gebhart/patrepeval huggingface dataset:
Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. (1997)

The overexpression in tumor cells of (proto)-oncogenic receptor tyrosine kinases such as epidermal growth factor receptor (EGFR) or ErbB2/neu (also known as HER-2) is generally thought to contribute to the development of solid tumors primarily through their effects on promoting uncontrolled cell proliferation. However, agents that antagonize the function of the protein products encoded by these (proto)-oncogenes are known to behave in vivo in a cytotoxic-like manner. This implies that such oncogenes may regulate critical cell survival functions, including angiogenesis. The latter could occur as a consequence of regulation of relevant growth factors by such oncogenes. We therefore sought to determine whether EGFR or ErbB2/neu may contribute to tumor angiogenesis by examining their effects on the expression of vascular endothelial cell growth factor (VEGF)/vascular permeability factor (VPF), one of the most important of all known inducers of tumor angiogenesis. We found that in vitro treatment of EGFR-positive A431 human epidermoid carcinoma cells, which are known to be heavily dependent on VEGF/VPF in vivo as an angiogenesis growth factor, with the C225 anti-EGFR neutralizing antibody caused a dose-dependent inhibition of VEGF protein expression. Prominent suppression of VEGF/VPF expression in vivo, as well as a significant reduction in tumor blood vessel counts, were also observed in established A431 tumors shortly after injection of the antibody as few as four times into nude mice. Transformation of NIH 3T3 fibroblasts with mutant ErbB2/neu, another EGFR-like oncogenic tyrosine kinase, resulted in a significant induction of VEGF/VPF, and the magnitude of this effect was further elevated by hypoxia. Moreover, treatment of ErbB2/neu-positive SKBR-3 human breast cancer cells in vitro with a specific neutralizing anti-ErbB2/neu monoclonal antibody (4D5) resulted in a dose-dependent reduction of VEGF/VPF protein expression. Taken together, the results suggest that oncogenic properties of EGFR and ErbB2/neu may, at least in part, be mediated by stimulation of tumor angiogenesis by up-regulating potent angiogenesis growth factors such as VEGF/VPF. These genetic changes may cooperate with epigenetic/environmental effects such as hypoxia to maximally stimulate VEGF/VPF expression. Therapeutic disruption of EGFR or ErbB2/neu protein function in vivo may therefore result in partial suppression of angiogenesis, a feature that could enhance the therapeutic index of such agents in vivo and endow them with anti-tumor effects, the magnitude of which may be out of proportion with their observed cytostatic effects in monolayer tissue culture.
Ultrasonography in Assessing Oropharyngeal Dysphagia (2013)

Ultrasonography, a portable, noninvasive, and radiation-free technique, had been applied for assessment of oropharyngeal swallowing function for decades. The most common application is for observing the tongue, larynx, and hyoid-bone movement by B-mode ultrasonography. Although some studies describing techniques of ultrasonography have been published, its clinical application is still not well known. Other methods such as M-mode ultrasonography, Doppler ultrasonography, three-dimensional reconstruction, or pixel analysis had been reported without promising results. The techniques of ultrasonography examination of the tongue and larynx/hyoid movement are introduced in this work; in addition, a brief review about the methods and application of ultrasonography in assessing swallowing function in different groups of patients had been described. Ultrasonography, instead of a substitution of videofluoroscopic swallowing study (VFSS), may be able to complement VFSS as a rapid examination tool for screening and for follow-up of swallowing function. Further large-scale quantitative analyses that provide diagnostic value and correlation with functional outcome are mandatory.
[Effect of methylmercury chloride on the c-fos expression in brain nerve cells of the rats]. (2001)

It is concluded that MMC could induce c-fos over-expression in the nerve cells of the rat brain, which could explain the mechanism of injury to brain development caused by MMC.
The Electronic Still Store: A Digital System for the Storage and Display of Still Pictures (1976)

