cssi/SciSciGPT-SciSciNet huggingface dataset:
Temporal Trends in Statin Prescriptions and Residual Cholesterol Risk in Patients With Stable Coronary Artery Disease Undergoing Percutaneous Coronary Intervention

Intensive low-density lipoprotein cholesterol (LDL-C) reduction with statins is recommended after elective percutaneous coronary intervention (PCI). We aimed to evaluate adherence to guideline-recommended statin therapy (GRST) and the rate of residual cholesterol risk (RCR) at follow-up after elective PCI. All patients who underwent elective PCI between January 2010 and May 2016 were prospectively included in this single-center study. GRST was defined as high-intensity statin (HIS) therapy for patients ≤75 years old and moderate-intensity statin (MIS) or HIS therapy for patients >75 years. RCR at follow-up was defined as 70 mg/dL for nonstatin-naive patients. A total of 2,653 patients were included, with 1,304 (49.2%) discharged with GRST. There was a significant increase in the number of patients discharged with GRST over time from 44.2% in 2010 to 63.0% in 2016 (p <0.001). Conversely, RCR at follow-up was present in 1,120 patients (42.2%) overall and remained stable over time. Risk factors of RCR at follow-up were female gender (odds ratio [OR]: 1.38; 95% confidence interval [CI] 1.13 to 1.70), previous myocardial infarction (OR: 1.37; 95% CI 1.12 to 1.64), smoking (OR: 1.30; 95% CI 1.01 to 1.67), higher LDL-C level at baseline (OR: 1.22; 95% CI 1.18 to 1.25). The presence of RCR was associated with an increased adjusted risk of death within 1 year of the second LDL-C measurement (adjHR: 2.78; 95% CI 1.15 to 6.67). In conclusion, although the rate of GRST at discharge has improved significantly over time in patients who underwent elective PCI, the prevalence of RCR at follow-up has not changed appreciably suggesting that further implementation of guidelines as well as novel or more intensive pharmacotherapy may be warranted.
What is the Functional Difference Between Sagittal With Metopic and Isolated Sagittal Craniosynotosis

INTRODUCTION The purpose of this study is to understand the neurological differences between patients born with combined sagittal and metopic craniosynostosis (SMc) and isolated sagittal craniosynostosis (ISc) by studying aberrations in functional brain connectivity and white matter microstructure, before surgery, utilizing functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). METHODS The authors collected DTI and resting-state (ie, no sedation and asleep) functional connectivity MRI data in 10 infant patients preoperatively: 5 in the SMc group (4.3 ± 1 months) and 5 in the ISc group (4.8 ± 1.1 months). Resting state fMRI imaging and DTI data were acquired using a 3-T Siemens Trio MRI system (Erlangen, Germany) while the infant patients slept. fMRI data were corrected for movement using SPM, underwent cerebrospinal fluid and white matter signal regression and further analyzed with BioImageSuite. For the DTI data, 3 diffusion runs were averaged, processed utilizing FMRIB Software Library, and analyzed statistically using BioImageSuite. RESULTS Comparing the SMc versus ISc groups, SMc demonstrated that there was increased connectivity, statistically significant differences, in neural networks between children with sagittal synostosis alone versus those with sagittal with metopic synostosis, in the right BA 31 and BA 23 (corresponding to the posterior cingulate cortex (PCC) (P < 0.001). Analysis of the DTI revealed increased fractional anisotropy (normal maturation of white tracts) in the SMc group in the cingulum compared to the ISc group (P < 0.05). Differences in the functional networks include increased connectivity right frontoparietal network (RFPN) in ISc and increased connectivity in the primary visual network (V1) in SMc (P < 0.001). CONCLUSION The SMc had increased connectivity as measured by fMR in the PCC, an area associated with attention deficit hyperactivity disorder. The DTI analysis demonstrated an increase in fractional anisotropy of the cingulum in the SMc group, a white matter tract projecting from the cingulate cortex; connections of the limbic (emotional regulation) system are instrumental. In SMc, increase of connectivity in the PCC correlates with an increase in maturation of the cingulum compared to ISc. There is increased connectivity of the RFPN network in the ISc and increased connectivity of the V1 network in the SMc patients. The SMc group has increased connectivity in the PCC, the original seed of the DMN network, and decreased connectivity to the RFPN network. The pattern of increased connectivity in the area of the DMN and decreased connectivity in the RFPN network is similar to the trend when comparing ADHD patients to normal controls. SMc has more similar functional network connectivity to ADHD as compared to ISc.
Failure to attune to language predicts autism in high risk infants.

