gebhart/patrepeval huggingface dataset:
Effects of the Position of the Simian Virus 40 Enhancer on Expression of Multiple Transcription Units in a Single Plasmid (1986)

We have examined the ability of the simian virus 40 72-base pair enhancer segment to simultaneously activate multiple transcription units with plasmids that contain one, two, or three simian virus 40-based transcription units in various arrangements. After transfection into CV1 cells, the expression of a marker gene, Ecogpt, was determined as a function of the position of that marker gene relative to the other transcription units and the position of the marker gene relative to enhancer elements on the plasmids. Two types of position effects were revealed by that analysis. The first, promoter occlusion, causes reduced transcription at a downstream promoter if transcription is initiated at a nearby upstream promoter. This effect does not involve enhancer elements directly, even though the effect is most pronounced when the downstream promoter lacks an enhancer element. The second effect stems from the ability of promoter sequences to reduce the effect of a single enhancer element on other promoters in the same plasmid. This latter effect is mediated by either promoters adjacent to the enhancer element or promoters interposed between the enhancer element and the other promoters on the plasmid.
FlyCam: practical panoramic video and automatic camera control (2002)

We describe computationally and materially inexpensive methods for panoramic video imaging. Digitally combining images from an array of inexpensive video cameras results in a wide-field panoramic camera, from inexpensive off-the-shelf hardware. We present methods that both correct lens distortion and seamlessly merge images into a panoramic video image. Electronically selecting a region of this results in a rapidly steerable "virtual camera". Because the camera is fixed with respect to the background, simple motion analysis can be used to track objects and people of interest. We present methods of motion analysis and algorithms for automatic camera control that mimic the actions of a human operator, using inexpensive and widely available hardware.
Shear thinning and thixotropy of HMHEC and HEC water solutions (2002)

Steady state viscosity and thixotropy of hydrophobically modified hydroxyethyl cellulose HMHEC and nonassociative cellulose water solutions are studied. Although all the samples are shear thinning, only the HMHEC is thixotropic, since the migration of hydrophobes to micelles is controlled by diffusion. The Cross model fits steady state curves. The Mewis model, a phenomenological model that proposes that the rate of change of viscosity when the shear rate is suddenly changed is related to the difference between the steady state and current values of viscosity raised to an exponent, fits structure construction experiments when the exponent, n, is estimated to be around 2. The Newtonian assumption used by Mewis cannot be used here, however. This seems to be related to the fact that the thickening is due to bridged micelle formation, which is a slow process, and also to topological constraints and entanglements, which are rapid processes. The kinetic parameter was redefined to k n in order to make it independent of initial conditions. So, k n depends only on how the shear affects the structure. k n reaches a plateau at shear rates too low to produce structure destruction and decreases at higher shear rates.
Efficient Homogeneous Catalysis in the Reduction of CO2 to CO (2005)

The well-defined copper(I) boryl complex [(IPr)Cu(Bpin)] [where IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, and pin = pinacolate: 2,3-dimethyl-2,3-butanediolate] deoxygenates CO2 rapidly and quantitatively, affording CO and the borate complex [(IPr)Cu(OBpin)]. The boryl may be regenerated by treatment with the diboron compound pinB-Bpin, giving the stable byproduct pinB-O-Bpin. The use of a copper(I) alkoxide precatalyst and stoichiometric diboron reagent results in catalytic reduction of CO2, with high turnover numbers (1000 per Cu) and frequencies (100 per Cu in 1 h) depending on supporting ligand and reaction conditions.
Release of Blood from the Splanchnic Circulation in Dogs (1972)

In dogs anesthetized with α-chloralose, passive alterations in splanchnic blood flow over a range of flows between 10 ml/kg min -1 and 50 ml/kg min -1 produced by a blood flow pump or by a change in perfusion pressure were associated with changes in splanchnic blood volume of 0.19 ± 0.1 (SD) ml/kg and 0.43 ± 0.15 ml/kg, respectively, for a change in flow of 1 ml/kg min -1 . Mechanical increase in splanchnic outflow resistance raised portal venous pressure from a control mean of 6.9 ± 4.1 mm Hg to 15.4 ± 3.5 mm Hg and increased splanchnic blood volume by 8.1 ± 2.2 ml/kg. Of the total change in splanchnic blood volume during an 18-second supramaximal stimulation of the thoracic splanchnic nerves, an estimated 65% was released "passively." The magnitude of this passive release was related linearly to splanchnic blood flow. During increased resistance to splanchnic outflow, the passive release was absolutely and relatively reduced, but the volume of blood actively released by constriction of capacitance elements was absolutely and relatively increased. During hemorrhage (7.2 ml/kg body weight), an average of 4.7 ± 0.6 ml/kg of blood (21% of the calculated splanchnic blood volume) was mobilized, and arterial blood pressure decreased an average of 5%. Repetition of the bleeding after bilateral splanchnicectomy passively mobilized 3.25 ± 0.9 ml/kg of blood (68% of the innervated value), but arterial blood pressure declined by an average of 20%.
Robust key generation from signal envelopes in wireless networks (2007)

