gebhart/patrepeval huggingface dataset:
A fully human CXCR4 antibody demonstrates diagnostic utility and therapeutic efficacy in solid tumor xenografts (2016)

For physiologically important cancer therapeutic targets, use of non-invasive imaging for therapeutic guidance and monitoring may improve outcomes for treated patients. The CXC chemokine receptor 4 (CXCR4) is overexpressed in many cancers including non-small cell lung cancer (NSCLC) and triple negative breast cancer (TNBC). CXCR4 overexpression contributes to tumor growth, progression and metastasis. There are several CXCR4-targeted therapeutic agents currently in clinical trials. Since CXCR4 is also crucial for normal biological functions, its prolonged inhibition could lead to unwanted toxicities. While CXCR4-targeted imaging agents and inhibitors have been reported and evaluated independently, there are currently no studies demonstrating CXCR4-targeted imaging for therapeutic guidance. Monoclonal antibodies (mAbs) are commonly used for cancer therapy and imaging. Here, an 89Zr-labeled human CXCR4-mAb (89Zr-CXCR4-mAb) was evaluated for detection of CXCR4 expression with positron emission tomography (PET) while its native unmodified analogue was evaluated for therapy in relevant models of NSCLC and TNBC. In vitro and in vivo evaluation of 89Zr-CXCR4-mAb showed enhanced uptake in NSCLC xenografts with a high expression of CXCR4. It also had the ability to detect lymph node metastases in an experimental model of metastatic TNBC. Treatment of high and low CXCR4 expressing NSCLC and TNBC xenografts with CXCR4-mAb demonstrated a therapeutic response correlating with the expression of CXCR4. Considering the key role of CXCR4 in normal biological functions, our results suggest that combination of 89Zr-CXCR4-mAb-PET with non-radiolabeled mAb therapy may provide a precision medicine approach for selecting patients with tumors that are likely to be responsive to this treatment.
Elimination of the musical noise phenomenon with the Ephraim and Malah noise suppressor (1994)

Presents a study of the noise suppression technique proposed by Ephraim and Malah (1984,1985). This technique has been used previously for the restoration of degraded audio recordings because it is free of the frequently encountered 'musical noise' artifact. It is demonstrated how this artifact is actually eliminated without bringing distortion to the recorded signal even if the noise is only poorly stationary.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Characterization of the Austin Chalk Producing Trend (1986)

ABSTRACT Fracture patterns and reservoir dual-characteristics are presented for a portion of the fractured Austin Chalk producing trend. The production histories of 1,235 wells from Giddings Field covering portions of Lee, Burleson, Washington, and Fayette counties were analyzed by decline curve analysis. Production of the average Austin Chalk well is usually characterized by an early rapid decline and a later slow decline. The average initial effective decline rate is about 90% per year, and lasts about six months to one year. For the later, less dramatic decline, the average is about 35% per year. Statistical results of well performance indicate no difficulty in finding oil in the Austin Chalk producing trend. However, areas of high fracture density must be encountered for a well to be profitable. A contour map of the iso-reserves was prepared for a better understanding of the fracture system and reservoir characteristics. Besides the general northeast-southwest production trend, the map shows anomalies in the fracture system and reservoir characteristics. A simple, rapid technique to estimate reservoir parameters directly from the double-decline behavior of log (rate) versus time curves is given. Values of flow capacity, storage capacity, dimensionless fracture storage parameter (ω), and dimensionless interporosity flow parameter (λ) can be estimated by this technique.
Vibrationally Mediated Negative Differential Resistance in a Single Molecule (2000)

A new mechanism for negative differential resistance (NDR) has been discovered and involves a single molecule in the junction of a scanning tunneling microscope. The NDR was observed at voltages corresponding to the vibrational energies of single pyrrolidine molecules on the (001) surface of copper at 9 K. This vibrationally mediated NDR contrasts with the previously known mechanisms which all involve the electronic states of the conducting media.
Sterilization of Microorganisms with Supercritical Carbon Dioxide (1987)

