gebhart/patrepeval huggingface dataset:
Differentiation and Enrichment of Hepatocyte-Like Cells from Human Embryonic Stem Cells In Vitro and In Vivo (2007)

Human embryonic stem cells (hESC) may provide a cell source for functional hepatocytes. The aim of this study is to establish a viable human hepatocyte-like cell line from hESC that can be used for cell-based therapies. The differentiated hESC were enriched by transducing with a lentivirus vector containing the green fluorescent protein (GFP) gene driven by the alpha1-antitrypsin promoter; the GFP gene is expressed in committed hepatocyte progenitors and hepatocytes. GFP+ hESC were purified by laser microdissection and pressure catapulting. In addition, differentiated hESC that were transduced with a lentivirus triple-fusion vector were transplanted into NOD-SCID mice, and the luciferase-induced bioluminescence in the livers was evaluated by a charge-coupled device camera. GFP+ hESC expressed a large series of liver-specific genes, and expression levels of these genes were significantly improved by purifying GFP+ hESC; our results demonstrated that purified differentiated hESC express nearly physiological levels of liver-specific genes and have liver-specific functions that are comparable to those of primary human hepatocytes. The differentiated hESC survived and engrafted in mouse livers, and human liver-specific mRNA and protein species were detected in the transplanted mouse liver and serum at 3 weeks after transplantation. This is the first time that human albumin generated by hESC-derived hepatocytes was detected in the serum of an animal model. This also represents the first successful transplantation of differentiated hESC in an animal liver and the first bioluminescence imaging of hESC in the liver. This study is an initial step in establishing a viable hepatocyte-like cell line from hESC. Disclosure of potential conflicts of interest is found at the end of this article.
The Discovery of Rolling Circle Amplification and Rolling Circle Transcription (2016)

Nucleic acid amplification is a hugely important technology for biology and medicine. While the polymerase chain reaction (PCR) has been highly useful and effective, its reliance on heating and cooling cycles places some constraints on its utility. For example, the heating step of PCR can destroy biological molecules under investigation and heat/cool cycles are not applicable in living systems. Thus, isothermal approaches to DNA and RNA amplification are under widespread study. Perhaps the simplest of these are the rolling circle approaches, including rolling circle amplification (RCA) and rolling circle transcription (RCT). In this strategy, a very small circular oligonucleotide (e.g., 25-100 nucleotides in length) acts as a template for a DNA or an RNA polymerase, producing long repeating product strands that serve as amplified copies of the circle sequence. Here we describe the early developments and studies involving circular oligonucleotides that ultimately led to the burgeoning rolling circle technologies currently under development. This Account starts with our studies on the design of circular oligonucleotides as novel DNA- and RNA-binding motifs. We describe how we developed chemical and biochemical strategies for synthesis of well-defined circular oligonucleotides having defined sequence and open (unpaired) structure, and we outline the unusual ways in which circular DNAs can interact with other nucleic acids. We proceed next to the discovery of DNA and RNA polymerase activity on these very small cyclic DNAs. DNA polymerase "rolling circle" activities were discovered concurrently in our laboratory and that of Andrew Fire. We describe the surprising efficiency of this process even on shockingly small circular DNAs, producing repeating DNAs thousands of nucleotides in length. RNA polymerase activity on circular oligonucleotides was first documented in our group in 1995; especially surprising in this case was the finding that the process occurs efficiently even without promoter sequences in the circle. We describe how one can encode cleavable sites into the product DNAs and RNAs from RCA/RCT, which can then be resolved into large quantities of almost pure oligonucleotides. Our Account then proceeds with a summary describing a broad variety of tools and methods built in many laboratories around the rolling circle concept. Among the important developments are the discovery of highly efficient DNA polymerases for RCA; the invention of exponential ("hyperbranched") RCA amplification made possible by use of a second primer; the development of the "padlock" process for detection of nucleic acids and proteins coupled with RCA; the use of circular oligonucleotides as vectors in cells to encode biologically active RNAs via RCT; and the use of small DNA circles to encode and extend human telomeres. Finally, we finish with some ideas about where the field may go in the future.
Three dimensional transparent structure segmentation and multiple 3D motion estimation from monocular perspective image sequences (2002)

