bluuebunny/crossref_metadata_2025 huggingface dataset:
The non–muscle actinopathy–associated mutation E334Q in cytoskeletal γ– actin perturbs interaction of actin filaments with myosin and ADF/cofilin family proteins
Authors: Greve Johannes N. , Marquardt Anja , Heiringhoff Robin , Reindl Theresia , Thiel Claudia , Donato Nataliya Di , Taft Manuel H. , Manstein Dietmar J.
Published: February 2024

Various heterozygous cytoskeletal γ–actin mutations have been shown to cause Baraitser–Winter cerebrofrontofacial syndrome, non–syndromic hearing loss, or isolated eye coloboma. Here, we report the biochemical characterization of human cytoskeletal γ–actin carrying mutation E334Q, a mutation that leads to a hitherto unspecified non–muscle actinopathy. Following expression, purification, and removal of linker and thymosin β4 tag sequences, the p.E334Q monomers show normal integration into linear and branched actin filaments. The mutation does not affect thermal stability, actin filament nucleation, elongation and turnover. Model building and normal mode analysis predict significant differences in the interaction of p.E334Q–filaments with myosin motors and members of the ADF/cofilin family of actin–binding proteins. Assays probing the interactions of p.E334Q–filaments with human class 2 and class 5 myosin motor constructs show significant reductions in sliding velocity and actin–affinity. E334Q differentially affects cofilin-mediated actin dynamics by increasing the rate of cofilin-mediated de novo nucleation of actin filaments and decreasing the efficiency of cofilin-mediated filament severing. Thus, it is likely that p.E334Q-mediated changes in myosin motor activity, as well as filament turnover contribute to the observed disease phenotype.
A latent clinical-anatomical dimension relating metabolic syndrome to brain structure and cognition
Authors: Petersen Marvin , Hoffstaedter Felix , Nägele Felix L. , Mayer Carola , Schell Maximilian , Rimmele D. Leander , Zyriax Birgit-Christiane , Zeller Tanja , Kühn Simone , Gallinat Jürgen , Fiehler Jens , Twerenbold Raphael , Omidvarnia Amir , Patil Kaustubh R. , Eickhoff Simon B. , Thomalla Götz , Cheng Bastian
Published: February 2024

The link between metabolic syndrome (MetS) and neurodegenerative as well cerebrovascular conditions holds substantial implications for brain health in at-risk populations. This study elucidates the complex relationship between MetS and brain health by conducting a comprehensive examination of cardiometabolic risk factors, cortical morphology, and cognitive function in 40,087 individuals. Multivariate, data-driven statistics identified a latent dimension linking more severe MetS to widespread brain morphological abnormalities, accounting for up to 71% of shared variance in the data. This dimension was replicable across sub-samples. In a mediation analysis we could demonstrate that MetS-related brain morphological abnormalities mediated the link between MetS severity and cognitive performance in multiple domains. Employing imaging transcriptomics and connectomics, our results also suggest that MetS-related morphological abnormalities are linked to the regional cellular composition and macroscopic brain network organization. By leveraging extensive, multi-domain data combined with a dimensional stratification approach, our analysis provides profound insights into the association of MetS and brain health. These findings can inform effective therapeutic and risk mitigation strategies aimed at maintaining brain integrity.
Volumetric trans-scale imaging of massive quantity of heterogeneous cell populations in centimeter-wide tissue and embryo
Authors: Ichimura Taro , Kakizuka Taishi , Taniguchi Yoshitsugu , Ejima Satoshi , Sato Yuki , Itano Keiko , Seiriki Kaoru , Hashimoto Hitoshi , Sugawara Ko , Itoga Hiroya , Onami Shuichi , Nagai Takeharu
Published: February 2024

We established a volumetric trans-scale imaging system with an ultra-large field-of-view (FOV) that enables simultaneous observation of millions of cellular dynamics in centimeter-wide three-dimensional (3D) tissues and embryos. Using a custom-made giant lens system with a magnification of ×2 and a numerical aperture (NA) of 0.25, and a CMOS camera with more than 100 megapixels, we built a trans-scale scope AMATERAS-2, and realized fluorescence imaging with a transverse spatial resolution of approximately 1.1 µm across an FOV of approximately 1.5×1.0 cm2. The 3D resolving capability was realized through a combination of optical and computational sectioning techniques tailored for our low-power imaging system. We applied the imaging technique to 1.2 cm-wide section of mouse brain, and successfully observed various regions of the brain with sub-cellular resolution in a single FOV. We also performed time-lapse imaging of a 1-cm-wide vascular network during quail embryo development for over 24 hr, visualizing the movement of over 4.0×105 vascular endothelial cells and quantitatively analyzing their dynamics. Our results demonstrate the potential of this technique in accelerating production of comprehensive reference maps of all cells in organisms and tissues, which contributes to understanding developmental processes, brain functions, and pathogenesis of disease, as well as high-throughput quality check of tissues used for transplantation medicine.
Sperm fertility in mice with oligo-astheno-teratozoospermia restored by in vivo injection and electroporation of naked mRNA
Authors: Vilpreux Charline , Martinez Guillaume , Fourquin Paul , Court Magali , Appaix Florence , Duteyrat Jean-Luc , Henry Maxime , Vollaire Julien , Ayad Camille , Yavuz Altan , De Macedo Lisa , Chevalier Geneviève , Llano Edgar Del , Lambert Emeline , Conte Sekou Ahmed , Wehbe Zeina , Giordani Elsa , Josserand Véronique , Brocard Jacques , Charles Coutton , Verrier Bernard , Ray Pierre F , Loeuillet Corinne , Arnoult Christophe , Escoffier Jessica
Published: February 2024

