Miracle-dz/UniFAR-FTUs huggingface dataset:
First Assessment in Humans of the Safety, Tolerability, Pharmacokinetics, and Ex Vivo Pharmacodynamic Antimalarial Activity of the New Artemisinin Derivative Artemisone

ABSTRACT In preclinical studies, artemisone (BAY 44-9585), a new artemisinin derivative, was shown to possess enhanced efficacy over artesunate, and it does not possess the neurotoxicity characteristic of the current artemisinins. In a phase I program with double-blind, randomized, placebo-controlled, single and multiple ascending oral-dose studies, we evaluated the safety, tolerability, pharmacokinetics, and ex vivo pharmacodynamic antimalarial activity of artemisone. Single doses (10, 20, 30, 40, and 80 mg) and multiple doses (40 and 80 mg daily for 3 days) of artemisone were administered orally to healthy subjects. Plasma concentrations of artemisone and its metabolites were measured by liquid chromatography/tandem mass spectrometry (LC/MS-MS). Artemisone was well tolerated, with no serious adverse events and no clinically relevant changes in laboratory and vital parameters. The pharmacokinetics of artemisone over the 10- to 80-mg range demonstrated dose linearity. After the single 80-mg dose, artemisone had a geometric mean maximum concentration of 140.2 ng/ml (range, 86.6 to 391.0), a short elimination half-life (t1/2) of 2.79 h (range, 1.56 to 4.88), a high oral clearance of 284.1 liters/h (range, 106.7 to 546.7), and a large volume of distribution of 14.50 liters/kg (range, 3.21 to 51.58). Due to artemisone's short t1/2, its pharmacokinetics were comparable after single and multiple dosing. Plasma samples taken after multiple dosing showed marked ex vivo pharmacodynamic antimalarial activities against two multidrug-resistant Plasmodium falciparum lines. Artemisone equivalent concentrations measured by bioassay revealed higher activity than artemisone measured by LC/MS-MS, confirming the presence of active metabolites. Comparable to those of other artemisinin's, artemisone's t1/2 is well suited for artemisinin-based combination therapy for the treatment of P. falciparum malaria.
Doubly Randomized Delayed-Start Design for Enrichment Studies with Responders or Nonresponders

High placebo response has been a major source of bias and is difficult to deal with in many central nervous system (CNS) clinical trials. This bias has led to a high failure rate in mood disorder trials even with known effective drugs. For cancer trials, the traditional parallel group design biases the inference on the maintenance effect of the new drug with the traditional time-to-treatment failure analysis. To minimize bias, we propose a doubly randomized delayed-start design for clinical trials with enrichment. The design consists of two periods. In the first period, patients can be randomized to receive several doses of a new drug or a control. In the second period, control patients of the first period of an enriched population can be rerandomized to receive the same or fewer doses of the new drug or to continue on the control. Depending on the clinical needs, different randomization ratios can be applied to the two periods. The essential feature is that the design is naturally adaptive because of the randomization for the second period. As a result, other aspects of the second period, such as the sample size, can be modified adaptively when an interim analysis is set up for the first period. At the end of the trial, response data from both randomizations are combined in an integrated analysis. Because of the enrichment in the second period, the design increases the probability of trial success and, in addition, reduces the required sample size. Thus, for clinical development, the design offers greater efficiency.
An economic paradigm for query processing and data migration in Mariposa

Many new database applications require very large volumes of data. Mariposa is a database system under construction at Berkeley responding to this need. This system combines the best features of traditional distributed database systems, object-oriented DBMSs, tertiary memory file systems and distributed file systems. Mariposa objects can be stored over thousands of autonomous sites and on memory hierarchies with very large capacity. This scale of the system leads to complex query execution and storage management issues, unsolvable in practice with traditional techniques. We propose an economic paradigm as the solution. A query receives a budges which it spends to obtain the answers. Each site attempts to maximize income by buying and selling storage objects, and processing queries for locally stored objects. We present the protocols which underlie the Mariposa economy. <<ETX>>
Multi-view reconstruction under varying illumination conditions

