Miracle-dz/UniFAR-FTUs huggingface dataset:
Acquisition of Aneuploidy Provides Increased Fitness during the Evolution of Antifungal Drug Resistance

The evolution of drug resistance is an important process that affects clinical outcomes. Resistance to fluconazole, the most widely used antifungal, is often associated with acquired aneuploidy. Here we provide a longitudinal study of the prevalence and dynamics of gross chromosomal rearrangements, including aneuploidy, in the presence and absence of fluconazole during a well-controlled in vitro evolution experiment using Candida albicans, the most prevalent human fungal pathogen. While no aneuploidy was detected in any of the no-drug control populations, in all fluconazole-treated populations analyzed an isochromosome 5L [i(5L)] appeared soon after drug exposure. This isochromosome was associated with increased fitness in the presence of drug and, over time, became fixed in independent populations. In two separate cases, larger supernumerary chromosomes composed of i(5L) attached to an intact chromosome or chromosome fragment formed during exposure to the drug. Other aneuploidies, particularly trisomies of the smaller chromosomes (Chr3–7), appeared throughout the evolution experiment, and the accumulation of multiple aneuploid chromosomes per cell coincided with the highest resistance to fluconazole. Unlike the case in many other organisms, some isolates carrying i(5L) exhibited improved fitness in the presence, as well as in the absence, of fluconazole. The early appearance of aneuploidy is consistent with a model in which C. albicans becomes more permissive of chromosome rearrangements and segregation defects in the presence of fluconazole.
A Prospective Study of Mortality from Cryptococcal Meningitis following Treatment Induction with 1200mg Oral Fluconazole in Blantyre, Malawi

Objective We have previously reported high ten-week mortality from cryptococcal meningitis in Malawian adults following treatment-induction with 800mg oral fluconazole (57% [33/58]). National guidelines in Malawi and other African countries now advocate an increased induction dose of 1200mg. We assessed whether this has improved outcomes. Design This was a prospective observational study of HIV-infected adults with cryptococcal meningitis confirmed by diagnostic lumbar puncture. Treatment was with fluconazole 1200mg/day for two weeks then 400mg/day for 8 weeks. Mortality within the first 10 weeks was the study end-point, and current results were compared with data from our prior patient cohort who started on fluconazole 800mg/day. Results 47 participants received fluconazole monotherapy. Despite a treatment-induction dose of 1200mg, ten-week mortality remained 55% (26/47). This was no better than our previous study (Hazard Ratio [HR] of death on 1200mg vs. 800mg fluconazole: 1.29 (95% CI: 0.77–2.16, p = 0.332)). There was some evidence for improved survival in patients who had repeat lumbar punctures during early therapy to lower intracranial pressure (HR: 0.27 [95% CI: 0.07–1.03, p = 0.055]). Conclusion There remains an urgent need to identify more effective, affordable and deliverable regimens for cryptococcal meningitis.
The characterization of gefitinib sensitivity and adverse events in patients with non-small cell lung cancer.

BACKGROUND Factors predicting gefitinib sensitivity and adverse events in non-small cell lung cancer (NSCLC) remain controversial. PATIENTS AND METHODS Correlations among clinicopathological characteristics, gefitinib sensitivity and adverse events were studied in 154 patients with NSCLC, whereas epidermal growth factor receptor (EGFR) mutations were analyzed in 44 patients. RESULTS Female, non-smoker, adenocarcinoma of stage I-II, and gefitinib effectiveness correlated with longer time to progression (TTP) and overall survival (OS), while the rate of interstitial lung disease in patients undergoing thoracic radiotherapy and stomatitis in females or those who never smoked were significantly higher. EGFR mutations were identified in 18 cases, and among 34 gefitinib-treated patients, 16 patients harboring mutations tended to do better, both in terms of TTP and OS. The results of the mutation analysis from surgical and non-surgical specimens were identical. CONCLUSION Certain clinicopathological characteristics and EGFR mutations can be either predictive of gefitinib sensitivity or adverse events.
Effective handling of dialogue state in the hidden information state POMDP-based dialogue manager

