Miracle-dz/UniFAR-FTUs huggingface dataset:
A Single Mutation in the Activation Site of Bovine Trypsinogen Enhances Its Accumulation in the Fermentation Broth of the Yeast Pichia pastoris

ABSTRACT We produced bovine trypsinogen in the yeast Pichia pastoris. Little or no trypsinogen was detected when the gene with its native leader sequence was expressed under the control of the strong aox1 promoter, suggesting that expression of the wild-type bovine trypsinogen was toxic to the cells. We altered the trypsinogen native propeptide sequence by replacing the lysine at position 6 with an aspartic acid, thus destroying the site in the propeptide cleaved by enterokinase and by trypsin. This mutant accumulated up to 10 mg of trypsinogen per liter in shake flask cultures and about 40 mg/liter in 6-liter fermentors. Trypsinogen could be activated in vitro with a dipeptidyl-aminopeptidase, which selectively removed the modified trypsinogen propeptide; the resulting trypsin was fully active and showed evidence of glycosylation. Thus, we have developed a novel protein production scheme that can be used for the expression of proteins, such as proteases, that are deleterious to the producing organism. This system relies on the expression of a zymogen that cannot be activated in vivo coupled with its in vitro purification and activation.
Comparing Performance and Energy Consumption of Android Applications: Native Versus Web Approaches

Mobile applications are usually developed in a native way, using languages and APIs specific for a given platform, hindering the portability. As an alternative, web technologies as JavaScript and PHP have been employed enabling a same implementation to be executed in different mobile platforms without any recompilation or recoding process. This paper compares the efficiency of Android applications developed in Java (native), in PHP, in JavaScript and using Node.js through experiments that evaluate execution time and energy consumption. Our experiments explore computation complexity and as well as communication aspects relevant for the PHP and Node.js approaches. Results indicate that native implementation is the best one, regarding performance and energy consumption until a certain processing load. As this load is significantly increased, the Node.js implementation presents the lowest execution times and energy consumption.
Performance study of multi-bit vote count with weak range

Approximate nearest neighbors search can be implemented by hashing based vote counting. This implementation can be extended to multi-bit case when vectors are hashed to multi-bit in each hashing. This improves the retrieval efficiency and saves the computation on hashing operation. The performance of multi-bit vote count can be further improved by the concept of weak range. In this manuscript, multi-bit Vote Count and reference side weak range for multi-bit vote count is discussed and its performance is compared with traditional Vote Count and enhanced Vote Count implemented by binary quantization. Simulation results show that, multi-bit Vote Count significantly improves the kNN accuracy and weak range implementation can further enhance the multi-bit Vote Count performance. Multi-bit Vote Count can also reduce the computational complexity by means of less hashing number required.
Post-Placement Power Optimization With Multi-Bit Flip-Flops

Optimization for power is always one of the most important design objectives in modern nanometer integrated circuit design. Recent studies have shown the effectiveness of applying multi-bit flip-flops to save the power consumption of the clock network. This paper presents: 1) a novel design methodology of applying multi-bit flip-flops at the post-placement stage, which can be seamlessly integrated in modern design flow; 2) a new problem formulation for post-placement optimization with multi-bit flip-flops; 3) flip-flop clustering and placement algorithms to simultaneously minimize flip-flop power consumption and interconnecting wirelength; and 4) a progressive window-based optimization technique to reduce placement deviation and improve runtime efficiency of our algorithms. Experimental results show that our algorithms are very effective in reducing not only flip-flop power consumption but also clock tree and signal net wirelength. Consequently, the power consumption of the clock network is minimized.
An integrated programming and development environment for adiabatic quantum optimization

Adiabatic quantum computing is a promising route to the computational power afforded by quantum information processing. The recent availability of adiabatic hardware has raised challenging questions about how to evaluate adiabatic quantum optimization (AQO) programs. Processor behavior depends on multiple steps to synthesize an adiabatic quantum program, which are each highly tunable. We present an integrated programming and development environment for AQO called Jade Adiabatic Development Environment (JADE) that provides control over all the steps taken during program synthesis. JADE captures the workflow needed to rigorously specify the AQO algorithm while allowing a variety of problem types, programming techniques, and processor configurations. We have also integrated JADE with a quantum simulation engine that enables program profiling using numerical calculation. The computational engine supports plug-ins for simulation methodologies tailored to various metrics and computing resources. We present the design, integration, and deployment of JADE and discuss its potential use for benchmarking AQO programs by the quantum computer science community.
Top‐down structural analysis of posttranslationally modified proteins by Fourier transform ion cyclotron resonance‐MS with hydrogen/deuterium exchange and electron capture dissociation

