gebhart/patrepeval huggingface dataset:
Therapy of murine leukemia with cyclophosphamide and immune Lyt-2+ cells: cytolytic T cells can mediate eradication of disseminated leukemia. (1986)

Several animal models have been developed in which the adoptive transfer of specifically immune syngeneic T cells has been shown to mediate the eradication of established tumors. In adoptive chemoimmunotherapy (ACIT) of disseminated FBL leukemia with cyclophosphamide and immune T cells, the major effector T cell has been shown to be a noncytolytic Lyt-1+2- T cell that mediates its therapeutic effect without the participation of CTL. Because studies in other models have suggested that CTL can mediate an anti-tumor effect, the efficacy of Lyt-2+ T cells rendered highly cytolytic before adoptive transfer in ACIT of disseminated FBL was examined. The results demonstrated that such CTL had a detectable but limited therapeutic effect in the treatment of FBL. Because this limited activity of transferred purified CTL might have reflected a requirement for helper T cells to produce IL 2 for promotion of the in vivo survival and proliferation of the CTL, the effect of administering IL 2 to tumor-bearing hosts after transfer of CTL was examined. A dose of IL 2 previously shown to induce in vivo proliferation of transferred T cells rendered CTL that were minimally effective alone curative in ACIT of FBL leukemia. Thus, either lymphokine-producing T cells or the lymphokines produced by these cells are necessary for the full expression of the in vivo therapeutic potential of CTL.
Genetic modification of human T lymphocytes for the treatment of hematologic malignancies (2012)

Modern chemotherapy regimens and supportive care have produced remarkable improvements in the overall survival of patients with hematologic malignancies. However, the development of targeted small molecules, monoclonal antibodies, and biological therapies that demonstrate greater efficacy and lower toxicity remains highly desirable in hematology, and oncology in general. In the context of biological therapies, T-lymphocyte based treatments have enormous potential. Donor lymphocyte infusion in patients relapsed after allogeneic hematopoietic stem cell transplant pioneered the concept that T lymphocytes can effectively control tumor growth, and this was then followed by the development of cell culture strategies to generate T lymphocytes with selective activity against tumor cells. Over the past decade, it has become clear that the adoptive transfer of ex vivo expanded antigen-specific cytotoxic T lymphocytes promotes sustained antitumor effects in patients with virus-associated lymphomas, such as Epstein-Barr virus related post-transplant lymphomas and Hodgkin's lymphomas. Because of this compelling clinical evidence and the concomitant development of methodologies for robust gene transfer to human T lymphocytes, the field has rapidly evolved, offering new opportunities to extend T-cell based therapies. This review summarizes the most recent biological and clinical developments using genetically manipulated T cells for the treatment of hematologic malignancies.
Temperature and Concentration Dependent Circular Dichroism of Mono‐ and Di‐cis Isomers of (3S,3′S)‐Astaxanthin Diacetate (1981)

Abstract The circular dichroism (CD.) spectra of all‐ trans ‐(3 S , 3′ S ) astaxanthin diacetate and its 9‐ cis , 13‐ cis , 9,9′‐di‐ cis , 9,13′‐di‐ cis , and 9,13‐di‐ cis isomers conform to the rules previously formulated for optically active carotenoids with a 4‐oxo‐β‐end ring containing an asymmetric C‐atom [1]. Thus the CD. bands of the all‐ trans and the di‐ cis isomers show the same signs whereas those of the mono‐ cis isomers have opposite signs. The CD. spectra of all the astaxanthin diacetate isomers invert sign upon cooling to −180°. The CD. spectra of the 9‐mono‐ cis and 9,9′‐di‐ cis isomers and to a lesser extent also those of the 9, 13′‐di‐ cis and 9, 13‐di‐ cis isomers are concentration dependent at −180°, with the longest wavelength band giving at the higher concentration a bisignate CD. curve under the main absorption characteristic of aggregation. This phenomenon has been observed only in isomers with a 9‐ cis linkage. It is suggested that steric hindrance prevents such aggregation taking place in the other isomers.
Quantitative analysis of Th1, Th2 and TGF-β1 cytokine expression in tumor, TIL and PBL of non-small cell lung cancer patients (1998)

