gebhart/patrepeval huggingface dataset:
Improved biodistribution, tumor targeting, and reduced immunogenicity in mice with a gamma 4 variant of Campath-1H. (1995)

Radiolabeled antibodies have shown promise for the treatment of lymphoma and for solid tumor targeting. Campath-1H is a humanized monoclonal antibody that reacts with the CD52 antigen present on human lymphoid and myeloid cells. Campath-1H is a gamma1 (G1) isotype that induces lymphopenia via an Fc-mediated mechanism(s). Isotype switches were engineered, and the resulting antibodies were expressed in NS0 mouse myeloma cells and biosynthetically radiolabeled with [35S]methionine. The forms included G1, G4, and a G4 variant that contained alanine substitutions at (EU numbering) Leu-235, Gly-237, and Glu-318. All isotypes bound antigen equivalently as assessed by target cell binding in vitro. The G4 variant had a greatly reduced capacity to interact with Fc receptor by virtue of reduced binding to THP-1 human myeloid cells and by a 1000-fold increase in EC50 to intermediate antibody-dependent cellular cytotoxicity. The pharmacokinetics of the isotypes were compared in CD-1 (nu/nu) mice bearing an experimental antigen-expressing tumor. The plasma half-life and tumor uptake were increased for the G4 variant. The G4 variant showed significantly less spleen, liver, and bone uptake but similar uptake in the lung, kidney, and stomach and lower tissue-to-blood ratios. Immunogenicity was assessed after repeated monthly administrations of unlabeled antibody in BALB/c mice. A 50% reduction in the incidence of anti-globulin response was observed for the G4 variant. These properties suggest that antibodies with reduced Fc receptor interaction merit additional study as potential targeting vehicles relative to other isotypes for radioimmunotherapy or situations where diminished normal tissue binding contributes to efficacy.
Preparation of a novel core-shell nanostructured gold colloid-silk fibroin bioconjugate by the protein in situ redox technique at room temperature. (2001)

A novel core-shell gold colloid-silk fibroin (SF) bioconjugate was prepared by the protein in situ redox technique at room temperature, in which the tyrosine (Tyr) residue of the SF, having strong electron donating properties, in situ reduced Au(III) ions to Au colloids showing a stable and highly monodispersed nature.
Modeling of CO2 Capture with Water Bubble Column Reactor (2020)

The demand for carbon capture is increasing over time due to rising CO2 levels in the atmosphere. Even though fossil emission could be decreased or even eliminated, there is a need to start removing CO2 from the atmosphere. The removed CO2 could be either stored permanently to a reservoir (CCS, Carbon Capture and Storage) or utilized as a raw material in a long-lasting product (CCU, Carbon Capture and Utilization). The capture of CO2 could be done by direct air capture, or capturing CO2 from biogenic sources. Amine absorption is the state-of-the-art method to capture CO2, but it has some drawbacks: toxicity, high heat demand, and sorbent sensitivity towards impurities such as sulfur compounds and degradation in cyclic operation. Another potential solvent for CO2 could be water, which is easily available and safe to use in many applications. The problem with water is the poorer solubility of CO2, compared with amines, which leads to larger required flow rates. This study analyzed the technical feasibility of water absorption in a counterflow bubble column reactor. A dynamic, one-dimensional multiphase model was developed. The gas phase was modeled with plug flow assumption, and the liquid phase was treated as axially dispersed plug flow. CO2 capture efficiency, produced CO2 mass flow rate, and the product gas CO2 content were estimated as a function of inlet gas and liquid flow rate. In addition, the energy consumption per produced CO2-tonne was calculated. The CO2 capture efficiency was improved by increasing the liquid flow rate, while the CO2 content in product gas was decreased. For some of the studied liquid flow rates, an optimum gas flow rate was found to minimize the specific energy consumption. Further research is required to study the integration and dynamical operation of the system in a realistic operation environment.
Multispectral Imaging Fluorescence Microscopy for Living Cells. (2002)