A three dimensional scene can be segmented using different cues, such as boundaries, texture, motion, discontinuities of the optical flow, stereo, models for structure, etc. We investigate segmentation based upon one of these cues, namely three dimensional motion. If the scene contain transparent objects, the two dimensional (local) cues are inconsistent, since neighboring points with similar optical flow can correspond to different objects. We present a method for performing three dimensional motion-based segmentation of (possibly) transparent scenes together with recursive estimation of the motion of each independent rigid object from monocular perspective images. Our algorithm is based on a recently proposed method for rigid motion reconstruction and a validation test which allows us to initialize the scheme and detect outliers during the motion estimation procedure. The scheme is tested on challenging real and synthetic image sequences. Segmentation is performed for the Ullmann's experiment of two transparent cylinders rotating about the same axis in opposite directions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Extended-cycle elutriation to adjust T-cell content in HLA-disparate bone marrow transplantation (1993)

We report the development of a double-cycle elutriation (DCE) technique separating 3 or greater logs of T cells from a stem-cell-enriched marrow fraction and the results of phase I T-cell depletion studies with HLA-disparate related bone marrow transplantation (BMT) donors in two patient groups. In group 1, 10 patients with refractory hematopoietic malignancies received combination chemotherapy, total body irradiation (TBI), and immunosuppression (pre- and post-BMT), and hematopoietic rescue with a marrow transplant, depleted of T cells by elutriation. Potentially to promote engraftment and a graft-versus-leukemia (GVL) effect, 0.5 to 0.75 x 10(5) T cells/kg were added back. All 10 patients engrafted. Five patients developed acute graft-versus-host disease (GVHD; four grade II, one grade III) and two subsequently developed chronic GVHD. Two patients have relapsed (median follow-up, 206 days; range, 46 to 1,035). Four patients died of BMT-related complications (three of infection, one of veno-occlusive disease [VOD]). Four patient are disease-free survivors (median follow-up, 960 days; range, 670 to 1,035). Group 2 included five infants, four with congenital lymphohematopoietic deficiencies and one with refractory acute lymphocytic leukemia (ALL). In these infants, busulfan and increased cyclophosphamide were substituted for TBI. Only the ALL patient received added T cells. Three patients engrafted: one has stable mixed chimerism, one relapsed with ALL, and one rejected the marrow. One patient had primary autologous recovery, while another failed to engraft. None developed GVHD. We conclude that, in this setting of HLA-disparate BMT with post-BMT antithymocyte globulin (ATG) and corticosteroids, DCE significantly depletes T cells from the marrow and that a defined number of T cells can be added without the occurrence of severe GVHD.
Muscle regeneration through myostatin inhibition (2005)

Multiple approaches to inhibiting myostatin are suggested by the recent elucidation of its signaling pathway. An inhibitor of myostatin may be the first drug specifically designed to enhance muscle growth and regeneration.
Enhanced predictive zonal search for single and multiple frame motion estimation (2002)

Motion Estimation (ME) for video coding has taken an entirely different direction with the emergence of zonal algorithms. These algorithms made it possible to significantly reduce, if not almost eliminate, the tremendous computational overhead of motion estimation that was incurred in a video encoding system, while having little if any loss in quality. In this paper we further improve on these algorithms with the introduction of the Enhanced Predictive Zonal Search Algorithm (EPZS). By considering an additional set of predictors, improving the thresholding process, and simplifying the search pattern employed by these algorithms, we not only manage in achieving better output quality, but also reduce complexity of the motion estimation process even further. Our algorithm was compared with the algorithms accepted in the Optimization Model 1.0 of MPEG-4, and our simulations prove its outright superiority versus the existing algorithms. Furthermore we present a 3-Dimensional implementation of EPZS, which can be easily applied in the case of multiple frame motion estimation (ITU H.263++ and H.26L).
InvasiveSalmonellaInfections in the United States, FoodNet, 1996–1999: Incidence, Serotype Distribution, and Outcome (2004)