Effective dialogue management is critically dependent on the information that is encoded in the dialogue state. In order to deploy reinforcement learning for policy optimization, dialogue must be modeled as a Markov Decision Process. This requires that the dialogue state must encode all relevent information obtained during the dialogue prior to that state. This can be achieved by combining the user goal, the dialogue history, and the last user action to form the dialogue state. In addition, to gain robustness to input errors, dialogue must be modeled as a Partially Observable Markov Decision Process (POMDP) and hence, a distribution over all possible states must be maintained at every dialogue turn. This poses a potential computational limitation since there can be a very large number of dialogue states. The Hidden Information State model provides a principled way of ensuring tractability in a POMDP-based dialogue model. The key feature of this model is the grouping of user goals into partitions that are dynamically built during the dialogue. In this article, we extend this model further to incorporate the notion of complements. This allows for a more complex user goal to be represented, and it enables an effective pruning technique to be implemented that preserves the overall system performance within a limited computational resource more effectively than existing approaches.
The Limbic System in Mammalian Brain Evolution

Previous accounts of mammalian brain allometry have relied largely on data from primates, insectivores and bats. Here we examine scaling of brain structures in carnivores, ungulates, xenarthrans and sirenians, taxa chosen to maximize potential olfactory and limbic system variability. The data were compared to known scaling of the same structures in bats, insectivores and primates. Fundamental patterns in brain scaling were similar across all taxa. Marine mammals with reduced olfactory bulbs also had reduced limbic systems overall, particularly in those structures receiving direct olfactory input. In all species, a limbic factor with olfactory and non-olfactory components was observed. Primates, insectivores, ungulate and marine mammals collectively demonstrate an inverse relationship between isocortex and limbic volumes, but terrestrial carnivores have high relative volumes of both, and bats low relative volumes of both. We discuss developmental processes that may provide the mechanistic bases for understanding these findings.
Dormancy of Cancer Cells with Suppression of AKT Activity Contributes to Survival in Chronic Hypoxia

A hypoxic microenvironment in tumors has been recognized as a cause of malignancy or resistance to various cancer therapies. In contrast to recent progress in understanding the acute response of cancer cells to hypoxia, the characteristics of tumor cells in chronic hypoxia remain elusive. We have identified a pancreatic cancer cell line, AsPC-1, that is exceptionally able to survive for weeks under 1% oxygen conditions while most tested cancer cell lines die after only some days under these conditions. In chronic hypoxia, AsPC-1 cells entered a state of dormancy characterized by no proliferation, no death, and metabolic suppression. They reversibly switched to active status after being placed again in optimal culture conditions. ATP turnover, an indicator of energy demand, was markedly decreased and accompanied by reduced AKT phosphorylation. Forced activation of AKT resulted in increased ATP turnover and massive cell death in vitro and a decreased number of dormant cells in vivo. In contrast to most cancer cell lines, primary-cultured colorectal cancer cells easily entered the dormant status with AKT suppression under hypoxia combined with growth factor–depleted conditions. Primary colorectal cancer cells in dormancy were resistant to chemotherapy. Thus, the ability to survive in a deteriorated microenvironment by entering into dormancy under chronic hypoxia might be a common property among cancer cells. Targeting the regulatory mechanism inducing this dormant status could provide a new strategy for treating cancer.
A novel adaptive unscented Kalman filter attitude estimation and control systems for 3U nanosatellite

A novel adaptive unscented Kalman filter (AUKF) based estimation algorithm is proposed for a 3U Cubsat. This small satellite employs a three axis magnetometer and three MEMS gyroscopes as well as three magnetic torque rods and one reaction wheel on the pitch axis. Unlike the existing UKF, in this paper, an n+1 sigma set is used to estimate the nanosatellite attitude instead of 2n + 1 sigma points as in a conventional UKF. Numerical Simulation results validate the performance of the proposed adaptive Kalman filter. There is no need for linearization of the nonlinear dynamics of the system. The estimated result tracks satellite attitude during the damping and stable control stages. Euler angles, gyro bias, and angular velocity of the satellite are estimated using this proposed AUKF with good convergence time and estimation accuracy.
On the Existence of Unconditionally Privacy-Preserving Auction Protocols