The preparation, storage, retrieval, and broadcasting of stills (slides and graphics) add up to a significant cost element that must be controlled in the operation of a typical television facility. The physical handling in using stills can damage the materials and result in human error. Furthermore, reserving a studio camera and/or a telecine chain to show stills is inefficient and not cost-effective. A new system to overcome these problems, the Electronic Still Store (ESS), has now been demonstrated by CBS and Ampex. The ESS can randomly search an electronic library of still pictures from a number of locations, arrange the stills in the order for playing, play them as fast as 1 still/s, and do these things without physically touching the media. The system makes available a current stock of about 1500 stills (those expected to be needed within the next 100 days) and a long-term stock of about 5000 stills. System control tasks are handled by an LSI-11 microcomputer which emulates the larger PDP-11/40. The core element of the ESS is a very reliable computer disc drive. The adaptation of the disc drive for storing PCM video requires only that the dissimilar standards of digitally encoded video and the computer peripheral be reconciled.
Possible roles of tumor necrosis factor in the pathology of malaria. (1987)

The authors have earlier proposed that tumor necrosis factor (TNF) might contribute to the pathology of malaria. Here they report the outcome of injecting recombinant human TNF/cachectin into normal mice and others with low parasitemias (6-35%) of Plasmodium vinckei. The object was to see how precisely the pathologic features of the terminal stages of this infection could be produced, when parasitemias are 70-80%. Hypoglycemia, mid-zonal liver damage, and pulmonary accumulation of neutrophils in the pulmonary vasculature, all of which are seen in severe P vinckei infection, occurred within 4-12 hours after the mildly infected mice received TNF/cachectin. Uninfected mice were much less susceptible. TNF/cachectin also increases plasma lactate, a change seen in both the human and rodent diseases. From these findings and the recent literature on TNF/cachectin, including its detection in serum from malarial patients, it seems likely that excessive release of this monokine could account for certain of the unexplained pathologic features of human malaria.
Biochemical Characterization of a Prokaryotic Phenylalanine Ammonia Lyase (2006)

Table 1: k cat and k cat /K m values associated with EncP and V83A EncP should be multiplied by 0.001.The data should read as follows: EncP k cat , 4.79 Ϯ 0.28 ms Ϫ1 ; EncP k cat /K m , 0.208 mM Ϫ1 s Ϫ1 ; V83A EncP k cat , 99.58 Ϯ 1.78 ms Ϫ1 ; V83A EncP k cat /K m , 0.829 mM Ϫ1 s Ϫ1 .The revised k cat data do not alter the conclusions of the paper.
Reaction Mechanism of Glutamate Carboxypeptidase II Revealed by Mutagenesis, X-ray Crystallography, and Computational Methods (2009)

Glutamate carboxypeptidase II (GCPII, EC 3.4.17.21) is a zinc-dependent exopeptidase and an important therapeutic target for neurodegeneration and prostate cancer. The hydrolysis of N-acetyl-l-aspartyl-l-glutamate (N-Ac-Asp-Glu), the natural dipeptidic substrate of the GCPII, is intimately involved in cellular signaling within the mammalian nervous system, but the exact mechanism of this reaction has not yet been determined. To investigate peptide hydrolysis by GCPII in detail, we constructed a mutant of human GCPII [GCPII(E424A)], in which Glu424, a putative proton shuttle residue, is substituted with alanine. Kinetic analysis of GCPII(E424A) using N-Ac-Asp-Glu as substrate revealed a complete loss of catalytic activity, suggesting the direct involvement of Glu424 in peptide hydrolysis. Additionally, we determined the crystal structure of GCPII(E424A) in complex with N-Ac-Asp-Glu at 1.70 A resolution. The presence of the intact substrate in the GCPII(E424A) binding cavity substantiates our kinetic data and allows a detailed analysis of GCPII/N-Ac-Asp-Glu interactions. The experimental data are complemented by the combined quantum mechanics/molecular mechanics calculations (QM/MM) which enabled us to characterize the transition states, including the associated reaction barriers, and provided detailed information concerning the GCPII reaction mechanism. The best estimate of the reaction barrier was calculated to be DeltaG(++) approximately 22(+/-5) kcal x mol(-1), which is in a good agreement with the experimentally observed reaction rate constant (k(cat) approximately 1 s(-1)). Combined together, our results provide a detailed and consistent picture of the reaction mechanism of this highly interesting enzyme at the atomic level.
Accurate detection and automatic match method for feature points using concentric circles array (2008)

