gebhart/patrepeval huggingface dataset:
Comparison of the L-asparaginases from Escherichia coli and Erwinia carotovora as immunosuppressants. (1974)

Summary The immunosuppressive effects of Escherichia coli and Erwinia carotovoral-asparaginases were examined in three systems: (a) the in vitro phytohemagglutinin-induced blastogenic response of rabbit blood leukocytes; (b) the humoral response of mice to sheep erythrocytes; and (c) the cell-mediated immune response of guinea pigs. The Er. carotovoral-asparaginase was 10 times more effective than the E. coli enzyme in inhibiting the blastogenic response in vitro. This was attributable to the greater glutaminase activity of the Er. carotovora enzyme, although it remains possible that the critical factor in blastogenesis is asparagine availability. In contrast to differences in the inhibition of transformation, the two microbial enzymes were equally effective in suppressing the antibody response to sheep erythrocytes, provided that the daily administration of enzyme was maintained until the time of serum sampling. When only a single enzyme dose was given together with antigen, then the E. coli enzyme was the more effective, an observation that could be interpreted solely in terms of the different half-lives of the two enzymes in the circulation. Neither enzyme influenced the cell-mediated immune response of guinea pigs to a protein-hapten conjugate, a test system in which glutaminase activity alone could have been expressed.
Effects of Protein Kinase CK2, Extracellular Signal-regulated Kinase 2, and Protein Phosphatase 2A on a Phosphatidic Acid-preferring Phospholipase A1 (2001)

A soluble, phosphatidic acid-preferring phospholipase A1, expressed in mature bovine testes but not in newborn calf testes, may contribute to the formation or function of sperm. Here we incubated a recombinant preparation of the phospholipase in vitro with several enzymes including protein kinase CK2 (CK2), extracellular signal-regulated kinase 2 (ERK2), and protein phosphatase 2A (PP2A) to identify effects that might be of regulatory importance in vivo. Major findings were that 1) CK2 phosphorylated the phospholipase on serines 93, 105, and 716; 2) ERK2 phosphorylated the enzyme on serine 730; 3) there was cross-antagonism between the reactions that phosphorylated serines 716 and 730; 4) PP2A selectively hydrolyzed phosphate groups that were esterified to serines 716 and 730; 5) CK2alpha formed a stable, MgATP/MgGTP-dependent complex with the phospholipase by a novel mechanism; and 6) the complex showed reduced phospholipase activity and resembled a complex identified in homogenates of macaque testis. These results provide the first available information about the effects of reactions of phosphorylation and dephosphorylation on the behavior of the phospholipase, shed light on properties of CK2alpha that may be required for the formation of complexes with its substrates, and raise the possibility that a complex containing CK2alpha and the phospholipase may play a special biological role in the testis.
Revascularization and Microcirculation of Freely Grafted Islets of Langerhans (2001)

A considerable number of experimental studies have demonstrated that the reestablishment of an appropriate microvascular supply is an essential prerequisite for successful pancreatic islet transplantation. Freely transplanted islets show the first signs of angiogenesis (i.e., capillary sprout formation and protrusion) as early as 2 days after transplantation, and the entire vascularization process is completed after 10 to 14 days. Cryopreservation and culture of the isolated islets before transplantation and hyperglycemia of the transplant recipient seem not to affect the vascularization process essentially. In addition, immunosuppressive drugs, such as cyclosporin A and 15-deoxyspergualin, do not or only slightly inhibit revascularization of syngeneic islets; however, they are not able to prevent completely xenograft-induced microvascular perfusion failure. In contrast, novel immunosuppressants (e.g., RS-61443) or dietary supplementation of the antioxidant vitamin E were shown to prevent microvascular graft rejection almost completely, including leukocyte recruitment and capillary perfusion failure. Thus the development of novel strategies to improve posttransplant islet function should include concepts that accelerate the vascularization process and protect the newly formed microvasculature from rejection-mediated injury. The improvement of islet graft vascularization and the maintenance of adequate microvascular perfusion will contribute to the increased success of pancreatic islet transplantation.
Evaluation of Chronic Insomnia (2000)

Insomnia is a condition which affects millions of individuals, giving rise to emotional distress, daytime fatigue, and loss of productivity. Despite its prevalence, it has received scant clinical attention. An adequate evaluation of persistent insomnia requires detailed historical information as well as medical, psychological and psychiatric assessment. Use of a classification system for sleep disorders and familiarity with major diagnostic groups will facilitate the clinician's evaluation and treatment. Thorough assessment also requires attention to the unique aspects of presentation and specific set of etiologies which are associated with particular age groups.
A fast vocabulary independent algorithm for spotting words in speech (2002)

