Miracle-dz/UniFAR-FTUs huggingface dataset:
Clathrin functions in the absence of heterotetrameric adaptors and AP180‐related proteins in yeast

The major coat proteins of clathrin‐coated vesicles are the clathrin triskelion and heterotetrameric associated protein (AP) complexes. The APs are thought to be involved in cargo capture and recruitment of clathrin to the membrane during endocytosis and sorting in the trans‐Golgi network/endosomal system. AP180 is an abundant coat protein in brain clathrin‐coated vesicles, and it has potent clathrin assembly activity. In Saccharomyces cerevisiae, there are 13 genes encoding homologs of heterotetrameric AP subunits and two genes encoding AP180‐related proteins. To test the model that clathrin function is dependent on the heterotetrameric APs and/or AP180 homologs, yeast strains containing multiple disruptions in AP subunit genes, as well as in the two YAP180 genes, were constructed. Surprisingly, the AP deletion strains did not display the phenotypes associated with clathrin deficiency, including slowed growth and endocytosis, defective late Golgi protein retention and impaired cytosol to vacuole/autophagy function. Clathrin‐coated vesicles isolated from multiple AP deletion mutants were morphologically indistinguishable from those from wild‐type cells. These results indicate that clathrin function and recruitment onto membranes are not dependent upon heterotetrameric adaptors or AP180 homologs in yeast. Therefore, alternative mechanisms for clathrin assembly and coated vesicle formation, as well as the role of AP complexes and AP180‐related proteins in these processes, must be considered.
Effects of dipyridamole on coronary collateralization and myocardial perfusion in patients with ischaemic cardiomyopathy.

AIMS There is evidence that oral dipyridamole, a nucleoside uptake blocker that increases myocardial adenosine levels, lessens myocardial ischaemia by inducing coronary collateral growth in animal models of ischaemic heart disease. However, whether dipyridamole can exert a similar effect in humans with coronary artery disease is controversial. METHODS AND RESULTS We studied 30 male patients (mean age 55+/-9 years) with coronary artery disease and left ventricular systolic dysfunction (ejection fraction >40%). Patients were randomized into three matched groups. Group A patients (n=10) received dipyridamole alone at a dose of 75 mg t.i. d. orally for 8 weeks. Group B patients (n=10) underwent exercise training at 60% of peak . VO(2)three times a week for 8 weeks, and received dipyridamole. Group C patients (n=10) had neither exercise testing nor dipyridamole. On study entry and after 8 weeks all patients underwent an exercise test with gas exchange analysis, dobutamine stress echocardiography, 201-thallium planar myocardial scintigraphy, and coronary angiography. Peak . VO(2)increased significantly only in trained patients. Thallium uptake of the collateral-dependent myocardium, coronary collateral score and wall thickening score increased significantly only in groups receiving dipyridamole, the greatest improvement being in group B patients. Plasma adenosine levels were also the highest in group B (P<0.001 vs A and C). Correlations were found between changes in adenosine levels and increases of both thallium uptake (r=-0.70;P=0.001) and collateralization (r=0.72;P=0.001). CONCLUSION Exercise training potentiates the effects of dipyridamole on coronary collateralization and myocardial perfusion in humans with ischaemic cardiomyopathy.
Modelling of Ozone Mass-Transfer through Non-Porous Membranes for Water Treatment

The mass transfer of ozone and oxygen into water through non-porous membranes was studied using computational fluid dynamics (CFD) modelling and fundamental convection-diffusion theory. Ozone is a gaseous oxidant that is widely applied in drinking water treatment. Membrane contactors are an alternative to conventional gas dispersion methods for injection of ozone gas mixtures into water. Few studies have explored computational approaches for membrane based ozone transport. In this investigation, quantitative concentration profiles across a single polydimethylsiloxane (PDMS) capillary membrane tube with internal gas flow and external liquid flow were obtained, including single mass transfer resistances and overall mass transfer coefficients for ozone and oxygen for varying membrane lengths, thicknesses, and laminar flow liquid side velocities. Both the influence of diffusivity and solubility of gases in the membrane were considered with the applied model. Previous studies have neglected the solubility of gases in the membranes in their analysis of ozone and oxygen gas fluxes. This work shows that the solubility has a significant impact of the overall mass transfer coefficients, in particular for oxygen. The main resistance for ozone was found in the liquid side, while for oxygen it was in the membrane. Mass transfer correlations based on heat transfer analogies revealed Sherwood (Sh) correlations for ozone and oxygen with good agreement to literature data, indicating that the applied computational model returns sensible results. The outcome of this study provides an initial basis for computational predictions of ozone and oxygen mass transfer for different membrane materials, flow conditions and reactor designs.
Anterior Decompression and Anterior Instrumentation of Tuberculosis of Cervicothoracic Spine by Cervicomanubrial Approach