Camera calibration is the basic of machine vision, the accuracy of feature point detection and the automation of camera calibration process is very important in actual high precision measurement. The planar pattern with circle feature has its own advantage compared with chessboard calibration pattern; it is easy to manufacture, and insensitive to threshold. Although there is a position distortion in detecting the projected centre of circle for perspective projection, the feature point which is the image of the center of the circle can be computed accurately based on the geometric and algebraic constrains of projected concentric circles. After the feature points is detected, the set of feature points on the calibration pattern and the points in the camera images must be matched, manual or user assisted methods are often used to solve the matching problem. This paper also describes a simple technique based on Delaunay triangulation to automatically match the feature points recovered by concentric circles. The experiments show that the method is excellent in actual camera calibration using concentric circles array.
Full-field optical coherence tomography by two-dimensional heterodyne detection with a pair of CCD cameras (2003)

A two-dimensional heterodyne detection technique based on the frequency-synchronous detection method [Jpn. J. Appl. Phys. 39, 1194 (2000)] is demonstrated for full-field optical coherence tomography. This technique, which employs a pair of CCD cameras to detect the in-phase and quadrature components of the heterodyne signal simultaneously, offers the advantage of phase-drift suppression in interferometric measurement. Horizontal cross-sectional images are acquired at the rate of 100 frames/s in a single longitudinal scan, with a depth interval of 6 microm, making the rapid reconstruction of three-dimensional images possible.
Selective activity of phenylacetate against malignant gliomas: resemblance to fetal brain damage in phenylketonuria. (1994)

Phenylacetate, a deaminated metabolite of phenylalanine, has been implicated in damage to immature brain in phenylketonuria. Because primary brain tumors are highly reminiscent of the immature central nervous system, these neoplasms should be equally vulnerable. We show here that sodium phenylacetate can induce cytostasis and reversal of malignant properties of cultured human glioblastoma cells, when used at pharmacological concentrations that are well tolerated by children and adults. Treated tumor cells exhibited biochemical alterations similar to those observed in phenylketonuria-like conditions, including selective decline in de novo cholesterol synthesis from mevalonate. Because gliomas, but not mature normal brain cells, are highly dependent on mevalonate for production of sterols and isoprenoids vital for cell growth, sodium phenylacetate would be expected to affect tumor growth in vivo while sparing normal tissues. Systemic treatment of rats bearing intracranial gliomas resulted in significant tumor suppression with no apparent toxicity to the host. The data indicate that phenylacetate, acting through inhibition of protein prenylation and other mechanisms, may offer a safe and effective novel approach to treatment of malignant gliomas and perhaps other neoplasms as well.
Proposing a novel technique to exclude the left ventricle with an assist device: insights from 4-dimensional flow magnetic resonance imaging (2016)

For the first time, intracardiac flows in an LVAD setting have been shown in vitro based on a mock porcine ex vivo heart failure model by applying 4D flow MRI. Differences in flow characteristics of the same model using a prosthesis sparing the LV cavity are encouraging to further investigate their potential to reduce potential LVAD-associated side-effects, such as intracavitary clotting and its sequelae.
Bias-controlled mechanism for a scanning tunnelling microscope (2006)

In this paper we describe a simple and low-cost circuit that limits the tunnelling current in a scanning tunnelling microscope, in order to protect the sample against sparks when using a bias higher than 1 V. During the evolution of the spark, when the current exceeds a predetermined value, a fast feedback control mechanism reduces the bias immediately and prevents the spark from developing. We show that this mechanism provides a better scanning image in comparison to a system without such a mechanism.
13 Building a Catalytic Active Site Using Only RNA (1999)

WHERE DO RIBOZYMES FIT IN THE RNA WORLD HYPOTHESIS? Two of the most fundamental requirements for life are information storage and catalytic function. Without storage, transfer, and replication of information, a system cannot learn from its past and improve its viability; that is, there can be no natural selection. Equally essential to life is catalytic (enzymatic) function. At the very least, there must be machinery to catalyze the copying of the informational molecules. This process must proceed with considerable fidelity, yet some frequency of errors is also necessary to provide the diversity that allows adaptation and evolution. Beyond replication of the genome, additional catalytic functions would be highly advantageous to provide basic metabolism for even a primitive self-reproducing system. In contemporary organisms information is stored in the form of DNA. However, the persistence of RNA genomes in many viruses shows us that this sister nucleic acid is competent for information storage, at least for small genomes. Biocatalytic function in the modern world is mostly the domain of protein enzymes, although ribonucleoproteins (RNPs) still catalyze the essential cellular reactions of protein synthesis and RNA splicing. By what evolutionary pathway did this DNA-RNA-protein solution to the problem of life come about? The finding that RNA, an informational molecule, can by itself catalyze biochemical reactions has rekindled enthusiasm for the possibility that a key intermediate stage was an RNA World, with RNA providing both information and function, genotype and phenotype. One version of this RNA World hypothesis is diagrammed in Figure 1. RNA...
Measuring the efficacy of vaccination in affording protection against plague. (1979)

