gebhart/patrepeval huggingface dataset:
Chemokine receptor CXCR4 downregulated by von Hippel–Lindau tumour suppressor pVHL (2003)

Organ-specific metastasis is governed, in part, by interactions between chemokine receptors on cancer cells and matching chemokines in target organs. For example, malignant breast cancer cells express the chemokine receptor CXCR4 and commonly metastasize to organs that are an abundant source of the CXCR4-specific ligand stromal cell-derived factor-1alpha (ref. 1). It is still uncertain how an evolving tumour cell is reprogrammed to express CXCR4, thus implementing the tendency to metastasize to specific organs. Here we show that the von Hippel-Lindau tumour suppressor protein pVHL negatively regulates CXCR4 expression owing to its capacity to target hypoxia-inducible factor (HIF) for degradation under normoxic conditions. This process is suppressed under hypoxic conditions, resulting in HIF-dependent CXCR4 activation. An analysis of clear cell renal carcinoma that manifests mutation of the VHL gene in most cases revealed an association of strong CXCR4 expression with poor tumour-specific survival. These results suggest a mechanism for CXCR4 activation during tumour cell evolution and imply that VHL inactivation acquired by incipient tumour cells early in tumorigenesis confers not only a selective survival advantage but also the tendency to home to selected organs.
Trojan Detection using IC Fingerprinting (2007)

Hardware manufacturers are increasingly outsourcing their IC fabrication work overseas due to their much lower cost structure. This poses a significant security risk for ICs used for critical military and business applications. Attackers can exploit this loss of control to substitute Trojan ICs for genuine ones or insert a Trojan circuit into the design or mask used for fabrication. We show that a technique borrowed from side-channel cryptanalysis can be used to mitigate this problem. Our approach uses noise modeling to construct a set of fingerprints/or an IC family utilizing side- channel information such as power, temperature, and electromagnetic (EM) profiles. The set of fingerprints can be developed using a few ICs from a batch and only these ICs would have to be invasively tested to ensure that they were all authentic. The remaining ICs are verified using statistical tests against the fingerprints. We describe the theoretical framework and present preliminary experimental results to show that this approach is viable by presenting results obtained by using power simulations performed on representative circuits with several different Trojan circuitry. These results show that Trojans that are 3-4 orders of magnitude smaller than the main circuit can be detected by signal processing techniques. While scaling our technique to detect even smaller Trojans in complex ICs with tens or hundreds of millions of transistors would require certain modifications to the IC design process, our results provide a starting point to address this important problem.
Fatal peptic ulcer complications and the use of non-steroidal anti-inflammatory drugs, aspirin, and corticosteroids. (1987)

Although non-steroidal anti-inflammatory drugs are known to cause peptic ulcer and its complications, controversy exists about the number of deaths from ulcer which are attributable to their use. A case-control study was therefore performed to determine whether prior use of non-steroidal and other anti-inflammatory compounds was associated with an increased case fatality rate from complications of peptic ulcer. Non-steroidal anti-inflammatory drugs were used by 39% of a series of 80 patients who had died from peptic ulcer complications and by 37% of 160 controls who were survivors matched for sex, age, ulcer site, and nature of complication (odds ratio 1.1; 95% confidence interval 0.6 to 2.1). Similarly, the rates of prior use of aspirin by cases and controls were almost identical (odds ratio 1.2; 95% confidence interval 0.5 to 1.9). Thus neither nonsteroidal anti-inflammatory drugs nor aspirin were associated with increased case fatality rates from peptic ulcer complications. In contrast, corticosteroids were associated with an increased mortality (odds ratio 4.2; 95% confidence interval 0.9 to 25.6). Although this increase in the estimated relative risk was not statistically significant, a review of the case records indicated that most deaths in steroid users were due to serious sepsis, indicating that there might be a causal association between use of the drugs and the mode of death.
A solid‐phase synthetic strategy for the preparation of peptide‐based affinity labels: synthesis of dynorphin A analogs (2000)

