gebhart/patrepeval huggingface dataset:
Data from A Multi-Institution Phase I Trial of Ruxolitinib in Patients with Chronic Myelomonocytic Leukemia (CMML) (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; To conduct a phase I clinical trial exploring the safety and efficacy of ruxolitinib, a JAK1/2 inhibitor, for chronic myelomonocytic leukemia (CMML).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Patients with CMML-1 were included without regard to previous therapy. Key exclusion criteria included an absolute neutrophil count (ANC) &lt;0.25 × 10&lt;sup&gt;3&lt;/sup&gt; cells/dL and a platelet count &lt;35 × 10&lt;sup&gt;3&lt;/sup&gt; cells/dL. Four cohorts were enrolled using a “rolling six” study design, with doses ranging from 5 to 20 mg twice daily of ruxolitinib in 5-mg dose escalations.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Between March 2013 and January 2015, 20 patients were enrolled and treated with ruxolitinib. Seventy percent of patients had the proliferative subtype and 47% had higher risk disease by the Global MD Anderson Scoring System. Eight patients (42%) received a prior hypomethylating agent. No dose-limiting toxicities for ruxolitinib were identified. One subject had grade (G)3 thrombocytopenia with no other drug-associated G3 or G4 adverse events. The mean duration of therapy was 122 days (range, 28–409 days). Four had hematologic improvement and one patient had a partial response per 2006 International Working Group (IWG) criteria. Five of 9 patients with splenomegaly had a reduction in spleen size. Ten of 11 patients with reported disease-related symptoms had clinically meaningful or complete resolution. When combining IWG and spleen responses, a total response rate of 35% (&lt;i&gt;n&lt;/i&gt; = 7) was identified. Correlative analysis demonstrated a reduction in inflammatory cytokines and GM-CSF–dependent STAT5 phosphorylation.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; The recommended phase II dose of ruxolitinib is 20 mg twice daily. We demonstrate that ruxolitinib has promising activity in CMML with particular benefit in those with disease-related B symptoms that warrants further study. &lt;i&gt;Clin Cancer Res; 22(15); 3746–54. ©2016 AACR&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;i&gt;See related commentary by Solary, p. 3707&lt;/i&gt;&lt;/p&gt;&lt;/div&gt;
Telomere-to-Telomere Genome Assembly of Bursaphelenchus okinawaensis Strain SH1 (2020)

<i>Bursaphelenchus okinawaensis</i> is a self-fertilizing, hermaphroditic, fungus-feeding nematode used as a laboratory model for the genus <i>Bursaphelenchus</i>, which includes the important pathogen <i>Bursaphelenchus xylophilus</i> Here, we report the nearly complete genome sequence of <i>B. okinawaensis</i> The 70-Mbp assembly contained six scaffolds (>11 Mbp each) with telomere repeats on their ends, indicating complete chromosomes.
Enhanced Performance of a Molecular Photoacoustic Imaging Agent by Encapsulation in Mesoporous Silicon Nanoparticles (2019)

Adv. Mater. 2018, 30, 1800512 The author (M.J.S.) wishes to correct the conflict of interest disclosure on this paper; in addition to being a founder and having an equity interest in Spinnaker Biosciences, Inc., M.J.S. also sits on its board of directors.
Emerging trends in COVID-19 treatment: learning from inflammatory conditions associated with cellular therapies (2020)

Coronavirus disease 2019 (SARS-CoV2) is an active global health threat for which treatments are desperately being sought. Even though most people infected experience mild to moderate respiratory symptoms and recover with supportive care, certain vulnerable hosts develop severe clinical deterioration. While several drugs are currently being investigated in clinical trials, there are currently no approved treatments or vaccines for COVID-19 and hence there is an unmet need to explore additional therapeutic options. At least three inflammatory disorders or syndromes associated with immune dysfunction have been described in the context of cellular therapy. Specifically, Cytokine Release Syndrome (CRS), Immune Reconstitution Inflammatory Syndrome (IRIS), and Secondary Hemophagocytic Lymphohistiocytosis (sHLH) all have clinical and laboratory characteristics in common with COVID19 and associated therapies that could be worth testing in the context of clinical trials. Here we discuss these diseases, their management, and potential applications of these treatment in the context of COVID-19. We also discuss current cellular therapies that are being evaluated for the treatment of COVID-19 and/or its associated symptoms.
Age-associated Senescent - T Cell Signaling Promotes Type 3 Immunity that Inhibits Regenerative Response (2021)