Abstract Young humans are typically sensitive to evolutionarily important aspects of information in the surrounding environment in a way that makes us thrive. Seeking to probe the putative disruptions of this process in infancy, I examined the statistical character of head movements in 52 9–10 mo-old infants, half at high familial risk (HR) for Autism Spectrum Disorders (ASD), who underwent an fMRI scan while listening to words spoken with alternating stress patterns on syllables. Relative to low risk (LR) infants, HR infants, in particular those showing the least rapid receptive language progress, had significantly lower noise-to-signal levels and increased symmetry. A comparison of patterns during a native language and a sleep scan revealed the most atypical ordering of signatures on the 3 tasks in a subset of HR infants, suggesting that the biological mechanism of language development is least acquisitive in those HR infants who go on to develop ASD in toddlerhood.
Parasitic Infections in Transplant Recipients: Toxoplasmosis, Strongyloidiasis, and Other Parasites

Toxoplasma gondii and Strongyloides stercoralis are important parasitic infections in transplant recipients. These helminths can lead to severe and often life-threatening disease in immunocompromised patients. Toxoplasma gondii can cause an undifferentiated febrile syndrome, encephalitis, pneumonitis, myocarditis, hepatitis, and retinochoroiditis, whereas S. stercoralis infestation, can lead to the hyperinfection syndrome, which carries a high mortality rate. Effective therapies are available for both, but high case-fatality rates result if these syndromes go unrecognized and are not treated promptly. Preventative measures for infected (and often asymptomatic) transplant recipients/candidates are highly effective in preventing overt disease for both parasites, including prophylactic anti-Toxoplasma therapy or ivermectin treatment for patients with occult strongyloidiasis in properly selected patients. Identifying transplant patients at risk for these syndromes is therefore critical, so that these measures can be instituted before life-threatening disease develops. Other important parasitic infections in transplant recipients include Trypanosoma cruzi (the agent of Chagas disease), visceral leishmaniasis, and the free-living amoebae Acanthamoeba and Balamuthia.
Exploring the Potential Impact of Louisville's Urban Heat Island on the Structure and Intensity of an Organized Convective Systems

Simulations of an organized convective system interacting with Louisville, KY were conducted to determine the impact of urban heat island (UHI) magnitude on the structure and intensity of convective storms. Four different simulations are presented: A control, two simulations in which the UHI is enhanced through observational nudging, and a simulation where the urban area is removed (no-city simulation). Results show that the downwind enhancement of convective cells increases with increasing UHI magnitude. However, large differences are also apparent between the control and the no-city simulations. This suggests that surface convergence caused by flow obstruction may be as influential to the modification of organized storms as the UHI, although the locations of these two effects are offset. Convergence due to flow obstruction is most noticeable on the upwind edge and over the center of the city while the impact of UHI magnitude is most noticeable on the downwind edge of the city.
Serum D-lactate concentrations in dogs with parvoviral enteritis.

BACKGROUND: Dogs infected with canine parvovirus (CPV) have compromised intestinal epithelial barrier integrity. Production of D‐lactate by enteric bacteria may directly reflect disease severity or contribute to metabolic acid‐base status in these dogs. HYPOTHESIS: Serum D‐lactate concentration will be increased in CPV dogs compared to healthy controls and correlate with markers of disease severity and acid‐base status. ANIMALS: Dogs with CPV undergoing treatment (n = 40) and healthy control dogs (n = 9). METHODS: Prospective observational study. Dogs with CPV had a baseline and daily CBC, venous blood gas with serum electrolyte concentrations, composite clinical severity score, and serum D‐lactate concentration performed. A single serum D‐lactate measurement was obtained from healthy control dogs. RESULTS: The CPV dogs had a higher D‐lactate concentration (mean ± SD) of 469 ± 173 μM compared to controls, 306 ± 45 μM (P < .001). There was no difference in baseline D‐lactate concentrations for CPV survivors (474 ± 28 μM), versus nonsurvivors (424 ± 116 μM; P = .70). D‐lactate concentration decreased over the first 4 days of treatment (−9.6 μM/d; P = .46). Dogs hospitalized for <4 days had lower baseline D‐lactate concentrations compared to those hospitalized ≥4 days (400 ± 178 μM versus 520 ± 152 μM; P = .03). No sustained correlation over time between serum D‐lactate concentration and clinical severity score or recorded acid‐base results. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum D‐lactate concentrations are higher in dogs with CPV compared to healthy controls but do not appear to be clinically relevant. No relationship identified between serum D‐lactate concentrations and markers of CPV disease severity, acid‐base status, or outcome.
THE EFFECT OF MEDIAL HAMSTRING WEAKNESS ON KNEE CONTACT FORCES DURING RUNNING

When used to reconstruct the anterior cruciate ligament (ACL), the medial hamstrings graft has been shown to produce lower rates of osteoarthritis (OA) than the patellar tendon graft. The goal of this study was to determine how reducing medial hamstring strength during surgery affects joint contact forces during loading, and hence the joint’s proclivity towards OA. A previously developed model of the entire body was used to perform a muscle-actuated forward dynamics simulation of running for two cases: normal muscle strength and medial hamstrings (i.e. semitendinosus and gracilis) weakened by 30%. The muscle forces from these simulations were then used to actuate a discrete element model in a forward dynamics simulation. Weakening the medial hamstrings caused an overall decrease in total hamstrings force by <1%, total quadriceps force by 2%, and cartilage contact force by 4%. This decreased force may be protective against long-term OA and hence may help explain the lower rates of OA in patients who receive medial hamstring grafts.
Radiopharmaceuticals for Prostate Cancer

