gebhart/patrepeval huggingface dataset:
Expression of the multidrug resistance proteins MRP2 and MRP3 in human hepatocellular carcinoma (2001)

Treatment of hepatocellular carcinoma (HCC) by chemotherapy is often impeded by the intrinsic multidrug resistance (MDR) of this frequent primary cancer of the liver. The MDR phenotype can be caused by ATP-dependent export of chemotherapeutic drugs across the plasma membrane being mediated by transporters of the MDR P-glycoprotein family or of the multidrug resistance protein (MRP) family. To elucidate the role of MRP family members in HCC, we analyzed the expression and subcellular localization of MRP1 (ABCC1), MRP2 (ABCC2) and MRP3 (ABCC3); all 3 isoforms have been shown to confer resistance to chemotherapeutic drugs. Semiquantitative RT-PCR demonstrated that MRP2 and MRP3 mRNA expression in HCC was at least 10-fold higher than MRP1 mRNA expression. MRP2 immunostaining was observed in 87% (33/38) of HCC samples. MRP2 was localized in the plasma membrane in a polarized fashion, either in trabecular structures resembling the canalicular membrane or in the luminal membrane when cells had a pseudoglandular arrangement. MRP3 was detected in all samples examined (9/9) by RT-PCR and by immunofluorescence microscopy. MRP3 was localized to the basolateral membrane of carcinoma cells. Double-label immunofluorescence microscopy with antibodies specific for MRP2 or MRP3 indicated that carcinoma cells expressed both MRP isoforms simultaneously. When MRP1 was detected by immunofluorescence microscopy, it was localized on the intracellular membranes of carcinoma cells. Thus, plasma membrane expression of MRP2 and MRP3, but not of MRP1, can contribute to the MDR phenotype of HCC.
An End-to-End Compression Framework Based on Convolutional Neural Networks (2017)

Deep learning, e.g., convolutional neural networks (CNNs), has achieved great success in image processing and computer vision especially in high level vision applications such as recognition and understanding. However, it is rarely used to solve low-level vision problems such as image compression studied in this paper. Here, we move forward a step and propose a novel compression framework based on CNNs. To achieve high-quality image compression at low bit rates, two CNNs are seamlessly integrated into an end-to-end compression framework. The first CNN, named compact convolutional neural network (ComCNN), learns an optimal compact representation from an input image, which preserves the structural information and is then encoded using an image codec (e.g., JPEG, JPEG2000 or BPG). The second CNN, named reconstruction convolutional neural network (RecCNN), is used to reconstruct the decoded image with high-quality in the decoding end. To make two CNNs effectively collaborate, we develop a unified end-to-end learning algorithm to simultaneously learn ComCNN and RecCNN, which facilitates the accurate reconstruction of the decoded image using RecCNN. Such a design also makes the proposed compression framework compatible with existing image coding standards. Experimental results validate that the proposed compression framework greatly outperforms several compression frameworks that use existing image coding standards with state-of-the-art deblocking or denoising post-processing methods.
Migraine: Preventive Treatment (2001)

Preventive treatment is designed to decrease headache frequency. It should be used if headaches are too frequent, disabling, or associated with worrisome neurological features or if acute treatment is overused or ineffective. The chosen drug should be given an adequate trial in the absence of interfering medications. Choose a drug based on its efficacy, adverse event profile, and the presence of coexistent conditions.
Vision-based sensor for real-time measuring of surface traction fields (2005)

The desire to reproduce and expand the human senses drives innovations in sensor technology. Conversely, human-interface research aims to allow people to interact with machines as if they were natural objects in a cybernetic, human-oriented way. We wish to unite the two paradigms with a haptic sensor as versatile as the sense of touch and developed for a dual purpose: to improve the robotic capability to interact with the physical world, and to improve the human capability to interact with the virtual world for emerging applications with a heightened sense of presence. We designed a sensor, dubbed GelForce, that acts as a practical tool in both conventional and novel desktop applications using common consumer hardware. By measuring a surface traction field, the GelForce tactile sensor can represent the magnitude and direction of force applied to the skin's surface using computer vision. This article is available with a short video documentary on CD-ROM.
Inactivation of Retroviruses with Preservation of Structural Integrity by Targeting the Hydrophobic Domain of the Viral Envelope (2005)