Abstract Aging is associated with immunological changes that compromise response to infections and vaccines, exacerbate inflammatory diseases and could potentially mitigate tissue repair. Even so, age-related changes to the immune response to tissue damage and regenerative medicine therapies remain unknown. Here, we characterized how aging induces senescence and immunological changes that inhibit tissue repair and therapeutic response to a clinical regenerative biological scaffold derived from extracellular matrix. Tissue signatures of inflammation and interleukin (IL)-17 signaling increased with injury and treatment in aged animals, and computational analysis uncovered age-associated senescent-T cell communication that promotes type 3 immunity in T cells. Local inhibition of type 3 immune activation using IL17-neutralizing antibodies improved healing and restored therapeutic response to the regenerative biomaterial, promoting muscle repair in older animals. These results provide insights into tissue immune dysregulation that occurs with aging that can be targeted to rejuvenate repair.
Triglyceride content of bovine oocytes and early embryos (1999)

A microfluorescence technique was used to measure the triglyceride content of a minimum of two bovine oocytes or preimplantation embryos up to the hatched blastocyst stage. Embryos were produced in vitro from abattoir-derived ovaries and grown in medium containing synthetic oviductal fluid, amino acids and BSA (SOFaaBSA medium); 10% fetal calf serum was added to some of the embryos at the four-cell stage. Before maturation, the triglyceride content of oocytes was 59 +/- 1.37 ng and it decreased (P < 0.05) after maturation to 46 +/- 0.85 ng. A decrease in triglyceride content (P < 0.05) was also observed after fertilization with the formation of the two-cell embryo (34 +/- 1.80 ng). In the absence of serum, the triglyceride content remained relatively constant from the two-cell to the hatched blastocyst stage. The triglyceride content of blastocysts produced in vivo was similar (33 +/- 0.70 ng) to that of blastocysts produced in vitro in the absence of serum. In contrast, the triglyceride content of embryos grown with 10% fetal calf serum increased steadily from the 9-16-cell stage to a value in hatched blastocysts (62 +/- 1.14 ng) almost double that in serum-free conditions. These results indicate that triglyceride may act as energy source during bovine oocyte maturation and fertilization and that the presence of serum causes excessive synthesis or accumulation of triglyceride in early embryos.
Growth dominant co-precipitation process to achieve high coercivity at room temperature in CoFe/sub 2/O/sub 4/ nanoparticles (2002)

Applications of CoFe/sub 2/O/sub 4/ are limited due to the lack of synthesis technique to produce monodispersed, single domain and high coercivity (H/sub c/) nanoparticles. Here, we describe the growth dominant co-precipitation process to achieve high H/sub c/, with moderate magnetization at room temperature (RT) in CoFe/sub 2/O/sub 4/ nanoparticles. It is well known that the particle size is closely related to the relative interdependence between the nucleation and growth steps, which in turn can strongly be affected by the solution chemistry and precipitation conditions. Based on this premise, the effect of 1) reaction temperature, 2) NaOH concentration, and 3) feeding rate of metal ions into the alkali solution were evaluated. The maximum H/sub c/ of 2.29 kOe (RT) was observed for the CoFe/sub 2/O/sub 4/ prepared at 98/spl deg/C, 1.13-mol NaOH, and the metal ion feeding rate of 0.00103 M/min. To improve the coercivity, single domain CoFe/sub 2/O/sub 4/ nanoparticles were produced by in situ growth of the CoFe/sub 2/O/sub 4/ seeds followed by size separation method. A coercivity of 4.3 kOe was achieved at RT for 40-nm single domain CoFe/sub 2/O/sub 4/ nanoparticles, which is close to the theoretical value of 5.3 kOe.
Data from Therapeutic Implications of a Human Neutralizing Antibody to the Macrophage-Stimulating Protein Receptor Tyrosine Kinase (RON), a c-MET Family Member (2023)