High‐resolution structural characterization of posttranslationally modified proteins represents a challenge for traditional structural biology methods such as crystallography and NMR. In this study, we have used top‐down hydrogen/deuterium exchange MS (HDX‐MS) with precursor ion selection and electron capture dissociation to determine the impact of oxidative modification on calmodulin (CaM) at an average resolution of 2.5 residues, with complete sequence coverage. The amide deuteration status of native CaM determined by this method correlates well with previously reported crystallographic and NMR data. In contrast, methionine oxidation caused almost complete deuteration of all residues in the protein in 10 s. The oxidative‐modification‐induced secondary and tertiary structure loss can be largely recovered upon calcium ligation, which also resulted in a substantial increase of amide protection in three of the four calcium‐binding loops in oxidatively modified CaM (CaMox). However, the structure of α‐helix VI is not restored by cofactor binding. These results are discussed in terms of different target binding and activation capabilities displayed by CaM and CaMox. The isoform‐specific top‐down HDX structural analysis strategy demonstrated in this study should be readily applicable to other oxidatively modified proteins and other types of PTMs, and may help decipher the structure and function of specific protein isoforms.
Tracking smart grid hackers

The next-generation smart grid will rely highly on telecommunications infrastructure for data transfer between various systems. Anywhere we have data transfer in a system is a potential security threat. When we consider the possibility of smart grid data being at the heart of our critical systems infrastructure it is imperative that we do all we can to ensure the confidentiality, availability and integrity of the data. A discussion on security itself is outside the scope of this paper, but if we assume the network to be as secure as possible we must consider what we can do to detect when that security fails, or when the attacks comes from the inside of the network. One way to do this is to setup a hacker-trap, or honeypot. A honeypot is a device or service on a network which appears legitimate, but is in-fact a trap setup to catch breech attempts. This paper identifies the different types of honeypot and describes where each may be used. The authors have setup a test honeypot system which has been live for some time. The test system has been setup to emulate a device on a utility network. The system has had many hits, which are described in detail by the authors. Finally, the authors discuss how larger-scale systems in utilities may benefit from honeypot placement.
THE EFFECTS OF TEXT ADAPTATION ON RATED APPEAL AND DIFFICULTY

This study was designed to investigate how low‐achieving readers rate high‐interest low vocabulary adaptations and their original story versions for difficulty and appeal. Five hundred and seventy‐six Title 1 junior and senior high school students were assigned randomly to read and rate one of eight story versions (three original versions and five adaptations). Significant differences in difficulty and appeal ratings were found across the eight story versions. Adaptations were rated as being easier than original stories. Generally, changes in length and readability did not affect appeal. The one exception to this finding was a story adaptation that also had a substantial content modification. The quality of a story was found to be the important factor affecting appeal.
Taking advantage of disaster: misrepresentation of housing shortage for political gain

Purpose - The purpose of this paper aims to explore the reports of housing shortages in post-Katrina New Orleans especially for low-income residents in the face of a returning working poor population. Despite the availability of housing vouchers by the New Orleans Housing Authority to any previous residents of New Orleans housing projects, a political uproar has claimed no homes are available and that destroying the previously failing New Orleans housing projects would amount to “forced homelessness. ” Design/methodology/approach - The analysis is done by reflecting on different commentary from persons claiming the housing projects must be preserved while also exploring the failed goals of the same public institutions. Further, a brief overview of the housing situation regarding availability of homes is conducted. Findings - The findings show that the poor of New Orleans are being misled about available housing, and there is a continuing process of decline in sovereignty of local public policy makers. Politicians benefit by elevating their public persona. Originality/value - The paper explores the political benefactors of perpetuating falsehoods in order to make political gains.
Structure and Persuasion: The Case of Advertising

The paper examines the problem of persuasion from a structuralist perspective. Since advertising is a highly competitive system of communication, which draws heavily on mechanisms of persuasion, it is ideally suited both to test and illustrate the case that structuralism makes. Following a certain procedure, any viable system of advertising campaigns can be decoded into a binary structure of an archetypal nature. Moreover, all the binary structures thus obtained, are themselves inter-related to form a first and tentative approximation of the grand structure of all advertising. This is the structure of the structures. It has been shown before, that structures can only be decoded from a complete system of communication. Similarly, it has been maintained, that the existence of the structures is essential to the understanding of the message. Since advertising is a sequential phenomenon, it follows that a campaign's power of persuasion is determined by the facility of the code. The more economical, clear and precise the structural definition, the higher is the level of effective communication. Second, at any point in time, the underlying structure of a competitive product field is determined by all the campaigns which are active in its sphere. But in mature fields the controlling archetype has already been established in the course of the history of the product field. A new campaign merely represents it in a new guise. In this sense the archetype precedes any new manifestation of it. Therefore, the effectivity of each new campaign is determined by its fidelity to the positive pole of the binary pair which constitutes its underlying structure. Finally, the power of persuasion is influenced by the nature of the archetype itself. In each product group, the rank order of effectivity can be established on the basis of empirical examination.
Association of analgesic use with prevalence of albuminuria and reduced GFR in US adults.

