gebhart/patrepeval huggingface dataset:
Monodisperse Emulsion Generation via Drop Break Off in a Coflowing Stream (1999)

We describe an experimental technique for the production of highly monodisperse emulsions (with minimum achievable polydispersities <3%). The phase to be dispersed is introduced into a coflowing, surfactant-laden continuous phase via a tapered capillary. Drops detach from the capillary when the streamwise forces exceed the force due to interfacial tension. Drop size is a function of the capillary tip diameter, the velocity of the continuous phase, the extrusion rate, and the viscosities and interfacial tension of the two phases. Emulsions composed of a variety of fluids and with drop sizes ranging from 2 to 200 μm have been produced using this technique.
JAK2 inhibition sensitizes resistant EGFR-mutant lung adenocarcinoma to tyrosine kinase inhibitors (2016)

Lung adenocarcinomas with mutant epidermal growth factor receptor (EGFR) respond to EGFR-targeted tyrosine kinase inhibitors (TKIs), but resistance invariably occurs. We found that the Janus kinase (JAK)/signal transduction and activator of transcription 3 (STAT3) signaling pathway was aberrantly increased in TKI-resistant EGFR-mutant non-small cell lung cancer (NSCLC) cells. JAK2 inhibition restored sensitivity to the EGFR inhibitor erlotinib in TKI-resistant cell lines and xenograft models of EGFR-mutant TKI-resistant lung cancer. JAK2 inhibition uncoupled EGFR from its negative regulator, suppressor of cytokine signaling 5 (SOCS5), consequently increasing EGFR abundance and restoring the tumor cells' dependence on EGFR signaling. Furthermore, JAK2 inhibition led to heterodimerization of mutant and wild-type EGFR subunits, the activity of which was then blocked by TKIs. Our results reveal a mechanism whereby JAK2 inhibition overcomes acquired resistance to EGFR inhibitors and support the use of combination therapy with JAK and EGFR inhibitors for the treatment of EGFR-dependent NSCLC.
PD1 blockade reverses the suppression of melanoma antigen-specific CTL by CD4+CD25Hi regulatory T cells (2009)

Regulatory CD4(+)CD25(Hi) T cells (Treg) and programmed death-1 (PD-1) molecule have emerged as pivotal players in immune regulation. However, the underlying mechanisms by which they impact antigen-specific CD8(+) immune responses in cancer patients and how they interact with each other under physiologic conditions remain unclear. Herein, we examined the relationship of PD-1 and its abrogation to the function of Treg in patients with melanoma using short-term in vitro assays to generate melanoma-specific T cells. We identified Treg in the circulation of vaccinated melanoma patients and detected PD-1 expression on vaccine-induced melanoma antigen-specific CTLs, as well as on and within Treg from patients' peripheral blood. Programmed death ligand (PD-L) 1 expression was also detected on patients' Treg. PD-1 blockade promoted the generation of melanoma antigen-specific CTLs and masked their inhibition by Treg. The mechanisms by which PD-1 blockade mediated immune enhancement included direct augmentation of melanoma antigen-specific CTL proliferation, heightening their resistance to inhibition by Treg and direct limitation of the inhibitory ability of Treg. PD-1 blockade reversed the increased expression of PD-1 and PD-L1 on melanoma antigen-specific CTL by Treg, rescued INF-gamma and IL-2 or INF-gamma and tumor necrosis factor-alpha co-expression and expression of IL-7 receptor by melanoma antigen-specific CTL which were diminished by Treg. PD-1 blockade also resulted in down-regulation of intracellular FoxP3 expression by Treg. These data suggest that PD-1 is importantly implicated in the regulation of Treg function in melanoma patients.
Influence of stretch on excitation threshold of single frog ventricular cells (1995)