In applications such as audio-indexing, spoken message retrieval and video-browsing, it is necessary to have the ability to detect spoken words that are outside the vocabulary of the speech recognizer used in these systems, in large amounts of speech at speeds many times faster than real-time. We present a fast, vocabulary independent, algorithm for spotting words in speech. The algorithm consists of a preprocessing stage and a coarse-to-detailed search strategy for spotting a word/phone sequence in speech. The preprocessing method provides a phone-level representation of the speech that can be searched efficiently. The coarse search, consisting of phone-ngram matching, identifies regions of speech as putative word hits. The detailed acoustic match is then conducted only at the putative hits identified in the coarse match. This gives us the desired accuracy and speed in word spotting. Overall, the algorithm has a speed of execution that is 2400 times faster than real-time.
Formation and manipulation of two-dimensional arrays of micron-scale particles in microfluidic systems by surface acoustic waves (2009)

The two-dimensional concentration and manipulation of micron-scale particles by orthogonal, surface acoustic, standing waves is demonstrated. The particles are organized by liquid pressure waves in a microfluidic system over a piezoelectric substrate and form a uniform two-dimensional array with a spacing governed by the mechanical nodes of the two orthogonal, surface acoustic, standing waves. The nodal spacing can be controlled in each orthogonal direction independently by adjustment of the radio frequency applied to the separate acoustic wave transducers. This technique could be used to enhance the particle concentrations at sensing locations in DNA or protein array detectors.
Regulation of manganese superoxide dismutase by lipopolysaccharide, interleukin-1, and tumor necrosis factor. Role in the acute inflammatory response. (1990)

We have demonstrated a dramatic induction of manganese superoxide dismutase (Mn-SOD) mRNA levels in response to lipopolysaccharide (LPS), interleukin-1, and tumor necrosis factor in pulmonary epithelial cells. These stimuli had no effect on the corresponding mRNA levels for the copper/zinc (Cu/Zn)-SOD. Identical treatments of pulmonary fibroblast cells with LPS showed only minor changes in the Mn-SOD mRNA levels demonstrating a cell type-specific effect for this acute inflammatory mediator. Furthermore, we have shown that hyperoxia has no effect within 24 h on Mn-or Cu/Zn-SOD mRNA levels in either fibroblasts or epithelial cells. The induction of Mn-SOD mRNA levels by LPS is completely inhibited by actinomycin. Treatment of cells with cycloheximide causes an induction equal to that for LPS, whereas co-treatment with cycloheximide and LPS resulted in a "super induction." This data is strongly suggestive of an important role for the Mn-SOD in the acute inflammatory response.
Structural Elucidation of the Specificity of the Antibacterial Agent Triclosan for Malarial Enoyl Acyl Carrier Protein Reductase (2002)

The human malaria parasite Plasmodium falciparum synthesizes fatty acids using a type II pathway that is absent in humans. The final step in fatty acid elongation is catalyzed by enoyl acyl carrier protein reductase, a validated antimicrobial drug target. Here, we report the cloning and expression of the P. falciparum enoyl acyl carrier protein reductase gene, which encodes a 50-kDa protein (PfENR) predicted to target to the unique parasite apicoplast. Purified PfENR was crystallized, and its structure resolved as a binary complex with NADH, a ternary complex with triclosan and NAD(+), and as ternary complexes bound to the triclosan analogs 1 and 2 with NADH. Novel structural features were identified in the PfENR binding loop region that most closely resembled bacterial homologs; elsewhere the protein was similar to ENR from the plant Brassica napus (root mean square for Calphas, 0.30 A). Triclosan and its analogs 1 and 2 killed multidrug-resistant strains of intra-erythrocytic P. falciparum parasites at sub to low micromolar concentrations in vitro. These data define the structural basis of triclosan binding to PfENR and will facilitate structure-based optimization of PfENR inhibitors.
Identification of diphtheria toxin via screening as a potent cell cycle and p53-independent cytotoxin for human prostate cancer therapeutics (1998)

The rational screening of cytotoxins allows the identification of cell cycle-independent agents of variable potency against human prostate cancer. DT-mediated cell death is cell cycle independent, and p53 independent, making it particularly attractive for application to cytoreductive gene therapy, targeted monoclonal antibodies, and prodrug delivery of toxins applied to human prostate cancer therapeutics.
An Antibody–Drug Conjugate That Targets Tissue Factor Exhibits Potent Therapeutic Activity against a Broad Range of Solid Tumors (2013)