For understanding the local immune response in human non-small cell lung cancer (NSCLC), we investigated both Th1 and Th2-type as well as TGF-beta1 cytokine mRNA expression in 10 fresh tumor biopsies, the corresponding tumor and short term TIL cell lines as well as patient PBMC. A methodology based on a highly sensitive quantitative RT-PCR was used. We found that IL-6 mRNA was highly expressed in all tumor biopsy samples analyzed (4 LLC, 3 ADC and 3 SCC). IL-10 mRNA was expressed in 7 of 10 biopsies whereas IL-4 mRNA expression was moderate. Analysis of type I cytokines revealed a low expression level of IL-2 mRNA, while IFNgamma and GM-CSF expression was high in the majority of the tumor lesions studied. Quantitatively, high amounts of Th2-type cytokine mRNA were detected at the tumor site with IL-6 as the predominant lymphokine. A high mRNA expression level of the immunosuppressive cytokine TGF-beta1 was observed in all NSCLC. To identify the cell types responsible for the production of TGF-beta1, IL-6, IL-10 and GM-CSF at the tumor site, tumor and TIL cell lines were derived from the corresponding biopsies. All the 3 tumor cell lines analysed were found to express high amount of TGF-beta1 but not IL-10 mRNA, 2 expressing IL-6 and GM-CSF. Five short term TIL cell lines established in the presence of IL-2 expressed high level of IL-10, IL-4 and IFNgamma but not IL-2 mRNA. Strikingly, high expression of IL-10 mRNA was also observed in all 6 patient PBMC analyzed as compared to controls. Together, our results indicate the existence of a local and peripheral Th-2-type cytokine pattern in patients bearing NSCLC.
Free synovium promotes meniscal healing: Synovium, muscle and synthetic mesh compared in dogs (1997)

We studied the effect of free synovium on the healing of tears in the avascular portion of the menisci in dogs. A longitudinal incision was made in the medial meniscus. In 35 dogs, a free graft of synovium was inserted into the tear and sutured. In 10 dogs, a free graft of quadriceps muscle was used. In 10 dogs, a Dacron mesh was inserted. In the contralateral knee, the tear was sutured without implantation as a control. 2, 4, 6, 8, and 12 weeks after the operation, the menisci were dissected. 11 of the 35 with free synovium were healed. The menisci with muscle grafts, those with Dacron mesh and those in the control group did not heal. Histology showed that tears were repaired with fibrous tissue. Microangiography showed that capillaries grew from the periphery, but they did not reach the tear.
<title>High data rate FSK via multicarrier implementations for wireless personal area networks</title> (2002)

In this paper, we propose a novel FSK scheme that enhances performance and throughput relative to traditional FSK. Specifically we propose a novel BFSK implementation where, rather than frequency f<sub>0</sub> representing bit '0' and f<sub>1</sub> representing bit '1', we transmit multiple, orthogonal, in-phase carriers around f<sub>0</sub> or f<sub>1</sub> to represent binary information. We demonstrate the high performance of this FSK system in frequency selective channels, where a simple coherent reception technique enables diversity gain (resulting in significant performance improvement relative to traditional BFSK). We also introduce the concept of dense pulse packaging (DPP) that ensures a doubling of the data rate with minimal cost in performance, by pseudo-orthogonal positioning of pulse shapes at the transmitter.
Toremifene for the Prevention of Prostate Cancer in Men With High Grade Prostatic Intraepithelial Neoplasia: Results of a Double-Blind, Placebo Controlled, Phase IIB Clinical Trial (2006)

Toremifene decreased the incidence of prostate cancer by 1 year and had a tolerability profile comparable to that of placebo in a high risk population.
Recent advances in globin research using genome‐wide association studies and gene editing (2016)

A long-sought goal in the hemoglobin field has been an improved understanding of the mechanisms that regulate the switch from fetal (HbF) to adult (HbA) hemoglobin during development. With such knowledge, the hope is that strategies for directed reactivation of HbF in adults could be devised as an approach to therapy for the β-hemoglobinopathies thalassemia and sickle cell disease. Recent genome-wide association studies (GWAS) led to identification of three loci (BCL11A, HBS1L-MYB, and the β-globin cluster itself) in which natural genetic variation is correlated with different HbF levels in populations. Here, the central role of BCL11A in control of HbF is reviewed from the perspective of how findings may be translated to gene therapy in the not-too-distant future. This summary traces the evolution of recent studies from the initial recognition of BCL11A through GWAS to identification of critical sequences in an enhancer required for its erythroid-specific expression, thereby highlighting an Achilles heel for genome editing.
Leptin and Adiponectin in the HIV Associated Metabolic Syndrome: Physiologic and Therapeutic Implications (2006)

