gebhart/patrepeval huggingface dataset:
Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies (2020)

BackgroundSleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.MethodsThe Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.Findings/ConclusionPafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3.Author SummarySleeping sickness (human African trypanosomiasis [HAT]) is caused by parasites, and has a chronic progressive course that may last from several months to several years before death occurs. The present studies were done to assess the effectiveness and safety of oral pafuramidine versus intramuscular pentamidine (the standard treatment), in patients with first stage HAT. The results indicated that, several months after treatment, pafuramidine administered for 10 days was as effective as pentamidine administered for 7 days, and it had a better safety profile than pentamidine. With further study, pafuramidine could be a promising alternative for patients with first stage HAT. In addition, the design of the studies can be used a guide for future studies for identification and delivery of treatment to affected individuals in rural Africa.
Leukocyte population dynamics in response to ovalbumin peptide immunization in DO11 mice (2007)

DO11 mice are transgenic mice, which have a T cell receptor (TCR) capable of specifically recognizing the protein ovalbumin. CD4 and CD8 T lymphocytes carrying this TCR be easily traced, making these mice a useful animal model in which to follow an immune response. Injection of ovalbumin peptide in adjuvant initiates an immune response, leading to changes in the various lymphocyte subsets responding to the stimulus. We expected to see an increase in the number of effector cells shortly after immunization, followed by the development of an ovalbumin-specific memory population of CD4 lymphocytes over long term. In order to monitor the different leukocyte populations participating in the response, we used flow cytometry coupled with surface staining for relevant cell markers. As expected, effector cell numbers showed a statistically significant increase at the 10-day timepoint, although both ovalbumin specific and nonspecific cells responded. This may be due to addition of adjuvant. over a 6-month period, immediate effectors disappeared and most cell populations returned to baseline levels. However, we could not find a CD4 memory cell population in the spleen. In addition to T cell,s we also monitored changes in other leukocyte population that might participate in the immune response. Future aims are to examine the immune response to ovalbumin in PECAM deficient mice. PECAM is a cell adhesion molecule, which mediates several steps of the immune response. The data generated by this project in wild-type mice will be used as a control to data obtained in PECAM knockout mice in order to clarify the role of PECAM in inflammation.
A 3D photon superposition/convolution algorithm and its foundation on results of Monte Carlo calculations* (2005)

Based on previous publications on a triple Gaussian analytical pencil beam model and on Monte Carlo calculations using Monte Carlo codes GEANT-Fluka, versions 95, 98, 2002, and BEAMnrc/EGSnrc, a three-dimensional (3D) superposition/convolution algorithm for photon beams (6 MV, 18 MV) is presented. Tissue heterogeneity is taken into account by electron density information of CT images. A clinical beam consists of a superposition of divergent pencil beams. A slab-geometry was used as a phantom model to test computed results by measurements. An essential result is the existence of further dose build-up and build-down effects in the domain of density discontinuities. These effects have increasing magnitude for field sizes < or =5.5 cm(2) and densities < or = 0.25 g cm(-3), in particular with regard to field sizes considered in stereotaxy. They could be confirmed by measurements (mean standard deviation 2%). A practical impact is the dose distribution at transitions from bone to soft tissue, lung or cavities.
Bump-and-hole engineering of human polypeptide N-acetylgalactosamine transferases to dissect their protein substrates and glycosylation sites in cells (2023)

Despite the known disease relevance of glycans, the biological function and substrate specificities of individual glycosyltransferases are often ill-defined. Here, we describe a protocol to develop chemical, bioorthogonal reporters for the activity of the GalNAc-T family of glycosyltransferases using a tactic termed bump-and-hole engineering. This allows identification of the protein substrates and glycosylation sites of single GalNAc-Ts. Despite requiring transfection of cells with the engineered transferases and enzymes for biosynthesis of bioorthogonal substrates, the tactic complements methods in molecular biology. For complete details on the use and execution of this protocol, please refer to Schumann et al. (2020)<sup>1</sup>, Cioce et al. (2021)<sup>2</sup>, and Cioce et al. (2022)<sup>3</sup>.
Ultrafast optical switching and power limiting in intersubband polaritonic metasurfaces (2021)

