gebhart/patrepeval huggingface dataset:
At least 27 alternatively spliced forms of the neural cell adhesion molecule mRNA are expressed during rat heart development. (1991)

The major membrane-associated or transmembrane isoforms of the neural cell adhesion molecule (NCAM) are generated by alternative splicing at the 3' end of the mRNA. Further diversity in NCAM structure is observed in the extracellular region of the polypeptide, where the insertion of additional amino acid residues can result from alternative splicing events occurring at the exon 7-exon 8 and exon 12-exon 13 junctions. Here we report the characterization of tissue-specific patterns of alternative splicing at the exon 12-exon 13 junction by using the polymerase chain reaction. Nine alternatively spliced sequences in rat heart between exon 12 and exon 13 were identified. Each sequence consisted of different combinations of the three small exons (15, 48, and 42 bp in length) and the AAG triplet that make up MSD1, the 108-bp muscle-specific sequence found in human skeletal muscle NCAM (G. Dickson, H.J. Gower, C. H. Barton, H. M. Prentice, V. L. Elsom, S. E. Moore, R. D. Cox, C. Quinn, W. Putt, and F. S. Walsh, Cell 50:1119-1130, 1987). Although the rat equivalent of MSD1 (designated 15+ 48+ 42+ 3+) was detected in all ages of heart examined, it was only one of four or five major splice combinations at any given age. The only alternatively spliced sequence found in the exon 7-exon 8 junction of heart NCAM mRNA was the 30-bp variable alternatively spliced exon previously identified in rat brain. Twenty-seven NCAM forms with distinct sequences were found by analysis of individual NCAM transcripts from postnatal day 1 heart tissue for alternative splicing at the exon 7-exon 8 junction, the exon 12-exon 13 junction and the 3' end. Several combinations of splicing patterns in these three different regions of the gene appeared to be preferentially expressed. The observation that the expression of alternatively spliced forms of NCAM is developmentally regulated suggests a role for NCAM diversity in cardiac development.
Identification of RNAs that bind to a specific protein using the yeast three-hybrid system (1999)

We have adapted the yeast three-hybrid system to identify RNA ligands for an RNA-binding protein. In this assay system, a protein-RNA interaction is detected by the reconstitution of a transcriptional activator using two hybrid proteins and a hybrid RNA. The RNA molecule is tethered to the promoter of a reporter gene by binding to a hybrid protein consisting of the bacteriophage MS2 coat protein fused to the DNA-binding protein LexA; the RNA-binding domain to be analyzed is fused to the transcriptional activation domain of the yeast Gal4 protein; and the bifunctional RNA consists of binding sites for the coat protein and for the other RNA-binding domain. We built an RNA library such that short fragments of genomic DNA from yeast were transcribed in yeast together with binding sites for the coat protein. We screened this hybrid RNA library for RNAs that bound to the yeast Snp1 protein, a homolog of the human U1-70K protein. The screen yielded as the strongest positive the fragment of U1 RNA that contains loop I, which is known to bind to Snp1 in U1 snRNP. We also identified four other RNA ligands that produced weaker three-hybrid signals, suggesting lower affinities for Snp1 as compared to U1 RNA. In addition, this search also yielded a set of RNA sequences that can activate transcription on their own when bound to a promoter through a protein interaction.
The TLR4-TRIF Pathway Protects against H5N1 Influenza Virus Infection (2011)

Prestimulation of the TLR4 pathway with lipopolysaccharide (LPS) protects mice from lethal infection with H5N1 influenza virus. Here, we reveal that the TLR4-TRIF pathway is required for this protective effect by using mice whose TLR4-related molecules were knocked out. Microarray analysis of primary mouse lung culture cells that were LPS pretreated and infected with an H5N1 virus indicated that TLR3 mRNA was upregulated. Primary lung culture cells of TLR3 knockout mice showed no response to LPS pretreatment against H5N1 virus infection, suggesting that TLR3 is also involved in the preventive effect of LPS. Our data suggest that the TLR4-TRIF axis has an important role in stimulating protective innate immunity against H5N1 influenza A virus infection and that TLR3 signaling is involved in this pathway.
Isolation of cyclo(His-Pro)-like immunoreactivity from human urine and demonstration of its immunologic, pharmacologic, and physico-chemical identity with the synthetic peptide. (1990)

