Miracle-dz/UniFAR-FTUs huggingface dataset:
Human single-chain Fv intrabodies counteract in situ huntingtin aggregation in cellular models of Huntington's disease

This investigation was pursued to test the use of intracellular antibodies (intrabodies) as a means of blocking the pathogenesis of Huntington's disease (HD). HD is characterized by abnormally elongated polyglutamine near the N terminus of the huntingtin protein, which induces pathological protein–protein interactions and aggregate formation by huntingtin or its exon 1-containing fragments. Selection from a large human phage display library yielded a single-chain Fv (sFv) antibody specific for the 17 N-terminal residues of huntingtin, adjacent to the polyglutamine in HD exon 1. This anti-huntingtin sFv intrabody was tested in a cellular model of the disease in which huntingtin exon 1 had been fused to green fluorescent protein (GFP). Expression of expanded repeat HD-polyQ-GFP in transfected cells shows perinuclear aggregation similar to human HD pathology, which worsens with increasing polyglutamine length; the number of aggregates in these transfected cells provided a quantifiable model of HD for this study. Coexpression of anti-huntingtin sFv intrabodies with the abnormal huntingtin-GFP fusion protein dramatically reduced the number of aggregates, compared with controls lacking the intrabody. Anti-huntingtin sFv fused with a nuclear localization signal retargeted huntingtin analogues to cell nuclei, providing further evidence of the anti-huntingtin sFv specificity and of its capacity to redirect the subcellular localization of exon 1. This study suggests that intrabody-mediated modulation of abnormal neuronal proteins may contribute to the treatment of neurodegenerative diseases such as HD, Alzheimer's, Parkinson's, prion disease, and the spinocerebellar ataxias.
Progression of HIV: follow‐up of Edinburgh injecting drug users with narrow seroconversion intervals in 1983–1985

ObjectiveTo describe progression and survival of individuals infected with HIV by injecting drug use in Edinburgh. Design and methodsFrom 313 HIV-infected patients with retrospectively estimated narrow seroconversion intervals, 260 infected via injecting drug use in the years 1983–1985 were selected for the study group. Main outcome measuresThe effects of gender, age, human leukocyte antigen (HLA) type and zidovudine (ZDV) treatment on progression and survival from seroconversion; Weibull estimates of the AIDS incubation distribution and the overall survival distribution; slopes of absolute CD4 lymphocyte loss (on the square root scale) and loss of CD4 percentage. ResultsThe cumulative progression rates at 10 years were 68% to CDC stage IV and 31% to AIDS with a mortality rate of 25%. Three-year survival rates for AIDS and CDC stage IV cases were 25 and 72%, respectively. Gender and age effects on progression or overall survival were not found, although those aged over 30 years experienced poorer survival from AIDS. A strong HLA (A1,B8,DR3) association with faster progression and poorer survival was found. Median survival was estimated by Weibull distribution to be 12.6 years; median AIDS-free time was estimated to be 11.6 years. CD4 cell loss was approximately linear when transformed to the square root scale as was the decline in CD4 percentage. Only HLA effects on slopes were found: A1,B8,DR3 was significantly associated with faster loss of both absolute CD4 cells and CD4 percentage (P < 0.001) and B27 was significantly associated with slower loss of CD4 percentage (P = 0.01). ConclusionsEdinburgh IDU do not seem to progress more rapidly than other cohorts with predominantly different risk activities. Older age was associated with poorer survival from AIDS but no gender effect was found for progression or overall survival. The clearest significant association with AIDS progression, mortality and loss of CD4 cells was the phenotype HLA A1,B8,DR3. In contrast HLA B27 was associated with slower loss of CD4 cells.
M2M communication delay challenges: Application and measurement perspectives