Highly nonlinear optical materials with fast third-order nonlinear optical response are crucial for the operation of all-optical photonic devices, such as switches for signal processing and computation, power limiters, and saturable absorbers. The nonlinear response of traditional optical materials is weak, thus requiring large light intensities to induce significant changes in their properties. Here we show that optical control of the coupling rate in subwavelength patch antennas coupled to intersubband transitions in multi-quantum-well semiconductor heterostructures can provide a giant third-order nonlinear response, on the order of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"> <mml:msup> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mn>3.4</mml:mn> <mml:mo>×</mml:mo> <mml:mn>10</mml:mn> </mml:mrow> </mml:mrow> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mo>−</mml:mo> <mml:mn>13</mml:mn> </mml:mrow> </mml:msup> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:msup> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mi>m</mml:mi> </mml:mrow> </mml:mrow> <mml:mn>2</mml:mn> </mml:msup> </mml:mrow> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mo>/</mml:mo> </mml:mrow> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:msup> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mi mathvariant="normal">V</mml:mi> </mml:mrow> </mml:mrow> <mml:mn>2</mml:mn> </mml:msup> </mml:mrow> </mml:math> , with a response time <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mo>&lt;</mml:mo> </mml:mrow> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mn>2</mml:mn> </mml:mrow> </mml:mrow> <mml:mspace width="thickmathspace"/> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mi mathvariant="normal">p</mml:mi> <mml:mi mathvariant="normal">s</mml:mi> </mml:mrow> </mml:mrow> </mml:math> . We utilize this effect to realize intersubband polaritonic metasurfaces and demonstrate their operation as highly nonlinear saturable and reverse saturable absorbers, enabling optical power limiters and other elements for all-optical modulation and control. Our approach enables a plethora of compact, low-power, highly nonlinear devices with spectral, temporal, and structured wavefront responses tailored by design.
Mutation of GmIPK1 Gene Using CRISPR/Cas9 Reduced Phytic Acid Content in Soybean Seeds (2022)

Phytic acid (PA) acts as an antinutrient substance in cereal grains, disturbing the bioavailability of micronutrients, such as iron and zinc, in humans, causing malnutrition. <i>GmIPK1</i> encodes the inositol 1,3,4,5,6-penta<i>kis</i>phosphate 2-kinase enzyme, which converts <i>myo</i>-inopsitol-1,3,4,5,6-penta<i>kis</i>phosphate (IP<sub>5</sub>) to <i>myo</i>-inositol-1,2,3,4,5,6-hexakisphosphate (IP<sub>6</sub>) in soybean (<i>Glycine max</i> L.). In this study, for developing soybean with low PA levels, we attempted to edit the <i>GmIPK1 <i>gene</i></i> using the CRISPR/<i>Cas9</i> system to <i>introduce</i> mutations into the <i>GmIPK1</i> gene with guide RNAs in soybean (cv. Kwangankong). The <i>GmIPK1</i> gene was disrupted using the CRISPR/Cas9 system, with sgRNA-1 and sgRNA-4 targeting the second and third exon, respectively. Several soybean <i>Gmipk1</i> gene-edited lines were obtained in the T<sub>0</sub> generation at editing frequencies of 0.1-84.3%. Sequencing analysis revealed various indel patterns with the deletion of 1-9 nucleotides and insertions of 1 nucleotide in several soybean lines (T<sub>0</sub>). Finally, we confirmed two sgRNA-4 <i>Gmipk1</i> gene-edited homozygote soybean T<sub>1</sub> plants (line #21-2: 5 bp deletion; line #21-3: 1 bp insertion) by PPT leaf coating assay and PCR analysis. Analysis of soybean <i>Gmipk1</i> gene-edited lines indicated a reduction in PA content in soybean T<sub>2</sub> seeds but did not show any defects in plant growth and seed development.
Improving Chinese/English OCR performance by using MCE-based character-pair modeling and negative training (2004)

In the past several years, we've been developing a high performance OCR engine for machine printed Chinese/ English documents. We have reported previously (1) how to use character modeling techniques based on MCE (minimum classification error) training to achieve the high recognition accuracy, and (2) how to use confidence-guided progressive search and fast match techniques to achieve the high recognition efficiency. In this paper, we present two more techniques that help reduce search errors and improve the robustness of our character recognizer. They are (1) to use MCE-trained character-pair models to avoid error-prone character-level segmentation for some trouble cases, and (2) to perform a MCE-based negative training to improve the rejection capability of the recognition models on the hypothesized garbage images during recognition process. The efficacy of the proposed techniques is confirmed by experiments in a benchmark test.
Novel heteroaromatic-based multi-branched dyes with enhanced two-photon absorption activityElectronic supplementary information (ESI) available: Experimental section. See http://www.rsc.org/suppdata/cc/b3/b305995b/ (2003)

