gebhart/patrepeval huggingface dataset:
Ofatumumab Is More Efficient than Rituximab in Lysing B Chronic Lymphocytic Leukemia Cells in Whole Blood and in Combination with Chemotherapy (2012)

Ofatumumab (OFA) is a human anti-CD20 Ab approved for treatment of fludarabine-refractory B chronic lymphocytic leukemia (B-CLL). The efficacy of different immunotherapeutic strategies is best investigated in conditions that are as physiologic as possible. We have therefore compared the activity OFA and rituximab (RTX), alone or in combination with chemotherapeutic agents in unmanipulated whole blood assays, using flow cytometry. OFA (10-100 μg/ml) lysed B-CLL targets in whole blood more efficiently and with faster kinetics than RTX, with a mean 56% lysis at 24 h compared with 16%. This activity of OFA was fully complement dependent, as shown by >99% inhibition by anti-C5 Ab eculizumab and a lack of NK cell activation in whole blood. OFA-mediated NK cell activation was blocked by complement. OFA-mediated lysis could be increased an additional 15% by blocking CD55 and CD59 complement inhibitors. Interestingly, OFA-mediated lysis correlated significantly with CD20 expression levels (r(2) = 0.79). OFA showed overlapping dose response curves similar to those for RTX in phagocytosis assays using either human macrophages or neutrophils. However, phagocytosis was inhibited in the presence of serum or whole blood. Finally, combined treatment with mafosfamide and fludarabine showed that these therapeutic drugs are synergistic in B-CLL whole blood assays and show superior activity when combined with OFA compared with RTX. These results confirm in B-CLL samples and in physiologic conditions the superior complement mediated cytotoxicity induced by OFA alone compared with RTX, the lack of NK cell activation, and phagocytosis in these conditions and suggest effective chemoimmunotherapy strategies using this new generation anti-CD20 Ab.
Hybrid microfluidics: A digital-to-channel interface for in-line sample processing and chemical separations (2009)

Microchannels can separate analytes faster with higher resolution, higher efficiency and with lower reagent consumption than typical column techniques. Unfortunately, an impediment in the path toward fully integrated microchannel-based labs-on-a-chip is the integration of pre-separation sample processing. Although possible in microchannels, such steps are challenging because of the difficulty in maintaining spatial control over many reagents simultaneously. In contrast, the alternative format of digital microfluidics (DMF), in which discrete droplets are manipulated on an array of electrodes, is well-suited for carrying out sequential chemical reactions. Here, we report the development of the first digital-channel hybrid microfluidic device for integrated pre-processing reactions and chemical separations. The device was demonstrated to be useful for on-chip labeling of amino acids and primary amines in cell lysate, as well as enzymatic digestion of peptide standards, followed by separation in microchannels. Given the myriad applications requiring pre-processing and chemical separations, the hybrid digital-channel format has the potential to become a powerful new tool for micro total analysis systems.
Spatiotemporal Residual Networks for Video Action Recognition (2016)

Two-stream Convolutional Networks (ConvNets) have shown strong performance for human action recognition in videos. Recently, Residual Networks (ResNets) have arisen as a new technique to train extremely deep architectures. In this paper, we introduce spatiotemporal ResNets as a combination of these two approaches. Our novel architecture generalizes ResNets for the spatiotemporal domain by introducing residual connections in two ways. First, we inject residual connections between the appearance and motion pathways of a two-stream architecture to allow spatiotemporal interaction between the two streams. Second, we transform pretrained image ConvNets into spatiotemporal networks by equipping these with learnable convolutional filters that are initialized as temporal residual connections and operate on adjacent feature maps in time. This approach slowly increases the spatiotemporal receptive field as the depth of the model increases and naturally integrates image ConvNet design principles. The whole model is trained end-to-end to allow hierarchical learning of complex spatiotemporal features. We evaluate our novel spatiotemporal ResNet using two widely used action recognition benchmarks where it exceeds the previous state-of-the-art.
B cell therapy with the anti‐CD22 monoclonal antibody epratuzumab: Comment on the editorial by St.Clair and Tedder (2006)