During the last decades, networks have evolved from stateless copper wires to complex, stateful communication paths. Furthermore, the delay in wired and wireless access networks has decreased substantially, such that previously negligible delay contributions become relevant parts of the total end-to-end delay. This can affect critical M2M applications such as Smart Grid communication that depend on timely data transfer. Their demand for deterministic communication paths conflicts with the common, cost-driven trend to share and optimize overall network capacity. This paper assesses contributions and bias of network technologies and systems onto end-to-end delay in today's access networks. The delay measurement results that are presented for various access networks provide (a) methodological considerations for accurate one-way delay measurements in these networks, (b) delay estimates for specific technologies as a guideline for M2M communication network selection, and (c) exemplary technology-specific anomalies that M2M applications must be prepared to handle. Integrating these findings into M2M applications is key to improve their communication's robustness, performance, and ability to handle anomalies appropriately.
Combining Static and Dynamic Typing in Ruby

Title of dissertation: Combining Static and Dynamic Typing in Ruby Michael Furr Doctor of Philosophy, 2009 Dissertation directed by: Professor Jeffrey S. Foster Department of Computer Science Many popular scripting languages such as Ruby, Python, and Perl are dynamically typed. Dynamic typing provides many advantages such as terse, flexible code and the ability to use highly dynamic language constructs, such as an eval method that evaluates a string as program text. However these dynamic features have traditionally obstructed static analyses leaving the programmer without the benefits of static typing, including early error detection and the documentation provided by type annotations. In this dissertation, we present Diamondback Ruby (DRuby), a tool that blends static and dynamic typing for Ruby. DRuby provides a type language that is rich enough to precisely type Ruby code, without unneeded complexity. DRuby uses static type inference to automatically discover type errors in Ruby programs and provides a type annotation language that serves as verified documentation of a method’s behavior. When necessary, these annotations can be checked dynamically using runtime contracts. This allows statically and dynamically checked code to safely coexist, and any runtime errors are properly blamed on dynamic code. To handle dynamic features such as eval, DRuby includes a novel dynamic analysis and transformation that gathers per-application profiles of dynamic feature usage via a program’s test suite. Based on these profiles, DRuby transforms the program before applying its type inference algorithm, enforcing type safety for dynamic constructs. By leveraging a program’s test suite, our technique gives the programmer an easy to understand trade-off: the more dynamic features covered by their tests, the more static checking is achieved. We evaluated DRuby on a benchmark suite of sample Ruby programs. We found that our profile-guided analysis and type inference algorithms worked well, discovering several previously unknown type errors. Furthermore, our results give us insight into what kind of Ruby code programmers “want” to write but is not easily amenable to traditional static typing. This dissertation shows that it is possible to effectively integrate static typing into Ruby without losing the feel of a dynamic language. Combining Static and Dynamic Typing in Ruby
Microfluidics-based wet spinning of protein microfibers as solid scaffolds for 3D cell cultivation

Here we propose a facile and versatile process to fabricate cell-sized protein microfibers using microfluidic spinning system and sacrificial layers of alginate. A precursor solution containing protein molecules and sodium alginate (Na-Alg), a buffer solution, and a gelation solution were introduced into the microfluidic devices, forming composite microfibers comprising Ca-Alg and the protein. After chemically cross-linking the protein molecules and removing the alginate polymer, microfibers made of proteins were obtained. We demonstrated two processes, uniform fiber production using a simple microchannel and parallel production of narrow fibers using multilayered microfluidic devices. As an application, we cultured mammalian cells within hydrogel matrices incorporating gelatin microfibers, and evaluated the effects of the fibers on cell proliferation and network formation. The presented microfluidic process would be useful for fabricating cell-sized microfibers made of proteins which are applicable to 3D cell cultivation and tissue engineering.
Assessment of potential advantages of relevant ions for particle therapy: a model based study.