Tissue factor (TF) is aberrantly expressed in solid cancers and is thought to contribute to disease progression through its procoagulant activity and its capacity to induce intracellular signaling in complex with factor VIIa (FVIIa). To explore the possibility of using tissue factor as a target for an antibody-drug conjugate (ADC), a panel of human tissue factor-specific antibodies (TF HuMab) was generated. Three tissue factor HuMab, that induced efficient inhibition of TF:FVIIa-dependent intracellular signaling, antibody-dependent cell-mediated cytotoxicity, and rapid target internalization, but had minimal impact on tissue factor procoagulant activity in vitro, were conjugated with the cytotoxic agents monomethyl auristatin E (MMAE) or monomethyl auristatin F (MMAF). Tissue factor-specific ADCs showed potent cytotoxicity in vitro and in vivo, which was dependent on tissue factor expression. TF-011-MMAE (HuMax-TF-ADC) was the most potent ADC, and the dominant mechanism of action in vivo was auristatin-mediated tumor cell killing. Importantly, TF-011-MMAE showed excellent antitumor activity in patient-derived xenograft (PDX) models with variable levels of tissue factor expression, derived from seven different solid cancers. Complete tumor regression was observed in all PDX models, including models that showed tissue factor expression in only 25% to 50% of the tumor cells. In conclusion, TF-011-MMAE is a promising novel antitumor agent with potent activity in xenograft models that represent the heterogeneity of human tumors, including heterogeneous target expression.
Semi-dense Visual Odometry for a Monocular Camera (2013)

We propose a fundamentally novel approach to real-time visual odometry for a monocular camera. It allows to benefit from the simplicity and accuracy of dense tracking - which does not depend on visual features - while running in real-time on a CPU. The key idea is to continuously estimate a semi-dense inverse depth map for the current frame, which in turn is used to track the motion of the camera using dense image alignment. More specifically, we estimate the depth of all pixels which have a non-negligible image gradient. Each estimate is represented as a Gaussian probability distribution over the inverse depth. We propagate this information over time, and update it with new measurements as new images arrive. In terms of tracking accuracy and computational speed, the proposed method compares favorably to both state-of-the-art dense and feature-based visual odometry and SLAM algorithms. As our method runs in real-time on a CPU, it is of large practical value for robotics and augmented reality applications.
0.13-$\mu$m CMOS Phase Shifters for X-, Ku-, and K-Band Phased Arrays (2007)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> Two 4-bit active phase shifters integrated with all digital control circuitry in 0.13-<formula formulatype="inline"><tex>$\mu{\hbox {m}}$</tex> </formula> RF CMOS technology are developed for X- and K<emphasis emphasistype="italic">u</emphasis>-band (8–18 GHz) and K-band (18–26 GHz) phased arrays, respectively. The active digital phase shifters synthesize the required phase using a phase interpolation process by adding quadrature-phased input signals. The designs are based on a resonance-based quadrature all-pass filter for quadrature signaling with minimum loss and wide operation bandwidth. Both phase shifters can change phases with less than about 2 dB of RMS amplitude imbalance for all phase states through an associated DAC control. For the X- and K<emphasis emphasistype="italic">u</emphasis>-band phase shifter, the RMS phase error is less than 10<formula formulatype="inline"> <tex>$^{\circ}$</tex></formula> over the entire 5–18 GHz range. The average insertion loss ranges from <formula formulatype="inline"><tex>$-{\hbox {3~dB}}$</tex></formula> to <formula formulatype="inline"><tex>$-{\hbox {0.2~dB}}$</tex> </formula> at 5–20 GHz. The input <formula><tex>${P}_{\rm 1dB}$</tex> </formula> for all 4-bit phase states is typically <formula formulatype="inline"> <tex>$-{\hbox{5.4}}\pm {\hbox{1.3~dBm}}$</tex></formula> at 12 GHz in the X- and K<emphasis emphasistype="italic">u</emphasis>-band phase shifter. The K-band phase shifter exhibits 6.5–13<formula formulatype="inline"><tex>$^{\circ}$</tex> </formula> of RMS phase error at 15–26 GHz. The average insertion loss is from <formula formulatype="inline"><tex>$-$</tex></formula>4.6 to <formula formulatype="inline"><tex>$-{\hbox {3~dB}}$</tex></formula> at 15–26 GHz. The input <formula><tex>${P}_{\rm 1dB}$</tex></formula> of the K-band phase shifter is <formula formulatype="inline"><tex>$-{\hbox{0.8}}\pm {\hbox{1.1~dBm}}$</tex> </formula> at 24 GHz. For both phase shifters, the core size excluding all the pads and the output 50 <formula><tex>$\Omega$</tex></formula> matching circuits, inserted for measurement purpose only, is very small, 0.33<formula formulatype="inline"><tex>$\,\times\,$</tex></formula>0.43 <formula formulatype="inline"> <tex>${\hbox {mm}}^{2}$</tex></formula>. The total current consumption is 5.8 mA in the X- and K<emphasis emphasistype="italic">u</emphasis>-band phase shifter and 7.8 mA in the K-band phase shifter, from a 1.5 V supply voltage. </para>
Efficient Inhibition of Intra-Peritoneal Tumor Growth and Dissemination of Human Ovarian Carcinoma Cells in Nude Mice by Anti-L1-Cell Adhesion Molecule Monoclonal Antibody Treatment (2006)

