gebhart/patrepeval huggingface dataset:
Deep x-ray lithography for micromechanics and precision engineering (invited) (1996)

Micromechanics, an emerging technology for sensor and actuator fabrication, has a large market potential that has already been exploited in the sensor area. Progress in actuators, devices that modify their environment and are fundamentally three dimensional, has been much more modest and is suffering from the availability of a fabrication tool with the necessary attributes. If the tool is based on photoresist technology, requirements include very large structure heights: in the millimeter range, for mask-defined prismatic photoresist shapes with flanks that differ from 90 degrees by less than 15 arc-seconds. Photoresist procedures that lead to these results are very different from their counterparts in the microelectronic industry. Thus, application is based on precast sheets of polymethyl methacrylate, PMMA, and solvent bonding followed by precision fly-cutting. Exposure is based on well-collimated x-ray sources, synchrotrons, with flux densities that can deposit 1,600 Joules per cubic centimeter in a finite time at the correct photoresist depth. Since PMMA has an absorption length that varies with photon energy, it is 100 micrometer at 3000 eV and increases to 1 cm at 20,000 eV, beamline and exposure designs center on transmission filters that control the low energy portion of the synchrotron spectrum. Since exposure latitude is large, overexposure by a factor of 15 is allowed, beamline and exposure design are relatively simple. Experiments via the Wisconsin machine, Aladdin, and the Brookhaven 2.6-GeV ring are being used to study the effectiveness issue of manufacturing with synchrotron radiation. Actuator test vehicles are linear and rotational magnetic micromotors with force outputs in the milli-Newton range. High energy exposures have produced large parts with submicron precision that are finding applications in ink jet printing and precision injection molding procedures. Both device types are unique to x-ray assisted processing.
Monolithic and Fully-Hybrid Backside Illuminated CMOS Imagers for Smart Sensing (2024)

Backside-thinned monolithic and fully-hybrid CMOS imagers possessing excellent imaging properties have been successfully designed, fabricated and tested. The document discusses the design, fabrication, and testing of both monolithic and fully-hybrid imagers, including their pixel structures, thinned detector arrays, and optimization for increased Quantum Efficiency through Anti Reflective Coating. It also covers backside thinning and processing techniques and the high yield of pixel and bump yield. The paper further explores improvements in crosstalk performance, sensor assembly images, and sensitivity to extreme ultra violet light. Finally, advancements into multi-layer 3D integrated systems for smart sensing applications using unique sensor designs are outlined.
Synthetic Pentasaccharides Do Not Cause Platelet Activation by Antiheparin-Platelet Factor 4 Antibodies (1999)

A synthetic selective inhibitor of factor Xa, the pentasaccharide SR90107A/Org31540 is in clinical development for the prophylaxis of postsurgical deep vein thrombosis. Another synthetic pentasaccharide with even more sustained inhibition of factor Xa, SanOrg34006, has also been developed. Both of these agents were tested in comparison to unfractionated heparin and a low molecular weight heparin (enoxaparin) for their relative platelet activation potential in heparin-induced thrombocytopenia assays. Sera from patients (n = 30) with heparin-induced thrombocytopenia were pooled and validated for heparin-dependent aggregation responses. Using heparin-platelet factor 4 Sepharose columns, antibodies to heparin-platelet factor 4 were purified from the same pool. The effects of heparin, enoxaparin, SR90107A/Org31540, and San-Org34006 were evaluated in a platelet aggregation assay using platelet donors (n = 10). At comparable concentrations, heparin and enoxaparin consistently produced platelet activation, whereas both pentasaccharides failed to produce a response at a concentration up to 100 micrograms/mL (approximately 50 microM). Similarly, in the 14C-serotonin release and flow cytometric assays, heparin and enoxaparin produced positive responses (n = 30), whereas the two pentasaccharides consistently failed to produce any effect. These observations suggest that the two pentasaccharides with highly selective anti-Xa activity are devoid of generating antiheparin-platelet factor 4 antibody, do not produce heparin-induced thrombocytopenic responses and may inhibit active heparin-induced thrombocytopenia antibody platelet activation.
Design and implementation of microarray gene expression markup language (MAGE-ML) (2002)