PURPOSE Different ion types offer different physical and biological advantages for therapeutic applications. The purpose of this work is to assess the advantages of the most commonly used ions in particle therapy, i.e., carbon ((12)C), helium ((4)He), and protons ((1)H) for different treatment scenarios. METHODS A treatment planning analysis based on idealized target geometries was performed using the treatment planning software TRiP98. For the prediction of the relative biological effectiveness (RBE) that is required for biological optimization in treatment planning the local effect model (LEM IV) was used. To compare the three ion types, the peak-to-entrance ratio (PER) was determined for the physical dose (PERPHY S), the RBE (PERRBE), and the RBE-weighted dose (PERBIO) resulting for different dose-levels, field configurations, and tissue types. Further, the dose contribution to artificial organs at risk (OAR) was assessed and a comparison of the dose distribution for the different ion types was performed for a patient with chordoma of the skull base. RESULTS The study showed that the advantages of the ions depend on the physical and biological properties and the interplay of both. In the case of protons, the consideration of a variable RBE instead of the clinically applied generic RBE of 1.1 indicates an advantage in terms of an increased PERRBE for the analyzed configurations. Due to the fact that protons show a somewhat better PERPHY S compared to helium and carbon ions whereas helium shows a higher PERRBE compared to protons, both protons and helium ions show a similar RBE-weighted dose distribution. Carbon ions show the largest variation of the PERRBE with tissue type and a benefit for radioresistant tumor types due to their higher LET. Furthermore, in the case of a two-field irradiation, an additional gain in terms of PERBIO is observed when using an orthogonal field configuration for carbon ions as compared to opposing fields. In contrast, for protons, the PERBIO is almost independent on the field configuration. Concerning the artificial lateral OAR, the volume receiving 20% of the prescribed RBE-weighted dose (V20) was reduced by over 35% using helium ions and by over 40% using carbon ions compared to protons. The analysis of the patient plan showed that protons, helium, and carbon ions are similar in terms of target coverage whereas the dose to the surrounding tissue is increasing from carbon ions toward protons. The mean dose to the brain stem can be reduced by more than 55% when using helium ions and by further 25% when using carbon ions instead of protons. CONCLUSIONS The comparison of the PERRBE and PERPHY S of the three ion types suggests a strong dependence of the advantages of the three ions on the dose-level, tissue type, and field configuration. In terms of conformity, i.e., dose to the normal tissue, a clear gain is expected using carbon or helium ions compared to protons.
Robust control with sliding mode for a quadrotor unmanned aerial vehicle

A robust control approach denoted sliding control of MIMO nonlinear system based on the output feedback linearization is developed to attenuate the parametric uncertainties. The scheme is dedicated to model of unmanned aerial vehicles (the quadrotor UAV). We assume that the model of the plant is not precise, due to nondeterministic knowledge of inertias parameters. Tracking control is used to stabilize the equilibrium of the system, while all the state supposed to be measurable. The analysis is based on tracking errors during transients and at the steady state, on performance, stability and robustness with respect to plant uncertainties. Simulation results are carried out.
Neuronal Density and Architecture (Gray Level Index) in the Brains of Autistic Patients

Although neuropathologic studies have centered on small samples, it is accepted that brains of autistic individuals tend to be large, on average. Knowledge regarding the cause of this macrocephaly is limited. Postmortem studies reveal little in terms of cortical dysplasia. Some of these studies suggest increased cell-packing density in subcortical structures. These neuronomorphometric studies have been subjective or based their conclusions on measures of neuronal density. Our study sought the possible presence of increased cell-packing density by using the Gray Level Index. The Gray Level Index is defined as the ratio of the area covered by Nissl-stained elements to unstained area in postmortem samples. Analyzed images included Brodmann's cortical areas 9, 21, and 22 of 9 autistic patients (7 males, 2 females; mean age of 12 years, with a range of 5 to 28 years) and 11 normal controls (7 males, 4 females; mean age of 14 years, with a range of 3 to 25 years). The overall multivariate test revealed significant differences both between autistic patients and controls (P = .001) and between hemispheres (P = .025). Follow-up univariate tests showed significant diagnosis-dependent effects in feature distance (P = .005), the standard deviation in distance (P = .016), and feature amplitude (P = .001). The overall mean Gray Level Index was 19.4% in controls and 18.7% in autism (P = .724). In autism, an increased number of minicolumns, combined with fewer cells per column (or their greater dispersion), results in no global difference in neuronal density. (J Child Neurol 2002;17:515-521).
Effects of rhBNP on myocardial fibrosis after myocardial infarction in rats.

