Miracle-dz/UniFAR-FTUs huggingface dataset:
High non-specific binding of the β1-selective radioligand 2-125I-ICI-H

Summary: Aim: As results of cardiac biopsies suggest, myocardial β1-adrenoceptor density is reduced in patients with chronic heart failure. However, changes in cardiac β2-adrenoceptors vary. With suitable radiopharmaceuticals single photon emission computed tomography (SPECT) and positron emission tomography (PET) offer the opportunity to assess β-adrenoceptors non-invasively. Among the novel racemic analogues of the established β1-selective adrenoceptor antagonist ICI 89.406 the iodinated 2-I-ICI-H showed high affinity and selectivity to β1-adrenoceptors in murine ventricular membranes. The aim of this study was its evaluation as a putative sub-type selective β1-adrenergic radioligand in cardiac imaging. Methods: Competition studies in vitro and in vivo were used to investigate the kinetics of 2-I-ICI-H binding to cardiac β-adrenoceptors in mice and rats. In addition, the radiosynthesis of 2-125I-ICI-H from the silylated precursor 2-SiMe3-ICI-H was established. The specific activity was 80 GBq/µmol, the radiochemical yield ranged from 70 to 80%. Results: The unlabelled compound 2-I-ICI-H showed high β1-selectivity and -affinity in the in vitro competition studies. In vivo biodistribution studies apparently showed low affinity to cardiac β-adrenoceptors. The radiolabelled counterpart 2-125I-ICI-H showed a high degree of non-specific binding in vitro and no specific binding to cardiac β1-adrenoceptors in vivo. Conclusion: Because of its high non-specific binding 2-125I-ICI-H is no suitable radiotracer for imaging in vivo.
The SILAC Fly Allows for Accurate Protein Quantification in Vivo*

Stable isotope labeling by amino acids in cell culture (SILAC) is widely used to quantify protein abundance in tissue culture cells. Until now, the only multicellular organism completely labeled at the amino acid level was the laboratory mouse. The fruit fly Drosophila melanogaster is one of the most widely used small animal models in biology. Here, we show that feeding flies with SILAC-labeled yeast leads to almost complete labeling in the first filial generation. We used these “SILAC flies” to investigate sexual dimorphism of protein abundance in D. melanogaster. Quantitative proteome comparison of adult male and female flies revealed distinct biological processes specific for each sex. Using a tudor mutant that is defective for germ cell generation allowed us to differentiate between sex-specific protein expression in the germ line and somatic tissue. We identified many proteins with known sex-specific expression bias. In addition, several new proteins with a potential role in sexual dimorphism were identified. Collectively, our data show that the SILAC fly can be used to accurately quantify protein abundance in vivo. The approach is simple, fast, and cost-effective, making SILAC flies an attractive model system for the emerging field of in vivo quantitative proteomics.
Mismatch Repair Polymorphisms and Colorectal Polyps: hMLH1 −93G>A Variant Modifies Risk Associated with Smoking

BACKGROUND AND AIM:Mutations in the mismatch repair (MMR) enzymes hMLH1 and hMSH6 are known causes of hereditary nonpolyposis colorectal cancer and act by inducing a mutator phenotype characterized by microsatellite instability. The aim of our study was to determine if polymorphisms in the DNA MMR genes hMLH1 and hMSH6 are associated with an increased risk of colorectal polyps, and to evaluate interactions with exposures known to cause DNA damage.METHODS:In a Minnesota-based case-control study of individuals with adenomas (N = 401), hyperplastic polyps (N = 195), or both adenomas and hyperplastic polyps (N = 123) versus polyp-free controls (N = 624), we investigated the role of hMLH1 −93G>A, hMLH1 I219V, and hMSH6 G39E polymorphisms in increasing the risk of colorectal polyps. Polytomous multivariate logistic regression analysis was used, adjusting for age, sex, body mass index, postmenopausal hormone use, aspirin use, and NSAID use.RESULTS:Overall, no evidence of an association between any of the three polymorphisms or hMLH1 haplotypes and colorectal polyps was observed. However, risk associated with the hMLH1 −93A variant differed by smoking: smoking-associated risks were stronger among those with variant −93AA or −93AG genotypes, showing a twofold greater risk of adenoma with >25 pack-years of smoking compared with nonsmokers, and a corresponding eightfold greater risk of hyperplastic polyps (genotype smoking: p-interaction = 0.02 for hyperplastic polyps and p-interaction = 0.08 for adenomas). CONCLUSIONS:These data are consistent with the observation that smoking is associated with MMR in colorectal neoplasia and suggest that the risk increase with smoking may differ by hMLH1 −93G>A genotype.
Gradient Descent for Spiking Neural Networks