Leptin and adiponectin represent two newly discovered adipose tissue derived hormones with important roles in energy homeostasis and insulin resistance. Their interrelations with the manifestations of the HIV associated metabolic syndrome and specific somatomorphic changes i.e. fat redistribution is reviewed. A synopsis of published studies is presented and the potential role of leptin and adiponectin is discussed. We have described an association of the HIV metabolic syndrome with a state of reduced insulin sensitivity due to adiponectin deficiency. The metabolic syndrome is also accompanied by leptin deficiency in lipoatrophic subjects and possibly by a leptin resistance state in lipohypertrophic patients. Adiponectin and / or leptin therapy in a manner similar to other leptin deficiency states may assist in the future management of such patients.
Familial Clustering of Autoimmune Disorders and Evaluation of Medical Risk Factors in Autism (1999)

Autism is an age-dependent neurologic disorder that is often associated with autoimmune disorders in the patients' relatives. To evaluate the frequency of autoimmune disorders, as well as various prenatal and postnatal events in autism, we surveyed the families of 61 autistic patients and 46 healthy controls using questionnaires. The mean number of autoimmune disorders was greater in families with autism; 46% had two or more members with autoimmune disorders. As the number of family members with autoimmune disorders increased from one to three, the risk of autism was greater, with an odds ratio that increased from 1.9 to 5.5, respectively. In mothers and first-degree relatives of autistic children, there were more autoimmune disorders (16% and 21%) as compared to controls (2% and 4%), with odds ratios of 8.8 and 6.0, respectively. The most common autoimmune disorders in both groups were type 1 diabetes, adult rheumatoid arthritis, hypothyroidism, and systemic lupus erythematosus. Forty-six percent of the autism group reported having relatives with rheumatoid diseases, as compared to 26% of the controls. Prenatal maternal urinary tract, upper respiratory, and vaginal infections; asphyxia; prematurity, and seizures were more common in the autistic group, although the differences were not significant. Thirty-nine percent of the controls, but only 11% of the autistic, group, reported allergies. An increased number of autoimmune disorders suggests that in some families with autism, immune dysfunction could interact with various environmental factors to play a role in autism pathogenesis.
On the Mechanisms for the Selective Action of Vitamin D Analogs* (1991)

A variety of analogs of 1,25-(OH)2D3 with less calcemic activity and lower receptor binding affinity than 1,25-(OH)2D3 have been developed. However, these compounds have equal or greater ability to differentiate leukemia cells and psoriatic fibroblasts and to suppress PTH synthesis and secretion. The mechanism for this selectivity has not been elucidated. Because the lower potency of ergocalciferol compared to cholecalciferol in preventing or curing rickets in chicks was associated with a lower affinity of the avian vitamin D binding protein (DBP) for vitamin D2, we tested five analogs with low calcemic activity including 22-oxa-1,25-(OH)2D3 (OCT), MC903, 1,25-(OH)2-16 ene-23-yne D3, 1,25-(OH)2-26,27 dihomo-22-ene-D3, and 1,25-(OH)2-24-trihomo-22-ene-D3 for their affinity for rat serum DBP. All analogs had a low affinity for DBP, ranging from 50-3000 times less than that of 1,25-(OH)2D3. OCT also bound with low affinity to dog and human serum DBP. We tested with OCT the possible consequences of its low affinity for serum DBP. One of the functions of DBP is to prolong the lifetime of 1,25-(OH)2D3 in circulation. Quantification of the metabolic clearance rate (MCR) of OCT in 8 normal dogs using a single bolus injection technique showed that OCT was cleared at a rate of 48.2 +/- 7.5 ml/min, approximately 6-7 times more rapidly than 1,25-(OH)2D3 (6.8 +/- 0.4 ml/min). The estimated half-life of OCT in the circulation was 2.5 +/- 0.3 h compared to 7.0 +/- 0.6; n = 7 for 1,25-(OH)2D3. As our primary interest is the potential of OCT in treating the secondary hyperparathyroidism of CRF, we also measured the MCR of OCT in 5/6 nephrectomized dogs. Uremia does not affect the rate of clearance of OCT from the circulation (MCR: 56.8 +/- 4.5; t1/2 = 2.1 +/- 0.2 n = 4). Despite its shorter half-life, OCT suppressed PTH secretion in vivo in uremic dogs. The effects of low binding to DBP on the percentage uremic dogs. The effects of low binding to DBP on the percentage of free sterol were determined using an ultrafiltration procedure. We compared the proportion of free (unbound) OCT and 1,25-(OH)2D3 in 0.1% BSA-PBS with concentrations of human serum ranging from 0-25%. The proportion of OCT in the free form was significantly higher than that of 1,25-(OH)2D3 for every serum concentration tested. The physiological relevance of a higher percentage of free OCT was tested in normal human macrophages.(ABSTRACT TRUNCATED AT 400 WORDS)
Drop zones (1998)

