gebhart/patrepeval huggingface dataset:
Discrimination of Methylcytosine from Hydroxymethylcytosine in DNA Molecules (2010)

Modified DNA bases are widespread in biology. 5-Methylcytosine (mC) is a predominant epigenetic marker in higher eukaryotes involved in gene regulation, development, aging, cancer, and disease. Recently, 5-hydroxymethylcytosine (hmC) was identified in mammalian brain tissue and stem cells. However, most of the currently available assays cannot distinguish mC from hmC in DNA fragments. We investigate here the physical properties of DNA with modified cytosines, in efforts to develop a physical tool that distinguishes mC from hmC in DNA fragments. Molecular dynamics simulations reveal that polar cytosine modifications affect internal base pair dynamics, while experimental evidence suggest a correlation between the modified cytosine's polarity, DNA flexibility, and duplex stability. On the basis of these physical differences, solid-state nanopores can rapidly discriminate among DNA fragments with mC or hmC modification by sampling a few hundred molecules in the solution. Further, the relative proportion of hmC in the sample can be determined from the electronic signature of the intact DNA fragment.
Megakaryocyte endomitosis is a failure of late cytokinesis related to defects in the contractile ring and Rho/Rock signaling (2008)

Megakaryocyte (MK) is the naturally polyploid cell that gives rise to platelets. Polyploidization occurs by endomitosis, which was a process considered to be an incomplete mitosis aborted in anaphase. Here, we used time-lapse confocal video microscopy to visualize the endomitotic process of primary human megakaryocytes. Our results show that the switch from mitosis to endomitosis corresponds to a late failure of cytokinesis accompanied by a backward movement of the 2 daughter cells. No abnormality was observed in the central spindle of endomitotic MKs. A furrow formation was present, but the contractile ring was abnormal because accumulation of nonmuscle myosin IIA was lacking. In addition, a defect in cell elongation was observed in dipolar endomitotic MKs during telophase. RhoA and F-actin were partially concentrated at the site of furrowing. Inhibition of the Rho/Rock pathway caused the disappearance of F-actin at midzone and increased MK ploidy level. This inhibition was associated with a more pronounced defect in furrow formation as well as in spindle elongation. Our results suggest that the late failure of cytokinesis responsible for the endomitotic process is related to a partial defect in the Rho/Rock pathway activation.
Dipicolylglycyl-phenylalanine zinc(ii): a metallopeptide with a built-in conformational switch and its homochiral helical coordination polymer (2003)

The peptide-zinc complex [(Dpg-Phe)Zn]2+ (Dpg = N,N-dipicolylglycine; Phe = phenylalanine) reversibly forms a homochiral P-helical coordination polymer upon switching the pH from mildly basic to mildly acidic.
A floating body cell (FBC) fully compatible with 90nm CMOS technology(CMOS IV) for 128Mb SOI DRAM (2006)

A 128Mb SOI DRAM with FBC (floating body cell) has been successfully developed for the first time. Two technologies have been newly implemented. (i) In order to realize full functionality and good retention characteristics, the well design has been optimized both for the array device and the peripheral circuit. (ii) Cu wiring has been used for bit line (BL) and source line (SL), which leads to increasing the signal of the worst bit in the array and also realizes the full compatibility with 90nm CMOS technology
Tumor antigen presentation by epidermal antigen-presenting cells in the mouse: modulation by granulocyte-macrophage colony-stimulating factor, tumor necrosis factor α, and ultraviolet radiation (1992)