We investigate whether it is possible to preserve privacy in sealed-bid auctions to a maximal extent. In particular, this paper focuses on <it>unconditional full privacy</it>, i.e., privacy that relies neither on trusted third parties (like auctioneers), nor on computational intractability assumptions (like the hardness of factoring). These constraints imply a scenario in which bidders exchange messages according to some predefined protocol in order to jointly determine the auction outcome without revealing any additional information. It turns out that the first-price sealed-bid auction can be emulated by an unconditionally fully private protocol. However, the protocol's round complexity is exponential in the bid size, and there is no more efficient protocol. On the other hand, we prove the impossibility of privately emulating the second-price sealed-bid auction for more than two bidders. This impossibility holds even when relaxing various privacy constraints such as allowing the revelation of all but one losing bid (while maintaining anonymity) or allowing the revelation of the second highest bidder's identity.
The Evolution of KTP Laser Vaporization of the Prostate

The search for a minimally invasive approach to the treatment of Lower Urinary Tract Symptoms (LUTS) suggestive of Benign Prostatic Hyperplasia (BPH) is probably as old as Transurethral Resection of the Prostate (TURP). In an effort to overcome the limitations and morbidities of TURP, and in light of evidence suggesting that medical treatment for BPH has a limited life-span, laser-based treatments have emerged during the last decade. Photoselective Vaporization of the Prostate (PVP) by the "GreenLight" KTP laser is considered one of the most promising options, one that is constantly evolving new technologies in prostate surgery. In this overview of KTP laser usage in BPH treatment, we will briefly discuss the evolution of this modality since it was first introduced and focus on the available evidence regarding safety, efficacy and cost parameters of its application.
A Millimeter-Scale Energy-Autonomous Sensor System With Stacked Battery and Solar Cells

An 8.75 mm3 microsystem targeting temperature sensing achieves zero-net-energy operation using energy harvesting and ultra-low-power circuit techniques. A 200 nW sensor measures temperature with -1.6 °C/+3 °C accuracy at a rate of 10 samples/sec. A 28 pJ/cycle, 0.4 V, 72 kHz ARM Cortex-M3 microcontroller processes temperature data using a 3.3 fW leakage per bit SRAM. Two 1 mm2 solar cells and a thin-film Li battery power the microsystem through an integrated power management unit. The complete microsystem consumes 7.7 μ W when active and enters a 550 pW data-retentive standby mode between temperature measurements. The microsystem can process temperature data hourly for 5 years using only the initial energy stored in the battery. This lifetime is extended indefinitely using energy harvesting to recharge the battery, enabling energy-autonomous operation.
The evolution of buildings and implications for the design of ubiquitous domestic environments

This paper considers how we may realize future ubiquitous domestic environments. Building upon previous work on how buildings evolve by Stewart Brand, we suggest the need to broaden existing considerations of interactive design for domestic environments. We identify a number of classes of research activity and the issues associated with these. We then consider the ways in which current buildings undergo continual change. In doing so we outline the stakeholders involved, the representations used and the way change is managed. We contrast our understanding of how buildings change with research activities before identifying new challenges that will need to be addressed by those involved in designing ubiquitous technologies for domestic environments.
The putative functional ecology and distribution of archaeal communities in sponges, sediment and seawater in a coral reef environment