The first examples of heterocycle-based multi-branched dyes with efficient two-photon absorption (TPA) activity are reported; the novel chromophores exhibit large TPA cross sections (as high as 1600 x 10(-50) cm4 s photon(-1) molecule(-1), measured with 150 fs laser pulses at 800 nm); a strong cooperative enhancement in the branched systems with respect to the one-dimensional sub-units is found.
Oral delivery of novel human IGF-1 bioencapsulated in lettuce cells promotes musculoskeletal cell proliferation, differentiation and diabetic fracture healing (2019)

Human insulin-like growth factor-1 (IGF-1) plays important roles in development and regeneration of skeletal muscles and bones but requires daily injections or surgical implantation. Current clinical IGF-1 lacks e-peptide and is glycosylated, reducing functional efficacy. In this study, codon-optimized Pro-IGF-1 with e-peptide (fused to GM1 receptor binding protein CTB or cell penetrating peptide PTD) was expressed in lettuce chloroplasts to facilitate oral delivery. Pro-IGF-1 was expressed at high levels in the absence of the antibiotic resistance gene in lettuce chloroplasts and was maintained in subsequent generations. In lyophilized plant cells, Pro-IGF-1 maintained folding, assembly, stability and functionality up to 31 months, when stored at ambient temperature. CTB-Pro-IGF-1 stimulated proliferation of human oral keratinocytes, gingiva-derived mesenchymal stromal cells and mouse osteoblasts in a dose-dependent manner and promoted osteoblast differentiation through upregulation of ALP, OSX and RUNX2 genes. Mice orally gavaged with the lyophilized plant cells significantly increased IGF-1 levels in sera, skeletal muscles and was stable for several hours. When bioencapsulated CTB-Pro-IGF-1 was gavaged to femoral fractured diabetic mice, bone regeneration was significantly promoted with increase in bone volume, density and area. This novel delivery system should increase affordability and patient compliance, especially for treatment of musculoskeletal diseases.
Accelerating Laboratory Automation Through Robot Skill Learning For Sample Scraping (2022)

The use of laboratory robotics for autonomous experiments offers an attractive route to alleviate scientists from tedious tasks while accelerating material discovery for topical issues such as climate change and pharmaceuticals. While some experimental workflows can already benefit from automation, sample preparation is still carried out manually due to the high level of motor function and dexterity required when dealing with different tools, chemicals, and glassware. A fundamental workflow in chemical fields is crystallisation, where one application is polymorph screening, i.e., obtaining a three dimensional molecular structure from a crystal. For this process, it is of utmost importance to recover as much of the sample as possible since synthesising molecules is both costly in time and money. To this aim, chemists scrape vials to retrieve sample contents prior to imaging plate transfer. Automating this process is challenging as it goes beyond robotic insertion tasks due to a fundamental requirement of having to execute fine-granular movements within a constrained environment (sample vial). Motivated by how human chemists carry out this process of scraping powder from vials, our work proposes a model-free reinforcement learning method for learning a scraping policy, leading to a fully autonomous sample scraping procedure. We first create a scenario-specific simulation environment with a Panda Franka Emika robot using a laboratory scraper that is inserted into a simulated vial, to demonstrate how a scraping policy can be learned successfully in simulation. We then train and evaluate our method on a real robotic manipulator in laboratory settings, and show that our method can autonomously scrape powder across various setups.
Prediction of Response to Drug Therapy in Psychiatric Disorders (2019)

Reprinted with permission from <i>Open Biol</i>. 8: 180031. The Royal Society.
Transmission and Pathogenesis of Swine-Origin 2009 A(H1N1) Influenza Viruses in Ferrets and Mice (2009)

Recent reports of mild to severe influenza-like illness in humans caused by a novel swine-origin 2009 A(H1N1) influenza virus underscore the need to better understand the pathogenesis and transmission of these viruses in mammals. In this study, selected 2009 A(H1N1) influenza isolates were assessed for their ability to cause disease in mice and ferrets and compared with a contemporary seasonal H1N1 virus for their ability to transmit to naïve ferrets through respiratory droplets. In contrast to seasonal influenza H1N1 virus, 2009 A(H1N1) influenza viruses caused increased morbidity, replicated to higher titers in lung tissue, and were recovered from the intestinal tract of intranasally inoculated ferrets. The 2009 A(H1N1) influenza viruses exhibited less efficient respiratory droplet transmission in ferrets in comparison with the highly transmissible phenotype of a seasonal H1N1 virus. Transmission of the 2009 A(H1N1) influenza viruses was further corroborated by characterizing the binding specificity of the viral hemagglutinin to the sialylated glycan receptors (in the human host) by use of dose-dependent direct receptor-binding and human lung tissue-binding assays.
Experimental Internet Haptic Collaboration using Virtual Coupling Schemes (2008)