Oligo-astheno-teratozoospermia (OAT), a recurent cause of male infertility, is the most frequent disorder of spermatogenesis with a probable genetic cause. Patients and mice bearing mutations in the
ARMC2
gene have a decreased sperm concentration, and individual sperm show multiple morphological defects and a lack of motility – a canonical OAT phenotype. Intracytoplasmic sperm injection (ICSI) is required to treat such a condition but it is associated with a small increase in birth defects in comparison to pregnancies not involving assisted conception . Consequently, new targeted treatments are needed to restore fertility. Here, a combination of
in vivo
injection and electroporation of capped and poly-A-tailed naked mRNA is tested as a strategy to treat
ARMC2
-related infertility in mouse. mRNAs coding for several reporter genes are tested and the efficiency and the kinetic of expression are assessed using
in vivo
and
in vitro
2D and 3D imaging experiments. We show that mRNA-coded reporter proteins are detected for up to 3 weeks in germ cells, making the use of mRNA possible to treat infertility. We compare these results with those obtained with a non-integrative plasmid Enhanced Episomal Vector (EEV), which induces low and transient expression in spermatogenic cells. Consequently, injection and electroporation of naked mRNA-
Armc2
into the testes of
Armc2
-deficient males were performed and we show the presence of normal and motile sperm in the epididymis. These motile sperm were able to produce embryos by IVF and ICSI. This study shows for the first time that mRNA-
Armc2
efficiently restores fertility and opens new paths for male infertility treatment.
RNA polymerase III is involved in regulating Plasmodium falciparum virulence
Authors: Diffendall Gretchen , Claës Aurélie , Barcons-Simon Anna , Nyarko Prince , Dingli Florent , Santos Miguel , Loew Damarys , Claessens Antoine , Scherf Artur
Published: February 2024

While often undetected and untreated, persistent seasonal asymptomatic malaria infections remain a global public health problem. Despite the presence of parasites in the peripheral blood, no symptoms develop. Disease severity is correlated with the levels of infected red blood cells (iRBCs) adhering within blood vessels. Changes in iRBC adhesion capacity has been linked to seasonal asymptomatic malaria infections, however how this is occurring is still unknown. Here we present evidence that RNA polymerase III (RNA Pol III) transcription in
Plasmodium falciparum
is downregulated in field isolates obtained from asymptomatic individuals during the dry season. Through experiments with in vitro cultured parasites, we have uncovered an RNA Pol III-dependent mechanism that controls pathogen proliferation and expression of a major virulence factor in response to external stimuli. Our findings establish a connection between
P. falciparum
cytoadhesion and a non-coding RNA family transcribed by Pol III. Additionally, we have identified
P. falciparum
Maf1 as a pivotal regulator of Pol III transcription, both for maintaining cellular homeostasis and responding adaptively to external signals. These results introduce a novel perspective that contributes to our understanding of
P. falciparum
virulence. Furthermore, it establishes a connection between this regulatory process and the occurrence of seasonal asymptomatic malaria infections.
Building a mathematical model of the brain
Authors: Skinner Frances
Published: February 2024

Automatic leveraging of information in a hippocampal neuron database to generate mathematical models should help foster interactions between experimental and computational neuroscientists.
Defect identification of bare printed circuit boards based on Bayesian fusion of multi-scale features
Authors: Han Xixi , Li Renpeng , Wang Boqin , Lin Zhibo
Published: February 2024

The aim of this article is to propose a defect identification method for bare printed circuit boards (PCB) based on multi-feature fusion. This article establishes a description method for various features of grayscale, texture, and deep semantics of bare PCB images. First, the multi-scale directional projection feature, the multi-scale grey scale co-occurrence matrix feature, and the multi-scale gradient directional information entropy feature of PCB were extracted to build the shallow features of defect images. Then, based on migration learning, the feature extraction network of the pre-trained Visual Geometry Group16 (VGG-16) convolutional neural network model was used to extract the deep semantic feature of the bare PCB images. A multi-feature fusion method based on principal component analysis and Bayesian theory was established. The shallow image feature was then fused with the deep semantic feature, which improved the ability of feature vectors to characterize defects. Finally, the feature vectors were input as feature sequences to support vector machines for training, which completed the classification and recognition of bare PCB defects. Experimental results show that the algorithm integrating deep features and multi-scale shallow features had a high recognition rate for bare PCB defects, with an accuracy rate of over 99%.
LFC-UNet: learned lossless medical image fast compression with U-Net
Authors: Liao Hengrui , Li Yue
Published: February 2024