MAGE will help microarray data producers and users to exchange information by providing a common platform for data exchange, and MAGE-STK will make the adoption of MAGE easier.
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma (2015)

Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipilimumab alone. In patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone. (Funded by Bristol-Myers Squibb; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).
Molecular Devices and Machines – A Journey into the Nano World (2003)

Preface.Reference.General Concepts.PART I: DEVICES FOR PROCESSING ELECTRONS AND ELECTRONIC ENERGY.Fundamental Principles of Electron and Energy Transfer.Wires and Related Systems.Switching Electron- and Energy-transfer Processes.Light-harvesting Antennae.Photoinduced Charge Separation and Solar Energy Conversion.PART II: MEMORIES, LOGIC GATES, AND RELATED SYSTEMS.Bistable Systems.Multistate-Multifunctional Systems.Logic Gates.PART III: MOLECULAR-SCALE MACHINES.Basic Principles of Molecular Machines.Spontaneous Mechanical-like Motions.Movements Related to Opening, Closing, and Translocation Functions.Rotary Movements.Threading-Dethreading Movements.Linear Movements.Motions in Catenanes.Appendix.Glossary.List of Abbreviations.Subject Index.
New Techniques for Treating an Anal Fistula (2012)

Surgery for an anal fistula may result in recurrence or impairment of continence. The ideal treatment for an anal fistula should be associated with low recurrence rates, minimal incontinence and good quality of life. Because of the risk of a change in continence with conventional techniques, sphincter-preserving techniques for the management complex anal fistulae have been evaluated. First, the anal fistula plug is made of lyophilized porcine intestinal submucosa. The anal fistula plug is expected to provide a collagen scaffold to promote tissue in growth and fistula healing. Another addition to the sphincter-preserving options is the ligation of intersphincteric fistula tract procedure. This technique is based on the concept of secure closure of the internal opening and concomitant removal of infected cryptoglandular tissue in the intersphincteric plane. Recently, cell therapy for an anal fistula has been described. Adipose-derived stem cells have two biologic properties, namely, ability to suppress inflammation and differentiation potential. These properties are useful for the regeneration or the repair of damaged tissues. This article discusses the rationales for, the estimated efficacies of, and the limitations of new sphincter-preserving techniques for the treatment of anal fistulae.
Time-Dependent Associations between Iron and Mortality in Hemodialysis Patients (2005)

The independent association between the indices of iron stores or administered intravenous iron, both of which vary over time, and survival in patients who are on maintenance hemodialysis (MHD) is not clear. It was hypothesized that the observed associations between moderately high levels of three iron markers (serum ferritin, iron, and iron saturation ratio) or administered intravenous iron and all-cause and cardiovascular death is due to the time-varying confounding effect of malnutrition-inflammation-cachexia syndrome (MICS). Time-dependent Cox regression models were examined using prospectively collected data of the 2-yr (July 2001 to June 2003) historical cohort of 58,058 MHD patients from virtually all DaVita dialysis clinics in the United States. After time-dependent and multivariate adjustment for case mix, administered intravenous iron and erythropoietin doses, and available surrogates of MICS, serum ferritin levels between 200 and 1200 ng/ml (reference 100 to 199 ng/ml), serum iron levels between 60 and 120 microg/ml (reference 50 to 59 microg/ml), and iron saturation ratio between 30 and 50% (reference 45 to 50%) were associated with the lowest all-cause and cardiovascular death risks. Compared with those who did not receive intravenous iron, administered intravenous iron up to 400 mg/mo was associated with improved survival, whereas doses >400 mg/mo tended to be associated with higher death rates. The association between serum ferritin levels >800 ng/ml and mortality in MHD patients seems to be due mostly to the confounding effects of MICS. For ascertaining whether the observed associations between moderate doses of administered intravenous iron and improved survival are causal or due to selection bias by indication, clinical trials are warranted.
Imaging cerebral blood flow through the intact rat skull with temporal laser speckle imaging (2006)

