Miracle-dz/UniFAR-FTUs huggingface dataset:
Validation and clinical application of a method to quantify efavirenz in cervicovaginal secretions from flocked swabs using liquid chromatography tandem mass spectrometry

Background : A liquid chromatography tandem mass spectrometry method to quantify drugs in dried cervicovaginal secretions from flocked swabs was developed and validated using the antiretroviral efavirenz as an example. Methods: Cervicovaginal swabs (CVS) were prepared by submerging flocked swabs in efavirenz-spiked plasma matrix. Time to full saturation, weight uniformity, recovery and room temperature stability were evaluated. Chromatographic separation was on a reverse-phase C18 column by gradient elution using 1mM ammonium acetate in water/acetonitrile at 400 µL/min. Detection and quantification were on a TSQ Quantum Access triple quadrupole mass spectrometer operated in negative ionisation mode. The method was used to quantify efavirenz in CVS samples from human immunodeficiency virus (HIV)-positive women in the VADICT study (NCT03284645). A total of 98 samples (35 paired intensive CVS and DBS pharmacokinetic samples, 14 paired sparse CVS and DBS samples) from 19 participants were available for this analysis. Results: Swabs were fully saturated within 15 seconds, absorbing 128 µL of plasma matrix with coefficient of variation (%CV) below 1.3%. The method was linear with a weighting factor (1/X) in the range of 25-10000 ng/mL with inter- and intra-day precision (% CV) of 7.69-14.9%, and accuracy (% bias) of 99.1-105.3%. Mean recovery of efavirenz from CVS was 83.8% (%CV, 11.2) with no significant matrix effect. Efavirenz remained stable in swabs for at least 35 days after drying and storage at room temperature. Median (range) CVS efavirenz AUC 0-24h was 16370 ng*h/mL (5803-22088), C max was 1618 ng/mL (610-2438) at a T max of 8.0 h (8.0-12), and C min was 399 ng/mL (110-981). Efavirenz CVS:plasma AUC 0-24h ratio was 0.41 (0.20-0.59). Conclusions: Further application of this method will improve our understanding of the pharmacology of other therapeutics in the female genital tract, including in low- and middle-income countries.
Use of Mother-Daughter Multi-Bioreactor Systems for Studies of Steady State Microbial Growth Space. Ema-tütre multireaktorite süsteemide kasutamine mikroorganismide püsiseisundis kasvuruumi uurimisel

7 KOKKUVÕTE . 8 LIST OF PUBLICATIONS . 9 ACKNOWLEDGEMENTS . 10 ABBREVIATIONS . 11 LIST OF SYMBOLS . 12 1 INTRODUCTION . 13 2 LITERATURE REVIEW . 15 2.1 THE CONCEPTS OF PHYSIOLOGICAL STATE AND GROWTH SPACE . 15 2.2 CULTIVATION METHODS TO ANALYSE THE GROWTH SPACE . 18 2.2.1 Material balance for Bioprocess . 19 2.2.2 Periodical, Semi‐Periodical and Con nuous Cul va on Methods . 20 2.2.3 Bat Cul va on . 22 2.2.4 Fed‐Batch . 22 2.2.5 Chemostat . 23 2.2.6 A‐stat . 24 2.2. 7 D‐stat . 25 2.2. 8 Auxostat . 25 2.2. 9 Auxo‐accelerostat . 26 2.3 COMBINING DIFFERENT CULTIVATION METHODS IN GROWTH SPACE ANALYSIS . 26 2.4 PERTURBATION ANALYSIS IN PHYSIOLOGY RESEARCH . 27 2.5 MULTI‐BIOREACTOR SYSTEMS AND THEIR APPLICATIONS . 28 2.6 HARDWARE FOR PHYSIOLOGICAL STATE CONTROL . 29 2.6. 1 Bioreactor Configura on and Size (Mass Transfer) . 29 2.6. 2 Environmental Parameters O2, pH and T . 30 2.6. 3 Substrate Addi on . 31 3 AIMS . 32 4 MATERIALS AND METHODS . 33 4.1 STRAINS, INOCULATION PROCEDURE AND CULTURE MEDIA . 33 4.2 ANALYTICAL METHODS . 33 4.3 CULTIVATION METHODS . 33 4.4 CULTIVATION SYSTEM . 34 4.5 THE MD SYSTEM . 34 4.6 POPULATION CHARACTERISTICS TO QUANTIFY THE PHYSIOLOGICAL STATE . 35 4.7 STATISTICAL ANALYSIS . 36 5 RESULTS AND DISCUSSION . 37 5.1 GROWTH SPACE ANALYSIS IN THE MD SYSTEM (PUBLICATIONS I, II, AND III). 37 5.1. 1 Growth Space Scanning and Perturba on Experiments in the MD System . 37
A Reliable Randomized Algorithm for the Closest-Pair Problem

