gebhart/patrepeval huggingface dataset:
Electromagnetic Torque Tweezers: A Versatile Approach for Measurement of Single-Molecule Twist and Torque (2012)

The well-established single-molecule force-spectroscopy techniques have recently been complemented by methods that can measure torque and twist directly, notably magnetic torque tweezers and the optical torque wrench. A limitation of the current torque measurement schemes is the intrinsic coupling between the force and torque degrees of freedom. Here we present electromagnetic torque tweezers (eMTT) that combine permanent and electromagnets to enable independent control of the force and torsional trap stiffness for sensitive measurements of single molecule torque and twist. Using the eMTT, we demonstrate sensitive torque measurements on tethered DNA molecules from simple tracking of the beads' (x,y)-position, obviating the need for any angular tracking algorithms or markers. Employing the eMTT for high-resolution torque measurements, we experimentally confirm the theoretically predicted torque overshoot at the DNA buckling transition in high salt conditions. We envision that the flexibility and control afforded by the eMTT will enable a range of new torque and twist measurement schemes from single-molecules to living cells.
A method for multi-codon scanning mutagenesis of proteins based on asymmetric transposons (2011)

Random mutagenesis followed by selection or screening is a commonly used strategy to improve protein function. Despite many available methods for random mutagenesis, nearly all generate mutations at the nucleotide level. An ideal mutagenesis method would allow for the generation of 'codon mutations' to change protein sequence with defined or mixed amino acids of choice. Herein we report a method that allows for mutations of one, two or three consecutive codons. Key to this method is the development of a Mu transposon variant with asymmetric terminal sequences. As a demonstration of the method, we performed multi-codon scanning on the gene encoding superfolder GFP (sfGFP). Characterization of 50 randomly chosen clones from each library showed that more than 40% of the mutants in these three libraries contained seamless, in-frame mutations with low site preference. By screening only 500 colonies from each library, we successfully identified several spectra-shift mutations, including a S205D variant that was found to bear a single excitation peak in the UV region.
Human Hepatocyte Isolation and Relationship of Cell Viability to Early Graft Function (2003)

Hepatocyte transplantation is emerging as an additional modality of treatment for patients with acute liver failure or liver-based metabolic disorders. The procedure requires isolation of high-quality hepatocytes from unused donor livers. Hepatocytes were isolated from 20 donor livers (11 right lobes, 3 left lateral segments, 6 whole livers) using a collagenase perfusion technique. Cell viability (median 56%, range 13-95%) and yield (median 1.4 x 10(9) cells, range 2.0 x 10(6)-1.8 x 10(10) cells) varied according to the tissue available. Fatty livers rejected for transplantation gave lower cell viability (median 45%, range 25-59%). There was a significant correlation between age of donor (median 21 years, range 7-66 years) and viability of isolated hepatocytes in vitro (r = -0.683, p = 0.001). The 13 segments of livers were from reduced/split grafts used for clinical transplantation in 9 children and 4 adults. There was no significant correlation between in vitro cell viability and clinical parameters including intensive care stay, serum aspartate aminotransferase,and international normalized ratio (in the first 7 days), and allograft rejection or other early posttransplant complications, in patients transplanted with the corresponding tissue.
Characterization and functional role of voltage gated cation conductances in the glucagon‐like peptide‐1 secreting GLUTag cell line (2004)

