gebhart/patrepeval huggingface dataset:
Stimulation of reverse transcriptase generated cDNAs with specific indels by template RNA structure: retrotransposon, dNTP balance, RT-reagent usage (2017)

RNA dependent DNA-polymerases, reverse transcriptases, are key enzymes for retroviruses and retroelements. Their fidelity, including indel generation, is significant for their use as reagents including for deep sequencing. Here, we report that certain RNA template structures and G-rich sequences, ahead of diverse reverse transcriptases can be strong stimulators for slippage at slippage-prone template motif sequence 3' of such 'slippage-stimulatory' structures. Where slippage is stimulated, the resulting products have one or more additional base(s) compared to the corresponding template motif. Such structures also inhibit slippage-mediated base omission which can be more frequent in the absence of a relevant stem-loop. Slippage directionality, base insertion and omission, is sensitive to the relative concentration ratio of dNTPs specified by the RNA template slippage-prone sequence and its 5' adjacent base. The retrotransposon-derived enzyme TGIRT exhibits more slippage in vitro than the retroviral enzymes tested including that from HIV. Structure-mediated slippage may be exhibited by other polymerases and enrich gene expression. A cassette from Drosophila retrotransposon Dme1_chrX_2630566, a candidate for utilizing slippage for its GagPol synthesis, exhibits strong slippage in vitro. Given the widespread occurrence and importance of retrotransposons, systematic studies to reveal the extent of their functional utilization of RT slippage are merited.
No Hypoglycemia After Subcutaneous Administration of Glucagon-Like Peptide-1 in Lean Type 2 Diabetic Patients and in Patients With Diabetes Secondary to Chronic Pancreatitis (2003)

We conclude that a GLP-1-based therapy would not be expected to be associated with an increased risk of hypoglycemia in insulin-sensitive type 2 diabetic patients.
Construction of an l-serine producing Escherichia coli via metabolic engineering (2014)

L-Serine is a nonessential amino acid, but plays a crucial role as a building block for cell growth. Currently, L-serine production is mainly dependent on enzymatic or cellular conversion. In this study, we constructed a recombinant Escherichia coli that can fermentatively produce L-serine from glucose. To accumulate L-serine, sdaA encoding the L-serine dehydratase, iclR encoding the isocitrate lyase regulator, and arcA encoding the aerobic respiration control protein were deleted in turn. In batch fermentation, the engineered E. coli strain YF-5 exhibited obvious L-serine accumulation but poor cell growth. To restore cell growth, aceB encoding the malate synthase was knocked out, and the engineered strain was then transformed with plasmid that overexpressed serA (FR) , serB, and serC genes. The resulting strain YF-7 produced 4.5 g/L L-serine in batch cultivation and 8.34 g/L L-serine in fed-batch cultivation.
Pertussis in Sweden after the cessation of general immunization in 1979 (1987)

Immunization against pertussis was introduced in Sweden in the 1950s and discontinued in 1979. This was followed by a low endemic level of pertussis for 3 years. Thereafter the incidence gradually increased and there were two outbreaks in 1983 and in 1985. In the period 1980 to 1985 pertussis was confirmed by culture or serology in 36,729 patients of which 11% were younger than 12 months of age and 69% were ages 1 to 6 years. An estimate of the total frequency of pertussis in preschool children was made from reports from a sample of the child health centers. The annual incidence rate per 100,000 population ages 0 to 6 years increased from the 700 cases in 1981 to 3200 in 1985. The ratio of total cases to those reported from the laboratories was 3:1 in 1981 and 2:1 in 1985. The cumulative incidence rate by the average age of 4 years was estimated at 16% of the unimmunized cohort born in 1980 compared with 5% of the immunized cohort born in 1978. The seriousness of pertussis was evaluated by studying the 2282 pertussis patients hospitalized from 1981 to the end of 1983. Forty-eight percent were infants younger than 12 months of age. Neurologic complications were noted in 4% and pneumonia in 14% of the hospitalized patients. Eleven children received assisted ventilation. Fatal outcomes were reported in 3 children (0.1%), 2 of whom had severe congenital disabilities.
Degradation of lamin B1 precedes oligonucleosomal DNA fragmentation in apoptotic thymocytes and isolated thymocyte nuclei. (1995)