The sterilizing effect of supercritical carbon dioxide (SC-C02) is described as compared with gaseous C02(G-C02) and liquid C02(L-C02). Baker’s yeast, Escherichia coli, Staphylococcus aureus and conidia of Aspergillus niger were sterilized by treating with SC-C02 at 200 atm and 35°C when the water content of each microorganism was 70 ~ 90%. However, dry cells with a water content of 2 ~ 10% could not be sterilized under the same conditions. No sterilizing effect from SC-C02 on endospores of Bacillus subtilis and B. s tear other mophilus was observed. G-C02 and L-C02 produced no sterilizing effect against both wet and dry baker’s yeast cells, while wet E. coli cells were sterilized with G-C02. Although dry conidia of A. niger could not be sterilized with SC-C02 alone, the addition of ethanol or acetic acid to SC-C02 made it possible to sterilize these. Without any decrease in their enzymatic activities, E. coli and baker’s yeast in α-amylase and lipase preparations were sterilized with SC-C02.
Attenuation of Bovine Parainfluenza Virus Type 3 in Nonhuman Primates and Its Ability to Confer Immunity to Human Parainfluenza Virus Type 3 Challenge (1988)

Bovine parainfluenza virus type 3 (PIV-3) was evaluated as a candidate live-virus vaccine to protect against infection with human PIV-3. The level of replication of bovine and human PIV-3 and the efficacy of immunization with bovine PIV-3 in protecting against subsequent challenge with human PIV-3 was evaluated in nonhuman primates. The duration and magnitude of replication of human and bovine PIV-3 in the upper and lower respiratory tracts of New World monkeys was similar, and animals infected with bovine PIV-3 developed resistance to challenge with human PIV-3. The replication of two bovine strains of PIV-3 was restricted 100- to 1000-fold in Old World primates but was sufficient to induce high levels of neutralizing antibody to human PIV-3. The combined properties of restricted replication and induction of a protective immune response to human PIV-3 in nonhuman primates make bovine PIV-3 a promising candidate for a live-virus vaccine to protect humans against disease caused by PIV-3.
Optomechanical design and fabrication of resonant microscanners for a scanning fiber endoscope (2006)

Scanning fiber optical endoscopy shows promise as a small, inexpensive imaging tool. Using this method of image acquisition, a scanning fiber is actuated at mechanical resonance, projecting a light spot across an imaged surface. Light backscattered from scanned spots is measured to form an image. The acquired image field of view, resolvable pixels, and frame rate are dependent on the dynamics of the optical fiber used as a resonant scanner. A finite-element analysis (FEA) model was constructed to predict scanning fiber dynamics, and compared with experimental results. A scanning fiber microfabrication process was developed that allows for the controlled manufacture of fiber scanners. Experimental results confirm that the theoretical model was accurate in predicting the system transfer function with less than 6% error in amplitude and less than 10% error in resonant frequency at the first two resonant modes of a cylindrical and a microfabricated fiber. The scanning fiber microfabrication process proved to be capable of repeatably etching notches in optical fibers as small as 2.00±0.05 mm in length and 15±2 µm in diameter. FEA was used to predict the effect of geometry change on microfabricated fiber scan dynamics, yielding candidate designs chosen for enhanced performance of future scanning endoscopes.
CYP1A2 Activity as Measured by a Caffeine Test Predicts Clozapine and Active Metabolite Norclozapine Steady-State Concentration in Patients With Schizophrenia (2001)