BACKGROUND Prolonged analgesic consumption may adversely affect kidney function. The relation of long-term analgesic use to markers of decreased kidney function has not been investigated in the general population. DESIGN Cross-sectional analysis. SETTING National Health and Nutrition Examination Survey conducted in 1999-2002. PARTICIPANTS Noninstitutionalized residents at least 20 years old (n = 8,057, representing 177.8 million adults). PREDICTORS Ever intake of an analgesic every day for at least a month defined habitual analgesic use, classified by product (aspirin, acetaminophen, ibuprofen, and selected prescription drugs) and years of use (<1, 1 to 5, and >5 years). OUTCOMES Albuminuria in random urine (albumin-creatinine ratio >or= 30 mg/g; n = 1,088) and reduced estimated glomerular filtration rate (eGFR; <60 mL/min/1.73 m(2), n = 852) using the Modification of Diet in Renal Disease Study equation and the composite of either. MEASUREMENTS Age-standardized prevalence in habitual analgesic users and non-habitual analgesic users and multivariable-adjusted odds ratios (ORs). RESULTS In US adults, 23.7% (95% confidence interval [CI], 21.7 to 25.6) reported habitual analgesic use. Multivariable-adjusted ORs for reduced eGFR prevalence in adults with habitual analgesic use of acetaminophen only, ibuprofen only, and aspirin only were 1.03 (95% CI, 0.6 to 1.7), 1.21 (95% CI, 0.7 to 2.1), and 0.95 (95% CI, 0.7 to 1.2) compared with non-habitual analgesic use, respectively. Corresponding ORs for prevalent albuminuria were 0.93 (95% CI, 0.7 to 1.3), 0.65 (95% CI, 0.4 to 1.2), and 0.86 (95% CI, 0.6 to 1.2). Association measures had intermediate levels for the composite marker of decreased kidney function and were not significant. No association between prevalent outcomes and habitual analgesic exposure duration of 5 years or longer or multiple product habitual analgesic consumption was observed. LIMITATIONS Reliability of self-reported analgesic use behavior was not assessed. CONCLUSIONS Habitual analgesic use of single or multiple products was not associated with increased prevalence of albuminuria or reduced eGFR.
A DVS-based pipelined reconfigurable instruction memory

Energy consumption is of significant concern in battery operated embedded systems. In the processors of such systems, the instruction cache consumes a significant fraction of the total energy. One of the most popular methods to reduce the energy consumption is to shut down idle cache banks. However, we observe that operating idle cache banks at a reduced voltage/frequency level along with the active banks in a pipelined manner can potentially achieve even better energy savings. In this paper, we propose a novel DVS-based pipelined reconfigurable instruction memory hierarchy called PRIM. A canonical example of our proposed PRIM consists of four cache banks. Two of these cache banks can be configured at runtime to operate at lower voltage and frequency levels than that of the normal cache. Instruction fetch throughput is maintained by pipelining the accesses to the low voltage banks. We developed a profile-driven compilation framework that analyzes applications and inserts the appropriate cache reconfiguration points. Our experimental results show that PRIM can significant reduce the energy consumption for popular embedded benchmarks with minimal performance overhead. We obtained 56.6% and 45.1% energy savings for aggressive and conservative VDD settings, respectively, at the expense of a 1.66% performance overhead.
TESS: Bayesian inference of lineage diversification rates from (incompletely sampled) molecular phylogenies in R

Summary Many fundamental questions in evolutionary biology entail estimating rates of lineage diversification (speciation – extinction). We develop a flexible Bayesian framework for specifying an effectively infinite array of diversification models—where rates are constant, vary continuously, or change episodically through time—and implement numerical methods to estimate parameters of these models from molecular phylogenies, even when species sampling is incomplete. Additionally we provide robust methods for comparing the relative and absolute fit of competing branching-process models to a given tree, thereby providing rigorous tests of biological hypotheses regarding patterns and processes of lineage diversification. Availability and implementation the source code for TESS is freely available at http://cran.r-project.org/web/packages/TESS/. Contact Sebastian.Hoehna@gmail.com
A COMPLIANT QUADRUPEDAL ROBOT FOR FAST , EFFICIENT , AND VERSATILE