&lt;div&gt;Abstract&lt;p&gt;RON is a member of the c-MET receptor tyrosine kinase family. Like c-MET, RON is expressed by a variety of epithelial-derived tumors and cancer cell lines and it is thought to play a functional role in tumorigenesis. To date, antagonists of RON activity have not been tested &lt;i&gt;in vivo&lt;/i&gt; to validate RON as a potential cancer target. In this report, we used an antibody phage display library to generate IMC-41A10, a human immunoglobulin G1 (IgG1) antibody that binds with high affinity (ED&lt;sub&gt;50&lt;/sub&gt; = 0.15 nmol/L) to RON and effectively blocks interaction with its ligand, macrophage-stimulating protein (MSP; IC&lt;sub&gt;50&lt;/sub&gt; = 2 nmol/L). We found IMC-41A10 to be a potent inhibitor of receptor and downstream signaling, cell migration, and tumorigenesis. It antagonized MSP-induced phosphorylation of RON, mitogen-activated protein kinase (MAPK), and AKT in several cancer cell lines. In HT-29 colon, NCI-H292 lung, and BXPC-3 pancreatic cancer xenograft tumor models, IMC-41A10 inhibited tumor growth by 50% to 60% as a single agent, and in BXPC-3 xenografts, it led to tumor regressions when combined with Erbitux. Western blot analyses of HT-29 and NCI-H292 xenograft tumors treated with IMC-41A10 revealed a decrease in MAPK phosphorylation compared with control IgG–treated tumors, suggesting that inhibition of MAPK activity may be required for the antitumor activity of IMC-41A10. To our knowledge, this is the first demonstration that a RON antagonist and specifically an inhibitory antibody of RON negatively affects tumorigenesis. Another major contribution of this report is an extensive analysis of RON expression in ∼100 cancer cell lines and ∼300 patient tumor samples representing 10 major cancer types. Taken together, our results highlight the potential therapeutic usefulness of RON activity inhibition in human cancers. (Cancer Res 2006; 66(18): 9162-70)&lt;/p&gt;&lt;/div&gt;
Abstract 547: Recombinant immunotoxins targeting B-cell maturation antigen induce complete responses in bone marrow myeloma mouse model (2019)

Background: Multiple myeloma (MM) is a B-cell malignancy for which new treatments are urgently needed. B-cell maturation antigen (BCMA) is a lineage-restricted differentiation protein highly expressed on MM and an ideal target for immunotherapy of MM. Recombinant immunotoxins (RITs) are chimeric proteins composed of the Fv or Fab portion of an antibody fused to a fragment of Pseudomonas Exotoxin A (PE). One of these, Lumoxiti, is FDA approved for the treatment of drug-resistant hairy cell leukemia, another B-cell malignancy. LMB-75 is an immunotoxin with an anti-BCMA dsFv of mAb BM306 fused to domain III of PE, and LMB-70 is an anti-BCMA Fab fused to domain III of PE. We previously treated H929 myeloma cells grown as subcutaneous tumors with anti-BCMA immunotoxins that are very effective in killing cultured cells and cells from patients. We observed tumor growth inhibition but not complete tumor responses. Goal: Here we used H929 cells to develop a bone marrow mouse model that is more relevant to human disease and to determine if these immunotoxins are more active against H929 cells growing in bone marrow.Methods: The NCI-H929 cell line was transfected with luciferase and GFP, recycled through the bone marrow of a mouse and enriched by flow to isolate cells with high GFP expression, which were used to inoculate tumors IV into NSG mice. Mice were treated IV with immunotoxins and tumor burden was assessed using bioluminescence imaging.Results: H929-luc-GFP cells grow uniformly in the bone marrow of mice, cause hind limb paralysis around day 40, and provide a relevant in vivo model for testing RITs. We achieved complete responses when treating mice with 1.5 mg/kg LMB-75 or LMB-70 given QODX5 beginning on days 4 or day 8. Mice in all treatment groups were disease free at 3 months. An immunotoxin targeting CD22, which is not expressed on H929 cells, or an anti-BCMA immunotoxin with a mutation that inactivates toxin activity did not have any anti-tumor activity.Conclusions: LMB-75 and LMB-70 induce complete, durable remissions of H929-luc-GFP cells growing in mouse bone marrow without toxicity to mice. These promising results support further pre-clinical development of these agents for MM.Citation Format: Zoe Shancer, Xiu-fen Liu, Emily King, Tapan Bera, Ira Pastan. Recombinant immunotoxins targeting B-cell maturation antigen induce complete responses in bone marrow myeloma mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 547.
Enantioselektivität der Biotransformation eines neuen Theophyllinderivats (1992)