The relationship of F1 antibody titre to protection against plague was investigated by subjecting seropositive laboratory rats to virulent challenge and observing for survival. The passive haemagglutination (PHA) test in microtitre was employed for serology. Rats vaccinated with live vaccine EV76 (51f), killed U.S.P. vaccine, or F1 antigen and challenged by subcutaneous inoculation of 1 x 10(3) to 5 x 10(5)Yersinia pestis survived at similar rates that, overall, equalled 6% at titres less than 1:16, 46% at titres of 1:32-1:64, 90% at titres of 1:128-1:256, and 96% at titres of 1:512-1:1024. Rats vaccinated with F1 antigen and rats that had been infected previously were challenged intranasally with 8.9 x 10(4)Y. pestis and subsequently demonstrated similar rates of survival that was zero at titres less than 1:128, 86% at titres of 1:128-1:256, and 100% at titres of 1:512-1:1024. The significance of titre of F1 antibody as a measure of seroimmunity against acute bubonic or pneumonic plague is discussed for rats, monkeys, and man.
Three Mechanisms Underlie KCNQ2/3 Heteromeric Potassium M-Channel Potentiation (2004)

The non-inactivating potassium M-current exerts a strong influence on neuronal excitability. The channels responsible for this current are made up of KCNQ subunits, and mutations in most of these produce human pathologies. Notably, in terms of excitation, mutations in either KCNQ2 or KCNQ3 lead to benign neonatal familial convulsions. Although a mere reduction of 25% in KCNQ2/3 function can increase excitability to epileptogenic levels, the potentiation of these subunits has anti-epileptogenic effects. After KCNQ2/3 heteromerization, current levels can augment as much as 10-fold, and we have discovered that there are three processes underlying this potentiation. First, there is an increase in the number of channels inserted in the membrane after heteromerization of the C-terminal region. Second, the N-terminal domain from KCNQ2 exerts a negative influence on the current level. Finally, Ala 315 of KCNQ3, a residue located in the inner vestibule after the selectivity filter, plays a critical role in preventing current flow in KCNQ3 homomeric channels, whereas it is permissive in heteromers in combination with Thr at the equivalent 276 position of KCNQ2.
Fatty acid utilization by L1210 murine leukemia cells. (1977)

L1210 murine leukemia cells grow in an ascites plasma that contains lipids, including 0.62 +/- 0.046 (S.E.) MICRONEq free fatty acid per ml. in vitro incubations demonstrated that isolated L1210 cells readily utilize free fatty acid that is added to the incubation medium. When the cells were incubated with albumin-bound [1-14C]palmitate, about 12 times more radioactivity was incorporated into cell lipids than was oxidized to CO2. Triacylglycerols contained 1.5 to 4 times more radioactivity than phospholipids, and from 48 to 69% of the phospholipid radioactivity was recovered in the choline phosphoglycerides. [1-14C]Palmitate utilization increased as the fatty acid concentration of the medium was raised, the largest increase occurring in the triacylglycerol fraction. Palmitate utilization also was increased by the presence of carbohydrates in the medium, their effectiveness (in descending order) being glucose, mannose, galactose, fructose, and glycerol. By contrast, ribose did not produce any stimulatory effect. During a 1-hr incubation, between 82 and 87% of the [1-14C]palmitate that was taken up remained as palmitic acid. From 8 to 15% was elongated to stearate, and only 2 to 3% was desaturated to palmitoleate and oleate. Based upon the lipid content, growth rate, and palmitate utilization rate of the cells, it appears that a major portion of the lipid requirements of the L1210 cell may be supplied by the fatty acid contained in the ascites plasma. In addition, our results suggest that most of the saturated fatty acid taken up is incorporated into cell lipids without structural modification.
The Burden of Atopic Dermatitis: Impact on the Patient, Family, and Society (2005)

