Miracle-dz/UniFAR-FTUs huggingface dataset:
Cellular Heparan Sulfate Participates in the Metabolism of Prions*

During prion diseases, the host protein PrPC is refolded into an abnormal conformer “prion” PrPSc. Histological and pharmacological data have suggested that glycosaminoglycans may be involved in the development of prion diseases. Here we present the first direct evidence that cellular glycosaminoglycans play a role in the biogenesis of PrPSc in prion-infected ScN2a cells. When ScN2a cells were incubated with estradiol β-d-xyloside to inhibit the glycosylation of proteoglycans, PrPSc was vastly reduced. Treating ScN2a-M cells with heparinase III, but not with heparinase I or chondroitinase ABC, caused a profound reduction of PrPSc. In contrast, neither the amount of PrPC nor its subcellular distribution were affected as assayed by immunofluorescence microscopy and flotation procedures. In vitro treatment of ScN2a membranes with heparinase III at either neutral or acidic pH did not reduce the level of protease-resistant PrPSc. The inhibitor of sulfation, sodium chlorate, vastly reduces PrPSc in ScN2a cells (Gabizon, R., Meiner, Z., Halimi, M., and Ben-Sasson, S. A. (1993) J. Cell. Physiol. 157, 319–325). Both soluble heparan sulfate and chondroitin sulfate partially restored the level of PrPSc in chlorate-treated cells. We conclude that heparinase III-sensitive, presumably undersulfated, cellular heparan sulfate plays a significant role in the biogenesis of PrPSc in ScN2a cells.
A Simple Model for the Distribution of Quiet-Sun Magnetic Field Strengths

We derive a first-order linear differential equation describing the shape of the probability density function (PDF) of magnetic field strengths in the quiet Sun. The modeling is very schematic. It considers convective motions which continuously supply and withdraw magnetic structures. In addition, a magnetic amplification mechanism increases the field strength up to a threshold that cannot be exceeded. These three basic ingredients provide PDFs in good agreement with the PDFs produced by realistic numerical simulations of magnetoconvection, as well as with quiet-Sun PDFs inferred from observations. In particular, the distribution is approximately lognormal, and it produces an excess of magnetic fields (i.e., a hump in the distribution) right before the maximum field strength. The success of this simple model may indicate that only a few basic ingredients shape the quiet-Sun PDF. Our approach provides a concise parametric representation of the PDF, as required to develop automatic methods of diagnostics.
Time-sequence histologic imaging of laser-treated cherry angiomas with in vivo confocal microscopy.

OBJECTIVE To chronicle the pathophysiologic changes that occur subsequent to laser treatment of vascular lesions, we used a confocal scanning laser microscope that yields high-resolution microscopic images of skin in vivo. METHODS Cherry angiomas were treated with the 585-nm flashlamp-pumped pulsed-dye laser (PDL) and the 568-nm continuous-wave krypton laser. Repeated confocal reflectance imaging was performed before and immediately after treatment, as well as after several hours, 1 day, 2 days, 1 week, 2 weeks, 3 weeks, and 4 weeks. RESULTS Before treatment, confocal images revealed dilated blood vessels ranging from 10 to 50 microm in caliber, closely spaced at 5 to 50 microm apart. After PDL treatment, amorphous cords of refractile material conformed to the shape of the original vessels, followed by dark nonrefractile spaces where the vessels once were. Inflammation and necrosis ensued, with eventual replacement after 3 weeks by normal-appearing skin. After krypton laser treatment, dark nonrefractile spaces appeared immediately, with subsequent inflammation, necrosis, and eventual healing by 4 weeks. CONCLUSION Confocal laser microscopic imaging elucidates the dynamic pathophysiologic events that occur after laser treatment of vascular lesions and has added insight into the different mechanisms of vessel damage induced by the PDL and krypton laser.
The current prevalence of sleep disordered breathing in congestive heart failure patients treated with beta-blockers.