This paper addresses the problem of complete and detailed 3D model reconstruction of objects filmed by multiple cameras under varying illumination. Firstly, initial normal maps are obtained to enhance the correspondence mapping. Then, the depth for every pixel is estimated by combining photometric constraint with occlusion robust photo-consistency. Finally, after filtering the point cloud, a Poisson surface reconstruction is applied to obtain a watertight mesh. In contrast with traditional photometric stereo techniques, the proposed algorithm does not directly calculate the photometric normal but integrates the photometric constraint into the depth estimation. Furthermore, different from classic multi-view stereo(MVS), we consider the counterpart under changing light conditions. The algorithm has been implemented based on our multi-camera and multi-light acquisition system. We validate the method by complete reconstruction of challenging real objects and show experimentally that this technique can greatly improve on correspondence-based MVS results.
Sarcopenia Is Associated with Cognitive Impairment Mainly Due to Slow Gait Speed: Results from the Korean Frailty and Aging Cohort Study (KFACS)

Sarcopenia and cognitive impairment may share common risk factors and pathophysiological pathways. We examined the association between impairments in specific cognitive domains and sarcopenia (and its defining components) in community-dwelling older adults. We analyzed 1887 patients who underwent cognitive function tests and dual-energy X-ray absorptiometry from the baseline data of adults aged 70–84 years obtained from the Korean Frailty and Aging Cohort Study. Those with disability in activities of daily living, dementia, severe cognitive impairment, Parkinson’s disease, musculoskeletal complaints, neurological disorders, or who were illiterate were excluded. Cognitive function was assessed using the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet, the Frontal Assessment Battery. For sarcopenia, we used the diagnostic criteria of the Asian Working Group for Sarcopenia. The prevalence of sarcopenia was 9.6% for men and 7.6% for women. Sarcopenia (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.04–2.99) and slow gait speed (OR 2.58, 95% CI 1.34–4.99) were associated with cognitive impairment in men. Only slow gait speed (OR 1.88, 95% CI 1.05–3.36) was associated with cognitive impairment in women. Sarcopenia is associated with cognitive impairment mainly due to slow gait speed. Our results suggested that cognitive impairment domains, such as processing speed and executive function, are associated with sarcopenia-related slow gait speed.
A radio frequency MOSFET driver

High power MOSFETs have become synonymous with power electronics applications. The ability of high power MOSFETs to act as a switch makes it the ideal switching device, where maximum voltage and zero current must occur when the device is open. When closed, the MOSFET must allow maximum current to flow with zero voltage across it. This technique of switching between maximum and zero voltage across the high power MOSFET is readily achieved at frequencies below 1 MHz. Raising the frequency to within the radio frequency range has often proved a problem since high power MOSFETs tend to have a frequency cut-off point. This paper attempts to address the switching habits and limits of high power MOSFETs within the radio frequency range by means of computer simulation and experimental verification
Ergodic Spectral Efficiency in MIMO Cellular Networks

This paper shows how the application of stochastic geometry to the analysis of wireless networks is greatly facilitated by: (<inline-formula> <tex-math notation="LaTeX">${i}$ </tex-math></inline-formula>) a clear separation of time scales; (<italic>ii</italic>) the abstraction of small-scale effects via ergodicity; and (<italic>iii</italic>) an interference model that reflects the receiver’s lack of knowledge of how each individual interference term is faded. These procedures render the analysis both more manageable and more precise, as well as more amenable to the incorporation of subsequent features. In particular, the paper presents analytical characterizations of the ergodic spectral efficiency of cellular networks with single-user multiple-input multiple-output and sectorization. These characterizations, in the form of easy-to-evaluate expressions, encompass the coverage, the distribution of spectral efficiency over the network locations, and the average thereof.
Properties of the hybrid form of the 26S proteasome containing both 19S and PA28 complexes

