gebhart/patrepeval huggingface dataset:
A GM-CSF and CD40L bystander vaccine is effective in a murine breast cancer model (2015)

The use of BCG bystander cell lines demonstrates proof of concept for anti-tumor activity and immunogenicity in an immunocompetent murine model of breast cancer. This vaccine is being evaluated in lung cancer and should be explored further in clinical trials of breast cancer patients at high risk of recurrence or in combination with other immunomodulatory agents.
Massive MU-MIMO downlink TDD systems with linear precoding and downlink pilots (2013)

We consider a massive MU-MIMO downlink time-division duplex system where a base station (BS) equipped with many antennas serves several single-antenna users in the same time-frequency resource. We assume that the BS uses linear precoding for the transmission. To reliably decode the signals transmitted from the BS, each user should have an estimate of its channel. In this work, we consider an efficient channel estimation scheme to acquire CSI at each user, called beamforming training scheme. With the beamforming training scheme, the BS precodes the pilot sequences and forwards to all users. Then, based on the received pilots, each user uses minimum mean-square error channel estimation to estimate the effective channel gains. The channel estimation overhead of this scheme does not depend on the number of BS antennas, and is only proportional to the number of users. We then derive a lower bound on the capacity for maximum-ratio transmission and zero-forcing precoding techniques which enables us to evaluate the spectral efficiency taking into account the spectral efficiency loss associated with the transmission of the downlink pilots. Comparing with previous work where each user uses only the statistical channel properties to decode the transmitted signals, we see that the proposed beamforming training scheme is preferable for moderate and low-mobility environments.
Cell cycle-dependent expression of mammalian ribonucleotide reductase. Differential regulation of the two subunits. (1985)

Consistent with its specialized role in DNA synthesis, the activity of ribonucleotide reductase is cell cycle-dependent, reaching its maximum during S-phase. This paper demonstrates, however, the levels of the two protein subunits, M1 and M2, of this enzyme vary independently of one another. The level of protein M1 was determined by use of a two-site monoclonal antibody-enzyme immunoassay and found to be constant throughout the cell cycle in bovine kidney MDBK cells. Pulse-chase experiments showed that the half-life of protein M1 was 15 h. This contrasts with our previous results demonstrating an S-phase-correlated increase in the concentration of protein M2 and a half-life of this subunit of 3 h. Therefore, ribonucleotide reductase is controlled during the cell cycle by the level of protein M2.
Thermal properties of AlAs/GaAs superlattices (1987)

Thermal properties of semiconductor superlattices have been investigated for the first time. The thermal properties of AlAs/GaAs superlattices were measured with the ac calorimetric method. It is found that the thermal diffusivity and thermal conductivity of the AlAs/GaAs superlattices are larger than those of the AlGaAs alloy due to the suppression of alloy scattering in the superlattice. However, the thermal diffusivity and thermal conductivity decrease with a decrease in the superlattice period and seem to approach those of the Al0.5Ga0.5As alloy in the limit of short-period superlattices.
Alpha 1-adrenergic stimulation of cardiac gene transcription in neonatal rat myocardial cells. Effects on myosin light chain-2 gene expression. (1988)

Previous studies have demonstrated that alpha-adrenergic stimulation of cultured, neonatal rat myocardial cells results in an increase in intracellular volume and protein content of cultured neonatal rat myocardial cells. Utilizing this model of cardiac hypertrophy, we have examined the effects of alpha-adrenergic stimulation on the accumulation of sarcomeres and the expression of a rat cardiac myofibrillar gene, myosin light chain-2 (MLC-2). Following alpha-adrenergic stimulation, cultured myocardial cells displayed a severalfold increase in the number of sarcomeric units, as assessed by electron microscopy, an increase in cellular MLC-2 content, and a 2-3 fold increase in the steady state levels of MLC-2 mRNA. This effect of alpha-adrenergic stimulation was accompanied by a 2-3-fold increase in total transcriptional activity, which was dependent on the concentration and duration of exposure to the agonist, and displayed alpha 1-adrenergic receptor specificity. The transcriptional response was not immediate, with a lag period of at least 1 h, and a maximal effect required continuous occupancy of the receptor. The increase in steady state levels of MLC-2 mRNA is regulated, in part, at the level of transcription of the cardiac MLC-2 gene. These results suggest that alpha 1-adrenergic stimulation may be important in the growth of the neonatal heart through the activation of total transcriptional activity. In addition, increases in the levels of myofibrillar proteins during myocardial cell growth and hypertrophy, may be mediated in part by the stimulation of transcription of myofibrillar genes.
Adiponectin receptor expression is elevated in colorectal carcinomas but not in gastrointestinal stromal tumors (2008)