We describe a new approach for the preparation of inactivated retroviruses for vaccine application. The lipid domain of the viral envelope was selectively targeted to inactivate proteins and lipids therein and block fusion of the virus with the target cell membrane. In this way, complete elimination of the infectivity of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) could be achieved with preservation of antigenic determinants on the surface of the viral envelope. Inactivation was accomplished by modification of proteins and lipids in the viral envelope using the hydrophobic photoinduced alkylating probe 1,5 iodonaphthylazide (INA). Treatment of HIV and SIV isolates with INA plus light completely blocked fusion of the viral envelope and abolished infectivity. The inactivated virus remained structurally unchanged, with no detectable loss of viral proteins. Modifications to envelope and nucleocapsid proteins were detected by changes in their elution pattern on reverse-phase high-performance liquid chromatography. These modifications had no effect on primary and secondary structure epitopes as determined by monoclonal antibodies. Likewise, the inactivated HIV reacted as well as the live virus with the conformation-sensitive and broadly neutralizing anti-HIV type 1 monoclonal antibodies 2G12, b12, and 4E10. Targeting the lipid domain of biological membranes with hydrophobic alkylating compounds could be used as a general approach for inactivation of enveloped viruses and other pathogenic microorganisms for vaccine application.
Metal–Organic Frameworks with Mechanically Interlocked Pillars: Controlling Ring Dynamics in the Solid-State via a Reversible Phase Change (2014)

Metal-organic framework (MOF) materials have been prepared that contain a mechanically interlocked molecule (MIM) as the pillaring strut between two periodic Zn-carboxylate layers. The MIM linker is a [2]rotaxane with a [24]crown-6 (24C6) macrocycle and an aniline-based axle with terminal pyridine donor groups. The single-crystal X-ray structures of MOFs UWDM-2 (1,4-diazophenyl-dicarboxylate) and UWDM-3 (1,4-biphenyl-dicarboxylate) show that both frameworks are large enough to contain the free volume required for rotation of the interlocked 24C6 macrocycle, but the frameworks are interpenetrated (UWDM-2, three-fold, and UWDM-3, two-fold). In particular, for UWDM-3 the 24C6 rings of the pillaring MIM are positioned directly inside the square openings of neighboring zinc dicarboxylate layers. Variable-temperature (VT) (2)H SSNMR demonstrated that the 24C6 macrocycles in UWDM-2 and UWDM-3 can only undergo restricted motions related to ring flexibility or partial rotation but are incapable of undergoing free rotation. VT-powder X-ray diffraction studies showed that upon activation of UWDM-3, by removing solvent, a phase change occurs. The new β-phase of UWDM-3 retained crystallinity, and (2)H SSNMR demonstrated that the 24C6 macrocyclic ring of the pillared MIM strut is now free enough to undergo full rotation. Most importantly, the phase change is reversible; the β version of the MOF can be reverted to the original α state by resolvation, thus demonstrating, for the first time, that the dynamics of a MIM inside a solid material can be controlled by a reversible phase change.
The impact of out-of-order commit in coarse-grain, fine-grain and simultaneous multithreaded architectures (2008)

Multithreaded processors in their different organizations (simultaneous, coarse grain and fine grain) have been shown as effective architectures to reduce the issue waste. On the other hand, retiring instructions from the pipeline in an out-of-order fashion helps to unclog the ROB when a long latency instruction reaches its head. This further contributes to maintain a higher utilization of the available issue bandwidth. In this paper, we evaluate the impact of retiring instructions out of order on different multithreaded architectures and different instruction fetch policies, using the recently proposed Validation Buffer microarchitecture as baseline out-of-order commit technique. Experimental results show that, for the same performance, out-of-order commit permits to reduce multithread hardware complexity (e.g., fine grain multithreading with a lower number of supported threads).
Lactulose–Mannitol Intestinal Permeability Test in Children With Diarrhea Caused by Rotavirus and Cryptosporidium (2000)

The results indicate that increased intestinal permeability caused by rotavirus or cryptosporidium infections in Peruvian infants less than 36 months of age is a significant but reversible phenomenon. The temporal relationship observed in the current study and the contribution of such alterations in intestinal mucosal integrity to the burden of diarrheal disease and the development of malnutrition in developing countries is discussed.
Complications of anterior approaches to the thoracolumbar spine. Emphasis on Kaneda instrumentation. (1994)