Solid-phase synthetic methodology was developed for the preparation of peptide-based affinity labels. The initial peptides synthesized were dynorphin A (Dyn A) analogs [Phe(p-X)4,D-Pro10]Dyn A(1-11)NH2 containing isothiocyanate (X=-N=C=S) and bromoacetamide (X=-NHCOCH2Br) groups. The peptides were assembled on solid supports using Fmoc-protected amino acids, and the side chain amine to be functionalized, Phe(p-NH2), was protected by the Alloc (allyloxycarbonyl) group. Following removal of the Alloc group by palladium(O), the reactive isothiocyanate and bromoacetamide functionalities were successfully introduced while the peptides were still attached to the resin. Synthesis of these peptides was carried out on polystyrene (PS) and polyethylene glycol-polystyrene (PEG-PS) resins containing the PAL [peptide amide linker, 5-(4-Fmoc-aminomethyl-3,5-dimethoxyphenoxy)valeric acid] linker. Both the rate of Alloc deprotection and the purity of the crude affinity-labeled peptides obtained were found to be dependent on the resin used for peptide assembly.
Crystal Structure of the Superfamily 1 Helicase from Tomato Mosaic Virus (2012)

The genomes of the Tomato mosaic virus and many other plant and animal positive-strand RNA viruses of agronomic and medical importance encode superfamily 1 helicases. Although helicases play important roles in viral replication, the crystal structures of viral superfamily 1 helicases have not been determined. Here, we report the crystal structure of a fragment (S666 to Q1116) of the replication protein from Tomato mosaic virus. The structure reveals a novel N-terminal domain tightly associated with a helicase core. The helicase core contains two RecA-like α/β domains without any of the accessory domain insertions that are found in other superfamily 1 helicases. The N-terminal domain contains a flexible loop, a long α-helix, and an antiparallel six-stranded β-sheet. On the basis of the structure, we constructed deletion mutants of the S666-to-Q1116 fragment and performed split-ubiquitin-based interaction assays in Saccharomyces cerevisiae with TOM1 and ARL8, host proteins that are essential for tomato mosaic virus RNA replication. The results suggested that both TOM1 and ARL8 interact with the long α-helix in the N-terminal domain and that TOM1 also interacts with the helicase core. Prediction of secondary structures in other viral superfamily 1 helicases and comparison of those structures with the S666-to-Q1116 structure suggested that these helicases have a similar fold. Our results provide a structural basis of viral superfamily 1 helicases.
The influence of preoperative drug treatment on the extent of hyperplasia of the thymus in primary thyrotoxicosis. (1975)

Thymic biopsies taken from women at the beginning of the operation of subtotal thyroidectomy were studied by the point-counting histometric technique. In all patients with primary thyrotoxicosis, the thymus is hyperplastic. After pretreatment with antithyroid drugs, the pattern of thymic involution with age is similar to, but at higher levels, than that in control groups of patients with non-toxic goitre in whom there is no evidence of immunological abnormality. By contrast, after propranolol pretreatment very little age involution is seen. The differences in the appearance of the thymus in female primary thyrotoxixosis patients prepared for operation with different drug treatment regimes are probably related to the pharmacological actions of the drugs and may indicate an interaction between primary immunological and secondary endocrinological factors in the disease process.
The Performance Improvement of a Multicarrier DS-CDMA System Using both Time-Diversity and Frequency Offset (1999)

In this paper, we show the robustness of a proposed system using both a frequency diversity and a time diversity effect when the channel assumptions are relaxed such that all subbands are not subject to independent fading. We take time-repetition coding with interleaving such that the repetition code symbols are spaced sufficiently far apart to guarantee time diversity. We also incorporate offset multicarriers into a proposed multicarrier DS-CDMA system in a different way compared to that of [10] to reduce the total multiple access interference. When we take a convolutional encoder instead of a time-repetition encoder, and again use both time diversity and frequency offset, then we can obtain the significant performance gain.
Chemosensitization of Prostate Cancer by Modulating Bcl-2 Family Proteins (2010)