Circulating adiponectin is inversely associated with colorectal carcinoma. However, adiponectin receptor expression has not been examined in normal gastrointestinal tissue, colorectal malignancies, or gastrointestinal stromal tumors (GISTs). We collected 40 colorectal carcinomas and 12 non-tumor colorectal tissue specimens from patients with colorectal cancer, as well as 45 tumor and 13 non-tumor specimens from patients with GIST. Expression and localization of adiponectin receptors (AdipoR1 and AdipoR2) were assessed using immunohistochemistry. We also confirmed expression of adiponectin receptors using rtPCR in matched normal and colorectal cancer specimens obtained from five patients. Finally, we detected adiponectin receptors and assessed adiponectin signaling in three colon cancer cell lines. Adiponectin receptor expression, assessed by either rtPCR or immunohistochemistry, was present in normal tissue and was significantly lower than in colorectal carcinomas. Among carcinomas, 95% displayed positive or strongly positive expression of AdipoR1 and 88% of AdipoR2, versus 8% and 0%, respectively, for non-tumor specimens (P<0.0001). AdipoR1 expression assessed by rtPCR was 1.6-fold higher in tumor than in non-tumor tissue (P<0.05). In addition, we found that adiponectin at physiological concentrations can activate in vitro intracellular signaling pathways in three colon cancer cell lines, expressing both adiponectin receptors 1 and 2. No significant differences in expression of adiponectin receptors in tumor versus non-tumor GI specimens were detected among patients with GIST. Colon cancer cell lines express adiponectin receptors, through which adiponectin activates in vitro intracellular signaling pathways. Adiponectin receptors are also detected in normal GI tissue and their expression is elevated in colorectal carcinomas, but not in GIST.
Identification of the essential cysteine residue in the active site of bovine pyruvate dehydrogenase. (1993)

Pyruvate dehydrogenase (E1), the first catalytic component of the bovine pyruvate dehydrogenase complex, is composed of two nonidentical subunits in a tetrameric alpha 2 beta 2 form. The sulfhydryl-specific reagent N-ethylmaleimide (NEM) was used to identify the reactivities and function of cysteinyl residues and subsequent identification of these residues in the active site of bovine E1. Treatment of E1 with 0.2 mM NEM resulted in loss (90%) of enzymatic activity; the inactivation followed bimolecular reaction kinetics. The inactivation was almost entirely prevented by thiamin pyrophosphate (TPP) and pyruvate; protection is probably due to formation of the hydroxyethylidene-TPP intermediate. To identify the reactive cysteinyl residues in the active site region, the nonessential SH groups in E1 were first modified with NEM in the presence of TPP and pyruvate. After quenching with dithiothreitol and removal of the substrate and cofactor by dialysis, the modified E1 was treated with [14C]NEM to label the exposed cysteinyl residue(s) in or near the active site region. The data indicate that NEM reacted in the active site region of the E1 component with a stoichiometry of 2 mol of [14C]NEM bound per mol of E1 tetramer. The initial rapid labeling of E1 with [14C]NEM established that incorporation was predominantly into the alpha subunit. A single radiolabeled peptide was isolated following V8 protease digestion of radiolabeled E1 by [14C]NEM. Sequence analysis of the labeled peptide derived from bovine E1 demonstrated that the labeled cysteinyl residue was equivalent to Cys-62 in the alpha subunit (mature form) of human E1.
Modulation of MHC class II transport and lysosome distribution by macrophage-colony stimulating factor in human dendritic cells derived from monocytes (2001)