Archaea play crucial roles in a number of key ecological processes including nitrification and methanogenesis. Although several studies have been conducted on these organisms, the roles and dynamics of coral reef archaeal communities are still poorly understood, particularly in host and nonhost biotopes and in high (HMA) and low microbial abundance (LMA) sponges. Here, archaeal communities detected in six distinct biotopes, namely, sediment, seawater and four different sponge species Stylissa carteri, Stylissa massa, Xestospongia testudinaria and Hyrtios erectus from the Spermonde Archipelago, SW Sulawesi, Indonesia were investigated using 454‐pyrosequencing of 16S rRNA genes (OTU cut‐off 97%). Archaeal communities from sediment and sponges were dominated by Crenarchaeota, while the seawater community was dominated by Euryarchaeota. The biotope explained almost 75% of the variation in archaeal composition, with clear separation between microbial assemblages from sediment, X. testudinaria and H. erectus (HMA). In contrast, samples from seawater and both Stylissa species (LMA) showed considerable overlap in the ordination and, furthermore, shared most abundant OTUs with the exception of a single dominant OTU specifically enriched in both Stylissa species. Predicted functional gene content in archaeal assemblages also revealed significant differences among biotopes. Different ammonia assimilation strategies were exhibited by the archaeal communities: X. testudinaria, H. erectus and sediment archaeal communities were enriched for glutamate dehydrogenase with mixed specificity (NAD(P)+) pathways, while archaeal planktonic communities were enriched for specific glutamate dehydrogenase (NADP+) and glutamate synthase pathways. Archaeal communities in Stylissa had intermediate levels of enrichment. Our results indicate that archaeal communities in different biotopes have distinct ecophysiological roles.
DECISION FEEDBACK EQUALIZATION FROM AN H 1 PERSPECTIVE

We approach the nonlinear decision feedback equalization problem from anH estimation point of view. Using the standard (and simplifying) assumption that all previous decisions are correct, we obtain an explicit parameterization of allH optimal decision feedback equalizers. In particular, under the above assumption, we show that MMSE decision feedback equalizers are H optimal. TheH approach also suggests a method for dealing with errors in previous decisions, and results in an equalization scheme with improved performance over other equalizers that do not take such errors into account.
Unsupervised Learning of Dynamic Resource Provisioning Policies for Cloud-Hosted Multitier Web Applications

Dynamic resource provisioning for Web applications allows for low operational costs while meeting service-level objectives (SLOs). However, the complexity of multitier Web applications makes it difficult to automatically provision resources for each tier without human supervision. In this paper, we introduce unsupervised machine learning methods to dynamically provision multitier Web applications, while observing user-defined performance goals. The proposed technique operates in real time and uses learning techniques to identify workload patterns from access logs, reactively identifies bottlenecks for specific workload patterns, and dynamically builds resource allocation policies for each particular workload. We demonstrate the effectiveness of the proposed approach in several experiments using synthetic workloads on the Amazon Elastic Compute Cloud (EC2) and compare it with industry-standard rule-based autoscale strategies. Our results show that the proposed techniques would enable cloud infrastructure providers or application owners to build systems that automatically manage multitier Web applications, while meeting SLOs, without any prior knowledge of the applications' resource utilization or workload patterns.
Deconvoluting the Cu2+ Binding Modes of Full-length Prion Protein*

The prion protein (PrP) is a cell-surface Cu2+-binding glycoprotein that when misfolded is responsible for a number of transmissible spongiform encephalopathies. Full-length PrP-(23–231) and constructs in which the octarepeat region has been removed, or His95 and His110 is replaced by alanine residues, have been used to elucidate the order and mode of Cu2+ coordination to PrP-(23–231). We have built on our understanding of the appearance of visible CD spectra and EPR for various PrP fragments to characterize Cu2+ coordination to full-length PrP. At physiological pH, Cu2+ initially binds to full-length PrP in the amyloidogenic region between the octarepeats and the structured domain at His95 and His110. Only subsequent Cu2+ ions bind to single histidine residues within the octarepeat region. Ni2+ ions are used to further probe metal binding and, like Cu2+, Ni2+ will bind individually to His95 and His110, involving preceding main chain amides. Competitive chelators are used to determine the affinity of the first mole equivalent of Cu2+ bound to full-length PrP; this approach places the affinity in the nanomolar range. The affinity and number of Cu2+ binding sites support the suggestion that PrP could act as a sacrificial quencher of free radicals generated by copper redox cycling.
‘Doctor, there is a lump in my heart’ – A rare case of a ventricular myxoma

