Miracle-dz/UniFAR-FTUs huggingface dataset:
Presenilin endoproteolysis mediated by an aspartyl protease activity pharmacologically distinct from γ‐secretase

Presenilin (PS)‐dependent γ‐secretase cleavage is the final proteolytic step in generating amyloid β protein (Aβ), a key peptide involved in the pathogenesis of Alzheimer's disease. PS undergoes endoproteolysis by an unidentified ‘presenilinase’ to generate the functional N‐terminal and C‐terminal fragment heterodimers (NTF/CTF) that may harbor the γ‐secretase active site. To better understand the relationship between presenilinase and γ‐secretase, we characterized the biochemical properties of presenilinase and compared them with those of γ‐secretase. Similar to γ‐secretase, presenilinase was most active at acidic pH 6.3. Aspartyl protease inhibitor pepstatin A blocked presenilinase activity with an IC50 of ∼ 1 µm. Difluoroketone aspartyl protease transition state analogue MW167 was relatively selective for presenilinase (IC50 < 1 µm) over γ‐secretase (IC50−16 µm). Importantly, removing the transition state mimicking moiety simultaneously abolished both presenilinase and γ‐secretase inhibition, suggesting that presenilinase, like γ‐secretase, is an aspartyl protease. Interestingly, several of the most potent γ‐secretase inhibitors (IC50 = 0.3 or 20 nm) failed to block presenilinase activity. Although de novo generation of PS1 fragments coincided with production of Aβin vitro, blocking presenilinase activity without reducing pre‐existing fragment levels permitted normal de novo generation of Aβ and amyloid intracellular domain. Therefore, presenilinase has characteristics of an aspartyl protease, but this activity is distinct from γ‐secretase.
Prospects for Human Longevity

From 1985 to 1995, death rates for the population aged 0 to 99 declined at an average annual rate of 1.5% in France, 1.2% in Japan, and 0.4% in the United States. These trends in mortality, if they continue, would yield a life expectancy at birth from 85 to 90 years in the 21st century. Given the presence of entropy in the life table, a life expectancy at birth of 100 years, if it ever occurs, is unlikely to arise until well past the time when everyone alive today has already died. Overly optimistic forecasts of life expectancy have already influenced important areas of public policy.
A Study of Indicators for Identifying Zero Variables in Interior-Point Methods

This study is concerned with constrained optimization problems where the only inequality constraints are nonnegativity constraints on the variables. In these problems, the ability to identify zero variables (binding constraints) early on in an iterative method is of considerable value and can be used to computational advantage. This work first gives a formal presentation of the notion of indicators for identifying zero variables, and then studies various indicators proposed in the literature for use with interior-point methods for linear programming. Both theory and experimentation are presented that speak strongly against the use of the variables as indicators; perhaps the most frequently used indicator in the literature. This study implies that an indicator proposed by Tapia is particularly effective in the context of primal-dual interior-point methods. The local rate of convergence for several indicators is also studied.
Mitotic phosphorylation of the TBP-containing factor SL1 represses ribosomal gene transcription.

Entry into mitosis is accompanied by a global repression of transcription. To investigate the molecular mechanisms which shut-down rRNA synthesis during mitosis, we have compared RNA polymerase I (Pol I) transcription in extracts from asynchronous and mitotic HeLa cells. We show by several experimental approaches that phosphorylation by cdc2/cyclin B inactivates the TBP-containing factor SL1 and thus abrogates Pol I transcription during mitosis. This finding links the cell's cycle with the transcriptional activity of Pol I and suggests a common mechanism for mitotic silencing of all three classes of nuclear RNA polymerases, i.e. reversible inactivation of the respective TBP-TAF complexes by (a) mitotic kinase(s).
AN ANALYTICAL AND EXPERIMENTAL STUDY OF ULTRASONIC LINEAR MOTORS

Preliminary notes Ultrasonic linear motors (ULMs) are widely used in many industrial applications and a full characterization of their behaviour is often needed. This paper presents a detailed analytical-experimental study of ULMs. First, the general structure and operation principle of ULMs are introduced. The actuator mechanics is then described using a simple piezoelectric model. Since, in practice, ULMs are most often used as actuators for positioning mechanisms, the proposed model includes electromechanical relations which offer designers a broad range of possibilities for precise positioning and reliable model-based control. Finally, ULMs are experimentally investigated to determine the conditions that allow an optimal performance.
Adaptive sliding mode control for quadrotor helicopters