A high percentage of patients with metastatic prostate cancer have evidence of bone metastases that are either symptomatic or visible on radiographic imaging (Roodman, N Engl J Med 350:1655–1664, 2004). Patients with osteoblastic metastatic disease often experience pain and have a high risk for pathologic fractures due to compromise of the affected bone. Therefore, treatment of the pain and complications from bone metastases can become complicated and costly (Roodman, N Engl J Med 350:1655–1664, 2004). Radiopharmaceuticals can be used in the treatment of bone metastases from prostate cancer. Strontium-89 and samarium-153 have been approved for the palliative treatment of bone metastases to decrease pain but have not been shown to have survival benefit. Radium-223 has been shown to be effective for pain control, as well as providing a survival benefit, for patients with castrate-resistant prostate cancer involving bone without visceral metastatic disease. This chapter discusses the characteristics of each radiopharmaceutical agent, as well as important information for managing patients undergoing treatment.
Who Benefits More from the College Expansion Policy? Evidence from China

Abstract This study extends the current literature on the relationship between educational expansion and social inequality by examining how the higher education expansion policy in China changed patterns of inequality across the country and within specific geographic regions. Results based on the Comparative Interrupted Time Series analyses indicate that although all individuals benefit from expansion in both overall and academic college enrollment, individuals from advantaged family backgrounds experience greater benefits. This is the case especially for middle and western regions of China. In the eastern region, inequality in overall college enrollment persists after expansion but that in academic college enrollment increases. These findings have implications for understanding the effects of expansion policies and whether they can reduce social inequality.
What Is the Story You Want to Tell? Utilizing the Narrative Arc as an Academic Writing Framework for Graduate Students in Health Promotion:

Writing well is an important skill for graduate students to learn. We contend that viewing the writing process through the lens of storytelling and narrative helps graduate students make clearer, m...
Design of Hathaani - A Robotic Violinist for Carnatic Music

We present a novel robotic violinist that is designed to play Carnatic music - a music system popular in the southern part of India. The robot plays the D string and uses a single finger mechanism inspired by the Chitravina - a fretless Indian lute. A fingerboard traversal system with a dynamic finger tip apparatus enables the robot to play gamakas - pitch based embellishments in-between notes, which are at the core of Carnatic music. A double roller design is used for bowing which reduces space, produces a tone that resembles the tone of a conventional violin bow, and facilitates super human playing techniques such as infinite bowing. The design also enables the user to change the bow hair tightness to help capture a variety of performing techniques in different musical styles. Objective assessments and subjective listening tests were conducted to evaluate our design, indicating that the robot can play gamakas in a realistic manner and thus, can perform Carnatic music.
MCX Cloud - a modern, scalable, high-performance and in-browser Monte Carlo simulation platform with cloud computing

Significance: Despite the ample progress made towards faster and more accurate Monte Carlo (MC) simulation tools over the past decade, the limited usability and accessibility of these advanced modeling tools remain key barriers towards widespread use among the broad user community. Aim: An open-source, high-performance, web-based MC simulator that builds upon modern cloud computing architectures is highly desirable to deliver state-of-the-art MC simulations and hardware acceleration to general users without the need for special hardware installation and optimization. Approach: We have developed a configuration-free, in-browser 3-D MC simulation platform -- MCX Cloud -- built upon an array of robust and modern technologies, including a Docker Swarm-based cloud-computing backend and a web-based graphical user interface (GUI) that supports in-browser 3-D visualization, asynchronous data communication, and automatic data validation via JavaScript Object Notation (JSON) schemas. Results: The front-end of the MCX Cloud platform offers an intuitive simulation design, fast 3-D data rendering, and convenient simulation sharing. The Docker Swarm container orchestration backend is highly scalable and can support high-demand GPU MC simulations using Monte Carlo eXtreme (MCX) over a dynamically expandable virtual cluster. Conclusion: MCX Cloud makes fast, scalable, and feature-rich MC simulations readily available to all biophotonics researchers without overhead. It is fully open-source and can be freely accessed at http://mcx.space/cloud.
Functional and Highly Crosslinkable HIV-1 Envelope Glycoproteins Enriched in a Pretriggered Conformation

Binding to the receptor, CD4, drives the pretriggered, "closed" (State-1) conformation of the human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer into more "open" conformations (States 2 and 3). Broadly neutralizing antibodies, which are elicited inefficiently, mostly recognize the State-1 Env conformation, whereas the more commonly elicited poorly neutralizing antibodies recognize States 2/3. HIV-1 Env metastability has created challenges for defining the State-1 structure and developing immunogens mimicking this labile conformation. The availability of functional State-1 Envs that can be efficiently crosslinked at lysine and/or acidic amino acid residues might assist these endeavors. To that end, we modified HIV-1AD8 Env, which exhibits an intermediate level of triggerability by CD4. We introduced lysine/acidic residues at positions that exhibit such polymorphisms in natural HIV-1 strains. Env changes that were tolerated with respect to gp120-gp41 processing, subunit association and virus entry were further combined. Two common polymorphisms, Q114E and Q567K, as well as a known variant, A582T, additively rendered pseudoviruses resistant to cold, soluble CD4 and a CD4-mimetic compound, phenotypes indicative of stabilization of the pretriggered State-1 Env conformation. Combining these changes resulted in two lysine-rich HIV-1AD8 Env variants (E.2 and AE.2) with neutralization- and cold-resistant phenotypes comparable to those of natural, less triggerable Tier 2/3 HIV-1 isolates. Compared with these and the parental Envs, the E.2 and AE.2 Envs were cleaved more efficiently and exhibited stronger gp120-trimer association in detergent lysates. These highly crosslinkable Envs enriched in a pretriggered conformation should assist characterization of the structure and immunogenicity of this labile state. IMPORTANCEThe development of an efficient vaccine is critical for combating HIV-1 infection worldwide. However, the instability of the pretriggered shape (State 1) of the viral envelope glycoprotein (Env) makes it difficult to raise neutralizing antibodies against HIV-1. Here, by introducing multiple changes in Env, we derived two HIV-1 Env variants that are enriched in State 1 and can be efficiently crosslinked to maintain this shape. These Env complexes are more stable in detergent, assisting their purification. Thus, our study provides a path to a better characterization of the native pretriggered Env, which should assist vaccine development.
UPRT, a suicide-gene therapy candidate in higher eukaryotes, is required for Drosophila larval growth and normal adult lifespan