STUDY OBJECTIVES Although sleep disordered breathing is thought to be common in patients with systolic heart failure, prior studies are difficult to interpret due to a variety of factors including small sample sizes, referral bias to sleep laboratories among participants, lack of modern medical therapy for congestive heart failure, and the failure to use modern techniques to assess breathing such as nasal pressure. Our objective was to determine the current prevalence of sleep disordered breathing in a state-of-the-art congestive heart failure clinic. METHODS We conducted a prospective study of consecutive patients who visited our heart failure clinic to assess the prevalence of sleep apnea in all eligible patients on maximal medical therapy. We used 4-channel recording equipment and modified Chicago criteria for scoring respiratory events (using heart rate response as a surrogate for arousal from sleep). RESULTS We observed that among the 108 participants, 61% had some form of sleep disordered breathing (31% central apnea with Cheyne Stokes respiration and 30% obstructive sleep apnea). Sleep disordered breathing was significantly associated with atrial fibrillation (OR = 11.56, p = 0.02) and worse functional heart failure class (OR = 2.77, p = 0.02), after adjusting for male sex, age over 60 years, body mass index, and left ventricular ejection fraction. CONCLUSIONS We conclude that both obstructive and central sleep apnea remain common in congestive heart failure patients despite advances in medical therapy, and that the previously reported high prevalence values are unlikely to be explained by referral bias or participation bias in prior studies. These data have important clinical implications for practitioners providing CHE therapy.
Population Based Training of Neural Networks

Neural networks dominate the modern machine learning landscape, but their training and success still suffer from sensitivity to empirical choices of hyperparameters such as model architecture, loss function, and optimisation algorithm. In this work we present \emph{Population Based Training (PBT)}, a simple asynchronous optimisation algorithm which effectively utilises a fixed computational budget to jointly optimise a population of models and their hyperparameters to maximise performance. Importantly, PBT discovers a schedule of hyperparameter settings rather than following the generally sub-optimal strategy of trying to find a single fixed set to use for the whole course of training. With just a small modification to a typical distributed hyperparameter training framework, our method allows robust and reliable training of models. We demonstrate the effectiveness of PBT on deep reinforcement learning problems, showing faster wall-clock convergence and higher final performance of agents by optimising over a suite of hyperparameters. In addition, we show the same method can be applied to supervised learning for machine translation, where PBT is used to maximise the BLEU score directly, and also to training of Generative Adversarial Networks to maximise the Inception score of generated images. In all cases PBT results in the automatic discovery of hyperparameter schedules and model selection which results in stable training and better final performance.
Renal morphology of the English sole (Parophrys vetulus).

The nephron of the English sole, Parophrys vetulus, is composed of the following regions: a renal corpuscle with few capillary loops and an extensive mesangial area with mesangial cell processes insinuated between endothelium and podocyte basement membrane; a ciliated neck segment with mucous-containing cells; the first major brush border segment with a broad vacuolated apical zone most closely resembling the mammalian proximal convoluted tubule; a second major brush border segment with the tallest most eosinophilic cells; a gradual transition to a third major brush border segment with lower, more basophilic cells; no distal convolution and a collecting tubule which empties into a collecting duct system. Granulated cells in the arteriolar media appeared to be modified smooth muscle cells.
Hepatic Synthesis and Urinary Elimination of Acetaminophen Glucuronide Are Exacerbated in Bile Duct-Ligated Rats

Renal and intestinal disposition of acetaminophen glucuronide (APAP-GLU), a common substrate for multidrug resistance-associated proteins 2 and 3 (Mrp2 and Mrp3), was assessed in bile duct-ligated rats (BDL) 7 days after surgery using an in vivo perfused jejunum model with simultaneous urine collection. Doses of 150 mg/kg b.w. (i.v.) or 1 g/kg b.w. (i.p.) of acetaminophen (APAP) were administered, and its glucuronide was determined in bile (only Shams), urine, and intestinal perfusate throughout a 150-min period. Intestinal excretion of APAP-GLU was unchanged or decreased (-58%) by BDL for the 150 mg and 1 g/kg b.w. doses of APAP, respectively. In contrast, renal excretion was increased by 200 and 320%, respectively. Western studies revealed decreased levels of apical Mrp2 in liver and jejunum but increased levels in renal cortex from BDL animals, whereas Mrp3 was substantially increased in liver and not affected in kidney or intestine. The global synthesis of APAP-GLU, determined as the sum of cumulative excretions, was higher in BDL rats (+51 and +110%) for these same doses of APAP as a consequence of a significant increase in functional liver mass, with no changes in specific glucuronidating activity. Expression of apical breast cancer resistance protein, which also transports nontoxic metabolites of APAP, was decreased by BDL in liver and renal cortex, suggesting a minor participation of this route. We demonstrate a more efficient hepatic synthesis and basolateral excretion of APAP-GLU followed by its urinary elimination in BDL group, the latter two processes consistent with up-regulation of liver Mrp3 and renal Mrp2.
Optics of Light Scattering Media: Problems and Solutions