Multispectral imaging technologies have been widely used in fields of astronomy and remote sensing. Interdisciplinary approaches developed in, for example, the National Aeronautics and Space Administration (NASA, USA), the Jet Propulsion Laboratory (JPL, USA), or the Communications Research Laboratory (CRL, Japan) have extended the application areas of these technologies from planetary systems to cellular systems. Here we overview multispectral imaging systems that have been devised for microscope applications. We introduce these systems with particular interest in live cell imaging. Finally we demonstrate examples of spectral imaging of living cells using commercially available systems with no need for user engineering.
Cellular Delivery of Neurotrophin-3 Promotes Corticospinal Axonal Growth and Partial Functional Recovery after Spinal Cord Injury (1997)

The injured adult mammalian spinal cord shows little spontaneous recovery after injury. In the present study, the contribution of projections in the dorsal half of the spinal cord to functional loss after adult spinal cord injury was examined, together with the effects of transgenic cellular delivery of neurotrophin-3 (NT-3) on morphological and functional disturbances. Adult rats underwent bilateral dorsal column spinal cord lesions that remove the dorsal corticospinal projections or underwent more extensive resections of the entire dorsal spinal cord bilaterally that remove corticospinal, rubrospinal, and cerulospinal projections. Long-lasting functional deficits were observed on a motor grid task requiring detailed integration of sensorimotor skills, but only in animals with dorsal hemisection lesions as opposed to dorsal column lesions. Syngenic primary rat fibroblasts genetically modified to produce NT-3 were then grafted to acute spinal cord dorsal hemisection lesion cavities. Up to 3 months later, significant partial functional recovery occurred in NT-3-grafted animals together with a significant increase in corticospinal axon growth at and distal to the injury site. These findings indicate that (1) several spinal pathways contribute to loss of motor function after spinal cord injury, (2) NT-3 is a neurotrophic factor for the injured corticospinal projection, and (3) functional deficits are partially ameliorated by local cellular delivery of NT-3. Lesions of the corticospinal projection may be necessary, but insufficient in isolation, to cause sensorimotor dysfunction after spinal cord injury in the rat.
AN EXPANDED TEST FOR SPEECH DISCRIMINATION UTILIZING CNC MONOSYLLABIC WORDS: NORTHWESTERN UNIVERSITY AUDITORY TEST NO. 6 (1966)

Abstract : Northwestern University Auditory Test No. 6 is composed of four lists of 50 consonant-nucleus-consonant (CNC) monosyllabic words each. The construction of the test followed the same scheme employed earlier in the development of N. U. Test No. 4, a less extensive version using the same type of material. The four lists of N.U. Test No. 6 were given twice to each of two subject groups--one group with normal hearing and another with sensorineural hypoacousis. During each administration, six ascending presentation levels were used ranging from -4-dB to 40-dB sensation level. The two groups yielded articulation functions highly similar to those obtained with the earlier test (N.U. Test No. 4). The new test (N.U. Test No. 6) appears to have good interlist equivalence and high test-retest reliability. It thus retains the desirable features of the earlier tool while doubling the inventory of items available for the measurement of phonemic discrimination.
Signal Peptide-Dependent Inhibition of MHC Class I Heavy Chain Translation by Rhesus Cytomegalovirus (2008)

The US2-11 region of human and rhesus cytomegalovirus encodes a conserved family of glycoproteins that inhibit MHC-I assembly with viral peptides, thus preventing cytotoxic T cell recognition. Since HCMV lacking US2-11 is no longer able to block assembly and transport of MHC-I, we examined whether this is also observed for RhCMV lacking the corresponding region. Unexpectedly, recombinant RhCMV lacking US2-11 was still able to inhibit MHC-I expression in infected fibroblasts, suggesting the presence of an additional MHC-I evasion mechanism. Progressive deletion analysis of RhCMV-specific genomic regions revealed that MHC-I expression is fully restored upon additional deletion of rh178. The protein encoded by this RhCMV-specific open reading frame is anchored in the endoplasmic reticulum membrane. In the presence of rh178, RhCMV prevented MHC-I heavy chain (HC) expression, but did not inhibit mRNA transcription or association of HC mRNA with translating ribosomes. Proteasome inhibitors stabilized a HC degradation intermediate in the absence of rh178, but not in its presence, suggesting that rh178 prevents completion of HC translation. This interference was signal sequence-dependent since replacing the signal peptide with that of CD4 or murine HC rendered human HCs resistant to rh178. We have identified an inhibitor of antigen presentation encoded by rhesus cytomegalovirus unique in both its lack of homology to any other known protein and in its mechanism of action. By preventing signal sequence-dependent HC translocation, rh178 acts prior to US2, US3 and US11 which attack MHC-I proteins after protein synthesis is completed. Rh178 is the first viral protein known to interfere at this step of the MHC-I pathway, thus taking advantage of the conserved nature of HC leader peptides, and represents a new mechanism of translational interference.
Purification and Functional Reconstitution of the Recombinant Large Mechanosensitive Ion Channel (MscL) of Escherichia coli (1995)

