Miracle-dz/UniFAR-FTUs huggingface dataset:
Two Distinct Amyloid β-Protein (Aβ) Assembly Pathways Leading to Oligomers and Fibrils Identified by Combined Fluorescence Correlation Spectroscopy, Morphology, and Toxicity Analyses*

Nonfibrillar assemblies of amyloid β-protein (Aβ) are considered to play primary roles in Alzheimer disease (AD). Elucidating the assembly pathways of these specific aggregates is essential for understanding disease pathogenesis and developing knowledge-based therapies. However, these assemblies cannot be monitored in vivo, and there has been no reliable in vitro monitoring method at low protein concentration. We have developed a highly sensitive in vitro monitoring method using fluorescence correlation spectroscopy (FCS) combined with transmission electron microscopy (TEM) and toxicity assays. Using Aβ labeled at the N terminus or Lys16, we uncovered two distinct assembly pathways. One leads to highly toxic 10–15-nm spherical Aβ assemblies, termed amylospheroids (ASPDs). The other leads to fibrils. The first step in ASPD formation is trimerization. ASPDs of ∼330 kDa in mass form from these trimers after 5 h of slow rotation. Up to at least 24 h, ASPDs remain the dominant structures in assembly reactions. Neurotoxicity studies reveal that the most toxic ASPDs are ∼128 kDa (∼32-mers). In contrast, fibrillogenesis begins with dimer formation and then proceeds to formation of 15–40-nm spherical intermediates, from which fibrils originate after 15 h. Unlike ASPD formation, the Lys16-labeled peptide disturbed fibril formation because the Aβ16–20 region is critical for this final step. These differences in the assembly pathways clearly indicated that ASPDs are not fibril precursors. The method we have developed should facilitate identifying Aβ assembly steps at which inhibition may be beneficial.
Distributed inferencing with ambient and wearable sensors

Wireless sensor networks enable continuous and reliable data acquisition for real-time monitoring in a variety of application areas. Due to the large amount of data collected and the potential complexity of emergent patterns, scalable and distributed reasoning is preferable when compared to centralised inference as this allows network wide decisions to be reached robustly without specific reliance on particular network components. In this paper, we provide an overview of distributed inference for both wearable and ambient sensing with specific focus on graphical models—illustrating their ability to be mapped to the topology of a physical network. Examples of research conducted by the authors in the use of ambient and wearable sensors are provided, demonstrating the possibility for distributed, real-time activity monitoring within a home healthcare environment. Copyright © 2010 John Wiley & Sons, Ltd.
An Ultrawideband MIMO Antenna With Dual Band-Notched Function

A new technique to achieve both good isolation and dual band-notched functions for ultrawideband (UWB) multiple-input-multiple-output (MIMO) antennas was developed. The proposed antenna consists of the radiation patch connected through a via with the strip placed beneath the patch. The strip not only provides another coupling path, but also serves as the impedance transformer, resulting in good isolation (S<sub>21</sub> <; -15 dB) and dual band rejection at WiMAX (3.4-3.7 GHz) and WLAN (5.15-5.35 and 5.725-5.825 GHz) over the UWB system operation (3.1-10.6 GHz). Without decoupling element or resonator, which is often placed between the antennas to acquire good isolation or band rejection, the proposed UWB MIMO antenna requires an individual antenna element size of only 11.2 12 mm<sup>2</sup> (0.12λ<sub>0</sub>×0.11λ<sub>0</sub>)and overall MIMO antenna size of 30 40 mm<sup>2</sup> (0.31λ<sub>0</sub>×0.41λ<sub>0</sub>). The edge-to-edge separation between antennas is , and separation between feeds is 0. 175λ<sub>0</sub> at 3.1 GHz. Detailed investigations of the parameters were performed, and the experimental results agree closely with the simulation results, demonstrating the feasibility of the proposed method.
Inhibiting the VEGF–VEGFR pathway in angiosarcoma, epithelioid hemangioendothelioma, and hemangiopericytoma/solitary fibrous tumor

