gebhart/patrepeval huggingface dataset:
Glycosaminoglycan Sulfation in Human Osteoarthritis (1998)

Chondroitin lyase products of aggrecan and small proteoglycans from normal and osteoarthritic cartilages were analyzed for chain internal Deltadisaccharides and terminal mono- or disaccharides. Chondroitin and dermatan sulfate chains from arthritic cartilages were of essentially normal size and internal sulfation but had significantly altered sulfation of the terminal residues. Whereas in normal cartilage, approximately 60% of terminal GalNAc4S was 4, 6-disulfated, it was reduced to approximately 30% in osteoarthritic cartilage. This is most likely due to a lower terminal GalNAc4, 6S-disulfotransferase activity and reveals that metabolic changes in osteoarthritis can affect this distinct sulfation step during chondroitin and dermatan sulfate synthesis. GlcAbeta1,3GalNAc6S-, the mimotope for antibody 3B3(-), was present on approximately 8 and approximately 10% of chains from normal and osteoarthritic cartilages, respectively. 3B3(-) assayed by immunodot blot was within the normal range for most osteoarthritic samples, with only 5 of 24 displaying elevated reactivity. This resulted not from a higher content of mimotope, but possibly from other structural changes in the proteoglycan that increase mimotope reactivity. In summary, chemical determination of sulfation isomers at the non-reducing termini of chondroitin and dermatan sulfate provides a reliable assay for monitoring proteoglycan metabolism not only during normal growth of cartilage but also during remodeling of cartilage in osteoarthritis.
T cell unresponsiveness to the mitogenic activity of OKT3 antibody results from a deficiency of monocyte Fc gamma receptors for murine IgG2a and inability to cross-link the T3-Ti complex. (1985)

We recently identified defective monocyte accessory function as the cause of T cell unresponsiveness to the mitogenic activity of OKT3 antibody in cultures of peripheral blood mononuclear cells (PBMC) from five healthy subjects, members of one family. We now report that the underlying abnormality in nonresponders is at the level of monocyte Fc gamma receptors for murine IgG2a. T cell unresponsiveness was not restricted to the signal provided by OKT3 but occurred also for two other anti-T3 antibodies of the IgG2a subclass, in contrast to a normal proliferative response to IgG1 anti-T3 antibodies in one of the OKT3 nonresponders. By using cytofluorography, we found that monocytes from responders but not from nonresponders bound OKT3-FITC to their membrane. The binding could be blocked by mouse IgG2a and by human IgG, but not by mouse IgG1 nor by serum albumin. The data suggest that, through specific Fc gamma receptors for murine IgG2a, monocytes bind the Fc portion of OKT3 during T cell activation. The function of this Fc gamma receptor binding was further studied by culturing PBMC from nonresponders on plates coated with affinity-purified goat anti-mouse IgG antibodies as a substitute for monocyte Fc gamma receptors. The addition of OKT3 to nonresponder PBMC, cultured on such plates, resulted in T cell activation, as evidenced by thymidine incorporation, IL 2 production, and expression of IL 2 receptors. Soluble anti-mouse IgG was not able to substitute for monocyte Fc gamma receptors. The results demonstrate the existence of polymorphism in monocyte Fc gamma receptors for murine IgG2a. They also substantiate that an essential helper function of monocytes in T cell activation by anti-T3 is to provide a matrix for multimeric binding of the Fc portion of the anti-T3 antibodies in order to cross-link T3 molecules.
Robotic visual servoing and robotic assembly tasks (1996)

Visual feedback has traditionally been used in the assembly process to a very limited extent. By incorporating high bandwidth visual feedback into the manipulator feedback loop, more flexible and adaptable robotic assembly systems can be developed. The authors present experimentally tested algorithms and propose solutions for the problem of dynamic sensor placement in assembly tasks.
Input signals to the plant circadian clock (2003)

Eukaryotes and some prokaryotes have adapted to the 24 h day/night cycle by evolving circadian clocks, which now control very many aspects of metabolism, physiology and behaviour. Circadian clocks in plants are entrained by light and temperature signals from the environment. The relative timing of internal and external events depends upon a complex interplay of interacting rhythmic controls and environmental signals, including changes in the period of the clock. Several of the phytochrome and cryptochrome photoreceptors responsible have been identified. This review concentrates on the resulting patterns of entrainment and on the multiple proposed mechanisms of light input to the circadian oscillator components.
CAR T Cell Therapy for Solid Tumors (2016)

