gebhart/patrepeval huggingface dataset:
Shear-Driven Redistribution of Surfactant Affects Enzyme Activity in Well-Mixed Femtoliter Droplets (2009)

We developed a microfluidic platform for splitting well-mixed, femtoliter-volume droplets from larger water-in-oil plugs, where the sizes of the daughter droplets were not limited by channel width. These droplets were separated from mother plugs at a microfabricated T-junction, which enabled the study of how increased confinement affected enzyme kinetics in droplets 4-10 microm in diameter. Initial rates for enzyme catalysis in the mother plugs and the largest daughter drops were close to the average bulk rate, while the rates in smaller droplets decreased linearly with increasing surface to volume ratio. Rates in the smallest droplets decreased by a factor of 4 compared to the bulk rate. Traditional methods for detecting nonspecific adsorption at the water-oil interface were unable to detect evidence of enzyme adsorption, including pendant drop tensiometry, laser scanning confocal microscopy of drops containing labeled proteins in microemulsions, and epifluorescence microscopy of plugs and drops generated on-chip. We propose the slowing of enzyme reaction kinetics in the smaller droplets was the result of increased adsorption and inactivation of enzymes at the water-oil interface arising from transient interfacial shear stresses imparted on the daughter droplets as they split from the mother plugs and passed through the constricted opening of the T-junction. Such stresses are known to modulate the interfacial area and density of surfactant molecules that can passivate the interface. Bright field images of the splitting processes at the junction indicate that these stresses scaled with increasing surface to volume ratios of the droplets but were relatively insensitive to the average flow rate of plugs upstream of the junction.
Mutant huntingtin's interaction with mitochondrial protein Drp1 impairs mitochondrial biogenesis and causes defective axonal transport and synaptic degeneration in Huntington's disease (2011)

The purpose of this study was to investigate the link between mutant huntingtin (Htt) and neuronal damage in relation to mitochondria in Huntington's disease (HD). In an earlier study, we determined the relationship between mutant Htt and mitochondrial dynamics/synaptic viability in HD patients. We found mitochondrial loss, abnormal mitochondrial dynamics and mutant Htt association with mitochondria in HD patients. In the current study, we sought to expand on our previous findings and further elucidate the relationship between mutant Htt and mitochondrial and synaptic deficiencies. We hypothesized that mutant Htt, in association with mitochondria, alters mitochondrial dynamics, leading to mitochondrial fragmentation and defective axonal transport of mitochondria in HD neurons. In this study, using postmortem HD brains and primary neurons from transgenic BACHD mice, we identified mutant Htt interaction with the mitochondrial protein Drp1 and factors that cause abnormal mitochondrial dynamics, including GTPase Drp1 enzymatic activity. Further, using primary neurons from BACHD mice, for the first time, we studied axonal transport of mitochondria and synaptic degeneration. We also investigated the effect of mutant Htt aggregates and oligomers in synaptic and mitochondrial deficiencies in postmortem HD brains and primary neurons from BACHD mice. We found that mutant Htt interacts with Drp1, elevates GTPase Drp1 enzymatic activity, increases abnormal mitochondrial dynamics and results in defective anterograde mitochondrial movement and synaptic deficiencies. These observations support our hypothesis and provide data that can be utilized to develop therapeutic targets that are capable of inhibiting mutant Htt interaction with Drp1, decreasing mitochondrial fragmentation, enhancing axonal transport of mitochondria and protecting synapses from toxic insults caused by mutant Htt.
Some Practical Universal Noiseless Coding Techniques (1979)

Some practical adaptive techniques for the efficient noiseless coding of a broad class of such data sources are developed and analyzed. Algorithms are designed for coding discrete memoryless sources which have a known symbol probability ordering but unknown probability values. A general applicability of these algorithms to solving practical problems is obtained because most real data sources can be simply transformed into this form by appropriate preprocessing. These algorithms have exhibited performance only slightly above all entropy values when applied to real data with stationary characteristics over the measurement span. Performance considerably under a measured average data entropy may be observed when data characteristics are changing over the measurement span.
Monocyte-chemo-attractant-protein-1 (mcp-1)-gene expression in cervical intra-epithelial neoplasias and cervical carcinomas (1999)