This paper proposes an adaptive method based on sliding mode control for quadrotor helicopters. The flight control system of quadrotor helicopters is a typical nonlinear and uncertain system. Sliding mode control (SMC) is a robust method to control nonlinear and uncertain systems, and can keep the system insensitive to uncertainties on the sliding surface. However, its design requires the knowledge of the bound on the uncertainties, and sometimes it could be a hard task to estimate accurately the bound. The goal is to design an adaptive control law based on sliding mode control without the knowledge of uncertainties and perturbations bound. This adaptive methodology provides a minimum value of control gain K(t) resulting in minimization of the chattering effect. In order to adjust quickly the control gain K(t), the attenuation factor is introduced in the region of quasi sliding mode in this paper. Finally, Simulation results demonstrate the effectiveness of the proposed control method.
Mobile Machine Learning Hardware at ARM: A Systems-on-Chip (SoC) Perspective

Machine learning is playing an increasingly significant role in emerging mobile application domains such as AR/VR, ADAS, etc. Accordingly, hardware architects have designed customized hardware for machine learning algorithms, especially neural networks, to improve compute efficiency. However, machine learning is typically just one processing stage in complex end-to-end applications, which involve multiple components in a mobile Systems-on-a-chip (SoC). Focusing on just ML accelerators loses bigger optimization opportunity at the system (SoC) level. This paper argues that hardware architects should expand the optimization scope to the entire SoC. We demonstrate one particular case-study in the domain of continuous computer vision where camera sensor, image signal processor (ISP), memory, and NN accelerator are synergistically co-designed to achieve optimal system-level efficiency.
Oncogenes and cancer

tors mentioned by Paul: Thl/Th2 cytokines; natural killer cells; markers that define cytotoxic, suppressor, activated, naive/memory, or primed T cell subsets; and quantitative HIV polymerase chain reaction. The language of AIDS immunology has changed over the years. It is imperative for the OAR to provide a much needed immunological thesaurus in order to give meaning to future AIDS trials. Biti Goldberg Dinitrochlorobenzene Study Group, San Francisco, CA 94114, USA Raphael B. Stricker HemaCare Corporation, 450 Sutter Street, Suite 1504, San Francisco, CA 94108, USA
Relations between passage rates of rumen fluid and particulate matter and foam production in rumen contents of cattle fed on different diets ad lib.

1. A group of six cattle, three of which had a non-bloating history (group A) and had been ruminally cannulated for the previous 2 years, and three with a history of being bloat-prone (group B) and which had been ruminally cannulated only 3 months before the study, were fed ad lib. on chopped lucerne (Medicago sotiva) hay, lucerne pellets, or a 100 g chopped hay and 900 g rolled barley grain/kg diet over three periods of 30 d each. Flow of rumen digesta, by reference to CoEDTA and chromium-mordanted fibres, and foam production from samples of rumen contents were measured. 2. Samples of rumen contents (50 ml) from group A produced foam heights of 150 and 60 mm, 2 and 4 h after feeding respectively, compared with 240 and 150 mm for group B (P < 0.05). 3. The fractional passage rate of the 1-2 mm particles mordanted with Cr did not differ (P > 0.05) between groups. 4. The fractional outflow rates (FOR) for CoEDTA 0-2 h and 2-7 h after feed was offered were 0.205 and 0.160/h for group A and 0.093 and 0.086/h for group B respectively (P < 0.05). 5. Rumen-fluid FOR 0-2 h and 2-7 h after provision of feed were significantly (P < 0.05) inversely correlated (r -0.74 and -0.85 respectively) with the amount of foam produced from rumen contents at these times.
Simulation of High-K Tunnel Barriers for Nonvolatile Floating Gate Memories