Clozapine is an atypical antipsychotic drug and displays efficacy in 30% to 60% of patients with schizophrenia who do not respond to traditional antipsychotics. A clozapine concentration greater than 1,150 nmol/L increases the probability of antipsychotic efficacy. However, plasma clozapine concentration can vary more than 45-fold during long-term treatment. The aim of this study was to assess the contribution of CYP1A2 to variability in steady-state concentration of clozapine and its active metabolite norclozapine. Patients with schizophrenia or schizoaffective disorder were prospectively monitored during clozapine treatment (N = 18). The in vivo CYP1A2 activity was measured using the caffeine metabolic ratio (CMR) in overnight urine. Trough plasma samples were drawn after at least 5 days of treatment with a constant regimen of clozapine. A significant negative association was found between the CMR and the dose-corrected clozapine (r(s) = -0.87,p < 0.01) and norclozapine (r(s) = -0.76,p < 0.01) concentrations. Nonsmokers displayed a higher clozapine (3.2-fold) and norclozapine (2.3-fold) concentration than smokers (p < 0.05). Furthermore, there was marked person-to-person variation in CYP1A2 activity during multiple-dose clozapine treatment (coefficient of variation = 60%). Age, weight, serum creatinine, and grapefruit juice consumption did not significantly contribute to variability in clozapine and norclozapine concentration (p > 0.05). In conclusion, CYP1A2 is one of the important contributors to disposition of clozapine during multiple-dose treatment. Although further in vitro experiments are necessary, the precise metabolic pathways catalyzed by CYP1A2 seem to be subsequent to the formation of norclozapine, hitherto less recognized quantitatively important alternate disposition routes, or both. From a clinical perspective, an environmentally induced or constitutively high CYP1A2 expression can lead to a decrease in steady-state concentration of clozapine as well as its active metabolite norclozapine. Thus, interindividual variability in CYP1A2 activity may potentially explain treatment resistance to clozapine in some patients. CYP1A2 phenotyping with a simple caffeine test may contribute to individualization of clozapine dosage and differentiate between treat ment noncompliance and high CYP1A2 activity.
Myosin light chain-2 luciferase transgenic mice reveal distinct regulatory programs for cardiac and skeletal muscle-specific expression of a single contractile protein gene. (1992)

To examine the relationship between the cardiac and skeletal muscle gene programs, the current study employs the regulatory (phosphorylatable) myosin light chain (MLC-2) as a model system. Northern blotting, primer extension, and RNase protection studies documented the high level expression of the cardiac MLC-2 mRNA in both mouse cardiac and slow skeletal muscle (soleus). Transgenic mouse lines harboring a 2100- or a 250-base pair rat cardiac MLC-2 promoter/luciferase fusion gene were generated, demonstrating high levels of luciferase activity in cardiac muscle, and only background luminescence in slow skeletal muscle and non-muscle tissues. As assessed by in situ hybridization, immunofluorescence, and luminescence assays of luciferase reporter activity in various regions of the heart, both the endogenous MLC-2 gene and the MLC-2 luciferase fusion gene were expressed exclusively in the ventricular compartment, with expression in the atrium at background levels. Point mutations within the conserved regulatory sites HF-1a and HF-1b significantly cripple ventricular muscle specificity, while mutation of the single E-box site was without effect, suggesting that ventricular muscle-specific expression occurs through an E-box-independent pathway. This study provides direct evidence that the cis regulatory sequences in the cardiac/slow twitch MLC-2 gene which confer cardiac and skeletal muscle-specific expression can be clearly segregated, suggesting that distinct regulatory programs may have evolved to control the tissue-specific expression of this single contractile protein gene in cardiac and skeletal muscle.
Enfuvirtide (T-20): Potentials and Challenges (2004)

Enfuvirtide is a fusion inhibitor used for the treatment of HIV infection. It is an injectable drug, with the patient being responsible for reconstitution as well as injection. The authors present the results of Phase III trials with enfuvirtide. A summary of efficacy, tolerability, pharmacokinetics, resistance, and adverse events from the Phase III trials with enfuvirtide is presented. Enfuvirtide is well tolerated, and no limiting pharmacokinetic interactions have been published thus far. A review of patient perception of self-injection is also summarized. The data reviewed demonstrate that most patients find self-injection easy and do not find that it interferes with activities of daily living. Data on injection site reactions (ISRs), one of the most common adverse events of enfuvirtide, is highlighted, as is nursing management of ISRs. Finally, the authors discuss research that could help further understanding of enfuvirtide and examine some barriers clinicians may face when prescribing this medication.
Purification and characterization of pumpkin long‐chain acyl‐CoA oxidase (1999)