Purpose of review This review highlights the current body of knowledge regarding the role of the vascular endothelial growth factor (VEGF) and its receptor (VEGFR) in angiosarcoma, epithelioid hemangioendothelioma (EHE), and hemangiopericytoma/solitary fibrous tumor (HPC/SFT). Therapeutic agents that target this pathway are reviewed. Recent findings Several phase II trials in advanced soft tissue sarcoma patients have investigated the efficacy of bevacizumab, an anti-VEGF antibody, as well as sunitinib, sorafenib, and pazopanib, VEGFR tyrosine kinase inhibitors (TKIs). Although response rates and progression-free survival periods were generally low, several angiosarcoma, EHE, and HPC/SFT patients demonstrated response or durable disease stabilization on these therapies. Biological mechanisms underlying the activity of these agents in angiosarcoma, EHE, and HPC/SFT are poorly understood. Some angiosarcoma tumors, however, harbor specific activating mutations in VEGFR2, which may be effectively targeted by VEGFR TKIs. Summary Inhibition of the VEGF/VEGFR pathway may be a rational and effective therapy for certain patients with angiosarcoma, EHE, and HPC/SFT, but more studies are needed to confirm these findings and to identify which patients will benefit from these agents.
Association of fibrin and interleukin 8 in human oral squamous cell carcinoma.

OBJECTIVE We have recently demonstrated that fibrin induces a specific, dose- and time-dependent upregulation of the angiogenic factor interleukin 8 (IL-8) from human oral squamous cell carcinoma (OSCC) cells in vitro. In this study we begin to test the hypothesis that fibrin induces IL-8 expression from tumor cells in vivo by studying their in vivo association in OSCC. STUDY DESIGN The presence of fibrin(ogen) was initially evaluated in 20 archival human OSCCs by means of immunohistochemistry with a polyclonal antibody. The presence of fibrin and IL-8 was then studied in 19 sections from 8 different patients' head and neck tumors (including 6 OSCCs) by means of immunohistochemistry with a monoclonal antibody against fibrin. These 8 tumors had been treated with inhibitors of new fibrin formation and degradation immediately after surgical removal. RESULTS Fibrin staining was found in 100% of the tumor sections tested. IL-8 staining was found in the cytoplasm of tumor cells in 100% of the studied tumors, including areas adjacent to fibrin. CONCLUSIONS These data demonstrate an in vivo association between fibrin and IL-8 in OSCC. These studies support our hypothesis that fibrin induces expression of protumorigenic factors such as IL-8 from tumor cells in vivo.
Functions of Sleep Architecture and the Concept of Protective Fields

This article focuses on the function of human sleep architecture and, where it adjoins, on the ultradian rhythm of NREM and REM cycles. In healthy adult human sleep, NREM and REM sleep succeed each other in 90-110 min intervals. This ultradian pattern of NREM/REM succession is cyclical. Sleep architecture relates to the shifting between sleep stages of varying sleep intensity and arousal thresholds. It has been found to follow a typical but non-cyclical pattern throughout the night. In the first third of the night, light sleep alternates predominantly with slow wave sleep (SWS). As sleep progresses, the amount of SWS typically decreases and REM sleep increases. In the last third of the night, light sleep almost exclusively alternates with REM sleep. The author postulates that one function of the non-cyclical succession of sleep stages is the erection and maintenance of a protective field around the sleeper. A protective field is to be understood as an area of relative safety, minimizing the chances for an intruder to enter the field without detection. The frequent shifts between sleep phases with low and high arousal thresholds allow a periodic screening of the sleep environment for danger signals. The relevant literature on sleep architecture, ultradian rhythms and its determinants is reviewed and the implications of the concept of protective fields are discussed.
Fair Transmission Rate Adjustment in Cooperative Vehicle Safety Systems Based on Multi-Agent Model Predictive Control

