gebhart/patrepeval huggingface dataset:
O3‐05–05: A novel approach for treatment of Alzheimer's disease: Antibodies against β‐secretase cleavage site of APP (2008)

Cerebral deposition of amyloid β (Aβ) peptides is considered a major event in the pathogenesis of Alzheimer's disease (AD). Active and passive immunization studies have shown that antibodies against Aβ peptides are effective in reducing Aβ levels and plaque pathology, as well as attenuating cognitive deficits in animal models of. However, the therapeutic potential of these antibodies in AD patients is limited because of adverse inflammatory reactions and cerebral hemorrhage, which are associated with the treatment. β-secretase APP cleaving enzyme 1 (BACE1) has became an attractive therapeutic target and many efforts are aimed towards its inhibition. However, recent studies showed that BACE1 is involved in processing other non-APP substrates. Here, we present a novel approach to inhibit Aβ production via antibodies against the β-secretase cleavage site (β-site) of amyloid precursor protein (APP). Using hybridoma technique we have isolated a panel of monoclonal antibodies against the APP β-site. Cellular and animal models of AD were used to investigate the effect of anti β-site antibodies on Aβ levels. Anti β-site antibodies bind human APP expressed by AD cellular model and internalize into the cells after APP binding at the plasma membrane. Antibodies mediated inhibition of β-secretase cleavage led to a 50% reduction of intracellular Aβ levels. The in-vivo feasibility of our approach was demonstrated using wild-type and transgenic animal models. Intracerebroventricular injection of anti β-site antibodies to non transgenic mice in which neprilysin activity was compromised led to 60% and 80% reduction in intracellular and extracellular brain soluble Aβ levels, respectively. Antibody administration via intraperitoneal injection to London mutated APP transgenic mice have reduced insoluble Aβ levels considerably. Antibody treatment did not induce any inflammatory or autoimmune responses. The presented approach limits APP processing by β-secretase, mainly through the endocytic pathway. Taken together, the data presented here highlights the therapeutic potential of anti β-site antibodies as an alternative strategy to limit Aβ production avoiding some of the obstacles that may be involved with BACE-1 inhibition methodologies.
Theory: general discussion (2021)

Justin Hargreaves opened the discussion of the paper by Graham Hutchings: Thank you very much indeed for your excellent presentation. Your lecture very nicely spanned studies across an extended period of investigation where the emphasis of the approaches for catalytic reaction mechanism determi
Recommendations for RSVP-TE and Segment Routing (SR) Label Switched Path (LSP) Coexistence (2018)

Operators are looking to introduce services over Segment Routing (SR)
LSPs in networks running Resource Reservation Protocol (RSVP-TE) LSPs.
In some instances, operators are also migrating existing services from
RSVP-TE to SR LSPs. For example, there might be certain services that
are well suited for SR and need to co-exist with RSVP-TE in the same
network. Such introduction or migration of traffic to SR might require
co-existence with RSVP-TE in the same network for an extended period
of time depending on the operator's intent. The following document
provides solution options for keeping the traffic engineering database
consistent across the network, accounting for the different bandwidth
utilization between SR and RSVP-TE.
Clinical Characteristics of Individuals With Germline Mutations in <i>BRCA1</i> and <i>BRCA2</i>: Analysis of 10,000 Individuals (2002)

PURPOSE: To assess the characteristics that correlate best with the presence of mutations in BRCA1 and BRCA2 in individuals tested in a clinical setting. PATIENTS AND METHODS: The results of 10,000 consecutive gene sequence analyses performed to identify mutations anywhere in the BRCA1 and BRCA2 genes (7,461 analyses) or for three specific Ashkenazi Jewish founder mutations (2,539 analyses) were correlated with personal and family history of cancer, ancestry, invasive versus noninvasive breast neoplasia, and sex. RESULTS: Mutations were identified in 1,720 (17.2%) of the 10,000 individuals tested, including 968 (20%) of 4,843 women with breast cancer and 281 (34%) of 824 with ovarian cancer, and the prevalence of mutations was correlated with specific features of the personal and family histories of the individuals tested. Mutations were as prevalent in high-risk women of African (25 [19%] of 133) and other non-Ashkenazi ancestries as those of European ancestry (712 [16%] of 4379) and were significantly less prevalent in women diagnosed before 50 years of age with ductal carcinoma in situ than with invasive breast cancer (13% v 24%, P = .0007). Of the 74 mutations identified in individuals of Ashkenazi ancestry through full sequence analysis of both BRCA1 and BRCA2, 16 (21.6%) were nonfounder mutations, including seven in BRCA1 and nine in BRCA2. Twenty-one (28%) of 76 men with breast cancer carried mutations, of which more than one third occurred in BRCA1. CONCLUSION: Specific features of personal and family history can be used to assess the likelihood of identifying a mutation in BRCA1 or BRCA2 in individuals tested in a clinical setting.
Measurement of the integrated luminosity of the Phase 2 data of the Belle II experiment * (2020)