One hundred eighty five consecutive patients underwent anterior decompression, stabilization, and/or fusion procedures of the thoracolumbar spine. At 1 year or more followup, the incidence of complications was analyzed. There were no iatrogenic spinal neurologic deficits and no deep wound infections. The most common complication was in 13 patients who developed more than 20 kyphosis. The use of Kaneda anterior instrumentation provided marked improvement in the prevention of this problem. A custom made carbon fiber reinforced cage packed with autogenous cancellous bone graft used in the treatment of ten patients with large corpectomy defects resulted in a good outcome.
A synthetic biology challenge: making cells compute (2007)

Advances in biology and engineering have enabled the reprogramming of cells with well-defined functions, leading to the emergence of synthetic biology. Early successes in this nascent field suggest its potential to impact diverse areas. Here, we examine the feasibility of engineering circuits for cell-based computation. We illustrate the basic concepts by describing the mapping of several computational problems to engineered gene circuits. Revolving around these examples and past studies, we discuss technologies and computational methods available to design, test, and optimize gene circuits. We conclude with discussion of challenges involved in a typical design cycle, as well as those specific to cellular computation.
19-kDa tumor antigen coded by early region E1b of adenovirus 2 is required for efficient synthesis and for protection of viral DNA. (1984)

The adenovirus E1b region (mp 4.5-11.2) codes for two major tumor antigens of 53 and 19 kDa. The lp+ locus maps within the 19-kDa tumor antigen-coding region and has been shown to play an essential role in cell transformation. We have investigated the role of the 19-kDa tumor antigen during productive virus growth using a specific Ad2 mutant (dl250) lacking most of the 19-kDa tumor antigen-coding region. Mutant dl250 grows more slowly and yields about 100-fold less progeny virus than Ad2 wt in human KB cells. In cells infected with mutant dl250, viral DNA is present at only about one-half the level of that of Ad2 wt. The defect in DNA accumulation appears to be both at the level of DNA synthesis and stability of newly synthesized DNA. In mutant-infected cells, newly replicated viral as well as cellular DNA are extensively degraded during late stages of viral infection. We have mapped a class of Ad12 (highly oncogenic group A) mutants (cyt) that are nononcogenic in newborn hamsters and induce DNA degradation to the 19-kDa tumor antigen-coding region by intertypic complementation analysis. These results strongly suggest that the 19-kDa tumor antigen plays an essential role in efficient viral DNA synthesis and protection of newly replicated viral DNA against cellular nucleases in addition to its role in cell transformation and tumorigenesis.
Novel Ring Cleavage Products in the Biotransformation of Biphenyl by the Yeast Trichosporon mucoides (2001)

The yeast Trichosporon mucoides, grown on either glucose or phenol, was able to transform biphenyl into a variety of mono-, di-, and trihydroxylated derivatives hydroxylated on one or both aromatic rings. While some of these products accumulated in the supernatant as dead end products, the ortho-substituted dihydroxylated biphenyls were substrates for further oxidation and ring fission. These ring fission products were identified by high-performance liquid chromatography, gas chromatography-mass spectrometry, and nuclear magnetic resonance analyses as phenyl derivatives of hydroxymuconic acids and the corresponding pyrones. Seven novel products out of eight resulted from the oxidation and ring fission of 3,4-dihydroxybiphenyl. Using this compound as a substrate, 2-hydroxy-4-phenylmuconic acid, (5-oxo-3-phenyl-2,5-dihydrofuran-2-yl)acetic acid, and 3-phenyl-2-pyrone-6-carboxylic acid were identified. Ring cleavage of 3,4,4'-trihydroxybiphenyl resulted in the formation of [5-oxo-3-(4'-hydroxyphenyl)-2,5-dihydrofuran-2-yl]acetic acid, 4-(4'-hydroxyphenyl)-2-pyrone-6-carboxylic acid, and 3-(4'-hydroxyphenyl)-2-pyrone-6-carboxylic acid. 2,3,4-trihydroxybiphenyl was oxidized to 2-hydroxy-5-phenylmuconic acid, and 4-phenyl-2-pyrone-6-carboxylic acid was the transformation product of 3,4,5-trihydroxybiphenyl. All these ring fission products were considerably less toxic than the hydroxylated derivatives.
Shift of pH-Value During Thermal Treatments in Buffer Solutions and Selected Foods (2010)