Much of studies on neural computation are based on network models of static neurons that produce analog output, despite the fact that information processing in the brain is predominantly carried out by dynamic neurons that produce discrete pulses called spikes. Research in spike-based computation has been impeded by the lack of efficient supervised learning algorithm for spiking networks. Here, we present a gradient descent method for optimizing spiking network models by introducing a differentiable formulation of spiking networks and deriving the exact gradient calculation. For demonstration, we trained recurrent spiking networks on two dynamic tasks: one that requires optimizing fast (~millisecond) spike-based interactions for efficient encoding of information, and a delayed memory XOR task over extended duration (~second). The results show that our method indeed optimizes the spiking network dynamics on the time scale of individual spikes as well as behavioral time scales. In conclusion, our result offers a general purpose supervised learning algorithm for spiking neural networks, thus advancing further investigations on spike-based computation.
DNA Translator and Aligner: HyperCard utilities to aid phylogenetic analysis of molecules

DNA Translator and Aligner are molecular phylogenetics HyperCard stacks for Macintosh computers. They manipulate sequence data to provide graphical gene mapping, conversions, translations and manual multiple-sequence alignment editing. DNA Translator is able to convert documented GenBank or EMBL documented sequences into linearized, rescalable gene maps whose gene sequences are extractable by clicking on the corresponding map button or by selection from a scrolling list. Provided gene maps, complete with extractable sequences, consist of nine metazoan, one yeast, and one ciliate mitochondrial DNAs and three green plant chloroplast DNAs. Single or multiple sequences can be manipulated to aid in phylogenetic analysis. Sequences can be translated between nucleic acids and proteins in either direction with flexible support of alternate genetic codes and ambiguous nucleotide symbols. Multiple aligned sequence output from diverse sources can be converted to Nexus, Hennig86 or PHYLIP format for subsequent phylogenetic analysis. Input or output alignments can be examined with Aligner, a convenient accessory stack included in the DNA Translator package. Aligner is an editor for the manual alignment of up to 100 sequences that toggles between display of matched characters and normal unmatched sequences. DNA Translator also generates graphic displays of amino acid coding and codon usage frequency relative to all other, or only synonymous, codons for approximately 70 select organism-organelle combinations. Codon usage data is compatible with spreadsheet or UWGCG formats for incorporation of additional molecules of interest. The complete package is available via anonymous ftp and is free for non-commercial uses.
Lateral hypothalamic GAD65 neurons are spontaneously firing and distinct from orexin‐ and melanin‐concentrating hormone neurons

Lateral hypothalamus (LH) contains GABA neurons involved in controlling metabolism and sleep. LH glutamic acid decarboxylase 65 (GAD65) GABA neurons are intrinsically depolarized, unlike classical GAD65 neurons of the cortex. LH GAD65 GABA neurons are distinct from most studied LH neurons (orexin and melanin‐concentrating hormone cells). A subset of LH GAD65 neurons are glucose inhibited. Our study adds new populations of glucose sensing neurons to the list of hypothalamic sugar sensors and introduces inhibitory circuit elements of the LH.
1. DECENTERING HISTORY: LOCAL STORIES AND CULTURAL CROSSINGS IN A GLOBAL WORLD