The L1 cell adhesion molecule is implicated in the control of proliferation, migration, and invasion of several tumor cell types in vitro. Recently, L1 overexpression was found to correlate with tumor progression of ovarian carcinoma, one of the most common causes of cancer-related deaths in gynecologic malignant diseases. To evaluate L1 as a potential target for ovarian cancer therapy, we investigated the effects of anti-L1 monoclonal antibodies (chCE7 and L1-11A) on proliferation and migration of L1-positive human SKOV3ip ovarian carcinoma cells in vitro and the therapeutic efficacy of L1-11A against i.p. SKOV3ip tumor growth in nude mice. In vitro, both anti-L1 antibodies efficiently inhibited the proliferation of SKOV3ip cells as well as other L1-expressing tumor cell lines (renal carcinoma, neuroblastoma, and colon carcinoma). On two cell lines, hyper-cross-linking of L1-11A with a secondary antibody was necessary for significant inhibition of proliferation, indicating that cross-linking of L1 is required for the antiproliferative effect. L1-negative prostate carcinoma cells were not influenced by antibody treatment. Biweekly treatment of ovarian carcinoma-bearing mice with L1-11A led to a dose-dependent and significant reduction of tumor burden (up to -63.5%) and ascites formation (up to -75%). This effect was associated with reduced proliferation within the tumors. L1-directed antibody-based inhibition of peritoneal growth and dissemination of human ovarian carcinoma cells represents important proof-of-principle for the development of a new therapy against one of the leading gynecologic malignant diseases.
Use of Liquid Biopsies in Clinical Oncology: Pilot Experience in 168 Patients (2016)

Our initial study demonstrates that ctDNA tests provide information complementary to that in tissue biopsies and may be useful in determining prognosis and treatment. Clin Cancer Res; 22(22); 5497-505. ©2016 AACR.
Novel Water-soluble Bacteriochlorophyll Derivatives for Vascular-targeted Photodynamic Therapy: Synthesis, Solubility, Phototoxicity and the Effect of Serum Proteins¶ (2005)

New negatively charged water-soluble bacteriochlorophyll (Bchl) derivatives were developed in our laboratory for vascular-targeted photodynamic therapy (VTP). Here we focused on the synthesis, characterization and interaction of the new candidates with serum proteins and particularly on the effect of serum albumin on the photocytotoxicity of WST11, a representative compound of the new derivatives. Using several approaches, we found that aminolysis of the isocyclic ring with negatively charged residues markedly increases the hydrophilicity of the Bchl sensitizers, decreases their self-association constant and selectively increases their affinity to serum albumin, compared with other serum proteins. The photocytotoxicity of the new candidates in endothelial cell culture largely depends on the concentration of the serum albumin. Importantly, after incubation with physiological concentrations of serum albumin (500-600 microM), WST11 was found to be poorly photocytotoxic (>80% endothelial cell survival in cell cultures). However, in a recent publication (Mazor, O. et al. [2005] Photochem. Photobiol. 81, 342-351) we showed that VTP of M2R melanoma xenografts with a similar WST11 concentration resulted in approximately 100% tumor flattening and >70% cure rate. We therefore propose that the two studies collectively suggest that the antitumor activity of WST11 and probably of other similar candidates does not depend on direct photointoxication of individual endothelial cells but on the vascular tissue response to the VTP insult.
The Hydrophilic Isoform of Glutamate Decarboxylase, GAD67, Is Targeted to Membranes and Nerve Terminals Independent of Dimerization with the Hydrophobic Membrane-anchored Isoform, GAD65 (1999)