Uracil phosphoribosyltransferase (UPRT) is a pyrimidine salvage pathway enzyme that catalyzes the conversion of uracil to uridine monophosphate (UMP). The enzyme is highly conserved from prokaryotes to humans and yet phylogenetic evidence suggests that UPRT homologues from higher-eukaryotes, including Drosophila, are incapable of binding uracil. Purified human UPRT also do not show any enzymatic activity in vitro, making microbial UPRT an attractive candidate for anti-microbial drug development, suicide-gene therapy, and cell-specific mRNA labeling techniques. Nevertheless, the enzymatic site of UPRT remains conserved across the animal kingdom indicating an in vivo role for the enzyme. We find that the Drosophila UPRT homologue, krishah (kri), codes for an enzyme that is required for larval growth, pre-pupal/pupal viability and long-term adult lifespan. Our findings suggest that UPRT from all higher eukaryotes is likely enzymatically active in vivo and challenges the previous notion that the enzyme is non-essential in higher eukaryotes and cautions against targeting the enzyme for therapeutic purposes. Our findings also suggest that expression of the endogenous UPRT gene will likely cause background incorporation when using microbial UPRT as a cell-specific mRNA labeling reagent in higher eukaryotes.
Dynamics of Soil Denitrifier Populations: Relationships between Enzyme Activity, Most-Probable-Number Counts, and Actual N Gas Loss

To better understand temporal variability in soil denitrification, denitrifying enzyme activity (DEA) and denitrifier populations (as determined by most-probable-number [MPN] counts) were measured in field and laboratory experiments. Measurements of DEA and MPN provided highly contradictory indications of denitrifier dynamics. In laboratory incubations, under conditions favoring active denitrification, the synthesis of new denitrifying enzymes and the actual amount of denitrification were closely related. In other experiments, however, both DEA and MPN counts were poor indicators of actual denitrification. In some cases, we found significant increases in DEA but no significant production of N gas. Except with unnaturally high substrate amendments, changes in DEA were small relative both to the persistently high DEA background and to changes in MPN. As estimated by MPN counts, denitrifier populations increased significantly during denitrification events. It was apparent that only a small fraction of the denitrifiers were included in the MPN counts, but it appeared that this isolatable fraction increased during periods of active denitrifier growth. Use of DEA as an index of biomass of cells which have synthesized denitrifying enzymes suggested that denitrifier populations were persistent, stable, and much larger than indicated by MPN procedures.
Electron Transport and Photophosphorylation in Chloroplasts as a Function of the Electron Acceptor

Electron acceptors may be divided into three distinct classes on the basis of the nature of the electron transport and phosphorylation processes which accompany their reduction by illuminated chloroplasts. Class I acceptors are reduced slowly in the absence of phosphorylation. The addition of ADP and Pi usually increases the rate 2- to 3-fold and up to 1.3 molecules of ATP are formed for each pair of electrons transferred to the acceptor. Uncouplers such as methylamine increase the rate of reduction still further. Most of the electron acceptors heretofore employed in studies of noncyclic photophosphorylation (ferredoxin, ferricyanide, viologens, and flavins) belong to this class. All are ionic or otherwise polar substances with negligible lipid solubilities. Class II acceptors are reduced rapidly whether or not phosphorylation occurs and the addition of uncouplers often does not increase the rapid rate of reduction. Little or no ATP is formed. Substances such as phenolindophenols belonging to this class have dual functions, serving both as electron acceptors and as uncouplers. They are weak acids, lipid-soluble in their nonionized, protonated forms. Their uncoupling function is enhanced as the pH is lowered and the amount of lipid-soluble acid increases. Class III acceptors are also reduced rapidly whether or not phosphorylation occurs and uncouplers again cause little or no increase in the rate of reduction. However, when ADP and Pi are added in the absence of uncouplers a high rate of phosphorylation is observed. The phosphorylation associated with Class III acceptors is usually more rapid than is the phosphorylation associated with Class I acceptors, especially at suboptimal pH. Nevertheless, over a wide range of conditions, the efficiency of phosphorylation in terms of electrons transported (P:e2) is rather precisely half of the efficiency observed when Class I acceptors are reduced. All nonionic, lipid-soluble acceptors we have investigated belong to Class III. Thus the lipid-soluble p-benzoquinone is a Class III acceptor but the lipid-insoluble p-benzoquinone sulfonate is a Class I acceptor. From these observations we conclude that electrons are transported to Class I acceptors through two sites of phosphorylation whereas the transport of electrons to Class III acceptors utilizes only one of the sites. Presumably lipid-soluble acceptors have access to and accept electrons from carriers which normally transfer electrons between the two sites of phosphorylation.
Antifreeze Proteins by Solid‐state NMR: Methods and Applications