Cooperative vehicle safety systems (CVSSs) rely on vehicular networking for broadcasting state information in order to track neighbors’ positions and, therefore, to predict potential collisions. In vehicular networking, a large number of vehicles compete for access to the limited channel resource, causing channel congestion. The vehicle tracking accuracy, which is the basis for CVSSs, therefore, can be heavily affected. Moreover, the available channel resources must be shared among vehicles in a fair way in order to maintain accurate tracking accuracy for each vehicle. To realize fair access to channel resources while maintaining an accurate tracking performance under conditions of dynamic vehicle density, in this paper, we present a distributed fair transmission rate control strategy, based on multi-agent model predictive control (MPC). We first propose a dynamic information dissemination rate model to capture the state information dissemination ability under conditions of dynamic vehicle density. Then, we present a multi-agent information dissemination model, in which each vehicle is controlled by a control agent that uses MPC and coordinates with its neighboring agents in order to determine its optimal transmission rate actions. We then design an augmented-Lagrangian-based distributed decision-making scheme to find the optimal transmission rate actions and, at the same time, reach an agreement on fair and efficient channel utilization among the vehicles. Simulation results confirm that the distributed transmission rate control strategy can guarantee fair access to channel resources while achieving the optimal vehicle tracking performance under conditions of dynamic vehicle density.
The secondary olfactory connections in two chondrichthians, the shark Scyliorhinus canicula and the ray Raja clavata

The secondary olfactory connections in the shark Scyliorhinus canicula and the ray Raja clavata have been studied with reduced silver techniques. After transction through the pedunculus olfactorus in Scyliorhinus degenerating fibers could be traced to the telencephalic hemisphere. On entering the henisphere these fibres subdivide into a small medial and a larger lateral olfactory tract. The medical olfactory tract also projects contralaterally to the submeningeal pallial zone via the commissural olfactoria inferior and to the stratum granulare bulbi olfactorii by way of the commissural olfactoria superio. The lateral olfactory tract distrubytes mainly to the pallium laterale. A striking difference between Scyliorhibnus and Raja is that in the latter no contralaterature for other cartilaginous fishes, it appears that the secondary olfactory connections of Sycliorhinus are more extensive than in other chondrichthians studied experimentally.
SIG on Interactive Computing in Outdoor Recreation

Interactive computing has impacted how people experience outdoor recreation. Nevertheless, the role of interactive computing in outdoor recreation can be complicated. Some people engage in outdoor recreation precisely to avoid distractions associated with pervasive interactive computing. Others use interactive computing to create, enhance or share outdoor recreation experiences. In this SIG, participants will discuss research questions and foundational theories that might guide future work related to interactive computing in outdoor recreation. The discussion will range from engineering issues to research methods. Attendees will have opportunities to stay connected after the SIG.
Analysis of cancer data: a data mining approach

Abstract: Even though cancer research has traditionally been clinical and biological in nature, in recent years data driven analytic studies have become a common complement. In medical domains where data and analytics driven research is successfully applied, new and novel research directions are identified to further advance the clinical and biological studies. In this research, we used three popular data mining techniques (decision trees, artificial neural networks and support vector machines) along with the most commonly used statistical analysis technique logistic regression to develop prediction models for prostate cancer survivability. The data set contained around 120 000 records and 77 variables. A k‐fold cross‐validation methodology was used in model building, evaluation and comparison. The results showed that support vector machines are the most accurate predictor (with a test set accuracy of 92.85%) for this domain, followed by artificial neural networks and decision trees.
Retinoblastoma protein phosphorylation via PI 3-kinase and mTOR pathway regulates adipocyte differentiation.

In the early phase of adipocyte differentiation, transient increase of DNA synthesis, called clonal expansion, and transient hyperphosphorylation of retinoblastoma protein (Rb) are observed. We investigated the role of these phenomena in insulin-induced adipocyte differentiation of 3T3-L1 cells. Insulin-induced clonal expansion, Rb phosphorylation and adipocyte differentiation were all inhibited by the PI 3-kinase inhibitors and rapamycin, but not the MEK inhibitor, whereas the MEK inhibitor, but not PI 3-kinase inhibitors or rapamycin, decreased c-fos induction. We conclude that insulin induces hyperphosphorylation of Rb via PI 3-kinase and mTOR dependent pathway, which promotes clonal expansion and adipocyte differentiation of 3T3-L1 cells.
The Use of Electron Probe MicroAnalysis to Determine the Thickness of Thin Films in Materials Science