The following two computational problems are studied:Duplicate grouping:Assume thatnitems are given, each of which is labeled by an integer key from the set {0,? ,U? 1}. Store the items in an array of sizensuch that items with the same key occupy a contiguous segment of the array.Closest pair:Assume that a multiset ofnpoints in thed-dimensional Euclidean space is given, whered? 1 is a fixed integer. Each point is represented as ad-tuple of integers in the range {0,? ,U? 1} (or of arbitrary real numbers). Find a closest pair, i.e., a pair of points whose distance is minimal over all such pairs.In 1976, Rabin described a randomized algorithm for the closest-pair problem that takes linear expected time. As a subroutine, he used a hashing procedure whose implementation was left open. Only years later randomized hashing schemes suitable for filling this gap were developed.In this paper, we return to Rabin's classic algorithm to provide a fully detailed description and analysis, thereby also extending and strengthening his result. As a preliminary step, we study randomized algorithms for the duplicate-grouping problem. In the course of solving the duplicate-grouping problem, we describe a new universal class of hash functions of independent interest.It is shown that both of the foregoing problems can be solved by randomized algorithms that useO(n) space and finish inO(n) time with probability tending to 1 asngrows to infinity. The model of computation is a unit-cost RAM capable of generating random numbers and of performing arithmetic operations from the set {+,? ,? ,div,log2,exp2}, wheredivdenotes integer division andlog2andexp2are the mappings from N to N? {0} withlog2(m)=? log2m? andexp2(m)=2mfor allm? N. If the operationslog2andexp2are not available, the running time of the algorithms increases by an additive term ofO(loglogU). All numbers manipulated by the algorithms consist ofO(logn+logU) bits.The algorithms for both of the problems exceed the time boundO(n) orO(n+loglogU) with probability 2? n? (1). Variants of the algorithms are also given that use onlyO(logn+logU) random bits and have probabilityO(n? ) of exceeding the time bounds, where ? 1 is a constant that can be chosen arbitrarily.The algorithms for the closest-pair problem also works if the coordinates of the points are arbitrary real numbers, provided that the RAM is able to perform arithmetic operations from {+,? ,? ,div} on real numbers, whereadivbnow means ? a/b? In this case, the running time isO(n) withlog2andexp2andO(n+loglog(? max/? max)) without them, where ? maxis the maximum and ? minis the minimum distance between any two distinct input points.
Statistical Properties of Query Strings

AbstractWe study the statistical properties of query search strings in the Gnutella peer-to-peer network andﬁnd that the distribution of query frequency (how often queries are made) closely follows a lognormaldistribution. We ﬁnd evidence for an upper bound on query cache performance and extend previousstudies of Gnutella query caching to model eﬀectiveness of such schemes. 1 Introduction The Gnutella ﬁle sharing system is an open architecture allowing peers to connect to one another and searchfor ﬁles, and download them from one another. Every node in the network is a so-called servant, havingthe properties of a server and a client. Each servant performs broadcast search queries and receives queryhits in response to queries. Queries have a ﬁnite time-to-live (TTL). Servants rebroadcast the queries ,decrementing the TTL each time until the TTL = 0 at which time the query is not rebroadcast.Since the fundamental operation of Gnutella, which is a database search, is a broadcast operation, itis of great interest to develop techniques that reduce the need to make such broadcasts. By studying thestatistics of query frequency, we are able to make predictions about the eﬃcacy of simple caching. For eachquery that comes to a node, if that node has previously cached the result of that query, there is no need tobroadcast it on, which results in a bandwidth savings for the node in question. In this work, we want tostudy the probability that a query is found in the cache as a function of the size of the cache. Ideally, theprobability of ﬁnding a query in the cache will grow rapidly as a function of size.
The Resilience of Property