The field of cancer immunotherapy has been re-energized by the application of chimeric antigen receptor (CAR) T cell therapy in cancers. These CAR T cells are engineered to express synthetic receptors that redirect polyclonal T cells to surface antigens for subsequent tumor elimination. Many CARs are designed with elements that augment T cell persistence and activity. To date, CAR T cells have demonstrated tremendous success in eradicating hematologic malignancies (e.g., CD19 CARs in leukemias). However, this success has yet to be extrapolated to solid tumors, and the reasons for this are being actively investigated. We characterize some of the challenges that CAR T cells have to surmount in the solid tumor microenvironment and new approaches that are being considered to overcome these hurdles.
Variable stability of a selectable provirus after retroviral vector gene transfer into human cells. (1986)

Human lymphoblasts deficient in the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) were infected with an amphotropic helper-free retroviral vector expressing human HPRT cDNA. The stability and expression of the HPRT provirus in five cell lines with different proviral integration sites were examined by determining HPRT mutation and reversion frequencies and by blot hybridization studies. Mutation to the HPRT-negative phenotype occurred at frequencies of approximately 4 X 10(-5) to 3 X 10(-6) per generation. Most mutations in each of the five cell lines were associated with partial or complete deletions or rearrangements of the provirus. Several mutants retained a grossly intact HPRT provirus, and in one such mutant HPRT shutdown resulted from a revertible epigenetic mechanism that was not associated with global changes in proviral methylation. Therefore, mutation and shutdown of the HPRT provirus in human lymphoblasts result from mechanisms similar to those reported for several other avian and mammalian replication-competent retroviruses.
Integration of an Immunosorbent Assay System:  Analysis of Secretory Human Immunoglobulin A on Polystyrene Beads in a Microchip (2000)

An immunosorbent assay system was integrated into a glass microchip. Polystyrene beads were introduced into a microchannel, and then human secretory immunoglobulin A (s-IgA) adsorbed on the bead surface was reacted with colloidal gold conjugated anti-s-IgA antibody and detected by a thermal lens microscope. The scale merits of liquid microspace on the molecular behavior remarkably contributed to reduced assay time. The integration cut the time necessary for the antigen-antibody reaction by 1/90, thus shortening the overall analysis time from 24 h to less than 1 h. Moreover, troublesome operations required for conventional immunosorbent assays could be replaced by simple operations.
Rapid implementation of therapeutic hypothermia in comatose out‐of‐hospital cardiac arrest survivors (2006)

Our simple, external cooling protocol can be implemented overnight in any system already treating post-resuscitation patients. It was well accepted, feasible and safe, but not optimal in terms of cooling rate. Neither safety concerns nor costs should be a barrier for implementation of TH.
Evolutionary Trace of G Protein-coupled Receptors Reveals Clusters of Residues That Determine Global and Class-specific Functions (2004)

G protein-coupled receptor (GPCR) activation mediated by ligand-induced structural reorganization of its helices is poorly understood. To determine the universal elements of this conformational switch, we used evolutionary tracing (ET) to identify residue positions commonly important in diverse GPCRs. When mapped onto the rhodopsin structure, these trace residues cluster into a network of contacts from the retinal binding site to the G protein-coupling loops. Their roles in a generic transduction mechanism were verified by 211 of 239 published mutations that caused functional defects. When grouped according to the nature of the defects, these residues sub-divided into three striking sub-clusters: a trigger region, where mutations mostly affect ligand binding, a coupling region near the cytoplasmic interface to the G protein, where mutations affect G protein activation, and a linking core in between where mutations cause constitutive activity and other defects. Differential ET analysis of the opsin family revealed an additional set of opsin-specific residues, several of which form part of the retinal binding pocket, and are known to cause functional defects upon mutation. To test the predictive power of ET, we introduced novel mutations in bovine rhodopsin at a globally important position, Leu-79, and at an opsin-specific position, Trp-175. Both were functionally critical, causing constitutive G protein activation of the mutants and rapid loss of regeneration after photobleaching. These results define in GPCRs a canonical signal transduction mechanism where ligand binding induces conformational changes propagated through adjacent trigger, linking core, and coupling regions.
Default ARTMAP (2004)