Invasive Salmonella infections are severe and can be life threatening. We analyzed population-based data collected during 1996-1999 by the Foodborne Diseases Active Surveillance Network (FoodNet), to determine the incidences, infecting serotypes, and outcomes of invasive Salmonella infection. We found that the mean annual incidence of invasive salmonellosis was 0.9 cases/100,000 population and was highest among infants (7.8 cases/100,000). The incidence was higher among men than women (1.2 vs. 0.7 cases/100,000; P<.001) and higher among blacks, Asians, and Hispanics than among whites (2.5, 2.0, and 1.3 cases/100,000 population, respectively, vs. 0.4 cases/100,000; all P<.001). Seventy-four percent of cases were caused by 8 Salmonella serotypes: Typhimurium, Typhi, Enteritidis, Heidelberg, Dublin, Paratyphi A, Choleraesuis, and Schwarzengrund. Of 540 persons with invasive infection, 386 (71%) were hospitalized and 29 (5%) died; 13 (45%) of the deaths were among persons aged > or =60 years. Invasive Salmonella infections are a substantial health problem in the United States and contribute to hospitalizations and deaths.
In Vitro Methods for Assessing Human Hepatic Drug Metabolism: Their use in Drug Development (1993)

(1993). In Vitro Methods for Assessing Human Hepatic Drug Metabolism: Their use in Drug Development. Drug Metabolism Reviews: Vol. 25, No. 4, pp. 453-484.
Assessing tissue viability with MR diffusion and perfusion imaging. (2003)

Differences among mean ratios of three regions investigated were greatest for the rCBF ratio. The rCBF ratio may be the most useful parameter in differentiating viable tissue that is likely to infarct without intervention, from tissue that will survive despite hypoperfusion. ADC, DW intensity, FA, and rCBV ratios may provide adjunctive information.
Influence of Membrane-Active Peptides on Lipospermine/DNA Complex Mediated Gene Transfer (1997)

To explore whether endosomal release presents a major barrier to lipospermine-mediated gene delivery, acidic membrane-active peptides derived from influenza virus or artificial sequences were incorporated into DNA/dioctadecylamidoglycylspermine (= Transfectam) complexes. Depending on the cell line used, gene expression levels are approximately 3-30-fold higher than those obtained by applying DNA complexed to optimal amounts of Transfectam alone. In addition, gene transfer efficiency of DNA complexes with lower amounts of Transfectam (1.5-2 charge equiv) is increased by a factor of up to 1000 by peptides INF6 (influenza virus derived sequence) and INF10 (artificial sequence). The helper lipids 1,2-dioleoylphosphatidylethanolamine, egg phosphatidylethanolamine, and 1,2-dioleoyl-racglycerol also can enhance the gene transfer. Thus, endosomal escape seems to be only a moderate barrier for optimized, positively charged DNA/Transfectam complexes, but a substantial bottleneck for less positively charged complexes.
CNTO 328, a monoclonal antibody to IL‐6, inhibits human tumor‐induced cachexia in nude mice (2004)

IL-6 is a multifunctional cytokine implicated in several cancers. IL-6 is a growth factor for certain tumors and contributes to drug resistance, cachexia and bone resorption. Cachexia is characterized by progressive weight loss and depletion of host reserves of adipose tissue and skeletal muscle. We have developed CNTO 328 (cCLB8), a human-mouse chimeric MAb to IL-6 (K(d) approx. 10(-12) M) that inhibits IL-6 function. A phase I study with CNTO 328 in multiple myeloma patients demonstrated that the antibody was safe and had a circulating half-life of approximately 17 days. Since IL-6 is implicated in cachexia, we hypothesized that CNTO 328 could inhibit tumor-induced cachexia. We used 2 human tumor-induced cachexia models in nude mice. In the first model, human melanoma cells were inoculated in female nude mice. Control treated animals lost 19% (+/-7.7%) body weight from day 0 to day 31, whereas CNTO 328 (10 mg/kg)-treated animals lost only 1.5% (+/-1.3%) body weight from day 0 to day 31 (p = 0.023). In the second cachexia model, human prostate tumor cells were injected into male nude mice. By day 29, control treated animals lost 6% (+/-3.5%) body weight, whereas CNTO 328 (10 mg/kg)-treated animals gained 7% (+/-4%) body weight (p = 0.01). Since CNTO 328 blocks human IL-6 but not mouse IL-6, the data indicate that tumor cell-secreted IL-6 directly contributes to body weight loss, highlighting the potential role for CNTO 328 as an anticachectic agent.
Highly reliable 100 mW operation of broad area InGaAlp visible light laser diode (1991)