In the field of medicine, the rapid advancement of medical technology has significantly increased the speed of medical image generation, compelling us to seek efficient methods for image compression. Neural networks, owing to their outstanding image estimation capabilities, have provided new avenues for lossless compression. In recent years, learning-based lossless image compression methods, combining neural network predictions with residuals, have achieved performance comparable to traditional non-learning algorithms. However, existing methods have not taken into account that residuals often concentrate excessively, hindering the neural network’s ability to learn accurate residual probability estimation. To address this issue, this study employs a weighted cross-entropy method to handle the imbalance in residual categories. In terms of network architecture, we introduce skip connections from U-Net to better capture image features, thereby obtaining accurate probability estimates. Furthermore, our framework boasts excellent encoding speed, as the model is able to acquire all residuals and residual probabilities in a single inference pass. The experimental results demonstrate that the proposed method achieves state-of-the-art performance on medical datasets while also offering the fastest processing speed. As illustrated by an instance using head CT data, our approach achieves a compression efficiency of 2.30 bits per pixel, with a processing time of only 0.320 seconds per image.
Identification of Male Sterile Lines and Floral Characterization of White Onion (Alium cepa)
Authors: Naveenkumar B S  , Veere Gowda R  , Padmini K  , Gayen Rajshree
Published: February 2024

The investigation was conducted at the Division of Vegetable Crops, IIHR- Bengaluru. The experiment was carried out with a Randomized block design with 10 treatments and 3 replications namely PW0-18, TW-18, PWR-18, RW-18, and AW-O-18 these Male sterile lines, and their respective fertile lines were identified by visual observation, staining, and bagging techniques.
An evaluation of bed shear stress under turbid flows
Authors: Thompson C. E. L. , Amos C. L. , Angelaki M. , Jones T. E. R. , Binks C. E.
Published: April 2006

This paper investigates the effect of various turbidity levels on the drag coefficient and bed shear stress in decelerating flows over a smooth bed. Turbid flows were simulated in a laboratory annular flume (Lab Carousel) using clay suspensions of different known mass concentrations. Flow velocity measurements were taken in the turbulent boundary layer and the values of bed drag coefficient and shear stress were calculated using the method of flow deceleration. Results showed that the bed drag coefficient responds significantly to an increase in the suspended sediment concentration (up to 20 g\L) showing a decrease of up to 50% in drag due to turbulence suppression. However, subsequent increases in mass concentration resulted in an increase in the drag coefficient reaching the clear water value at approximately 200 g\L because of the influence of viscosity. Thus the application of the law of the wall in flows of high concentrations of suspended cohesive sediments up to 200 g\L results in overestimation of the bed shear stress.
Genotype by environment interactions in viability and developmental time in populations of cactophilic Drosophila
Authors: Fanara J. J. , Folguera G. , Iriarte P. F. , Mensch J. , Hasson E.
Published: April 2006

The genetic and ecological basis of viability and developmental time differences between Drosophila buzzatii and D. koepferae were analysed using the isofemale line technique. Several isofemale lines were sampled from pairs of allopatric/sympatric populations of each species. Flies were reared in media prepared with decaying tissues of two of the main natural cactus hosts of each species. This experimental design enabled us to evaluate the relative contribution of phenotypic plasticity, genetic variation and genotype by environment interaction (G × E) to total phenotypic variation for two fitness traits, viability and developmental time. Our results revealed significant G × E in both traits, suggesting that the maintenance of genetic variation can be explained, at least in part, by diversifying selection in different patches of a heterogeneous environment in both species. However, the relative importance of the factors involved in the G × E varied between traits and populations within species. For viability, the G × E can be mainly attributed to changes in the rank order of lines across cacti. However, the pattern was different for developmental time. In D. buzzatii the G × E can be mainly accounted for by changes in among line variance across cacti, whereas changes in the rank order of lines across cacti was the main component in D. koepferae. These dissimilar patterns of variation between traits and species suggest that the evolutionary forces shaping genetic variation for developmental time and viability vary between populations within species and between species.
Surface tension influences cell shape and phagocytosis in alveolar macrophages
Authors: Akei Hiroko , Whitsett Jeffrey A. , Buroker Michelle , Ninomiya Takafumi , Tatsumi Haruyuki , Weaver Timothy E. , Ikegami Machiko
Published: April 2006

The effect of surface tension on alveolar macrophage shape and phagocytosis was assessed in vivo and in vitro. Surface tension was regulated in vivo by conditionally expressing surfactant protein (SP)-B in Sftpb−/−mice. Increased surface tension and respiratory distress were produced by depletion of SP-B and were readily reversed by repletion of SP-B in vivo. Electron microscopy was used to demonstrate that alveolar macrophages were usually located beneath the surfactant film on the alveolar surfaces. Reduction of SP-B increased surface tension and resulted in flattening of alveolar macrophages on epithelial surfaces in vivo. Phagocytosis of intratracheally injected fluorescent microbeads by alveolar macrophages was decreased during SP-B deficiency and was restored by repletion of SP-B in vivo. Incubation of MH-S cells, a mouse macrophage cell line, with inactive surfactant caused cell flattening and decreased phagocytosis in vitro, findings that were reversed by the addition of sheep surfactant or phospholipid containing SP-B. SP-B controls surface tension by forming a surfactant phospholipid film that regulates shape and nonspecific phagocytic activity of alveolar macrophages on the alveolar surface.
Ultrasound for Cancer Investigation: An Anecdotal History
Authors: Hill C. R.
Published: April 2006

