gebhart/patrepeval huggingface dataset:
Neonatal VH, D, and JH gene usage in rabbit B lineage cells. (1994)

The neonatal antibody repertoire in both mouse and humans differs from that of the adult repertoire in that the neonatal repertoire uses a limited set of JH-proximal VH genes but the adult repertoires use many different VH genes. Rabbits are unusual in that adults use only three or four VH genes, with approximately 80% of the B cells using VH1, the 3'-most VH gene. To investigate whether the repertoire of neonatal rabbits differs from that of adults, we analyzed VH, D, and JH gene usage in B cells of neonatal rabbits. A total of 68 rearranged VDJ genes was cloned from mRNA and genomic DNA isolated from lymphoid tissues of newborn to 10-day-old rabbits. We found that 74% of the VDJ gene rearrangements utilized VH1 and 15% utilized the genes that we designated VHx or VHy. From the remaining VDJ genes we identified seven novel VH genes, one, VHz, which was found in mRNA. We conclude that the repertoire of utilized VH genes in neonates is limited and is similar to that of adult rabbits. We also found the D1, D2a, D2b, and JH4 gene segments preferentially rearranged. We suggest that the preferential usage of VH, D, and JH gene segments in VDJ genes is caused by preferential rearrangement rather than by selective expansion of B cells that utilize the gene segments.
A 16384-bit high-density CCD memory (1976)

A 16384-bit charge-coupled device (CCD) memory has been developed for mass storage memory system application where moderate latency, high data rate and low system cost are required. The chip measures only 3.45/spl times/4.29 mm/SUP 2/ (136/spl times/169 mil/SUP 2/), fits a standard 16-pin package, and is organized as four separate shift registers of 4096 bits, each with its own data input and data output terminals. A two-level polysilicon gate n-channel process was used for device fabrication. A condensed serial-parallel-serial (CSPS) structure was found to provide the highest packing density. Only two external clocks are required driving capacitances of 60 pF each at one-half the data transfer rate. Operations at data rates of 100 kHz to 10 MHz have been demonstrated experimentally, the on-chip power dissipation at 10 MHz being less than 20 /spl mu/W/bit.
A Highly Efficient Recombineering-Based Method for Generating Conditional Knockout Mutations (2003)

Phage-based Escherichia coli homologous recombination systems have recently been developed that now make it possible to subclone or modify DNA cloned into plasmids, BACs, or PACs without the need for restriction enzymes or DNA ligases. This new form of chromosome engineering, termed recombineering, has many different uses for functional genomic studies. Here we describe a new recombineering-based method for generating conditional mouse knockout (cko) mutations. This method uses homologous recombination mediated by the lambda phage Red proteins, to subclone DNA from BACs into high-copy plasmids by gap repair, and together with Cre or Flpe recombinases, to introduce loxP or FRT sites into the subcloned DNA. Unlike other methods that use short 45-55-bp regions of homology for recombineering, our method uses much longer regions of homology. We also make use of several new E. coli strains, in which the proteins required for recombination are expressed from a defective temperature-sensitive lambda prophage, and the Cre or Flpe recombinases from an arabinose-inducible promoter. We also describe two new Neo selection cassettes that work well in both E. coli and mouse ES cells. Our method is fast, efficient, and reliable and makes it possible to generate cko-targeting vectors in less than 2 wk. This method should also facilitate the generation of knock-in mutations and transgene constructs, as well as expedite the analysis of regulatory elements and functional domains in or near genes.
An immunohistochemical and clinicopathological study of gastrointestinal stromal tumors (1999)