Background: Evaluation of result of anterior cervical approach with manubriotomy and anterior instrumentation in tuberculosis of cervicothoracic spine in terms of the neurological recovery, reconstruction of spine and prevention of deformity along with relief of pain. Materials and Methods: All five patients with cervicothoracic caries spine had surgery through anterior cervical approach with manubriotomy in our hospital and underwent excision of the involved vertebrae and intervertebral discs followed by anterior spinal reconstruction with titanium spacer cage filled with cancellous iliac crest bone graft and Orion plate with locking screw. Antitubercular drugs were administered for 12 months. The follow-up period ranged from 12 to 36 months. Results: Analysis of result was done on the basis of clinical and radiological criteria. Clinical assessment based on Frankel grade and modified JOA score showed significant improvement from preoperative findings. Radiological assessment showed osteointegration, no spinal instability and no progression of the deformity. The pain control, based on visual analog scale changed from a pre-operative average of 7.5 to 2 at the last follow-up thereby indicating significant improvement and all patients returned to preoperative functional status. One patient had transient hoarseness of voice. No other complication had been encountered in the immediate post operative and during the follow-up period. Conclusions: Our study showed that anterior cervical approach with manubriotomy and anterior insertion of titanium cage, filled with autogenous bone graft, secured with locking plate instrumentation has a successful role in the eradication of infection, neurological recovery, segmental spinal reconstruction and it also reduces surgical time, blood loss, and surgical complications and approach related comorbidity in follow up period. Level of EvidenceLevel 4, Case series
Rotation velocities of white dwarfs. III. DA stars with convective atmospheres

The sharp Hα NLTE line cores of hydrogen-rich (DA) white dwarfs allow their projected rotational velocities to be determined. High resolution optical spectra of 22 stars obtained with the Keck I telescope are matched by synthetic spectra computed from a grid of NLTE model atmospheres. In this paper, the third in a series on white dwarf rotation, we concentrate preferentially on DA white dwarfs with convective atmospheres, i.e. with T e f f < 14000 K. Previous analyses found DA white dwarfs hotter than 14000 K to be very slow rotators and rarely show any spectroscopically detectable rotation. For 19 of our programme stars we were able to derive projected rotational velocities or upper limits. No rotation could be detected for seven stars in our sample. However twelve stars show significant line broadening. In the case of the ZZ Ceti star G 117-B15A, the observed Hα line profile cannot be matched by a rotationally broadened profile as its line core is too narrow. Combining our results with those from two similar studies, we have obtained information on the rotation or other line broadening mechanisms (such as caused by magnetic fields) of 56 DA white dwarfs. The fraction of rotating DA white dwarfs whose line profiles can be matched for a vanishing projected rotation velocity is high for hot white dwarfs with radiative atmospheres (25 out of 28). Amongst the cool white dwarfs with presumedly convective atmospheres, only for a few stars (8 out of 22) has no additional line broadening to be invoked to explain their observed Hα line profiles. We conjecture that the physics of Hα line formation in convective DA while dwarf atmospheres is not yet sufficiently well understood and additional observational and theoretical efforts have to be made.
Mapping of QTLs related with wood quality and developmental characteristics in hybrids (Eucalyptus grandis x Eucalyptus urophylla)