Replacing silicon dioxide tunnel dielectrics in nonvolatile floating gate memories by high-K materials may pave the way to continued scaling of state of the art flash memories. To evaluate the requirements for barrier height, programming voltages and injection speed, we have calculated WKB currents through single layer and multilayer high-K based dielectrics. For a single layer minimal barrier height of about 2eV, limited by thermionic current, we find Fowler-Nordheim programming voltages of about 7-9V. In order to further reduce the voltage or enhance the injection tunnel current, symmetric triple layers of sequence low-K/highK/low-K are proposed. Asymmetric structures are also briefly discussed.
Sensor data distribution and knowledge inference framework for a cognitive-based distributed storage sink environment

Large-scale sensor data distributions and knowledge inferences are major challenges for cognitive-based distributed storage environments. Cognitive storage sinks play an essential role in addressing these challenges. In a data-concentrated distributed cognitive sensor environment, cognitive storage sinks regulate the data distribution operations and infer knowledge from the large amounts of sensor data that are distributed across the conventional sensors. Embedding cognitive functions in conventional sensors is unreasonable, and the knowledge-processing limitations of conventional sensors create a serious problem. To overcome this problem, we propose a cognitive co-sensor platform across a large-scale distributed environment. Further, we propose a distributed data distribution framework (DDD-framework) for effective data distributions and a distributed knowledge inference framework (DKI-framework) that infers useful patterns for building knowledge intelligence. The analysis and discussion demonstrate that these frameworks can be adequately instigated for the purpose of optimal data distribution and knowledge inference within the horizon of a real-time distributed environment.
Understanding Conflicts in Agile Adoption through Technological Frames

In this paper, adoption of a new software development method is viewed as socio-technical innovation and change; a framework based on Bijkerâ€™s Technological Frames (TF) is developed and used to model this innovation and change. To illustrate this process findings from one case study of a large organization adopting the agile software development method are presented. Qualitative data were collected from observations, interviews, and documents and analysed using TFs. The authorsâ€™ findings show that viewing agile adoption as socio-technical innovation and change provides results that resonate with existing research in the area and extends it. The key contribution of this case study to the socio-technical literature on systems development is a practical demonstration of how TFs can be used to facilitate the socio-technical understanding and identification of conflicts between stakeholder groups while going through the adoption of a new software development method.
Effect of irbesartan on angiotensin II-induced hypertrophy of human proximal tubular cells.

BACKGROUND Intrarenal activation of the renin angiotensin system (RAS) plays an important role in mediating renal fibrosis. Both angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II (AngII) receptor antagonists have been shown to exert a protective role against diabetic and non-diabetic nephropathy. However, the exact mechanism of how blocking local RAS prevents renal fibrosis is unclear. The present study was to investigate the influence of a new AngII receptor antagonist, irbesartan (Irb), on AngII-induced hypertrophy in human proximal tubular cell line (HK-2). METHODS The cell line, HK-2, was grown in Dulbeccos's Modified Eagle's Medium containing 10% heat-inactivated fetal calf serum. After rested in serum-free medium for 24 hours, the effects of Irb on AngII (10(-7) mol/L)-induced [(3)H]-leucine incorporation, total protein content (measured by the Coomassie brilliant blue G250 method), and change in cell size (determined by scanning electron microscopy) were observed. The influence of Irb on the cell cycle was analyzed by fluorescence activated cell sorter (FACS) flow cytometry. RESULTS AngII induced cell hypertrophy in a time and dose dependent manner. Stimulation of cells with AngII for 48 hours resulted in a increase in [(3)H]-leucine incorporation [0 hour: (5584 +/- 1016) cpm/10(5) cells vs 48 hours: (10741 +/- 802) cpm/10(5) cells, P < 0.05], which was significantly attenuated by treatment with Irb. AngII significantly increased the total protein content in HK-2 cells [control: (0.169 +/- 0.011) mg/10(5) cells vs AngII group: (0.202 +/- 0.010) mg/10(5) cells, P < 0.05], which was also markedly inhibited by cotreatment with Irb (P < 0.01). Scanning electron microscopy showed that AngII induced an increase in average physical cell size, which was significantly inhibited by Irb [control: (11.92 +/- 1.62) microm; AngII group: (20.63 +/- 3.83) micro m; AngII + Irb group: (13.59 +/- 3.15) micro m; P < 0.01 vs control, respectively]. Furthermore, flow cytometry revealed that AngII arrested cells in the G(0)-G(1) phase, which was significantly reversed by treatment with Irb [G(0)-G(1) cells in AngII group: (76.09 +/- 1.82)%, in AngII + Irb group: (67.00 +/- 2.52)%, P < 0.05]. CONCLUSION Irb can inhibit AngII-induced hypertrophy in HK-2 cells.
Nitrification in the Hyporheic Zone of a Desert Stream Ecosystem

