Miracle-dz/UniFAR-FTUs huggingface dataset:
AZ-4217: A High Potency BACE Inhibitor Displaying Acute Central Efficacy in Different In Vivo Models and Reduced Amyloid Deposition in Tg2576 Mice

Aβ, the product of APP (amyloid precursor protein), has been implicated in the pathophysiology of Alzheimer's disease (AD). β-Site APP cleaving enzyme1 (BACE1) is the enzyme initiating the processing of the APP to Aβ peptides. Small molecule BACE1 inhibitors are expected to decrease Aβ-peptide generation and thereby reduce amyloid plaque formation in the brain, a neuropathological hallmark of AD. BACE1 inhibition thus addresses a key mechanism in AD and its potential as a therapeutic target is currently being addressed in clinical studies. Here, we report the discovery and the pharmacokinetic and pharmacodynamic properties of BACE1 inhibitor AZ-4217, a high potency compound (IC50 160 pm in human SH-SY5Y cells) with an excellent in vivo efficacy. Central efficacy of BACE1 inhibition was observed after a single dose in C57BL/6 mice, guinea pigs, and in an APP transgenic mouse model of cerebral amyloidosis (Tg2576). Furthermore, we demonstrate that in a 1 month treatment paradigm BACE1 inhibition of Aβ production does lower amyloid deposition in 12-month-old Tg2576 mice. These results strongly support BACE1 inhibition as concretely impacting amyloid deposition and therefore potentially an important approach for therapeutic intervention in AD.
Harming is more intentional than helping because it is more probable: the underlying influence of probability on the Knobe effect

ABSTRACT Knobe [2003. Intentional action and side effects in ordinary language. Analysis, 63, 190–194] demonstrated that people’s intentionality judgments in side effects depend on the outcome of the side-effect, indicating that people’s judgments of intentionality of action depend on not only the intention of the actor but also on the result of the action. However, on the basis of findings in judgment and decision making, the current study proposes another hypothesis to Knobe’s (2003) results: the participants’ intentionality judgments are related to not only the outcomes themselves but also the probabilities of outcomes predicted from the action. To test this hypothesis, the present study employed an identical experimental procedure to Knobe (2003), except that it required not only intentionality but also probability judgments for outcomes that resulted from the actions of a company president. The results replicated the findings of Knobe (2003) and showed a relationship between probability and intentionality judgment.
An Adoption Model of Electronic Government Services in Malaysia: Electronic Labor Exchange (ELX) (Model Ambil Guna Perkhidmatan Kerajaan Elektronik di Malaysia: Pasaran Buruh Elektronik (ELX))

This paper examines factors influencing adoption of electronic government services among end-users of Electronic Labor Exchange (ELX) in Malaysia. The objective of the paper is to understand how end-users perceived e-Government as a primary government interaction channel and the factors that affect their level of usage. The proposed adoption model integrates a number of measurement criteria such as, system quality, information quality, security, efficiency, satisfaction, usage and system’s benefits adapted from previous studies. To gauge the relationships between these constructs, several statistical analysis techniques such as factor analyses and Structural Equation Modeling (SEM) were conducted. The study finds that both information quality and efficiency positively affect satisfaction; security positively affects usage; and both usage and satisfaction positively affect benefits. However, the results of the study reject the hypotheses that the other two service quality components namely usability and functionality, and security positively affect satisfaction. The results also reject the hypotheses that service quality (efficiency, functionalty, and usability), information quality and satisfaction influence usage. The results implied the urgent need to improve eGovernment services in terms of functionality, usability, security in order to improve end-users’ satisfaction, usage and long-term loyalty to the system. ABSTRAK Kertas ini menyelidik faktor yang memengaruhi ambil guna perkhidmatan kerajaan elektronik dalam kalangan pengguna Pasaran Buruh Elektronik (ELX) di Malaysia. Tujuan kertas ini adalah untuk memahami bagaimana tanggapan pengguna akhir terhadap e-Kerajaan sebagai saluran interaksi utama kerajaan dan faktor yang mempengaruhi tingkat penggunaannya. Model yang dicadangkan menyepadukan berbagai kriteria pengukuran seperti kualiti sistem, kualiti maklumat keselamatan, kecekapan, kepuasan, penggunaan dan faedah sistem yang diubahsuai daripada kajian lepas. Untuk menentukan hubungan antara berbagai konstruk tersebut beberapa teknik statistik seperti analisis faktor dan pemodelan persamaan struktur dilakukan. Kajian mendapati kedua-dua kualiti maklumat dan kecekapan mempengaruhi kepuasan pengguna secara positif. Walau bagaimanapun, keputusan kajian menolak hipotesis bahawa dua komponen kualiti perkhidmatan iaitu kebolehgunaan dan kefungsiaan, dan keselamatan mempengaruhi kepuasan secara positif. Kajian juga menolak hipotesis bahawa kualiti perkhidmatan (kecekapan, kefungsiaan, dan kebergunaan), kualiti maklumat dan kepuasan mempengaruhi penggunaan. Keputusan kajian menunjukkan keperluan segera untuk membaiki perkhidmatan-perkhidmatan e-Kerajaan umumnya dan ELX khususnya terutama dari segi kefungsiaan, kebergunaan, dan keselamatan untuk membaiki kepuasan, penggunaan dan loyalti jangka panjang pengguna akhir kepada sistem e-Kerajaan.
PENGEMBANGAN MODEL PROGRAM PRAKTEK KERJA INDUSTRI SISWA BERBASIS KARAKTER BATAK DI SMK KECAMATAN SIDIKALANG