SCOPUS: le.j
A comparison of corneal autografts with homografts. (1998)

Autografts provided protection against immunologic graft rejection. However, because corneal autografts yielded unpredictable amounts of astigmatism, their outcomes are not necessarily better than those of homografts.
Modeling the complexity of genetic networks: Understanding multigenic and pleiotropic regulation (1996)

Abstract Molecular genetics presents an increasingly complex picture of the genome and biological function. Evidence is mounting for distributed function, redundancy, and combinatorial coding in the regulation of genes. Satisfactory explanation will require the concept of a parallel processing signaling network. Here we provide an introduction to Boolean networks and their relevance to present‐day experimental research. Boolean network models exhibit global complex behavior, self‐organization, stability, redundancy and periodicity, properties that deeply characterize biological systems. While the life sciences must inevitably face the issue of complexity, we may well look to cybernetics for a modeling language such as Boolean networks which can manageably describe parallel processing biological systems and provide a framework for the growing accumulation of data. We finally discuss experimental strategies and database systems that will enable mapping of genetic networks. The synthesis of these approaches holds an immense potential for new discoveries on the intimate nature of genetic networks, bringing us closer to an understanding of complex molecular physiological processes like brain development, and intractable medical problems of immediate importance, such as neurodegenerative disorders, cancer, and a variety of genetic diseases.
Targeting CD20 in Follicular NHL: Novel Anti-CD20 Therapies, Antibody Engineering, and the Use of Radioimmunoconjugates (2005)

Rituximab (chimeric anti-CD20 monoclonal antibody) is widely employed in the treatment of patients with B cell non-Hodgkin lymphoma (NHL). This agent has activity in both indolent and aggressive disease, alone and in combination with chemotherapy. Unfortunately, however, many patients develop resistant disease. Ongoing efforts to improve outcomes include changes in dose and schedule, as well as the use of other biologic agents or antibodies that may enhance activity when administered together with rituximab. A relatively new focus is the development of engineered anti-CD20 antibodies that are optimized for their capability to mediate antibody-mediated cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). Human or humanized structures have also been employed to potentially improve these attributes, as well as to improve on pharmacokinetics and immunogenicity. Other studies in NHL have clearly demonstrated that radiolabeled anti-CD20 antibodies (such as I-131 tositumomab and Y-90 ibritumomab tiuxetan) may be useful in relapsed and refractory disease, and have potential utility as part of initial treatment as well. Further studies of these modified anti-CD20 antibodies are ongoing in order to optimize their use for maximal clinical benefit.
Direct Oxidation of β‐Aryl Substituted Aldehydes to α,β‐Unsaturated Aldehydes Promoted by an o‐Anisidine–Pd(OAc)2 Co‐catalyst (2009)

An o-anisidine-Pd(OAc)2 catalytic system for the direct co-catalytic Saegusa oxidation of beta-aryl substituted aldehydes to alpha,beta-unsaturated aldehydes has been developed. The use of o-anisidine in place of (S)-diphenylprolinol made the process more simply and cost-effective. The process not only features the use of unmodified aldehydes rather than enol silyl ethers, but also gives moderate to good yields (44-72%).
Processive degradation of proteins by the ATP-dependent Clp protease from Escherichia coli. Requirement for the multiple array of active sites in ClpP but not ATP hydrolysis. (1994)