The macrophage-colony stimulating factor (M-CSF) has been already shown to affect the function of dendritic cells (DC). Therefore, the differentiation of dendritic cells into macrophages (M(PHI)) might represent a pathway which could inhibit the immune response initiated by DC. Because Major Histocompatibility Complex class II molecules (MHC-II) are crucial for DC function, we asked whether M-CSF may influence the intracellular transport of MHC-II in monocyte derived DC. We found that, at early stages, M-CSF induced first a rapid redistribution of MHC-II from the MHC-II containing compartments (MIIC) to the plasma membrane and second an increase in MHC-II synthesis as observed with LPS or TNF-(alpha). These processes were associated with the sorting of MHC-II from lysosomal membranes which underwent a drastic structural reorganization. However, in contrast to tumor necrosis factor (TNF)-(alpha) or lipopolysaccharide (LPS), M-CSF neither potentiated the allostimulatory function of DC nor allowed the stabilization of MHC-II at the cell surface, but rather increased MHC-II turnover. We conclude that the rapid modulation of MHC-II transport and distribution may participate in the inhibitory effect of M-CSF on DC function and differentiation.
INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53 (1999)

The INK4a/ARF locus encodes upstream regulators of the retinoblastoma and p53 tumor suppressor gene products. To compare the impact of these loci on tumor development and treatment response, the Emu-myc transgenic lymphoma model was used to generate genetically defined tumors with mutations in the INK4a/ARF, Rb, or p53 genes. Like p53 null lymphomas, INK4a/ARF null lymphomas formed rapidly, were highly invasive, displayed apoptotic defects, and were markedly resistant to chemotherapy in vitro and in vivo. Furthermore, INK4a/ARF(-/-) lymphomas displayed reduced p53 activity despite the presence of wild-type p53 genes. Consequently, INK4a/ARF and p53 mutations lead to aggressive tumors by disrupting overlapping tumor suppressor functions. These data have important implications for understanding the clinical behavior of human tumors.
Comprehensive Mechanistic Analysis of Hits from High-Throughput and Docking Screens against β-Lactamase (2008)

High-throughput screening (HTS) is widely used in drug discovery. Especially for screens of unbiased libraries, false positives can dominate "hit lists"; their origins are much debated. Here we determine the mechanism of every active hit from a screen of 70,563 unbiased molecules against beta-lactamase using quantitative HTS (qHTS). Of the 1,274 initial inhibitors, 95% were detergent-sensitive and were classified as aggregators. Among the 70 remaining were 25 potent, covalent-acting beta-lactams. Mass spectra, counter-screens, and crystallography identified 12 as promiscuous covalent inhibitors. The remaining 33 were either aggregators or irreproducible. No specific reversible inhibitors were found. We turned to molecular docking to prioritize molecules from the same library for testing at higher concentrations. Of 16 tested, 2 were modest inhibitors. Subsequent X-ray structures corresponded to the docking prediction. Analog synthesis improved affinity to 8 microM. These results suggest that it may be the physical behavior of organic molecules, not their reactivity, that accounts for most screening artifacts. Structure-based methods may prioritize weak-but-novel chemotypes in unbiased library screens.
The growth of polio virus in human diploid fibroblasts grown with cellulose microcarriers in suspension cultures. (1987)

Human diploid fibroblasts have been successfully grown with cellulose fiber microcarriers in suspension giving values of between 1 to 2 X 10(6) cells/ml. When infected with polio virus type 1 titers were obtained which were at least as good or better than those obtained with monkey kidney cells and similar to that obtained with Vero cells. Good results were also obtained using conventional microcarriers such as Cytodex, Biosilon and Gelibeads. Our results suggest that many of the technical difficulties in growing human diploid fibroblasts on microcarriers can be overcome allowing these cells to be a favourable alternative to heteroploid cells as a substrate for viral vaccine production.
Inhibition of mycobacteria by garlic extract (Allium sativum) (1985)

Thirty strains of mycobacteria, consisting of 17 species, were inhibited by various concentrations of garlic extract incorporated in Middlebrook 7H10 agar. The concentration required ranged from a low of 1.34 mg/ml to a high of 3.35 mg/ml of media. When there were multiple strains of a species, a mean inhibitory concentration was determined for that species. Six strains of Mycobacterium tuberculosis required a mean inhibitory concentration of 1.67 mg/ml of media.
Using Microseismic Events to Constrain Fracture Network Models and Implications for Generating Fracture Flow Properties for Reservoir Simulation (2008)

