gebhart/patrepeval huggingface dataset:
Limiting the Testing of Aspartate Aminotransferase: Using the Proper Upper Limit of the Reference Interval of Alanine AminotransferaseThe Authors’ Reply (2016)

Limiting the Testing of AST: A Diagnostically Nonspecific Enzyme," in which the authors claimed that only aspartate aminotransferase (AST) could be measured when alanine aminotransferase (ALT) exceeds a predetermined limit, and so a substantial health care budget could be saved. That is a great idea. However, some questions need to be clarified about this article. According to the description in the Materials and Methods section, the objects tested were in the city of Edmonton, which is the capital of Alberta, Canada. However, the upper limit of the reference interval (ULRI) of ALT 1,2 (30 U/L) used in the article came from Italy. Our questions are as follows: (1) is the ULRI used in this article suitable to evaluate the objects? and (2) why did the authors not use the reference intervals of ALT 3 that have been generated from the local area? In addition, we found that only the reference intervals of AST were cited in the article but not that of ALT.
Physical Layer Security in Cooperative NOMA Hybrid VLC/RF Systems (2020)

Integrating visible light communication (VLC) and radio-frequency (RF) networks can improve the performance of communication systems in terms of coverage and data rates. However, adding RF links to VLC networks weakens the secrecy performance due to the broadcast and ubiquitous nature of RF links. This paper studies the physical layer security (PLS) in cooperative non-orthogonal multiple access (CoNOMA) hybrid VLC/RF systems. Consider a VLC system, where two entrusted users close to a VLC access point (AP) help an out-of-coverage legitimate user using RF signals in the presence of an eavesdropper. The AP transmits data to both entrusted users and the legitimate user using the principle of NOMA, where the entrusted users harvest energy from the received light intensity, decode the legitimate user's message, forward it using a RF link, and then decode their messages. It is required to maximize the secrecy rate at the legitimate user under quality-of-service (QoS) constraints using beamforming and DC-bias and power allocation. Different solutions are proposed for both active and passive eavesdropper cases, using semidefinite relaxation, zero-forcing, beamforming, and jamming. Numerical results compare between the different proposed approaches and show how the proposed approaches contribute in improving the secrecy performance of the proposed model.
Cryogenic Operation of Silicon Photonic Modulators (2012)

For the first time, simulation and operation of a silicon photonic modulator are demonstrated at cryogenic temperatures. The device operated at 5Gbps and 10Gbps at a temperature of 115K opening application areas in harsh environments.
First-in-human study of MM-141: A novel tetravalent monoclonal antibody targeting IGF-1R and ErbB3. (2014)

3068^ Background: MM-141 is a novel tetravalent bi-specific monoclonal antibody that binds IGF-1R and ErbB3, and blocks both ligand dependent and independent IGF-1R/ErbB3/PI3K/AKT/mTOR signaling. In preclinical xenograft models, MM-141 was more active than a combination of anti-ErbB3 and anti-IGF-1R monoclonal antibodies. MM-141 potentiated the activity of gemcitabine, paclitaxel, docetaxel, tamoxifen, and everolimus. These results support the clinical development of MM-141 and a multi-arm Phase 1 study is underway. The completed monotherapy arm of this trial will be reported Methods: This is a Phase 1 dose-escalation study evaluating safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) properties of MM-141 as monotherapy (Arm A, n=15) and in combination with everolimus (Arm B) or with nab-paclitaxel and gemcitabine (Arm C). Patients in Arm A were dosed in a “3+3” design at weekly doses of 6 mg/kg (n=3), 12 mg/kg (n=4), or 20 mg/kg (n=4), or at biweekly doses of 40 mg/kg (n=4). Doses were escalated until the maximum tolerated dose (MTD) was identified, or until MM-141 was shown to be tolerable at the highest planned dose. Results: Arm A enrolled 15 patients with advanced solid tumors into the dose escalation portion of the study. No dose-limiting toxicities were observed at weekly dose levels of 6mg/kg, 12mg/kg, and 20mg/kg, or at the biweekly dose of 40mg/kg. Adverse events, regardless of relationship, that were reported with a frequency >15% included: vomiting (7/15), nausea (6/15), fatigue (4/15), abdominal pain (4/15), increased AP (4/15), dyspnea (4/15), diarrhea (3/15), anemia (3/15), increased AST (3/15), and rash (3/15). The safety, tolerability, PK and PD profile support weekly and biweekly MM-141 dosing. Detailed PK and PD data will be presented for all cohorts. Disease stabilization was observed in patients with Ewing’s Sarcoma (1) and parotid gland carcinoma (1). An expansion cohort at a weekly dose of 20mg/kg (Arm D) is ongoing in patients with hepatocellular carcinoma. Data summarized here are from a data lock at 01/15/2014. Conclusions: A recommended dose level for MM-141 on each of weekly and bi-weekly schedules was established. Clinical trial information: NCT01733004.
African Environmental Ethics: Keys to Sustainable Development Through Agroecological Villages (2021)