Resilience is essential to the ability of property to face transforming social and environmental change. For centuries, property has responded to such change through a dialectical process that identifies emerging disciplinary perspectives and debates conflicting values and norms. This dialectic promotes the resilience of property, allowing it to adapt to changing conditions and needs. Today the mainstream economic theory dominating common law property is progressively being intertwined with constitutionally protected property, undermining its long-term resilience. The coupling of the economic vision of ordinary property with constitutional property embeds the assumptions, choices, and values of the economic theory into both realms of property without regard for property’s other relational planes.A real-life theory of property — one based on a theory-practice link — sees the property landscape as a function of interactions among possible property arrangements and other perspective-based systems, including natural systems. Understanding property as a function of those relational planes is important to preserving its resilience. Research on the dynamics of change in social-ecological systems provides important insight into how institutions, like property, that manage resources can promote resilience. The mainstream economic theory lacks the openness and interdisciplinary inclusion needed to handle complex disturbances, ignoring conflicting perspectives and alternative visions that have played a significant role in the evolution of property. Often presented as involving either/or choices, the mainstream theory takes a singular perspective that overlooks important dialectical interactions. As subsystems of larger natural systems, complex societies need a resilient property system open to different perspectives and new knowledge if they are to handle the serious challenges of the future.
Design of low power barrel shifter and vedic multiplier with kogge-stone adder using reversible logic gates

The modern systems are denser and faster. But these systems consume more power. The variants of power dissipation are dynamic power, leakage power, short circuit power and static power dissipation. Adders, Shifters and Multipliers are the essential building blocks of any Digital Signal Processor (DSP) architecture. Hence design of these building blocks to dissipate less power is of utmost importance in digital system design. In order to reduce this power dissipation, there are many low power approaches such as Multi-Vth, reducing the voltage swing, clock gating, use of reversible logic gates etc. The main advantage of designing circuit using reversible logic gates is that the designed circuits will be compatible with the available resources. Reversible Logic gates are that logic gates which have the same number of inputs and outputs and all the outputs are unique for a given input combination. These gates are used to reduce the power dissipation due to loss of information bits. The functional verification of the conventional and reversible Kogge-stone Adder, Vedic Multiplier and Barrel Shifter is performed using Verilog in Xilinx ISE and the power, delay and area of the Kogge-stone Adder, Vedic Multiplier and Barrel Shifter are computed using Cadence RTL compiler software in 90 nm technology. The proposed reversible Vedic Multiplier consumed 0.621 % less power than the conventional Vedic Multiplier. The power dissipation of reversible Barrel Shifter is found to be 26.49 % less than conventional Barrel Shifter.
Early procurement of scarlet macaws and the emergence of social complexity in Chaco Canyon, NM

Significance New accelerator mass spectrometer (AMS) 14C dates of scarlet macaw (Ara macao) skeletons from Chaco Canyon in northwestern New Mexico reveal the earliest (A.D. 900–975) direct evidence for procurement of this Neotropical species by Pueblo people from Mesoamerica. By directly dating the macaws, we demonstrate the existence of long-distance acquisition networks throughout much (A.D. 900–1150) of Chaco’s history. In contrast to models of societal evolution that attribute procurement of macaws to the 11th-century peak of Chacoan influence and architectural expansion, most 14C dates significantly predate this period. We propose that access to and control of these important status markers from Mesoamerica before A.D. 1040 was thus linked to the early formalization of social hierarchy in Chaco. High-precision accelerator mass spectrometer (AMS) 14C dates of scarlet macaw (Ara macao) skeletal remains provide the first direct evidence from Chaco Canyon in northwestern New Mexico that these Neotropical birds were procured from Mesoamerica by Pueblo people as early as ∼A.D. 900–975. Chaco was a prominent prehistoric Pueblo center with a dense concentration of multistoried great houses constructed from the 9th through early 12th centuries. At the best known great house of Pueblo Bonito, unusual burial crypts and significant quantities of exotic and symbolically important materials, including scarlet macaws, turquoise, marine shell, and cacao, suggest societal complexity unprecedented elsewhere in the Puebloan world. Scarlet macaws are known markers of social and political status among the Pueblos. New AMS 14C-dated scarlet macaw remains from Pueblo Bonito demonstrate that these birds were acquired persistently from Mesoamerica between A.D. 900 and 1150. Most of the macaws date before the hypothesized apogeal Chacoan period (A.D. 1040–1110) to which they are commonly attributed. The 10th century acquisition of these birds is consistent with the hypothesis that more formalized status hierarchies developed with significant connections to Mesoamerica before the post-A.D. 1040 architectural florescence in Chaco Canyon.
Text2Loc: 3D Point Cloud Localization from Natural Language