The large mechanosensitive ion channel (MscL) of Escherichia coli was expressed on a plasmid encoding MscL as a fusion protein with glutathione S-transferase in an Escherichia coli strain containing a disruption in the chromosomal mscL gene. After purification of the fusion protein using glutathione-coated beads, thrombin cleavage allowed recovery of the MscL protein. The purified protein was reconstituted into artificial liposomes and found to be fully functional when examined with the patch-clamp technique. The reconstituted recombinant MscL protein formed ion channels that exhibited characteristic conductance and pressure sensitivity and were blocked by the mechanosensitive ion channel inhibitor gadolinium. The recombinant MscL protein was also used to raise specific anti-MscL polyclonal antibodies which abolished channel activity when preincubated with the MscL protein.
Hive (2009)

The size of data sets being collected and analyzed in the industry for business intelligence is growing rapidly, making traditional warehousing solutions prohibitively expensive. Hadoop [3] is a popular open-source map-reduce implementation which is being used as an alternative to store and process extremely large data sets on commodity hardware. However, the map-reduce programming model is very low level and requires developers to write custom programs which are hard to maintain and reuse.
ATOM (1994)

ATOM (Analysis Tools with OM) is a single framework for building a wide range of customized program analysis tools. It provides the common infrastructure present in all code-instrumenting tools; this is the difficult and time-consuming part. The user simply defines the tool-specific details in instrumentation and analysis routines. Building a basic block counting tool like Pixie with ATOM requires only a page of code. ATOM, using OM link-time technology, organizes the final executable such that the application program and user's analysis routines run in the same address space. Information is directly passed from the application program to the analysis routines through simple procedure calls instead of inter-process communication or files on disk. ATOM takes care that analysis routines do not interfere with the program's execution, and precise information about the program is presented to the analysis routines at all times. ATOM uses no simulation or interpretation. ATOM has been implemented on the Alpha AXP under OSF/1. It is efficient and has been used to build a diverse set of tools for basic block counting, profiling, dynamic memory recording, instruction and data cache simulation, pipeline simulation, evaluating branch prediction, and instruction scheduling.
Comparison of microsurgical suture with fibrin glue connection of the sciatic nerve in rabbits. (1997)

The regeneration of the sciatic nerve after microsuture was compared with the connection of transected nerve with a coagulum of autologous blood plasma in 20 rabbits. The epineuroperineural suture was performed in 10 rabbits (group A). The severed nerve was approximated with fibrin glue of autologous blood plasma in 10 rabbits (group B). Their skin sensation margin during a 3-month-period of regeneration was examined, 90 days after surgery the connection was inspected and the nerve conduction velocity was measured across the site of the anastomosis. The microsuture was found to be firm in all 10 animals of group A. On the other hand, in 2 animals of group B, the glue failed to keep the nerve stumps approximated (dehiscence occurred in 20% of the animals). There were no significant differences found on clinical and electrophysiological testing of regenerated nerves of both groups. The method of autologous fibrin glue in the repair of peripheral nerve transection does not provide a sufficiently firm connection. This procedure with the preparation of the centrifuged plasma is a more time-consuming method in comparison with the microsuture. Epineuroperineural microsuture with maximal effort to adapt the corresponding nerve fibres remains the method of choice for peripheral nerve reconstruction.
Optimization of CDT-1 and XYL1 Expression for Balanced Co-Production of Ethanol and Xylitol from Cellobiose and Xylose by Engineered Saccharomyces cerevisiae (2013)