Penelitian ini bertujuan untuk: (1) menemukan model penyelenggaraan Praktek kerja industri berbasis karakter Batak di SMK Kecamatan Sidikalang; (2) mengetahui luaran (output) penyelenggaraan prakterk kerja industri berbasis karakter Batak; (3) dan mengetahui respon pengelola Prakerin terhadap model yang digunakan. Jenis penelitian dan pengembangan ini dilaksanakan di tiga sekolah yaitu SMK Swasta Arina Sidikalang, SMK Pariwisata Prima Sidikalang, dan SMK Negeri 1 Sidikalang. Jumlah sampel penelitian 125 siswa dengan teknik purposive sampling. Data dikumpulkan dengan inventori, lembar kuisioner, dan dokumentasi. Uji hipotesis dilakukan dengan uji-t dan proses penghitungan dilakukan dengan bantuan SPPS. Dari tiga kali uji coba ditemukan hasil rata-rata karakter siswa; uji coba I sebesar 92,93 %, uji coba II sebesar 93,78 %, dan uji coba ke III sebesar 94,94%. Dan hasil penelitian menunjukkan bahwa: (1) model Prakerin Berbasis Karakter Batak cocok digunakan dalam penyelenggaraan program prakerin siswa SMK di Sidikalang; (2) luaran (output) dari model Prakerin berbasis karakter Batak yaitu: religius, disiplin, kerja keras, kerja sama, tanggung jawab, jujur, dan sopan yang dimiliki siswa lebih tinggi secara signifikan dibanding model konvensional, model manajemen Prakerin berbasis karakter Batak memiliki tingkat signifikansi yang tinggi dan mampu secara efektif mengembangkan karakter siswa menjadi lebih baik dan dapat dikembangkan sebagai alternatif penyelenggaraan program praktik kerja industri pada SMK. (3) respon pengelola program dan manajemen perusahaan terhadap model penyelenggaraan Prakerin Berbasis Karakter Batak dalam kategori sangat baik.
Arteriogenesis depends on circulating monocytes and macrophage accumulation and is severely depressed in op/op mice

It has been suggested that monocytes/macrophages represent the pivotal cell type during early adaptive growth of pre‐existent arterial anastomoses toward functional collateral arteries (arteriogenesis) upon arterial occlusion. This hypothesis was supported by previous studies providing evidence that elevation of the peripheral monocyte count, increased monocyte survival (e.g., granulocyte macrophage‐colony stimulating factor), as well as enhanced attraction or adhesion (e.g., monocyte chemoattractant protein 1; intercellular adhesion molecule 1) of the latter cells correlates directly with the arteriogenic response to restore tissue perfusion. However, the experimental proof of the essential role of monocytes/macrophages remains to be given. We therefore hypothesized that arteriogenesis is reduced in a genuine, nonpharmocologically induced monocyte/macrophage‐deficient model of femoral artery occlusion in osteopetrotic (op/op) mice. Total leukocyte count did not differ between op/op mice and control (B6C3Fe a/a‐Csf1+/+) mice. op/op mice show a significant monocytopenia (0.67%±0.38% vs. 1.53%±0.32%), granulocytosis (33.66%±6.67% vs. 22.83±7.47%), and a concomitant, relative lymphopenia (65.67%±6.58% vs. 75.65%±7.31%). Microsphere‐based perfusion measurement 7 days after femoral artery occlusion demonstrated a significantly reduced perfusion restoration upon femoral artery occlusion in op/op mice as compared with controls (28.19%±0.91% vs. 47.88%±2.49%). The application of a novel method of high resolution (microfocus X‐ray system) angiography revealed a reduction of proliferation and diameter of collateral arteries. Quantitative immunohistology showed significantly lower numbers of macrophages in the surrounding tissue of proliferating arteries. This study provides additional evidence for the preeminent role of monocytes/macrophages during arteriogenesis in a genuine model of monocyte deficiency, i.e., without pharmacological intervention.
High-Performance Modulators and Switches for Silicon Photonic Networks-on-Chip