Chemokines play a central role in the chemotactic activation of immunological effector cells. One of the currently best characterized chemokines is the monocyte-chemo-attractant protein-1 (MCP-1), which is involved in the cross-talk with cells of the monocyte-macrophage lineage. Since macrophages and macrophage-derived cytokines appear to be important in the transcriptional regulation of "high-risk" types of human papillomaviruses (HPV), we monitored MCP-1 expression by in situ hybridization (ISH) in histologically distinct stages of cervical intra-epithelial neoplasms (CIN), cervical cancer and non-HPV-associated cases of erosive endocervicitis. Here, we demonstrate that high-grade dysplasia (CIN III, n = 9) completely lacks both MCP-1 expression and CD68+-macrophage infiltration, while MCP-1-specific signals were occasionally detectable in one out of 5 CIN-II and in one out of 3 CIN-I lesions. Inspection of hyperplastic squamous epithelium adjacent to cervical carcinomas reveals high MCP-1 expression and accumulation of infiltrating macrophages. In contrast, no macrophages could be detected in corresponding hyperplastic tissue areas surrounding CIN-II and CIN-III lesions, although MCP-1 was found to be highly expressed. Finally, in agreement with our earlier in vitro data, invasive carcinomas of the cervix uteri showed MCP-1-specific hybridization signals and macrophage infiltration only in the stroma surrounding the carcinoma cells and in endothelial cells of capillaries, especially at the invasion front of the tumor, while the inner mass of the carcinomas was completely negative. On the other hand, ISH and histochemical evaluation of inflammatory, non-HPV-associated cases of erosive endocervicitis indicate strong MCP-1 expression, which is regularly accompanied by chemotactic appearance of macrophages. These observations indicate that dysregulation of MCP-1-gene expression may represent an important step during HPV-linked carcinogenesis, allowing the escape of virus-positive cells from local immune response.
Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin) (2016)

The genome is the target of some of the most effective chemotherapeutics, but most of these drugs lack DNA sequence specificity, which leads to dose-limiting toxicity and many adverse side effects. Targeting the genome with sequence-specific small molecules may enable molecules with increased therapeutic index and fewer off-target effects. N-methylpyrrole/N-methylimidazole polyamides are molecules that can be rationally designed to target specific DNA sequences with exquisite precision. And unlike most natural transcription factors, polyamides can bind to methylated and chromatinized DNA without a loss in affinity. The sequence specificity of polyamides has been extensively studied in vitro with cognate site identification (CSI) and with traditional biochemical and biophysical approaches, but the study of polyamide binding to genomic targets in cells remains elusive. Here we report a method, the crosslinking of small molecules to isolate chromatin (COSMIC), that identifies polyamide binding sites across the genome. COSMIC is similar to chromatin immunoprecipitation (ChIP), but differs in two important ways: (1) a photocrosslinker is employed to enable selective, temporally-controlled capture of polyamide binding events, and (2) the biotin affinity handle is used to purify polyamide-DNA conjugates under semi-denaturing conditions to decrease DNA that is non-covalently bound. COSMIC is a general strategy that can be used to reveal the genome-wide binding events of polyamides and other genome-targeting chemotherapeutic agents.
Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase-Activating Polypeptide Stimulate the Induction of Th2 Responses by Up-Regulating B7.2 Expression (1999)

Abstract Vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase-activating polypeptide (PACAP), two structurally related neuropeptides produced within the lymphoid microenvironment, modulate several immunologic functions. We have recently demonstrated that VIP and PACAP enhance the macrophage costimulatory activity for naive CD4+ T cells exposed to allogeneic or anti-CD3 stimuli through the differential regulation of the B7 costimulatory molecules. In this study, we report on the role of VIP and PACAP on macrophage B7 expression and costimulatory function for Ag-primed CD4+ T cells, and on the macrophage-induced regulation of Th1/Th2 differentiation in vitro and in vivo. VIP and PACAP up-regulate the costimulatory activity of macrophages for Ag-primed CD4+ T cells. VIP-/PACAP-treated macrophages gain the ability to induce Th2-type cytokines such as IL-4 and IL-5 and reduce Th1-type cytokines such as IFN-γ and IL-2. In vivo administration of VIP or PACAP in Ag-immunized mice reduce the numbers of IFN-γ-secreting cells and enhance the numbers of IL-4-secreting cells. One of the consequences of the VIP-/PACAP-induced shift in cytokine profile is a change in the Ag-specific Ig isotype, increasing IgG1 and decreasing IgG2a levels. Finally, the preferential differentiation into Th2 effector cells after Ag stimulation induced by VIP-/PACAP-treated macrophages is mediated through the up-regulation of B7.2 expression.
Self-assembly of block copolymer thin films (2010)