n The present work aimed to characterize and identify QTLs for wood quality and growth traits in E. grandis x E. urophylla hybrids. For this purpose a RAPD linkage map was developed for the hybrids (LOD=3 and r=0.40) containing 52 markers and 12 linkage groups. Traits related to wood quality and growth were evaluated in the QTL analyses. QTL analyses were performed using chi-square tests, single-marker, interval mapping and composite interval mapping analyses. All approaches led to the identification of similar QTLs associated with wood density, cellulose pulp yield and percentage of extractives, which were detected and confirmed by both the interval mapping and composite interval mapping methodologies. Some QTLs regions were confirmed only by the composite interval mapping methodology: percentage of soluble lignin, percentage of insoluble lignin, CBH and total height. Overlapping QTLs regions were detected, and these, can be the result of major genes involved in the regulation and control of the growth traits by epistatic interactions. In order to evaluate the effect of early selection using RAPD molecular data, molecular markers adjacent to QTLs were used genotype selection. The analysis of selection differential values suggests that for all the traits the phenotypic selection at seven years should generate larger genetic gains than early selection assisted by molecular markers and the combination of the strategies should elevate the selection efficiency.
Nanocrystalline structure of nanobump generated by localized photoexcitation of metal film

The extreme cooling rates in material processing can be achieved in a number of current and emerging femtosecond laser techniques capable of highly localized energy deposition. The mechanisms of rapid solidification of a nanoscale region of a metal film transiently melted by a localized photoexcitation are investigated in a large-scale atomistic simulation. The small size of the melted region, steep temperature gradients, and fast two-dimensional electron heat conduction result in the cooling rate exceeding 1013 K/s and create conditions for deep undercooling of the melt. The velocity of the liquid/crystal interface rises up to the maximum value of ∼80 m/s during the initial stage of the cooling process and stays approximately constant as the temperature of the melted region continues to decrease. When the temperature drops down to the level of ∼0.6Tm, a massive homogeneous nucleation of the crystal phase inside the undercooled liquid region takes place and prevents the undercooled liquid from reaching th.
Heterogeneity of the proliferative fraction and cyclin D1/CCND1 gene amplification in head and neck squamous cell carcinoma.

High proliferative fraction and cyclin D1/CCND1 gene amplification have been associated with certain aggressive features of head and neck squamous carcinoma in some studies, but not in others. The differences may be related to the intratumoral heterogeneity of these factors. Moreover, the interrelationship between these seemingly related factors has not been determined. In order to determine the correlation between tumor proliferative fractions and CCND1 gene amplification, 3 spatially different samples from each of 32 primary head and neck squamous cell carcinomas (HNSCC) were separately analyzed by flow cytometry. A mixture of these specimens was also minced and snap frozen for molecular studies. DNA was extracted from patient lymphocytes, normal appearing squamous epithelium, and tumors. A genomic DNA probe containing the first exon of CCND1 was used for hybridization by Southern technique. A 5.6 kb genomic DNA probe of immunoglobulin heavy chain was used as an internal standard for quantification of CCND1 gene amplification. Our results showed that 30% of the tumor cases manifested intratumoral heterogeneity (> 50% differences) of their proliferative activity. The highest value was used for correlation with gene amplification. Eleven (34.4%) of the 32 tumors showed CCND1 amplification (2-10-fold). When the proliferative fraction was dichotomized into high and low groups based on the mean value (> or = 13%), a highly statistical correlation between CCND1 amplification and tumor proliferation was obtained (P < 0.001). No significant correlation between gene amplification and other clinicopathologic parameters was noted. (ABSTRACT TRUNCATED AT 250 WORDS)
Effects of haemophilic arthropathy on health‐related quality of life and socio‐economic parameters