Preface. Preface to First Edition. List of Abbreviations * List of Captions and Tables. Introduction * Single Light Scattering * Radiative Transfer * Light Scattering and Radiative Transfer in Densely Packed Disperse Media * Applications. Appendix I: Refractive Indices. Appendix II: Exact Solutions of Light Scattering Problem for Uniform Two-Layered and Optically Active Spherical Particles. Appendix III: Special Functions. Appendix IV: Light Scattering on the Internet. Appendix V: Phase Functions. References.
Emphasizing temporal-based user profile modeling in the context of session search

In this paper, we aim at modeling the user profile containing timely relevant information extracted from his interactions with search engines. We considered a time-sensitive user profile that provides relevant and fresh information inferred from his submitted queries, reformulated queries and clicked results. We used a unique profile that integrates current and recurrent interactions within a session giving more importance to recent interactions without ignoring the old ones. We conducted experiments using the 2013 TREC Session track and the ClueWeb12 collection that showed the effectiveness of our approach compared to state-of-the-art ones.
Screening Ingredients from Herbs against Pregnane X Receptor in the Study of Inductive Herb-Drug Interactions: Combining Pharmacophore and Docking-Based Rank Aggregation

The issue of herb-drug interactions has been widely reported. Herbal ingredients can activate nuclear receptors and further induce the gene expression alteration of drug-metabolizing enzyme and/or transporter. Therefore, the herb-drug interaction will happen when the herbs and drugs are coadministered. This kind of interaction is called inductive herb-drug interactions. Pregnane X Receptor (PXR) and drug-metabolizing target genes are involved in most of inductive herb-drug interactions. To predict this kind of herb-drug interaction, the protocol could be simplified to only screen agonists of PXR from herbs because the relations of drugs with their metabolizing enzymes are well studied. Here, a combinational in silico strategy of pharmacophore modelling and docking-based rank aggregation (DRA) was employed to identify PXR's agonists. Firstly, 305 ingredients were screened out from 820 ingredients as candidate agonists of PXR with our pharmacophore model. Secondly, DRA was used to rerank the result of pharmacophore filtering. To validate our prediction, a curated herb-drug interaction database was built, which recorded 380 herb-drug interactions. Finally, among the top 10 herb ingredients from the ranking list, 6 ingredients were reported to involve in herb-drug interactions. The accuracy of our method is higher than other traditional methods. The strategy could be extended to studies on other inductive herb-drug interactions.
Efficient estimation of log‐normal means with application to pharmacokinetic data

In this paper, the problem of interest is efficient estimation of log‐normal means. Several existing estimators are reviewed first, including the sample mean, the maximum likelihood estimator, the uniformly minimum variance unbiased estimator and a conditional minimal mean squared error estimator. A new estimator is then proposed, and we show that it improves over the existing estimators in terms of squared error risk. The improvement is more significant with small sample sizes and large coefficient of variations, which is common in clinical pharmacokinetic (PK) studies. In addition, the new estimator is very easy to implement, and provides us with a simple alternative to summarize PK data, which are usually modelled by log‐normal distributions. We also propose a parametric bootstrap confidence interval for log‐normal means around the new estimator and illustrate its nice coverage property with a simulation study. Our estimator is compared with the existing ones via theoretical calculations and applications to real PK studies. Copyright © 2005 John Wiley & Sons, Ltd.
Autophagy in human health and disease.