We discovered that laser speckle temporal contrast analysis (LSTCA) is able to access the two-dimensional (2D) cerebral blood flow velocity and vessel structure through the intact rat skull. It is demonstrated that LSTCA can significantly suppress the influence of the laser speckle from the stationary structure, such as the skull, and thus reveal the blood flow and morphology of blood vessels through the laser speckle images recorded from the intact rat skull.
Binding of soluble CD4 proteins to human immunodeficiency virus type 1 and infected cells induces release of envelope glycoprotein gp120. (1991)

Human immunodeficiency virus (HIV) infects cells after binding of the viral envelope glycoprotein gp120 to the cell surface recognition marker CD4. gp120 is noncovalently associated with the HIV transmembrane envelope glycoprotein gp41, and this complex is believed responsible for the initial stages of HIV infection and cytopathic events in infected cells. Soluble constructs of CD4 that contain the gp120 binding site inhibit HIV infection in vitro. This is believed to occur by competitive inhibition of viral binding to cellular CD4. Here we suggest an alternative mechanism of viral inhibition by soluble CD4 proteins. We demonstrate biochemically and morphologically that following binding, the soluble CD4 proteins sT4, V1V2,DT, and V1[106] (amino acids 1-369, 1-183, and -2 to 106 of mature CD4) induced the release of gp120 from HIV-1 and HIV-1-infected cells. gp120 release was concentration-, time-, and temperature-dependent. The reaction was biphasic at 37 degrees C and did not take place at 4 degrees C, indicating that binding of soluble CD4 was not sufficient to release gp120. The appearance of free gp120 in the medium after incubation with sT4 correlated with a decrease in envelope glycoprotein spikes on virions and exposure of a previously cryptic epitope near the amino terminus of gp41 on virions and infected cells. The concentration of soluble CD4 proteins needed to induce the release of gp120 from virally infected cells also correlated with those required to inhibit HIV-mediated syncytium formation. These results suggest that soluble CD4 constructs may inactivate HIV by inducing the release of gp120. We propose that HIV envelope-mediated fusion is initiated following rearrangement and/or dissociation of gp120 from the gp120-gp41 complex upon binding to cellular CD4, thus exposing the fusion domain of gp41.
The gene encoding a new mitogenic factor in a Streptococcus pyogenes strain is distributed only in group A streptococci (1994)

We recently cloned a gene encoding a new mitogenic factor (MF) from Streptococcus pyogenes NY-5. In the present study, we determined the distribution of this MF gene (mf) by PCR based upon its sequence. Of 371 streptococcal group A strains isolated from clinical specimens, 370 (99.7%) were positive for mf. The strain that was negative for the MF gene was also negative for the streptolysin O gene (slo). Some streptococcal strains belonging to groups C and G were negative for mf but positive for slo. Group B strains were negative for both. Furthermore, we examined the presence of mf in 54 strains belonging to 28 families and found mf only in group A streptococci. These results indicate that mf is distributed specifically in group A streptococci and the presence of mf in clinical samples strongly suggests infection with group A streptococci.
Selection of peptide inhibitors of interactions involved in complex protein assemblies: association of the core and surface antigens of hepatitis B virus. (1995)

As an example for studies of contacts involved in complex biological systems, peptide ligands that bind to the core antigen of hepatitis B virus (HBcAg) have been selected from a random hexapeptide library displayed on filamentous phage. Affinity-purified phage bearing aa sequence LLGRMK, or some related sequences, bound full-length or truncated HBcAg but did not bind denatured HBcAg. The long (L), but not the short (S), hepatitis B virus envelope polypeptide, when synthesized in an in vitro system, bound firmly to HBcAg, indicating that interaction between HBcAg and the pre-S region of the L polypeptide is critical for virus morphogenesis. This interaction was inhibited by peptide ALLGRMKG, suggesting that this and related small molecules may inhibit viral assembly.
Testatin : A cystatin-related gene expressed during early testis development (1998)