ClpP, the proteolytic component of the ATP-dependent ClpAP protease, is composed of 12 identical subunits and has intrinsic degradative activity against short peptides. Degradation of proteins and some peptides by ClpP requires the regulatory component ClpA and ATP. Peptide and protein substrates have been used to distinguish the roles of nucleotide binding and nucleotide hydrolysis in the activation of ClpAP protease. ATP binding alone promoted interaction between ClpA and ClpP, affected the substrate response curves for very short peptides, and activated degradation of larger peptides that were not degraded by ClpP alone. ATP hydrolysis did not increase in proportion to the increase in peptide bond hydrolysis of short peptides. However, ATP hydrolysis was strictly required for degradation of proteins such as alpha-casein; there was no indication of even limited cleavage of protein substrates when nonhydrolyzable analogs of ATP were used. Most large peptides and proteins were degraded in multiple sites without release of high molecular weight intermediates. Partial inactivation of ClpP with diisopropyl fluorophosphate produced ClpP with one to three active subunits/dodecamer. When only a few active sites were available in the active complex of ClpAP, degradation of large peptides and proteins released significant amounts of high molecular weight intermediates. Thus, processive degradation of protein substrates is a function of the multiple array of proteolytic active sites within the ClpP dodecamer.
Electroless Ni‐P Deposition on Silicon with Pd Activation (1992)

The electroless Ni‐P deposition on silicon with Pd activation was investigated by Rutherford backscattering spectrometry (RBS) and electron microscopy. An "RBS double‐layer" structure with different composition was simulated to evaluate the composition profiles of the films produced by electroless deposition with Pd activation. During deposition on Si with Pd activation, the initially formed alloy was found to contain approximately two times more P than that formed after long deposition times. To explain the distribution of P in alloy suggested that the catalytic properties of the surface change during the deposition process. The thickness of the layer also changes during deposition. It was observed that the maximum thickness of layer ranges from 2400 to 2500 Å. Contact hole to silicon device with a 0.5 μm depth p‐n junctions and a 1.5 μm nominal sizes were filled by after Pd activation. The contact resistivity on n‐type silicon ( and ) was in the 10−8 Ω · cm2 range after a 450°C nitrogen annealing cycle for 30 min.
Ursodeoxycholic Acid Treatment of Cholesterol Gallstone Disease (1994)

Bile acid dissolution therapy alone or in combination with extracorporeal shock-wave lithotripsy continues to be a safe and effective non-surgical treatment for highly selected patients with cholesterol gallstone disease. Its disadvantages are the duration of drug treatment and potential stone recurrence. Its advantages, however, are non-invasiveness, low rate of morbidity, and lack of mortality. Considering the variety of options in modern gallstone therapy, the careful selection of treatment should be tailored to the individual patient's clinical and personal situation. This will involve the patient in the decision-making process.
Constituents of Cannabis sativa (1979)

Wild growing Cannabis from different altitudes and locations was collected in northern India. Plant material from each collection was analyzed quantitatively for ten cannabinoids by GC. The average total cannabinoid content of plants growing above 2,000 m was 1.33 %, whereas below 2,000 m the average total cannabinoid content was 2.74 %. Morphological characteristics were recorded. Data obtained from wild growing Indian Cannabis (twenty variants) are compared with data obtained from the same variants grown in Mississippi, USA.
Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects. (1993)

Blood was taken at the first antenatal clinic from 56,049 pregnant women. Neural tube defect (NTD) pregnancies (81) were compared to controls (247) for plasma vitamin B12 (B12) (ng/l), plasma folate (microgram/l), and red cell folate (RCF) (microgram/l). Median values were significantly different and were, respectively, 243 and 296 (p = 0.001); 3.47 and 4.59 (p = 0.002); and 269 and 338 (p < 0.001). There was a significant correlation between plasma B12 and RCF in cases (r = 0.31, p = 0.004) but not in controls (r = 0.02, p = 0.725). In cases only, multiple regression showed that both plasma B12 and plasma folate influenced the maternal RCF (multiple r = 0.68, p < 0.001). Plasma folate and plasma B12 were independent risk factors for NTDs, suggesting that the enzyme methionine synthase is involved directly or indirectly in the aetiology. The levels of folate and B12 where increased risk occurred were not those usually associated with deficiency, calling for a re-evaluation of their recommended daily allowances. Whether the aetiology is purely nutritional or a metabolic defect, this study suggests that consideration should be given to including B12 as well as folic acid in any programme of supplementation or food fortification to prevent NTDs.
Binary Constraint System Games and Locally Commutative Reductions (2013)