Glucagon-like peptide-1 (GLP-1) is released from intestinal L-cells in response to nutrient ingestion. It is currently under therapeutic evaluation because it enhances insulin secretion in type 2 diabetes. Previous studies using the GLP-1 secreting cell line GLUTag have shown that the cells are electrically active, and that the action potential frequency is regulated by nutrients. In this study we characterize voltage gated currents underlying this electrical activity and correlate the electrophysiological findings with gene expression determined by microarrays. Whole cell voltage clamp experiments designed to separate different ionic components revealed rapidly inactivating sodium currents sensitive to tetrodotoxin, calcium currents sensitive to nifedipine and omega-conotoxin GVIA, and sustained as well as rapidly inactivating potassium currents, which were sensitive to TEA and 4-AP, respectively. In perforated patch experiments we also observed hyperpolarization-activated currents which were inhibited by ZD7288. The amplitude of the sodium current was approximately 10 times that of the other depolarizing currents and tetrodotoxin abolished action potential firing. In secretion experiments, however, nifedipine, but not tetrodotoxin, omega-conotoxin GVIA or ZD7288, inhibited glucose-induced GLP-1 release. Consistent with this finding, the intracellular Ca2+ response to glucose was impaired by nifedipine but not by tetrodotoxin. Thus, in GLUTag cells, GLP-1 release is not dependent on the firing of Na+-carrying action potentials but requires membrane depolarization and Ca2+ entry through L-type Ca2+ channels. Understanding the characteristics of the currents and the molecular identification of the underlying channels in GLP-1 secreting cells might facilitate the development of agents to enhance GLP-1 secretion in vivo.
Fingolimod and Sphingosine-1-Phosphate — Modifiers of Lymphocyte Migration (2006)

Multiple sclerosis is considered an autoimmune disease in which CD4+ T cells and macrophages destroy oligodendrocytes, which synthesize and maintain axonal myelin sheaths in the central nervous system (CNS). This misguided attack results in progressive focal demyelination that can cause severe neurologic disability. In this issue of the Journal, Kappos et al. (pages 1124–1140) report that the immunosuppressant fingolimod (also called FTY720 or 2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol hydrochloride) exerted considerable therapeutic effects in a small, placebo-controlled clinical trial involving patients with relapsing multiple sclerosis. Patients who received oral fingolimod once daily had a rapid reduction in disease activity, reflected in significant reductions in . . .
Bubble engineering for biomedical valving applications (2002)

Within the overall objective of developing a low dead volume technology for basic microfluidic valving, shunting and switching functionalities, the use of microbubbles is proposed. As a case study, a normally-closed, bubble-based microvalve design is presented. The valve, implemented using an all-Pyrex technology, can withstand high pressures limited only by the degree to which the vertical etch rate of Pyrex can be controlled. Measurements made on several prototypes show valve breaking pressures of approximately 180 kPa (gage) which closely match theoretically predicted values. A geometry-based trap is used to form bubbles of air with long persistence times (>24 hours). Presentation of the microvalve is followed by a general discussion of design and engineering issues surrounding the control and creation of microbubbles for microfluidic applications. Issues include bubble pinning at sharp transitions and inclusions, and actuation.
Confining the state of light to a quantum manifold by engineered two-photon loss (2015)

Physical systems usually exhibit quantum behavior, such as superpositions and entanglement, only when they are sufficiently decoupled from a lossy environment. Paradoxically, a specially engineered interaction with the environment can become a resource for the generation and protection of quantum states. This notion can be generalized to the confinement of a system into a manifold of quantum states, consisting of all coherent superpositions of multiple stable steady states. We have confined the state of a superconducting resonator to the quantum manifold spanned by two coherent states of opposite phases and have observed a Schrödinger cat state spontaneously squeeze out of vacuum before decaying into a classical mixture. This experiment points toward robustly encoding quantum information in multidimensional steady-state manifolds.
Inverse modeling using multi-block PLS to determine the environmental conditions that provide optimal cellular function (2004)

Diverse sets of environmental factors were used to systematically perturb the metabolic behavior associated with pre-conditioning and plasma supplementation. To probe metabolic state of hepatocytes, metabolic flux analysis was used to obtain the metabolic profile. We applied a multi-block partial least square (MPLS) model to relate environmental factors and fluxes to levels of intracellular lipids and urea synthesis. The MPLS model identified: (1) the most influential environmental factors and (2) how the metabolic pathways are altered by these factors. Finally, we inverted the MPLS model to determine the concentrations and types of environmental factors required to obtain the most economical solution for achieving optimal levels of cellular function for practical situations.
622 Mb/s, 144 km transmission using a bidirectional fiber amplifier repeater (1993)