Measurements of cyclo(His-Pro) levels in human urine were carried out by specific radioimmunoassay. Cyclo(His-Pro)-like immunoreactivity in Human urine was found to be immunologically, pharmacologically, and physico-chemically identical to that of synthetic cyclo(His-Pro). The concentration of urinary cyclo(His-Pro) in 24-h collection was 1133.8 +/- 122.5 nmol/L, with a range of 606 to 1865 nmol/L. The daily excretion rate of cyclo(His-Pro) was 1812 +/- 248 nmol cyclo(His-Pro)/g creatinine, or 1814 +/- 199 nmol cyclo(His-Pro/day.
ANALYSIS OF HEPATIC STEATOSIS AFTER PEDIATRIC LIVING DONOR LIVER TRANSPLANTATION (2008)

Wakayama, K1; Taniguchi, M1; Shimamura, T2; Suzuki, T3; Yamashita, K1; Furukawa, H3; Todo, S1 Author Information
Lymphomas with concurrent BCL2 and MYC translocations: the critical factors associated with survival (2009)

BCL2 and MYC are oncogenes commonly deregulated in lymphomas. Concurrent BCL2 and MYC translocations (BCL2(+)/MYC(+)) were identified in 54 samples by karyotype and/or fluorescence in situ hybridization with the aim of correlating clinical and cytogenetic characteristics to overall survival. BCL2(+)/MYC(+) lymphomas were diagnosed as B-cell lymphoma unclassifiable (BCLU; n = 36) with features intermediate between Burkitt lymphoma and diffuse large B-cell lymphoma (DLBCL); DLBCL (n = 17), or follicular lymphoma (n = 1). Despite the presence of a t(14;18), 5 cases were BCL2 protein-negative. Nonimmunoglobulin gene/MYC (non-IG/MYC) translocations occurred in 24 of 54 cases (44%) and were highly associated with DLBCL morphology (P < .001). Over a median follow-up of 5.3 years, 6 patients remained in remission and 32 died within 6 months of the MYC(+) rearrangement, irrespective of whether MYC(+) occurred at diagnosis (31 of 54) or transformation (23 of 54; P = .53). A non-IG/MYC translocation partner, absent BCL2 protein expression and treatment with rituximab-based chemotherapy, were associated with a more favorable outcome, but a low International Prognostic Index score and DLBCL morphology were independent predictors of overall survival. A comprehensive cytogenetic analysis of BCL2 and MYC status on all aggressive lymphomas may identify a group of high-risk patients who may benefit from chemotherapeutic regimens that include rituximab and/or BCL2-targeted therapy.
Advanced Soldier Thermoelectric Power System for Power Generation from Battlefield Heat Sources (2010)

The U.S. military uses large amounts of fuel during deployments and battlefield operations. This project sought to develop a lightweight, small form-factor, soldier-portable advanced thermoelectric (TE) system prototype to recover and convert waste heat from various deployed military equipment (i.e., diesel generators/engines, incinerators, vehicles, and potentially mobile kitchens), with the ultimate purpose of producing power for soldier battery charging, advanced capacitor charging, and other battlefield power applications. The technical approach employed microchannel technology, a unique “power panel” approach to heat exchange/TE system integration, and newly-characterized LAST (lead-antimony-silver-telluride) and LASTT (lead-antimony-silver-tin-telluride) TE materials segmented with bismuth telluride TE materials in designing a segmented-element TE power module and system. This project researched never-before-addressed system integration challenges (thermal expansion, thermal diffusion, electrical interconnection, thermal and electrical interfaces) of designing thin “power panels” consisting of alternating layers of thin, microchannel heat exchangers (hot and cold) sandwiching thin, segmented-element TE power generators. The TE properties, structurally properties, and thermal fatigue behavior of LAST and LASTT materials were developed and characterized such that the first segmented-element TE modules using LAST / LASTT materials were fabricated and tested at hot-side temperatures = 400 °C and cold-side temperatures = 40 °C. LAST / LASTT materials were successfully segmented with bismuth telluride and electrically interconnected with diffusion barrier materials and copper strapping within the module electrical circuit. A TE system design was developed to produce 1.5-1.6 kW of electrical energy using these new TE modules from the exhaust waste heat of 60-kW Tactical Quiet Generators as demonstration vehicles.
Nanoparticle-Based Diagnosis and Therapy (2006)