Block copolymers self-assemble on nanometer length scales, making them ideal for emerging nanotechnologies. Many applications (e.g., templating, membranes) require the use of block copolymers in thin film geometries (∼100 nm thickness), where self-assembly is strongly influenced by surface energetics. In this review, we discuss the roles of surface and interfacial effects on self-assembly, with a specific focus on confinement, substrate surface modification, and thermal and solvent annealing conditions. Finally, we comment on novel techniques for manipulating and characterizing thin films, motivating the use of gradient and high-throughput methods for gaining a comprehensive picture of self-assembly to enable advanced nanotechnologies.
Relationships Among Mycobacteria and Nocardiae Based upon Deoxyribonucleic Acid Reassociation (1973)

The degree of renaturation between Nocardia farcinica 330 deoxyribonucleic acid (DNA) and DNA from 17 nocardial strains and 11 mycobacterial strains, and between Mycobacterium smegmatis 405 DNA and DNA from 11 mycobacterial strains and 14 nocardial strains was determined by using the nitrocellulose membrane filter technique. These results indicated that some cultures designated N. farcinica were identical to some cultures designated N. asteroides but that other strains called N. asteroides were distinctly different. The species M. smegmatis was homogeneous and distinct from the other species examined. Data comparing the extent of nucleotide sequences shared by M. smegmatis 405 DNA and DNA from nine other mycobacterial strains, as determined by the membrane filter technique and by monitoring DNA reassociation optically, were similar. The extent of reassociation between M. tuberculosis H37Ra DNA and DNA from 14 mycobacterial strains was determined optically. DNA from M. bovis BCG was 86% homologous with M. tuberculosis H37Ra DNA. The other mycobacterial DNA preparations examined were less than 40% homologous with M. tuberculosis H37Ra DNA. The genome sizes of the mycobacteria examined ranged between 2.5 x 10(9) daltons and 4.5 x 10(9) daltons.
Microwave performance of optically fabricated T-gate thin film silicon-on-sapphire based MOSFET's (1995)

Microwave characteristics of n and p-MOS transistors fabricated in thin film (50 and 100 nm) silicon-on-sapphire with T-gate lengths drawn at 0.5 and 0.7 μm are reported. The observed f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</sub> was as high as 32 GHz for a n-MOS 0.7 μm gate length device. Minimum noise figure values of 1.4, 1.8, and 2.1 dB at 2, 8, and 12 GHz respectively were obtained in a 100 nm thick n-channel device. N-channel device results were comparable in the 50 and 100 nm films. For the p-channel FETs, the thinner, more highly stressed films gave significantly better results than the thicker p-channel films. At 2 GHz, p-FET noise figures as low as 1.7 dB were found. These results are, to the authors' knowledge, the lowest reported noise figures for either the p- or n-channel devices of any silicon based FET technology. Thinner films showed better voltage gain (g/sub m//g/sub out/) than the thicker films.
Apolipoprotein E Regulates the Integrity of Tight Junctions in an Isoform-dependent Manner in an in Vitro Blood-Brain Barrier Model (2011)

Apolipoprotein E (apoE) is a major apolipoprotein in the brain. The ε4 allele of apoE is a major risk factor for Alzheimer disease, and apoE deficiency in mice leads to blood-brain barrier (BBB) leakage. However, the effect of apoE isoforms on BBB properties are as yet unknown. Here, using an in vitro BBB model consisting of brain endothelial cells and pericytes prepared from wild-type (WT) mice, and primary astrocytes prepared from human apoE3- and apoE4-knock-in mice, we show that the barrier function of tight junctions (TJs) was impaired when the BBB was reconstituted with primary astrocytes from apoE4-knock-in mice (apoE4-BBB model). The phosphorylation of occludin at Thr residues and the activation of protein kinase C (PKC)η in mBECs were attenuated in the apoE4-BBB model compared with those in the apoE3-BBB model. The differential effects of apoE isoforms on the activation of PKCη, the phosphorylation of occludin at Thr residues, and TJ integrity were abolished following the treatment with an anti-low density lipoprotein receptor-related protein 1 (LRP1) antibody or a LRP1 antagonist receptor-associated protein. Consistent with the results of in vitro studies, BBB permeability was higher in apoE4-knock-in mice than in apoE3-knock-in mice. Our studies provide evidence that TJ integrity in BBB is regulated by apoE in an isoform-dependent manner.
Back-Side Illuminated Photogate CMOS Active Pixel Sensor Structure With Improved Short Wavelength Response (2011)