This essay proposes African-based ethical solutions to profound human problems and a working African model to address those problems. The model promotes sustainability through advanced agroecological and information communication technologies. The essay's first section reviews the ethical ground of that model in the work of the Senegalese scholar, Cheikh Anta Diop. The essay's second section examines an applied African model for translating African ethical speculation into practice. Deeply immersed in European and African ethics, Godfrey Nzamujo developed the Songhaï Centers to solve the problem of rural poverty in seventeen African countries. Harnessing advanced technologies within a holistic agroecological ecosystem, Nzamujo's villages furnish education spanning the fields of ethics, information communication technology, microbiology, international development, and mechanical, electrical, civil and biological engineering in a community-based and centered development enterprise. The essay proposes a global consortium of ecovillages based on Nzamujo's model. The final section explores funding methods for the consortium. The conclusion contemplates a return to Africa to supplement environmental ethics that enhance life's future on earth.
Detecting Insect Flight Sounds in the Field: Implications for Acoustical Counting of Mosquitoes (2007)

A prototype field-deployable acoustic insect flight detector was constructed from a noise-canceling microphone coupled to an off-the-shelf digital sound recorder capable of 10 h recordings. The system was placed in an urban forest setting 25 times over the course of the summer of 2004, collecting 250 h of ambient sound recordings that were downloaded to a personal computer and used to develop detection routines. These detection routines operated on short segments of sound (0.093 s, corresponding to 4096 samples at 44100 Hz). A variety of approaches were implemented to detect insect flight tones. Simple approaches, involving sensing the fundamental frequency (1st harmonic) and 2nd harmonic, were capable of detecting insects, but generated large numbers of false positives because of other ambient sounds including human voices, birds, frogs, automobiles, aircraft, sirens, and trains. In contrast, combining information from the first four harmonics, from the interharmonic regions, and from the sound envelope, reduced false positives greatly. Specifically, in the 250 h of recordings, 726 clear insect buzzes were detected by the final algorithm, with only 52 false positives (6.5%). Running the final algorithm with all criteria liberalized by 20% increased the number of clear insect buzzes by 8%, to 784, but increased false positives to 471 (28% of total detections). The potential of using this approach for detecting mosquito activity using low-cost sensors is discussed.
Determining the Dispersive Features of Nanophotonic Structures Based on Hybrid FEM/TMM Technique (2019)

Determining the dispersion relation of nanophotonic structures is one of the biggest challenges especially for nano-scale inhomogeneous structures where several efforts have been directed. Here, we present a technique that leverages the accuracy and simplicity of the combination of transfer matrix method (TMM) and finite element method (FEM). This hybrid technique allows us to find the spatial dispersion, coupling strength and nature of the generated modes.
Stability of Poly(amide acid) Solutions (1998)