Abstract Microseismic monitoring of hydraulic fracture stimulation treatments has done much to diminish the expectation of engineers and geoscientists that symmetrical bi-wing fractures extending away from the well bore from as a result of the treatment. Mapping of microseismic event locations indicates that more often, zones of high complexity form which suggest multiple rock failure mechanisms could be in play during the stimulation treatment. The complexity of the failure is further complicated, or perhaps explained, by the interaction of the perturbed stresses with existing fractures in the reservoir relative to the unperturbed stress state of the reservoir. Existing fracture planes favorably oriented for shear will fail at lower stresses than are required to create new fractures. Geologic mapping and regional to local in-situ stress information will allow informed interpretation of the resulting microseismicity patterns as well as providing predictive capability for fracturing patterns of treatments in subsequent area wells and production planning. Correlative to the improved fracture mapping is the use of the fracture interpretation as input to fractured reservoir modeling and fractured reservoir simulation. Utilizing microseismicity data not only to constrain location of fractures, but also fracture size, shape and orientation allows creation of improved fractured reservoir models based on geologic concepts and supported by the real time data. In this paper two examples are presented from a hydraulic stimulation of North American mid-continent wells that were monitored with a surface-based geophone array. The resulting microseismicity patterns in both wells show that the fracture development was strongly influenced by pre-existing discontinuities (fractures or faults), which are easily explained by geologic and in-situ stress analysis. The fracture interpretation and microseismicity data from one example is used to generate a discrete fracture network from which fracture flow properties are created in a geocellular model. The resulting model provides a quantitative framework for production history mapping and reservoir behavior, with hard constraints for the behavior of the dominant fractures in the fracture network.
Atomic Layer Epitaxy Growth of Tantalum Oxide Thin Films from Ta (  OC 2 H 5 ) 5 and  H 2 O (1995)

The deposition of thin films by atomic layer epitaxy (ALE) was investigated in the temperature range of 150 to 450°C using and water as precursors. Because of the thermal self‐decomposition of the self‐limiting ALE growth was achieved only below 350°C. All the films grown were amorphous as examined by x‐ray diffraction analysis. The films grown at 250 and 325°C were stoichiometric within the accuracy of Rutherford backscattering spectrometry and contained 4 and 0.6 atom percent (a/o) hydrogen as determined by nuclear reaction analysis, respectively. Except for the outermost surface, the content of carbon residues was below 3 a/o as analyzed by x‐ray photoelectron spectroscopy. The films exhibited smooth surfaces as observed by scanning electron microscopy and relatively uniform thicknesses with 7% deviation in the gas flow direction. The refractive index of the films increased with deposition temperature stabilizing at 2.23 at temperatures higher than 300°C. The permittivities for the films grown at 250 and 325°C were 21 and 25, respectively, and leakage current densities at 1 MV/cm electric field were 4.0 and 2.3 mA/cm2, respectively.
Application of the Cre recombinase/loxP system further enhances antitumor effects in cell type-specific gene therapy against carcinoembryonic antigen-producing cancer. (1999)

A considerable number of studies of cancer have shown that the cell type-specific promoter is an effective tool for selective expression of foreign genes in tumor cells. However, few reports have demonstrated significant in vivo antitumor effects using this strategy thus far, possibly because the low activity of such a promoter results in insufficient expression of genes in cancer cells as well as in insignificant antitumor effects, even when the cells are infected by highly efficient gene transfer methods. To overcome this problem, we used the Cre/loxP system for the cell type-specific gene therapy against carcinoembryonic antigen (CEA)-producing cancer. We constructed a pair of recombinant Ads. One expresses the Cre recombinase (Cre) gene under the control of the CEA promoter (Ad.CEA-Cre). The other contains the herpes simplex virus thymidine kinase (HSV-TK) gene separated from the strong CAG promoter by insertion of the neomycin resistance (neo) gene (Ad.lox-TK). The HSV-TK gene of the latter Ad is designed to be activated through excisional deletion of the neo gene by Cre enzyme released from the former one only when CEA-producing cells are infected simultaneously with these Ads. Coinfection by these Ads rendered a human CEA-producing cancer cell line 8.4-fold more sensitive to ganciclovir (GCV) compared with infection by Ad.CEA-TK alone, the HSV-TK gene of which is directly regulated by the CEA promoter. On the other hand, coinfection with these Ads did not significantly change the GCV sensitivity of non-CEA-producing cells. Intratumoral injection of Ad.CEA-Cre combined with Ad.lox-TK followed by GCV treatment almost completely eradicated CEA-producing tumors established in the subcutis of athymic mice, whereas intratumoral injection of Ad.CEA-TK with GCV administration at most retarded the growth of inoculated tumors. These results suggest distinct advantages of the Cre/loxP system applied in the conventional cell type-specific gene therapy against cancer.
A Ca2+ binding cyclic peptide derived from the α‐subunit of LFA‐1: inhibitor of ICAM‐1 /LFA‐1‐mediated T‐cell adhesion (1999)