When light of a short wavelength, typically blue light, is incident on the polysilicon gate of an image sensor, it tends to be absorbed significantly. This has hindered the extensive application of photogate (PG) CMOS image sensor. To overcome this difficulty, a new backside illuminated (BSI) photogate CMOS active pixel sensor structure is proposed. While maintaining other specifications at similar level as those of the front-side illuminated (FSI) structure, the proposed new BSI structure with inverted gate is shown to reduce the absorption effectively. Based on the 0.35 μm CMOS process, the new BSI CMOS image sensor structure is simulated with Synopsys' MEDICI two-dimensional device simulator, and the simulation results show that while maintaining the crosstalk at similar level, the collecting efficiency is improved by 14.89% in the new BSI structure.
Parainfluenza Virus 5 Expressing Wild-Type or Prefusion Respiratory Syncytial Virus (RSV) Fusion Protein Protects Mice and Cotton Rats from RSV Challenge (2017)

Human respiratory syncytial virus (RSV) is the leading cause of pediatric bronchiolitis and hospitalizations. RSV can also cause severe complications in elderly and immunocompromised individuals. There is no licensed vaccine. We previously generated a parainfluenza virus 5 (PIV5)-vectored vaccine candidate expressing the RSV fusion protein (F) that was immunogenic and protective in mice. In this work, our goal was to improve the original vaccine candidate by modifying the PIV5 vector or by modifying the RSV F antigen. We previously demonstrated that insertion of a foreign gene at the PIV5 small hydrophobic (SH)-hemagglutinin-neuraminidase (HN) junction or deletion of PIV5 SH increased vaccine efficacy. Additionally, other groups have demonstrated that antibodies against the prefusion conformation of RSV F have more potent neutralizing activity than antibodies against the postfusion conformation. Therefore, to improve on our previously developed vaccine candidate, we inserted RSV F at the PIV5 SH-HN gene junction or used RSV F to replace PIV5 SH. We also engineered PIV5 to express a prefusion-stabilized F mutant. The candidates were tested in BALB/c mice via the intranasal route and induced both humoral and cell-mediated immunity. They also protected against RSV infection in the mouse lung. When they were administered intranasally or subcutaneously in cotton rats, the candidates were highly immunogenic and reduced RSV loads in both the upper and lower respiratory tracts. PIV5-RSV F was equally protective when administered intranasally or subcutaneously. In all cases, the prefusion F mutant did not induce higher neutralizing antibody titers than wild-type F. These results show that antibodies against both pre- and postfusion F are important for neutralizing RSV and should be considered when designing a vectored RSV vaccine. The findings also that indicate PIV5-RSV F may be administered subcutaneously, which is the preferred route for vaccinating infants, who may develop nasal congestion as a result of intranasal vaccination.<b>IMPORTANCE</b> Despite decades of research, human respiratory syncytial virus (RSV) is still a major health concern for which there is no vaccine. A parainfluenza virus 5-vectored vaccine expressing the native RSV fusion protein (F) has previously been shown to confer robust immunity against RSV infection in mice, cotton rats, and nonhuman primates. To improve our previous vaccine candidate, we developed four new candidates that incorporate modifications to the PIV5 backbone, replace native RSV F with a prefusion-stabilized RSV F mutant, or combine both RSV F and PIV5 backbone modifications. In this work, we characterized the new vaccine candidates and tested their efficacies in both murine and cotton rat models of RSV infection. Most importantly, we found that PIV5-based RSV vaccine candidates were efficacious in preventing lower respiratory tract infection as well as in reducing the nasal viral load when administered via the subcutaneous route.
The X-Ray Crystal Structure Analysis of the Refined Complex formed by Bovine Trypsin andp-Amidinophenylpyruvate at 1.4 Å Resolution (1983)