Nanoparticles are at the leading edge of the rapidly developing field of material science in nanotechnology with many potential applications in clinical medicine and research. Due to their unique size-dependent properties nanoparticles offer the possibility to develop both new therapeutic and diagnostic tools. The ability to incorporate drugs into nanosystems displays a new paradigm in pharmacotherapy that could be used for cell-targeted drug delivery. Nontargeted nanosystems such as nanocarriers that are coated with polymers or albumin and solid lipid particles have been used to transport a large number of compounds. However, nowadays drugs can be coupled to nanocarriers that are specific for cells and/or organs. Thus, drugs that are either trapped within the carriers or deposited in subsurface oil layers could be specifically delivered to organs, tumors and cells. These strategies can be used to concentrate drugs in selected target tissues thus minimizing systemic side effects and toxicity. In addition to these therapeutic options, nanoparticle-based "molecular" imaging displays a field in which this new technology has set the stage for an evolutionary leap in diagnostic imaging. Based on the recent progress in nanobiotechnology, nanoparticles have the potential to become useful tools as therapeutic and diagnostic tools in the near future.
Dynamic Presentation of Immobilized Ligands Regulated through Biomolecular Recognition (2010)

To mimic the dynamic regulation of signaling ligands immobilized on extracellular matrices or on the surfaces of neighboring cells for guidance of cell behavior and fate selection, we have harnessed biomolecular recognition in combination with polymer engineering to create dynamic surfaces on which the accessibility of immobilized ligands to cell surface receptors can be reversibly interconverted under physiological conditions. The cell-adhesive RGD peptide is chosen as a model ligand. RGD is fused to the C-terminus of a leucine zipper domain A, and this fusion polypeptide is immobilized on surfaces through a residue at the N-terminus. The immobilized RGD can be converted from a cell-accessible to a cell-inaccessible state by addition of a conjugate of poly(ethylene) glycol (PEG) and another leucine zipper domain B (B-PEG). Heterodimerization between A and B allows coimmobilization of the PEG, which shields RGD from access by cells. The shielded RGD can be converted back to a cell-accessible state by addition of nonimmobilized polypeptide A, which competes with the immobilized A for binding to B-PEG and removes B-PEG from the surface. This molecular design offers several advantages: the interconversion is reversible; the ligand remains immobilized during dynamic regulation so that cells are not exposed to the soluble form of the ligand that potentially has detrimental effects; the precision of the on/off states is assured by the molecular-level uniformity of the ligand and PEG coimmobilized through leucine zipper heterodimerization. The method can be readily adapted for dynamic regulation of other immobilized bioactive ligands of interest.
A Pivotal Role for the Natural Interferon α–producing Cells (Plasmacytoid Dendritic Cells) in the Pathogenesis of Lupus (2001)

The human type I IFN gene family consists of 13 genes encoding IFN-α subtypes and one gene each for IFN-β and -ω. The type I IFN proteins show similarities with respect to both structure and function; for instance, they are typically produced by cells exposed to virus and interact with the same
Laboratory Protocols for Conditional Gene Targeting (1997)

Abstract Conditional gene targeting is an emerging technique for introducing mutations into the genes of laboratory mice. This collection of protocols comes from one of the world's premier laboratories for gene targeting The Institute of Genetics in Cologne and is intended for newcomers to the field as well as more experienced researchers. Topics covered include: the Cre/loxP recombination system and gene targeting in ES cells; gene targeting strategies; Cre/loxP recombination system; Gene targeting vectors consideration and use of loxP; nonselectable modifications and removal of selection marker genes; large deletions; gene replacement; chromosomal translocations; targeted integrations; conditional gene modification; LoxP-containing transgenes; conditional gene targeting; working with ES cells; ES cell transfection overview; embryonic feeder cells; ES cells handling and use; ES cell culture and transfection; ES clone picking; identification of homologous recombinants; freezing ES clones; thawing ES clones; genomic DNA preparation; cre-mediated neomycin deletion in ES cells; generation of mice preparation; mouse breeding for ES cell injection or aggregation; injection needles and holders; blastocyst preparation/injection; embryo aggregation; blastocyst transfer;
Screening and optimization strategies for macromolecular crystal growth (1994)