Cancer surgery had been largely a blind art until, in 1949, a British surgeon working in Minneapolis exploited the potential of a US naval radar training device, in which a 15-MHz ultrasonic beam substituted for the radar. Within the next 5 years John Wild had reported work on the basis of much of modern practice: grey-scale imaging of tumours, quantitative tissue characterization, echo-endoscopy and even the question of possible hazards. Wild's work was stopped dead in 1955 by bureaucratic politics and, in spite of spectacular and eventually successful litigation, never recovered. In the following years, fashion in scanner design was aimed at outlining organ boundaries, with use of bi-stable display devices, consequent loss of grey-scale information, and general failure to image tumours. An exception to this trend was the work of the Commonwealth Acoustic Laboratory, in Sydney, who developed obstetric scanners with very good grey-scale representation. Helped by this, the author's group, at the Institute of Cancer Research and Royal Marsden Hospital, developed a series of scanners that were intended for abdominal and breast work, and which enabled, for the first time, visualization of a range of soft tissue pathology. It was curiosity as to the acoustic scattering processes underlying this visualization technique that led our group and others to embark on substantial, and still ongoing, studies of the physics of the subject.
The Neural Tube Defect: Issues of Prenatal Diagnosis, Genetic Counselling, Prevention and Management
Authors: Acharya Ganesh , Jonsrud Christoffer , Maltau Jan Martin
Published: April 2006

Neural tube defects (NTDs) are among the most common major congenital abnormalities with a prevalence rate of approximately 1 per 1000 births, although it varies significantly according to geographical location. NTDs represent the first congenital malformations shown to be preventable through simple public health measures. Ensuring adequate periconceptional folic acid intake prevents both occurrence and recurrence of a significant proportion of NTDs, but distinguishing folate resistant NTDs is not yet possible. Despite improvements in the prenatal screening, diagnosis and management of NTDs, antenatal prediction and prevention of neurological disabilities after birth remains difficult, with over one-third of long-term survivors continuing to require daily care. Ultrasound examination has virtually replaced amniotic fluid AFP and cholinesterase measurement for the diagnosis of NTDs. Emphasis now should be on primary prevention, early detection and prevention of long-term morbidity. Effective prenatal diagnosis and proper genetic counselling provides parents with a variety of options that may be appropriate for their individual situation.
Spectrum of Ultrasound Diagnoses in Patients Presenting via the Fast-track Deep Vein Thrombosis Service: A Pictorial Review
Authors: Wilde Susan , Wilson Paddy
Published: April 2006

In the last decade ultrasound has become the gold standard for evaluating symptomatic patients with suspected deep vein thrombosis (DVT). As well as reliably confirming or excluding DVT, ultrasound can diagnose alternative or co-existent pathologies, which may be contributing to the patient's symptoms. We present a series of patients who were all referred through the fast-track DVT service in whom other unsuspected pathologies were found at the original ultrasound examination.
Self-heating of Diagnostic Ultrasound Transducers in Air and in Contact with Tissue Mimics
Authors: Calvert Justine , Duck Francis
Published: April 2006

The temperature rises at the surface of diagnostic ultrasound transducers in air and in contact with a tissue-equivalent phantom have been compared. Twenty-five transducers from seven different manufacturers were studied in imaging and pulsed Doppler modes. Comparisons were made between the temperature rise at 200 s 'in air' and 'on phantom' using two standard tissue mimicking materials (TMMs). Temperature rises in contact with the phantom (ΔTp) were always lower than those in air (ΔTa). Using a phantom that included a 1·5-mm silicone rubber layer to mimic the skin, the relative temperature rises ΔTp/ΔTa varied from 43 to 87 % with an average of 60%. The two TMMs gave comparable temperature rises despite their different compositions. Relative temperature rise depended slightly on frequency (2·5% MHz−1) and was higher on average in imaging mode than in pulsed Doppler mode. Linear relationships were observed between temperature rise and acoustic power, and relative temperature rise and silicone rubber thickness (∼11.5% mm−1). The phantoms gave rise to broadly similar temperature rises to those on skin, although the 1·5-mm silicone rubber skin-mimic layer may give a slight over-estimate of temperature rise for some transducers.
Steam‐Explosion Pretreatment for Enhancing Anaerobic Digestion of Municipal Wastewater Sludge
Authors: Dereix Marcela , Parker Wayne , Kennedy Kevin
Published: April 2006

This study evaluated the use of steam explosion as a pretreatment for municipal wastewater treatment sludges and biosolids as a technique for enhancing biogas generation during anaerobic digestion. Samples of dewatered anaerobic digester effluent (biosolids) and a mixture of thickened waste activated sludge (TWAS) and biosolids were steam‐exploded under differing levels of intensity in this study. The results indicate that steam explosion can solublize components of these sludge streams. Increasing the intensity of the steam‐explosion pressure and temperature resulted in increased solublization. The steam‐explosion pretreatment also increased the bioavailability of sludge components under anaerobic digestion conditions. Increasing the steam‐explosion intensity increased the ultimate yield of methane during anaerobic digestion. Batch anaerobic digestion tests suggested that pretreatment at 300 psi was the most optimal condition for enhanced biogas generation while minimizing energy input. Semicontinuous anaerobic digestion revealed that the results that were observed in the batch tests were sustainable in prolonged operation. Semicontinuous digestion of the TWAS/biosolids mixture that was pretreated at 300 psi generated approximately 50% more biogas than the controls. Semicontinuous digestion of the pretreated biosolids resulted in a 3‐fold increase in biogas compared with the controls. Based on capillary suction test results, steam‐explosion pretreatment at 300 psi improved the dewaterability of the final digested sludge by 32 and 45% for the TWAS/biosolids mixture and biosolids, respectively, compared with controls. The energy requirements of the nonoptimized steam‐explosion process were substantially higher than the additional energy produced from enhanced digestion of the pretreated sludge. Substantial improvements in energy efficiency will be required to make the process viable from an energy perspective.
United States v. Duarte-Acero
Authors: Sloss David L.
Published: April 2006

In United States v. Duarte-Acero, the Eleventh Circuit Court of Appeals held that the International Covenant on Civil and Political Rights does not regulate the extraterritorial conduct of U.S. government agents. Additionally, the court held that the Covenant is not self-executing and therefore that it does not create individual rights that are judicially enforceable in U.S. courts.
Podkolzina v. Latvia. App. No. 46726/99
Authors: Caron David D. , Hoffmeister Frank
Published: April 2006

Podkolzinav. Latvia. App. No. 46726/99. At . European Court of Human Rights, April 9, 2002.