Production of ethanol and xylitol from lignocellulosic hydrolysates is an alternative to the traditional production of ethanol in utilizing biomass. However, the conversion efficiency of xylose to xylitol is restricted by glucose repression, causing a low xylitol titer. To this end, we cloned genes CDT-1 (encoding a cellodextrin transporter) and gh1-1 (encoding an intracellular β-glucosidase) from Neurospora crassa and XYL1 (encoding a xylose reductase that converts xylose into xylitol) from Scheffersomyces stipitis into Saccharomyces cerevisiae, enabling simultaneous production of ethanol and xylitol from a mixture of cellobiose and xylose (main components of lignocellulosic hydrolysates). We further optimized the expression levels of CDT-1 and XYL1 by manipulating their promoters and copy-numbers, and constructed an engineered S. cerevisiae strain (carrying one copy of PGK1p-CDT1 and two copies of TDH3p-XYL1), which showed an 85.7% increase in xylitol production from the mixture of cellobiose and xylose than that from the mixture of glucose and xylose. Thus, we achieved a balanced co-fermentation of cellobiose (0.165 g/L/h) and xylose (0.162 g/L/h) at similar rates to co-produce ethanol (0.36 g/g) and xylitol (1.00 g/g).
A Multipurpose Toolkit to Enable Advanced Genome Engineering in Plants (2017)

We report a comprehensive toolkit that enables targeted, specific modification of monocot and dicot genomes using a variety of genome engineering approaches. Our reagents, based on transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, are systematized for fast, modular cloning and accommodate diverse regulatory sequences to drive reagent expression. Vectors are optimized to create either single or multiple gene knockouts and large chromosomal deletions. Moreover, integration of geminivirus-based vectors enables precise gene editing through homologous recombination. Regulation of transcription is also possible. A Web-based tool streamlines vector selection and construction. One advantage of our platform is the use of the Csy-type (CRISPR system yersinia) ribonuclease 4 (Csy4) and tRNA processing enzymes to simultaneously express multiple guide RNAs (gRNAs). For example, we demonstrate targeted deletions in up to six genes by expressing 12 gRNAs from a single transcript. Csy4 and tRNA expression systems are almost twice as effective in inducing mutations as gRNAs expressed from individual RNA polymerase III promoters. Mutagenesis can be further enhanced 2.5-fold by incorporating the Trex2 exonuclease. Finally, we demonstrate that Cas9 nickases induce gene targeting at frequencies comparable to native Cas9 when they are delivered on geminivirus replicons. The reagents have been successfully validated in tomato (<i>Solanum lycopersicum</i>), tobacco (<i>Nicotiana tabacum</i>), <i>Medicago truncatula</i>, wheat (<i>Triticum aestivum</i>), and barley (<i>Hordeum vulgare</i>).
Targeting B Cell Maturation Antigen (BCMA) in Multiple Myeloma: Potential Uses of BCMA-Based Immunotherapy (2018)

The approval of the first two monoclonal antibodies targeting CD38 (daratumumab) and SLAMF7 (elotuzumab) in late 2015 for treating relapsed and refractory multiple myeloma (RRMM) was a critical advance for immunotherapies for multiple myeloma (MM). Importantly, the outcome of patients continues to improve with the incorporation of this new class of agents with current MM therapies. However, both antigens are also expressed on other normal tissues including hematopoietic lineages and immune effector cells, which may limit their long-term clinical use. B cell maturation antigen (BCMA), a transmembrane glycoprotein in the tumor necrosis factor receptor superfamily 17 (TNFRSF17), is expressed at significantly higher levels in all patient MM cells but not on other normal tissues except normal plasma cells. Importantly, it is an antigen targeted by chimeric antigen receptor (CAR) T-cells, which have already shown significant clinical activities in patients with RRMM who have undergone at least three prior treatments, including a proteasome inhibitor and an immunomodulatory agent. Moreover, the first anti-BCMA antibody-drug conjugate also has achieved significant clinical responses in patients who failed at least three prior lines of therapy, including an anti-CD38 antibody, a proteasome inhibitor, and an immunomodulatory agent. Both BCMA targeting immunotherapies were granted breakthrough status for patients with RRMM by FDA in Nov 2017. Other promising BCMA-based immunotherapeutic macromolecules including bispecific T-cell engagers, bispecific molecules, bispecific or trispecific antibodies, as well as improved forms of next generation CAR T cells, also demonstrate high anti-MM activity in preclinical and even early clinical studies. Here, we focus on the biology of this promising MM target antigen and then highlight preclinical and clinical data of current BCMA-targeted immunotherapies with various mechanisms of action. These crucial studies will enhance selective anti-MM response, transform the treatment paradigm, and extend disease-free survival in MM.
Obesity resistance and enhanced glucose metabolismin mice transplanted with white adipose tissue lackingacyl CoA:diacylglycerol acyltransferase 1 (2003)