PA28 is a γ‐interferon‐induced complex that associates with the 20S proteasome and stimulates breakdown of small peptides. Recent immunoprecipitation studies indicate that, in vivo, PA28 also exists in larger complexes that also contain the 19S particle, which is required for ATP‐ubiquitin‐dependent degradation of proteins. However, because of its lability, the structure and properties of this larger complex remain unclear. Here, we demonstrate that, in vitro, PA28 can associate with 'singly capped’ 26S (i.e. 19S–20S) proteasomes. Electron microscopy of the resulting structures revealed one PA28 ring at one end of the 20S particle and a 19S complex at the other. These hybrid complexes show enhanced hydrolysis of small peptides, but no significant increase in rates of protein breakdown. Nevertheless, during breakdown of proteins, the complexes containing PA28αβ or PA28α generated a pattern of peptides different from those generated by 26S proteasomes, without altering mean product length. Presumably, this change in peptides produced accounts for the capacity of PA28 to enhance antigen presentation.
Loss of Function in Heparan Sulfate Elongation Genes EXT1 and EXT 2 Results in Improved Nitric Oxide Bioavailability and Endothelial Function

Background Heparanase is the major enzyme involved in degradation of endothelial heparan sulfates, which is associated with impaired endothelial nitric oxide synthesis. However, the effect of heparan sulfate chain length in relation to endothelial function and nitric oxide availability has never been investigated. We studied the effect of heterozygous mutations in heparan sulfate elongation genes EXT1 and EXT2 on endothelial function in vitro as well as in vivo. Methods and Result Flow‐mediated dilation, a marker of nitric oxide bioavailability, was studied in Ext1+/− and Ext2+/− mice versus controls (n=7 per group), as well as in human subjects with heterozygous loss of function mutations in EXT1 and EXT2 (n=13 hereditary multiple exostoses and n=13 controls). Endothelial function was measured in microvascular endothelial cells under laminar flow with or without siRNA targeting EXT1 or EXT2. Endothelial glycocalyx and maximal arteriolar dilatation were significantly altered in Ext1+/− and Ext2+/− mice compared to wild‐type littermates (glycocalyx: wild‐type 0.67±0.1 μm, Ext1+/− 0.28±0.1 μm and Ext2+/− 0.25±0.1 μm, P<0.01, maximal arteriolar dilation during reperfusion: wild‐type 11.3±1.0%), Ext1+/− 15.2±1.4% and Ext2+/− 13.8±1.6% P<0.05). In humans, brachial artery flow‐mediated dilation was significantly increased in hereditary multiple exostoses patients (hereditary multiple exostoses 8.1±0.8% versus control 5.6±0.7%, P<0.05). In line, silencing of microvascular endothelial cell EXT1 and EXT2 under flow led to significant upregulation of endothelial nitric oxide synthesis and phospho‐endothelial nitric oxide synthesis protein expression. Conclusions Our data implicate that heparan sulfate elongation genes EXT1 and EXT2 are involved in maintaining endothelial homeostasis, presumably via increased nitric oxide bioavailability.
The role of the high-density lipoprotein receptor SR-BI in cholesterol metabolism

The HDL receptor scavenger receptor class B type I (SR-BI), which mediates selective HDL cholesterol uptake, plays a role in murine HDL metabolism, reverse cholesterol transport and whole-body cholesterol homeostasis. SR-BI is found in the liver, where its expression is regulated by estrogen, dietary cholesterol and fat, and controls murine plasma HDL cholesterol levels and bile cholesterol secretion. SR-BI is also highly expressed in rodent steroidogenic cells, where it facilitates cholesterol uptake for storage or steroid hormone synthesis and where its expression is regulated by trophic hormones. The detailed mechanism(s) underlying SR-BI-mediated selective cholesterol uptake have not yet been elucidated. Further analysis of the molecular and cellular bases of SR-BI regulation and function should provide new insights into the physiology and pathophysiology of cholesterol metabolism.
Hybrid precoding using long-term channel statistics for massive MIMO systems

Hybrid analog/digital precoding in the downlink of multiuser massive MIMO systems can reduce the number of RF chains hence reducing total cost and improving power efficiency. Having few RF chains, however, makes it difficult for a base station to acquire instantaneous channel state information across all antennas. We develop a hybrid technique that uses only long-term (slowly changing) channel statistics in computing the analog precoding matrix. The proposed analog precoder is designed to maximize signal-to-leakage-plus-noise ratio (SLNR) when combined with a baseband precoder. We also propose a constrained precoder design that reduces the effect of a hardware constraint where the analog precoders are realized with phase shifters.
Nitric oxide and carbon monoxide diffusing capacity after a 1‐h oxygen dive to 9 m of sea water