Immunohistochemical and clinicopathological features of 58 gastrointestinal stromal tumors (GIST) were studied. One occurred in the esophagus, 41 in the stomach, nine in the small intestine, and seven in the large intestine. By using indirect immunoperoxidase staining for Cajal cell markers (c-kit protein and CD34), smooth muscle markers (alpha-smooth muscle actin, desmin, heavy caldesmon and calponin) and Schwann cell markers (S-100 protein and Leu 7), GIST were classified into five groups, such as Cajal cell type (n = 9), myogenic type (n = 5), Schwann cell type (n = 2), mixed cell type (n = 40) and undifferentiated type (n = 2). c-kit Protein (42/58; 72%) and CD34 (45/58; 78%) were commonly and diffusely expressed in GIST. Novel smooth muscle markers, caldesmon (29/58; 50%) and calponin (18/58; 31%), were useful in detecting myogenic characters of GIST. S-100 protein was expressed in 16 (28%) tumors, two of which were also reactive with Leu 7 (CD57). Three small bowel tumors with skeinoid fibers expressed the Cajal cell markers, and were categorizable in GIST. Clinicopathological analyses using aggressive (n = 21) and non-aggressive (n = 21) GIST indicated that the malignant potential was correlated with the intestinal location, large tumor size, high cellularity, necrosis, solid (non-interlacing bundled) pattern of growth, negativity of c-kit protein and/or CD34, high mitotic count, and high MIB-1 labeling.
Compression of palettized images with progressive coding of the color information (2000)

This paper introduces a new compression method for palettized images, which supports progressive refinement of the color information in contrast to the resolution refinement used in standard methods like interlaced GIF. Such, fine image details can be recognized after decoding only a small part of the compressed image data. Achieved compression ratios are comparable to those of interlaced GIF or PNG. The method combines color map sorting with bitplane by bitplane prediction and Golomb coding of the pixel field.
TRIBUTE: A Phase III Trial of Erlotinib Hydrochloride (OSI-774) Combined With Carboplatin and Paclitaxel Chemotherapy in Advanced Non–Small-Cell Lung Cancer (2005)

Erlotinib with concurrent carboplatin and paclitaxel did not confer a survival advantage over carboplatin and paclitaxel alone in patients with previously untreated advanced NSCLC. Never smokers treated with erlotinib and chemotherapy seemed to experience an improvement in survival and will undergo further investigation in future randomized trials.
Thiophene systems. 9. Thienopyrimidinedione derivatives as potential antihypertensive agents (1988)

A series of thieno[3,4-d]-, thieno[3,2-d]-, and thieno[2,3-d]pyrimidine-2,4-diones with (phenylpiperazinyl)alkyl substitution at N-3 have been synthesized and evaluated for antihypertensive effects in spontaneously hypertensive rats (SHR). These 49 compounds were compared to the vasodilator standards prazosin and the isosteric quinazoline-2,4-dione SGB 1534. Substitution at the 2-, 3-, or 4-position of the phenyl ring was examined, with that at the 2-position more potent than 4-substitution while the isomeric 3-substituted compounds were least potent. Neither alkylation nor acylation at the N-1 position improved the antihypertensive effects as compared to hydrogen. The three thienopyrimidine-2,4-diones (3-5) that contain a [(2-methoxyphenyl)piperazinyl]ethyl moiety at N-3 and hydrogen at N-1 were found to be potent oral antihypertensive agents in the SHR with doses (mg/kg, po) for reducing systolic blood pressure (SBP) by 50 mmHg (ED-50SBP) of 0.21, 0.19, and 1.0, respectively. The compounds 1-5 were further evaluated for alpha blocking potency by measuring the iv doses necessary to antagonize the phenylephrine pressor response by 50% (ED50) in the SHR. The ED50 values (micrograms/kg) are 10.4, 3.3, 1.7, 2.1, and 15.4, respectively. These results clearly show that all three thiophene systems have potent activity as antihypertensive agents and that 3 and 4 are more potent than 1 or 2 as alpha 1-antagonists in vivo.
Regulation of Photosystem I Reaction Center Genes in Synechocystis sp. Strain PCC 6803 during Light Acclimation (2005)