Electron Probe MicroAnalysis (EPMA) was born around 1950 when Raymond Castaing, a French graduate student working under the supervision of Andre Guinier, built his first microanalyser (Castaing & Guinier, 1950; Castaing, 1951; Grillon & Philibert, 2002). The principle of EPMA is to bombard the sample surface with a focused electron beam and to collect the X-rays emitted from the sample. The X-rays are dispersed using Bragg diffraction on a mobile monochromator, which enables to get the whole X-ray spectrum from zero to more than 10 keV. The technique of dispersion is called WDS (Wavelength Dispersive X-ray Spectroscopy). The spectrum is made of continuous background (Bremstrahlung emission) and characteristic peaks, which allow elemental qualitative and quantitative analysis of the material. EPMA-WDS can be carried out in dedicated instruments called “microprobes” (usually fitted with 4 WDS spectometers) or in high current Scanning Electron Microscopes (SEM) equipped with one single WDS spectrometer. More recently, Energy Dispersive X-ray Spectroscopy has been developed and has nowadays become a cheap and widespread technique. Most SEM in materials science laboratories are equipped with an EDS spectrometer. EPMA-EDS performances are far below those of EPMA-WDS with regards to sensitivity and spectral resolution, although it can achieve very good qualitative and quantitative results in many cases. EPMA quantification of the sample composition is usually possible by using a standard material of known composition. Unfortunately there is in general no direct proportionality between the concentration of an element and the X-ray emission intensity (peak height) coming from this element. Since the early years of EPMA, many models have been proposed in the literature to correlate the concentration of an element and the associated X-ray emission intensity: ZAF (Philibert & Tixier, 1968), MSG (Packwood & Brown, 1981), PAP and XPP (Pouchou & Pichoir, 1987; Pouchou et al., 1990). The XPP model (implemented in several microanalysis software packages) has now reached a good level of maturity and reliability, even in difficult situations involving light elements and strong bulk absorption. It is based on an accurate calculation of the (z) curve, which describes the depth-dependence of the X-ray emission intensity of a particular line in the sample. In EPMA analysis of
Inhaled fluticasone

We read with interest the paper by Dr Wedzicha and colleagues on cell and cytokine measurements in exacerbations of COPD.1 We feel there are two factors which are worthy of comment. The authors described their patients as being predominantly those with chronic bronchitis. They presented with an exacerbation that consisted of the cardinal features described by Anthonisen and colleagues—namely, combinations of increased breathlessness, increased sputum volume, and increased sputum purulence.2 In view of the fact that increased sputum purulence is a feature of exacerbations, we are surprised at the lack of increase in neutrophils seen in the exacerbations described in the paper. Even if half the patients did not have purulent sputum, we would have expected to have seen an overall increase in the number of neutrophils in the samples …
Late Pleistocene Western Camel (Camelops Hesternus) Hunting in Southwestern Canada

Abstract Late Pleistocene large mammal extinctions in North America have been attributed to a number of factors or combination of factors, primarily climate change and human hunting, but the relative roles of these factors remain much debated. Clo-vis-period hunters exploited species such as mammoth, but many now extinct species such as camels were seemingly not hunted. Archaeological evidence from the Wally’s Beach site in southern Canada, including stone tools and butchered bone, provide the first evidence that Clovis people hunted North American camels. Archaeologists generally dismiss human hunting as a significant contributor to Pleistocene extinctions in North America, but Wally’s Beach demonstrates that human hunting was more inclusive than assumed and we must continue to consider hunting as a factor in Pleistocene extinctions.
Pharmacokinetics of Lopinavir/Ritonavir in HIV/Hepatitis C Virus–Coinfected Subjects With Hepatic Impairment