article Free Access Share on Drop zones: an extension to LiveDoc Authors: Thomas Bonura View Profile , James R. Miller View Profile Authors Info & Claims ACM SIGCHI BulletinVolume 30Issue 2April 1998 pp 59–63https://doi.org/10.1145/279044.279157Published:01 April 1998Publication History 4citation56DownloadsMetricsTotal Citations4Total Downloads56Last 12 Months6Last 6 weeks3 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my Alerts New Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
The role of short RNA loops in recognition of a single-hairpin exon derived from a mammalian-wide interspersed repeat (2015)

Splice-site selection is controlled by secondary structure through sequestration or approximation of splicing signals in primary transcripts but the exact role of even the simplest and most prevalent structural motifs in exon recognition remains poorly understood. Here we took advantage of a single-hairpin exon that was activated in a mammalian-wide interspersed repeat (MIR) by a mutation stabilizing a terminal triloop, with splice sites positioned close to each other in a lower stem of the hairpin. We first show that the MIR exon inclusion in mRNA correlated inversely with hairpin stabilities. Employing a systematic manipulation of unpaired regions without altering splice-site configuration, we demonstrate a high correlation between exon inclusion of terminal tri- and tetraloop mutants and matching tri-/tetramers in splicing silencers/enhancers. Loop-specific exon inclusion levels and enhancer/silencer associations were preserved across primate cell lines, in 4 hybrid transcripts and also in the context of a distinct stem, but only if its loop-closing base pairs were shared with the MIR hairpin. Unlike terminal loops, splicing activities of internal loop mutants were predicted by their intramolecular Watson-Crick interactions with the antiparallel strand of the MIR hairpin rather than by frequencies of corresponding trinucleotides in splicing silencers/enhancers. We also show that splicing outcome of oligonucleotides targeting the MIR exon depend on the identity of the triloop adjacent to their antisense target. Finally, we identify proteins regulating MIR exon recognition and reveal a distinct requirement of adjacent exons for C-terminal extensions of Tra2α and Tra2β RNA recognition motifs.
Functional anatomy of canine cardiac nerves (1975)

In 20 anesthetized dogs the thoracic autonomic nerves were carefully exposed in order to determine which produced cardiovascular responses when the afferent or efferent component of each was stimulated. Efferent parasympathetic and sympathetic fibers arise from the caudal cervical ganglion regions bilaterally as well as from the vagus caudally to that ganglion. The majority of negative chromotropic, dromotropic and inotropic fibers arise from the vagus or near the recurrent laryngeal nerves; however, some small parasympathetic fibers also arise from the vagi down to the level of the pulmonary vessels. Efferent sympathetic nerves are relatively large with the exception of the stellate cardiac nerves, and produce specific positive chronotropic or inotropic responses. Afferent fibers are numerous in the recurrent cardiac, innominate, ventromedial and dorsal nerves and not very numerous in both stellate cardiac nerves as well as in the nerves at the level of the pulmonary vessels; thus there are numerous cholinergic and adrenergic efferent fibers which exhibit specific chronotropic or inotropic responses. The correlation between neural anatomy and specific physiological cardiodynamics illustrates beautifully the interrelationship of structure and function which exists within the autonomic nervous system.
Immunomodulatory Drugs (2005)

After nearly decades of extinction as a sedative and antiemetic, thalidomide reemerged as the parent compound of a novel and promising class of therapeutics termed the immunomodulatory drugs (IMiDs). The analogues of thalidomide, CC-5013 (lenalidomide, Revlimid) and CC-4047 (Actimid) are more potent regulators of cellular immune and cytokine response while lacking some of the dose limiting side effects of the parent compound, such as neurologic toxicity. Preclinical data will be reviewed that outlines these drugs' effects on tumor necrosis alpha, interleukin 12, angiogenesis, and T-cell function. The evolution of the use of thalidomide as a therapeutic for diseases such as multiple myeloma and myelodysplastic syndrome and the promising initial results of the new IMiDs will be reviewed.
Antiviral efficacy of NS3‐serine protease inhibitor BILN‐2061 in patients with chronic genotype 2 and 3 hepatitis C†‡ (2005)