Abstract From April to July 2018, a data sample at the peak energy of the resonance was collected with the Belle II detector at the SuperKEKB electron-positron collider. This is the first data sample of the Belle II experiment. Using Bhabha and digamma events, we measure the integrated luminosity of the data sample to be ( , where the first uncertainty is statistical and the second is systematic. This work provides a basis for future luminosity measurements at Belle II.
A tunable continuous-wave terahertz generator based on 1.3-μm dual-mode laser diode and travelling-wave photodiode (2013)

We demonstrate the tunable continuous-wave (CW) terahertz generator based on the &lambda;/4 phase-shifted 1.3 &mu;m dual-mode laser diode (DML) and travelling-wave photodiode (TWPD). The DML and TWPD operate as an optical beat source and terahertz photomixer, respectively. The laser diodes (LDs) operating at the 1.3 &mu;m have more suitable characteristics as optical beat sources than the LDs operating at 1.55 &mu;m because of their high efficiency and better thermal stability. The micro-heaters are integrated on top of each DFB LD for mode beat frequency tuning. The fabricated DML was continuously tuned from 230 GHz to 1485 GHz by increasing the temperature of each DFB section independently via integrated micro-heaters. The high-speed TWPD with an InGaAs absorber was designed and fabricated to efficiently generate the photomixing terahertz CW. A complementary log-periodic antenna was integrated with the TWPD to radiate the generated terahertz wave with minimum reflection in the wide frequency range. The terahertz characteristics of the tunable CW terahertz generator based on the DML and TWPD were measured in a fiber-coupled, homodyne terahertz photomixing system. Our results of the tunable CW terahertz generator show the feasibility of a compact and highly efficient CW terahertz spectrometer and imager.
Dystrophin restoration therapy improves both the reduced excitability and the force drop induced by lengthening contractions in dystrophic mdx skeletal muscle (2016)

We demonstrated for the first time that (i) the increased susceptibility to contraction-induced muscle injury in mdx mice is mainly attributable to reduced muscle excitability; (ii) dystrophin-based therapy improves fragility of the dystrophic skeletal muscle by preventing reduction in muscle excitability.
Adaptive window excitation coding in low-bit-rate CELP coders (2000)

A new paradigm for efficient coding of the fixed-codebook excitation in CELP coders at low-bit rates is presented. In this scheme, the non-zero components of the fixed-codebook excitation are localized to a set of windows whose locations are dependent on the pitch frequency and on the energy contour of a modified residual signal. Highly efficient coding is thus achieved by allocating most of the fixed excitation bits to capture the essential excitation events. The paradigm is validated by computer simulation of a variable-rate speech codec. The performance of the codec is evaluated by informal subjective tests comparing it with TIA standard variable rate speech codecs. The results confirm that the proposed scheme can be used to reproduce speech at average bit rates from 2.3 to 3.4 kbps with very high quality and intelligibility.
T-helper cell responses to HIV envelope peptides in cord blood: protection against intrapartum and breast-feeding transmission (2001)

T-helper cell responses to HIV envelope peptides were detected in more than one-third of newborns of HIV-infected women; no new infections were acquired by these infants at the time of delivery or post-natally through breast-feeding if these T-helper cell responses were detected in cord blood.
Hexrotor UAV platform enabling dextrous interaction with structures-flight test (2013)

In this paper, we present the development of Dexterous Hexrotor, a hexrotor UAV platform with canted thrusters, enabling dexterous interaction with structures. Aerial mobile manipulation is an emerging niche in the field of mobile manipulation. Although there has been a fair amount of study of free-flying satellites with graspers and yielded impressive results, it is hampered a lack of appropriate testbeds for aerial mobile manipulation. Typical helicopters or quadrotors cannot instantaneously resist or apply an arbitrary force in the plane perpendicular to the rotor axis. They lack of force closure (a term from the dexterous manipulation community), which makes them inadequate for complex mobile manipulation tasks. The Collaborative Mechatronics Lab is addressing this instrumentation gap with the development of Dexterous Hexrotor to eventually host a low-cost, lightweight Stewart-Gough platform that can be combined as a macro/micro mobile manipulation system. Based on the concept of force closure, the new type of 6 DoFs hexrotor UAV provides the unique capability of being able to resist any applied wrench, or generalized force-torque. In this paper, we describe how Dexterous Hexrotor provides this important capability. We also describe the flight test which Dexterous Hexrotor is exhibiting holonomic behavior.
Mannan‐binding lectin deficiency modulates the humoral immune response dependent on the genetic environment (2008)