Nitrification in the hyporheic zone of Sycamore Creek, a Sonoran Desert stream, was examined, focusing on the association between respiration and nitrate production. Subsurface respiration in Sycamore Creek is highest in regions of hydrologic downwelling where organic matter derived from the stream surface is transported into the hyporheic zone. Similarly, nitrification was closely related to hydrologic exchange between the surface and hyporheic zone. Nitrification in downwelling regions averaged 13.1 μ gNO3-N· L sediments-1· h-1 compared with 1.7 μ gNO3-N· L sediments-1· h-1 in upwelling regions. Hyporheic respiration also varies temporally as a result of flash floods which scour and remove algae from the stream and thus reduce the pool of organic matter to support subsurface metabolism. Nitrification was also significantly affected by flooding; nitrification increased from an average of only 3.0 μ gNO3-N· L sediments-1· h-1 immediately following floods to 38.5 μ gNO3-N· L sediments-1· h-1 late in succession. Nitrification was significantly correlated with hyporheic respiration, supporting the hypothesis that nitrification is fueled by mineralization of organic nitrogen to ammonium. The coupling between subsurface respiration and nitrification is one step in a cyclic interaction between surface and hyporheic zones and serves to transform nitrogen from an organic to inorganic form.
Effects of Learning Climate and Registered Nurse Staffing on Medication Errors

BACKGROUND Despite increasing recognition of the significance of learning from errors, little is known about how learning climate contributes to error reduction. OBJECTIVES The purpose of this study was to investigate whether learning climate moderates the relationship between error-producing conditions and medication errors. METHODS A cross-sectional descriptive study was done using data from 279 nursing units in 146 randomly selected hospitals in the United States. Error-producing conditions included work environment factors (work dynamics and nurse mix), team factors (communication with physicians and nurses' expertise), personal factors (nurses' education and experience), patient factors (age, health status, and previous hospitalization), and medication-related support services. Poisson models with random effects were used with the nursing unit as the unit of analysis. RESULTS A significant negative relationship was found between learning climate and medication errors. It also moderated the relationship between nurse mix and medication errors: When learning climate was negative, having more registered nurses was associated with fewer medication errors. However, no relationship was found between nurse mix and medication errors at either positive or average levels of learning climate. Learning climate did not moderate the relationship between work dynamics and medication errors. DISCUSSION The way nurse mix affects medication errors depends on the level of learning climate. Nursing units with fewer registered nurses and frequent medication errors should examine their learning climate. Future research should be focused on the role of learning climate as related to the relationships between nurse mix and medication errors.
On Crossing Fitness Valleys with the Baldwin Effect

Escaping local optima and crossing fitness valleys to reach higher-fitness regions of a fitness landscape is a ubiquitous concept in much writing on evolutionary difficulty. The Baldwin effect, an interaction between non-heritable lifetime plasticity (e.g. learning) and evolution, has been shown to be able to guide evolutionary change and ‘smooth out’ abrupt fitness changes in fitness landscapes –thus enabling genetic evolution that would otherwise not occur. However, prior work has not provided a detailed study or analysis on the saddle-crossing ability of the Baldwin effect in a simple multi-peaked landscape. Here we provide analytic and simulation studies to investigate the effectiveness and limitations of the Baldwin effect in enabling genotypic evolution to cross fitness valleys. We also discuss how canalisation, an aspect of many prior models of the Baldwin effect, is unnecessary for the Baldwin effect and a hindrance to its valley-crossing ability.
A bidirectional planar monopole antenna array for WiFi/Bluetooth and LTE mobile applications