Aging characteristics of four poly(amide acid) solutions were followed using gel permeation chromatography. NASA LaRC(Tm) PETI-5 was found to be the most stable over a period of about 270 days.
Practical authenticated pattern matching with optimal proof size (2015)

We address the problem of authenticating pattern matching queries over textual data that is outsourced to an untrusted cloud server. By employing cryptographic accumulators in a novel optimal integrity-checking tool built directly over a suffix tree, we design the first authenticated data structure for verifiable answers to pattern matching queries featuring fast generation of constant-size proofs. We present two main applications of our new construction to authenticate: (i) pattern matching queries over text documents, and (ii) exact path queries over XML documents. Answers to queries are verified by proofs of size at most 500 bytes for text pattern matching, and at most 243 bytes for exact path XML search, independently of the document or answer size. By design, our authentication schemes can also be parallelized to offer extra efficiency during data outsourcing. We provide a detailed experimental evaluation of our schemes showing that for both applications the times required to compute and verify a proof are very small---e.g., it takes less than 10μs to generate a proof for a pattern (mis)match of 10 2 characters in a text of 10 6 characters, once the query has been evaluated.
Influence of the emitter coverage on interdigitated back contact (IBC) silicon heterojunction (SHJ) solar cells (2014)

Modelling and experimental results on IBC SHJ solar cells are presented in this paper. Different rear emitter designs are studied by 2D simulation and tested on experimental devices. IBC SHJ cells are fabricated with the SLASH process based on laser patterning steps, and the performance of such devices is shown to be limited by the rear emitter geometry (contacting scheme and total emitter fraction). On one hand IBC SHJ cells have to be carefully designed concerning the contacting scheme due to distributed series resistance effects. On the other hand SHJ technology allows a very high surface passivation level, and this reduces the influence of the emitter fraction on the cells performances.
Influence of hemoglobin vesicles, cellular‐type artificial oxygen carriers, on human umbilical cord blood hematopoietic progenitor cellsin vitro (2008)

Hemoglobin vesicles (HbVs), liposomal oxygen carriers containing human hemoglobin, are candidates for development as clinically useful blood substitutes. Although HbVs are shown to distribute transiently into the bone marrow in animal models, the influence of HbVs on human hematopoietic stem/progenitor cells has not yet been studied. Therefore, we investigated the influence of HbVs at a concentration of up to 3 vol/vol % on the clonogenic activity (in semisolid culture) and proliferative activity (in liquid culture) of human hematopoietic progenitor cells derived from umbilical cord blood (CB) in vitro. Continuous exposure of CB mononuclear cells to HbVs tended to decrease the number and size of mature-committed colonies and most notably reduced the number of colonies of high-proliferative potential colony-forming cells (HPP-CFC). In contrast, exposure to HbVs for 20 h or 3 days, which is more relevant to the clinical setting, had no effect on the number of mature-committed colonies and only modestly decreased the number of HPP-CFC. Continuous exposure (10 days) to HbVs significantly suppressed the cellular proliferation and differentiation of both the erythroid and myeloid lineages in liquid culture. Again, short exposure (20 h or 3 days) did not affect these parameters. Thus, our results show that HbVs, under conditions relevant to the clinical setting, have no adverse effect on human CB hematopoietic progenitor activity in vitro.
An Efficient and Stereoselective Synthesis of the Monomeric Counterpart of Marinomycin A (2007)

[structure: see text] The monomeric counterpart of marinomycin A, an antitumor-antibiotic marine natural product, was synthesized efficiently in 11 steps from the commercially available ethyl (R)-(-)-3-hydroxybutyrate. The strategy was highlighted by a crucial regio- and stereoselective cross-metathesis to form the C20-C21 double bond, enantioselective allyltitanations to control the configuration of the C17, C23, and C25 stereogenic centers, and a stereocontrolled construction of the tetraene moiety based on an original Horner-Wadsworth-Emmons olefination followed by a Pd-catalyzed cross-coupling.
Single‐Molecule Enzymology for Diagnostics: Profiling Alkaline Phosphatase Activity in Clinical Samples (2021)