Chromatin condensation and nuclear envelope breakdown are characteristic features of apoptotic cell death, but the mechanisms underlying these phenomena have not been identified. Solubilization of nuclear lamin is responsible for both events in mitosis. In this work, we report that glucocorticoids stimulate rapid degradation of lamin B1 that occurs before oligonucleosomal DNA fragmentation in apoptotic thymocytes. Protease inhibitors and the Ca2+ buffering agent BAPTA-AM block lamin degradation and DNA fragmentation, indicating that the processes are regulated by similar or identical mechanisms. Incubation of isolated thymocyte nuclei with Ca2+ stimulates lamin degradation before the detection of oligonucleosomal DNA fragments. However, in contrast to lamin dissolution during mitosis and some other forms of apoptosis, glucocorticoid-induced degradation of lamin B1 in thymocytes is not accompanied by dephosphorylation-mediated activation of cdc2. Our results demonstrate that lamin degradation is an early feature of apoptosis in thymocytes and suggest that chromatin condensation and breakdown of the nuclear envelope may occur as a result of disruption of nuclear lamina architecture.
Reduction in levels of the cyclin-dependent kinase inhibitor p27 kip-1 coupled with transforming growth factor β neutralization induces cell-cycle entry and increases retroviral transduction of primitive human hematopoietic cells (1998)

Successful gene therapy depends on stable transduction of hematopoietic stem cells. Target cells must cycle to allow integration of Moloney-based retroviral vectors, yet hematopoietic stem cells are quiescent. Cells can be held in quiescence by intracellular cyclin-dependent kinase inhibitors. The cyclin-dependent kinase inhibitor p15(INK4B) blocks association of cyclin-dependent kinase (CDK)4/cyclin D and p27(kip-1) blocks activity of CDK2/cyclin A and CDK2/cyclin E, complexes that are mandatory for cell-cycle progression. Antibody neutralization of beta transforming growth factor (TGFbeta) in serum-free medium decreased levels of p15(INK4B) and increased colony formation and retroviral-mediated transduction of primary human CD34(+) cells. Although TGFbeta neutralization increased colony formation from more primitive, noncycling hematopoietic progenitors, no increase in M-phase-dependent, retroviral-mediated transduction was observed. Transduction of the primitive cells was augmented by culture in the presence of antisense oligonucleotides to p27(kip-1) coupled with TGFbeta-neutralizing antibodies. The transduced cells engrafted immune-deficient mice with no alteration in human hematopoietic lineage development. We conclude that neutralization of TGFbeta, plus reduction in levels of the cyclin-dependent kinase inhibitor p27, allows transduction of primitive and quiescent hematopoietic progenitor populations.
Internal Friction of Subnanometera-SiO2Films (1995)

In order to determine whether strong interactions between defects are responsible for the spectral distribution of the low energy excitations that are believed to exist in all amorphous solids, we have measured the low temperature internal friction of thin $a$-Si${\mathrm{O}}_{2}$ films with thicknesses ranging from 0.75 to 1000 nm. The internal friction of these films is found to be identical to that of bulk $a$-Si${\mathrm{O}}_{2}$. From this it is concluded that interactions, if significant at all, are limited to distances less than 0.75 nm.
Calmodulin Binding and Inhibition of Cardiac Muscle Calcium Release Channel (Ryanodine Receptor) (2001)

Metabolically (35)S-labeled calmodulin (CaM) was used to determine the CaM binding properties of the cardiac ryanodine receptor (RyR2) and to identify potential channel domains for CaM binding. In addition, regulation of RyR2 by CaM was assessed in [(3)H]ryanodine binding and single-channel measurements. Cardiac sarcoplasmic reticulum vesicles bound approximately four CaM molecules per RyR2 tetramer in the absence of Ca(2+); in the presence of 100 microm Ca(2+), the vesicles bound 7.5 CaM molecules per tetramer. Purified RyR2 bound approximately four [(35)S]CaM molecules per RyR tetramer, both in the presence and absence of Ca(2+). At least four CaM binding domains were identified in [(35)S]CaM overlays of fusion proteins spanning the full-length RyR2. The affinity (but not the stoichiometry) of CaM binding was altered by redox state as controlled by the presence of either GSH or GSSG. Inhibition of RyR2 activity by CaM was influenced by Ca(2+) concentration, redox state, and other channel modulators. Parallel experiments with the skeletal muscle isoform showed major differences in the CaM binding properties and regulation by CaM of the skeletal and cardiac ryanodine receptors.
Parallel-Connected Solar PV System to Address Partial and Rapidly Fluctuating Shadow Conditions (2009)