In Podkolzina v. Latvia, the European Court of Human Rights held that Latvia violated the applicant's right to stand as a candidate for parliamentary elections, as set out in Article 3 of Protocol No. I to the European Convention on Human Rights in striking the applicant off the list of registered candidates due to allegedly inadequate language skills. The Court ordered Latvia to pay 9,000 for nonpecuniary damages and for costs and expenses.

The applicant, a member of the Russian-speaking minority in Latvia, acquired an official language certificate in January 1997. The certificate was issued by a regional board of the State Language Centre, composed of five examiners. On the basis of written and oral examinations that were evaluated in accordance with criteria and levels of competence defined by legal regulations, the five-member board certified that Podkolzina's command of the Latvian language corresponded to the “third level.”
State Immunity, Human Rights, and Jus Cogens: A Critique of the Normative Hierarchy Theory
Authors: Caplan Lee M.
Published: April 2006

When Sulaiman Al-Adsani traveled from the United Kingdom to Kuwait to repel Saddam Hussein’s invasion in 1991, he never dreamed he would depart with bruises and burns inflicted by the very government he had sought to defend. According to Al-Adsani, his troubles began when he was accused of releasing sexual videotapes of Sheikh Jaber Al-Sabah Al-Saud Al-Sabah, a relative of the emir of Kuwait, into general circulation. After the first Gulf war, with the aid of government troops, the sheikh exacted his revenge by breaking into Al-Adsani’s house, beating him, and transporting him to a Kuwaiti state prison, where his beatings continued for days. Al-Adsani was subsequently taken at gunpoint in a government car to the palace of the emir’s brother, where his ordeal intensified. According to Al-Adsani, his head was repeatedly submerged in a swimming pool filled with corpses and his body was badly burned when he was forced into a small room where the sheikh set fire to gasoline-soaked mattresses.
The Fifty-Fifth Session of the International Law Commission
Authors: Matheson Michael J. , Bickler Sara
Published: April 2006

The International Law Commission held its fifty-fifth session in Geneva from May 5 to June 6, and from July 7 to August 8, 2003, under the chairmanship of Enrique Candioti of Argentina. The Commission elected Roman Kolodkin of the Russian Federation, Constantin Economides of Greece, Teodor Melescanu of Romania, and Michael Matheson of the United States to fill the vacancies resulting from the death of Valery Kuznetsov of the Russian Federation, the election of Bruno Simma of Germany and Peter Tomka of Slovakia to the International Court of Justice, and the resignation of Robert Rosenstock of the United States.
Toward Authoritativeness: The ICJ Ruling on Israel’s Security Wall
Authors: Folk Richard A.
Published: April 2006

On July 9, 2004, the International Court of Justice issued its advisory opinion on the legal consequences of Israel’s construction of a security wall on occupied Palestinian territory, declaring that the wall was in violation of international law. The advisory opinion also indicated that Israel should forthwith cease construction of the wall, dismantle what had been so far constructed, and make reparations to the Palestinians for all damages caused by the project. On July 20, 2004, at the Tenth Emergency Session of the General Assembly, Resolution ES-10/15 was adopted by a vote of 150 in favor, 6 opposed, and 10 abstentions, demanding that Israel comply with the legal obligations as specified by the advisory opinion.
Functional Polymorphisms of UCP2 and UCP3 Are Associated With a Reduced Prevalence of Diabetic Neuropathy in Patients With Type 1 Diabetes
Authors: Rudofsky Gottfried , Schroedter Antonia , Schlotterer Andreas , Voron’ko Olga E. , Schlimme Martin , Tafel Joerg , Isermann Berend H. , Humpert Per M. , Morcos Michael , Bierhaus Angelika , Nawroth Peter P. , Hamann Andreas
Published: April 2006

OBJECTIVE—We studied the association between polymorphisms in the UCP genes and diabetes complications in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS—We analyzed 227 patients with type 1 diabetes using PCR and subsequent cleavage by restriction endonucleases for the promoter variants A-3826G in the UCP1 gene, G-866A in the UCP2 gene, and C-55T in the UCP3 gene.

RESULTS—No effect of the A-3826G polymorphism in the UCP1 gene on diabetes complications was found. Patients who were heterozygous or homozygous for the G-866A polymorphism in the UCP2 gene or the C-55T polymorphism in the UCP3 gene had a significantly reduced prevalence of diabetic neuropathy (UCP2: odds ratio 0.44 [95% CI 0.24–0.79], P = 0.007; UCP3: 0.48 [0.25–0.92], P = 0.031), whereas there was no association with other diabetes complications. This effect was stronger when G-866A and C-55T occurred in a cosegregatory manner (UCP2 and UCP3: 0.28 [0.12–0.65], P = 0.002). Furthermore, a multiple logistic regression model showed an age- and diabetes duration–independent effect of the cosegregated polymorphisms on the prevalence of diabetic neuropathy (P = 0.013).