The excitation threshold of enzymatically dissociated single frog ventricular myocytes was measured as a function of cell length or sarcomere length. Field stimulation with 3 ms duration rectangular current pulses was applied via two platinum wire electrodes oriented either parallel or perpendicular to the long axis of the cell. Excitation threshold was measured as the amplitude of applied current, with an error of less than 1%. Single cells were held isometrically by two glass pipettes and wrapped around an optical fibre, which was used to control cell length. Sarcomere length was measured using video microscopy and a phase-locked loop system. Changes in cell length and sarcomere length were induced by mechanical stretch and release of the whole cell. The excitation threshold decreased with increasing resting length (preload), and increased with decrease of the cell length back to its original length, regardless of the orientation of the electric field. The measured change in excitation threshold with stretch was of the order of 1%/% strain. These results suggest that stretch affects the excitation threshold of cardiac cells by factors other than simple shape changes in the cell, perhaps through the activity of mechanosensitive ionic channels.
Preparation of leukoreduced whole blood for transfusion in austere environments; effects of forced filtration, storage agitation, and high temperatures on hemostatic function (2018)

Diagnostic study, level IV.
Systematic Deletion Analysis of Ricin A-Chain Function (1995)

The A-chain of ricin is a cytotoxic RNA N-glycosidase that inactivates ribosomes by depurination of the adenosine at position 4324 in 28 S rRNA. Of the 267 amino acids in the protein, 222 could be deleted, in one or another of 74 mutants, without the loss of the capacity to catalyze hydrolysis of a single specific nucleotide in rRNA (Morris, K. N., and Wool, I. G. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 4869-4873). The 45 amino acids that could not be omitted when the deletions were in sets of 20, 5, or 2 residues have now been deleted one at a time; 9 of these deletion mutants retained activity. A RNP-like structural motif in ricin A-chain that may mediate binding to ribosomal RNA has been identified.
Initial results of in vivo non-invasive cancer imaging in the human breast using near-infrared photoacoustics (2007)

Near-infrared photoacoustic images of regions-of-interest in 4 of the 5 cases of patients with symptomatic breasts reveal higher intensity regions which we attribute to vascular distribution associated with cancer. Of the 2 cases presented here, one is especially significant where benign indicators dominate in conventional radiological images, while photoacoustic images reveal vascular features suggestive of malignancy, which is corroborated by histopathology. The results show that photoacoustic imaging may have potential in visualizing certain breast cancers based on intrinsic optical absorption contrast. A future role for the approach could be in supplementing conventional breast imaging to assist detection and/or diagnosis.
Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages (2008)

Increased evidence suggests that cancer-associated inflammation supports tumor growth and progression. We have previously shown that semaphorin 4D (Sema4D), a ligand produced by different cell types, is a proangiogenic molecule that acts by binding to its receptor, plexin B1, expressed on endothelial cells (Conrotto, P., D. Valdembri, S. Corso, G. Serini, L. Tamagnone, P.M. Comoglio, F. Bussolino, and S. Giordano. 2005. Blood. 105:4321-4329). The present work highlights the role of Sema4D produced by the tumor microenvironment on neoplastic angiogenesis. We show that in an environment lacking Sema4D, the ability of cancer cells to generate tumor masses and metastases is severely impaired. This condition can be explained by a defective vascularization inside the tumor. We demonstrate that tumor-associated macrophages (TAMs) are the main cells producing Sema4D within the tumor stroma and that their ability to produce Sema4D is critical for tumor angiogenesis and vessel maturation. This study helps to explain the protumoral role of inflammatory cells of the tumor stroma and leads to the identification of an angiogenic molecule that might be a novel therapeutic target.
Development of BCG as a live recombinant vector system: potential use as an HIV vaccine. (1991)

Bacille Calmette-Guèrin (BCG), a live attenuated tubercle bacillus, is currently the most widely used vaccine in the world. Because of its unique characteristics, including low toxicity, adjuvant potential, and long-lasting immunity, BCG represents a novel vaccine vehicle with which to deliver protective antigens of multiple pathogens. We have developed episomal and integrative expression vectors employing regulatory sequences of major BCG heat shock proteins for stable maintenance and expression of foreign antigens in BCG vaccine strains (22). Shuttle plasmids capable of autonomous replication in Escherichia coli and BCG were constructed with a DNA cassette containing a minimal replicon derived from the Mycobacterium fortuitum plasmid pAL5000. Efficient and stable chromosomal integration of recombinant plasmids into BCG was achieved using a DNA segment containing the mycobacteriophage L5 attachment site and integrase coding sequence. Using the BCG hsp60 and hsp70 stress gene promoters, we were able to express Escherchia coli beta-galactosidase to levels in excess of 10% of total cell protein. The major antigens of HIV-1 gag, pol, and env were also stably expressed using our vector systems. The recombinant BCG elicited long-lasting humoral and cellular immune responses to these antigens in mice. Antibody responses to beta-galactosidase using as few as 200 colony-forming units were detected 6 weeks after immunization, and titers (1:30,000) were sustained for more than 10 weeks. Cellular immune responses, of both cytotoxic T cell (CTL) and helper T lymphocytes, were detected to beta-galactosidase. CTL responses were also induced to the HIV-1 envelope protein. Thus, we have demonstrated stable recombinant antigen expression, processing, and presentation using our recombinant BCG vector system. This live recombinant vector system shows promise as a universally applicable and safe vaccine vehicle for protection against various infectious diseases.
Analysis of Uniform Hashing (1983)