Solar photovoltaic (PV) arrays in portable applications are often subject to partial shading and rapid fluctuations of shading. In the usual series-connected wiring scheme, the residual energy generated by partially shaded cells either cannot be collected (if diode bypassed) or, worse, impedes collection of power from the remaining fully illuminated cells (if not bypassed). Rapid fluctuation of the shading pattern makes maximum power point (MPP) tracking difficult; generally, there will exist multiple local MPPs, and their values will change as rapidly as does the illumination. In this paper, a portable solar PV system that effectively eliminates both of the aforementioned problems is described and proven. This system is capable of simultaneously maximizing the power generated by every PV cell in the PV panel. The proposed configuration consists of an array of parallel-connected PV cells, a low-input-voltage step-up power converter, and a simple wide bandwidth MPP tracker. Parallel-configured PV systems are compared to traditional series-configured PV systems through both hardware experiments and computer simulations in this paper. Study results demonstrate that, under complex irradiance conditions, the power generated by the new configuration is approximately twice that of the traditional configuration. The solar PV system can be widely used in many consumer applications, such as PV vests for cell phones and music players.
The SWI/SNF Chromatin-remodeling Complex Is a Cofactor for Tat Transactivation of the HIV Promoter (2006)

Tat is a critical viral transactivator essential for human immunodeficiency virus (HIV) gene expression. Activation involves binding to an RNA stem-loop structure and recruitment of the positive transcription elongation factor b. Tat also induces the remodeling of a single nucleosome in the HIV promoter. However, the mechanism of this remodeling has remained unclear. Knockdown of INI-1 and BRG-1, two components of the SWI/SNF chromatin-remodeling complex, suppressed Tat-mediated transactivation. Cells lacking INI-1 (G401 and MON) or BRG-1 (C33A) exhibited defective transactivation by Tat that was restored upon INI-1 and BRG-1 expression, respectively. Tat was co-immunoprecipitated with several SWI/SNF subunits, including INI-1, BRG-1, and beta-actin. The SWI/SNF complex interacted with the integrated HIV promoter in a Tat-dependent manner. We also found that INI-1 and BRG-1 synergized with the p300 acetyltransferase to activate the HIV promoter. This synergism depended on the acetyltransferase activity of p300 and on Tat Lys(50) and Lys(51). In conclusion, Tat-mediated activation of the HIV promoter requires the SWI/SNF complex in synergy with the coactivator p300.
Impact of the Crystal Structure on Solar Cell Parameters of Ribbon Growth on Substrate (RGS) Solar Cells (2008)

Ribbon Growth on Substrate (RGS) is a cost-effective method to produce silicon wafers directly from molten silicon without material losses due to wire sawing. This technique decouples crystallization and pulling direction of the silicon wafers which results in good wafer quality at a very high production speed of about one wafer per second. The multicrystalline wafers have typical grain sizes between 0.1 mm and 0.5 mm so that spatially resolved investigations of the effect of the crystal structure on cell performance are expected to improve wafer production and cell processing. One processed RGS solar cell was measured with Light Beam Induced Current (LBIC) and Lock-In Thermography (LIT) and the data was correlated with dislocation densities and electron microscopy investigations. In regions where the as grown wafer is thinner compared to the average wafer thickness, the internal quantum efficiency shows a tendency towards lower values. This can be traced back to high defect densities introduced by mechanical stresses during casting. An Energy Dispersive X-ray (EDX) analysis revealed carbon and oxygen impurities and possible precipitates. Also metal impurities in some of the defect-rich regions were found which may affect their electronic properties.
Epithelial Membrane Protein 2 Controls VEGF Expression in ARPE-19 Cells (2013)

This study establishes a novel connection between EMP2 and VEGF and may reflect either a direct effect through the tetraspan web or an indirect change through FAK activation. This connection is functionally significant. In addition to the direct use of anti-VEGF antibodies, modulation of EMP2 with impact on VEGF is potentially a distinct therapeutic target for the treatment of neovascularization associated with retinal diseases that involve pathologic angiogenesis.
Statistical Object Recognition (1993)