Cyanobacteria acclimate to changes in incident light by adjusting photosystem stoichiometry through regulation of PSI accumulation. To gain a deeper insight into this control mechanism in Synechocystis sp. strain PCC 6803, we studied the expression and regulation of the psaAB operon, encoding the reaction center proteins of PSI, during the initial stage of acclimation to changes in the intensity and quality of light. The psaAB operon was transcribed as a dicistronic transcript, which was processed into smaller, putatively monocistronic psaA and psaB transcript species. Dark treatment of the cells inhibited the psaAB transcription, whereas re-illumination of dark-adapted cells reactivated the transcription slowly in a process requiring de novo protein synthesis. Transfer of cells from white to orange light, favoring excitation of PSII, stimulated the psaAB transcription, whereas far-red light, primarily exciting PSI, down-regulated the transcription of the psaAB operon. These results, together with down-regulation of psaAB transcription upon the addition of electron transport inhibitors under constant white light illumination, suggested that the photosynthetic redox poise affects the psaAB transcription activity in the light. Pulse-labeling experiments demonstrated that light-induced modulations in the translation rate of the PsaA protein closely parallel the transcription rate of the psaAB operon, indicating that transcriptional regulation plays the major role in determining the content of PSI reaction center proteins and, thereby, PSI complexes, during light acclimation. The scantiness of PsaA translation in darkness despite the abundance of psaA transcripts demonstrated that the comprehensive regulation of PSI accumulation also involves regulation at the level of translation.
White blood cell differentiation using a solid state flow cytometer (1993)

A flow cytometer using a solid state light source and detector was designed and built. For illumination of the sample stream two types of diode lasers (670 nm and 780 nm) were tested in a set-up designed to differentiate human leukocytes by means of light scattering. The detector is an avalanche photodiode, which was used to detect the weak scattered light in the orthogonal direction. The new flow cytometer set-up is very small, relatively cheap and yields similar results as a standard flow cytometer set-up using a helium-neon laser and photomultipliers.
Mementos (2011)

Transiently powered computing devices such as RFID tags, kinetic energy harvesters, and smart cards typically rely on programs that complete a task under tight time constraints before energy starvation leads to complete loss of volatile memory. Mementos is a software system that transforms general-purpose programs into interruptible computations that are protected from frequent power losses by automatic, energy-aware state checkpointing. Mementos comprises a collection of optimization passes for the LLVM compiler infrastructure and a linkable library that exercises hardware support for energy measurement while managing state checkpoints stored in nonvolatile memory. We evaluate Mementos against diverse test cases in a trace-driven simulator of transiently powered RFID-scale devices. Although Mementos's energy checks increase run time when energy is plentiful, they allow Mementos to safely suspend execution when energy dwindles, effectively spreading computation across zero or more power failures. This paper's contributions are: a study of the runtime environment for programs on RFID-scale devices; an energy-aware state checkpointing system for these devices that is implemented for the MSP430 family of microcontrollers; and a trace-driven simulator of transiently powered RFID-scale devices.
Maturation decreases responsiveness of human bone marrow B lineage cells to stromal-derived factor 1 (SDF-1) (1999)

We compared the chemotactic responsiveness of different subsets of human B lineage cells to stromal derived factor-1 (SDF-1). High percentages (30-40% of input) of purified bone marrow progenitors including non-B lineage progenitors, pro-B cells, and pre-B cells migrated to SDF-1alpha, demonstrating that SDF-1 is an efficacious chemoattractant of these cells. Pro-B cells responded optimally to a lower concentration of SDF-1 than other subsets, demonstrating that SDF-1 is a more potent chemoattractant of this subset. A lower percentage (10-15% of input) of mature B lymphocytes migrated to SDF-1alpha than pro-B cells, demonstrating that responsiveness of B lineage cells to SDF-1 decreases during differentiation. Inhibition by anti-CXCR4 mAb demonstrated that migration of B lineage cells to SDF-1 was completely dependent on CXC chemokine receptor-4 (CXCR4). Mature B cells expressed higher levels of CXCR4 receptors than uncommitted progenitors and pro-B cells, despite differences in responsiveness to SDF-1. CXCR4 receptors expressed by unresponsive and SDF-1-responsive B cells bound SDF-1alpha with similar affinities (K(D) = 1.7-3.3 x 10(-9) M). Therefore, elements downstream from CXCR4 appear to regulate responsiveness of B cells to SDF-1. We speculate that SDF-1 and CXCR4 direct migration of progenitor cells in microenvironments that promote B lymphopoiesis.
Claudins 6, 9, and 13 are developmentally expressed renal tight junction proteins (2006)