To prevent extensive pulmonary lesions in submerged oxygen divers lung function like the forced vital capacity (FVC) or the diffusing capacity for carbon monoxide (DL,co) are used to monitor pulmonary oxygen toxicity (POT). As the diffusing capacity for nitric oxide (DL,no) measures more accurately the membrane diffusing capacity compared to DL,co we hypothesized that DL,no is superior in monitoring the onset of physiological changes indicative of POT as compared to DL,co or FVC.
Optimal MISO UWB pre-equalizer design with spectral mask constraints

In this paper, we propose a novel optimization-based pre-equalization filter (PEF) design for multiple-input single-output (MISO) direct-sequence ultra-wideband (DS-UWB) systems with pre-Rake combining. The key feature in our design is that we explicitly take into account spectral mask constraints which are usually imposed by telecommunications regulation and standardization bodies. This avoids the need for an inefficient power back-off, which is necessary for existing pre-equalizer and pre-Rake designs that are designed solely based on average transmit power constraints. Simulation results confirm that the proposed PEF design leads to significant performance gains over UWB PEF structures without any explicit spectral mask considerations. Furthermore, the use of multiple transmit antennas is shown to provide substantial combining gains compared to single-antenna transmitter structures. We also investigate the impact of certain system and optimization parameters on the performance of the proposed PEF design.
You ‘Might’ Be Afected: An Empirical Analysis of Readability and Usability Issues in Data Breach Notifications

Data breaches place afected individuals at signifcant risk of identity theft. Yet, prior studies have shown that many consumers do not take protective actions after receiving a data breach notifcation from a company. We analyzed 161 data breach notifcations sent to consumers with respect to their readability, structure, risk communication, and presentation of potential actions. We fnd that notifcations are long and require advanced reading skills. Many companies downplay or obscure the likelihood of the receiver being afected by the breach and associated risks. Moreover, potential actions and ofered compensations are frequently described in lengthy paragraphs instead of clearly listed. Little information is provided regarding an action’s urgency and efectiveness; little guidance is provided on which actions to prioritize. Based on our fndings, we provide recommendations for designing more usable and informative data breach notifcations that could help consumers better mitigate the consequences of being afected by a data breach.
Route Maintenance by Delegation Anssi Kalliolahti

Non-static networks have inherent requirements for routing protocols. These include various ad hoc-, mobile-, peer-topeerand overlay networks. The network nodes have often more possibilities, or obligations, to affect how the packets traverse through the intermediate nodes. However, it is not practical to leave all the routing and packet processing tasks to the end-points only. Neither is the other extreme, where a third party specified intermediate carries out the all tasks. In this paper, we discuss how the delegation can be used to give the nodes a right to delegate specified tasks to intermediate nodes, delegates that the end-points select explicitly by themselves. We study two different proposals of delegation utilization, the delegation oriented architecture and delegation of signalling rights.
Analysis of Nitrogen Removal Processes in a Subsurface Flow Carbonate Sand Filter Treating Municipal Wastewater

Abstract Controlled experiments were carried out in a mesoscale subsurface flow sand filter treating municipal wastewater from a single household. The system consisted of a 50 cm high vertical flow column (pre-filter) with unsaturated flow and a 3 m long horizontal sub-surface flow unit (main filter) with saturated flow. Fluxes of nitrogen and carbon were analyzed in 4 different operating conditions (low and high loading, with and without the prefilter unit). Water samples were taken from the inlet, the outlet and within the sand filter at different depths and locations and analysed for water quality (Tot N, NO3-N, NH4-N, TOC, DOC, CODcr, BOD5, SS, pH, and EC) and dissolved gas content (N2O, CH4, and CO2). Emissions of N2O, CH4, and CO2 were measured with the closed-chamber technique adjacent to water quality sampling points. The results show that prefiltering in a vertical, unsaturated flow column changed the incoming ammonium to nitrate during low loading. During high loading part of the ammonium nitrified in the pre-filter was lost by denitrification. Within the horizontal main filter there were two pathways for the incoming nitrate: denitrification and dissimilatory nitrate reduction to ammonium (DNRA).
Conceptual Scheme for Text Classification System