The broadcast nature of a wireless link provides a natural eavesdropping and intervention capability to an adversary. Thus, securing a wireless link is essential to the security of a wireless network, and key generation algorithms are necessary for securing wireless links. However, traditional key agreement algorithms can be very costly in many settings, e.g. in wireless ad-hoc networks, since they consume scarce resources such as bandwidth and battery power.
Expression of YAV Proteins and Vaccination against Viral Ascites among Cultured Juvenile Yellowtail (2000)

Yellowtail ascites virus (YAV) is a member of the family Birnaviridae and causes viral ascites among juvenile yellowtail (Seriola quinqueradiata). We have reported the cloning and expression of two viral cDNAs, the first being segment A encoding a polyprotein of viral capsid proteins (VP2 and VP3) and a protease (NS), and the second being VP2-epitope encoding serotype-specific epitope region on VP2, using a baculovirus expression system. Another viral cDNA encoding a polyprotein of NS and VP3 was cloned and expressed in this study. For the expression of NS/VP3 (YAV nt 1626 to 3066) in insect cells a 31-kDa protein, corresponding to VP3 was detected, indicating an appropriate posttranslational processing of NS/VP3 polypeptide by NS protease itself. The analysis of the N-terminal amino acid sequence of this protein showed that NS protease may cleave an Ala-Ser bond. A study of the potential for vaccination of yellowtail fry by injection of insect cell lysates infected with baculovirus, containing either cDNA of segment A, VP2-epitope, or NS/VP3 was undertaken. Only a vaccination with cell lysates infected with a recombinant virus carrying the full length of YAV segment A gene demonstrated approximately the same effect as that of inactivated YAV. This result suggested that all proteins VP2, VP3, and NS are required for an effective vaccination.
Defective NF-κB Signaling in Metastatic Head and Neck Cancer Cells Leads to Enhanced Apoptosis by Double-Stranded RNA (2011)

Ligands to several Toll-like receptors (TLR), which mediate innate immune responses and chronic inflammation have been used as adjuvants to immunotherapy to enhance their antitumor activity. In particular, double-stranded RNAs that are cognate ligands of TLR3 have been used to trigger proapoptotic activity in cancer cells. However, a mechanistic understanding of TLR3-mediated apoptosis and its potential involvement in controlling tumor metastasis has been lacking. In this study, we used paired cell lines and fresh tumor specimens, derived from autologous primary and metastatic head and neck squamous cell carcinoma, to investigate the role of TLR3 signaling in metastatic progression. Compared with primary tumor cells, metastatic tumor cells were highly sensitive to TLR3-mediated apoptosis after double-stranded RNA treatment. Enhanced apoptosis in metastatic cells was dependent on double-stranded RNA and TLR3 and also the TLR3 effector signaling protein TRIF. Downstream responses requiring NF-κB were critical for apoptosis in metastatic cells, the defects in which could be resuscitated by alternative pathways of NF-κB activation. By elucidating how TLR3 ligands trigger apoptosis in metastatic cells, our findings suggest insights into how to improve their clinical use.
Resistance to RET-Inhibition in RET-Rearranged NSCLC Is Mediated By Reactivation of RAS/MAPK Signaling (2017)