A binary constraint system game is a two-player one-round non-local game defined by a system of Boolean constraints. The game has a perfect quantum strategy if and only if the constraint system has a quantum satisfying assignment [R. Cleve and R. Mittal, arXiv:1209.2729]. We show that several concepts including the quantum chromatic number and the Kochen-Specker sets that arose from different contexts fit naturally in the binary constraint system framework. The structure and complexity of the quantum satisfiability problems for these constraint systems are investigated. Combined with a new construct called the commutativity gadget for each problem, several classic NP-hardness reductions are lifted to their corresponding quantum versions. We also provide a simple parity constraint game that requires $Ω(\sqrt{n})$ EPR pairs in perfect strategies where $n$ is the number of variables in the constraint system.
Risks of Affective Illness Among First-Degree Relatives of Bipolar I Old-Order Amish Probands (1992)

Data from bipolar I old-order Amish families suggest that the morbid risk of illness is not significantly different in this population when compared with estimates of risk from previous studies. The age-corrected rates of bipolar I, bipolar II, and major depressive disorder among first-degree relatives are 8.7, 3.7, and 11.6, respectively. Risk of illness is not significantly different among male and female relatives and among relatives of male and female probands. Consistent with other reports, the rate of illness is higher among relatives of probands with early-onset disease. In contrast with previous reports, there does not appear to be a cohort effect in this population.
FGFR3 Stimulates Stearoyl CoA Desaturase 1 Activity to Promote Bladder Tumor Growth (2012)

Fibroblast growth factor receptor 3 (FGFR3) belongs to a family of receptor tyrosine kinases that control cell proliferation, differentiation, and survival. Aberrant activation of FGFR3 via overexpression or mutation is a frequent feature of bladder cancer; however, its molecular and cellular consequences and functional relevance to carcinogenesis are not well understood. Through transcriptional profiling of bladder carcinoma cells subjected to short hairpin RNA knockdown of FGFR3, we identified a gene-signature linking FGFR3 signaling with de novo sterol and lipid biosynthesis and metabolism. We found that FGFR3 signaling promotes the cleavage and activation of the master transcriptional regulator of lipogenesis, sterol regulatory element-binding protein 1(SREBP1/SREBF1), in a PI3K-mTORC1-dependent fashion. In turn, SREBP1 regulates the expression of key lipogenic enzymes, including stearoyl CoA desaturase 1 (SCD1/SCD). SCD1 is the rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids and is crucial for lipid homeostasis. In human bladder cancer cell lines expressing constitutively active FGFR3, knockdown of SCD1 by siRNA markedly attenuated cell-cycle progression, reduced proliferation, and induced apoptosis. Furthermore, inducible knockdown of SCD1 in a bladder cancer xenograft model substantially inhibited tumor progression. Pharmacologic inhibition of SCD1 blocked fatty acid desaturation and also exerted antitumor activity in vitro and in vivo. Together, these findings reveal a previously unrecognized role of FGFR3 in regulating lipid metabolism to maintain tumor growth and survival, and also identify SCD1 as a potential therapeutic target for FGFR3-driven bladder cancer.
Discovery of a Tetrahydropyrimidin-2(1H)-one Derivative (TAK-442) as a Potent, Selective, and Orally Active Factor Xa Inhibitor (2010)