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1993.
Experimental demonstration of noninvasive transskull adaptive focusing based on prior computed tomography scans (2003)

Developing minimally invasive brain surgery by high-intensity focused ultrasound beams is of great interest in cancer therapy. However, the skull induces strong aberrations both in phase and amplitude, resulting in a severe degradation of the beam shape. Thus, an efficient brain tumor therapy would require an adaptive focusing, taking into account the effects of the skull. In this paper, we will show that the acoustic properties of the skull can be deduced from high resolution CT scans and used to achieve a noninvasive adaptive focusing. Simulations have been performed with a full 3-D finite differences code, taking into account all the heterogeneities inside the skull. The set of signals to be emitted in order to focus through the skull can thus be computed. The complete adaptive focusing procedure based on prior CT scans has been experimentally validated. This could have promising applications in brain tumor hyperthermia but also in transcranial ultrasonic imaging.
Occlusal changes during and after Herbst treatment: a cephalometric investigation (1986)

The aim of this study was to evaluate quantitatively sagittal, skeletal and dental changes occurring during and after Herbst treatment and relate these changes to alteration in the occlusion. Lateral roentgenograms in centric occlusion were analysed. The sample consisted of 40 Class II, division 1 cases treated with the Herbst appliance for an average period of 7 months. The subjects were re-examined 6 and 12 months post treatment. The results revealed the following: during the treatment period all subjects were treated to Class I or overcorrected Class I or Class III dental arch relationships. Overjet and sagittal molar relationship improved by an average of 6.9 mm and 6.3 mm respectively. This was a result of a 2.2 mm greater mandibular than maxillary growth, a 2.3 mm lingual movement of the maxillary incisors, a 2.4 mm labial movement of the mandibular incisors, a 2.0 mm distal movement of the maxillary molars and a 2.1 mm mesial movement of the mandibular molars. During the post treatment period of 12 months the occlusion settled into Class I in all subjects. Overjet and sagittal molar relationship relapsed by an average of 2.2 mm and 1.7 mm respectively. About 90 per cent of the occlusal relapse occurred during the first 6 months post treatment. In 58 per cent of the subjects the occlusal relapse was exclusively a result of tooth movements while unfavourable maxillary and mandibular jaw growth contributed to the relapse in 42 per cent of the subjects. As Herbst treatment is performed during a relatively short period, the dentition will be in a state of instability after the appliance is removed. Post treatment retention as well as interocclusal adjustments with an activator are therefore recommended.
Prevention of Metastasis by a Polyamine Synthesis Inhibitor in an Animal Bone Metastasis Model (2000)

In order to better understand the development of skeletal metastases, we developed an appropriate animal model, as the natural progression of metastases in humans cannot be studied on the cellular level. In this study, we established a new animal model which developed bone metastasis in a bone grafted subcutaneously. C57BL/6 mice, which had received a bone (femur or tibia) transplanted in the dorsal subcutis, were injected with B16 melanoma cells into the left heart ventricle. Metastasis was found in approximately 70% of the extraskeletal bones. Using this model, the antimetastatic effect of a polyamine synthesis inhibitor was investigated. Inhibitors of the polyamine biosynthetic pathway have received considerable attention for their potential use in the treatment of cancer as they are responsible for the greatly increased production of the polyamines putrescine, spermidine, and spermine. A polyamine synthesis inhibitor, methylglyoxal-bis(cyclopentylamidinohydrazone) MGBCP, was investigated for its inhibitory effects on bone metastases. MGBCP (20 mg/kg) was administered intraperitoneally every day for 4 weeks and demonstrated strong inhibitory effects on bone metastases. MGBCP inhibited angiogenesis in the transplanted bone and the growth of B16 melanoma cells, thus suggesting a preventive mechanism in bone metastasis. No remarkable adverse effects of MGBCP were observed in any animal throughout the experimental period. Our results indicate that MGBCP has a strong potential for use as an anti-metastatic drug.
The amino terminus of mammalian nucleolin specifically recognizes SV40 T-antigen type nuclear localization sequences. (1993)