Oncogenic rearrangements in <i>RET</i> are present in 1%-2% of lung adenocarcinoma patients. Ponatinib is a multi-kinase inhibitor with low-nanomolar potency against the RET kinase domain. Here, we demonstrate that ponatinib exhibits potent antiproliferative activity in RET fusion-positive LC-2/ad lung adenocarcinoma cells and inhibits phosphorylation of the RET fusion protein and signaling through ERK1/2 and AKT. Using distinct dose escalation strategies, two ponatinib-resistant LC-2/ad cell lines, PR1 and PR2, were derived. PR1 and PR2 cell lines retained expression, but not phosphorylation of the RET fusion and lacked evidence of a resistance mutation in the RET kinase domain. Both resistant lines retained activation of the MAPK pathway. Next-generation RNA sequencing revealed an oncogenic NRAS p.Q61K mutation in the PR1 cell. PR1 cell proliferation was preferentially sensitive to siRNA knockdown of NRAS compared with knockdown of RET, more sensitive to MEK inhibition than the parental line, and NRAS dependence was maintained in the absence of chronic RET inhibition. Expression of NRAS p.Q61K in RET fusion expressing TPC1 cells conferred resistance to ponatinib. PR2 cells exhibited increased expression of EGFR and AXL. EGFR inhibition decreased cell proliferation and phosphorylation of ERK1/2 and AKT in PR2 cells, but not LC-2/ad cells. Although AXL inhibition enhanced PR2 sensitivity to afatinib, it was unable to decrease cell proliferation by itself. Thus, EGFR and AXL cooperatively rescued signaling from RET inhibition in the PR2 cells. Collectively, these findings demonstrate that resistance to ponatinib in RET-rearranged lung adenocarcinoma is mediated by bypass signaling mechanisms that result in restored RAS/MAPK activation. <i>Mol Cancer Ther; 16(8); 1623-33. ©2017 AACR</i>.
Genetic characterization of the stabilizing functions of a region of broad-host-range plasmid RK2 (1990)

One of the regions responsible for the stable inheritance of the broad-host-range plasmid RK2 is contained within the PstI C fragment, located from coordinates 30.8 to 37.0 kb (P.N. Saurugger, O. Hrabak, H. Schwab, and R.M. Lafferty, J. Biotechnol. 4:333-343, 1986). Genetic analysis of this 6.2-kb region demonstrated that no function was present that stabilized by selectively killing plasmid-free segregants. The sequence from 36.0 to 37.0 kb mediated a twofold increase in plasmid copy number, but this region was not required for stabilization activity. The PstI C fragment was shown to encode a multimer resolution system from 33.1 to 35.3 kb. The resolution cis-acting site was mapped to 140 bp, sequenced, and observed to contain two directly repeated sequences of 6 and 7 bases and two perfect inverted repeats of 6 and 8 bases. The trans-acting factor(s) was mapped and functionally determined to encode a resolvase capable of catalyzing recombination at high frequency between cis-acting sites in either direct or inverted orientation. Multimer resolution alone did not account for complete plasmid stabilization by the PstI C fragment, since removal of regions adjacent to the 35.3-kb border of the minimal mrs locus dramatically reduced stabilization. The minimal region required for complete stabilization, from 32.8 to 35.9 kb, was capable of fully stabilizing plasmids independently of the replicon or the recA proficiency of the host. Stabilization activity was also fully expressed in several diverse gram-negative bacteria, whereas the F plasmid par locus functioned only in Escherichia coli. On the basis of these observations, we conclude that under the growth conditions used, the minimal stabilization locus encodes both an mrs activity and a stabilization activity that has the properties of a par locus.
Calcium/calmodulin‐dependent kinase activity is required for efficient induction of osteoclast differentiation and bone resorption by receptor activator of nuclear factor kappa B ligand (RANKL) (2007)

Calcium/calmodulin-dependent protein kinase (CaMK) is a major down stream mediator of Ca(2+) signaling in a wide range of cellular functions, including ion channel and cell cycle regulation and neurotransmitter synthesis and release. Here we have investigated the role of the CaMK signaling pathway in osteoclast differentiation and bone resorption. We observed that the CaMKI, CaMKII gamma isoforms were present in both bone-marrow derived macrophages and RAW264.7 murine macrophage cell line, and that expression persisted during osteoclast differentiation in the presence of receptor activator of nuclear factor kappa B (NF-kappaB) ligand (RANKL). RANKL-induced differentiation was accompanied by increased cyclic AMP response element transcriptional activity, and ERK phosphorylation, which are both downstream targets of CaMK. Two selective inhibitors of CaMKs, KN-93 and KN-62, inhibited osteoclastogenesis in a time and concentration-dependent manner. This was accompanied by suppression of cathepsin K expression and osteoclastic bone resorption, which are markers for differentiated osteoclast function. KN-93 and KN-62 both inhibited RANKL-induced ERK phosphorylation and CREB transcriptional activity. These findings imply a role for CaMK in osteoclast differentiation and bone resorption.
Requirement of the SH3 and SH2 Domains for the Inhibitory Function of Tyrosine Protein Kinase p50csk in T Lymphocytes (1995)