PURPOSE We aimed to observe the effects and mechanism of rhBNP treatment on myocardial fibrosis (MF) after myocardial infarction (MI). METHODS SPF rats were separated into 3 groups: normal, MI (ligation of left coronary artery), and MI + rhBNP (recombinant human brain natriuretic peptide). Rats in MI + rhBNP group were given 30 μg/kg for 2 days before modeling and for 4 weeks after modeling. mRNA levels and the expression levels of TGF-β1 (transforming growth factor) and CTGF (connective tissue growth factor) in 3 groups were analyzed using the RT-qPCR and western blotting analysis, respectively. Furthermore, myocardial volume fraction (CVF) was analyzed using the Sirius Red F3B (SR) while the percentage of type I and III collagen in 3 groups were analyzed using the immunohistochemical staining. RESULTS Compared with the normal group, the levels of TGF-β1, CTGF, CVF, type I and III collagen were higher in MI group. However, mRNA levels of TGF-β1 and CTGF were significantly decreased in MI + rhBNP compared to MI groups. Expression of TGF-β1 was lower while that of CTGF was higher in MI + rhBNP group than that in MI group. Besides, CVF, and type I and III collagen were lower in MI + rhBNP group compared with MI group. CONCLUSION rhBNP could significantly decrease the TGF-β1 and CTGF levels in post-MI so as to inhibit the type I and III collagen deposition in MF of post-MI. rhBNP will be benefit for the improvement of MF.
Reliability of the McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey among black and white women

Background: Coronary heart disease (CHD) mortality rates are higher among women, particularly black, than men. Women’s mortality rates may reflect difficulty in recognizing CHD prodromal symptoms (PS) but reliable screening instruments for women are scarce. The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey (MAPMISS) captures women’s PS presentation, but has limited testing among black women. Aim: To assess the test–retest reliability of the MAPMISS PS section for black and white women. Methods: The sample was recruited from women enrolled in a longitudinal study examining the predictive validity of the MAPMISS. The MAPMISS was re-administered to 42 women (22 white, 20 black) 3–5 days after baseline assessment. Results: Women endorsed an average of 7.5 PS (SD 4.8; range 0–20) initially and 7.6 (SD 4.7; range 0–20) at retest. Over half of the women (54.8%) of both races endorsed the same number of PS at test and retest; for 69%, the number endorsed at both testings differed by no more than one. Percentage agreement and kappa statistics on the number ofPS endorsed were excellent overall and by race. PS test and retest scores, reflecting PS intensity and frequency, were highly correlated overall (r = 0.92, p < 0.001) and separately for white (r = 0.93, p < 0.001) and black women (r = 0.91,p < 0.001). Racial differences were insignificant. Conclusions: Findings indicate (i) the MAPMISS PS score has excellent test–retest reliability (r = 0.92) when administered to women without a history of CHD, and (ii) test–retest reliability is as strong for black (r = 0.91) as for white women (r = 0.93).
Anaerobic Oxidation of Methane Coupled to Nitrite Reduction by Halophilic Marine NC10 Bacteria

ABSTRACT Anaerobic oxidation of methane (AOM) coupled to nitrite reduction is a novel AOM process that is mediated by denitrifying methanotrophs. To date, enrichments of these denitrifying methanotrophs have been confined to freshwater systems; however, the recent findings of 16S rRNA and pmoA gene sequences in marine sediments suggest a possible occurrence of AOM coupled to nitrite reduction in marine systems. In this research, a marine denitrifying methanotrophic culture was obtained after 20 months of enrichment. Activity testing and quantitative PCR (qPCR) analysis were then conducted and showed that the methane oxidation activity and the number of NC10 bacteria increased correlatively during the enrichment period. 16S rRNA gene sequencing indicated that only bacteria in group A of the NC10 phylum were enriched and responsible for the resulting methane oxidation activity, although a diverse community of NC10 bacteria was harbored in the inoculum. Fluorescence in situ hybridization showed that NC10 bacteria were dominant in the enrichment culture after 20 months. The effect of salinity on the marine denitrifying methanotrophic culture was investigated, and the apparent optimal salinity was 20.5‰, which suggested that halophilic bacterial AOM coupled to nitrite reduction was obtained. Moreover, the apparent substrate affinity coefficients of the halophilic denitrifying methanotrophs were determined to be 9.8 ± 2.2 μM for methane and 8.7 ± 1.5 μM for nitrite.
Cl 2 channels in basolateral renal medullary membranes XII . Anti-rbClC-Ka antibody blocks MTAL Cl 2 channels