Nucleolin is a major nucleolar protein in mammalian cells that is thought to be involved in ribosome biogenesis. The discovery that nucleolin shuttles between the cytoplasm and the nucleus raises the possibility that it is also involved in transporting ribosomal or nuclear proteins to the nucleus. The three structural domains of nucleolin bear a striking resemblance to the domains of a previously identified yeast protein NSR1, although the two proteins do not share a high degree of sequence similarity. NSR1 specifically recognizes the nuclear localization sequence (NLS) of both the simian virus large T antigen (SV40 T-antigen) and the yeast histone H2B by ligand blot analysis, and is a candidate for a receptor involved in the initial stages of nuclear transport. We report here that nucleolin, either purified from Chinese hamster ovary (CHO) cells or expressed in yeast, also specifically recognizes the wild-type, but not a mutant, histone H2B nuclear localization sequence by ligand blot analysis. The NLS recognition site is located within the N-terminal domain of both proteins. In showing that nucleolin, a protein that moves between the cytoplasm and the nucleus, also has the ability to interact with nuclear localization signals, our data support the idea that shuttling nucleolar proteins play a role in nuclear transport.
Polarity, integrin, and extracellular matrix dynamics in the postischemic rat kidney (1998)

Acute renal failure (ARF) as a consequence of ischemic injury is a common disease affecting 5% of the hospitalized population. Despite the fact that mortality from ARF is high, there has been little improvement in survival rates over the last 40 years. The pathogenesis of ARF may be related to substantial changes in cell-cell and cell-extracellular matrix interactions mediated by beta1-integrins. On the basis of in vitro and in vivo studies, reorganization of beta1-integrins from basal to apical surfaces of injured tubular epithelia has been suggested to facilitate epithelial detachment, contributing to tubular obstruction and backleak of glomerular filtrate. In this study, we examine integrin and extracellular matrix dynamics during epithelial injury and repair using an in vivo rat model of unilateral ischemia. We find that, soon after reperfusion, beta1-integrins newly appear on lateral borders in epithelial cells of the S3 segment but are not on the apical surface. At later times, as further injury and regeneration coordinately occur, epithelia adherent to the basement membrane localize beta1 predominantly to basal surfaces even while the polarity of other marker proteins is lost. At the same time, amorphous material consisting of depolarized exfoliated cells fills the luminal space. Notably, beta1-integrins are not detected on exfoliated cells. A novel finding is the presence of fibronectin, a glycoprotein of plasma and the renal interstitium, in tubular spaces of the distal nephron and to a lesser extent S3 segments. These results indicate that beta1-integrins dramatically change their distribution during ischemic injury and epithelial repair, possibly contributing to cell exfoliation initially and to epithelial regeneration at later stages. Together with the appearance of large amounts of fibronectin in tubular lumens, these alterations may play a significant role in the pathophysiology of ARF.
CD8+ T cell concentration determines their efficiency in killing cognate antigen–expressing syngeneic mammalian cells in vitro and in mouse tissues (2010)

We describe a quantitative model for assessing the cytolytic activity of antigen-specific CD8+ T cells in vitro and in vivo in which the concentration of antigen-specific CD8+ T cells determines the efficiency with which these cells kill cognate antigen-expressing melanoma cells in packed cell pellets, in three-dimensional collagen-fibrin gels in vitro, and in established melanomas in vivo. In combination with a clonogenic assay for melanoma cells, collagen-fibrin gels are 4,500-5,500-fold more sensitive than the packed cell pellet-type assays generally used to measure CD8+ T cell cytolytic activity. An equation previously used to describe neutrophil bactericidal activity in vitro and in vivo also describes antigen-specific CD8+ T cell-mediated cytolysis of cognate antigen-expressing melanoma cells in collagen-fibrin gels in vitro and in transplanted tumors in vivo. We have used this equation to calculate the critical concentration of antigen-specific CD8+ T cells, which is the concentration of these cells required to hold constant the concentration of a growing population of cognate antigen-expressing melanoma cells. It is approximately 3.5x10(5)/ml collagen-fibrin gel in vitro and approximately 3x10(6)/ml or /g melanoma for previously published studies of ex vivo-activated adoptively transferred tumor antigen-specific CD8+ T cell killing of cognate antigen-expressing melanoma cells in established tumors in vivo. The antigen-specific CD8+ T cell concentration required to kill 100% of 2x10(7)/ml cognate antigen-expressing melanoma cells in collagen fibrin gels is >or=10(7)/ml of gel.