Mannan-binding lectin (MBL) is a plasma protein implicated in innate immune defence against a broad range of microorganisms, including viruses. It is also thought that MBL plays a role in the recruitment of the specific clonal immune response. This was studied by injecting soluble hepatitis B surface antigen (HBsAg) intravenously into mice deficient in both MBL-A and MBL-C (MBL DKO mice). The MBL DKO animals on mixed genetic background (SV129EvSv x C57BL/6) produced higher antibody titres than the wild-type littermates. After primary challenge with the antigen the immunoglobulin M anti-HBsAg antibody titres were threefold higher in the MBL DKO mice than in the wild-type mice. Following the boost, the immunoglobulin G anti-HBsAg antibody titres were 10-fold higher in the MBL DKO mice, suggesting that MBL plays a role in a negative feedback regulation of adaptive immunity. However, the modulating effect of MBL was dependent on the genetic environment. The MBL DKO mice backcrossed on a C57BL/6 background showed the opposite response with the MBL DKO mice now producing fewer antibodies than the wild-type animals, whereas MBL deficiency in mice with the SV129EvSv background did not show any effect in antibody production. These findings indicate that the modifying effect of MBL on the humoral immune response is influenced by the genetic environment.
High-Density Polyethylene Piping Butt-Fusion Joint Examination Using Ultrasonic Phased Array (2010)

With the increasing use of high-density polyethylene (HDPE) piping for nuclear applications, nondestructive evaluation is an important tool for evaluation of the integrity in fused joints. This paper will discuss the method of using ultrasonic phased array for inspecting butt-fusion (BF) joints in HDPE piping. The benefit of phased array is the ability to perform a volumetric inspection using multiple angles, which greatly increases the probability of detection of defects and allows the data to be analyzed using a representative two-dimensional image of the joint. It has been determined that successfully producing BF joints is highly dependent on environmental and mating-surface conditions. The primary defects of concern are lack-of-fusion, an area of the joint where there is no bond, cold fusion, an area of partial bond, and inclusion. Phased array has successfully demonstrated the ability of detecting and characterizing these defects using low frequency ultrasound. Factors addressed include joint location, wall thickness, material temperature, transducer wedge material, and manual versus automated data acquisition.
High-efficiency hybrid III&amp;#x2013;V/Si external cavity DBR laser for 3-&amp;#x00B5;m SOI waveguides (2012)

We report a 9.5% wall-plug-efficient un-cooled external-cavity DBR laser built with a III-V-semiconductor reflective-SOA edge-coupled to an SOI waveguide containing a Bragg grating mirror. The hybrid laser is suitable for power efficient, CMOS-compatible optical transmitters.
Zr(IV), Ti(IV), and V(III) complexes of some benzimidazole, benzothiazole, and benzoxazole ligands: characterization and catalyst efficiency in ethylene polymerization (2016)

Fifteen complexes of 2, 2-bis- (benzimidazole, benzothiazole, and benzoxazole) compounds with Zr(IV), Ti(IV), and V(III) metal centers were synthesized, characterized, activated with methyalumoxane (MAO), and then tested for catalytic ethylene polymerization. The activities of the various catalysts were found to be functions of the hetero atoms in the ligand frameworks. The activity of the catalyst system \textbf{6}/MAO was found to be 1372 kg PE/mol cat. h. The polyethylene produced with the catalyst system 6/MAO showed high molecular weights (1.84 $\times $ 10$^{6}$ g/mol) and broad molecular weight distributions (PD = 11). This could result from different interactions of the MAO counter ion with the heteroatoms of the catalyst ligand generating different active sites. The effect of the polymerization temperature of the polymers produced with catalyst 6/MAO was also investigated.
Characterising resistance to fatigue crack growth in adhesive bonds by measuring release of strain energy (2016)

Measurement of the energy dissipation during fatigue crack growth is used as a technique to gain more insight into the physics of the crack growth process. It is shown that the amount of energy dissipation required per unit of crack growth is determined by Gmax, whereas the total amount of energy available for crack growth in a single cycle is determined by (Δ √g)2.
ChemInform Abstract: Development of Highly Selective Organic Reactions Catalyzed by Designed Amine Organocatalysts (2011)