A successful 144.2-km transmission of a 622-Mb/s signal through standard single-mode fibers using a bidirectional fiber amplifier repeater is demonstrated. The bit-error-rate measurement showed neither sensitivity degradation nor BER floor in the bidirectional transmission, suggesting a great potential of system improvement and capacity increase of the existing system by the use of the repeater.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Innate Immune Responses to Lung-Stage Helminth Infection Induce Alternatively Activated Alveolar Macrophages (2006)

While it is well established that infection with the rodent hookworm Nippostrongylus brasiliensis induces a strongly polarized Th2 immune response, little is known about the innate host-parasite interactions that lead to the development of this robust Th2 immunity. We exploited the transient pulmonary phase of N. brasiliensis development to study the innate immune responses induced by this helminth parasite in wild-type (WT) and severe-combined immune deficient (SCID) BALB/c mice. Histological analysis demonstrated that the cellular infiltrates caused by N. brasiliensis transit through the lungs were quickly resolved in WT mice but not in SCID mice. Microarray-based gene expression analysis demonstrated that there was a rapid induction of genes encoding molecules that participate in innate immunity and in repair/remodeling during days 2 to 4 postinfection in the lungs of WT and SCID mice. Of particular note was the rapid upregulation in both WT and SCID mice of the genes encoding YM1, FIZZ1, and Arg1, indicating a role for alternatively activated macrophages (AAMs) in pulmonary innate immunity. Immunohistochemistry revealed that nearly all alveolar macrophages became YM1-producing AAMs as early as day 2 postinfection. While the innate responses induced during the lung phase of N. brasiliensis infection were similar in complexity and magnitude in WT and SCID mice, only mice with functional T cells were capable of maintaining elevated levels of gene expression beyond the innate window of reactivity. The induction of alternatively activated alveolar macrophages could be important for dampening the level of inflammation in the lungs and contribute to the long-term decrease in pulmonary inflammation that has been associated with helminth infections.
microRNAs: small molecules with big roles –C. elegans to human cancer (2008)

miRNAs (microRNAs) were first discovered as critical regulators of developmental timing events in Caenorhabditis elegans. Subsequent studies have shown that miRNAs and cellular factors necessary for miRNA biogenesis are conserved in many organisms, suggesting the importance of miRNAs during developmental processes. Indeed, mutations in the miRNA-processing pathway induce pleiotropic defects in development, which accompany perturbation of correct expression of target genes. However, control of gene expression in development is not the only function of miRNAs. Recent work has provided new insights into the role of miRNAs in various biological events, including aging and cancer. C. elegans continues to be helpful in facilitating a further understanding of miRNA function in human diseases.
Reduced default mode network suppression during a working memory task in remitted major depression (2015)

Insufficient default mode network (DMN) suppression was linked to increased rumination in symptomatic Major Depressive Disorder (MDD). Since rumination is known to predict relapse and a more severe course of MDD, we hypothesized that similar DMN alterations might also exist during full remission of MDD (rMDD), a condition known to be associated with increased relapse rates specifically in patients with adolescent onset. Within a cross-sectional functional magnetic resonance imaging study activation and functional connectivity (FC) were investigated in 120 adults comprising 78 drug-free rMDD patients with adolescent- (n = 42) and adult-onset (n = 36) as well as 42 healthy controls (HC), while performing the n-back task. Compared to HC, rMDD patients showed diminished DMN deactivation with strongest differences in the anterior-medial prefrontal cortex (amPFC), which was further linked to increased rumination response style. On a brain systems level, rMDD patients showed an increased FC between the amPFC and the dorsolateral prefrontal cortex, which constitutes a key region of the antagonistic working-memory network. Both whole-brain analyses revealed significant differences between adolescent-onset rMDD patients and HC, while adult-onset rMDD patients showed no significant effects. Results of this study demonstrate that reduced DMN suppression exists even after full recovery of depressive symptoms, which appears to be specifically pronounced in adolescent-onset MDD patients. Our results encourage the investigation of DMN suppression as a putative predictor of relapse in clinical trials, which might eventually lead to important implications for antidepressant maintenance treatment.
The Treatment of Prostatic Hypertrophy by a New “Shrinkage” Method (1934)