I-A+ epidermal antigen-presenting cells (APCs, Langerhans cells) have been shown to present tumor-associated antigens (TAAs) and to induce tumor immunity in vivo. This study examined the effects of ultraviolet radiation (UVR) and the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF-alpha) on the ability of epidermal cells (ECs) to induce or to elicit immunity against the murine spindle cell tumor S1509a. Naive syngeneic mice were immunized three times at weekly intervals with ECs that had been cultured in GM-CSF for 18 h and then pulsed with TAA derived from S1509a. This resulted in protective immunity against subsequent tumor challenge, providing a model to study the conditions required for sensitization against TAAs by epidermal APCs. Culture of ECs in GM-CSF was required for induction of significant protective tumor immunity, and UV irradiation or incubation in TNF-alpha for 2 h after GM-CSF incubation abrogated the immunostimulatory effect of GM-CSF. However, unlike UVR, TNF-alpha did not significantly inhibit the induction of immunity when ECs were exposed to TNF-alpha before overnight incubation in GM-CSF, together with GM-CSF, or after pulsing with TAA, and anti-TNF-alpha antibody treatment did not abrogate the effects of UVR on this system. Furthermore, TNF-alpha incubation of ECs augmented their ability to elicit delayed-type hypersensitivity (DTH) and also enhanced elicitation of DTH by GM-CSF-cultured ECs, whereas UV-irradiation reduced it in a dose-dependent fashion. Taken together, these results demonstrate that GM-CSF, TNF-alpha, and UVR are significant regulators of tumor antigen presentation by epidermal APCs and that the effects of the cytokines examined differ with regard to induction or elicitation of immunity.
Homology‐based control of gene expression patterns in transgenic petunia flowers (1998)

Plant transgenes may participate in two types of homology-based gene silencing. One requires transcript homology, is post-transcriptional, and is referred to as cosuppression; the other requires promoter homology, is transcriptional, and is similar to paramutation. This paper uses flower color transgenes to address the hierarchical operation of both mechanisms in plants carrying two transgene copies. It is shown that cosuppression of homologous, endogenous flower color genes by single-copy transgenes requires that the transgene be driven by a strong promoter and that the degree of cosuppression is highly sensitive to increasing transgene dosage. Together, these observations suggest that cosuppression should be a sensitive reporter of epigenetic changes in transgene transcription, such as might be caused by paramutation-like interactions between transgene loci. Intercrosses bringing together two homologous transgene loci, one a known epimutable reporter and the other a transgene inverted repeat, result in complete loss of cosuppression in some outcross progeny and a qualitative change in morphology-based patterns of cosuppression in other outcross progeny. This paramutation-like behavior suggests that the transgenes may be altered at the transcriptional level, eliminating cosuppression altogether or changing the spatial pattern of transgene transcription to produce a new pattern of cosuppression. Dev. Genet. 22:100–109, 1998. © 1998 Wiley-Liss, Inc.
Serum concentrations of myoglobin vs human heart-type cytoplasmic fatty acid-binding protein in early detection of acute myocardial infarction (1997)

We compared the diagnostic utility of serum concentrations of human heart-type cytoplasmic fatty acid-binding protein (H-FABPc), myoglobin, and their ratio for the early diagnosis of acute myocardial infarction (AMI) in 104 healthy volunteers and 165 patients at admission within 6 h of the onset of chest pain. The ROC curves of the H-FABPc [0.946, 95% confidence interval (CI) = 0.913-0.979] and myoglobin (0.895, 95% CI = 0.846-0.944) between patients with AMI and healthy volunteers were significantly greater than the area under the ratio of myoglobin to H-FABPc (0.823, 95% CI = 0.765-0.881). In 165 patients, the sensitivity (81.8%, 95% CI = 74.2-89.4%), specificity (86.4%, 95% CI = 78.1-94.6%), and predictive accuracy (83.6%, 95% CI = 78.0-89.3%) of H-FABPc > 12 micrograms/L in diagnosing AMI were significantly higher than those of myoglobin, and were similar to those of the combination of H-FABPc > 12 micrograms/L and the ratio < or = 14. We conclude that H-FABPc is a more sensitive and specific marker than myoglobin for the early diagnosis of AMI, and that their ratio cannot give a clear advantage over the measurement of H-FABPc alone.
Carbon nanotube circuits: opportunities and challenges (2013)