Pumpkin ( Cucurbita sp.) long‐chain acyl‐CoA oxidase (ACOX) (EC 1.3.3.6) was purified to homogeneity by hydrophobic interaction, hydroxyapatite, affinity, and anion exchange chromatographies. The purified isoenzyme is a dimeric protein, consisting of two apparently identical 72‐kDa subunits. The protein is exclusively localized in glyoxysomes. The enzyme catalyzes selectively the oxidation of CoA esters of fatty acids with 12–18 C atoms and exhibits highest activity with C‐14 fatty acids, but no activity with isobutyryl‐CoA and isovaleryl‐CoA (branched chain) or glutaryl‐CoA (dicarboxylic). The enzyme is strongly inhibited by high concentrations of palmitoyl‐CoA and weakly inhibited by high concentration of myristoyl‐CoA. It is also inhibited by Triton X‐100 at concentrations above 0.018% (w/v) the critical micellar concentration. The consequences of the substrate inhibition for the evaluation of long‐chain ACOX activity in plant tissues are discussed.
Dipole Moment and Molecular Structure. (1936)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDipole Moment and Molecular Structure.N. V. SidgwickCite this: Chem. Rev. 1936, 19, 3, 183–194Publication Date (Print):December 1, 1936Publication History Published online1 May 2002Published inissue 1 December 1936https://pubs.acs.org/doi/10.1021/cr60064a003https://doi.org/10.1021/cr60064a003research-articleACS PublicationsRequest reuse permissionsArticle Views500Altmetric-Citations9LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Regulation of leukemic cell adhesion, proliferation, and survival by β-catenin (2002)

In epithelial cells beta-catenin plays a critical role as a component of the cell-cell adhesion apparatus and as a coactivator of the TCF/LEF (T-cell transcription factor/lymphoid enhancer binding factor) family of transcription factors. Deregulation of beta-catenin has been implicated in the malignant transformation of cells of epithelial origin. However, a function for beta-catenin in hematologic malignancies has not been reported. beta-Catenin is not detectable in normal peripheral blood T cells but is expressed in T-acute lymphoblastic leukemia cells and other tumor lines of hematopoietic origin and in primary lymphoid and myeloid leukemia cells. beta-Catenin function was examined in Jurkat T-acute lymphoblastic leukemia cells. Overexpression of dominant-negative beta-catenin or dominant-negative TCF reduced beta-catenin nuclear signaling and inhibited Jurkat proliferation and clonogenicity. Similarly, these constructs inhibited proliferation of K562 and HUT-102 cells. Reduction of beta-catenin expression with beta-catenin antisense down-regulated adhesion of Jurkat cells in response to phytohemagglutinin. Incubation of Jurkat cells with anti-Fas induced caspase-dependent limited proteolysis of beta-catenin N- and C-terminal regions and rapid redistribution of beta-catenin to the detergent-insoluble cytoskeleton, concomitant with a marked decline in nuclear beta-catenin signaling. Fas-mediated apoptosis was potentiated by inhibition of beta-catenin nuclear signaling. The data suggest that beta-catenin can play a significant role in promoting leukemic cell proliferation, adhesion, and survival.
Modulation of epidermal growth factor receptor proto-oncogene transcription by a promoter site sensitive to S1 nuclease. (1988)