Reductive amination of 4 with (RS)-2 is an improved method to obtain 7-((RS)2-((RS)-1-Methyl-2-phenyl-ethylamino)propyl)-theophylline (3) (ratio of diastereomers 1:1) compared with SN-displacement of proxyphyllintosylate with (RS)-2 (ratio of diastereomers 9:1). Due to steric hindrance 3 is no noteworthy prodrug for the intermediate formation of (RS)-2 in rats. The enantioselectivity of 2 after a single oral dose of 3 is determined in 24-h urine by HPLC on a Cyclobond-column using the isoindole derivatives, formed from o-phthalaldehyde, thioglycolic acid, and 2. The R(-)-amphetamine isomer is formed to a lesser amount (34.8%, range 32-37%) than the S(+)-isomer (65.2%, range 63-68%).
Improving Transformer-Kernel Ranking Model Using Conformer and Query Term Independence (2021)

The Transformer-Kernel (TK) model has demonstrated strong reranking performance on the TREC Deep Learning benchmark -- and can be considered to be an efficient (but slightly less effective) alternative to other Transformer-based architectures that employ (i) large-scale pretraining (high training cost), (ii) joint encoding of query and document (high inference cost), and (iii) larger number of Transformer layers (both high training and high inference costs). Since, a variant of the TK model -- called TKL -- has been developed that incorporates local self-attention to efficiently process longer input sequences in the context of document ranking. In this work, we propose a novel Conformer layer as an alternative approach to scale TK to longer input sequences. Furthermore, we incorporate query term independence and explicit term matching to extend the model to the full retrieval setting. We benchmark our models under the strictly blind evaluation setting of the TREC 2020 Deep Learning track and find that our proposed architecture changes lead to improved retrieval quality over TKL. Our best model also outperforms all non-neural runs ("trad") and two-thirds of the pretrained Transformer-based runs ("nnlm") on NDCG@10.
Job Shop Scheduling Using Genetic and Heuristic Exchange Algorithms for AGVs (2022)

Solving a job shop scheduling problem (JSSP) entails allocating entire jobs to machines to minimize the processing time. Generally, the transit time between machines is not considered in the conventional JSSP because it is shorter than the processing time. In a real production environment, however, the transit time of an autonomous ground vehicle (AGV) is long due to the need to solve random problems, such as finding an indirect route or avoiding collisions. Moreover, AGVs sometimes need to transport the job on directional roads with upstream and downstream constraints. Therefore, we present an AGV job scheduling algorithm considering the transit time. This study considers not only the transportation times of the jobs from one machine to another but also collisions on limited roads, similar to in a real environment. A near-optimal job sequence was obtained by combining the genetic algorithm (GA) with simulation and was comparing this with the traditional method. Additionally, this paper presents heuristics that deal with deadlocks in the process of combining JSSP and simulation. The combination of GA and heuristics was tested using various simulations.
Addition of substrate-binding domains increases substrate-binding capacity and specific activity of a chitinase fromTrichoderma harzianum (2001)

Chitinase Chit42 from Trichoderma harzianum CECT 2413 is considered to play an important role in the biocontrol activity of this fungus against plant pathogens. Chit42 lacks a chitin-binding domain (ChBD). We have produced hybrid chitinases with stronger chitin-binding capacity by fusing to Chit42 a ChBD from Nicotiana tabacum ChiA chitinase and the cellulose-binding domain from cellobiohydrolase II of Trichoderma reesei. The chimeric chitinases had similar activities towards soluble substrate but higher hydrolytic activity than the native chitinase on high molecular mass insoluble substrates such as ground chitin or chitin-rich fungal cell walls.
Frequency Noise and Phase-Locking of a Quantum Cascade Laser-Pumped, 1.073 Terahertz Molecular Laser using a 1560nm Frequency Comb (2019)