The adult proximal tubule is a low-resistance epithelium where there are high rates of both active transcellular and passive paracellular NaCl transport. We have previously demonstrated that the neonatal rabbit and rat proximal tubule have substantively different passive paracellular transport properties than the adult proximal tubule, which results in a maturational change in the paracellular passive flux of ions. Neonatal proximal tubules have a higher P(Na)/P(Cl) ratio and lower chloride and bicarbonate permeabilities than adult proximal tubules. Claudins are a large family of proteins which are the gate keepers of the paracellular pathway, and claudin isoform expression determines the permeability characteristics of the paracellular pathway. Previous studies have shown that claudins 1, 2, 3, 4, 5, 7, 8, 10, 11, 12, 15, and 16 are expressed in the adult mouse kidney. To determine whether there are developmental claudin isoforms, we compared the claudin isoforms present in the neonatal and adult kidney using RT-PCR to detect mRNA of claudin isoforms. Claudin 6, claudin 9, and claudin 13 were either not expressed or barely detectable in the adult mouse kidney using traditional PCR, but were expressed in the neonatal mouse kidney. Using real-time RT-PCR, we were able to detect a low level of claudin 6 mRNA expression in the adult kidney compared with the neonate, but claudin 9 and claudin 13 were only detected in the neonatal kidney. There was the same maturational decrease in these claudin proteins with Western blot analysis. Immunohistochemistry showed high levels of expression of claudin 6 in neonatal proximal tubules, thick ascending limb, distal convoluted tubules, and collecting ducts in a paracellular distribution but there was no expression of claudin 6 in the adult kidney. Using real-time RT-PCR claudin 6 and 9 mRNA were present in 1-day-old proximal convoluted tubules and were virtually undetectable in proximal convoluted tubules from adults. Claudin 13 was not detectable in neonatal or adult proximal convoluted tubules. In summary, we have identified developmentally expressed claudin isoforms, claudin 6, claudin 9, and claudin 13. These paracellular proteins may play a role in the maturational changes in paracellular permeability.
Infusion of Cytotoxic T Cells for the Prevention and Treatment of Epstein-Barr Virus–Induced Lymphoma in Allogeneic Transplant Recipients (1998)

Epstein-Barr virus (EBV) causes potentially lethal immunoblastic lymphoma in up to 25% of children receiving bone marrow transplants from unrelated or HLA-mismatched donors. Because this complication appears to stem from a deficiency of EBV-specific cytotoxic T cells, we assessed the safety and efficacy of donor-derived polyclonal (CD4(+) and CD8(+)) T-cell lines as immunoprophylaxis and treatment for EBV-related lymphoma. Thirty-nine patients considered to be at high risk for EBV-induced lymphoma each received 2 to 4 intravenous infusions of donor-derived EBV-specific T lymphocytes, after they had received T-cell-depleted bone marrow from HLA-matched unrelated donors (n = 33) or mismatched family members (n = 6). The immunologic effects of this therapy were monitored during and after the infusions. Infused cells were identified by detection of the neo marker gene. EBV-specific T cells bearing the neo marker were identified in all but 1 of the patients. Serial analysis of DNA detected the marker gene for as long as 18 weeks in unmanipulated peripheral blood mononuclear cells and for as long as 38 months in regenerated lines of EBV-specific cytotoxic T cells. Six patients (15.5%) had greatly increased amounts of EBV-DNA on study entry (>2, 000 genome copies/10(6) mononuclear cells), indicating uncontrolled EBV replication, a complication that has had a high correlation with subsequent development of overt lymphoma. All of these patients showed 2 to 4 log decreases in viral DNA levels within 2 to 3 weeks after infusion and none developed lymphoma, confirming the antiviral activity of the donor-derived cells. There were no toxic effects that could be attributed to prophylactic T-cell therapy. Two additional patients who did not receive prophylaxis and developed overt immunoblastic lymphoma responded fully to T-cell infusion. Polyclonal donor-derived T-cell lines specific for EBV proteins can thus be used safely to prevent EBV-related immunoblastic lymphoma after allogeneic marrow transplantation and may also be effective in the treatment of established disease.
Idiotypic protein‐pulsed dendritic cell vaccination in multiple myeloma (1999)