The effect of hepatic impairment on lopinavir/ritonavir pharmacokinetics was investigated. Twenty‐four HIV‐1‐infected subjects received lopinavir 400 mg/ritonavir 100 mg twice daily prior to and during the study: 6 each with mild or moderate hepatic impairment (and hepatitis C virus coinfected) and 12 with normal hepatic function. Mild and moderate hepatic impairment showed similar effects on lopinavir pharmacokinetics. When the 2 hepatic impairment groups were combined, lopinavir Cmax and AUC12 were increased 20% to 30% compared to the controls. Hepatic impairment increased unbound lopinavir AUC12 by 68% and Cmax by 56%. The effect of hepatic impairment on low‐dose ritonavir pharmacokinetics was more pronounced in the moderate impairment group (181% and 221% increase in AUC12 and Cmax, respectively) than in the mild impairment group (39% and 61% increase in AUC12 and Cmax, respectively). While lopinavir/ritonavir dose reduction is not recommended in subjects with mild or moderate hepatic impairment, caution should be exercised in this population.
Differential Phenotype Profile between Main Right Ventricular Chamber and Outflow Tract in Chronic Pulmonary Hypertension: Echocardiographic Observation

Objectives Right ventricular (RV) dilatation and systolic dysfunction are known remodeling changes occurring in chronic pulmonary hypertension and are likely the result of increases in pulmonary vascular resistance (PVR). It remains unclear whether PVR affects primarily the main RV chamber (mRVc) or the RV outflow tract (RVOT). Methods Standard echocardiography data were collected from a heterogeneous population of 85 consecutive patients (mean age of 54 ± 12 years and mean pulmonary artery systolic pressure of 56 ± 28 mm Hg) to determine how PVR affected size and function of both RV chambers. Results Regarding size, PVR correlated more with mRVc end systolic area (r = 0.77; P < 0.0001) than either mRVc end diastolic area (r = 0.58; P < 0.0001) or RVOT systolic length (r = 0.54; P < 0.0001), although it did not correlate with RVOT end diastolic length. In terms of fractional area change, a stronger negative correlation was seen between PVR and mRVc (r = −0.77; P < 0.0001) than with PVR and RVOT (r = −0.69; P < 0.0001). Systolic velocity of the tricuspid annulus was the best parameter in identifying elevated PVR. Conclusions Based on the echocardiography results, increasing PVR values appear to result in differential RV remodeling with significant mRVc dilation and systolic dysfunction when compared with RVOT. It is important to determine whether the different RV remodeling processes occur in all patients with chronic pulmonary hypertension, regardless of etiology; alter therapeutic response; or determine clinical outcomes.
Inferior vena cava filter insertion through the popliteal vein: enabling the percutaneous endovenous intervention of deep vein thrombosis with a single venous access approach in a single session.

PURPOSE We aimed to evaluate the efficiency of placing an inferior vena cava (IVC) filter through the same popliteal vein access site used for percutaneous endovenous intervention in patients with extensive lower extremity deep vein thrombosis. METHODS This retrospective study included 21 patients who underwent IVC filter insertion through the popliteal vein over a three-year period. Patient medical records were reviewed for the location of the deep vein thrombosis, result of filter removal, and total number of endovascular procedures needed for filter insertion and recanalization of the lower extremity venous system. Follow-up lower extremity computed tomography (CT) venography was also reviewed in each patient to assess the degree of filter tilt in the IVC. RESULTS All patients had extensive lower extremity deep vein thrombosis involving the iliac vein and/or femoral vein. Seventeen patients showed deep vein thrombosis of the calf veins. In all patients, IVC filter insertion and the recanalization procedure were performed during a single procedure through the single popliteal vein access site. In the 17 patients undergoing follow-up CT, the mean tilt angle of the filter was 7.14°±4.48° in the coronal plane and 8.77°±5.49° in the sagittal plane. Filter retrieval was successful in 16 of 17 patients (94.1%) in whom filter retrieval was attempted. CONCLUSION Transpopliteal IVC filter insertion is an efficient technique that results in low rates of significant filter tilt and enables a single session procedure using a single venous access site for filter insertion and percutaneous endovenous intervention.