The pH value is one of the most important process parameters during thermal treatments, regardless if the medium is a simple buffer solution or a complex food matrix. When the temperature increases after an initial measurement of the pH at ambient temperature (25°C), a significant pH shift could occur, which could produce incomparable results in different buffer solutions or lead to side reactions during food preservation. Consequently, a measurement cell was constructed to record online the pH-value and temperature up to 130°C. By applying the Nernst equation, it was possible to exclude the temperature-dependent influence of the pH glass electrode on the total pH value. The pH shift was measured over a wide temperature range (ΔT 20–130°C) in the most commonly used buffer solutions and some selected food matrices. The ΔpH of certain buffer solutions, namely TRIS and ACES, showed a significant pH decrease of −2.01 ± 0.08 (ΔT 20–130°C) and −1.27 ± 0.1 (ΔT 20–130°C), respectively, whereas the pH of PBS buffer solution was nearly independent of temperature. The ΔpH decrease recorded in milk (−0.89 ± 0.6, ΔT 20–130°C) as well as commercial and self-made baby food (−0.56 ± 0.05, ΔT 20–130°C) is of special interest for the food industry to get a deeper insight in occurring reactions during thermal preservation processes.
An alternatively processed mRNA generated from human hepatocyte growth factor gene (1991)

We recently reported the isolation and sequencing of cDNA for human hepatocyte growth factor (hHGF) [Miyazawa, K., Tsubouchi, H., Naka, D., Takahashi, K., Okigaki, M., Arakaki, N., Nakayama, H., Hirono, S., Sakiyama, O., Takahashi, K., Gohda, E., Daikuhara, Y. & Kitamura, N. (1989) Biochem. Biophys. Res. Commun. 163, 967-973]. In the present study, we report the sequence of another cDNA clone for a shorter form of hHGF mRNA. Comparison of the sequence with that of the hHGF cDNA revealed that the two sequences are identical in their 5' ends up to 865 nucleotides downstream from the translation-initiation site, then completely diverge from each other. By Northern blot analysis, the hHGF-related 1.5-kb mRNA, which corresponded to the newly isolated cDNA variant, was identified in human placenta. Sequence analysis of a human genomic HGF clone showed that the diverged 3'-terminal portion of the mRNA is generated by alternative RNA-processing events utilizing a specific exon. The mRNA could encode a short hHGF molecule of 290 amino acids corresponding to the N-terminal portion of hHGF which consists of 728 amino acids. In order to examine the effect of the predicted translation product on hepatocyte growth, an expression plasmid for the cDNA variant was constructed and transfected into Cos cells. Immunoblotting analysis showed that the transfected Cos cells produced a protein of about 33 kDa. The protein product did not stimulate DNA synthesis by rat hepatocytes in primary culture.
STAT3 Is Required for the gp130-mediated Full Activation of the c-myc Gene (1999)

The signal transducers and activators of transcription (STAT) family members have been implicated in regulating the growth, differentiation, and death of normal and transformed cells in response to either extracellular stimuli, including cytokines and growth factors, or intracellular tyrosine kinases. c-myc expression is coordinately regulated by multiple signals in these diverse cellular responses. We show that STAT3 mostly mediates the rapid activation of the c-myc gene upon stimulation of the interleukin (IL)-6 receptor or gp130, a signal transducing subunit of the receptor complexes for the IL-6 cytokine family. STAT3 does so most likely by binding to cis-regulatory region(s) of the c-myc gene. We show that STAT3 binds to a region overlapping with the E2F site in the c-myc promoter and this site is critical for the c-myc gene promoter- driven transcriptional activation by IL-6 or gp130 signals. This is the first identification of the linkage between a member of the STAT family and the c-myc gene activation, and also explains how the IL-6 family of cytokines is capable of inducing the expression of the c-myc gene.
Synthesis and biological activity of a ketomethylene analog of a tripeptide inhibitor of angiotensin converting enzyme (1980)

An analogue of a tripeptide inhibitor of angiotensin converting enzyme, Bz-Phe-Gly-Pro, has been synthesized in which the amide bond connecting phenylalanine and glycine has been replaced by a ketomethylene group. This nonpeptide analogue, 20, shows more potent converting enzyme inhibiting activity, I50 = 0.07 microM, than Bz-Phe-Gly-Pro, I50 = 9.4 microM, or than the orally active D-3-mercapto-2-methylpropanoyl-L-proline (captopril, 1), I50 = 0.30 microM. Compound 20 has a Ki of 1.06 X 10(-7) and either competitive or noncompetitive enzyme kinetics depending on what substrate is used in the converting enzyme assay. In tests for inhibition of angiotensin I induced contractions in the guinea pig ileum, 20 has one-tenth the activity of 1.
Induction of HIV‐1 envelope (gp120)‐specific cytotoxic T lymphocyte responses in mice by recombinant CHO cell‐derived gp120 is enhanced by enzymatic removal of N‐linked glycans (1994)