Today the determination of successful crystallization conditions for a particular macromolecule remains a highly empirical process. Sparse-matrix and grid-screening procedures are rapid and economical means to determine preliminary crystallization conditions. During optimization the variable set (pH, precipitant type and precipitant concentration) utilized in these procedures is screened in an attempt to determine appropriate conditions for the nucleation and growth of single crystals suitable for X-ray diffraction analysis. Unfortunately, in many cases this strategy will not produce single crystals suitable for X-ray diffraction analysis. We have explored, in an empirical sense, other tools for use during optimization. First, a new screening protocol is evaluated which employs less classical precipitating agents. Second, a set of 24 electrostatic crosslinking agents are evaluated for their ability to promote crystallization. Third, a panel of more than 30 detergents are evaluated for their ability to prevent sample aggregation and influence crystal growth.
ASIC hardware implementations for 512-bit hash function Whirlpool (2008)

Hardware architectures for the 512-bit hash function Whirlpool, which is one of the ISO/IEC 10118-3 standard algorithms, are proposed and the performances of the proposed architectures are evaluated using a 0.18-μm CMOS standard cell library. The fastest implementation achieved a throughput of 9.59 Gbps with a gate count of 167.4K, which is two times faster than the fastest conventional implementation on an FPGA platform. A compact implementation obtained 38.9 Kgates with 2.49 Gbps. The FIPS 180-2 standard hash functions SHA-256 and SHA-512, which are the most popular algorithms in practical use, were also synthesized using the same ASIC library for performance comparisons. The small and fast SHA-256 implementations achieved 11.0 Kgates with 726 Mbps and 30.7 Kgates with 1.97 Gbps, respectively. The gate count and throughput are both approximately 1/4 those of to Whirlpool, and thus the hardware efficiencies defined as the throughput/gate are almost the same for SHA-256/-512 and Whirlpool in the present implementations. However, Whirlpool is more flexible than SHA-256/-512 in terms of the variety of hardware architectures. The various architectures for the datapath and primitive function blocks are also described in the present paper.
Measurement of Emotions (2012)

Work is an emotional experience. Employees experience fear over losing their jobs, anger over being treated unfairly, and anxiety about impending deadlines. However, they also derive warmth and gratitude when interacting with coworkers, pride from working for a virtuous organization, and a sense of personal growth from job accomplishments. Mixed in with these experiences are the emotions that individuals bring with them to work, such as distress about a family member’s illness, frustration over morning traffi c, or underlying psychopathological issues that cannot simply “be left at the company’s door.” Collectively, these numerous and varied emotions have signifi cant implications for employees’ physical and psychological well-being and for their ability to function eff ectively at work (for reviews, see articles in Table 5.1).
Mechanisms of Renal Release of Renin by Electrical Stimulation of the Brainstem in the Cat (1974)

Electrical stimulation of the dorsolateral pons for 5-minute periods in anesthetized cats produced a rise in blood pressure of 40%, a reduction in renal blood flow of 28%, and an increase in the rate of renin release (the product of renal plasma flow and the venoarterial difference of plasma renin activity) of more than 100% in intact kidneys. Comparison of an intact kidney with the contralateral denervated one showed that denervation abolished the decrease in renal blood flow and the increase in renin release induced by pontine stimulation. Infusion of phenoxybenzamine into an otherwise intact kidney prevented the decrease in renal blood flow on that side, but brain-induced renin release was at least equal to that from the contralateral kidney in which the vasomotor response remained unchanged. Treatment of the animal with intravenously administered propranolol (1.3-3.0 mg/kg) abolished any rise in renin release, although propranolol accentuated the reduction in renal blood flow during stimulation of the brainstem. We concluded that the increased renal release of renin induced by electrical stimulation of a pressor area of the brainstem was dependent on intact renal nerves and on mechanisms blocked by propranolol but was not dependent on changes in renal blood flow or on renal alpha receptors.
Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets (2008)

Information is presented on the calorically restricted ketogenic diet (CRKD) as an alternative therapy for brain cancer. In contrast to normal neurons and glia, which evolved to metabolize ketone bodies as an alternative fuel to glucose under energy-restricted conditions, brain tumor cells are largely glycolytic due to mitochondrial defects and have a reduced ability to metabolize ketone bodies. The CRKD is effective in managing brain tumor growth in animal models and in patients, and appears to act through antiangiogenic, anti-inflammatory, and proapoptotic mechanisms.
CCR2 Deficiency Decreases Intimal Hyperplasia After Arterial Injury (2002)