Umform hashing or random probing is often used as a theoretical model of certain types of hashing schemes based on open addressmg, and, m pamcular, of double hashing. Earlier analyses of umform hashing are extended here to multlrecord buckets. Three different situations are analysed: initial loadmg assuming uniform access frequencies, frequency loading assuming nonuniform access frequencies, and the dynamic behavior when msertions and deletions occur. Stmple "closed" formulas cannot be found, but numerical results are readily computed. For larger bucket sizes the retrieval performance is signdicanfly better than that of linear probing and separate chaining Hence double hashing and similar techniques are competmve alternatives also for organizing externally stored files.
Congenital osteoclast deficiency in osteopetrotic (op/op) mice is cured by injections of macrophage colony-stimulating factor. (1991)

Osteopetrotic (op/op) mice have a severe deficiency of osteoclasts, monocytes, and peritoneal macrophages because of a defect in the production of functional macrophage colony-stimulating factor (M-CSF) resulting from a mutation within the M-CSF gene. In this study, we examined whether daily 5-microgram injections of purified recombinant human M-CSF (rhM-CSF) for 14 d would cure these deficiencies in the mutant mice. Monocytes in the peripheral blood of the op/op mice were significantly increased in number after subcutaneous injections of the factor two or three times a day. In contrast, osteopetrosis in the long bones of op/op mice was completely cured by only one injection of rhM-CSF per day. Bone trabeculae in the diaphyses were removed. Many osteoclasts were detected on the surface of bone trabeculae in the metaphyses. Although development of tooth germs of uninjected op/op mice was impaired, rhM-CSF injection restored the development of molar tooth germs and led to tooth eruption as a consequence of the recovery of bone-resorbing activity. These results demonstrate that M-CSF is one of the factors responsible for the differentiation of osteoclasts and monocyte/macrophages under physiological conditions.
In Vivo Analysis of DNA Methylation Patterns Recognized by Specific Proteins: Coupling ChIP and Bisulfite Analysis (2004)

The three-way connection between DNA methylation, chromatin configuration, and transcriptional regulation is under increasing attention, but the fine rules governing the epigenetic control are still poorly understood. In several studies, the authors have concluded that the methylation status of CpG sites could be critical for the binding of factors to DNA and, consequently, for chromatin conformation. We tested the possibility that a novel technical approach combining chromatin immunoprecipitation and bisulfite genomic sequencing analysis (ChIP-BA) could provide useful information on the role of specific CpG methylation patterns in driving the association in vivo of proteins to given genomic regions. Our results show that ChIP-BA permits the establishment in vivo of the methylation patterns required for the binding of a methyl-CpG binding protein and, in addition, can potentially identify methylation patterns that do not allow a protein to bind specific genomic regions. Possible fields of application are discussed. We believe that wide use of ChIP-BA could make possible the exploration of a novel aspect of the intricate epigenetic web.
First‐trimester maternal plasma cytokine levels, pre‐pregnancy body mass index, and spontaneous preterm delivery (2009)

These findings suggest that the association between first-trimester plasma cytokine levels and sPTD may depend on pre-pregnancy body mass index.
Vision-based Location Recognition using Scale-Invariant Feature Transform for Airship (2007)