Priming of CD8+ cytotoxic T lymphocyte (CTL) responses with recombinant proteins has been facilitated by the development of novel adjuvants that deliver antigens into the class I major histocompatibility complex (MHC) pathway. However, the extent to which secondary structure or glycosylation of these proteins prevents priming of class I MHC-restricted CTL responses is not clear. To address this issue, recombinant HIV-1 gp120 envelope proteins produced in yeast insect, or mammalian cells were compared for the ability to elicit CD8+ CTL activity in mice. Envelope-specific CD8+ T lymphocytes were detected in BALB/c mice immunized with env 2-3, a 55-kDa yeast-derived envelope protein that is not glycosylated and lacks a native conformation. This response was directed against a previously described epitope in the V3 region of gp120, as well as a newly identified epitope located near the carboxy-terminus of the molecule. Similar levels of V3-directed CTL activity were observed in mice immunized with recombinant gp120 produced in insect (Spodoptera fugiperda) cells using a baculovirus expression system (gp120BAC). In contrast, induction of CTL responses was considerably less efficient when mice were immunized with gp120CHO, a native, fully glycosylated envelope protein produced in mammalian CHO cells. Denaturation of gp120CHO prior to immunization was not sufficient to prime CTL responses. However, envelope-specific CD8+ CTL activity was elicited when N-linked glycans were removed by treatment with an endoglycosidase. Possible mechanisms by which N-linked glycans influence delivery or processing of recombinant proteins for class I MHC presentation, and the implications of these findings for the design of subunit vaccines, are discussed.
Assays for Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Reverse ADCC (Redirected Cytotoxicity) in Human Natural Killer Cells (2003)

Crosslinking of molecules involved in the recognition of target cells elicits natural killer (NK) cell cytotoxicity, inducing either release of preformed cytotoxic mediators via granule exocytosis, or (enhanced) expression of ligands for target cell membrane-associated molecules that transduce apoptotic signals, e.g., Fas Ligand (FasL) or TRAIL (reviewed in refs. ,). Target cell recognition by NK cells occurs via either of two ways: (1) receptors capable of binding molecules on the target cells that include, but are not limited to, adhesion molecules and the identities of which are incompletely defined (reviewed in ref. ); and (2) receptors for the Fc fragment of IgG (FcγRIIIA, CD 16) (, reviewed in ref. ). The latter bind immunecomplexed IgG and therefore target cells that, not recognized spontaneously by NK cells, are sensitized with anti-target cell antibodies (Abs) of the IgG class. The two types of cytotoxicity elicited are referred to as “spontaneous” and “Ab-dependent’ cell-mediated cytotoxicity (ADCC).
Isolation and characterization of a precursor form of lysosomal α‐glucosidase from human urine (1984)

A two-step procedure is described for the isolation of lysosomal alpha-glucosidase from human urine. In the second step, affinity chromatography on Sephadex G-100, two fractions with acid alpha-glucosidase activity were obtained. Fraction I contained alpha-glucosidase of Mr 109000, whereas fraction II contained components of Mr 76000 and 70000. alpha-Glucosidase in fraction I had an Mr similar to that of the precursor of alpha-glucosidase detected in the medium of fibroblasts after labelling with [14C]leucine. The components in fraction II had Mr identical to those of the mature forms of alpha-glucosidase found in placenta or cultured human skin fibroblasts. alpha-Glucosidase in fraction I contained mannose 6-phosphate (3.5 mol/mol polypeptide). No mannose 6-phosphate was present in the components in fraction II. Fraction I, but not fraction II, was avidly endocytosed by alpha-glucosidase-deficient cultured human skin fibroblasts. Endocytosis of fraction I was inhibited by mannose 6-phosphate. The pH optimum and Km values for p-nitrophenyl alpha-glucoside, maltose and glycogen of fractions I and II alpha-glucosidase were almost identical. However, the activity with glycogen relative to that of either p-nitrophenyl alpha-glucoside or maltose was lower in fraction I than in fraction II. It is concluded that fraction I consists of the precursor form of alpha-glucosidase and fraction II of the mature forms of the enzyme. The importance of urine as a source of precursors of lysosomal enzymes is discussed.