The X-ray crystal structure of the complex formed by bovine beta-trypsin and the potent small inhibitor p-amidinophenylpyruvate at pH 7.6, has been determined by difference Fourier methods at 1.4 A resolution and subsequently refined to a crystallographic R value of 0.191, applying diagonal matrix least-squares procedures including energy constraints. The amidino and the phenyl group of this inhibitor are bound to the specificity pocket, essentially as previously observed in benzamidine-trypsin. The reactive Ser195 O gamma of trypsin forms a covalent bond of length 1.7 A to the carbonyl carbon of the pyruvate group. The hybridization of this carbonyl carbon is just between trigonal and tetrahedral. The imidazole ring of His57 is in a correct orientation to form bonds via its N epsilon 2 hydrogen to one of the carboxylate oxygens of p-amidinophenylpyruvate and to Ser195 O gamma. The probable proton shift makes Ser195 O gamma more nucleophilic and the attacked carbonyl carbon of p-amidinophenylpyruvate more electrophilic and thus facilitates bond formation. These specific interactions offer a qualitative explanation for the unique binding properties of p-amidinophenylpyruvate and for the applicability of the quantitative structure-activity relations previously found by Markwardt and coworkers for three series of p-amidinophenylalkanone compounds with carbonyl groups in alpha-, beta- and gamma-position to the phenyl ring.
Human umbilical cord blood‐derived mesenchymal stem cells (hUCB‐MSC) inhibit the proliferation of K562 (human erythromyeloblastoid leukaemic cell line) (2012)

hUCB-MSC (human umbilical cord blood-derived mesenchymal stem cells) offer an attractive alternative to bone marrow-derived MSC for cell-based therapy by being less invasive a source of biological material. We have evaluated the effect of hUCB-MSC on the proliferation of K562 (an erythromyeloblastoid cell line) and the cytokine secretion pattern of hUCB-MSC. Co-culturing of hUCB-MSC and K562 resulted in inhibition of proliferation of K562 in a dose-dependent manner. However, the anti-proliferative effect was reduced in transwells, suggesting the importance of direct cell-to-cell contact. hUCB-MSC inhibited proliferation of K562, arresting them in the G0 /G1 phase. NO (nitric oxide) was not involved in the hUCB-MSC-mediated tumour suppression. The presence of IL-6 (interleukin 6) and IL-8 were obvious in the hUCB-MSC conditioned media, but no significant increase was found in 29 other cytokines. Th1 cytokines, IFNα (interferon α), Th2 cytokine IL-4 and Th17 cytokine, IL-17 were not secreted by hUCB-MSC. There was an increase in the number of hUCB-MSC expressing the latent membrane-bound form of TGFβ1 co-cultured with K562. The anti-proliferative effect of hUCB-MSC was due to arrest of the growth of K562 in the G0 /G1 phase. The mechanisms underlying increased IL-6 and IL-8 secretion and LAP (latency-associated peptide; TGFβ1) by hUCB-MSC remains unknown.
The kinesin-like protein KLP61F is essential for mitosis in Drosophila. (1993)

We report here that disruption of a recently discovered kinesin-like protein in Drosophila melanogaster, KLP61F, results in a mitotic mutation lethal to the organism. We show that in the absence of KLP61F function, spindle poles fail to separate, resulting in the formation of monopolar mitotic spindles. The resulting phenotype of metaphase arrest with polyploid cells is reminiscent of that seen in the fungal bimC and cut7 mutations, where it has also been shown that spindle pole bodies are not segregated. KLP61F is specifically expressed in proliferating tissues during embryonic and larval development, consistent with a primary role in cell division. The structural and functional homology of the KLP61F, bimC, cut7, and Eg5 kinesin-like proteins demonstrates the existence of a conserved family of kinesin-like molecules important for spindle pole separation and mitotic spindle dynamics.
Operating Modes of Dynamic Power Supply Transmitter Amplifiers (2014)

Any amplifier operated with a varying supply voltage is actually a three-port circuit, having two inputs and one output. When an amplifier is characterized as a three-port for dynamic supply voltage operation, three separate operating modes appear: linear L-mode and the two nonlinear modes C-mode and P-mode. Each of these modes, along with their relationships and differences, are identified, characterized, and discussed. Relations of these modes to the dynamic power supply transmitter techniques of envelope tracking and/or direct polar are presented. Measurements are reported that provide experimental verification for these amplifier operating modes.