In this paper, we present a vision-based airship location recognition system using scale-invariant feature transform. The proposed system is consists of three steps: the location database building, the feature extraction and the location recognition. In location database building step, scale-invariant features detected from obtained images in the pre-exploration are indexed into a location database. The next step extracts the features from the images which are acquired from airship mounted camera during its exploration. In final step, we use the voting scheme through matching results between the indexed features of location database and features of images acquired by an airship to determine its location. The proposed system applies to indoor scenes of our building. The experimental results show the recognition performance.
The D2-MAC-Packet System for All Transmission Channels (1985)

Based on research carried out within the European Broadcasting Union (EBU), the CCETT in France has developed a new DBS transmittal system for all channels. The D2-MAC-packet system, as it is called, joins other segments of the MAC family developed by the EBU. Its features include four simultaneously broadcast channels, improved picture quality, capability of transmittal over various cable networks, the same standard for VHF-UHF broadcasting, and no absolute limitation on bandwidth reduction. A brief summary of the various stages of the system and its characteristics is given, together with some practical results and measurements obtained in DBS, VHF, and MA TV or CA TV.
한의대생들의 의사소통 관련요인 (2012)

Purpose: The purposes of this study was to identify communication competency in oriental medicine students and to provide basic resources of oriental medical education program. Methods: : From August 21 to September 22, 2009, 158 oriental medical students were surveyed using structured questionnaires. Data were analyzed using descriptive statistics using the SPSS program. Results: The average of self-esteem and interpersonal relation were each 3.09 (±0.451), 86.3 (±11.19), communication type was congruence (2.74), placating (2.62), super-reasonable (2.35), irrelevant (2.22), blaming (2.19). There was a statistically significant difference between 2nd grade of pre-oriental medical course and 2nd grade of oriental medical course in super-reasonable of communication type. Self-esteem and interpersonal relation explained 52.1% of variances in congruence communication competency. Conclusions: The results of this study indicate that development of communication competency in oriental medical students need to consider the interpersonal relation and self-esteem.
A Quantitative Analysis of New Bone Formation by Induction in Compositive Grafts of Bone Marrow and Bone Matrix (1980)

LINDHOLM, T. SAM M.D.; URIST, MARSHALL R. M.D.Editor(s): KATZ, JACOB F. M.D. Author Information
Identification and characterization of human MT5-MMP, a new membrane-bound activator of progelatinase a overexpressed in brain tumors. (1999)

A cDNA encoding a new member of the membrane-type (MT) matrix metalloproteinase (MMP) family has been identified and cloned from a human brain cDNA library. The isolated cDNA encodes a polypeptide of 645 amino acids that displays a similar domain organization as other MMPs, including a predomain with the activation locus, a zinc-binding site, and a hemopexin domain. The deduced amino acid sequence contains a COOH-terminal extension, rich in hydrophobic residues and similar in size to the equivalent domains identified in MT-MMPs. Immunofluorescence and Western blot analysis of COS-7 cells transfected with the isolated cDNA revealed that the encoded protein is localized in the plasma membrane. On the basis of these features, this novel human MMP has been called MT5-MMP because it represents the fifth member of the MT-MMP subfamily of MMPs. Fluorescent in situ hybridization experiments showed that the human MT5-MMP gene (MMP-24) maps to 20q11.2, a region frequently amplified in tumors from diverse sources. Northern blot analysis demonstrated that MT5-MMP is predominantly expressed in brain, kidney, pancreas, and lung. In addition, MT5-MMP transcripts were detected at high levels compared to normal brain tissue in a series of brain tumors, including astrocytomas and glioblastomas. The catalytic domain of MT5-MMP, produced in Escherichia coli as a fusion protein with glutathione S-transferase, exhibits a potent proteolytic activity against progelatinase A, leading to the generation of the Mr 62,000 active form of this enzyme. These data suggest that MT5-MMP may contribute to the activation of progelatinase A in tumor tissues, in which it is overexpressed, thereby facilitating tumor progression.
Expression of FGFR3 with the G380R Achondroplasia Mutation Inhibits Proliferation and Maturation of CFK2 Chondrocytic Cells (2000)