Previous studies from our laboratory have shown that the cytosolic tyrosine protein kinase p50csk is involved in the negative regulation of T-cell activation (L.M. L. Chow, M. Fournel, D. Davidson, and A. Veillette, Nature [London] 365:156-160, 1993). This function most probably reflects the ability of Csk to phosphorylate the inhibitory carboxy-terminal tyrosine of p56lck and p59fynT, two Src-related enzymes abundantly expressed in T lymphocytes. Herein, we have attempted to better understand the mechanisms by which Csk participates in the inhibitory phase of T-cell receptor signalling. Our results demonstrated that the Src homology 3 (SH3) and SH2 domains of p50csk are crucial for its negative impact on T-cell receptor-mediated signals. As these two sequences were not essential for phosphorylation of the carboxy-terminal tyrosine of a Src-like product in yeast cells, we postulated that they mediate protein-protein interactions allowing the recruitment of p50csk in the vicinity of activated Lck and/or FynT in T cells. In complementary studies, it was observed that linkage of a constitutive membrane targeting signal to the amino terminus of Csk rescued the deleterious impact of a point mutation in the SH2 domain of p50csk. This observation suggested that the SH2 sequence is in part necessary to translocate p50csk from the cytoplasm to the plasma membrane, where Src-related enzymes are located. Nevertheless, constitutive membrane localization was unable to correct the effect of complete deletion of the SH3 or SH2 sequence, implying that these domains provide additional functions necessary for the biological activity of p50csk.
Ki67 and PIM1 expression predict outcome in mantle cell lymphoma treated with high dose therapy, stem cell transplantation and rituximab: a Cancer and Leukemia Group B 59909 correlative science study (2008)

The proliferation index in mantle cell lymphoma (MCL) has not been validated in the context of aggressive therapy regimens in the rituximab era. We assessed Ki67 and PIM1 (a cell cycle-related gene upregulated in blastoid MCL) expression by immunohistochemistry in a phase II study Cancer and Leukemia Group B 59909 of aggressive chemotherapy and rituximab followed by autologous stem cell transplantation plus rituximab in untreated MCL patients <70 years of age. As a continuous variable or using a cutoff of 35%, higher image analysis (IA Ki67, n = 52) was associated with shorter progression free survival (PFS) (P < or = 0.030) and event free survival (EFS) (P < or = 0.017). PIM1 expression (n = 50) was associated with PFS (P = 0.033) and EFS (P = 0.043). Bivariate Cox models showed IA Ki67 and PIM1 were independent of clinical factors. High Ki67 (>35%) is an important independent prognostic marker in aggressively treated MCL in the rituximab era. PIM1 expression predicts poor outcome and, given its potential role as a therapeutic target, deserves further study.
Resolution of infection status of human immunodeficiency virus (HIV)‐ seroindeterminate donors and high‐risk seronegative individuals with polymerase chain reaction and virus culture: absence of persistent silent HIV type 1 infection in a high‐prevalence area (1992)

To address concerns over the prevalence of silent (antibody-negative) infections among blood donors and high-risk populations, a combination of proviral amplification by polymerase chain reaction (PCR) and viral isolation by co-culture techniques was employed to resolve the human immunodeficiency virus type 1 (HIV-1) infection status of well-characterized groups of suspect blood donors and others identified in the blood bank setting. No silent infections were found in 65 follow-up samples from 26 persistently HIV-1-seroindeterminate blood donors, 16 persistently seronegative heterosexual partners of infected transfusion recipients, and 6 high-risk seronegative homosexual men identified through donor look-back investigations. In contrast, 21 seropositive controls tested positive. These results suggest a low prevalence of persistently silent infections in at-risk populations, even in high HIV prevalence regions. The PCR assay, with a co-detected internal positive control, and appropriate confirmatory algorithms, was found to be a useful direct assay to rule out infection, especially in concert with confirmatory virus isolation.
Conservation of Critical Functional Domains in Murine Plasminogen Activator Inhibitor-1 (2004)