Antifreeze proteins (AFPs) are a class of ice-binding proteins that help cold-adapted organisms survive at subzero temperatures. Although the solution and crystal structures of many AFPs are known, solid-state NMR spectroscopy remains one of the few techniques with which their functional, ice-bound state can be studied at atomic resolution. This article describes solid-state NMR methods that investigate the protein–ice interaction of AFPs, methods that measure their remaining hydration shell, and methods that monitor the structural changes of AFPs on ice binding. Applications of these methods on type I and type III AFPs are presented. Keywords: frozen solution; protein hydration; protein binding; ice
A Hardware Counters Based Tool for System Monitoring

In this paper we describe the extensions to the RVision tool to support hardware performance counters monitoring at system level. This monitoring tool is useful for system administrators to detect applications that need tuning. We present a case study using a parallel version of the Swim benchmark from the SPEC suite, running on an Intel Pentium III Linux cluster, where we show a performance improvement of 25%. In addition we present some intrusion measurements showing that our implementation has very low intrusion even with high monitoring frequencies.
U.S. Policy to Promote Democracy in the Middle East

The U.S is committed to supporting democracy in the Arab world during the Bush administration after the failure in the Iraqi war. This interest changed during Obama years who put Arab – Israeli conflict as priority for his administration. The U.S also has other agendas, most notably the security aspects of the so-called “war on terror”. When these agendas collide, however, the U.S’s democracy commitments are perceived to suffer. The author presents recommendations for an improved relationship between the U.S and the Arab world, with a focus on a long-term, flexible and credible support for democracy building, emphasizing the need not to let democracy and human rights objectives be subordinated to other agendas, not least because the different sets of objectives are mutually supportive.
I/O-conscious data preparation for large-scale web search engines

Given that commercial search engines cover billions of web pages, efficiently managing the corresponding volumes of disk-resident data needed to answer user queries quickly is a formidable data manipulation challenge. We present a general technique for efficiently carrying out large sets of simple transformation or querying operations over external-memory data tables. It greatly reduces the number of performed disk accesses and seeks by maximizing the temporal locality of data access and organizing most of the necessary disk accesses into long sequential reads or writes of data that is reused many times while in memory. This technique is based on our experience from building a functionally complete and fully operational web search engine called Yuntis. As such, it is in particular well suited for most data manipulation tasks in a modern web search engine and is employed throughout Yuntis. The key idea of this technique is co-ordinated partitioning of related data tables and corresponding partitioning and delayed batched execution of the transformation and querying operations that work with the data. This data and processing partitioning is naturally compatible with distributed data storage and parallel execution on a cluster of workstations. Empirical measurements on the Yuntis prototype demonstrate that our technique can improve the performance of external-memory data preparation runs by a factor of 100 versus a straightforward implementation.
Numerically exact calculation of electromagnetic heat transfer between a dielectric sphere and plate

We present a numerically exact calculation of electromagnetic heat transfer between a dielectric sphere and plate. We compare the calculation to a recent experiment. Our calculations unify various approximations previously used to treat this problem, and provide a basis for new physical insights into the design of nanoscale thermal transfer experiments.
Deficiency of Fucosidase Results in Acrosomal Dysgenesis and Impaired Sperm Maturation

Although a variety of glycosyltransferases and glycosidases have been implicated in spermatogenesis and posttesticular sperm maturation, the biological role of these enzymes in these processes is largely unknown. We describe reproductive sequelae in a cohort of male dogs suffering from fucosidosis, a heritable lysosomal storage disorder caused by a severe deficiency of alpha-L-fucosidase. There was a reduction in the total number of sperm in the ejaculate. Only 3-5% of sperm were motile. None of the sperm were found to be morphologically normal. The predominant morphological defects observed were malformed acrosomes (56%) and retained proximal cytoplasmic droplets (92%), indicating that spermiogenesis and sperm maturation were impaired. The cytoplasm of all cellular components of the testis and excurrent ducts were vacuolated. The vacuolation resulted from enlargement of lysosomes caused by accumulation of compounds that are otherwise cleaved/degraded when lysosomal hydrolases are present normally. It is possible that impairment in spermatogenesis, particularly morphogenesis of the acrosome, is due to physical damage caused by anomalous enlargement of lysosomes. Although an unambiguous causal relationship could not be established, it is evident from the available information that the derangement in events associated with epididymal sperm maturation, namely acquisition of motility and shedding of the cytoplasmic droplet, is likely due to lack of fucosidase leading to impaired sperm membrane modification. This heritable condition in dogs may serve as a spontaneously occurring knock-out model for further elucidating the role of alpha-L-fucosidase in spermatogenesis and sperm maturation.
The transcription factor Lmx1b maintains Wnt1 expression within the isthmic organizer