The stringent on- and off-chip communications demands of future-generation chip multiprocessors require innovative and potentially disruptive technology solutions, such as chip-scale photonic transmission systems. A space-switched, wavelength-parallel photonic network-on-chip has been shown to equip users with high-bandwidth, low-latency links in an energy-efficient manner. Here, experimental measurements on fabricated silicon photonic devices verify a large set of the components needed to construct these networks. The proposed system architecture is reviewed to motivate the demanding performance requirements of the components. Then, systems-level investigations are delineated for multiwavelength electrooptic modulators and photonic switching elements arranged in 1 × 2, 2 × 2, and 4 × 4 formations. Compact (~10 ¿m), high-speed (4 Gb/s) modulators, having a large degree of channel scalability (four channels demonstrated), are demonstrated with excellent data integrity (bit error rates (BERs) <10-12). Meanwhile, switches are shown to transfer extensive throughput bandwidths (250 Gb/s) with fast switching speeds (<1 ns) and sufficient extinction ratios (>10 dB). Data integrity is also verified for the switches (BERs < 10-12) with power penalty measurements amid dynamic operation. These network component demonstrations verify the feasibility of the proposed system architecture, while previous works have verified its efficacy.
Late-Time Observations of SN 2006gy: Still Going Strong

Owing to its extremely high luminosity and long duration, supernova (SN) 2006gy radiated more energy in visual light than any other known SN. Two hypotheses to explain its high luminosity at early times—that it was powered by shock interaction with circumstellar material (CSM) as implied by its Type IIn spectrum, or that it was fueled by radioactive decay from a large mass of 56Ni synthesized in a pair-instability SN—predicted different late-time properties. Here we present observations of SN 2006gy obtained more than a year after discovery. We were unable to detect it at visual wavelengths, but clear near-infrared (IR) K′ and H-band detections show that it is still at least as luminous as the peak of a normal Type II SN. We also present spectra giving an upper limit to the late-time Hα luminosity of ≲1039 erg s−1. Based on the weak late-time Hα, X-ray, and radio emission, combined with the difficulty of explaining the shift to IR wavelengths, we can rule out ongoing CSM interaction as the primary late-time power source of SN 2006gy. Instead, we propose that the evolution of SN 2006gy is consistent with one of two possible scenarios: (1) a pair-instability SN plus modest CSM interaction, where the radioactive decay luminosity shifts to the IR because of dust formation; or (2) an IR echo, where radiation emitted during peak luminosity heats a pre-existing dust shell at radii near 1 light year, requiring the progenitor star to have ejected another shell of ~10 M☉ about 1500 yr before the SN.
Hearing Loss and Congenital CMV Infection: A Systematic Review

BACKGROUND AND OBJECTIVE: Hearing loss caused by congenital cytomegalovirus (cCMV) infection was first observed in 1964. Today cCMV is the most common cause of nonhereditary sensorineural hearing loss in childhood. Our objective was to provide an overview of the prevalence of cCMV-related hearing loss, to better define the nature of cCMV-associated hearing loss, and to investigate the importance of cCMV infection in hearing-impaired children. METHODS: Two reviewers independently used Medline and manual searches of references from eligible studies and review articles to select cohort studies on children with cCMV infection with audiological follow-up and extracted data on population characteristics and hearing outcomes. RESULTS: Thirty-seven studies were included: 10 population-based natural history studies, 14 longitudinal cohort studies, and 13 retrospective studies. The prevalence of cCMV in developed countries is 0.58% (95% confidence interval, 0.41–0.79). Among these newborns 12.6% (95% confidence interval, 10.2–16.5) will experience hearing loss: 1 out of 3 symptomatic children and 1 out of 10 asymptomatic children. Among symptomatic children, the majority have bilateral loss; among asymptomatic children, unilateral loss predominates. In both groups the hearing loss is mainly severe to profound. Hearing loss can have a delayed onset, and it is unstable, with fluctuations and progression. Among hearing-impaired children, cCMV is the causative agent in 10% to 20%. Despite strict selection criteria, some heterogeneity was found between selected studies. CONCLUSIONS: This systematic review underscores the importance of cCMV as a cause of sensorineural hearing loss in childhood.
Atoh1-dependent rhombic lip neurons are required for temporal delay between independent respiratory oscillators in embryonic mice