GAD67, the larger isoform of the gamma-aminobutyric acid-synthesizing enzyme glutamic acid decarboxylase, is a hydrophilic soluble molecule, postulated to localize at nerve terminals and membrane compartments by heterodimerization with the smaller membrane-anchored isoform GAD65. We here show that the dimerization region in GAD65 is distinct from the NH(2)-terminal membrane-anchoring region and that a membrane anchoring GAD65 subunit can indeed target a soluble subunit to membrane compartments by dimerization. However, only a fraction of membrane-bound GAD67 is engaged in a heterodimer with GAD65 in rat brain. Furthermore, in GAD65-/- mouse brain, GAD67, which no longer partitions into the Triton X-114 detergent phase, still anchors to membranes at similar levels as in wild-type mice. Similarly, in primary cultures of neurons derived from GAD65-/- mice, GAD67 is targeted to nerve terminals, where it co-localizes with the synaptic vesicle marker SV2. Thus, axonal targeting and membrane anchoring is an intrinsic property of GAD67 and does not require GAD65. The results suggest that three distinct moieties of glutamate decarboxylase localize to membrane compartments, an amphiphilic GAD65 homodimer, an amphiphilic GAD65/67 heterodimer, tethered to membranes via the GAD65 subunit, and a hydrophilic GAD67 homodimer, which associates with membranes by a distinct mechanism.
Stereochemistry of Dehydrogenation by D-Galactose Oxidase (1971)

The stereochemistry of dehydrogenation of the primary carbinol group of D-galactose by D-galactose oxidase has been determined. Using D-galactose-6-d and methyl β-D-galactopyranoside-6-d, it has been established that the reaction involves removal of the pro-S 6-hydrogen atom. This conclusion is based on product analysis, and on the relative impact of the deuterium isotope effect on oxidation rates of substrates having different R:S deuteration patterns. The absolute configurations at C-6 of these substrates have been determined by selective chemical transformations to products of known configuration. The rotational conformation of the 6-carbinol group of D-galactose and its possible relationship to the specificity of the enzyme are discussed, as well as the stereochemistry of reductive deuteration of aldehydo sugar derivatives.
Expression of the Xanthomonas campestris pv. vesicatoria hrp gene cluster, which determines pathogenicity and hypersensitivity on pepper and tomato, is plant inducible (1992)

The hrp gene cluster from Xanthomonas campestris pv. vesicatoria determines functions necessary not only for pathogenicity on the host plants pepper and tomato but also for the elicitation of the hypersensitive reaction on resistant host and nonhost plants. Transcriptional orientation and expression of the hrp loci were determined with hrp::Tn3-gus fusions. In addition, expression of the hrp loci was studied by RNA hybridization experiments. Expression of the hrp genes was not detectable after growth of the bacteria in complex medium or in minimal medium. However, high levels of induction of hrp gene expression were measured during growth of the bacteria in the plant. To search for a plant molecule responsible for this induction, we examined a variety of materials of plant origin for their ability to induce hrp gene expression. Filtrates from plant suspension cultures induced hrp genes to levels comparable to those induced in the plant. The inducing molecule(s) was found to be heat stable and hydrophilic and to have a molecular mass of less than 1,000 daltons.
Serum amyloid A protein induces production of matrix metalloproteinases by human synovial fibroblasts. (1998)

Serum amyloid A (SAA) is a precursor protein for amyloid A, which is a constituent for amyloid fibrils in secondary amyloidosis. To determine the role of SAA in the articular destruction in patients with rheumatoid arthritis (RA), we investigated the effects of SAA on the production of matrix metalloproteinases (MMPs) by rheumatoid synovial fibroblasts. SAA stimulated rheumatoid synovial fibroblasts to produce MMP-2 and MMP-3 in a dose-dependent manner. Pretreatment of synovial fibroblasts with cycloheximide prevented SAA-mediated MMP-2 and MMP-3 secretion. When SAA-containing media were immunodepleted by anti-SAA-specific antibody, SAA-mediated MMP secretion was also abrogated. The level of MMP-3 mRNA was increased in SAA-stimulated synovial fibroblasts compared with that of control cells. Our data indicate that SAA is a potent inducer of MMPs in the RA synovium and may play a critical role in the degradation of extracellular matrix in the rheumatoid joint.