In this paper we present the results from several global-scale haptic collaboration experiments that were performed using the Internet. These experiments consist of three virtual coupling schemes proposed to maintain position coherency in a networked haptic virtual environment (NHVE). We compared two of our virtual coupling schemes—which represent a peer-to-peer architecture—to the third—with a client-server architecture. We set up a packet reflector network at our collaborator servers (Italy, Canada and North Carolina, USA) to perform the experiments with subjects located within the same laboratory. Our largest one-way latency was in the order of 200 ms for the packet reflector situated in Italy. The virtual coupling parameters were chosen so that it resulted in stable operation for all the delay values that were tested. User datagram protocol (UDP) was used for haptic data communication because of the high transmission rate requirement for NHVEs. There were three experiments carried out in total: two of them at the packet transmission rate of 1000 Hz with a change in the virtual coupling parameters in scheme 2, and the third one, which tested the three virtual coupling schemes at two fixed transmission rates of 500 Hz and 100 Hz. Locally, the haptic update rate was maintained at 1000 Hz during all the experiments. Our results demonstrate that the peer-to-peer virtual coupling schemes can be used for maintaining position coherency in a NHVE. We also show that the position error and the force rendered to the users increase with the reduction in the packet transmission rate. Given that these experiments were performed through the actual Internet, this work proves valuable for global-scale stable haptic collaboration using the Internet.
Antibiofilm Activities of a Novel Chimeolysin against Streptococcus mutans under Physiological and Cariogenic Conditions (2016)

Streptococcus mutans often survives as a biofilm on the tooth surface and contributes to the development of dental caries. We investigated the efficacy of ClyR, an engineered chimeolysin, against S. mutans biofilms under physiological and cariogenic conditions. Susceptibility tests showed that ClyR was active against all clinical S. mutans isolates tested as well as S. mutans biofilms that displayed resistance to penicillin. The S. mutans biofilms that formed on hydroxyapatite discs under physiological sugar conditions and cariogenic conditions were reduced ∼2 logs and 3 logs after treatment with 100 μg/ml ClyR, respectively. In comparison, only a 1-log reduction was observed in the chlorhexidine gluconate (ChX)-treated group, and no killing effect was observed in the NaF-treated group. A mouse dental colonization model showed that repeated use of ClyR for 3 weeks (5 μg/day) reduced the number of colonized S. mutans cells in the dental plaques significantly (P < 0.05) and had no harmful effects on the mice. Furthermore, toxicity was not noted at concentrations exceeding those used for the in vitro and in vivo studies, and ClyR-specific antibodies could not be detected in mouse saliva after repeated use of ClyR in the oral cavity. Our data collectively demonstrate that ClyR is active against S. mutans biofilms both in vitro and in vivo, thus representing a preventative or therapeutic agent for use against dental caries.
joHn Keit H WooD e a abor Dagem Centra Da na pessoa no b rasi L (2014)

resumo: Este artigo tem como objetivo expor as contribuicoes de John Keith Wood para a Abordagem Centrada na Pessoa (ACP) no Brasil, a partir dos seus trabalhos com a ACP desenvolvida por Carl Ransom Rogers. Trabalhamos com o seu material biblio- grafico publicado na area e com entrevistas realizadas com Lucila Assumpcao, viuva de John Wood, e Vera Cury, ex-aluna e sua amiga. Concluimos que a vida e a obra de John Wood estao totalmente entrelacadas, e que nao e possivel compreender uma sem a outra. Quanto as suas principais contribuicoes, consideramos que sua perspectiva de trabalho com grupos teve sempre como pano de fundo uma visao holistica, imparcial, ambigua e humana. John Keith Wood pode ser considerado, alem de um desmistificador da abordagem, um dos sucessores de Carl Rogers que mais desenvolveram as possibilidades de construcao e aplicacao da ACP. Palavras-chave: Psicologia humanista; Abordagem centrada na pessoa; Carl Rogers; John Wood. Abstract: This article aims to expose the contributions of John Keith Wood to Person-Centered Approach (PCA) in Brazil, hav- ing as start point his work with the PCA developed by Carl Ransom Rogers. We worked based on John Woods scientific publica- tions and interviews conducted with Lucila Assumpcao, Johns widower, and Vera Cury, his student and great friend. We came to the conclusion that John Woods life and work are fully weaved, and that it is not possible to understand one without refer- ring to the other. His main contributions refer to his work with groups, whose functioning has, as its background, the develop- ment of a holistic, impartial, ambiguous, and humanistic perspective. John Keith Wood can be considered a demystifier of the approach and one of the successors of Rogers that most developed possibilities for the implementations of the PCA.