CONCLUSIONS—Our data indicate that both the G-866A polymorphism in the UCP2 gene and the C-55T polymorphism in the UCP3 gene are associated with a reduced risk of diabetic neuropathy in type 1 diabetes. Thus, the results presented here support the hypothesis that higher expression of uncoupling protein might prevent mitochondria-mediated neuronal injury and, ultimately, diabetic neuropathy.
Recent Trends in Cardiovascular Complications Among Men and Women With and Without Diabetes
Authors: Booth Gillian L. , Kapral Moira K. , Fung Kinwah , Tu Jack V.
Published: April 2006

OBJECTIVE—To compare recent trends in cardiovascular disease (CVD) outcomes among men and women with diabetes with those in the nondiabetic population.

RESEARCH DESIGN AND METHODS—We conducted a retrospective cohort study using provincial health claims data to identify adults with (n = 670,602) and without (n = 9,190,721) diabetes living in Ontario, Canada, between 1 April 1992 and 31 March 2000. We compared changes in the annual age-/sex-adjusted rates and numbers of subjects admitted for acute myocardial infarction (AMI) and stroke and of deaths from AMI, stroke, and all causes between those with and without diabetes.

RESULTS—Over the 8-year period, the rate of patients admitted for AMI and stroke fell to a greater extent in the diabetic than the nondiabetic population (AMI: −15.1 vs. −9.1%, P < 0.0001; stroke: −24.2 vs. 19.4%, P < 0.0001). Diabetic patients experienced similar reductions in case-fatality rates related to AMI and stroke than those without diabetes (−44.1 vs. −33.2%, P = 0.1; −17.1 vs. −16.6%, P = 0.9, respectively). Declines in all-cause mortality were also comparable in the two populations. Over the same period, the number of diabetes cases increased from 405,471 to 670,602. Thus, while CVD rates fell, the number of events occurring in this population rose substantially (AMI: +44.6%, stroke: +26.1%, AMI deaths: +17.2%, and stroke deaths: +13.2%).

CONCLUSIONS—Our findings demonstrate a significant reduction in the rate of people affected by CVD within the diabetic population. However, as the number of people with diabetes rises, so may the absolute burden of CVD in our society.
Physical Activity and Life Expectancy With and Without Diabetes
Authors: Jonker Jacqueline T. , De Laet Chris , Franco Oscar H. , Peeters Anna , Mackenbach Johan , Nusselder Wilma J.
Published: April 2006

OBJECTIVE—Physical activity is associated with a reduced risk of developing diabetes and with reduced mortality among diabetic patients. However, the effects of physical activity on the number of years lived with and without diabetes are unclear. Our aim is to calculate the differences in life expectancy with and without type 2 diabetes associated with different levels of physical activity.

RESEARCH DESIGN AND METHODS—Using data from the Framingham Heart Study, we constructed multistate life tables starting at age 50 years for men and women. Transition rates by level of physical activity were derived for three transitions: nondiabetic to death, nondiabetic to diabetes, and diabetes to death. We used hazard ratios associated with different physical activity levels after adjustment for age, sex, and potential confounders.

RESULTS—For men and women with moderate physical activity, life expectancy without diabetes at age 50 years was 2.3 (95% CI 1.2–3.4) years longer than for subjects in the low physical activity group. For men and women with high physical activity, these differences were 4.2 (2.9–5.5) and 4.0 (2.8–5.1) years, respectively. Life expectancy with diabetes was 0.5 (−1.0 to 0.0) and 0.6 (−1.1 to −0.1) years less for moderately active men and women compared with their sedentary counterparts. For high activity, these differences were 0.1 (−0.7 to 0.5) and 0.2 (−0.8 to 0.3) years, respectively.

CONCLUSIONS—Moderately and highly active people have a longer total life expectancy and live more years free of diabetes than their sedentary counterparts but do not spend more years with diabetes.
A Low Brain Serotonergic Neurotransmission in Children With Type 1 Diabetes Detected Through the Intensity Dependence of Auditory-Evoked Potentials
Authors: Manjarrez Gabriel , Herrera Rocio , Leon Monica , Hernandez-R Jorge
Published: April 2006

OBJECTIVE—To determine in children with type 1 diabetes the plasma free fraction of l-tryptophan (FFT) and the intensity-dependent auditory-evoked potentials (IDAEPs) as indicators of possible changes in brain serotonergic neurotransmission.

RESEARCH DESIGN AND METHODS—A prospective and comparative study was performed in children with type 1 diabetes and normal control subjects. We measured FFT, bound and total plasma l-tryptophan, neutral amino acids (NAAs), albumin, free fatty acids (FFAs), glucose, and HbA1c(A1C) and recorded IDAEPs with four intensities (40, 60, 90, and 103 dB).

RESULTS—The glycemia, A1C, FFAs, and NAAs in plasma were significantly elevated. The FFT and the FFT-to-total l-tryptophan and FFT-to-NAA ratios were reduced. The latencies of N1 and P2 increased at all intensities and the slope of the amplitude/stimulus intensity function (ASF slope) of the N1/P2 component significantly increased.