This essay was first presented at the 2010 Ludwig Holberg Prize Symposium in Bergen, Norway, where I, as the prize recipient, was asked to describe my work and its import for our period of globalization. The essay first traces the interconnected processes of "decentering" history in Western historiography in the half century after World War II: the move to working people and "subaltern classes"; to women and gender; to communities defined by ethnicity and race; to the study of non-Western histories and world or global history, in which the European trajectory is only one of several models. Can the historian hold onto the subjects of "decentered" social and cultural history, often local and full of concrete detail, and still address the perspectives of global history? To suggest an answer to this question, I describe my own decentering path from work on sixteenth-century artisans in the 1950s to recent research on non-European figures such as the Muslim "Leo Africanus" (Hasan al-Wazzan). I then offer two examples in which concrete cases can serve a global perspective. One is a comparison of the literary careers of Ibn Khaldun and Christine de Pizan in the scribal cultures on either side of the Mediterranean in the late fourteenth and early fifteenth centuries. The other is the transmission and transformation of practices of divination, healing, and detection from Africa to the slave communities of Suriname in the seventeenth and eighteenth centuries.
RIORITY B ASED RSA C RYPTOGRAPHIC T ECHNIQUE

The RSA algorithm is one of the most commonly used efficient cryptographic algorithms. It provides the required amount of confidentiality, data integrity and privacy. This paper integrates the RSA Algorithm with round-robin priority scheduling scheme in order to extend the level of security and reduce the effectiveness of intrusion. It aims at obtaining minimal overhead, increased throughput and privacy. In this method the user uses the RSA algorithm and generates the encrypted messages that are sorted priority-wise and then sent. The receiver, on receiving the messages decrypts them using the RSA algorithm according to their priority. This method reduces the risk of man-in-middle attacks and timing attacks as the encrypted and decrypted messages are further jumbled based on their priority. It also reduces the power monitoring attack risk if a very small amount of information is exchanged. It raises the bar on the standards of information security, ensuring more efficiency.
On the Simulation of Adaptive Measurements via Postselection

In this note we address the question of whether any any quantum computational model that allows adaptive measurements can be simulated by a model that allows postselected measurements. We argue in the favor of this question and prove that adaptive measurements can be simulated by postselection. We also discuss some potentially stunning consequences of this result such as the ability to solve #P problems.
Correlates of aortic stiffness progression in patients with resistant hypertension: importance of clinic and ambulatory blood pressure changes

Objectives: Correlates of serial aortic stiffness changes were scarcely evaluated. We aimed to evaluate them in patients with resistant hypertension, with particular attention to the importance of changes in clinic and ambulatory blood pressures (BP). Methods: In a prospective study, two carotid–femoral pulse wave velocity (cf-PWV) measurements (three measures in each occasion) were performed with the Complior equipment in 442 resistant hypertensive patients over a mean follow-up of 4.6 years. Multivariable regressions assessed the independent correlates of changes in cf-PWV. All analyses were further adjusted for baseline cf-PWV and BP values, and for the time interval between measurements. Results: Carotid–femoral PWV had a median increase of 0.11 m/s per year (1.1% per year). Overall, 224 patients (51%) had an increase or persisted with high cf-PWV, whereas 218 (49%) reduced or persisted with low values. On multivariable regressions, both changes in clinic SBP (partial correlation 0.34, P < 0.001) and in 24-h SBP (partial correlation 0.40, P < 0.001) were correlates of changes in cf-PWV. This means that the white-coat effect, defined as the difference between clinic and daytime BPs, affected cf-PWV changes (partial correlation 0.19, P < 0.001). The other independent correlates of aortic stiffness progression were older age, presence of diabetes, higher waist circumference and worse renal function. Conclusion: The exaggerated white-coat effect, by acutely increasing clinic BPs during cf-PWV examination, may partially obscure the beneficial effects of reducing ambulatory BP levels on aortic stiffness attenuation. Arterial stiffness measurements under ambulatory conditions may be needed to correctly assess aortic stiffness changes in resistant hypertensive patients.
A Discontinuity Adaptive Prior for Image Denoising

presence of noise in digital images degrades the visual quality by corrupting the information associated with the image. The aim of denoising is to restore an image from its noisy version by preserving signal information. In this paper, we are considering an image corrupted by additive Gaussian noise. The image is modeled as Markov random field (MRF) and an estimation of maximum-a-posteriori (MAP) is obtained using graduated non-convexity. The results are compared with other spatial domain filtering methods. The discontinuity adaptive prior helps in preserving edge information. The results suggest that proposed method has an improved performance. Keywordsdenoising, Markov random field, Discontinuity adaptive, Graduated non-convexity.
Human Galectin 3 Binding Protein Interacts with Recombinant Adeno-Associated Virus Type 6