The default ARTMAP algorithm and its parameter values specified here define a ready-to-use general-purpose neural network system for supervised learning and recognition.
Piezoelectric displacement sensing with a single-electron transistor (2002)

We propose a displacement sensing scheme for rf mechanical resonators made from GaAs, based on detecting the piezoelectrically induced charge. By using a single-electron transistor to detect the charge, we calculate that a significantly higher displacement sensitivity can be achieved than by using capacitive displacement sensing, primarily due to the strong piezoelectric coupling strength. We estimate a displacement sensitivity of order 10−17 m/Hz1/2 for a 1 GHz GaAs resonator. Our model solves the coupled electromechanical response self-consistently, including the effects of both dissipative and reactive electronic circuit elements on the resonator behavior.
Vagal Nerve Stimulation: Overview and Implications for Anesthesiologists (2006)

Vagal nerve stimulation is an important adjunctive therapy for medically refractory epilepsy and major depression. Additionally, it may prove effective in treating obesity, Alzheimer's disease, and some neuropsychiatic disorders. As the number of approved indications increases, more patients are becoming eligible for surgical placement of a commercial vagal nerve stimulator (VNS). Initial VNS placement typically requires general anesthesia, and patients with previously implanted devices may present for other surgical procedures requiring anesthetic management. In this review, we will focus on the indications for vagal nerve stimulation (both approved and experimental), proposed therapeutic mechanisms for vagal nerve stimulation, and potential perioperative complications during initial VNS placement. Anesthetic considerations during initial device placement, as well as anesthetic management issues for patients with a preexisting VNS, are reviewed.
Theory of Lost Circulation Pressure (1990)

ABSTRACT Conventional theories predicting borehole breakdown pressure assume breakdown occurs when the tangential stress at the borehole exceeds the tensile strength of the formation. Fracturing tests conducted during the DEA-13 joint industry project, however, showed that when drilling fluid was used as an injection fluid, borehole breakdown did not occur until the well pressure significantly exceeded the pressure which resulted in a tangential stress equal to the rock tensile strength even with a large surface flaw. The test results have shown that all drilling muds have a tendency to seal narrow natural fractures or fractures created by high borehole pressure. The sealing effect of the mud stabilizes fractures and prevents fracture propagation. This effect is one of the primary factors for controlling wellbore stability. In this paper, a theory of fracture initiation and fracture propagation around a borehole whose stability is enhanced by drilling fluid interaction, has been developed and shown to be consistent not only with all the DEA-13 laboratory results, but also with various field evidence. The results show that lost circulation pressure is highly dependent on the Young's modulus of the formation, wellbore size, and type of the drilling fluid, although the conventional theories have ignored these facts.
A recombinant chimeric plasminogen activator with high affinity for fibrin has increased thrombolytic potency in vitro and in vivo. (1991)

A recombinant plasminogen activator with high fibrin affinity and specificity was expressed by transfecting hybridoma cells with a plasmid that combines sequence coding for low molecular mass (32 kDa) single-chain urokinase-type plasminogen activator [scuPA(32kDa)] and anti-fibrin monoclonal antibody 59D8. The expression of the recombinant molecule [r-scuPA(32kDa)-59D8] was optimized by replacing the 3' untranslated region (initially that of high molecular mass scuPA) in the plasmid with the 3' untranslated region of either beta-globin or mouse immunoglobulin. This modification resulted in a greater than 100-fold improvement in the level of protein expression. The 103-kDa r-scuPA(32kDa)-59D8 protein displayed catalytic activity indistinguishable from that of high molecular mass scuPA and fibrin binding comparable to that of native antibody 59D8. r-scuPA(32kDa)-59D8 was 6 times more potent than high molecular mass scuPA in lysing a human plasma clot in vitro and was 20 times more potent than high molecular mass scuPA in the rabbit jugular vein model of thrombolysis. Molecules of this type may serve as prototypes for highly specific, antibody-targeted enzymes suitable for human use.
Progress and properties of high-power coherent vertical-cavity surface-emitting laser arrays (1993)