Monocyte chemoattractant protein (MCP)-1 is upregulated in atherosclerotic plaques and in the media and intima of injured arteries. CC chemokine receptor 2 (CCR2) is the only known functional receptor for MCP-1. Mice deficient in MCP-1 or CCR2 have marked reductions in atherosclerosis. This study examines the effect of CCR2 deficiency in a murine model of femoral arterial injury. Four weeks after injury, arteries from CCR2(-/-) mice showed a 61.4% reduction (P<0.01) in intimal area and a 62% reduction (P<0.05) in intima/media ratio when compared with CCR2(+/+) littermates. The response of CCR2(+/-) mice was not significantly different from that of CCR2(+/+) mice. Five days after injury, the medial proliferation index, determined by bromodeoxyuridine incorporation, was decreased by 59.8% in CCR2(-/-) mice when compared with CCR2(+/+) littermates (P<0.05). Although leukocytes rapidly adhered to the injured arterial surface, there was no significant macrophage infiltration in the arterial wall of either CCR2(-/-) or CCR2(+/+) mice 5 and 28 days after injury. These results demonstrate that CCR2 plays an important role in mediating smooth muscle cell proliferation and intimal hyperplasia in a non-hyperlipidemic model of acute arterial injury. CCR2 may thus be an important target for inhibiting the response to acute arterial injury.
Selective Stimulation of T Cell Subsets with Antibody-Cytokine Immune Complexes (2006)

Interleukin-2 (IL-2), which is a growth factor for T lymphocytes, can also sometimes be inhibitory. Thus, the proliferation of CD8+ T cells in vivo is increased after the injection of a monoclonal antibody that is specific for IL-2 (IL-2 mAb), perhaps reflecting the removal of IL-2-dependent CD4+ T regulatory cells (T regs). Instead, we show here that IL-2 mAb augments the proliferation of CD8+ cells in mice simply by increasing the biological activity of preexisting IL-2 through the formation of immune complexes. When coupled with recombinant IL-2, some IL-2/IL-2 mAb complexes cause massive (>100-fold) expansion of CD8+ cells in vivo, whereas others selectively stimulate CD4+ T regs. Thus, different cytokine-antibody complexes can be used to selectively boost or inhibit the immune response.
Iron Chelators and Therapeutic Uses (2003)

Abstract Iron is an essential cofactor in a variety of biological redox reactions; life without this metal is virtually unknown. Because of its exceptionally poor solubility in the biosphere, bacteria produce relatively low molecular weight, virtually iron(III)‐specific, ligands, siderophores, for the purpose of acquiring this transition metal. On the other hand, higher eukaryotes generate proteins to acquire and store iron. In humans, the process of iron absorption and processing is very tightly controlled. However, the lack of an efficient means of elimination can, under certain conditions, result in iron overload, which can elicit oxidative tissue damage through the Fenton reaction. Accordingly, chelating agents have been tested over the last several decades for the purpose of rendering excess iron excretable. The currently accepted therapy for global iron overload, as occurs after repeated blood transfusions, is a siderophore, desferrioxamine B (DFO), which is administered subcutaneously as its mesylate salt (Desferal). Two synthetic agents, diethylenetriamine pentaacetic acid (DTPA) and 1,2‐dimethyl‐3‐hydroxypyridin‐4‐one (Ferriprox, deferiprone, L1), have been used for the treatment of iron overload as well. Unfortunately, all three of these ligands have drawbacks. The kinetics and lack of oral bioavailability of DFO require that this compound be administered subcutaneously 12 h/day, up to 6 days/week, a regimen with which many patients find it difficult to comply. The lack of chelating specificity of DTPA restricts its use to those who cannot tolerate therapy with DFO; questions remain unanswered regarding the efficacy and toxicity profile of L1. The ongoing efforts to find a worthy successor to DFO include the use of a synthetic agent, N,N ′‐bis(2‐hydroxybenzyl)ethylenediamine‐ N,N ′‐diacetic acid (HBED), which, although it would require subcutaneous administration, is significantly more efficient than DFO. Another avenue is using siderophores (e.g., desferrithiocin, parabactin) as platforms from which to design either orally or parenterally active iron chelators. Because of the necessity of striking a balance between efficacy (i.e., sufficient iron chelation) and toxicity (i.e., excessive iron removal), drug development in the arena of iron chelation therapy presents unique challenges. However, the application of sensible drug design principles predicated on our understanding of iron metabolism, modern synthetic techniques, and the use of appropriate animal models should bring about improved therapeutic agents for the treatment of both global and focal iron overload in the years to come.