The epidermal growth factor (EGF) receptor is the functional target of the mitogen EGF and the cellular homolog of the avian erythroblastosis virus erbB oncogene product. Regulation of expression of the proto-oncogene encoding the EGF receptor can be elucidated by studying the structure and function of the gene promoter outside the confines of the cell. Previously, we reported the isolation of the human EGF receptor gene promoter. The promoter is highly GC rich, contains no TATA or CAAT box, and has multiple transcription start sites. An S1 nuclease-sensitive site has now been found 80 to 110 base pairs (bp) upstream from the major in vivo transcription initiation site. Two sets of direct repeat sequences were found in this area; both conform to the motif TCCTCCTCC. When deletion mutations were made in this region of the promoter by using either Bal 31 exonuclease or S1 nuclease, we found that in vivo activity dropped three- to fivefold, on the basis of transient-transfection analysis. Examination of nuclear protein binding to normal and mutated promoter DNAs by gel retardation analysis and DNase I footprinting revealed that two specific factors bind to the direct repeat region but cannot bind to the S1 nuclease-mutated promoter. One of the specific factors is the transcription factor Sp1. The results suggest that these nuclear trans-acting factors interact with the S1 nuclease-sensitive region of the EGF receptor gene promoter and either directly or indirectly stimulate transcription.
Oxidative stress in systemic lupus erythematosus and rheumatoid arthritis patients: relationship to disease manifestations and activity (2011)

Oxidative stress was increased and more profound in RA than SLE and could well reflect disease activity, with special attention to SLE patients with alopecia and nephritis. Medications used are closely related to the oxidant/antioxidant imbalance. Considering antioxidants in novel therapeutic strategies is important in SLE and RA patients.
Non-Speculative Load-Load Reordering in TSO (2017)

In Total Store Order memory consistency (TSO), loads can be speculatively reordered to improve performance. If a load-load reordering is seen by other cores, speculative loads must be squashed and re-executed. In architectures with an unordered interconnection network and directory coherence, this has been the established view for decades. We show, for the first time, that it is not necessary to squash and re-execute speculatively reordered loads in TSO when their reordering is seen. Instead, the reordering can be hidden form other cores by the coherence protocol. The implication is that we can irrevocably bind speculative loads. This allows us to commit reordered loads out-of-order without having to wait (for the loads to become non-speculative) or without having to checkpoint committed state (and rollback if needed), just to ensure correctness in the rare case of some core seeing the reordering. We show that by exposing a reordering to the coherence layer and by appropriately modifying a typical directory protocol we can successfully hide load-load reordering without perceptible performance cost and without deadlock. Our solution is cost-effective and increases the performance of out-of-order commit by a sizable margin, compared to the base case where memory operations are not allowed to commit if the consistency model could be violated.
Increased superoxide anion release from human endothelial cells in response to cytokines. (1986)

To study the effects of macrophage and lymphocyte-derived factors on superoxide anion (O2-) generation and release from human umbilical vein endothelial cells (EC), cultured EC were stimulated by ultrapure interleukin 1 (IL 1) and recombinant interferon-gamma (IFN-gamma), and the O2- released into the supernatant was measured. Both of these cytokines enhanced O2- release in a dose and time-dependent manner. Addition of a combination of IL 1 and IFN-gamma, each in submaximal concentration, produced an additive effect on O2- release. It would appear from these findings that cytokines released by macrophages and lymphocytes during inflammatory reactions can promote O2- generation and release from human EC. O2- released from EC may alter the basement membrane of blood vessels and the surrounding connective tissue, and in this way promote the vascular injury and angiogenesis associated with local inflammation.
Inhibitors of the Nonmevalonate Pathway of Isoprenoid Biosynthesis as Antimalarial Drugs (1999)

A mevalonate-independent pathway of isoprenoid biosynthesis present in Plasmodium falciparum was shown to represent an effective target for chemotherapy of malaria. This pathway includes 1-deoxy-D-xylulose 5-phosphate (DOXP) as a key metabolite. The presence of two genes encoding the enzymes DOXP synthase and DOXP reductoisomerase suggests that isoprenoid biosynthesis in P. falciparum depends on the DOXP pathway. This pathway is probably located in the apicoplast. The recombinant P. falciparum DOXP reductoisomerase was inhibited by fosmidomycin and its derivative, FR-900098. Both drugs suppressed the in vitro growth of multidrug-resistant P. falciparum strains. After therapy with these drugs, mice infected with the rodent malaria parasite P. vinckei were cured.