The objective of this work is to study the conformation of cyclic peptide (1), cyclo (1, 12) Pen1-Gly2-Val3-Asp4-Val5-Asp6-Gln7-+ ++Asp8-Gly9-Glu10-Thr11-Cys12, in the presence and absence of calcium. Cyclic peptide 1 is derived from the divalent cation binding sequence of the alpha-subunit of LFA-1. This peptide has been shown to inhibit ICAM-1-LFA-1 mediated T-cell adhesion. In order to understand the structural requirements for this biologically active peptide, its solution structure was studied by nuclear magnetic resonance (NMR), circular dichroism (CD) and molecular dynamics simulations. This cyclic peptide exhibits two types of possible conformations in solution. Structure I is a loop-turn-loop type of structure, which is suitable to bind cations such as EF hand proteins. Structure II is a more extended structure with beta-hairpin bend at Asp4-Val5-Asp6-Gln7. There is evidence that alterations in the conformation of LFA-1 upon binding to divalent cations cause LFA-1 to bind to ICAM-1. To understand this mechanism, the cation-binding properties of the peptide were studied by CD and NMR. CD studies indicated that the peptide binds to calcium and forms a 1 : 1 (peptide: calcium) complex at low calcium concentrations and multiple types of complexes at higher cation concentrations. NMR studies indicated that the conformation of the peptide is not significantly altered upon binding to calcium. The peptide can inhibit T-cell adhesion by directly binding to ICAM-1 or by disrupting the interaction of the alpha and beta-subunits of LFA-1 protein. This study will help us to understand the mechanism(s) of action of this peptide and will improve our ability to design a better inhibitor of T-cell adhesion.
A SEX-LINKED RECESSIVE DISORDER WITH RETARDATION OF GROWTH, PECULIAR HAIR, AND FOCAL CEREBRAL AND CEREBELLAR DEGENERATION (1962)

In two generations of the G. family, five males suffered from a cerebral degenerative disorder characterized by (1) peculiar stubby white hair with the microscopic picture of pili torti, monilethrix, and trichorrexis nodosa; (2) early and severe retardation; and (3) severe neurological impairment beginning within the first month or two of life and rapidly progressing to decerebration. A sex-linked recessive trait has been implicated. Postmortem examination in two cases revealed a widespread degeneration of the cerebral grey matter, secondary degeneration of the cerebral white matter, and a diffuse atrophy of the cerebellar cortex. Plasma amino acid chromatography showed consistently elevated glutamic acid. The significance of this finding is unknown. Other biochemical investigations were found to be within normal limits. The suggestion is offered that the condition described represents a new clinical syndrome due to an inherited error in metabolism.
MID2, a Homologue of the Opitz Syndrome Gene MID1: Similarities in Subcellular Localization and Differences in Expression During Development (1999)

The B-box family is an expanding new family of genes encoding proteins involved in diverse cellular functions such as developmental patterning and oncogenesis. A member of this protein family, MID1, is the gene responsible for the X-linked form of Opitz G/BBB syndrome, a developmental disorder characterized by defects of the midline structures. We now report the identification of MID2, a new transcript closely related to MID1. MID2 maps to Xq22 in human and to the syntenic region on the mouse X chromosome. The two X-linked genes share the same domains, the same exon-intron organization, a high degree of similarity at the protein level and the same subcellular localization, both being confined to the cytoplasm in association to micro-tubular structures. The expression pattern studied by RNA in situ hybridization in mouse revealed that Mid2 is expressed early in development and the highest level of expression is detected in the heart, unlike Mid1 for which no expression was detected in the developing heart. Together, these data suggest that midin and MID2 have a similar biochemical function but a different physiological role during development.