Cells in the caudal mesencephalon and rostral metencephalon become organized by signals emanating from the isthmus organizer (IsO). The IsO is associated with the isthmus, a morphological constriction of the neural tube which eventually defines the mesencephalic/ metencephalic boundary (MMB). Here we report that the transcription factor Lmx1b is expressed and functions in a distinct region of the IsO. Lmx1b expression is maintained by the glycoprotein Fgf8, a signal capable of mediating IsO signaling. Lmx1b, in turn, maintains the expression of the secreted factor Wnt1. Our conclusions are substantiated by the following: (i) Lmx1b mRNA becomes localized to the isthmus immediately after Fgf8 initiation, (ii) Wnt1 expression is localized to the Lmx1b expression domain, but with slightly later kinetics, (iii) Fgf8-soaked beads generate similar domains of expression for Lmx1b and Wnt1 and (iv) retroviral-mediated expression of Lmx1b (Lmx1b/RCAS) maintains Wnt1 expression in the mesencephalon. Ectopic Lmx1b is insufficient to alter the expression of a number of other genes expressed at the IsO, suggesting that it does not generate a new signaling center. Instead, if we allow Lmx1b/RCAS-infected brains to develop longer, we detect changes in mesencephalic morphology. Since both ectopic and endogenous Lmx1b expression occurs in regions of the isthmus undergoing morphological changes, it could normally play a role in this process. Furthermore, a similar phenotype is not observed in Wnt1/RCAS-infected brains, demonstrating that ectopic Wnt1 is insufficient to mediate the effect of ectopic Lmx1b in our assay. Since Wnt1 function has been linked to the proper segregation of mesencephalic and metencephalic cells, we suggest that Lmx1b and Wnt1 normally function in concert to affect IsO morphogenesis.
Mammalian Petrosal from the Upper Jurassic Morrison Formation of Fruita, Colorado

ABSTRACT A partial petrosal from the Upper Jurassic Morrison Formation of the Fruita Paleontological Area of western Colorado preserving the pars cochlearis and part of the pars canalicularis is described. The endocast of the inner ear showing the cochlea, vestibule, lateral semicircular canal, and the terminal ends of the anterior and posterior semicircular canals is reconstructed from µCT scans. This specimen is only the fourth petrosal known from the Morrison Formation. Mammals known from Fruita include Fruitafossor windsheffeli Luo and Wible, 2005, the triconodontid Priacodon fruitaensis Rasmussen and Callison, 1981, the plagiaulacoid multituberculate Glirodon grandis Engelmann and Callison, 1999, and unnamed spalacotheriids and dryolestoids. The partial petrosal and its endocast share significant features with dryolestoids from the Upper Jurassic of Guimarota, Portugal, including a separate fenestra cochleae and cochlear canaliculus, and a cochlea that is coiled more than 200°. In light of these simi...
Invariant measures on G/Γ for split simple Lie groups G

We study the left action α of a Cartan subgroup on the space X = G/Γ, where Γ is a lattice in a simple split connected Lie group G of rank n > 1. Let μ be an α-invariant measure on X. We give several conditions using entropy and conditional measures, each of which characterizes the Haar measure on X. Furthermore, we show that the conditional measure on the foliation of unstable manifolds has the structure of a product measure. The main new element compared to the previous work on this subject is the use of noncommutativity of root foliations to establish rigidity of invariant measures. © 2003 Wiley Periodicals, Inc.
A plausible mechanism for gene correction by chimeric oligonucleotides.

Self-complementary chimeric oligonucleotides that consist of DNA and 2‘-O-methyl RNA nucleotides arranged in a double-hairpin configuration can elicit a point mutation when targeted to a gene sequence. We have used a series of structurally diverse chimeric oligonucleotides to correct a mutant neomycin phosphotransferase gene in a human cell-free extract. Analysis of structure−activity relationships demonstrates that the DNA strand of the chimeric oligonucleotide acts as a template for high-fidelity gene correction when one of its bases is mismatched to the targeted gene. By contrast, the chimeric strand of the oligonucleotide does not function as a template for gene repair. Instead, it appears to augment the frequency of gene correction by facilitating complex formation with the target. In the presence of RecA protein, each strand of a chimeric oligonucleotide can hybridize with double-stranded DNA to form a complement-stabilized D-loop. This reaction, which may take place by reciprocal four-strand exchan...
The influence of perceived risk of exposure to human immunodeficiency virus on medical students' planned specialty choices

The purpose of this report is to determine the influence of the acquired immunodeficiency syndrome (AIDS) epidemic on medical students' training and career plans through a prospective, anonymous self-administered survey of 10 Likert-scaled (1 strongly agree to 5 strongly disagree) responses to statements assessing attitude toward patients with human immunodeficiency virus (HIV), adequacy of knowledge and experience with HIV, and influence of HIV on career choices. The study was done at a major AIDS referral university teaching hospital. The participants were first- through fourth-year medical students in spring 1990. A 72% (of 451 students) response revealed that both surgery and emergency medicine were perceived as high risk of exposure specialties. Students indicated an overall willingness to care for HIV-positive patients (mean, 2.54) and a general adequacy of knowledge and experience (mean 2.54). The AIDS epidemic has had little influence for training, future career, and practice locations (mean, 4.06). Responses differed by class year. The later class years were more willing to care for HIV patients (P < .001) and indicated more knowledge and experience with HIV (P < .001). Influence on career, training and practice location choices were without class trend. In contrast to some studies, this group of medical students had relatively positive attitudes toward patients with HIV and were not particularly influenced by the AIDS epidemic regarding career choices.
Suppression of polyclonal immunoglobulin production by a soluble factor produced by a human thymus hybridoma