Abstract Enzymes can be used as biomarkers for a variety of diseases. However, profiling enzyme activity in clinical samples is challenging due to the heterogeneity in enzyme activity, and the low abundance of the target enzyme in biofluids. Single‐molecule methods can overcome these challenges by providing information on the distribution of enzyme activities in a sample. Here, we describe the concept of using the single‐molecule enzymology (SME) method to analyze enzymatic activity in clinical samples. We present recent work focused on measuring alkaline phosphatase isotypes in serum samples using SME. Future work will involve improving and simplifying this technology, and applying it to other enzymes for diagnostics.
Impact-Enhanced Multi-Beam Piezoelectric Converter for Energy Harvesting in Autonomous Sensors (2012)

This work proposes and experimentally validates a piezoelectric vibration energy harvester, which exploits the impact of a central compliant driving beam onto two piezoelectric parallel bimorph beams on flexible steel. At suitable mechanical excitation conditions, the central driving beam impacts the piezo beams and triggers a nonlinear frequency-up conversion mechanism that improves the overall effectiveness, i.e. increases the overall rms output voltage and widens the equivalent bandwidth of the converter with respect to the condition of the noninteracting linear converters.
Lysosome and HER3 (ErbB3) Selective Anticancer Agent Kahalalide F:  Semisynthetic Modifications and Antifungal Lead-Exploration Studies (2007)

Kahalalide F (1) shows remarkable antitumor activity against different carcinomas and has recently completed phase I clinical trials and is being evaluated in phase II clinical studies. The antifungal activity of this molecule has not been thoroughly investigated. In this report, we focused on acetylation and oxidation of the secondary alcohol of threonine, as well as reductive alkylation of the primary amine of ornithine, and each product was evaluated for improvements in antifungal activity. 1 and analogues do not exhibit antimalarial, antileishmania, or antibacterial activity; however, the antifungal activity against different strains of fungi was particularly significant. This series of compounds was highly active against Fusarium spp., which represents an opportunistic infection in humans and plants. The in vitro cytotoxicity for the new analogues of 1 was evaluated in the NCI 60 cell panel. Analogue 5 exhibited enhanced potency in several human cancer cell lines relative to 1.
An integrated computational pipeline for designing high-affinity nanobodies with expanded genetic codes (2021)

Protein engineering and design principles employing the 20 standard amino acids have been extensively used to achieve stable protein scaffolds and deliver their specific activities. Although this confers some advantages, it often restricts the sequence, chemical space, and ultimately the functional diversity of proteins. Moreover, although site-specific incorporation of non-natural amino acids (nnAAs) has been proven to be a valuable strategy in protein engineering and therapeutics development, its utility in the affinity-maturation of nanobodies is not fully explored. Besides, current experimental methods do not routinely employ nnAAs due to their enormous library size and infinite combinations. To address this, we have developed an integrated computational pipeline employing structure-based protein design methodologies, molecular dynamics simulations and free energy calculations, for the binding affinity prediction of an nnAA-incorporated nanobody toward its target and selection of potent binders. We show that by incorporating halogenated tyrosines, the affinity of 9G8 nanobody can be improved toward epidermal growth factor receptor (EGFR), a crucial cancer target. Surface plasmon resonance (SPR) assays showed that the binding of several 3-chloro-l-tyrosine (3MY)-incorporated nanobodies were improved up to 6-fold into a picomolar range, and the computationally estimated binding affinities shared a Pearson's r of 0.87 with SPR results. The improved affinity was found to be due to enhanced van der Waals interactions of key 3MY-proximate nanobody residues with EGFR, and an overall increase in the nanobody's structural stability. In conclusion, we show that our method can facilitate screening large libraries and predict potent site-specific nnAA-incorporated nanobody binders against crucial disease-targets.
Structure of murine Tcl1 at 2.5 Å resolution and implications for the TCL oncogene family (2001)