From the Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston (A.M.K.C., S.W.R.); and the Howard Hughes Medical Institute and Department of Internal Medicine, Center for Autophagy Research, University of Texas Southwestern Medical Center, Dallas (B.L.). Address reprint requests to Dr. Choi at the Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, or at amchoi@rics.bwh. harvard.edu.
Design of 60- and 77-GHz Narrow-Bandpass Filters in CMOS Technology

This paper investigates the design and implementation of millimeter-wave narrow-bandpass filters in a standard 0.18- m CMOS technology. Filters with a measured 10% 3-dB bandwidth at 60 and 77 GHz are realized in a thin-film microstrip structure by using the lowest metallization layer as a ground plane. The impact of dissipation losses of the filters is also examined. It is found that the metallization losses in the coupled-line filter as well as the ground plane are the main reasons for the insertion loss.
Reexamination of the folding of BPTI: predominance of native intermediates

Bovine pancreatic trypsin inhibitor (BPTI) continues to be the only protein for which a detailed pathway of folding has been described. Previous studies led to the conclusion that nonnative states are well populated in the oxidative folding of BPTI. This conclusion has broadly influenced efforts to understand protein folding. The population of intermediates present during the folding of BPTI has been reexamined by modern separation techniques. It was found that all well-populated folding intermediates contain only native disulfide bonds. These data emphasize the importance of native protein structure for understanding protein folding.
An optimization approach for the synthesis of AUTOSAR architectures

Synthesis of automotive architectures is a complex problem that needs an automated support. AUTOSAR, standard for the specification of automotive architectures, defines a synthesis process of software components and their connections in a set of fixed-priority OS tasks distributed over a network of ECUs. During the synthesis process software components are allocated on ECU-s. Since each component encapsulates a set of so-called runnable entities, synthesis completes by partitioning runnable entities in OS tasks with assigned fixed priorities. This paper proposes an optimization approach for the synthesis of AUTOSAR architectures based on genetic algorithms and mixed integer linear programming techniques. Optimization criteria consider end-to-end timing responses and memory consumption.
Machining of Titanium and its Alloys—a Review

Even though a new generation of tool materials is now available which is revolutionizing machinability of a large number of work materials, the machining of titanium continues to be a problem. In the present paper an analysis of the main machining problems, chip formation, tool wear and wear mechanisms, are presented. Alternative methods of machining such expensive and difficult-to-machine materials are also indicated; these include the use of rotary and ledge tools along with ultrasonic assistance.
The Labor of Caregiving: A Theoretical Model of Caregiving During Potentially Fatal Illness

The purpose of this study was to explore the influence that chronic and potentially fatal illness has on the caregiving process over time. Data were collected through in-depth interviews with 26 family caregivers of people experiencing AIDS or advanced cancer over a 4-month period. Constant comparative analysis was used to analyze the data. A substantive theory of family caregiving for people with life-threatening illnesses was developed around a core organizing theme: the labor of caregiving. Four phases emerged: becoming a caregiver, taking care, midwifing the death, and taking the next step. This study validates the taking-care or “tasks” aspect of caregiving, revealing that issues and tasks vary in each phase of caregiving. The key role of the caregiver in contributing to the quality of life of the ill person was apparent in the initial phase of an illness as well as at the time of death.
Modeling and Implementation of Object-Oriented E-Commerce Platform

The object technology has been recognized as a paradigm for building an e-commerce Web site. Components have been thought to be the next evolution of objects. Currently, most applications of object and component technologies focused on using the encapsulation feature of the object technology. Encapsulation can help build the site faster but could not make renovation and enhancement efficient. In this paper we propose a method that incorporates inheritance and polymorphism into the design and implementation process of an e-commerce Web site. The proposed method is verified through the construction of an e-commerce Web site. We evaluate our method and compare it with other methods by experiments. It has shown that the proposed method not only facilitates the design and implementation of an e-commerce Web site but also makes the management, maintenance, and expansion of an e-commerce Web site more efficient. Furthermore, the objects are easier to be shared, reused, and assembled to a component.
A comparison of the clinical manifestations of feeding whole and hydrolysed chicken to dogs with hypersensitivity to the native protein.