Abstract A human thymus cell hybridoma was established using thymus cells obtained from a patient with common variable hypogammaglobulinemia and associated thymoma. This hybridoma secreted a suppressor factor for polyclonal antibody synthesis. Supernatants of this hybrid showed 40–80% suppression of both IgM and IgG synthesis by pokeweed mitogen-stimulated human peripheral blood lymphocytes. Hybridoma supernatants were suppressive for immunoglobulin production only if added within the initial 48 h of the seven-day culture period. Suppression of antibody production by the hybridoma supernatant was prevented by preabsorption with T lymphocytes. Further, the suppressor factor was shown to inhibit antibody production in reconstructed cultures containing T4 + cells and B cells, yet the suppression could be abrogated by increasing the number of T4 + cells. The hybrid supernatant had no affect on the proliferation of human mononuclear cells in response to pokeweed mitogen, lipopolysaccharide, concanavalin A or alloantigen but inhibited phytohemagglutinin-induced proliferation. The target cell population for the inhibition of phytohemagglutinin responsiveness was shown to be a T4 + lymphocyte (helper inducer T cell). These results suggest that thymus hybridoma cells can produce immunoregulatory products that act through the modulation of T4 + lymphocyte function. To our knowledge this is the first human thymus cell hybridoma to be reported. Studies on such cell lines may provide important information on immunoregulatory thymic factors.
TCR γ δ+ dendritic epidermal T cells as constituents of skin-associated lymphoid tissue

The epidermis of all strains of normal mice is populated by two distinct dendritic, bone marrow-derived cells: Langerhans cells and CD4-CD8- Thy-1+ dendritic epidermal T cells (DETC). The overwhelming majority of DETC are an unusually homogeneous population of thymic-dependent cells which express CD3-associated T-cell antigen receptors (TCRs) of the gamma/delta type, thereby distinguishing them from conventional CD4+CD8- or CD4-CD8+ T cells expressing CD3-associated alpha/beta TCR. Most DETC are ontogenetically primitive, derived from early fetal thymocytes with a preferential, but poorly understood tropism for the epidermis. Like the TCR on other populations of gamma/delta cells, which preferentially populate other epithelia such as in the gut and lung, the TCR on most DETC selectively utilize particular variable (V) gene segments (i.e., V gamma 3 and V delta 1 for DETC vs V gamma 5 and V delta 4 or V delta 6 for intestinal intraepithelial lymphocytes). However, unlike other gamma/delta populations whose TCR junctional regions exhibit marked heterogeneity, DETC junctional diversity is extremely limited. This lack of TCR heterogeneity among DETC suggests they recognize a narrow range of physiologic ligands (antigens) and that this recognition is restricted not by conventional polymorphic class-I or class-II MHC molecules, but rather by relatively nonpolymorphic self MHC-like molecules of the class Ib MHC type [e.g., Qa, TL, and CD1 (T6)]. Additional studies are required to clarify precisely what DETC recognize, their relevant biological functions, as well as their relationship(s) to the gamma/delta cells recently identified in human skin.
Stenting After Optimal Lesion Debulking (SOLD) Registry Angiographic and Clinical Outcome

Background—Coronary stenting has reduced restenosis in focal de novo lesions, but its impact has been less pronounced in complex lesion subsets. Preliminary data suggest a role for plaque burden in promoting intimal hyperplasia after stent implantation. The aim of this study was to test the hypothesis that plaque removal with directional atherectomy before stent implantation may lower the intensity of late neointimal hyperplasia, reducing the incidence of in-stent restenosis. Methods and Results—Seventy-one patients with 90 lesions underwent directional atherectomy before coronary stenting. Intravascular ultrasound–guided stenting was performed in 73 lesions (81%). Clinical success was achieved in 96% of patients. Procedural complications were as follows: emergency bypass surgery in 1 patient (1.4%), who died 2 weeks later; Q-wave myocardial infarction in 2 patients (2.8%); and non–Q-wave myocardial infarction in 8 patients (11.3%). None of the patients had stent thrombosis at follow-up. Angiographic foll...
Colonisation of the Pacific by Bembidion beetles (Coleoptera : Carabidae), with description of Bembidion tahitiense, sp. nov. from Tahiti, French Polynesia