CONCLUSIONS—The decrease of the FFT in plasma and increase in the N1/P2 component amplitude may reflect a functional relationship between the brain serotonergic activity with the N1/P2 changes. The increase of the ASF slope in children with type 1 diabetes suggests that the response of the auditory cortex to sound intensity stimulus may be regulated by the serotonergic tone and that decreased serotonergic neurotransmission may provoke a different behavior of sensory cortices. Therefore, the IDAEP (N1/P2 component) may be an electrophysiological indicator of brain changes of serotonergic neurotransmission in children with type 1 diabetes. These changes may be related to psychoemotional manifestations observed in diabetic children such as anxiety and depression.
Lidar target-strength measurements on Northeast Atlantic mackerel (Scomber scombrus)
Authors: Tenningen Eirik , Churnside James H. , Slotte Aril , Wilson James J.
Published: April 2006

A linearly polarized green (532 nm) laser and a digital video camera were used to determine the reflectivity (R) and lidar (LIght Detection And Ranging) target strength (TS) of live mackerel by comparison with a standard calibration target. The measured reflectivity was 0.0141 ± 0.0005 when the receiver was copolarized with the laser and 0.0092 ± 0.0004 when the receiver was cross-polarized. The corresponding TS values were −42.66 ± 0.24 dB for the copolarized channel and −44.86 ± 0.23 dB for the cross-polarized channel. The depolarization ratio (depolarized return over total return) of 0.396 is very different from earlier measurements of sardine, suggesting that depolarization might be useful for species identification.
Observing seasonal bottom pressure variability in the North Pacific with GRACE
Authors: Bingham R. J. , Hughes C. W.
Published: April 2006

Using monthly gravity field solutions from GRACE together with output from an ocean model we assess the ability of GRACE to observe seasonal ocean bottom pressure variability in the North Pacific. First, the spatial structure and temporal evolution of the long‐term mean seasonal bottom pressure cycle in the North Pacific is characterised in the context of the ocean model. It is then shown that a mean seasonal cycle based on a limited subset of the model output corresponding to the intervals over which the GRACE monthly solutions were formed is representative of this long‐term seasonal cycle. It is therefore concluded that the significant features of the seasonal cycle should be present in the GRACE data. Agreement is found between the ocean model and GRACE estimates of the bottom pressure seasonal cycle, thus demonstrating the worth of GRACE as a tool for studying ocean dynamics.
Impact of solid Earth tide models on GPS coordinate and tropospheric time series
Authors: Watson C. , Tregoning P. , Coleman R.
Published: April 2006

Unmodelled sub‐daily periodic signals can propagate into time series of daily geodetic coordinates and tropospheric estimates at various different frequencies. Geophysical interpretations of geodetic products, particularly at seasonal timescales, can therefore be affected by poorly modelled signals in the geodetic analysis. In this study, we use two solid Earth tide models (IERS2003 and IERS1992) and analyses of global GPS data to demonstrate how this process occurs. Aliased annual and semi‐annual signals are evident in the vertical component of the GPS time series, with the amplitudes increasing as a function of latitude up to approximately 2.0 and 0.4 mm, respectively. Tropospheric zenith delay estimates show differences at the 2 mm level, with a dominant diurnal frequency. These results have significant implications in regard to the geophysical interpretation of GPS time series computed using the outdated IERS1992 model and, more generally, for any mis‐ or unmodelled periodic signals that affect geodetic sites.
Ground experimental demonstration on remote sensing of neutral particles in the upper atmosphere using artificial ion beam
Authors: Sugimoto Sachiko , Kuninaka Hitoshi , Nishiyama Kazutaka , Sakamoto Yusuke
Published: April 2006

Sounding rockets and satellites have been dedicated to measuring “natural” energetic neutral atoms (ENAs) in order to investigate ring current ions and precipitating ions. We studied the remote sensing method on the neutral particles in the upper atmosphere using “artificial” ENA in the laboratory. The measurement scheme is described below. A space‐borne plasma generator emits beam ions, which experience charge exchange collision with neighboring neutral particles to transform into artificial ENAs. Once ENAs are produced, they draw ballistic trajectories holding information, such as density and composition. In the upper atmosphere between 200 km and 700 km altitude, the primary constituent is atomic oxygen, to which krypton ion beams are sensitive. Measurement of artificial ENA at a remote region reveals global distribution of the neutral particles with high resolutions in time and space. One of the feasibility studies demonstrated the density measurement of O2 out of the mixture of O2 and N2 using a xenon ion beam in the laboratory.
Application of a dual unscented Kalman filter for simultaneous state and parameter estimation in problems of surface‐atmosphere exchange
Authors: Gove J. H. , Hollinger D. Y.
Published: April 2006