We tackle the problem of 3D point cloud localization based on a few natural linguistic descriptions and introduce a novel neural network, Text2Loc, that fully interprets the semantic relationship between points and text. Text2Loc follows a coarse-to-fine localization pipeline: text-submap global place recognition, followed by fine localization. In global place recognition, relational dynamics among each textual hint are captured in a hierarchical transformer with max-pooling (HTM), whereas a balance between positive and negative pairs is maintained using text-submap contrastive learning. Moreover, we propose a novel matching-free fine localization method to further refine the location predictions, which completely removes the need for complicated text-instance matching and is lighter, faster, and more accurate than previous methods. Extensive experiments show that Text2Loc improves the localization accuracy by up to $2\times$ over the state-of-the-art on the KITTI360Pose dataset. Our project page is publicly available at \url{https://yan-xia.github. io/projects/text2loc/}.
Heavy-Traffic Limits for the G/H2*/n/mQueue

We establish heavy-traffic stochastic-process limits for queue-length, waiting-time and overflow stochastic processes in a class ofG/GI/n/m queueing models withn servers andm extra waiting spaces. We let the arrival process be general, only requiring that it satisfy a functional central limit theorem. To capture the impact of the service-time distribution beyond its mean within a Markovian framework, we consider a special class of service-time distributions, denoted byH2*, which are mixtures of an exponential distribution with probabilityp and a unit point mass at 0 with probability 1- p. These service-time distributions exhibit relatively high variability, having squared coefficients of variation greater than or equal to one. As in Halfin and Whitt (1981, Heavy-traffic limits for queues with many exponential servers,Oper. Res.29 567-588), Puhalskii and Reiman (2000, The multiclassGI/PH/N queue in the Halfin-Whitt regime.Adv. Appl. Probab.32 564-595), and Garnett, Mandelbaum, and Reiman (2002. Designing a call center with impatient customers.Manufacturing Service Oper. Management,4 208-227), we consider a sequence of queueing models indexed by the number of servers,n, and letn tend to infinity along with the traffic intensities ? nso that v n (1 - ? n ) ? for -8 << 8. To treat finite waiting rooms, we letm n v n ? for 0 < ? < 8. With the specialH2* service-time distribution, the limit processes are one-dimensional Markov processes, behaving like diffusion processes with different drift and diffusion functions in two different regions, above and below zero. We also establish a limit for theG/M/n/m+ M model, having exponential customer abandonments.
Managerial trustworthiness and social exchange with the organization

Purpose – The purpose of this paper is to examine how managerial trustworthiness and social exchange with the organization integrate with perceived organizational support to relate to supervisor‐rated job performance and self‐report organizational commitment.Design/methodology/approach – A sample of 119 full‐time employees from a variety of occupations at a single organization completed surveys. Their supervisor rated job performance.Findings – This paper finds that managerial trustworthiness was positively related to job performance and organizational commitment via POS and social exchange with the organization; and that POS was related to organizational commitment through social exchange with the organization.Research limitations/implications – Limitations include cross‐sectional data from a single organization. Strengths include non self‐report ratings of job performance. Future research should consider experimental and longitudinal designs to capture causality.Practical implications – Organizations ma.
Is workplace spirituality associated with business ethics

Purpose – The purpose of this paper is to empirically explore the potential association between spirituality and business ethics in a hotel workplace. Design/methodology/approach – A scenario-based quantitative approach was used to collect data from 165 practicing professionals in the hotel industry. Findings – The results show that spirituality, as measured by the Spiritual Transcendence Scale (STS), did not correlate significantly with measures of ethical perception, ethical judgment, ethical intention or perceived moral intensity. There was, however, evidence to suggest that spirituality may be able to contribute incrementally to future research. Research limitations/implications – This study demonstrates that the dynamic associations between spirituality and ethics may produce different outcomes in different industry settings. Practical implications – If hotel companies focus on developing ethical standards, the effects on the business ethics of managers could be considerably greater than relying on t.
Arabidopsis PHYTOCHROME INTERACTING FACTOR Proteins Promote Phytochrome B Polyubiquitination by COP1 E3 Ligase in the Nucleus[C][W]