Summary. Although prophylactic treatment is advised for all children with severe haemophilia, the optimal regimen is still under discussion. Should all joint bleeds be prevented, or can a limited amount of arthropathy be tolerated in adulthood without loss of quality of life? To answer this question, the effect of haemophilic arthropathy on health‐related quality of life (HRQoL) needs to be quantified. In a retrospective study, the effect of arthropathy on HRQoL and socio‐economic parameters was assessed in a single‐centre cohort of 96 patients with severe and moderate haemophilia with a minimum age of 13 years. Arthropathy was measured by the radiological Pettersson score of the elbows, knees and ankles (maximum: 78 points). HRQoL was assessed by the Short Form 36 (SF36), measuring eight domains of health. Labourforce participation and medical consumption were assessed using a separate questionnaire. Patients were studied at a mean age of 28.6 years (range: 13–54), the mean time between evaluation and the last Pettersson score was 0.4 years (SD: 1.1). The overall median Pettersson score was 13 (range: 0–78). There was a trend towards lower quality of life with increasing Pettersson scores and age, especially in the physical domains of the SF36. An age‐adjusted analysis showed that arthropathy had a small but significant effect on HRQoL in the domain of ‘physical function’ of the SF36, but not on its other domains, or on labourforce participation and medical consumption. Thus suggesting that the SF36 can be used to assess the effects of haemophilic arthropathy, especially in the domain of ‘physical function’.
The CELLULOSE SYNTHASE-LIKE A and CELLULOSE SYNTHASE-LIKE C families: recent advances and future perspectives

The CELLULOSE SYNTHASE (CESA) superfamily of proteins contains several sub-families of closely related CELLULOSE SYNTHASE-LIKE (CSL) sequences. Among these, the CSLA and CSLC families are closely related to each other and are the most evolutionarily divergent from the CESA family. Significant progress has been made with the functional characterization of CSLA and CSLC genes, which have been shown to encode enzymes with 1,4-β-glycan synthase activities involved in the biosynthesis of mannan and possibly xyloglucan backbones, respectively. This review examines recent work on the CSLA and CSLC families from evolutionary, molecular, and biochemical perspectives. We pose a series of questions, whose answers likely will provide further insight about the specific functions of members of the CSLA and CSLC families and about plant polysaccharide biosynthesis is general.
Femtosecond Laser Fabrication of Monolithically Integrated Microfluidic Sensors in Glass

Femtosecond lasers have revolutionized the processing of materials, since their ultrashort pulse width and extremely high peak intensity allows high-quality micro- and nanofabrication of three-dimensional (3D) structures. This unique capability opens up a new route for fabrication of microfluidic sensors for biochemical applications. The present paper presents a comprehensive review of recent advancements in femtosecond laser processing of glass for a variety of microfluidic sensor applications. These include 3D integration of micro-/nanofluidic, optofluidic, electrofluidic, surface-enhanced Raman-scattering devices, in addition to fabrication of devices for microfluidic bioassays and lab-on-fiber sensors. This paper describes the unique characteristics of femtosecond laser processing and the basic concepts involved in femtosecond laser direct writing. Advanced spatiotemporal beam shaping methods are also discussed. Typical examples of microfluidic sensors fabricated using femtosecond lasers are then highlighted, and their applications in chemical and biological sensing are described. Finally, a summary of the technology is given and the outlook for further developments in this field is considered.
Refined crustal and uppermost mantle structure of southern California by ambient noise adjoint tomography

Kai Wang,1 Yingjie Yang,1 Piero Basini,2,* Ping Tong,3 Carl Tape4 and Qinya Liu2,5 1ARC Centre of Excellence for Core to Crust Fluid System and GEMOC ARC National Key Centre, Earth and Planetary Sciences, Macquarie University, Sydney, 2109, Australia. E-mail: wangkaim8@126.com 2Department of Physics, University of Toronto, Toronto, Ontario, M5S 1A1 , Canada 3Division of Mathematical Sciences, School of Physical and Mathematical Sciences and Asian School of the Environment, Nanyang Technological University, Singapore, 639798, Singapore 4Geophysical Institute and Department of Geosciences, University of Alaska Fairbanks, Fairbanks, AK 99775-7320, USA 5Department of Earth Sciences, University of Toronto, Toronto, Ontario, M5S 1A1, Canada
A prospective study of sleep duration and pneumonia risk in women.