All motor behaviors require precise temporal coordination of different muscle groups. Breathing, for example, involves the sequential activation of numerous muscles hypothesized to be driven by a primary respiratory oscillator, the preBötzinger Complex, and at least one other as-yet unidentified rhythmogenic population. We tested the roles of Atoh1-, Phox2b-, and Dbx1-derived neurons (three groups that have known roles in respiration) in the generation and coordination of respiratory output. We found that Dbx1-derived neurons are necessary for all respiratory behaviors, whereas independent but coupled respiratory rhythms persist from at least three different motor pools after eliminating or silencing Phox2b- or Atoh1-expressing hindbrain neurons. Without Atoh1 neurons, however, the motor pools become temporally disorganized and coupling between independent respiratory oscillators decreases. We propose Atoh1 neurons tune the sequential activation of independent oscillators essential for the fine control of different muscles during breathing. DOI: http://dx.doi. org/10.7554/eLife.02265. 001
Can early dark energy be detected in non-linear structure?

We present the first study of early dark energy cosmologies using N-body simulations to investigate the formation of a non-linear structure. In contrast to expectations from semi-analytic approaches, we find that early dark energy does not imprint a unique signature on the statistics of non-linear structures. Investigating the non-linear power spectra and halo mass functions, we show that universal mass functions hold for early dark energy, making its presence difficult to distinguish from A cold dark matter. Since early dark energy biases the baryon acoustic oscillation scale, the lack of discriminating power is problematic.
High efficiency high step-up DC/DC converters - a review

The renewable energy sources such as PV modules, fuel cells or energy storage devices such as super capacitors or batteries deliver output voltage at the range of around 12 to 70 VDC. In order to connect them to the grid the voltage level should be adjusted according to the electrical network standards in the countries. First of all the voltage should be stepped up to sufficient level at which the DC/AC conversion can be performed to AC mains voltage requirements. Overall performance of the renewable energy system is then affected by the efficiency of step-up DC/DC converters, which are the key parts in the system power chain. This review is focused on high efficiency step-up DC/DC converters with high voltage gain. The differentiation is based on the presence or lack of galvanic isolation. A comparison and discussion of different DC/DC step-up topologies will be performed across number of parameters and presented in this paper.
Effect of human papillomavirus 16/18 L1 viruslike particle vaccine among young women with preexisting infection: a randomized trial.

CONTEXT Viruslike particle human papillomavirus (HPV) vaccines were designed to prevent HPV infection and development of cervical precancers and cancer. Women with oncogenic HPV infections might consider vaccination as therapy. OBJECTIVE To determine whether vaccination against HPV types 16 and 18 increases the rate of viral clearance in women already infected with HPV. DESIGN AND SETTING Phase 3, masked, community-based randomized trial conducted in 2 provinces of Costa Rica. PARTICIPANTS A total of 2189 women aged 18 to 25 years who were recruited between June 2004 and December 2005. Participants were positive for HPV DNA at enrollment, had at least 6 months of follow-up, and had follow-up HPV DNA results. INTERVENTION Participants were randomly assigned to receive 3 doses of a bivalent HPV-16/18 L1 protein viruslike particle AS04 candidate vaccine (n = 1088) or a control hepatitis A vaccine (n = 1101) over 6 months. MAIN OUTCOME MEASURES Presence of HPV DNA was determined in cervical specimins by a molecular hybridization assay using chemiluminescence with HPV RNA probes and by polymerase chain reaction using SPF10 primers and a line probe assay detection system before vaccination and by polymerase chain reaction after vaccination. We compared rates of type-specific viral clearance using generalized estimating equations methods at the 6-month visit (after 2 doses) and 12-month visit (after 3 doses) in the 2 study groups. RESULTS There was no evidence of increased viral clearance at 6 or 12 months in the group who received HPV vaccine compared with the control group. Clearance rates for HPV-16/18 infections at 6 months were 33.4% (82/248) in the HPV vaccine group and 31.6% (95/298) in the control group (vaccine efficacy for viral clearance, 2.5%; 95% confidence interval, -9.8% to 13.5%). Human papillomavirus 16/18 clearance rates at 12 months were 48.8% (86/177) in the HPV vaccine group and 49.8% (110/220) in the control group (vaccine efficacy for viral clearance, -2.0%; 95% confidence interval, -24.3% to 16.3%). There was no evidence of a therapeutic effect for other oncogenic or nononcogenic HPV categories, among women receiving all vaccine doses, among women with single infections, or among women stratified by the following entry variables: HPV-16/18 serology, cytologic results, HPV DNA viral load, time since sexual debut, Chlamydia trachomatis or Neisseria gonorrhoeae infection, hormonal contraceptive use, or smoking. CONCLUSION In women positive for HPV DNA, HPV-16/18 vaccination does not accelerate clearance of the virus and should not be used to treat prevalent infections. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00128661.
Discriminative Transfer Subspace Learning via Low-Rank and Sparse Representation