A major challenge in oncology is the development of chemoresistance. This often occurs as cancer progresses and malignant cells acquire mechanisms to resist insults that would normally induce apoptosis. The onset of androgen independence in advanced prostate cancer is a prime example of this phenomenon. Overexpression of the pro-survival/anti-apoptotic proteins Bcl-2, Bcl-xL, and Mcl-1 are hallmarks of this transition. Here we outline the evolution of therapeutics designed to either limit the source or disrupt the interactions of these pro-survival proteins. By either lessening the stoichiometric abundance of Bcl-2/xL/Mcl-1 in reference to their pro-apoptotic foils or freeing these pro-apoptotic proteins from their grip, these treatments aim to sensitize cells to chemotherapy by priming cells for death. DNA anti-sense and RNA interference have been effectively employed to decrease Bcl-2 family mRNA and protein levels in cell culture models of advanced prostate cancer. However, clinical studies are lagging due to in vivo delivery challenges. The burgeoning field of nanoparticle delivery holds great promise in helping to overcome the challenge of administering highly labile nucleic acid based therapeutics. On another front, small molecule inhibitors that block the hetero-dimerization of pro-survival with pro-apoptotic proteins have significant clinical advantages and have advanced farther in clinical trials with promising early results. Most recently, a peptide has been discovered that can convert Bcl-2 from a pro-survival to a pro-apoptotic protein. The future may lie in targeting multiple steps of the apoptotic pathway, including Bcl-2/xL/Mcl-1, to debilitate the survival capacity of cancer cells and make chemotherapy induced death their only option.
Late Failure in Vein Grafts (1978)

Late failure of autologous vein grafts often results from excessive subendothelial fibromuscular hyperplasia. Varying factors have been implicated in this process, but the exact etiology remains unclear. In this study, three groups of animals were studied which had sections of common carotid artery replaced with autologous vein grafts. Group I had simple replacement, while Groups II and III had grafts supported by either tightly woven or loose mesh dacron prostheses. Thrombosis occurred only in the unsupported grafts. Unsupported grafts also had more subendothelial proliferation when compared to the loose mesh group. The combined thickness of the intima-media correlated inversely with the number of vasa present within the vein graft wall, i.e. significantly more vascularization was found in the mesh supported group when compared to the other groups. Grafts supported with the tightly woven prosthesis were relatively impervious to the ingrowth of vasa vasora. The data suggest that persistent distension of the graft wall by intra-arterial pressure influences the degree of subendothelial fibromuscular hyperplasia and may be interrelated to revascularization of the graft wall per se.
Oxygen-carrying perfluorochemical emulsion as an adjuvant to radiation therapy in mice. (1984)

The potential of an oxygen-carrying perfluorochemical emulsion (PFCE) to enhance radiation damage in Lewis lung tumor growing in C57BL/6J X DBA/2J F1 mice was examined. PFCE and 95% O2:5% CO2 (carbogen) breathing caused a significant enhancement of single-fraction radiation damage measured by the growth delay assay. The dose-response effect of PFCE was very broad; doses as small as 0.5 ml/mouse were effective, and doses of 0.3 to 0.4 ml/mouse gave maximal enhancement. The peak dose-modifying factor was 2.8 +/- 0.6 (S.E.). The addition of 0.3 ml of perfluorochemical-free annex solution with carbogen breathing produced a smaller enhancement in tumor growth delay; the dose-modifying factor was 1.5 +/- 0.2. When the perfluorochemical treatment was added to a fractionated course of radiation therapy, a dose-modifying effect of 1.8 +/- 0.3 was obtained. Oxygen-carrying PFCE may provide a nontoxic, clinically useful method of increasing the effectiveness of radiation therapy and of certain chemotherapeutic agents.
Intracellular localisation of human HIF-1α hydroxylases:implications for oxygen sensing (2003)

Hypoxia-inducible factor1 (HIF-1) is an essential transcription factor for cellular adaptation to decreased oxygen availability. In normoxia the oxygen-sensitive alpha-subunit of HIF-1 is hydroxylated on Pro564 and Pro402 and thus targeted for proteasomal degradation. Three human oxygen-dependent HIF-1 alpha prolyl hydroxylases (PHD1, PHD2, and PHD3) function as oxygen sensors in vivo. Furthermore, the asparagine hydroxylase FIH-1 (factor inhibiting HIF) has been found to hydroxylate Asp803 of the HIF-1 C-terminal transactivation domain, which results in the decreased ability of HIF-1 to bind to the transcriptional coactivator p300/CBP. We have fused these enzymes to the N-terminus of fluorescent proteins and transiently transfected the fusion proteins into human osteosarcoma cells (U2OS). Three-dimensional 2-photon confocal fluorescence microscopy showed that PHD1 was exclusively present in the nucleus, PHD2 and FIH-1 were mainly located in the cytoplasm and PHD3 was homogeneously distributed in cytoplasm and nucleus. Hypoxia did not influence the localisation of any enzyme under investigation. In contrast to FIH-1, each PHD inhibited nuclear HIF-1 alpha accumulation in hypoxia. All hydroxylases suppressed activation of a cotransfected hypoxia-responsive luciferase reporter gene. Endogenous PHD2mRNA and PHD3mRNA were hypoxia-inducible, whereas expression of PHD1mRNA and FIH-1mRNA was oxygen independent. We propose that PHDs and FIH-1 form an oxygen sensor cascade of distinct subcellular localisation.
Zhang et al. (2022) Data for journal publication (2022)