This paper presents a novel bidirectional planar monopole antenna array, with its feeding network, to apply for WiFi/Bluetooth and LTE mobile standards. The planar array is comprised of monopole antenna elements that utilise Archimedean spiral slots, inspired as resonance paths, in order to generate multi-band performance. Contrary to conventional structures, the feeding network is composed of three Wilkinson power dividers, for the purpose of providing synchronised output signals over the required frequency range, miniaturising dissipation losses and decreasing mutual coupling. Simulation and measurement results are presented for a single antenna element, an initial Wilkinson power divider and a four-element planar array, which reside on FR4 substrates. Successfully comparison between simulated and measured results verifies that the single antenna element achieves a 10 dB reflection coefficient from 2.2GHz to 2.9GHz, and the planar antenna array illustrates a 10 dB return loss bandwidth from 2.4GHz to 3.1GHz, which could cover WiFi/Bluetooth (2.45GHz) and LTE (2.6GHz) mobile applications. The proposed planar monopole antenna array also obtains large gain, high efficiency, narrow beam, low side lobe level and highly symmetric bidirectional radiation pattern in both E- and H-plane.
Comparing Composite vs. Wave-Cores in a novel dark-silicon methodology

As transistor scaling continues to push us into new design spaces, where power density is increasingly a major performance constraint, there have been moves to explore solutions which exploit so-called Dark Silicon, the UCSD Greendroid project being a notable exemplar. In this paper, we explore one novel dark silicon methodology, based on a heterogeneous multi-accelerator system model and an implicit execution model for the host processor. We also highlight a back-end translation methodology from raw machine code into data-flow style hardware cores, and introduce two distinct implementation styles. We then demonstrate comparative power benefits as compared to a relevant CPU model, assuming a 65nm benchmark technology node for both cases.
Antigen presentation in the murine oral epithelium

We have previously reported that the buccal mucosa can support delayed type hypersensitivity (DTH) reactions to contact sensitizers. In the present study, we show that cells isolated from the buccal epithelium are able to present soluble exogenous antigens to specific T cells. Single cell suspensions obtained by enzymatic dispersion of buccal epithelial sheets could present the native protein antigen hen‐egg lysozyme (HEL) to the I‐Ak‐restricted CD4+ T‐cell hybridoma specific for a.a 46–61 on HEL. T‐cell activation resulted in interleukin‐2 (IL‐2) production which could be inhibited by anti‐major histocompatibility complex (MHC) class‐II antibodies of pertinent specificity. Immunohistochemical staining of whole buccal epithelial sheets revealed that all MHC II positive cells had a dendritic morphology and expressed ATPase activity, indicating that these cells represent a major antigen‐presenting cell (APC) population in this tissue. Furthermore, single cell suspensions isolated from buccal epithelium (BEC) after local in vivo administration of either a native soluble protein, a synthetic dodecapeptide, or a contact sensitizer were able to activate antigen‐specific T cells ex vivo. Kinetic analyses indicated that maximal APC activity in the oral epithelium occurred within 1 hr after local antigen administration, and had essentially vanished after 24 hr. Conversely, APC activity was undetectable in draining cervico‐mandibular lymph node cell suspensions recovered 1 hr after local antigen injection but became manifest after 3–24 hr. These observations suggest that dendritic cells can acquire antigens in the buccal epithelium and migrate to draining lymph nodes where they present processed antigen to MHC class II‐restricted T cells. This APC population may thus be a critical element in the initiation of Th1‐driven DTH responses in the oral mucosa.
Cost-effectiveness of a stepped care intervention to prevent depression and anxiety in late life: randomised trial

Background There is an urgent need for the development of cost-effective preventive strategies to reduce the onset of mental disorders. Aims To establish the cost-effectiveness of a stepped care preventive intervention for depression and anxiety disorders in older people at high risk of these conditions, compared with routine primary care. Method An economic evaluation was conducted alongside a pragmatic randomised controlled trial (ISRCTN26474556). Consenting individuals presenting with subthreshold levels of depressive or anxiety symptoms were randomly assigned to a preventive stepped care programme (n = 86) or to routine primary care (n = 84). Results The intervention was successful in halving the incidence rate of depression and anxiety at €563 (£412) per recipient and €4367 (£3196) per disorder-free year gained, compared with routine primary care. The latter would represent good value for money if the willingness to pay for a disorder-free year is at least €5000. Conclusions The prevention programme generated depression- and anxiety-free survival years in the older population at affordable cost.