ABSTRACT Recombinant adeno-associated viruses (rAAVs) hold enormous potential for human gene therapy. Despite the well-established safety and efficacy of rAAVs for in vivo gene transfer, there is still little information concerning the fate of vectors in blood following systemic delivery. We screened for serum proteins interacting with different AAV serotypes in humans, macaques, dogs, and mice. We report that serotypes rAAV-1, -5, and -6 but not serotypes rAAV-2, -7, -8, -9, and -10 interact in human sera with galectin 3 binding protein (hu-G3BP), a soluble scavenger receptor. Among the three serotypes, rAAV-6 has the most important capacities for binding to G3BP. rAAV-6 also bound G3BP in dog sera but not in macaque and mouse sera. In mice, rAAV-6 interacted with another protein of the innate immune system, C-reactive protein (CRP). Furthermore, interaction of hu-G3BP with rAAV-6 led to the formation of aggregates and hampered transduction when the two were codelivered into the mouse. Based on these data, we propose that species-specific interactions of AAVs with blood proteins may differentially impact vector distribution and efficacy in different animal models.
BMI changes in adolescents treated with bupropion SR for smoking cessation

Adolescent overweight and obesity and smoking continue to be very important health challenges because of their lasting effects on overall health. Weight gain after smoking cessation is a barrier to quitting as well as a negative consequence to health. This study reports changes in the body mass index (BMI) z‐scores of adolescent smokers participating in a dose‐ranging clinical trial of bupropion SR (150 mg/day and 300 mg/day) for smoking cessation.
Post-discharge nursing problems of spinal cord injured patients: on which ” elds can nurses contribute to rehabilitation?

Objective: To identify nursing problems of spinal cord injured (SCI) patients after discharge from clinical rehabilitation and to identify gaps in the nursing care regarding the prevention of these problems. Design: The study had an exploratory character and was divided into three phases. Phase 1 had a qualitative nature. Eight patients were interviewed to obtain insight into experienced problems after discharge. In phase 2, a panel of experts regarding nursing care for SCI patients selected nursing problems out of all problems mentioned. Phase 3 consisted of a mailed questionnaire including the nursing problem areas identified in phase 2, which was sent to all patients that were discharged during the last 18 months before the study. Setting: Specialist rehabilitation centre, the Netherlands. Subjects: Eight patients participated in phase 1 (100% response rate), 35 nurses participated in phase 2 (87.5% response rate) and 35 patients participated in phase 3 (62.5% response rate). Results: The most important nursing problems in the response group appeared to be: limitations to activities of daily living, having difficulties in asking for help (assertiveness), pain, coping with the disability, dependency on personal help and problems with changed bladder regulation. The respondents made several suggestions for improving nursing care, involving both clinical care and care after discharge. Conclusions: SCI patients experience serious problems after discharge from clinical rehabilitation. Nurses can give input on a wide variety of these problems.
Study of visuospatial skill in patients with dementia

Objectives: To assess the visuospatial function in different types of dementia with the visual object and space perception (VOSP) battery and to relate the degree of visuospatial dysfunction with different types and stages of dementia. Materials and Methods: A sample of 53 participants with dementia and equal number of age-, sex-, and education-matched controls were recruited for the study. Participants were evaluated for visuospatial skill using VOSP test battery. The scores of dementia patients were compared with controls and within dementia cohort scores were compared based on stage of dementia. Results: The dementia group scored low in all of the subtests of the VOSP battery in comparison to controls. Alzheimer′s disease (AD), dementia of Lewy bodies (DLB), and vascular dementia (VaD) patients performed more poorly than controls in all subtests examining object perception and space perception. The three semantic variants of frontotemporal dementia (FTD) patients scored low in all four subtests of object perception, whereas behavioral variant FTD (bvFTD) patients performed normally. The scores deteriorated with the advancement of dementia in all patients from the dementia groups. Conclusions: Visuospatial function is significantly impaired in dementia patients particularly in AD, DLB, and VaD patients from the beginning, and the impairment is severe in advanced disease stages.
Examination of the usefulness of non-invasive stroke volume variation monitoring for adjusting fluid supplementation during laparoscopic adrenalectomy in patients with pheochromocytoma.