A dual unscented Kalman filter (UKF) was used to assimilate net CO2 exchange (NEE) data measured over a spruce‐hemlock forest at the Howland AmeriFlux site in Maine, USA, into a simple physiological model for the purpose of filling gaps in an eddy flux time series. In addition to filling gaps in the measurement record, the UKF approach provides continuous estimates of model parameters and uncertainty. The process explicitly recognizes uncertainty in the measurement data and model structure, providing approximate, effectively optimal state and parameter estimates with less subjectivity than in many previous gap‐filling methods. The dual UKF is a recursive predictor‐corrector estimation method whereby noisy measurement data are used to continuously update nonlinear process model predictions of the desired states, in this case net ecosystem exchange, among others. Two parallel filters are run simultaneously in the dual approach, one for state and the other for parameter estimation. The unscented transformation employs a deterministic sampling of “sigma points” from the joint density that captures the first two moments of the distribution to the second order. Nonlinear process models are applied to these sigma points to propagate the joint density within the filter framework. The UKF estimate of annual NEE in 2000 at the Howland Forest totaled −296.4 ± 2.4 g carbon m−2 (mean ± standard deviation) using nocturnal data when the square root of the momentum flux (u*) exceeded 0.25 m s−1. This NEE value is about 9% higher than a previous estimate where gaps were filled by physiological models fitted to monthly, seasonal, and annual data. Model estimates are sensitive to the threshold set for accepting or rejecting nocturnal flux data (“u* threshold”), and we show that uncertainty in annual estimates is dominated by the choice of u* threshold.
Comparative Genomics ofBrassica oleraceaandArabidopsis thalianaReveal Gene Loss, Fragmentation, and Dispersal after Polyploidy
Authors: Town Christopher D. , Cheung Foo , Maiti Rama , Crabtree Jonathan , Haas Brian J. , Wortman Jennifer R. , Hine Erin E. , Althoff Ryan , Arbogast Tamara S. , Tallon Luke J. , Vigouroux Marielle , Trick Martin , Bancroft Ian
Published: April 2006

We sequenced 2.2 Mb representing triplicated genome segments of Brassica oleracea, which are each paralogous with one another and homologous with a segmentally duplicated region of the Arabidopsis thaliana genome. Sequence annotation identified 177 conserved collinear genes in the B. oleracea genome segments. Analysis of synonymous base substitution rates indicated that the triplicated Brassica genome segments diverged from a common ancestor soon after divergence of the Arabidopsis and Brassica lineages. This conclusion was corroborated by phylogenetic analysis of protein families. Using A. thaliana as an outgroup, 35% of the genes inferred to be present when genome triplication occurred in the Brassica lineage have been lost, most likely via a deletion mechanism, in an interspersed pattern. Genes encoding proteins involved in signal transduction or transcription were not found to be significantly more extensively retained than those encoding proteins classified with other functions, but putative proteins predicted in the A. thaliana genome were underrepresented in B. oleracea. We identified one example of gene loss from the Arabidopsis lineage. We found evidence for the frequent insertion of gene fragments of nuclear genomic origin and identified four apparently intact genes in noncollinear positions in the B. oleracea and A. thaliana genomes.
Mathematical modeling of gravitational effects on the circulation: importance of the time course of venous pooling and blood volume changes in the lungs
Authors: van Heusden K. , Gisolf J. , Stok W. J. , Dijkstra S. , Karemaker J. M.
Published: April 2006

A dip in blood pressure (BP) in response to head-up tilt (HUT) or active standing might be due to rapid pooling in the veins below the heart (preload) or muscle activation-induced drop in systemic vascular resistance (afterload). We hypothesized that, in the cardiovascular response to passive HUT, where, in contrast to active standing, little BP dip is observed, features affecting the preload play a key role. We developed a baroreflex model combined with a lumped-parameter model of the circulation, including viscoelastic stress-relaxation of the systemic veins. Cardiac contraction is modeled using the varying-elastance concept. Gravity affects not only the systemic, but also the pulmonary, circulation. In accordance with the experimental results, model simulations do not show a BP dip on HUT; the tilt-back response is also realistic. If it is assumed that venous capacities are steady-state values, the introduction of stress-relaxation initially reduces venous pooling. The resulting time course of venous pooling is comparable to measured impedance changes. When venous pressure-volume dynamics are neglected, rapid (completed within 30 s) venous pooling leads to a drop in BP. The direct effect of gravity on the pulmonary circulation influences the BP response in the first ∼5 s after HUT and tilt back. In conclusion, the initial BP response to HUT is mainly determined by the response of the venous system. The time course of lower body pooling is essential in understanding the response to passive HUT.
BK channel β1-subunit regulation of calcium handling and constriction in tracheal smooth muscle
Authors: Semenov Iurii , Wang Bin , Herlihy Jeremiah T. , Brenner Robert
Published: April 2006

The large-conductance, Ca2+-activated K+(BK) channels are regulators of voltage-dependent Ca2+entry in many cell types. The BK channel accessory β1-subunit promotes channel activation in smooth muscle and is required for proper tone in the vasculature and bladder. However, although BK channels have also been implicated in airway smooth muscle function, their regulation by the β1-subunit has not been investigated. Utilizing the gene-targeted mice for the β1-subunit gene, we have investigated the role of the β1-subunit in tracheal smooth muscle. In mice with the β1-subunit-knockout allele, BK channel activity was significantly reduced in excised tracheal smooth muscle patches and spontaneous BK currents were reduced in whole tracheal smooth muscle cells. Knockout of the β1-subunit resulted in an increase in resting Ca2+levels and an increase in the sustained component of Ca2+influx after cholinergic signaling. Tracheal constriction studies demonstrate that the level of constriction is the same with knockout of the β1-subunit and BK channel block with paxillin, indicating that BK channels contribute little to airway relaxation in the absence of the β1-subunit. Utilizing nifedipine, we found that the increased constriction caused by knockout of the β1-subunit could be accounted for by an increased recruitment of L-type voltage-dependent Ca2+channels. These results indicate that the β1-subunit is required in airway smooth muscle for control of voltage-dependent Ca2+influx during rest and after cholinergic signaling in BK channels.