This repository contains dataset for Zhang et al. (2022) publication.
Comparative Adverse Cardiac Effects of Pimobendan and Benazepril Monotherapy in Dogs with Mild Degenerative Mitral Valve Disease: A Prospective, Controlled, Blinded, and Randomized Study (2007)

Abstract Background: Pimobendan (PIMO) is an inodilator that may have some beneficial effects in canine degenerative mitral valve disease (MVD). However, little information is available about its cardiac effects in dogs without systolic myocardial dysfunction. Hypothesis: Compared to benazepril (BNZ), an angiotensin-converting enzyme inhibitor, PIMO may worsen valve regurgitation in early canine MVD. Animals: Twelve Beagles with asymptomatic MVD were randomized into 2 groups (n = 6) receiving BNZ or PIMO at dosages of 0.25 mg/kg PO q24h and q12h respectively, for 512 days. Methods: The study followed a blinded, randomized, prospective, and parallel group design. After day 512, the dogs were necropsied, and cardiac histopathology was performed in a blinded manner. Results: A significant treatment effect was observed as soon as day 15 with increased systolic function in the PIMO group by comparison to baseline value as assessed by fractional shortening (P &amp;lt; .0001) and tissue Doppler variables (P= .001). Concurrently, the maximum area and peak velocity of the regurgitant jet signal increased (P &amp;lt; .001), whereas these variables remained stable in the BNZ group. Histologic grades of mitral valve lesions were more severe in the PIMO group than in the BNZ group. Moreover, acute focal hemorrhages, endothelial papillary hyperplasia, and infiltration of chordae tendinae with glycosaminoglycans were observed in the mitral valves of dogs from the PIMO group but not in those of the BNZ group. Conclusions and Clinical Importance: PIMO has adverse cardiac functional and morphologic effects in dogs with asymptomatic MVD. Additional investigation in dogs with symptomatic MVD is now warranted.
The sequential development of abnormal prion protein accumulation in mice with Creutzfeldt-Jakob disease. (1992)

The distribution and sequential development of prion protein (PrP) accumulation in the central nervous system (CNS) and non-neuronal organs of mice infected with Creutzfeldt-Jakob disease (CJD) were investigated immunohistochemically using a new pretreatment method that greatly enhanced the immunoreactivity of PrP. Prion protein accumulation in the CNS was first detected at 30 days after inoculation and then developed near the inoculation site or periventricular area, and later spread to the whole cerebrum and then to the pons. Its staining took some characteristic forms. Among non-neuronal organs, PrP accumulated in the follicular dendritic cells (FDCs) in spleen, lymph node, Peyer's patch, and thymus. FDCs staining appeared in spleen, lymph node, and Peyer's patch at 21 or 30 days after inoculation, and in thymus at 90 days. Germinal centers developed in the thymus of some CJD-infected mice. No PrP staining was detected in any examined organs of age-matched control mice.
A Convenient Synthesis of 3-Aryl-2-Methyl-3,4-Dihydro-1(2H)-Isoquinolones and -1,2,3,4-Tetrahydroisoquinolines (2000)

Abstract A new methodology for the synthesis of 3-aryl-2-methyl-3,4-dihydro-2H-isoquinolin-l-ones and 3-aryl-2-methyl-1,2,3,4-tetrahydroisoquinolines is reported.
A Sodium-Dependent Neutral-Amino-Acid Transporter Mediates Infections of Feline and Baboon Endogenous Retroviruses and Simian Type D Retroviruses (1999)