This work identifies COP1 as the ubiquitin E3 ligase for not only phytochrome B but also other members of the stable phytochrome family and shows that PIF transcription factors enhance phyB ubiquitination by COP1 in vitro. It provides a molecular mechanism for the termination of red light signal transduction. Many plant photoresponses from germination to shade avoidance are mediated by phytochrome B (phyB). In darkness, phyB exists as the inactive Pr in the cytosol but upon red (R) light treatment, the active Pfr translocates into nuclei to initiate signaling. Degradation of phyB Pfr likely regulates signal termination, but the mechanism is not understood. Here, we show that phyB is stable in darkness, but in R, a fraction of phyB translocates into nuclei and becomes degraded by 26S proteasomes. Nuclear phyB degradation is mediated by COP1 E3 ligase, which preferentially interacts with the PhyB N-terminal region (PhyB-N). PhyB-N polyubiquitination by CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) in vitro can be enhanced by different PHYTOCHROME INTERACTING FACTOR (PIF) proteins that promote COP1/PhyB interaction. Consistent with these results, nuclear phyB accumulates to higher levels in pif single and double mutants and in cop1-4. Our results identify COP1 as an E3 ligase for phyB and other stable phytochromes and uncover the mechanism by which PIFs negatively regulate phyB levels.
Textbook Outcome: A Composite Measure for Quality of Elective Aneurysm Surgery

Objective: To investigate a new composite quality measurement, which comprises a desirable outcome for elective aneurysm surgery, called “Textbook Outcome” (TO). Background: Single-quality indicators in vascular surgery are often not distinctive and insufficiently reflect the quality of care. Methods: All patients undergoing elective abdominal aortic aneurysm repair, registered in the Dutch Surgical Aneurysm Audit between 2014 and 2015 were included. TO was defined as the percentage of patients who had abdominal aortic aneurysm-repair without intraoperative complications, postoperative surgical complications, reinterventions, prolonged hospital stay [endovascular aneurysm repair (EVAR) ⩽4 d, open surgical repair (OSR) ⩽10 d], readmissions, and postoperative mortality (⩽30 d after surgery/at discharge). Case-mix adjusted TO rates were used to compare hospitals and to compare individual hospital results for different procedures. Results: Five thousand one hundred seventy patients were included, of whom 4039 were treated with EVAR and 1131 with OSR. TO was achieved in 71% of EVAR and 53% of OSR. Important obstacles for achieving TO were a prolonged hospital stay, postoperative complications, and readmissions. Adjusted TO rates varied from 38% to 89% (EVAR) and from 0% to 97% (OSR) between individual hospitals. Hospitals with a high TO for OSR also had a high TO for EVAR; however, a high TO for EVAR did not implicate a high TO for OSR. Conclusions: TO generates additional information to evaluate the overall quality of the care of elective aneurysm surgery, which subsequently can be used by hospitals to improve the quality of their care.
Acute Coronary Syndrome in Mashhad, Northeastern of Iran: Report of a Decade

Background: Acute coronary syndrome (ACS) is a major cause of morbidity and mortality all over the world. Despite substantial efforts that have been made over the last decades, ACS management still remains challenging in most of the regions. Objectives: This study describes the characteristics and trends of outcomes for ACS patients in a decade in north-east of Iran. Methods: In this cross-sectional study, two tertiary academic hospitals of Mashhad University of Medical Sciences in Iran were investigated during a 10-year period starting from January 1, 2007. Patients were identified according to their final diagnosis at discharge using the international classification of diseases 10th revision (ICD-10). The ten-year trend of prevalence of ACS was plotted. The outcomes (alive, death) were compared between the two types of myocardial infarction (MI) (ST-elevation myocardial infarction (STEMI), and non-ST elevation myocardial infarction (NSTEMI)/unspecific). Results: During the study period, there were a total of 9068 admissions for acute MI or unstable angina. The mean age of admitted patients was 61.6 ± 13.7 years and the majority (67.8%) was male. The in-hospital mortality rate was 12.3% (927), which was significantly higher in NSTEMI/unspecific AMI compared to STEMI patients (15.3% vs. 9.8%, P < 0.001). Females were significantly older than males (65.7 ± 12.5 vs. 59.6 ± 13.8, P < 0.001) and have higher mortality rates compared to males (16.7 vs. 10.1, P < 0.001). The prevalence rate of all MI categories had an increasing secular trend, though the mortality rate was decreased. Conclusions: Although the prevalence rate of AMI has slightly increased, the mortality rate has decreased. Close cooperation between general practitioners, health providers and cardiologists are of great importance in this field.