Winters, Christopher J., Ludwika Zimniak, W. Brian Reeves, and Thomas E. Andreoli. Cl2 channels in basolateral renal medullary membranes. XII. Anti-rbClC-Ka antibody blocks MTAL Cl2 channels. Am. J. Physiol. 273 (Renal Physiol. 42): F1030–F1038, 1997. —Cl2 channels in the medullary thick ascending limb (MTAL) studied by either patchclamp technique or reconstitution into lipid bilayers are activated by increases in intracellular Cl2 concentrations. rbClC-Ka, a ClC Cl2 channel, may represent this channel. We therefore evaluated the role of rbClC-Ka in transcellular MTAL Cl2 transport in two separate ways. First, an antibody was raised against a fusion protein containing a 153-amino acid fragment of rbClC-Ka. Immunostaining of rabbit kidney sections with the antibody was localized to basolateral regions of MTAL and cortical thick ascending limb (CTAL) segments and also to the cytoplasm of intercalated cells in the cortical collecting duct. Second, Cl2 uptake and efflux were measured in suspensions of mouse MTAL segments. Cl2 uptake was bumetanide sensitive and was stimulated by treatment with a combination of vasopressin 1 forskolin 1 dibutyryl adenosine 38,5-cyclic monophosphate (DBcAMP). Cl2 efflux was also increased significantly by vasopressin 1 forskolin 1 DBcAMP from 114 6 20 to 196 6 36 nmol ·mg protein21 ·45 s21 (P 5 0.003). Cl2 efflux was inhibited by the Cl2 channel blocker diphenylamine-2-carboxylate (154 6 26 vs. 70 6 21 nmol ·mg protein21 ·45 s21, P 5 0.003). An antirbClC-Ka antibody, which inhibits the activity of MTAL Cl2 channels in lipid bilayers, reduced Cl2 efflux from intact MTAL segments (154 6 28 vs. 53 6 14 nmol ·mg protein21 ·45 s21, P 5 0.02). These results support the view that rbClC-Ka is the basolateral membrane Cl2 channel that mediates vasopressin-stimulated net Cl2 transport in the MTAL segment.
Developmental Eye Movement Test: What is it Really Measuring?

Purpose. The Developmental Eye Movement (DEM) test is commonly used as a clinical visual-verbal ocular motor assessment tool. However, while the DEM test ratio has been reported to correlate with horizontal saccadic eye movements, there have been no published comparative studies of the DEM test and objective eye movement measures. The aim of this study was to compare DEM test performance with explicit quantification of saccadic eye movements, reading performance, symptomatology and visual processing speed, to assess the validity of the DEM test in clinical practice. Methods. One hundred fifty-eight children aged 8 to 11 years completed the DEM test and a battery of eye movement tasks, recorded by a Microguide 1000 infrared eye tracker. All subjects completed a symptomatology survey. Reading performance and visual processing data was collected for 77 and 75 children, respectively. Results. One hundred twenty-nine of the 158 subjects (81.65%) passed the DEM test. There was no significant correlation between any component of DEM test performance and quantitative eye movement parameters (gain, latency, asymptotic peak velocity, and number of corrective saccades) or symptomatology. There were significant correlations between DEM test outcome and reading performance, and with visual processing speed. Conclusions. DEM test performance does not correlate with saccadic eye movement skills or symptomatology. However, it is related to reading performance and visual processing speed. This study suggests that although DEM test times may not correlate directly with eye movement parameters, they do correlate with aspects of reading performance and thus may serve a diagnostic role in clinical practice.