No AccessJournal of Urology1 Nov 1934The Treatment of Prostatic Hypertrophy by a New "Shrinkage" Method1 Thomas J. Kirwin Thomas J. KirwinThomas J. Kirwin View All Author Informationhttps://doi.org/10.1016/S0022-5347(17)72375-0AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail © 1934 by The American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byPATEL A, QUINT R and FUCHS G (2018) APPLICATIONS OF ELECTRICAL ENERGY TO THE PROSTATE: AN EVOLUTIONARY PERSPECTIVEJournal of Urology, VOL. 159, NO. 6, (1802-1809), Online publication date: 1-Jun-1998.Mostafid A, Harrison N, Dawkins G and Fletcher M (2018) Interstitial Radiofrequency Therapy of the Prostate: Results of a Pilot StudyJournal of Urology, VOL. 155, NO. 6, (1946-1949), Online publication date: 1-Jun-1996. Volume 32Issue 5November 1934Page: 481-494 Advertisement Copyright & Permissions© 1934 by The American Urological Association Education and Research, Inc.MetricsAuthor Information Thomas J. Kirwin More articles by this author Expand All Advertisement PDF downloadLoading ...
ELEVATED TRYPTASE, NERVE GROWTH FACTOR, NEUROTROPHIN-3 AND GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR LEVELS IN THE URINE OF INTERSTITIAL CYSTITIS AND BLADDER CANCER PATIENTS (1999)

These findings may account for several clinical and pathological features found in interstitial cystitis and bladder cancer. Although preliminary due to the limited numbers of patients, they also suggest that increased levels of neurotrophin-3, nerve growth factor, glial cell line-derived neurotrophic factor and tryptase in the urine could serve as a basis for adjunct diagnosis, monitoring and treatment of interstitial cystitis.
Molecular Cloning and Expression of Palmitoyl-protein Thioesterase 2 (PPT2), a Homolog of Lysosomal Palmitoyl-protein Thioesterase with a Distinct Substrate Specificity (1997)

Palmitoyl-protein thioesterase is a lysosomal hydrolase that removes long chain fatty acyl groups from modified cysteine residues in proteins. Mutations in this enzyme were recently shown to underlie the hereditary neurodegenerative disorder, infantile neuronal ceroid lipofuscinosis, and lipid thioesters derived from acylated proteins were found to accumulate in lymphoblasts from individuals with the disorder. In the current study, we describe the cloning and expression of a second lysosomal thioesterase, palmitoyl-protein thioesterase 2 (PPT2), that shares an 18% identity with palmitoyl-protein thioesterase. Transient expression of a PPT2 cDNA led to the production of a glycosylated lysosomal protein with palmitoyl-CoA hydrolase activity comparable with palmitoyl-protein thioesterase. However, PPT2 did not remove palmitate groups from palmitoylated proteins that are substrates for palmitoyl-protein thioesterase. In cross-correction experiments, PPT2 did not abolish the accumulation of protein-derived lipid thioesters in palmitoyl-protein thioesterase-deficient cell lines. These results indicate that PPT2 is a lysosomal thioesterase that possesses a substrate specificity that is distinct from that of palmitoyl-protein thioesterase.
Kinetics of Response in Lymphoid Tissues to Antiretroviral Therapy of HIV-1 Infection (1997)