We discuss the potential of using coherently-coupled vertical cavity surface emitting laser arrays as high-intensity light sources. In particular, the design and performance of a novel two-dimensional phase-coupled grid Contact vertical cavity Surface Emitting Laser Array (C- SELA) is reported. We discuss the optical properties of the C-SELA; in addition to the usual out-of-phase array mode, we demonstrate in-phase SELA coupling. We introduce a simple physical model to describe our experimental results. Over 1.2 Watt optical power emission is obtained at room temperature from an electrically-excited 10 X 10 C-SELA. This laser array exhibited a low threshold current density of only 600 Amps/cm<SUP>2</SUP> and over 60% single-ended differential quantum efficiency.
Pathology of non-thermal irreversible electroporation (N-TIRE)-induced ablation of the canine brain (2013)

This study describes the neuropathologic features of normal canine brain ablated with non-thermal irreversible electroporation (N-TIRE). The parietal cerebral cortices of four dogs were treated with N-TIRE using a dose-escalation protocol with an additional dog receiving sham treatment. Animals were allowed to recover following N-TIRE ablation and the effects of treatment were monitored with clinical and magnetic resonance imaging examinations. Brains were subjected to histopathologic and ultrastructural assessment along with Bcl-2, caspase-3, and caspase-9 immunohistochemical staining following sacrifice 72 h post-treatment. Adverse clinical effects of N-TIRE were only observed in the dog treated at the upper energy tier. MRI and neuropathologic examinations indicated that N-TIRE ablation resulted in focal regions of severe cytoarchitectural and blood-brain-barrier disruption. Lesion size correlated to the intensity of the applied electrical field. N-TIRE-induced lesions were characterized by parenchymal necrosis and hemorrhage; however, large blood vessels were preserved. A transition zone containing parenchymal edema, perivascular inflammatory cuffs, and reactive gliosis was interspersed between the necrotic focus and normal neuropil. Apoptotic labeling indices were not different between the N-TIRE-treated and control brains. This study identified N-TIRE pulse parameters that can be used to safely create circumscribed foci of brain necrosis while selectively preserving major vascular structures.
Efficient outer join data skew handling in parallel DBMS (2009)

Large enterprises have been relying on parallel database management systems ( PDBMS ) to process their ever-increasing data volume and complex queries. The scalability and performance of a PDBMS comes from load balancing on all nodes in the system. Skewed processing will significantly slow down query response time and degrade the overall system performance. Business intelligence tools used by enterprises frequently generate a large number of outer joins and require high performance from the underlying database systems. Although extensive research has been done on handling skewed processing for inner joins in PDBMS, there is no known research on data skew handling for parallel outer joins. We propose a simple and efficient outer join algorithm called OJSO (Outer Join Skew Optimization) to improve the performance and scalability of parallel outer joins. Our experimental results show that the OJSO algorithm significantly speeds up query elapsed time in the presence of data skew.
A computer program for selection of oligonucleotide primers for polymerase chain reactions (1990)

We have designed a computer program which rapidly scans nucleic acid sequences to select all possible pairs of oligonucleotides suitable for use as primers to direct efficient DNA amplification by the polymerase chain reaction. This program is based on a set of rules which define in generic terms both the sequence composition of the primers and the amplified region of DNA. These rules (1) enhance primer-to-target sequence hybridization avidity at critical 3'-end extension initiation sites, (2) facilitate attainment of full length extension during the 720C phase, by minimizing generation of incomplete or nonspecific product and (3) limit primer losses occurring from primer-self or primer-primer homologies. Three examples of primer sets chosen by the program that correctly amplified the target regions starting from RNA are shown. This program should facilitate the rapid selection of effective and specific primers from long gene sequences while providing a flexible choice of various primers to focus study on particular regions of interest.
Back-action of a driven nonlinear resonator on a superconducting qubit (2012)