The aging characteristics of broad area InGaAlP visible light laser diodes have been investigated. Asymmetric coatings and a highly p-doped cladding layer were employed. Highly reliable operation, as high as 100 mW for more than 2000 h has been realised at 15°C.
Correlation between circulating CD27high plasma cells and disease activity in patients with systemic lupus erythematosus (2003)

Flow cytometric monitoring of B cell subsets in the peripheral blood provides new insights into abnormalities of B cell function in SLE and may also be a diagnostically valuable option for monitoring the activity of this autoimmune disease.
A novel anti‐inflammatory peptide from human lipocortin 5 (1991)

1. A novel anti-inflammatory peptide (residues 204-212) of human recombinant lipocortin 5 (hrLC5) found on the high similarity region with uteroglobin is described. 2. Peptide 204-212 dose-dependently inhibited the contractions of rat isolated stomach strips elicited by porcine pancreatic phospholipase A2 (PLA2). Contractions caused by arachidonic acid (AA), prostaglandin E2 (PGE2) and 5-hydroxytryptamine were not affected. No direct enzyme inhibition was observed in a radiochemical assay. 3. PGE2 release by both human fibroblasts and rat macrophages was reduced by peptide 204-212 in a dose-dependent manner. 4. The development of carrageenin-induced oedema in rats was significantly inhibited by the local administration of peptide 204-212. 5. The pattern and potency of the biological effects of peptide 204-212 are similar to those of antiflammin 2, a lipocortin 1-derived peptide. 6. It is suggested that peptide 204-212 may represent the active site responsible for the anti-inflammatory properties of lipocortin 5.
A Basis for Analyzing Test-Retest Reliability (1945)

Three sources of variation in experimental results for a test are distinguished: trials, persons, and items. Unreliability is defined only in terms of variation over trials. This definition leads to a more complete analysis than does the conventional one; Spearman's contention is verified that the conventional approach—which was formulated by Yule—introduces unnecessary hypotheses. It is emphasized that at least two trials are necessary to estimate the reliability coefficient. This paper is devoted largely to developing lower bounds to the reliability coefficient that can be computed from but a single trial ; these avoid the experimental difficulties of making two independent trials. Six different lower bounds are established, appropriate for different situations. Some of the bounds are easier to compute than are conventional formulas, and all the bounds assume less than do conventional formulas. The terminology used is that of psychological and sociological testing, but the discussion actually provides a general analysis of the reliability of the sum of n variables.
Simultaneous Immunohistochemical Detection of Tumor Cells in Lymph Nodes and Bone Marrow Aspirates in Breast Cancer and Its Correlation With Other Prognostic Factors (2001)

OTCs detected by simultaneous immunohistochemical analysis of axillary lymph nodes and bone marrow demonstrate independent metastatic pathways. Although OTCs were significantly more frequent in patients with other unfavorable prognostic factors, they were confirmed as an independent prognostic factor for pT1-2N0M0, R0 breast cancer patients.
Monoclonal Antibody Therapy in Lymphoid Malignancies (2000)

The concept of targeted therapy for patients with advanced cancer has intrigued researchers for many years. The lymphoid malignancies are particularly good candidates for this therapeutic approach, due to the identification of multiple lymphocyte-specific antigens. The recent introduction of rituximab marks the beginning of a new era in the treatment of lymphoid malignancies. Rituximab is one of the most active single agents for patients with refractory indolent lymphoma, producing response rates of approximately 50%, with low toxicity and a brief duration of treatment. Additional uses of rituximab are being evaluated in ongoing clinical trials, and are briefly reviewed. As a first-line agent, responses of approximately 70% are produced in patients with indolent lymphoma, with minimal toxicity. A substantial percentage of patients can be successfully retreated with rituximab, with second remission durations longer than the first remission (14-16 months versus 12 months). Multiple combination regimens using rituximab plus chemotherapy are also being evaluated. Although the role of these combined approaches is incompletely defined, high complete response rates can be obtained, with a higher rate of molecular complete remission (i.e., eradication of detectable bcl-2 rearrangements) than has been observed in patients receiving chemotherapy alone. Rituximab is also being evaluated in other CD20(+) lymphoid malignancies including large-cell lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. Within the next 12 months, several additional monoclonal antibodies will be available for the treatment of lymphoid malignancies. These include the radioimmunoconjugates tositumomab (Bexxar) and ibritumomab (Zevalin), as well as Campath-1H (anti-CD52) monoclonal antibody. Early clinical data with each of these agents are also briefly reviewed.
Observation of blue phases in chiral networks (1993)