In this paper, we address the problem of unsupervised domain transfer learning in which no labels are available in the target domain. We use a transformation matrix to transfer both the source and target data to a common subspace, where each target sample can be represented by a combination of source samples such that the samples from different domains can be well interlaced. In this way, the discrepancy of the source and target domains is reduced. By imposing joint low-rank and sparse constraints on the reconstruction coefficient matrix, the global and local structures of data can be preserved. To enlarge the margins between different classes as much as possible and provide more freedom to diminish the discrepancy, a flexible linear classifier (projection) is obtained by learning a non-negative label relaxation matrix that allows the strict binary label matrix to relax into a slack variable matrix. Our method can avoid a potentially negative transfer by using a sparse matrix to model the noise and, thus, is more robust to different types of noise. We formulate our problem as a constrained low-rankness and sparsity minimization problem and solve it by the inexact augmented Lagrange multiplier method. Extensive experiments on various visual domain adaptation tasks show the superiority of the proposed method over the state-of-the art methods. The MATLAB code of our method will be publicly available at http://www.yongxu. org/lunwen.html.
The infrared emission of ultraviolet-selected galaxies from z = 0 to z = 1

Aims. We want to study the IR (>8 μm) emission of galaxies selected on the basis of their rest-frame UV light in a very homogeneous way (wavelength and luminosity) from z = 0 to z = 1. We compare their UV and IR rest-frame emission to study the evolution in dust attenuation with z as well as to check if a UV selection is capable of tracking all star formation. This UV selection will also be compared to a sample of Lyman break galaxies selected at z ≃ 1. Methods. We select galaxies in UV (1500-1800 A) rest-frame at z = 0, z = 0.6-0.8, z = 0.8-1.2, and with as Lyman break galaxies at z = 0.9-1.3, the samples are compiled to sample the same range of luminosity at any redshift. The UV rest-frame data come from GALEX for z 0 sources. The evolution in the IR and UV luminosities with z is analysed for individual galaxies as well as in terms of luminosity functions. Results. The L I R/Lu v ratio is used to measure dust attenuation. This ratio does not seem to evolve significantly with z for the bulk of our sample galaxies, but some trends are found for both galaxies with a strong dust attenuation and UV luminous sources: galaxies with L IR/ L uv > 10 are more frequent at z > 0 than at z = 0, and the largest values of L IR /L UV are found for UV faint objects; in contrast, the most luminous galaxies of our samples (L UV > 2 x 10 10 L ⊙ ), detected at z = 1, exhibit a lower dust attenuation than fainter ones. The value of L IR /L UV increases with the K rest-frame luminosity of the galaxies at all redshifts considered and shows a residual anticorrelation with L u v. The most massive and UV luminous galaxies exhibit quite high specific star formation rates. Lyman break galaxies exhibit systematically lower dust attenuation than UV-selected galaxies of same luminosity, but similar specific star formation rates. The analysis of the UV + IR luminosity functions leads to the conclusion that up to z = 1, most of the star formation activity of UV-selected galaxies is emitted in IR. Although we are able to infer information about all the star formation from our UV selection at z = 0.7, at z = 1 we miss a large fraction of galaxies more luminous than ≃10 11 L ⊙ . The effect is found to be larger for Lyman break galaxies.