Abstract Review: 113 refs.
Six‐Membered Ring Systems: Pyridines and Benzo Derivatives (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
COBRA: A Parallelizable Authenticated Online Cipher Without Block Cipher Inverse (2014)

Abstract. We present a new, misuse-resistant scheme for online authen-ticated encryption, following the framework set forth by Fleischmann et al. (FSE 2012). Our scheme, COBRA, is roughly as efficient as the GCM mode of operation for nonce-based authenticated encryption, perform-ing one block cipher call plus one finite field multiplication per message block in a parallelizable way. The major difference from GCM is that COBRA preserves privacy up to prefix under nonce repetition. However, COBRA only provides authenticity against nonce-respecting adversaries. As compared to COPA (ASIACRYPT 2013), our new scheme requires no block cipher inverse and hence enjoys provable security under a weaker assumption about the underlying block cipher. In addition, COBRA can possibly perform better than COPA on platforms where finite field mul-tiplication can be implemented faster than the block cipher in use, since COBRA essentially replaces half of the block cipher calls in COPA with finite field multiplications.
Analyse fonctionnelle du promoteur du gène codant le recepteur du GnRH de rat (2001)

Le GnRH, un neuropeptide hypothalamique, interagit avec son recepteur antehypophysaire, le R-GnRH, pour stimuler la synthese et la secretion des gonadotrophines LH et FSH, qui regulent fonction gonadique. Plusieurs hormones, dont le GnRH, modulent le niveau d'expression du gene du R-GnRH. Afin d'elucider les bases moleculaires de la regulation transcriptionnelle de ce gene, nous avons clone chez le rat 3,3 kb de sa region 5'-flanquante, puis localise les sites d'initiation de transcription hypophysaires. Les experiences de transfection transitoire dans les lignees gonadotropes αT3-1 et Lβ3T2 demontrent l'existence d'un enhancer distal (GnSE) induisant une activite maximale uniquement dans contexte du promoteur proximal de 500 pb. De nouvelles analyses, completees par des experiences gel-retard, ont revele que le GnSE comporte 2 elements actifs qui lient respectivement des facteurs apparentes a LIM et GATA, et que son activite est relayee par une sequence proximale restreinte a 50 pb, incluant un site SF-1 fonctionnel. Nous avons egalement demontre l'activation via la voie dependante de l'AMPc du promoteur du R-GnRH par le PACAP (pituitary adenylate cyclase-activating polypeptide), un peptide hypophysiotrope. En attestent les effets mimetiques des activateurs de cette voie, ainsi que l'inhibition de cette stimulation par sur-expression du PKI, un inhibiteur de la PKA. L'element de reponse au PACAP est bipartite, avec une premiere region (PARE 1), comprenant SF-1, et une deuxieme (PARE II) liant une proteine de type CREB (CRE-binding protein). Des facteurs inconnus se lient aussi a PARE I et semblent interagir avec la proteine SF-1. Nos travaux etablissent le role substantiel de SF-1, a la fois dans l'expression constitutive du gene R-GnRH en tant que mediateur d'une activite enhancer, et dans sa regulation par le PACAP via la voie des PKA. L'approche par transgenese initiee au laboratoire devra permettre de suivre son expression hypophysaire ou non, au cours du developpement et dans des situations physiologiques determinantes.
Phase I study of interleukin-2 and interferon alfa-2a as outpatient therapy for patients with advanced malignancy. (1990)

Twenty-six patients were treated in this phase I study with the combination of interleukin-2 (IL2) administered as a continuous infusion and interferon alfa-2a (IFN alpha-2a) administered intramuscularly to patients in an outpatient setting. The maximum-tolerated dose of both agents given as outpatient therapy was 2 x 10(6) U/m2 days 1 to 5 of IL2 and 9 x 10(6) U/m2 days 1, 3, and 5 of IFN alpha-2a for 4 consecutive weeks. A 2- to 4-week rest period was permitted after each 4 weeks of treatment. Fatigue was the treatment-limiting toxicity, and serious clinical or laboratory abnormalities occurred infrequently during this study. Patients with colon cancer metastatic to the liver tolerated treatment worse than patients with other tumors. Twelve of the 15 patients with renal cell cancer were assessable for response determinations. Of these 12 patients, three exhibited complete tumor regression, three have had partial objective regression, and three patients experienced stabilization of rapidly progressive disease. This therapy appears to be well tolerated in an outpatient treatment setting and shows significant activity against advanced renal cell cancer.
Questionnaire to nephrologists: Withdrawal from hemodialysis in a patient in the terminal stage of malignancy. (2003)