To isolate genes involved in morphogenic aspects of testis development, and which may act in cell signaling pathways downstream of the testis-determining gene Sry, we have developed a modified mRNA differential display method named signal peptide differential display. It was used to target those genes that encode proteins having a signal peptide sequence. By using this method, we isolated a gene named testatin. This gene was found to be related to a group of genes that encodes cysteine protease inhibitors known as cystatins. Cystatins and their target proteases have been associated with tumor formation and metastasis, but also are involved in natural tissue remodeling events such as bone resorption and embryo implantation. We show that testatin expression is restricted to fetal gonads and adult testis. Furthermore, testatin is expressed during testis cord formation in pre-Sertoli cells, believed to be the site of Sry action, at a time immediately after the peak of Sry expression. This finding suggests that testatin might be activated by transcription factors that are known to orchestrate the early testis development pathway. This gene therefore represents one of the putative downstream targets likely to have an essential role in tissue reorganization during early testis development.
SMAD4 Regulates Cell Motility through Transcription of N-Cadherin in Human Pancreatic Ductal Epithelium (2014)

Expression of the cellular adhesion protein N-cadherin is a critical event during epithelial-mesenchymal transition (EMT). The SMAD4 protein has been identified as a mediator of transforming growth factor-β (TGF-β) superfamily signaling, which regulates EMT, but the mechanisms linking TGF-β signaling to N-cadherin expression remain unclear. When the TGF-β pathway is activated, SMAD proteins, including the common mediator SMAD4, are subsequently translocated into the nucleus, where they influence gene transcription via SMAD binding elements (SBEs). Here we describe a mechanism for control of CDH2, the gene encoding N-cadherin, through the canonical TGFβ-SMAD4 pathway. We first identified four previously undescribed SBEs within the CDH2 promoter. Using telomerase immortalized human pancreatic ductal epithelium, we found that TGF-β stimulation prompted specific SMAD4 binding to all four SBEs. Luciferase reporter and SMAD4-knockdown experiments demonstrated that specific SMAD4 binding to the SBE located at -3790 bp to -3795 bp within the promoter region of CDH2 was necessary for TGF-β-stimulated transcription. Expression of N-cadherin on the surface of epithelial cells facilitates motility and invasion, and we demonstrated that knockdown of SMAD4 causes decreased N-cadherin expression, which results in diminished migration and invasion of human pancreatic ductal epithelial cells. Similar reduction of cell motility was produced after CDH2 knockdown. Together, these findings suggest that SMAD4 is critical for the TGF-β-driven upregulation of N-cadherin and the resultant invasive phenotype of human pancreatic ductal epithelial cells during EMT.
Bericht über die International Joint Conference on Neural Networks '89. (1990)

The Delphi method identified consensus recommendations on a broad range of intraoperative techniques and postoperative management practices for primary breast augmentation with Natrelle 410. These recommendations and priorities provide surgeons with a framework that, together with the surgeon's experience, will contribute to optimal clinical outcomes with Natrelle 410.
Enhanced Inhibition of Orthopoxvirus Replication In Vitro by Alkoxyalkyl Esters of Cidofovir and Cyclic Cidofovir (2002)

The nucleotide phosphonates cidofovir (CDV) and cyclic cidofovir (cCDV) are potent antiviral compounds when administered parenterally but are not well absorbed orally. These compounds have been reported to have activity against orthopoxvirus replication in vitro and in animal models when administered parenterally or by aerosol. To obtain better oral activity, we synthesized a novel series of analogs of CDV and cCDV by esterification with two long-chain alkoxyalkanols, 3-hexadecyloxy-1-propanol (HDP-CDV; HDP-cCDV) or 3-octadecyloxy-1-ethanol (ODE-CDV; ODE-cCDV). Their activities were evaluated and compared with those of CDV and cCDV in human foreskin fibroblast (HFF) cells infected with vaccinia virus (VV) or cowpox virus (CV) using a plaque reduction assay. The 50% effective concentrations (EC(50)s) against VV in HFF cells for CDV and cCDV were 46.2 and 50.6 microM compared with 0.84 and 3.8 microM for HDP-CDV and HDP-cCDV, respectively. The EC(50)s for ODE-CDV and ODE-cCDV were 0.20 and 1.1 microM, respectively. The HDP analogs were 57- and 13-fold more active than the parent nucleotides, whereas the ODE analogs were 231- and 46-fold more active than the unmodified CDV and cCDV. Similar results were obtained using CV. Cytotoxicity studies indicated that although the analogs were more toxic than the parent nucleotides, the selective index was increased by 4- to 13-fold. These results indicate that the alkoxyalkyl esters of CDV and cCDV have enhanced activity in vitro and need to be evaluated for their oral absorption and efficacy in animal models.
Molecular motors hijacking by intracellular pathogens (2005)

