosyl-tRNA synthetase (CYT-18) with the intron ribozyme T wort orf142-I2 is solved. The interaction surface is different than that used by CYT-18 to bind tRNATyr when it is functioning as a tyrosyl-tRNA synthetase. The protein serves as a scaffold that extends the intron, facilitating its splicing function. The ‘RNA world’ hypothesis holds that during evolution the structural and enzymatic functions initially served by RNA were assumed by proteins, leading to the latter’s domination of biological catalysis. This progression can still be seen in modern biology, where ribozymes, such as the ribosome and RNase P, have evolved into protein-dependent RNA catalysts (‘RNPzymes’). Similarly, group I introns use RNA-catalysed splicing reactions, but many function as RNPzymes bound to proteins that stabilize their catalytically active RNA structure1,2. One such protein, the Neurospora crassa mitochondrial tyrosyl-tRNA synthetase (TyrRS; CYT-18), is bifunctional and both aminoacylates mitochondrial tRNATyr and promotes the splicing of mitochondrial group I introns3. Here we determine a 4.5-A co-crystal structure of the Twort orf142-I2 group I intron ribozyme bound to splicing-active, carboxy-terminally truncated CYT-18. The structure shows that the group I intron binds across the two subunits of the homodimeric protein with a newly evolved RNA-binding surface distinct from that which binds tRNATyr. This RNA binding surface provides an extended scaffold for the phosphodiester backbone of the conserved catalytic core of the intron RNA, allowing the protein to promote the splicing of a wide variety of group I introns. The group I intron-binding surface includes three small insertions and additional structural adaptations relative to non-splicing bacterial TyrRSs, indicating a multistep adaptation for splicing function. The co-crystal structure provides insight into how CYT-18 promotes group I intron splicing, how it evolved to have this function, and how proteins could have incrementally replaced RNA structures during the transition from an RNA world to an RNP world.
Temperature dependence of collision broadening and shift in the NO A ← X (0, 0) band in the presence of argon and nitrogen

Abstract A rapid-tuning intracavity-doubled cw dye laser was used to resolve absorption lineshapes in the NO A ← X (0,0) band at 226 nm. Lineshapes acquired both in room-temperature cells and in a shock tube were fit to Voigt profiles to measure the collision broadening and shift for various colliders. The room-temperature (295 K) broadening coefficients were determined to be 0.503 cm-1atm-1 for argon broadener and 0.583 cm-1atm-1 for nitrogen broadener. The corresponding room-temperature (295 K) shift coefficients were found to be -0.159 and -0.180 cm-1atm-1, respectively. No dependence on rotational quantum number was observed for either width or shift. The room-temperature self-broadening and shift coefficients were found to be 0.551 and -0.171 cm-1atm-1, based on measurements on a single J″ line. By performing shock-tube measurements to 2800 K, the temperature exponents for the broadening and shift coefficients were determined to be -0.65 and -0.58 for argon collider and -0.75 and -0.56 for nitrogen collider, respectively. In all profiles, evidence of collision-induced lineshape asymmetries were observed.
A neurochemical heterogeneity of the rat striatum as measured by in vivo electrochemistry and microdialysis

Abstract The neurochemical heterogeneity of the rat striatum was assessed in vivo by measuring subregional changes in extracellular dopamine and DOPAC by in vivo electrochemistry and microdialysis in response to amphetamine and the D2 antagonist, (−)-sulpiride. Both in vivo electrochemical and microdialysis experiments indicated a significant rostrocaudal gradient in dopamine release following amphetamine. The increase in dopamine release was highest in the rostral areas (over 800% of baseline values) and lowest in the most caudal subregion (425% of baseline). No lateromedial differences in dopamine release were observed. DOPAC levels decreased in dialysates but were similar for all 6 subregions examined. In contrast, D2 blockade with (−)-sulpiride revealed a lateromedial gradient in the increases seen for dopamine and DOPAC such that greater increases were observed in the lateral subregions. (−)-Sulpiride did not produce any differential effects along the rostrocaudal axis. The regional gradients detected in extracellular fluid changes of dopamine and DOPAC indicate that dopamine release is locally regulated by an interaction between the density of dopaminergic innervation to a particular subregion and the D2 receptor density.
Siting of antimony dopants and gallium in Ba8Ga16Ge30 clathrates grown from gallium flux

A series of antimony-doped Ba8Ga16Ge30 clathrates was grown as large crystals from gallium flux. These compounds form in the cubic space group Pm3n, with the unit cell parameter varying from 10.784(5) to 10.9008(6) A as the amount of GaSb substituting for germanium atoms in the framework is increased. It was found that more antimony than extra gallium was incorporated into the material and that a specific site (the 24k Wyckoff site) was favored by this element. 71 Ga NMR was carried out to determine the siting of gallium; it fills the 6c site preferentially.