Recent studies have identified the white adipose tissue (WAT) as an important endocrine organ that regulates energy and glucose metabolism via a number of secreted factors. Mice lacking acyl CoA:diacylglycerol acyltransferase 1 (DGAT1), a key enzyme in mammalian triglyceride synthesis, are protected against diet-induced obesity and glucose intolerance because of increased energy expenditure and enhanced insulin sensitivity. Because DGAT1 is highly expressed in WAT, we hypothesized that DGAT1 deficiency affects the expression of adipocyte-derived factors that regulate energy and glucose metabolism. Here we show that the transplantation of DGAT1-deficient WAT decreases adiposity and enhances glucose disposal in wild-type mice. Analysis of DGAT1-deficient WAT revealed a twofold increase in the expression of adiponectin, a molecule that enhances fatty acid oxidation and insulin sensitivity, and this increase may account in part for the transplantation-induced metabolic changes. Our results highlight the importance of the endocrine function of WAT and suggest that an alteration in this function contributes to the increased energy expenditure and insulin sensitivity in DGAT1-deficient mice.
Increased 2-Methoxyestradiol Production in Human Coronary Artery Versus Aortic Smooth Muscle Cells: Potential Role in Mediating the Cardioprotective Effects of Estradiol (2000)

P86 Estradiol (E) protects premenopausal women against coronary artery disease (CAD), however, the mechanisms involved remain unclear. Recent findings that E protects neointima formation in α and β estrogen receptor(ER) knockout mice suggest that the effects may be mediated via an ER independent mechanism. Because 2-methoxyestradiol(2MeOE),an endogenous metabolite of E with no affinity for ER, is more potent than E in inhibiting vascular smooth muscle cell (SMC) growth, it is feasible that 2MeOE mediates the protective effects of E. Since formation of 2MeOE involves the methylation of 2-hydroxyestradiol (2OHE; major estradiol metabolite)by COMT, the protective effects of estradiol on the coronary circulation may be due in part to the efficient conversion of E and 2OHE to 2MeOE in coronary vascular SMCs. To test this hypothesis, we compared the kinetics of 2MeOE synthesis in human aortic (A) versus coronary artery (CA) SMCs. Incubation of human ASMCs and CASMCs with 10μM 2OHE resulted in a time-dependent formation of 2MeOE. As compared to ASMCs, CASMCs were twice as effective in metabolizing 2OHE to 2MeOE and the Vmax and Km were 15.7±.7 vs 38.3±.9 pmol 2MeOE/10 6 cells/min and .35±.07 vs .12±.02 μM, respectively. Rat ASMCs and porcine aortic endothelial cells (ECs) also metabolized 2OHE to 2MeOE, the Vmax being 17.1±.8 and 14.22±.3 pmol/10 6 cells/min, respectively, and Km of 0.48±.1 and 0.32±.04μM,respectively. Our findings indicate that vascular SMCs and ECs effectively metabolize 2OHE to 2MeOE and that as compared to ASMCs, CASMCs have increased COMT activity and 2MeOE formation.Thus, local metabolism of 2OHE to 2MeOE may mediate the anti-vasoocclusive effects of E via an ER-independent mechanism. Moreover, increased COMT activity may selectively protect the coronary artery by generating more 2MeOE and this may be responsible for the decreased incidence of CAD in premenopausal women.