ABSTRACT The type D simian retroviruses cause immunosuppression in macaques and have been reported as a presumptive opportunistic infection in a patient with AIDS. Previous evidence based on viral interference has strongly suggested that the type D simian viruses share a common but unknown cell surface receptor with three type C viruses: feline endogenous virus (RD114), baboon endogenous virus, and avian reticuloendotheliosis virus. Furthermore, the receptor gene for these viruses has been mapped to human chromosome 19q13.1–13.2. We now report the isolation and characterization of a cell surface receptor for this group of retroviruses by using a human T-lymphocyte cDNA library in a retroviral vector. Swiss mouse fibroblasts (NIH 3T3), which are naturally resistant to RD114, were transduced with the retroviral library and then challenged with an RD114-pseudotyped virus containing a dominant selectable gene for puromycin resistance. Puromycin selection yielded 12 cellular clones that were highly susceptible to a β-galactosidase-encoding lacZ(RD114) pseudotype virus. Using PCR primers specific for vector sequences, we amplified a common 2.9-kb product from 10 positive clones. Expression of the 2.9-kb cDNA in Chinese hamster ovary cells conferred susceptibility to RD114, baboon endogenous virus, and the type D simian retroviruses. The 2.9-kb cDNA predicted a protein of 541 amino acids that had 98% identity with the previously cloned human Na + -dependent neutral-amino-acid transporter B o . Accordingly, expression of the RD114 receptor in NIH 3T3 cells resulted in enhanced cellular uptake of l -[ 3 H]alanine and l -[ 3 H]glutamine. RNA blot (Northern) analysis suggested that the RD114 receptor is widely expressed in human tissues and cell lines, including hematopoietic cells. The human B o transporter gene has been previously mapped to 19q13.3, which is closely linked to the gene locus of the RD114 receptor.
Port wine stain coagulation experiments with a 540‐nm continuous wave dye‐lase (1983)

Treatment of port wine stains with a continuous wave dye laser at 540 nm was performed in three patients. Coagulation of the capillary blood plexus without damaging the epidermis and superficial dermis was shown to be possible for laser energy densities between 5 J/cm2 and 6.5 J/cm2. Vascular destruction was realised up to about 0.3 mm dermal depth. After 5 months the skin was perfectly normal. A comparison with argon laser treatment was made.
Cutting Edge: Inducible Costimulator Protein Regulates Both Th1 and Th2 Responses to Cutaneous Leishmaniasis (2002)

The CD28 family member inducible costimulator protein (ICOS) has an important role in T cell differentiation and Ig class switching. To investigate the role of ICOS in vivo, ICOS-/- mice were infected s.c. with Leishmania mexicana. While wild-type mice developed large, cutaneous lesions, the growth of lesions and tissue histopathology was significantly delayed in ICOS-/- mice. ICOS-/- mice exhibited marked decreases in both Th1 and Th2 cytokine production and profound defects in L. mexicana-specific Ig isotype class switching to IgG1 and IgG2a and reduced total IgE levels. Our findings indicate that ICOS is a key regulator of both Th1 and Th2 responses and has a role in controlling cutaneous L. mexicana infection.
A Description of Eddying Motions and Flow Patterns Using Critical-Point Concepts (1987)

The field of fluid mechanics is rapidly advancing, driven by unprecedented volumes of data from experiments, field measurements, and large-scale simulations at multiple spatiotemporal scales. Machine learning (ML) offers a wealth of techniques to extract ...Read More
Implanted myoblasts not only fuse with myofibers but also survive as muscle precursor cells (1993)

Intramuscular implanted myoblasts can fuse with existing myofibers. Here we report that implanted primary myoblasts marked with retroviral transgenes can also persist as muscle precursor cells. These cells can be recovered as viable myoblasts from muscles of recipient mice even months after myoblast implantation, and they can fully resume expression of the transgenes in culture. Upon re-implantation into muscles, they again not only fuse with existing myofibers, but also survive as muscle precursor cells in the tissue. These reserve myogenic cells should be able to contribute to host myofibers in muscle regeneration when the recombinant myofibers are damaged, providing an additional mechanism to maintain a persistent expression of transgenes delivered by myoblast-mediated gene transfer.