The paper describes an application of classification algorithms to the text categorization problem. Author proposes a conceptual scheme for an automatic text categorization system. This system must operate with various text representation models and data mining methods. The novelty of this system consists in advanced implementation of JSM method for automatic hypothesis generation — an original logical-combinatorial technology of data mining, which is developed in Russia by several research groups.
Recognition of emotion in a realistic dialogue scenario

Nowadays modern automatic dialogue systems are able to understand complex sentences instead of only a few commands like Stop or No. In a call-center, such a system should be able to determine in a critical phase of the dialogue if the call should be passed over to a human operator. Such a critical phase can be indicated by the customer's vocal expression. Other studies prooved that it is possible to distinguish between anger and neutral speech with prosodic features alone. Subjects in these studies were mostly people acting or simulating emotions like anger. In this paper we use data from a so-called Wizard of Oz (WoZ) scenario to get more realistic data instead of simulated anger. As shown below, the classi cation rate for the two classes "emotion" (class E) and "neutral" (class :E) is signi cantly worse for these more realistic data. Furthermore the classi cation results are heavily speaker dependent. Prosody alone might thus not be su cient and has to be supplemented by the use of other knowledge sources such as the detection of repetitions, reformulations, swear words, and dialogue acts.
Ett välstämt piano - till rätt melodi? : Metautvärdering av Skolverkets nationella utvärdering av grundskolan 2003

Under 2002-03 genomforde Skolverket den hittills storsta utvarderingen av svensk skola, den s.k. Nationella utvarderingen 2003 (NU-03). Utvarderingen involverade ett stort antal forskare samt ca 20 .
A Pilot Study on the Diagnostic Accuracy of Proadrenomedullin and Proatrial Natriuretic Peptide in Lower Respiratory Tract Infections

Background : Pneumonia is the leading cause of death among infectious diseases in developed countries. However, the severity of pneumonia requiring hospitalization often makes the initial diagnosis difficult because of an equivocal clinical picture or interpretation of the chest film. The objective of the present study was to assess the usefulness of the plasma levels of mid-regional proadrenomedullin (MR-proADM) and mid-regional proatrial natriuretic peptide (MR-proANP) in differentiating pneumonia from other lower respiratory tract infections (LRTIs). Methods : A retrospective study was conducted. The plasma levels of MR-proADM and MR-proANP were measured in 85 patients hospitalized for LRTIs, 56 of whom with diagnosis of pneumonia and 29 with other LRTIs. Results : The patients with pneumonia had increased MR-proADM levels (median 1.46 nmol/L [IQR 25-75, 0.82-2.02 nmol/L]) compared with the patients with other LRTIs (median 0.88 nmol/mL [0.71-1.39 nmol/L]) (p= 0.04). However, the MR-proANP levels did not show differences between the groups. The optimal threshold of MR-proADM to predict pneumonia was 1.5 nmol/L, which yielded a sensitivity of 51.7% (95% CI, 38.0-65.3), a 79.3% specificity (95% CI, 60.3-92.0), and an odds ratio of 6.64 (95% CI, 1.32-32.85). The combination of this parameter with C-reactive protein in an “and” rule increased the specificity for detecting pneumonia significantly. Conclusion : MR-proADM levels (but not MR-proANP levels) are increased in patients with pneumonia although its discriminatory power is moderate.
Multiplicative Representations for Unsupervised Semantic Role Induction

In unsupervised semantic role labeling, identifying the role of an argument is usually informed by its dependency relation with the predicate. In this work, we pro-pose a neural model to learn argument embeddings from the context by explicitly incorporating dependency relations as multiplicative factors, which bias argu-ment embeddings according to their dependency roles. Our model outperforms existing state-of-the-art embeddings in un-supervised semantic role induction on the CoNLL 2008 dataset and the SimLex999 word similarity task. Qualitative results demonstrate our model can effectively bias argument embeddings based on their dependency role.