Carbon Nanotube Field-Effect Transistors (CNFETs) are excellent candidates for building highly energy-efficient digital systems. However, imperfections inherent in carbon nanotubes (CNTs) pose significant hurdles to realizing practical CNFET circuits. In order to achieve CNFET VLSI systems in the presence of these inherent imperfections, careful orchestration of design and processing is required: from device processing and circuit integration, all the way to large-scale system design and optimization. In this paper, we summarize the key ideas that enabled the first experimental demonstration of CNFET arithmetic and storage elements. We also present an overview of a probabilistic framework to analyze the impact of various CNFET circuit design techniques and CNT processing options on system-level energy and delay metrics. We demonstrate how this framework can be used to improve the energy-delay-product (EDP) of CNFET-based digital systems.
Engineering a Prostate-Specific Membrane Antigen–Activated Tumor Endothelial Cell Prodrug for Cancer Therapy (2012)

Heterogeneous expression of drug target proteins within tumor sites is a major mechanism of resistance to anticancer therapies. We describe a strategy to selectively inhibit, within tumor sites, the function of a critical intracellular protein, the sarcoplasmic/endoplasmic reticulum calcium adenosine triphosphatase (SERCA) pump, whose proper function is required by all cell types for viability. To achieve targeted inhibition, we took advantage of the unique expression of the carboxypeptidase prostate-specific membrane antigen (PSMA) by tumor endothelial cells within the microenvironment of solid tumors. We generated a prodrug, G202, consisting of a PSMA-specific peptide coupled to an analog of the potent SERCA pump inhibitor thapsigargin. G202 produced substantial tumor regression against a panel of human cancer xenografts in vivo at doses that were minimally toxic to the host. On the basis of these data, a phase 1 dose-escalation clinical trial has been initiated with G202 in patients with advanced cancer.
Localized Surface Plasmon Resonance Sensing of Lipid-Membrane-Mediated Biorecognition Events (2005)

Supported phospholipid bilayers (SPBs) have emerged as important model systems for studies of the natural cell membrane and its components, which are essential for the integrity and function of cells in all living organisms, and also constitute common targets for therapeutic drugs and in disease diagnosis. However, the preferential occurrence of spontaneous SPB formation on silicon-based substrates, but not on bare noble-metal surfaces, has so far excluded the use of the localized surface plasmon resonance (LSPR) sensing principle for studies of lipid-membrane-mediated biorecognition reactions. This is because the LSPR phenomenon is associated with, and strongly confined to, the interfacial region of nanometric noble-metal particles. This problem has been overcome in this study by a self-assembly process utilizing localized rupture of phospholipid vesicles on silicon dioxide in the bottom of nanometric holes in a thin gold film. The hole-induced localization of the LSPR field to the voids of the holes is demonstrated to provide an extension of the LSPR sensing concept to studies of reactions confined exclusively to SPB-patches supported on SiO2. In particular, we emphasize the possibility of performing label-free studies of lipid-membrane-mediated reaction kinetics, including the compatibility of the assay with array-based reading (approximately 7 x 7 microm2) and detection of signals originating from bound protein in the zeptomole regime.
Predicting amputation in severe ischaemia. The value of transcutaneous PO2 measurement (1988)

The predictive value of the pedal transcutaneous oxygen tension (tcPO2) and of the distal systolic blood pressure (SBP) in forecasting the necessity for later amputation has been studied in 26 patients suffering from severe chronic ischaemia of the lower limbs. In all these patients vascular surgery had failed or not been possible, and they were threatened by amputation; they suffered from trophic lesions, or pain at rest, or both. The great toe SBP averaged 10 mmHg (range 0 to 60 mmHg) and the pedal tcPO2 10 mmHg (range 2 to 45 mmHg). After six minutes of oxygen inhalation there was an increase in pedal tcPO2 of 9 mmHg (0 to 50 mmHg). After a follow-up period averaging 7 months (range 10 days to 13 months), 13 patients underwent an amputation and nine (five of whom had been amputated) died. The great toe SBP in the patients who required amputation was initially lower than in those who did not. The pedal tcPO2 also was lower in amputated than in non-amputated patients. There was no amputation in the group showing an increase of at least 10 mmHg after six minutes of oxygen inhalation; and conversely, all patients in whom the pedal tcPO2 increased less than 10 mmHg were amputated. Thus increase in the pedal tcPO2 after oxygen inhalation appears the best criterion for estimating the prognosis of severely ischaemic limbs.
A Protocol for Generation of Clinical Grade mRNA‐Transfected Monocyte‐Derived Dendritic Cells for Cancer Vaccines (2003)