Tcl1 and Mtcp1, members of the Tcl1 family, are implicated in T-cell prolymphocytic leukemia. The crystal structure of a dimer of murine Tcl1 has been determined at 2.5 A resolution with an R factor of 0.225. Murine Tcl1, human Tcl1 and Mtcp1 share very similar subunit structures, with RMS differences of 0.6 and 1.4 A for C(alpha) atoms, respectively, while the sequences share 50 and 36% identity, respectively. These structures fold into an eight-stranded beta-barrel of unique topology and high internal symmetry of 1.1-1.3 A for the two halves of human and murine Tcl1 and 1.7 A for Mtcp1, despite the low 12-13% sequence identity. The molecular surfaces of all three structures showed a common planar region which is likely to be involved in protein-protein interactions.
Effects of volume expansion and parathyroid hormone on total renal blood flow and its intracortical distribution. (1977)

Clearance and renal blood flow studies were performed during hydropenia, 2.5 and 10 percent steady-state saline expansion, and acute administration of parathyroid hormone (PTH) in chronically thyroparathyroidectomized (TPTX) dogs and during hydropenia and 10 percent expansion in intact dogs. Renal cortical blood flow distribution was measured with radioactive microspheres In TPTX dogs, 2.5 percent expansion increased sodium excretion but did not alter total or intracortical blood flow. With 10 percent expansion, sodium excretion and juxtamedullary (zone 4) blood flow increased in both TPTX and intact dogs. There was no correlation between the changes in sodium excretion and zone 4 fractional blood flow in either group. Although the acute administration of PTH to TPTX dogs did not alter total or intracortical blood flow, control period hemodynamic data revealed an inner shift of flow in TPTX as compated to intact dogs.These results indicate that (1) massive (10 percent), but not mild (2.5 percent), volume expansion produces an inner shift of cortical blood flow; (2) this shift does not correlate with sodium excretion, nor is it influenced by thyroparathyroidectomy: and (3) PTH does not acutely alter renal blood flow distribution, but its chronic absence is associated with a shift of flow to the inner cortex.
How the European Union manages an apostate member in times om crisis : Examination of the Euro crisis management and Greek austerities (2016)

How the European Union manages an apostate member in times om crisis : Examination of the Euro crisis management and Greek austerities
Long-range surface plasmon resonance sensor with liquid micro-channels to maintain the symmetry condition of the refractive index (2010)

We propose a method to maintain the symmetry of the refractive index with respect to an Au film, in which the refractive indices are the same near both surfaces of the Au film, for LRSPR (long-range surface plasmon resonance) sensors. Maintenance of the symmetry is necessary for exciting the LRSPR mode. However, because the buffer layer under the Au film is usually made of a solid dielectric material with a constant refractive index, the quality of the measurement is reduced when the refractive index of the analyte used is dramatically different from that of the buffer layer. To solve this problem, the proposed sensor is equipped with liquid channels under the Au film. The Au film used in this study was supported by a thin (100 nm) polymer film forming parallel, one-dimensional liquid channels with a 29 µm pitch. Because the analyte solution flows in the channels, both surfaces of the Au film face the same analyte. Thus, this configuration automatically satisfies the symmetry condition for analytes with a wide range of refractive indices. We examined the validity of the sensor and compared it to that of a conventional sensor by measuring the LRSPR for five analyte solutions with different refractive indices. LRSPR dips were clearly observed for all of the analytes tested. The dip of the conventional LRSPR sensor became shallow when the refractive index increased, with the final dip depth being 65% of the initial dip depth for a refractive index of 1.358. In contrast, the dip depth of the proposed LRSPR sensor remained constant over the entire measured refractive index range of 1.331 to 1.358. These results indicate that the proposed sensor maintains the symmetry condition and confirm that the proposed method is effective for highly sensitive LRSPR measurements for a wide variety of analyte species.
Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption (2011)

Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of approximately 2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 x 10(-8) to P = 4 x 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P &lt; 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P &lt; 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.