Cargoes are transported intracellularly along cytoskeletal tracks composed of actin or tubulin. Their movement involves the action of molecular motor proteins that generate directed movement along microtubules or actin filaments. The three classes of molecular motors--kinesins, dyneins and myosins--are involved in a multiplicity of biological movements such as mitosis, positioning of organelles, intracellular transports and also vesicular sorting through membrane tubulation and fission and delivery to their target compartment. Intracellular pathogens use this molecular machinery to reach their site of replication, to leave their host or to control the dynamics of membrane exchanges with their replication compartment.
Phosphorylated α-Synuclein Is Ubiquitinated in α-Synucleinopathy Lesions (2002)

alpha-Synuclein is one of the major components of intracellular fibrillary aggregates in the brains of a subset of neurodegenerative disorders, including Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and Hallervorden-Spatz disease, which are referred to as alpha-synucleinopathies. We have shown previously (Fujiwara, H., Hasegawa, M., Dohmae, N., Kawashima, A., Masliah, E., Goldberg, M. S., Shen, J., Takio, K., and Iwatsubo, T. (2002) Nat. Cell Biol. 4, 160-164) that alpha-synuclein deposited in synucleinopathy brains is extensively phosphorylated at Ser-129 and migrates at 15 kDa. Here we examined the biochemical characteristics of the additional, higher molecular mass species of phosphorylated alpha-synuclein-positive polypeptides that also are recovered in the Sarkosyl-insoluble fraction of synucleinopathy and migrate at about 22 and 29 kDa. These 22 and 29 kDa bands were positive for three different anti-ubiquitin antibodies and comigrated perfectly with in vitro ubiquitinated alpha-synuclein that may correspond to mono- and diubiquitinated alpha-synuclein, respectively. Furthermore, cyanogen bromide cleavage of the 22 and 29 kDa polypeptides shifted the mobility to 19 and 26 kDa, respectively, and they retained immunoreactivity for both ubiquitin and alpha-synuclein. Finally, protein sequence analysis showed that the 19 kDa band contained two amino-terminal sequences of alpha-synuclein and ubiquitin. These results strongly suggest that phosphorylated alpha-synuclein is targeted to mono- and diubiquitination in synucleinopathy brains, which may have implications for mechanisms of these diseases.
Infection induces a positive acute phase apolipoprotein E response from a negative acute phase gene: role of hepatic LDL receptors* (2008)

Apolipoprotein E (apoE) plays important roles in lipid homeostasis, anti-inflammation, and host defense. Since tissue apoE mRNA levels have been reported to decrease during inflammatory responses, we were surprised to find that plasma apoE levels were significantly elevated during septic infections in both humans and mice. This apparent paradox was also observed during lipopolysaccharide-induced acute inflammation in mice: plasma levels of apoE increased up to 4-fold despite sharply decreased apoE gene expression in the liver, macrophages, and extrahepatic tissues. We hypothesized that apoE levels were augmented by decreased plasma clearance. Our analysis revealed that apoE associated principally with HDL in mice and that apoE was cleared from the circulation principally via LDL receptors. The acute inflammatory response decreased LDL receptor expression in the liver and significantly reduced the rate of apoE clearance. In contrast, the same inflammatory stimuli increased LDL receptor expression in macrophages. Our results define a novel acute phase mechanism that increases circulating apoE levels as apoE production decreases. Diminished hepatic LDL receptor expression may thus cooperate with elevated LDL receptor expression in macrophages to facilitate the forward transport of apoE and its associated lipids to these key defense cells.