Plasminogen activator inhibitor-1 is the main physiological regulator of tissue-type plasminogen activator in normal plasma. In addition to its critical function in fibrinolysis, plasminogen activator inhibitor-1 has been implicated in roles in other physiological and pathophysiological processes. To investigate structure-function aspects of mouse plasminogen activator inhibitor-1, the recombinant protein was expressed in Escherichia coli and purified. Five variant recombinant murine proteins (R76E, Q123K, R346A, R101A, and Q123K/R101A) were also generated using site-directed mutagenesis. The variant (R346A) was found to be defective in its inhibitory activity against tissue plasminogen activator relative to its wild-type counterpart. Enzyme-linked immunosorbent assay and surface plasmon resonance experiments demonstrated reduced vitronectin-binding affinity of the (Q123K) variant (K(D) = 1800 nm) relative to the wild-type protein (K(D) = 5.4 nm). Kinetic analyses indicated that the (Q123K) variant had a slower association (k(on) = 2.92 x 10(4) m(-1) s(-1)) to, and a faster dissociation from, vitronectin (k(off) = 5.3 x 10(-2) s(-1)), (wild-type k(on) = 1.03 x 10(6) m(-1) s(-1) and k(off) = 5.27 x 10(-3) s(-1)). The Q123K/R101A variant demonstrated an even lower vitronectin-binding ability. Low density lipoprotein receptor-related protein binding was decreased for the (R76E) variant. It was also demonstrated that the plasminogen activator inhibitor-1/vitronectin complex decreased the interaction of plasminogen activator inhibitor-1 with low density lipoprotein receptor-related protein. These results indicate that the complex interactions traditionally associated with different plasminogen activator inhibitor-1 functions apply to the murine system, thus showing a commonality of subtle functions among different species and evolutionary conservation of this protein. Further, this study provides additional evidence that the human hemostasis system can be studied effectively in the mouse, which is a great asset for investigations with gene-altered mice.
Chenodeoxycholic acid therapy for hypertriglyceridaemia in men. (1978)

1 Ten consecutive patients with hypertriglyceridaemia who adhered to a low carbohydrate diet without complete control of serum triglycerides were started on chenodeoxycholic acid 750 mg daily and followed monthly for 6 months. Nine of these patients were then followed for a further month on placebo capsules and thereafter monthly for a further 6 months on clofibrate 2 g daily. 2 The mean serum triglyceride level fell by 36% after dietary treatment alone (P less than 0.05) and by 47% from initial values on diet plus chenodeoxycholic acid (P less than 0.01). In the nine patients who proceeded to clofibrate therapy there was a rise in triglyceride levels on placebo capsules to the level achieved by diet alone, and a further fall on diet plus clofibrate of 47% of initial values (P less than 0.05). 3 Chenodeoxycholic acid therapy is effective in the management of hypertriglyceridaemia not completely cured by dietary measures, and may be as efficacious as clofibrate.
Progress in Multimodality Imaging: Truly Simultaneous Ultrasound and Magnetic Resonance Imaging (2007)

Multimodality medical imaging takes advantage of the strengths of different imaging modalities to provide a more complete picture of the anatomy under investigation. Many complementary modalities have been combined to form such systems and some are gaining use clinically. One combination that has not been developed, in large part due to technical difficulties, is a combined magnetic resonance (MR) and ultrasound (US) imaging system. Such a system offers the potential to combine the strengths of these modalities in a wide range of diagnostic and therapeutic applications. The goal of this study was to evaluate the feasibility of performing simultaneous multimodality US and MR imaging. An US imaging system capable of operation in a clinical MR imager was developed, and methods to perform simultaneous imaging were investigated. Simultaneous imaging was feasible without any mutual interference by either filtering the transmitted and received US signal, or by synchronizing data acquisition between the two imaging systems. Spatial registration between the two modalities was achieved by using a reference phantom with implanted glass beads in orthogonal planes. Excellent agreement was observed between spatial measurements of an object made with both modalities, and the feasibility of using this system in vivo was demonstrated in a rabbit model. Simultaneous US and MR imaging is achievable, and can provide complementary information about an object under investigation. This demonstration of technical feasibility and the development of a prototype system open up the potential to investigate the promising clinical applications of this combined technology.