Bembidion (Sloanephila) tahitiense, sp. nov. is described from Mont Mauru, an isolated massif of Tahiti Nui volcano. Based on evidence from seven genes (four nuclear protein-coding, one mitochondrial protein-coding, two nuclear ribosomal), its sister group is the Australian B. jacksoniense Guerin-Meneville, with which it shares a synapomorphic spur on the ostium of the male genitalia. In contrast to B. jacksoniense, B. tahitiense is brachypterous, with rounded humeri, constricted posterior pronotal margins and convex body form. Examination of the seven genes in two species of the Hawaiian subgenus Nesocidium Sharp reveals that the sister group of Nesocidium is subgenus Zecillenus Lindroth from New Zealand. These two subgenera belong to the Ananotaphus complex, a clade inhabiting Australia, New Zealand and Hawaii. The relationships of the second Hawaiian subgenus, Gnatholymnaeum Sharp, are less clear, although Gnatholymnaeum belongs to the Bembidion series (along with Sloanephila and the Ananotaphus complex). Bembidion beetles colonised the Society and Hawaiian islands independently from source areas in the south-west Pacific. Based on parsimonious reconstructions of flight-wing configuration, the Tahitian and Hawaiian colonisations involved winged individuals. Colonisation of the Society and Hawaiian islands by carabid beetles of two other tribes – Platynini and Moriomorphini – follow the dispersal patterns hypothesised for Bembidion.
Temperature and community consequences of the loss of foundation species: Surfgrass (Phyllospadix spp., Hooker) in tidepools

By ameliorating environmental conditions, mediating species interactions and regulating resource availability in ecosystems, habitat-forming, foundation species underlie the structure and function of many ecological communities. Current and predicted human-induced changes to ecosystems require a mechanistic understanding of how foundation species enable the persistence of diverse, functioning ecological communities. By manipulating the abundance of a putative foundation species of rocky intertidal tidepool communities, the seagrass Phyllospadix spp. (surfgrass), this study assesses how surfgrass affects the thermal environment and structure of tidepool communities over a period of two years. Surfgrass removal pools experienced temperatures up to 10 °C higher than control pools during low tide. Changes in community composition of sessile organism accompanied this change in thermal regime. Over two years, removal pools saw a significant decline in the abundance of coralline crusts and bare space and an increase in the abundance of foliose red algae while control pool communities remained stable. At the level of functional groups, community similarity metrics showed pool communities became more variable in space in response to surfgrass removal, demonstrating that pool communities diverge dramatically in the absence of surfgrass. In removal pools, recovery of surfgrass was limited with less than 25% of pre-removal abundance after two years. However, removal pool communities shifted toward species compositions that favor surfgrass recruitment and suggest a mechanism by which surfgrass recovery may be enhanced over the long-term. Surfgrass clearly play a foundational role in tidepools by reducing pool temperatures and act to stabilize tidepool communities.
SU‐GG‐T‐246: Systematics Review of Patient‐Specific Plan Dose Verification in IMRT and RapidArc Treatments by Ion‐Chamber Measurements

Purpose: To review the accuracy and systematic trend of patient‐specific plan dose verification by ion chamber measurements for 272 IMRT and RapidArc clinical cases of brain, spine, head‐and‐neck, prostate, lung,liver and pelvis‐non‐prostate treatments. Methods & Materials: A BrainLAB IMRT QA Phantom and a 0.125 cc ion‐chamber (PTW 31010) was used to measure composite dose at a high‐dose and low‐gradient point near iso‐center. Measured doses are compared to calculated doses in treatment planning systems for a total of 272 clinical cases, of which 203 are IMRT treatments planned in BrainSCAN and 69 are RapidArc treatments planned in Eclipse. Distributions of percentage differences between measured dose and planned dose are reviewed to extract the mean, standard deviation and range of the differences, from which confidence levels of |mean deviation|+1.96×SD are determined and compared to the action levels recommended by AAPM TG‐119. Results: For the 203 IMRT cases, the mean percentage difference was −1.89%, the standard deviation was 1.28%, the range of the differences was −4.67% to 4.17%, the confidence level was determined to be 4.40%. For the 69 RapidArc cases, the mean percentage difference was −0.17%, the standard deviation was 2.38%, range of the differences was −4.76% to 5.15%, the confidence level was determined to be 4.83%. Conclusion: The results of ion‐chamber dose verification for 272 patient‐specific IMRT and RapidArc plans were reviewed. The confidence levels determined from the IMRT cases (4.40%) and the RapidArc cases (4.83%) are better or close to the confidence levels of 4.5%∼4.7% established in AAPM TG‐119 by planning and delivering multiple IMRT plans on a suite of 7 phantom cases among 9 institutions. Significantly more clinical cases will be included for extracting disease‐site specific confidence levels, particularly for RapicArc treatments where DMLC motion speed, gantry speed and dose‐rate are all utilized in plan optimization and delivery.
Hydrodynamic models for the diffusivity of type A botulinum neurotoxin

The times-to-maximum effect of type A botulinum neurotoxin (BoNT/A) depend to some extent on biophysical and biochemical variables. These times range from <3 h (isolated nerve-muscle preparations) to 1-3 weeks (healthy human volunteers). Hydrodynamic equations were solved for different models, some of which produced values of the diffusion coefficient (D) that are comparable to those of other proteins. Other results differed by up to five orders of magnitude. Because the in vivo findings were not related to an unusually small value for D, we propose that there is a protective reservoir for BoNT/A in vivo and possibly for other serotypes.
Direct Methoxypyridine Functionalization Approach to Magellanine-Type Lycopodium Alkaloids

A concise enantioselective approach to the tetracyclic core of the magellanine-type Lycopodium alkaloids is reported. Key to this approach is the use of the Hajos–Parrish reaction to set a challenging quaternary stereocenter, thereby guiding the stereoselectivity for the remainder of the synthesis, as well as the use of a palladium-mediated direct pyridine functionalization reaction to forge the tetracyclic core.