Idiotypic protein (Id) produced by myeloma cells is clone-specific and may be a suitable tumor-specific antigen for immune targeting. Advances in dendritic cell (DC) technology suggest the opportunity for using this potent antigen presentation system to deliver myeloma Id to the autologous host to elicit anti-tumor immune responses. We have generated DCs from adherent PBMCs from 6 patients with IgG myeloma. These cells were pulsed with the autologous Id and a control vaccine, KLH, and re-infused i.v. back to the patients on 3 separate occasions. Immune responses to KLH and autologous Id were measured and clinical responses monitored. We found that all treatments were well tolerated without any side effects. All patients developed both B- and T-cell responses to KLH, suggesting the integrity of the host immune system to mount immune responses to an antigen delivered using our vaccination strategy. Id-specific responses were also observed. PBMC proliferative responses to Id were observed in 5 of the 6 patients following treatment. In 2 patients, the responses were associated with the production of IFN-γ. There were also increases in cytotoxic T-cell precursor frequencies for Id-pulsed autologous targets in 3 patients. B-cell responses characterized by the production of anti-Id IgM occurred in 3 and anti-Id IgG in 4 of the 5 evaluated patients. In 1 patient, a modest (25%) but consistent drop in the serum Id level was observed. Id-pulsed DC vaccination can therefore elicit potentially useful anti-myeloma immune responses in patients with multiple myeloma. Int. J. Cancer 83:215–222, 1999. © 1999 Wiley-Liss, Inc.
Lck Dephosphorylation at Tyr-394 and Inhibition of T Cell Antigen Receptor Signaling by Yersinia Phosphatase YopH (2004)

A key virulence factor for Yersinia pestis, the etiologic agent of plague, is the tyrosine phosphatase YopH, which the bacterium injects into host cells. We report that treatment of human T lymphocytes with a recombinant membrane-permeable YopH resulted in severe reduction in intracellular tyrosine phosphorylation and inhibition of T cell activation. The primary signal transducer for the T cell antigen receptor, the Lck tyrosine kinase, was specifically precipitated by a substrate-trapping YopH mutant, and Lck was dephosphorylated at its positive regulatory site, Tyr-394, in cells containing active YopH. By turning off Lck, YopH blocks T cell antigen receptor signaling at its very first step, effectively preventing the development of a protective immune response against this lethal bacterium.
Lyophilized phytosomal nanocarriers as platforms for enhanced diosmin delivery: optimization and ex vivo permeation (2013)

Diosmin (DSN) is an outstanding phlebotonic flavonoid with a tolerable potential for the treatment of colon and hepatocellular carcinoma. Being highly insoluble, DSN bioavailability suffers from high inter-subject variation due to variable degrees of permeation. This work endeavored to develop novel DSN loaded phytosomes in order to improve drug dissolution and intestinal permeability. Three preparation methods (solvent evaporation, salting out, and lyophilization) were compared. Nanocarrier optimization encompassed different soybean phospholipid (SPC) types, different solvents, and different DSN:SPC molar ratios (1:1, 1:2, and 1:4). In vitro appraisal encompassed differential scanning calorimetry, infrared spectroscopy, particle size, zeta potential, polydispersity index, transmission electron microscopy, drug content, and in vitro stability. Comparative dissolution studies were performed under sink versus non-sink conditions. Ex vivo intestinal permeation studies were performed on rats utilizing noneverted sac technique and high-performance liquid chromatography analysis. The results revealed lyophilization as the optimum preparation technique using SPC and solvent mixture (Dimethyl sulphoxide:t-butylalchol) in a 1:2 ratio. Complex formation was contended by differential scanning calorimetry and infrared data. Optimal lyophilized phytosomal nanocarriers (LPNs) exhibited the lowest particle size (316 nm), adequate zeta-potential (-27 mV), and good in vitro stability. Well formed, discrete vesicles were revealed by transmission electron microscopy, drug content, and in vitro stability. Comparative dissolution studies were performed. LPNs demonstrated significant enhancement in DSN dissolution compared to crude drug, physical mixture, and generic and brand DSN products. Permeation studies revealed 80% DSN permeated from LPNs via oxygenated rat intestine compared to non-detectable amounts from suspension. In this study, LPNs (99% drug loading) could be successfully tailored for DSN with improved dissolution and permeation characteristics, which is promising for lowering the influence of exogenous factors and increasing drug delivery.
Timing of New Black Box Warnings and Withdrawals for Prescription Medications (2002)

Serious ADRs commonly emerge after Food and Drug Administration approval. The safety of new agents cannot be known with certainty until a drug has been on the market for many years.