Twenty-six dogs with known adverse food reactions were fed whole chicken for 14 days. From this group, 12 dogs with cutaneous manifestations following exposure to chicken meat were selected and randomly divided into two groups (n = 6). Each group was then fed hydrolysed chicken or hydrolysed soy for 14 days in a blinded crossover design with a 17-day washout period between each diet. Assessments of a CADESI (Canine Atopic Dermatitis Extent and Severity Index) score and pruritus were performed throughout the entire study, and combined in a global score (GS). Serum was collected weekly for the measurement of chicken- and soy-specific IgG and IgE. Dogs displayed the most severe clinical response when eating whole chicken compared to baseline (P < 0.001). The GS was significantly reduced in 11 of the 12 dogs when fed hydrolysed chicken were compared to those fed whole chicken (3.58 ± 2.81 versus 20.38 ± 14.65, P < 0.01). Serum immunoglobulin G and E responses were variable and did not show relationship with specific dietary exposure.
Dissociation of CAK from Core TFIIH Reveals a Functional Link between XP-G/CS and the TFIIH Disassembly State

Transcription factor II H (TFIIH) is comprised of core TFIIH and Cdk-activating kinase (CAK) complexes. Here, we investigated the molecular and cellular manifestation of the TFIIH compositional changes by XPG truncation mutations. We showed that both core TFIIH and CAK are rapidly recruited to damage sites in repair-proficient cells. Chromatin immunoprecipitation against TFIIH and CAK components revealed a physical engagement of CAK in nucleotide excision repair (NER). While XPD recruitment to DNA damage was normal, CAK was not recruited in severe XP-G and XP-G/CS cells, indicating that the associations of CAK and XPD to core TFIIH are differentially affected. A CAK inhibition approach showed that CAK activity is not required for assembling pre-incision machinery in vivo or for removing genomic photolesions. Instead, CAK is involved in Ser5-phosphorylation and UV-induced degradation of RNA polymerase II. The CAK inhibition impaired transcription from undamaged and UV-damaged reporter, and partially decreased transcription of p53-dependent genes. The overall results demonstrated that a) XP-G/CS mutations affect the disassembly state of TFIIH resulting in the dissociation of CAK, but not XPD from core TFIIH, and b) CAK activity is not essential for global genomic repair but involved in general transcription and damage-induced RNA polymerase II degradation.
Hamartoma of the breast: a clinicopathological review

Aims: To review 25 cases of breast hamartoma and discuss the pathological criteria, and the usefulness of imaging modalities, fine needle aspiration cytology (FNAC), and needle core biopsy in the diagnosis. Methods: The hamartomas were assessed for interlobular fibrotic stroma, stromal adipose tissue content, pseudo-angiomatous stromal hyperplasia, and epithelial changes (hyperplasia, adenosis or apocrine metaplasia, and cyst formation). All imagings, previous FNACs, and biopsies were also reviewed. Results: Imaging (mammography, ultrasound, and magnetic resonance imaging) was performed in 18 cases, and mostly showed encapsulated masses with a heterogeneous appearance. Microscopically, all hamartomas demonstrated good demarcation with fibrous tissue condensation. Adipose tissue was noted in all cases (5–90%; mean, 31%), and interlobular fibrosis in 21 cases. Benign epithelial hyperplasia occurred in 10 cases, and pseudo-angiomatous stromal hyperplasia or cystic ducts in eight cases each. Apocrine metaplasia, calcification, stromal giant cells, and adenosis occurred in four cases or less. Two cases showed coexisting ductal carcinoma in situ limited to within the hamartoma. Needle core biopsies (four cases) and FNAC (14 cases) were largely insufficient, inconclusive, or non-specific. Conclusions: Hamartomas do not possess specific diagnostic histological features. The role of FNAC and needle core biopsy in making the diagnosis is limited, and requires clinical and radiological correlation to avoid underdiagnosis.