Coagulation enzyme factor Xa (FXa) is a particularly promising target for the development of new anticoagulant agents. We previously reported the imidazo[1,5-c]imidazol-3-one derivative 1 as a potent and orally active FXa inhibitor. However, it was found that 1 predominantly undergoes hydrolysis upon incubation with human liver microsomes, and the human specific metabolic pathway made it difficult to predict the human pharmacokinetics. To address this issue, our synthetic efforts were focused on modification of the imidazo[1,5-c]imidazol-3-one moiety of the active metabolite 3a, derived from 1, which resulted in the discovery of the tetrahydropyrimidin-2(1H)-one derivative 5k as a highly potent and selective FXa inhibitor. Compound 5k showed no detectable amide bond cleavage in human liver microsomes, exhibited a good pharmacokinetic profile in monkeys, and had a potent antithrombotic efficacy in a rabbit model without prolongation of bleeding time. Compound 5k is currently under clinical development with the code name TAK-442.
A Nonpeptidyl Mimic of Superoxide Dismutase with Therapeutic Activity in Rats (1999)

Many human diseases are associated with the overproduction of oxygen free radicals that inflict cell damage. A manganese(II) complex with a bis(cyclohexylpyridine)-substituted macrocyclic ligand (M40403) was designed to be a functional mimic of the superoxide dismutase (SOD) enzymes that normally remove these radicals. M40403 had high catalytic SOD activity and was chemically and biologically stable in vivo. Injection of M40403 into rat models of inflammation and ischemia-reperfusion injury protected the animals against tissue damage. Such mimics may result in better clinical therapies for diseases mediated by superoxide radicals.
Targeted Amplicon Sequencing (TAS): A Scalable Next-Gen Approach to Multilocus, Multitaxa Phylogenetics (2011)

Next-gen sequencing technologies have revolutionized data collection in genetic studies and advanced genome biology to novel frontiers. However, to date, next-gen technologies have been used principally for whole genome sequencing and transcriptome sequencing. Yet many questions in population genetics and systematics rely on sequencing specific genes of known function or diversity levels. Here, we describe a targeted amplicon sequencing (TAS) approach capitalizing on next-gen capacity to sequence large numbers of targeted gene regions from a large number of samples. Our TAS approach is easily scalable, simple in execution, neither time-nor labor-intensive, relatively inexpensive, and can be applied to a broad diversity of organisms and/or genes. Our TAS approach includes a bioinformatic application, BarcodeCrucher, to take raw next-gen sequence reads and perform quality control checks and convert the data into FASTA format organized by gene and sample, ready for phylogenetic analyses. We demonstrate our approach by sequencing targeted genes of known phylogenetic utility to estimate a phylogeny for the Pancrustacea. We generated data from 44 taxa using 68 different 10-bp multiplexing identifiers. The overall quality of data produced was robust and was informative for phylogeny estimation. The potential for this method to produce copious amounts of data from a single 454 plate (e.g., 325 taxa for 24 loci) significantly reduces sequencing expenses incurred from traditional Sanger sequencing. We further discuss the advantages and disadvantages of this method, while offering suggestions to enhance the approach.
Plume avoidance maneuver planning using mixed integer linear programming (2001)

This paper extends a recently-developed path planning method to account for plume impingement, which is a key concern for on-orbit rendezvous and formation flying spacecraft. The approach designs fueloptimal trajectories for multiple vehicles using a combination of linear and integer programming. The vehicles are required to move from an initial dynamic state to a final state without colliding with each other or firing the thrusters in a way that would hit another vehicle. This problem is written as a linear program with mixed integer/linear constraints that prohibit collisions and plume impingements. A key benefit of this approach is that the problem can be readily solved using the AMPL language and CPLEX optimization software with a Matlab interface. Examples are given of this method applied to satellite cluster reconfiguration, ISS remote camera maneuvering and ground vehicle guidance. l
Transformation of back-propagation networks in multiresolution learning (1994)

We proposed to train a backpropagation network using the multiresolution learning method. We first train a backpropagation network with input at a coarsest resolution, then gradually refine the input into finer resolution. The problem is to transform the connection weights of the backpropagation network from a coarsest level into a finest level. The objective of it is to improve the convergence rate of the networks. We evaluate two schemes for this network transformation. One is the wavelet approach and the other is the average splitting approach. Experimental results demonstrated the ability of this approach.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>