本邦では, 透析患者の終末期において, 血液透析 (HD) が安定して施行できている患者の自己決定を尊重し, HDを中止することについての生命倫理学的研究は殆どない. 今回, われわれは, 透析医 (552名) を対象として, 安定したHDを受けている悪性腫瘍終末期症例を提示し, いくつかのシナリオに対して, HDを中止するか, 継続するかの意識調査と, advance directives (AD), 尊厳死, 尊厳生についてどのように考えているかの意識調査を全国的規模で行った.434名 (78.6%) から回答が得られたが, 有効回答は427名 (77.4%) であった. ADおよび尊厳死が法的に認められていない現状において, ADの有無で比較すると, (1) 家族がHD中止を申し出た場合, (2) 家族がHD継続を申し出た場合とも, ADがあるとHDを中止する回答は有意に増加した ((1) 48.0%→78.9%, (2) 0.2%→2.6%). さらに延命療法を中止しても法的責任は問われないと仮定すると, ADがあるとさらにHDを中止する回答は増加した ((1) 90.9%, (2) 11.9%). ADと尊厳死を必要であると回答した透析医はそれぞれ74.0%, 83.1%であったが, 法制化も必要と回答した透析医は56.4%, 63.7%に減少した. 尊厳死と尊厳生の比較では, 尊厳生を支持する透析医は, 尊厳死を支持する透析医よりも多かった (47.1%, 15.9%).今回の結果は, 現状でも, 透析医および家族が患者の自己決定を尊重すると, ADによる尊厳死が行われる可能性があることを示唆し, 多くの透析医がADや尊厳死を必要と考えている. 一方, 尊厳生は人間にとって非常に大切なことであり, 尊厳死よりもこの言葉を支持する透析医が多かったと考える. すべての国民は個人として生きる権利を認められており, 本邦では, 終末期にも自分が考える尊厳ある生き方を貫くということから始め, 家族および社会が納得する範囲で, 先ず尊厳生によるADが自己決定のために重要であると認識させる努力をすべきである.
A Splitting-Based Iterative Algorithm for GPU-Accelerated Statistical Dual-Energy X-Ray CT Reconstruction (2020)

When dealing with material classification in baggage at airports, Dual-Energy Computed Tomography (DECT) allows characterization of any given material with coefficients based on two attenuative effects: Compton scattering and photoelectric absorption. However, straightforward projection-domain decomposition methods for this characterization often yield poor reconstructions due to the high dynamic range of material properties encountered in an actual luggage scan. Hence, for better reconstruction quality under a timing constraint, we propose a splitting-based, GPU-accelerated, statistical DECT reconstruction algorithm. Compared to prior art, our main contribution lies in the significant acceleration made possible by separating reconstruction and decomposition within an Alternating Direction Method of Multipliers (ADMM) framework. Experimental results, on both synthetic and real-world baggage phantoms, demonstrate a significant reduction in time required for convergence.
Optical Polymer Having a High Refractive Index and High Abbe Number Prepared by Radical Polymerization Using 2,5-BiS(2-Thia-3-Butenyl)-1,4-Dithiane (1998)

Abstract Novel poly(vinylsulfide)s were prepared by addition polymerization using 2,5-bis(2-thia-3-butenyl)-1,4-dithiane (TBD) with a radical initiator for an optical polymer having a high refractive index (nD) and Abbe number (v). Homopolymerization of TBD (72.9% conversion) and copolymerization with acrylonitrile or acrylates having nonpolar groups (50.4–81.3% conversion according to the comonomers used) in a limited composition range yielded hard and transparent polymers suitable for application in optics. The methacrylates used yielded no polymeric product as a result of the copolymerization. The obtained polymers had Tg, nD and v ranging between 41.0–124.0°C, 1.678–1.546 and 34.1–43.8, respectively, except that poly(TBD) did not exhibit Tg below 200°C, and it had the highest nD Most of the polymers have higher nD and v than those of other conventional optical polymers and moreover, their values are comparable to those of flint glasses. The copolymerizability of TBD and the group contribution to nD and v are discussed based on the Q-e scheme and on the Lorentz-Lorenz equation, respectively. This work shows that TBD serves as a useful material for the preparation of polymers having high nD and v along with a Tg of more than 100°C, and that the polymers thus obtained are promising optical materials.