PURPOSE OF THE STUDY The measurement of stroke volume variation (SVV) using the FloTrac™ system (Edwards Lifescience, USA) is useful to estimate cardiac preload. We evaluated the benefits of SVV monitoring for adjusting fluid supplementation during laparoscopic adrenalectomy under anesthesia in patients with pheochromocytoma. SUBJECTS AND METHODS Among 10 patients who underwent laparoscopic adrenalectomy for pheochromocytoma in our institution from June 2004 to December 2009, SVV was not monitored in 5 patients (group I) and in the other 5 patients (group II), SVV monitoring was performed. Subject age, height and body weight, total volume of fluid supplemented, blood loss, urine output and net fluid in-out balance during the procedure were retrospectively assessed. In those with SVV monitoring, infusion volume was adjusted for SVV less than 13%. RESULTS There were significant differences in the patient age and body weight between the two groups (group I: 64.2 years old and 55.1 kg; group II: 43.6 years old and 71.7 kg). Both total infusion volume and urine output were significantly higher in group I compared with group II (5,610 vs. 2,400 ml and 1,125 vs. 750 ml, respectively). Total blood loss was similar between the two groups. Values of the net fluid balance divided by the body weight and total anesthesia period (hr) were significantly lower in group II compared with group I (I; +13.2 in group I and +6.2 in group II, ml/kg/hr). CONCLUSIONS These data suggest that SVV monitoring is helpful to estimate the optimal volume for fluid supplementation and could prevent excessive fluid infusion during surgical procedures.
Healing properties of surface-coated polycaprolactone-co-lactide scaffolds: A pilot study in sheep

The aim of this pilot study was to evaluate the bioactive, surface-coated polycaprolactone-co-lactide scaffolds as bone implants in a tibia critical size defect model. Polycaprolactone-co-lactide scaffolds were coated with collagen type I and chondroitin sulfate and 30 piled up polycaprolactone-co-lactide scaffolds were implanted into a 3 cm sheep tibia critical size defect for 3 or 12 months (n = 5 each). Bone healing was estimated by quantification of bone volume in the defects on computer tomography and microcomputer tomography scans, plain radiographs, biomechanical testing as well as by histological evaluations. New bone formation occurred at the proximal and distal ends of the tibia in both groups. The current pilot study revealed a mean new bone formation of 63% and 172% after 3 and 12 months, respectively. The bioactive, surface coated, highly porous three-dimensional polycaprolactone-co-lactide scaffold stack itself acted as a guide rail for new bone formation along and into the implant. These preliminary data are encouraging for future experiments with a larger group of animals.
Attribute Embedding with Visual-Semantic Ambiguity Removal for Zero-shot Learning

Conventional zero-shot learning (ZSL) methods recognise an unseen instance by projecting its visual features to a semantic space that is shared by both seen and unseen categories. However, we observe that such a one-way paradigm suffers from the visual-semantic ambiguity problem. Namely, the semantic concepts (e.g. attributes) cannot explicitly correspond to visual patterns, and vice versa. Such a problem can lead to a huge variance in the visual features for each attribute. In this paper, we investigate how to remove such semantic ambiguity based on the observed visual appearances. In particular, we propose (1) a novel latent attribute space to mitigate the gap between visual appearances and semantic expressions; (2) a dual-graph regularised embedding algorithm called Visual-Semantic Ambiguity Removal (VSAR) that can simultaneously extract the shared components between visual and semantic information and mutually align the data distribution based on the intrinsic local structures of both spaces; (3) a new zero-shot recognition framework that can deal with both instance-level and category-level ZSL tasks. We validate our method on two popular zero-shot learning datasets, AwA and aPY. Extensive experiments demonstrate that our proposed approach significantly outperforms the state-of-the-art methods.