This paper introduces StarlETH, a compliant quadrupedal robot that is designed to study fast, efficient, and versatile locomotion. The platform is fully actuated with high compliant series elastic actuation, making the system torque controllable and at the same time well suited for highly dynamic maneuvers. We additionally emphasize key elements of a powerful real time control and simulation environment. The work is concluded with a number of experiments that demonstrate the performance of the presented hardware and controllers.
Counselling refugee young people: an exploration of therapeutic approaches

This paper presents and discusses the key findings from a study that considered significant issues that affect refugees and asylum‐seekers, and explored beneficial counselling approaches relevant to this group. In‐depth narrative interviews were conducted with three counsellors and three specialist children’s support advisors. Data were analysed using the methods of comparative analysis and theme mapping from a grounded theory approach. The key findings reveal that counsellors do not work from a particular approach but adapt a variety of therapeutic methods to the needs of the child. In addition, they focus on the therapeutic relationship; take into account lack of safety and loss of home, traumatic experiences and impacts, and resilience of the child; stress that both short‐term and long‐term therapy is beneficial; and show a concern over lack of specialised training for counsellors and obstacles to accessing counselling. Understanding the needs of young refugees and asylum‐seekers in the United Kingdom and considering counsellors’ experiences and perspectives on approaches has highlighted implications for practice, which include the necessity for more counsellors to be culturally reflexive and open‐minded in working with this group. In addition, this study may influence the way in which higher education professionals can develop research on refugee children and incorporate relevant pastoral care across the curriculum to accommodate refugee children from a wide diversity of backgrounds and experiences.
Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis

Engagement of the Fas receptor (CD95) initiates multiple signaling pathways that lead to apoptosis, such as the formation of death-inducing signaling complex (DISC), activation of caspase cascades, and the generation of the lipid messenger, ceramide. Sphingomyelin (SM) is a major component of lipid rafts, which are specialized structures that enhance the efficiency of membrane receptor signaling and are a main source of ceramide. However, the functions of SM in Fas-mediated apoptosis have yet to be clearly defined, as the responsible genes have not been identified. After cloning a gene responsible for SM synthesis, SMS1, we established SM synthase–defective WR19L cells transfected with the human Fas gene (WR/Fas-SM(−)), and cells that have been functionally restored by transfection with SMS1 (WR/Fas-SMS1). We show that expression of membrane SM enhances Fas-mediated apoptosis through increasing DISC formation, activation of caspases, efficient translocation of Fas into lipid rafts, and subsequent Fas clustering. Furthermore, WR/Fas-SMS1 cells, but not WR/Fas-SM(−) cells, showed a considerable increase in ceramide generation within lipid rafts upon Fas stimulation. These data suggest that a membrane SM is important for Fas clustering through aggregation of lipid rafts, leading to Fas-mediated apoptosis.
Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma

Bevacizumab, an antibody against vascular endothelial growth factor (VEGF), is a promising, yet controversial, drug in human glioblastoma treatment (GBM). Its effects on tumor burden, recurrence, and vascular physiology are unclear. We therefore determined the tumor response to bevacizumab at the phenotypic, physiological, and molecular level in a clinically relevant intracranial GBM xenograft model derived from patient tumor spheroids. Using anatomical and physiological magnetic resonance imaging (MRI), we show that bevacizumab causes a strong decrease in contrast enhancement while having only a marginal effect on tumor growth. Interestingly, dynamic contrast-enhanced MRI revealed a significant reduction of the vascular supply, as evidenced by a decrease in intratumoral blood flow and volume and, at the morphological level, by a strong reduction of large- and medium-sized blood vessels. Electron microscopy revealed fewer mitochondria in the treated tumor cells. Importantly, this was accompanied by a 68% increase in infiltrating tumor cells in the brain parenchyma. At the molecular level we observed an increase in lactate and alanine metabolites, together with an induction of hypoxia-inducible factor 1α and an activation of the phosphatidyl-inositol-3-kinase pathway. These data strongly suggest that vascular remodeling induced by anti-VEGF treatment leads to a more hypoxic tumor microenvironment. This favors a metabolic change in the tumor cells toward glycolysis, which leads to enhanced tumor cell invasion into the normal brain. The present work underlines the need to combine anti-angiogenic treatment in GBMs with drugs targeting specific signaling or metabolic pathways linked to the glycolytic phenotype.