Abstract A G380R substitution in the transmembrane-spanning region of FGFR3 (FGFR3Ach) results in constitutive receptor kinase activity and is the most common cause of achondroplastic dwarfism in humans. The epiphyseal growth plates of affected individuals are disorganized and hypocellular and show aberrant chondrocyte maturation. To examine the molecular basis of these abnormalities, we used a chondrocytic cell line, CFK2, to stably express the b variant of wild-type FGFR3 or the the constitutively active FGFR3Ach. Overexpression of FGFR3 had minimal effects on CFK2 proliferation and maturation compared with the severe growth retardation found in cells expressing FGFR3Ach. Cells expressing the mutant receptor also showed an abnormal apoptotic response to serum deprivation and failed to undergo differentiation under appropriate culture conditions. These changes were associated with altered expression of integrin subunits, which effectively led to a switch in substrate preference of the immature cell from fibronectin to type II collagen. These in vitro observations support those from in vivo studies indicating that FGFR3 mediates an inhibitory influence on chondrocyte proliferation. We now suggest that the mechanism is related to altered integrin expression.
Parallel Solution-Phase Synthesis of a 2,6,8,9-Tetrasubstituted Purine Library via a Sulfur Intermediate (2005)

Purine analogues exhibiting a wide range of pharmacological activities have been considered a privileged structure in medicinal chemistry. In addition, the purine core consisting of four points of structural diversity is a well-sought scaffold in combinatorial chemistry. Although most of the efforts have been focused on 2,6,9-, 6,8,9-, or 2,8,9-trisubstituted purines, syntheses of 2,6,8,9-tetrasubstituted purines are rare. This paper presents a parallel solution phase approach for the synthesis of fully substituted purines via a 6-sulfur-substituted pyrimidine as the key intermediate. This strategy combining construction and modification of the purine ring thus increases the structural diversity of the final products. Sequential substitution of chlorines in 4,6-dichloro-2-methyl-5-nitropyrimidine with primary amine and benzylmercaptan afforded the 4-(substituted)amino-6-benzylthio-5-nitropyrimidine, which was readily converted to its diaminopyrimidine analogue by reduction of the nitro group. The diaminopyrimidine intermediate was cyclized to construct the purine ring with a C-8 substituent. Eventual oxidation of sulfur to sulfone and subsequent displacement by a primary or secondary amine provided the desired 2,6,8,9-tetrasubstituted purine analogues. This synthetic methodology was validated with the synthesis of a 216-member purine library.
Functional status and well-being of patients with chronic conditions. Results from the Medical Outcomes Study. (1989)

Enhancing daily functioning and well-being is an increasingly advocated goal in the treatment of patients with chronic conditions. We evaluated the functioning and well-being of 9385 adults at the time of office visits to 362 physicians in three US cities, using brief surveys completed by both patients and physicians. For eight of nine common chronic medical conditions, patients with the condition showed markedly worse physical, role, and social functioning; mental health; health perceptions; and/or bodily pain compared with patients with no chronic conditions. Each condition had a unique profile among the various health components. Hypertension had the least overall impact; heart disease and patient-reported gastrointestinal disorders had the greatest impact. Patients with multiple conditions showed greater decrements in functioning and well-being than those with only one condition. Substantial variations in functioning and well-being within each chronic condition group remain to be explained.
Structural study of DNA duplexes containing the (6-4) photoproduct by fluorescence resonance energy transfer (2001)

Fluorescence resonance energy transfer (FRET) experiments have been performed to elucidate the structural features of oligonucleotide duplexes containing the pyrimidine(6-4)pyrimidone photoproduct, which is one of the major DNA lesions formed at dipyrimidine sites by UV light. Synthetic 32mer duplexes with and without the (6-4) photoproduct were prepared and fluorescein and tetramethylrhodamine were attached, as a donor and an acceptor, respectively, to the aminohexyl linker at the C5 position of thymine in each strand. Steady-state and time-resolved analyses revealed that both the FRET efficiency and the fluorescence lifetime of the duplex containing the (6-4) photoproduct were almost identical to those of the undamaged duplex, while marked differences were observed for a cisplatin-modified duplex, as a model of kinked DNA. Lifetime measurements of a series of duplexes containing the (6-4) photoproduct, in which the fluorescein position was changed systematically, revealed a small unwinding at the damage site, but did not suggest a kinked structure. These results indicate that formation of the (6-4) photoproduct induces only a small change in the DNA structure, in contrast to the large kink at the (6-4) photoproduct site reported in an NMR study.