Myxomas are the commonest primary cardiac tumours. They may be asymptomatic, and picked up incidentally, or be the cause of congestive heart failure, arrhythmias and/or murmurs. Echocardiography is necessary for diagnosis. Surgical resection is recommended to prevent further complications. A rare symptomatic ventricular myxoma is presented in this case report.
Electromechanical analysis of length-related resistance and contact resistance of conductive knitted fabrics

Conductive fabrics usually exhibit two types of electrical resistance: the length-related resistance and contact resistance. The length-related resistance increases with the applied extensile force, whereas the contact resistance decreases with the contact force. The resistance of conductive knitted fabrics could be modeled by the superposition of the length-related resistance and contact resistance. Three experiments were conducted to investigate the resistance of conductive yarns: two overlapped conduct yarns and conductive knitting stitches under unidirectional extensile forces, respectively; and the corresponding empirical equations were developed. The relationship of the resistance, tensile force, fabric length and width were established. The fitting curves with high coefficient of determinations (>0.94) and low standard errors (<0.18) given by the modeling equations were achieved. Therefore, the proposed model could be used to compute the resistance of the conductive knitting fabrics under unidirectional extension.
Very cold dust in the peculiar dwarf elliptical galaxy NGC 205

ISO observations of NGC 205 between 120 and 200 µm resolve the emission from 20–24 K cold dust. It is extended to about 7. 5×7. 5 with bright concentrations in a 1. 5 north-south elongated area, similar to the that seen in HI. Supplemented by IRAS and mm literature data, the photometry of the total galaxy and the central region is disentangled. It indicates the presence of very cold dust below 10 K which would be the first such detection in an elliptical galaxy.
Antitumor Constituents of the Wetland Plant Nymphoides peltata: A Case Study for the Potential Utilization of Constructed Wetland Plant Resources

The efficient utilization of plant resources is a necessary and important measure for sustainable management of constructed wetlands. Screening bioactive metabolites from wetland plants could reveal potential solutions for the utilization of constructed wetland plant resources. In this study, the constructed wetland macrophyte Nymphoides peltata was screened for constituents with antitumor activity. The secondary metabolites of N. peltata were extracted and separated by MCI gel, silica gel, and Sephadex gel column chromatography. Antitumor tests were then carried out with MTT assay against the human prostate cancer cell PC3 and the human osteosarcoma cell U2OS. The secondary metabolite group with the most significant antitumor activity was further examined, and four constituents were obtained and identified. This study provides a scientific basis for the potential efficient utilization of N. peltata and other constructed wetland plant resources.
Novel functions of thrombomodulin in inflammation

The objective of this study was to review the mechanisms by which thrombomodulin (TM) may modulate inflammation. The data were taken from published research performed by other laboratories and our own experimental results. TM is a transmembrane glycoprotein receptor and cofactor for thrombin in the protein C anticoagulant system. Recent studies have revealed that TM has activities, both dependent and independent of either protein C or thrombin, that affect biological systems beyond the coagulation pathway. This review highlights recent insights, provided by in vitro and in vivo analyses, into how the unique structural domains of TM effectively modify coagulation, fibrinolysis, and inflammation in health and disease. A paradigm is presented to describe how these apparently distinct functions are integrated to maintain homeostasis under stress conditions. Finally, we explore the potential diagnostic and therapeutic utility of dissecting out the structure–function correlates of TM. We conclude that TM plays a central role in regulating not only hemostasis but also inflammation, thus providing a close link between these processes. Elucidation of the molecular mechanisms by which TM functions will likely provide novel targets for therapeutic intervention.