Summary form only given. Recently, a novel type of molecular THz laser with ~mW-level output power was demonstrated [1,2]. This laser is optically pumped by a mid-IR Quantum Cascade Laser (QCL), therefore resulting in a much more compact, frequency agile and deployable source compared to standard, CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> -laser pumped, far-infrared gas lasers. This achievement has revived the interest for molecular THz lasers, in particular for their exploitation as low-phase noise THz local oscillators (LOs) operating at room temperature. Compared to CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> -laser pumping, a QCL pump offers an unrivalled frequency agility that allows accessing an unprecedented number of molecular transitions. On the other hand, its lower frequency stability can potentially impact the frequency noise of the THz laser source [3-5]. Here we report the first measurement of the frequency noise power spectral density (PSD) of a 1.073THz ammonia laser pumped by a 10.3μm QCL. This is achieved by using a commercial harmonic mixer to generate a beating between the ammonia laser frequency and the 1080 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sup> harmonic of the 1GHz repetition rate of a custom-made, 1560nm frequency comb (FC). We then exploit a voltage-controlled oscillator to track the beat-note signal and realize the frequency to amplitude conversion [6]. The measured frequency noise PSD is shown in Fig.1. In the range ~30-100kHz we find a frequency noise <; 10Hz <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> /Hz (-95dBc), limited by the noise of the QCL current driver. We will show that the value of the frequency noise PSD depends on the relative position of the pump frequency with respect to center of the Doppler-broadened pump transition line. To further elucidate the effect of the stability of the pump laser we also measured the frequency noise PSD of a CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> -pumped, 2.5THz methanol laser, reaching 0.1Hz <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> /Hz (-110dBc) at 40kHz from the carrier, limited by the frequency noise of the FC harmonic. Finally, we will show that it is possible to actively phase-lock the QCL-pumped ammonia laser to the FC repetition rate harmonic by controlling the QCL drive current, demonstrating a sub-Hz linewidth. These results pave the way to the development of QCL-pumped molecular lasers as compact, low-phase noise THz sources operating a room temperature.
Five-year results of a clinical pilot study utilizing a pedicle-lengthening osteotomy for the treatment of lumbar spinal stenosis (2018)

OBJECTIVE Lumbar spinal stenosis (LSS) is a common condition that leads to significant disability, particularly in the elderly. Current therapeutic options have certain drawbacks. This study evaluates the 5-year clinical and radiographic results of a minimally invasive pedicle-lengthening osteotomy (PLO) for symptomatic LSS. METHODS A prospective, single-arm, clinical pilot study was conducted involving 20 patients (mean age 61.7 years) with symptomatic LSS treated by a PLO procedure at 1 or 2 lumbar levels. All patients had symptoms of neurogenic claudication or radiculopathy secondary to LSS, and had not improved after a minimum 6-month course of nonoperative treatment. Eleven patients had a Meyerding grade I degenerative spondylolisthesis in addition to LSS. Clinical outcomes were measured using the Oswestry Disability Index, Zürich Claudication Questionnaire, 12-Item Short Form Health Survey, and a visual analog scale for back and leg pain. Procedural variables, neurological outcomes, adverse events, and radiological imaging (plain radiographs and CT scans) were collected at the 1.5-, 3-, 6-, 9-, 12-, 24-, and 60-month time points. RESULTS The PLOs were performed through percutaneous incisions, with minimal blood loss in all cases. There were no operative complications. Four adverse events occurred during the follow-up period. Statistically significant improvement was observed in each of the outcome instruments and maintained over the 5-year follow-up period. Imaging studies, reviewed by an independent radiologist, showed no evidence of device subsidence, migration, breakage, or heterotopic ossification. Thin-slice CT scans documented healing of the osteotomy site in all patients at the 6-month time point and an increase of 115% in the mean cross-sectional area of the spinal canal. CONCLUSIONS Treatment of patients with symptomatic LSS with a PLO procedure provided substantial enlargement of the area of the spinal canal and favorable clinical results for both disease-specific and non–disease-specific outcome measures at all follow-up time points out to 5 years. Future research is needed to compare this technique to alternative therapies for LSS.
Combined Optimization of FFE and DFE Equalizations (2018)

The rapid growth of data centers along with the development of faster computers, tablets and phones drive a constant demand for networks with higher data rates, that is limited by channel bandwidth. Equalization methods are used to recover the signal attenuated by channel, crosstalk, jitter and other noise. Different optimization algorithms are applied to find the best parameters for each equalization. When optimization algorithms work separately with Feed Forward Equalization (FFE) and Decision Feedback Equalization (DFE), found tap coefficients of FFE and DFE do not give optimal result during joint equalization. In the present paper FFE and DFE joint optimization algorithm is introduced that can be solved analytically. Proposed joint optimization method allows FFE and DFE tap coefficients to collaborate and leads to the optimal equalization result. The proposed method is fast, easy to implement and efficient. The algorithm can be generalized for multi-level signals as well.