Atopic dermatitis is a common disease of increasing prevalence. Affected individuals must cope with a significant psychosocial burden, in addition to dealing with the medical aspects of the disease. Furthermore, because this is primarily a disease of childhood, family members, especially parents, are also affected by the condition. Individuals and family members are burdened with time-consuming treatment regimens for the disease, as well as dietary and household changes. The financial impact of atopic dermatitis on families can also be great. Moreover, the cost to society is significant, with estimates ranging from less than 100 dollars to more than 2000 dollars per patient per year. It is estimated that the direct cost of atopic dermatitis in the United States alone is almost 1 billion dollars per year. Reducing the onus of this disease must take into account the full breadth of its burden. Targeting parents and caregivers with education and psychosocial support can decrease family and personal burden, which in turn may decrease the cost of treating the condition because of better medical, psychosocial, and family outcomes.
Therapeutic efficacy of mouse-human chimeric anti-ganglioside GM2 monoclonal antibody against multiple organ micrometastases of human lung cancer in NK cell-depleted SCID mice (1998)

The development of distant metastases to multiple organs is a critical problem in the treatment of human lung cancer. In this study, we evaluated the therapeutic efficacy of a mouse-human chimeric anti-ganglioside GM2 (GM2) monoclonal antibody (MAb), KM966 against metastasis formation of GM2-positive human lung cancer cells inoculated intravenously (i.v.) into natural killer (NK) cell-depleted severe combined immunodeficient (SCID) mice. GM2-positive human small cell lung cancer (SCLC), SBC-3 cells (1 x 10(6)), injected through a tail vein into NK cell-depleted SCID mice, formed large number of metastatic colonies in the liver, kidneys and lymph nodes by 42 days after inoculation (day 42). KM966, but not control MAb, given on days 2 and 7, almost completely inhibited metastasis formation of SBC-3 cells in the liver, kidneys and lymph nodes in a dose-dependent fashion. Moreover, treatment with KM966 at advanced stages of metastasis (even from day 28) significantly suppressed multiple organ metastases of SBC-3 cells. The anti-metastatic effect of KM966 in vivo was mainly due to an antibody-dependent cell-mediated cytotoxicity (ADCC) reaction mediated by macrophages of the SCID mice. Our findings suggest that the mouse-human chimeric anti-GM2 MAb, KM966 may be useful for eradicating multiple organ micrometastases of lung cancer in humans.
Low blood ISG15 mRNA and progesterone levels are predictive of non-pregnant dairy cows (2006)

ISG15 is induced by conceptus-derived interferon-tau in the endometrium on days 15-45 of pregnancy. It was hypothesized that pregnancy induces blood cell ISG15 gene expression and that low blood ISG15 mRNA levels provide an indication of non-pregnant cows on day 18. Blood was collected either on day 18 (n = 78) or on days 15-21, 25, and 32 (n = 21; serial collection) from dairy cows following artificial insemination (AI). Plasma progesterone concentration was determined using RIA. ISG15 mRNA levels were determined using real-time PCR. Pregnancy was diagnosed on day 32 using transrectal ultrasound. ISG15 mRNA levels increased after day 16, peaked at day 20 and then declined to day 16 levels by 32 days following AI. The average pregnancy rate was 43% based on blood cell ISG15 mRNA. The average pregnancy rate was 33% based on the transrectal ultrasound. Lower levels of ISG15 mRNA or progesterone during serial collections were 100% accurate in predicting non-pregnant cows based on day 32 transrectal ultrasound. However, detection of ISG15 mRNA yielded 78% accuracy in predicting pregnant cows, while progesterone yielded 58% accuracy. Average plasma progesterone based on pregnancy status according to ultrasound was consistently higher in pregnant (> 4 ng/ml) when compared with non-pregnant cows from days 15 to 32, except on day 16. It is concluded that detection of low blood ISG15 mRNA levels during serial collection from days 17 to 25 serves as an accurate indicator of cows that are not pregnant, thus allowing re-synchronization and insemination.