BILN-2061, a specific and potent peptidomimetic inhibitor of the HCV NS3 protease, has recently been shown to markedly lower serum hepatitis C virus (HCV)-RNA levels in patients chronically infected with HCV genotype 1 in three 2-day proof of principle studies. The aim of the current study was to assess the antiviral efficacy of BILN-2061 in patients with genotypes 2 and 3 HCV infection. The antiviral efficacy, pharmacokinetics, and tolerability of 500 mg twice-daily BILN-2061 given as monotherapy for 2 days in 10 patients chronically infected with non-genotype 1 HCV (genotype 2: n = 3; genotype 3: n =7) and minimal liver fibrosis (Ishak score 0-2) were assessed in a placebo-controlled (placebo n = 2), double-blind pilot study. HCV-RNA levels decreased by > or =1 log(10) copies/mL in 4 of 8 patients treated with BILN-2061. One patient showed a weak response of <1 log(10) copies/mL. Three of 8 treated patients showed no response. There was no correlation between baseline viral concentration or genotype and response. BILN-2061 exhibited good systemic exposure after oral administration and was well tolerated. In conclusion, the antiviral efficacy of the HCV serine protease inhibitor BILN-2061 is less pronounced and more variable in patients with HCV genotype 2 or 3 infection compared with previous results in patients with HCV genotype 1. A lower affinity of BILN-2061 for the NS3 protease of genotypes 2 and 3 HCV is most likely a major contributor to these findings.
NIF (neurite-inducing factor): a novel peptide inducing neurite formation in PC12 cells (1986)

Neurite-inducing factor (NIF) is a novel protein that has been partially purified from mouse submaxillary glands. NIF induces neurite formation in PC12 pheochromocytoma cells, and the NIF-induced neurites are indistinguishable from NGF-induced neurites in both their morphology and the time course of their formation. Neurite-inducing activity can be recovered at a position corresponding to a molecular weight of 20,000 Da after fractionation of partially purified preparations via SDS-PAGE. Partially purified preparations of NIF are about half as potent as pure beta NGF, and since the neurite-inducing activity does not correspond to any of the major proteins in this fraction, specific activity of purified NIF will probably be significantly greater than the 60 ng/ml found for our partially purified material. NIF is distinct from beta NGF by four criteria: (1) antibodies to beta NGF can block the activity of beta NGF, but not the activity of NIF; (2) beta NGF can induce ornithine decarboxylase (ODC) in PC12 cells at concentrations significantly below those required to induce neurites, while NIF induces ODC only at concentrations greatly in excess of those required to induce neurite formation; (3) by the criterion of SDS-PAGE, there is insufficient beta NGF in our partially purified preparations of NIF to explain the biological activity of this fraction; and (4) the biological activity of NIF has a molecular weight (20,000 Da) that is distinct from beta NGF (13,000 Da). We conclude that NIF is probably a novel peptide that is very active in promoting morphological differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)
An architecture for interactive applications (2002)

An architecture that can serve as an open, public-switched network platform for interactive video and multimedia applications is proposed. It assumes a public broadband backbone network, and wideband (1.5 Mb/s or more) access capability. Motivation for the proposed architecture is provided, and some realization aspects for candidate applications are indicated. The video on demand application is treated in detail. A design for networked multimedia file servers (information warehouses) is proposed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Three times weekly glatiramer acetate in relapsing–remitting multiple sclerosis (2013)

GA 40mg sc tiw is a safe and effective regimen for the treatment of RRMS, providing the convenience of fewer sc injections per week.
Fully Integrated Truck Information and Control Systems (TIACS) (1983)

&lt;div class="htmlview paragraph"&gt;Electronic sub-systems are being developed for heavy duty trucks. However, these sub-systems are being developed as individual entities i.e., information, monitoring, recording, control systems etc. This paper identifies the current, near term, and long range system requirements and suggests ideas for a fully integrated Truck Information And Control System (TIACS) aimed at an orderly approach to a vehicle electronic system for heavy duty trucks.&lt;/div&gt;