We study the backaction of a driven nonlinear resonator on a multilevel superconducting qubit. Using unitary transformations on the multilevel Jaynes-Cummings Hamiltonian and quantum optics master equation, we derive an analytical model that goes beyond linear response theory. Within the limits of validity of the model, we obtain quantitative agreement with experimental and numerical data, both in the bifurcation and in the parametric amplification regimes of the nonlinear resonator. We show in particular that the measurement-induced dephasing rate of the qubit can be rather small at high drive power. This is in contrast to measurement with a linear resonator where this rate increases with the drive power. Finally, we show that, for typical parameters of circuit quantum electrodynamics, correctly describing measurement-induced dephasing requires a model going beyond linear response theory, such as the one presented here.
PHOTO-CLICKABLE SEPARATION GELS ENABLE TARGETED PROTEOMICS OF CANCER BIOMARKER ISOFORMS: A 'SINGLE CHANNEL, MULTI-STAGE' STRATEGY (2011)

We introduce a ‘hands free’ proteomic tool with the potential to radically transform the status quo of cancer protein biomarker validation. Here, we focus on a challenging and broadly relevant target in this analyte class - the prostate cancer marker prostate-specific antigen (PSA). We introduce light-activatable, volume accessible polyacrylamide separation gels (LAVAgels) that capture electrophoretically separated PSA isoforms within a highly multiplexed (16-channel) microfluidic assay format. The 3D LAVAgel matrix offers unprecedented target capture duty, with capture efficiencies greater than 100fold higher than for existing surface chemistries. Our optofluidic separations strategy harnesses tremendous micro/nanoscale transport advantages to yield unmatched speed and efficiency – major barriers to realizing high-throughput proteomics.
Interaction of CTLA‐4 (CD152) with CD80 or CD86 inhibits human T‐cell activation (1999)

Occupancy of CTLA-4 (cytotoxic T-lymphocyte antigen-4 or CD152) negatively regulates the activation of mouse T lymphocytes, as indicated by the fate of CTLA-4-deficient mice, by the impact of anti-CTLA-4 monoclonal antibodies (mAbs) on mouse T-cell activation in vitro and by the impact of CTLA-4 blockade on the course of experimental tumoral, autoimmune, alloimmune or infectious disease in this animal. The function of human CTLA-4, however, remains less clear. The expression and function of human CTLA-4 were further explored. CTLA-4 was expressed under mitogenic conditions only, its expression being, at least partially, dependent on the secretion of interleukin-2. Memory T cells expressed CTLA-4 with faster kinetics than naive T cells. The functional role of human CTLA-4 was assessed utilizing a panel of four anti-CTLA-4 mAbs that blocked the interaction between CTLA-4 and its ligands. These mAbs, in immobilized form, profoundly inhibited the activation of T cells by immobilized anti-CD3 mAb in the absence of anti-CD28 mAb, but co-stimulated T-cell activation in the presence of anti-CD28 mAb. Finally, and importantly, blockade of the interaction of CTLA-4 with its ligands using soluble anti-CTLA-4 mAbs, in intact form or as Fab fragments, enhanced T-cell activation in several polyclonal or alloantigen-specific CD80- or CD80/CD86-dependent assays, as measured by cytokine production, cellular proliferation or cytotoxic responses. It is concluded that interaction of CTLA-4 with its functional ligands, CD80 or CD86, can down-regulate human T-cell responses, probably by intracellular signalling events and independent of CD28 occupancy.
Engineering a novel biosynthetic pathway in Escherichia coli for production of renewable ethylene glycol (2015)

Ethylene glycol (EG) is an important commodity chemical with broad industrial applications. It is presently produced from petroleum or natural gas feedstocks in processes requiring consumption of significant quantities of non-renewable resources. Here, we report a novel pathway for biosynthesis of EG from the renewable sugar glucose in metabolically engineered Escherichia coli. Serine-to-EG conversion was first achieved through a pathway comprising serine decarboxylase, ethanolamine oxidase, and glycolaldehyde reductase. Serine provision in E. coli was then enhanced by overexpression of the serine-biosynthesis pathway. The integration of these two parts into the complete EG-biosynthesis pathway in E. coli allowed for production of 4.1 g/L EG at a cumulative yield of 0.14 g-EG/g-glucose, establishing a foundation for a promising biotechnology.