Abstract We report the first observation of cholesteric blue phases in chiral anisotropic polymer networks. In two-component mixtures of a chiral and a non-chiral diacrylate, we observed typical textures of BPI, BPII and BPIII phases. By photopolymerization of these materials at constant temperature we obtained blue phase networks. After polymerization, the blue phases were stored, which enabled us to further study them without any temperature control.
No Difference in Intestinal Strontium Absorption After an Oral or an Intravenous 1,25(OH)2D3 bolus in Normal Subjects (1999)

It has been suggested that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) stimulates intestinal calcium absorption less via the intravenous (iv) than the oral route, because the first avoids direct contact of the drug with the enterocytes. However, no study has addressed the issue directly. This investigation was designed to measure the effect of a single oral or iv dose of 1,25(OH)2D3 on calcium absorption, using stable strontium (Sr) as a surrogate for calcium, and measuring the Sr fractional absorbed dose (FAD%) over 240 minutes after Sr administration. In 10 healthy volunteers, five tests were performed in a cross-over design, with a wash-out period between two consecutive tests: Sr absorption without 1,25(OH)2D3 (test A); Sr absorption immediately after either oral (test B) or iv (test C) 1,25(OH)2D3 (1.5 microg/m2 of body surface area [BSA]); Sr absorption (24 hr after either oral (test D) or iv (test E) 1, 25(OH)2D3 (1.5 microg/m2 BSA). The concurrent administration of 1, 25(OH)2D3 and Sr (tests B and C) did not significantly change the area under the Sr FAD%-time curve with respect to test A (test A: 4090 +/- 345; test B: 4510 +/- 345; test C: 4210 +/- 345), whereas Sr absorption was significantly increased (p < 0.001) when Sr was given 24 hr after either oral or iv 1,25(OH)2D3 (test D: 5710 +/- 345; test E: 5510 +/- 345). It was concluded that 1,25(OH)2D3 is likely to influence calcium absorption significantly only via its genomic effect, independent of its administration route.
Selected Arylpiperazines Are Capable of Reversing Multidrug Resistance in Escherichia coli Overexpressing RND Efflux Pumps (2005)

Several arylpiperazines capable of reversing multidrug resistance (MDR) in Escherichia coli overexpressing acrAB and acrEF but not in pump-deficient mutant strains were identified. 1-(1-Naphthylmethyl)-piperazine, one of the more active compounds, enhanced susceptibility to fluoroquinolones and other agents and increased the intracellular concentration of levofloxacin and ethidium bromide, suggesting efflux pump inhibition as the mechanism of MDR reversal.
A MATHEMATICAL THEORY OF ADAPTIVE CONTROL PROCESSES (1959)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Effects of Verapamil on Spinal Anesthesia with Local Anesthetics (1995)

The primary mode of action of local anesthetics is through sodium channel and axonal conduction blockade.Local anesthetics also have extensive effects on presynaptic calcium channels that must function to stimulate the release of neurotransmitters. Thus, interference with calcium channel conductance may enhance spinal anesthesia with local anesthetics. The present study was designed to investigate the effects of the intrathecal calcium channel blocker, verapamil, on the spinal anesthesia from lidocaine and tetracaine. Male Sprague-Dawley rats were chronically implanted with lumbar intrathecal catheters. Tail-flick (TF) and mechanical paw pressure (MPP) tests were used to assess thermal and mechanical nociceptive threshold, respectively. Motor function was assessed using a modified Langerman's scale. Intrathecal lidocaine or tetracaine alone showed the prolongation of TF latency, the increase of MPP threshold, and the increase in motor function scale in a time- and dose-dependent manner. Although intrathecal verapamil alone demonstrated neither sensory nor motor block at the doses used (50-200 micro gram), the combination of lidocaine (20, 50, 100, or 200 micro gram) or tetracaine (10, 20, 50, or 100 micro gram) and verapamil (50 micro gram) produced the more potent and prolonged antinociception and motor block when compared with local anesthetics alone. We interpreted these results to indicate that the intrathecal calcium channel blocker, verapamil, potentiates spinal anesthesia with local anesthetics. (Anesth Analg 1995;80:444-8)