STUDY OBJECTIVE Experimental data suggest sleep deprivation may impair host immunity. We sought to assess the effect of poor sleep on pneumonia risk. DESIGN Prospective, observational cohort study. PARTICIPANTS 56,953 female nurses (ages 37 to 57 years old) participating in the Nurses' Health Study II cohort free of cancer, cardiovascular disease, diabetes, and asthma with no prior history of pneumonia. MEASUREMENTS AND RESULTS At baseline, participants reported their average sleep duration and whether this quantity was adequate for them. Questionnaires ascertaining a new pneumonia diagnosis were mailed every 2 years. Cases required physician diagnosis and chest radiograph confirmation. Cox proportional hazards models were used to assess the relative risk for incident pneumonia over 4 years. Over 217,500 person-years, 977 cases of pneumonia were identified. Relative to 8-h sleepers, both short and long sleep durations were associated with elevated pneumonia risk. The age-adjusted relative risk for pneumonia was 1.70 (95% CI 1.30-2.23) in those sleeping ≤ 5 h and 1.49 (95% CI 1.12-1.98) in those sleeping ≥ 9 h. After adjusting for potential confounders, the relative risks were 1.39 (95% CI: 1.06-1.82) in those sleeping ≤ 5 h and 1.38 (95% CI 1.04-1.84) in those sleeping ≥ 9 h. Perceived inadequate sleep was also associated with pneumonia with a relative risk of 1.50 (95% CI 1.29-1.74) in multivariate models. CONCLUSIONS Both reduced and prolonged habitual sleep durations are associated with increased risk of pneumonia. Further research is needed to understand how sleep habits can influence immunity.
Genome-Wide Association Scan for Diabetic Nephropathy Susceptibility Genes in Type 1 Diabetes

OBJECTIVE Despite extensive evidence for genetic susceptibility to diabetic nephropathy, the identification of susceptibility genes and their variants has had limited success. To search for genes that contribute to diabetic nephropathy, a genome-wide association scan was implemented on the Genetics of Kidneys in Diabetes collection. RESEARCH DESIGN AND METHODS We genotyped ∼360,000 single nucleotide polymorphisms (SNPs) in 820 case subjects (284 with proteinuria and 536 with end-stage renal disease) and 885 control subjects with type 1 diabetes. Confirmation of implicated SNPs was sought in 1,304 participants of the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study, a long-term, prospective investigation of the development of diabetes-associated complications. RESULTS A total of 13 SNPs located in four genomic loci were associated with diabetic nephropathy with P < 1 × 10−5. The strongest association was at the FRMD3 (4.1 protein ezrin, radixin, moesin [FERM] domain containing 3) locus (odds ratio [OR] = 1.45, P = 5.0 × 10−7). A strong association was also identified at the CARS (cysteinyl-tRNA synthetase) locus (OR = 1.36, P = 3.1 × 10−6). Associations between both loci and time to onset of diabetic nephropathy were supported in the DCCT/EDIC study (hazard ratio [HR] = 1.33, P = 0.02, and HR = 1.32, P = 0.01, respectively). We demonstratedexpression of both FRMD3 and CARS in human kidney. CONCLUSIONS We identified genetic associations for susceptibility to diabetic nephropathy at two novel candidate loci near the FRMD3 and CARS genes. Their identification implicates previously unsuspected pathways in the pathogenesis of this important late complication of type 1 diabetes.
Electrophysiological phenotyping in genetically engineered mice 1

Berul, Charles I. Electrophysiological phenotyping in genetically engineered mice. Physiol Genomics 13: 207–216, 2003; 10.1152/physiolgenomics.00183. 2002. —Advances in transgene and gene targeting technology have enabled sophisticated manipulation of the mouse genome, providing important insights into the molecular mechanisms underlying cardiac conduction, arrhythmogenesis, and sudden cardiac death. The mouse is currently the principal mammalian model for studying biological processes, particularly related to cardiac pathophysiology. Murine models have been engineered harboring gene mutations leading to inherited structural and electrical disorders of the heart due to transcription factor mutations, connexin protein defects, and G protein and ion channelopathies. These mutations lead to phenotypes reminiscent of human clinical disease states including congenital heart defects, cardiomyopathies, and long-QT syndrome, creating models of human electrophysiological disease. Functional analyses of the underlying molecular mechanisms of resultant phenotypes require appropriate and sophisticated experimental methodology. This paper reviews current in vivo murine electrophysiology study techniques and genetic mouse models pertinent to human arrhythmia disorders.