With the aim of producing large quantities of mRNA-transfected monocyte-derived dendritic cells (DCs) to be used as cancer vaccines, a new clinical grade procedure has been developed. Peripheral blood mononuclear cells (PBMCs) obtained by leukapheresis were enriched for monocytes by immunomagnetic depletion of CD19+ B cells and CD2+ T cells employing the ISOLEX 300i device. After 5 days of culture of enriched monocytes in gas permeable Teflon bags, using serum-free medium supplemented with granulocyte/macrophage-colony stimulating factor and interleukin-4 (IL-4), immature DCs were generated. Following transfection with mRNA from three human prostate cancer cell lines (DU145, LNCaP and PC-3), employing a newly developed square wave electroporation procedure, the immature DCs were immediately transferred to Teflon bags and matured for 48 h, using serum-free medium supplemented with IL-1alpha, IL-6, tumour necrosis factor-alpha and PGE2. The electroporation procedure efficiently transferred mRNA into the DCs with minor effect on the viability of the cells. The generated matured transfected DCs show high expression of the antigens CD83, CD80, CD86 and human leucocyte antigen-DR. Freezing and thawing of the transfected matured DCs had minor effect on cell viability and the phenotype. From 4 x 109 PBMCs, about 1 x 108 transfected matured DCs are produced. The thawed transfected DCs were able to elicit primary T-cell responses in vitro against antigens encoded by the prostate cancer mRNA as shown by enzyme-linked immunospot assay using mock-transfected DCs as control. Based on these results, clinical trials in cancer patients have been initiated.
Experimental hepatitis and role of cytokines. (1997)

Activated T lymphocytes appear to be responsible for liver damage in chronic active hepatitis and autoimmune liver disease. We described three experimental mouse models of T cell dependent liver injury. D-galactosamine (GalN)-sensitized mice challenged with either T cell activating anti-CD3 monoclonal antibody (mAb) or with the superantigen staphylococcal enterotoxin B (SEB) developed severe liver injury characterized by internucleosomal DNA fragmentation as well as by histological hallmarks of hepatocyte apoptosis, both preceding the increase of plasma transaminases. Administration of the T cell mitogen concanavalin A (Con A) to unsensitized mice also resulted in hepatic apoptosis and the ensuing necrosis. Anti-CD3 mAb as well as SEB or Con A induced the release of systemic tumor necrosis factor (TNF), interferon gamma (IFN gamma), and various other cytokines. Passive immunization against TNF or pretreatment with immunosuppressive drugs such as cyclosporin A, FK 506 or dexamethasone protected mice from liver injury. T lymphocytes were identified as effector cells of Con A in vivo i) by proof of resistance of athyrnic nude mice against Con A and ii) by restoration of susceptibility in nude by lymphocyte transfer from control mice. Moreover, antibody-dependent depletion of CD4+ T cells fully protected against Con A, whereas depletion of CD8+ T cells failed to prevent liver injury. These results indicated that cytokines released following T helper cell activation rather than cytotoxic T cells mediated liver injury. We recently found that IFN gamma is also a critical mediator of Con A-induced hepatic damage. In conclusion, these T cell-dependent models of inflammatory liver injury allow the investigation of basic principles of hepatic disorders associated with T cell activation and infiltration as well as pharmacological in vivo studies for the development of hepatoprotective drugs.
Lie groups, space-variant Fourier analysis and the exponential chirp transform (1996)