In lymphoid tissue, where human immunodeficiency virus-type 1 (HIV-1) is produced and stored, three-drug treatment with viral protease and reverse transcriptase inhibitors markedly reduced viral burden. This was shown by in situ hybridization and computerized quantitative analysis of serial tonsil biopsies from previously untreated adults. The frequency of productive mononuclear cells (MNCs) initially diminished with a half-life of about 1 day. Surprisingly, the amount of HIV-1 RNA in virus trapped on follicular dendritic cells (FDCs) decreased almost as quickly. After 24 weeks, MNCs with very few copies of HIV-1 RNA per cell were still detectable, as was proviral DNA; however, the amount of FDC-associated virus decreased by >/=3.4 log units. Thus, 6 months of potent therapy controlled active replication and cleared >99.9 percent of virus from the secondary lymphoid tissue reservoir.
Drug Testing for Residual Progression of Diabetic Kidney Disease in Mice Beyond Therapy with Metformin, Ramipril, and Empagliflozin (2020)

Add-on treatment with BIO for only 4 weeks attenuates progression of CKD beyond MRE therapy in mice with type 2 diabetes. Additional drug combinations may help to further delay ESKD in type 2 diabetes.
A study of Through-Silicon-Via impact on the 3D stacked IC layout (2009)

Through-Silicon-Via (TSV) is the enabling technology for the fine-grained 3D integration of multiple dies into a single stack. These TSVs occupy non-negligible silicon area because of their sheer size. This significant silicon area occupied by the TSVs and the interconnections made to the TSVs greatly affect area, power, performance, and reliability of 3D IC layouts. Well-managed TSVs alleviate congestion, reduce wirelength, and improve performance, whereas excessive TSVs not only increase the die area, but also have negative impact on many design objectives. In this paper, we study the impact of TSV on various aspects of 3D layouts. We use GDSII layouts of 2D and 3D designs, and thoroughly compare the pros and cons of TSV usage. We propose a new force-directed 3D gate-level placement that efficiently handles TSVs. In addition, we present an algorithm that assigns TSVs to nets to complete routing that involves TSVs. This algorithm, together with our 3D placer, is integrated into a commercial P&R tool to generate fully validated GDSII layouts. Our experiments based on synthesized benchmarks indicate that our algorithms help generate GDSII layouts of 3D designs that are optimized in terms of area, wirelength, and metal layer count.
Requirement of Lyn and Syk tyrosine kinases for the prevention of apoptosis by cytokines in human eosinophils. (1996)

In allergic diseases, the cytokines interleukin (IL)5 and granulocyte/macrophage colony-stimulating factor (GM-CSF) are upregulated and have been proposed to cause blood and tissue eosinophilia by inhibition of eosinophil apoptosis. We demonstrate herein, in freshly isolated human eosinophils, that the IL-3/IL-5/GM-CSF receptor beta subunit interacts with cytoplasmic tyrosine kinases to induce phosphorylation of several cellular substrates, including the beta subunit itself. The Lyn and Syk intracellular tyrosine kinases constitutively associate at a low level with the IL-3/IL-5/GM-CSF receptor beta subunit in human eosinophils. Stimulation with GM-CSF or IL-5 results in a rapid and transient increase in the amount of Lyn and Syk associated with the IL-3/IL-5/GM-CSF receptor beta subunit. Lyn is required for optimal tyrosine phosphorylation and activation of Syk. In contrast, Syk is not required for optimal tyrosine phosphorylation and activation of Lyn. These data suggest that Lyn is proximal to Syk in a tyrosine kinase cascade that transduces IL-3, IL-5, or GM-CSF signals. Compatible with this model, both Lyn and Syk are essential for the activation of the antiapoptotic pathway(s) induced through the IL-3/IL-5/GM-CSF receptor beta subunit in human eosinophils.
A modified TILLING approach to detect induced mutations in tetraploid and hexaploid wheat (2009)

We have generated reverse genetics TILLING resources for pasta and bread wheat and achieved a high mutation density in both populations. We also developed a modified screening method that will lower barriers to adopt this promising technology. We hope that the use of this reverse genetics resource will enable more researchers to pursue wheat functional genomics and provide novel allelic diversity for wheat improvement.