The use of visual representations in which retinal neurons receptive fields are not constant over the visual field is universal in the visual systems of higher vertebrates, and is coming to play an important role in active vision applications. The breaking of translation symmetry that is unavoidably associated with non-uniform sampling presents a major algorithmic complication for image processing. In this paper we use a Lie group approach to derive a kernel which provides a quasi-shift (i.e. approximate shift) invariant template matching capability, under normal convolution in the distorted (range) coordinates of the non-uniform mapping. We work out the special case of the log-polar mapping, which is of great interest in vision; in this case, we call the associated linear integral transform the "exponential chirp transform" (ECT). The method is, however, general for other forms of mapping, or warp, function.
A single retroviral gag precursor signal peptide recognized by FBL-3 tumor-specific cytotoxic T lymphocytes (1995)

Several dominant T-cell receptors of cytotoxic T-lymphocyte (CTL) clones specific for FBL-3 tumor antigen were clonally amplified in mixed lymphocyte tumor cell cultures derived from an individual immune mouse. Every CTL clone analyzed had a common specificity for a single epitope in the precursor to cell membrane-associated nonstructural gag-encoded protein, Pr75gag, which can be minimally identified by nine amino acid residues, SIVLCCLCL. This epitope is located within the hydrophobic signal sequence motif that mediates translocation of the protein into the endoplasmic reticulum. These novel observations suggest that expression of Pr75gag in FBL-3 tumor cells led to the amplification of CTLs which recognize the signal sequence of the nonstructural gag-encoded glycoprotein precursor.
Plasminogen activator inhibitor-1 inhibitors: a patent review (2006 – present) (2013)

Although there is still no PAI-1 inhibitor being evaluated in a clinical setting or approved for human therapy, research in this field has progressed, and promising new compounds have been designed. Most research has focused on improving the pharmacological profile of these compounds, which will hopefully allow them to proceed to clinical studies. Despite the need for further testing and research, the potential use of PAI-1 inhibitors for treating cardiovascular disease appears quite promising.
Novel combination therapy for human colon cancer with adenovirus-mediated wild-typep53 gene transfer and DNA-damaging chemotherapeutic agent (1997)

Alteration of the wild-type (wt) p53 gene by mutation, deletion or re-arrangement is a major factor in the development of human colon cancer. Recent studies have demonstrated that p53 might be an essential component of the apoptotic pathway triggered by DNA-damaging stimuli such as chemotherapeutic agents and ionizing radiation. We examined the anti-tumor effects of adenovirus-mediated wt-p53 gene transfer in combination with a chemotherapeutic drug on the human colon cancer cell line WiDr, which is homozygous for a mutation in the p53 gene. Treatment with the chemotherapeutic drug cisplatin following infection with a replication-deficient, recombinant adenoviral vector expressing wt-p53 (termed AdCMVp53) significantly suppressed the growth of WiDr cells compared to single treatments alone. To evaluate the in vivo efficacy of AdCMVp53 and cisplatin given sequentially, WiDr cells were inoculated s.c. in nu/nu mice. After 3 days, AdCMVp53 was injected s.c. into the area where tumor cells were implanted, followed by i.p. administration of cisplatin. Analysis of initial growth inhibition at 21 days demonstrated a profound therapeutic cooperativity, though administration of either AdCMVp53 or cisplatin alone was followed only by a slowing of growth. Our results suggest that gene therapy using wt-p53-expressing adenovirus in combination with a chemotherapeutic DNA-damaging drug could be a useful strategy for treating human colon cancer.
A framework for fast and accurate collision detection for haptic interaction (2003)

We present a framework for fast and accurate collision detection for haptic interaction with polygonal models. Given a model, we pre-compute a hybrid hierarchical representation, consisting of uniform grids and trees of tight-fitting oriented bounding box trees (OBB-Trees). At run time, we use hybrid hierarchical representations and exploit frame-to-frame coherence for fast proximity queries. We describe a new overlap test, which is specialized for intersection of a line segment with an oriented bounding box for haptic simulation and takes 6-36 operations excluding transformation costs. The algorithms have been implemented as part of H-COLLIDE and interfaced with a PHANToM arm and its haptic toolkit, GHOST, and applied to a number of models. As compared to the commercial implementation, we are able to achieve up to 20 times speedup in our experiments and sustain update rates over 1000 Hz on a 400 MHz Pentium II.