gebhart/patrepeval huggingface dataset:
Costimulation Blockade, Busulfan, and Bone Marrow Promote Titratable Macrochimerism, Induce Transplantation Tolerance, and Correct Genetic Hemoglobinopathies with Minimal Myelosuppression (2001)

Mixed hemopoietic chimerism has the potential to correct genetic hemological diseases (sickle cell anemia, thalassemia) and eliminate chronic immunosuppressive therapy following organ transplantation. To date, most strategies require either recipient conditioning (gamma-irradiation, depletion of the peripheral immune system) or administration of "mega" doses of bone marrow to facilitate reliable engraftment. Although encouraging, many issues remain that may restrict or prevent clinical application of such strategies. We describe an alternative, nonirradiation based strategy using a single dose of busulfan, costimulation blockade, and T cell-depleted donor bone marrow, which promotes titratable macrochimerism and a reshaping of the T cell repertoire. Chimeras exhibit robust donor-specific tolerance, evidenced by acceptance of fully allogeneic skin grafts and failure to generate donor-specific proliferative responses in an in vivo graft-versus-host disease model of alloreactivity. In this model, donor cell infusion and costimulation blockade without busulfan were insufficient for tolerance induction as donor-specific IFN-gamma-producing T cells re-emerged and skin grafts were rejected at approximately 100 days. When applied to a murine beta-thalassemia model, this approach allows for the normalization of hemologic parameters and replacement of the diseased red cell compartment. Such a protocol may allow for clinical application of mixed chimerism strategies in patients with end-stage organ disease or hemoglobinopathies.
Low-Temperature Annealing for Highly Conductive Lead Chalcogenide Quantum Dot Solids (2010)

Electrical conductivity in quantum dot solids is crucial for application in devices. In addition to the well-known ligand exchange strategies for enhanced conductivity, the current study examined the optical, structural, and electrical properties of ethanedithiol-treated layer-by-layer (LbL) assembled quantum dot solid (QDS) films following low-temperature annealing (room temperature to 170 °C). As the annealing temperature increased, it was induced that the average separation between nanocrystal quantum dots is decreased, and accordingly, the overall conductivity of the QDS increased exponentially. From a simplified percolation model, the activation energy of temperature-dependent quantum dot attachment was estimated to be around 0.26−0.27 eV both for PbS and PbSe quantum dot solids. Furthermore, the results of this study indicated that device applications requiring higher conductivity, attainable through high-temperature annealing, may also require repassivation after annealing.
Vitamin D and Calcium Are Required during Denosumab Treatment in Osteoporosis with Rheumatoid Arthritis (2017)

The aim of this 12-month retrospective study was to evaluate differences in the outcomes of denosumab alone or denosumab combined with vitamin D and calcium supplementation in patients having osteoporosis (OP) with rheumatoid arthritis (RA). Patients were divided into the denosumab monotherapy group (denosumab group, 22 cases) or denosumab plus vitamin D supplementation group (combination group, 21 cases). We measured serum bone alkaline phosphatase (BAP), N-terminal propeptide of type 1 collagen (P1NP), tartrate-resistant acid phosphatase (TRACP)-5b, and urinary N-terminal telopeptide of type-I collagen (NTX) at baseline, 1 week, and 1, 2, 4, 6, 8, and 12 months. We also assessed bone mineral density (BMD) of the lumbar 1-4 vertebrae (L-BMD) and bilateral total hips (H-BMD) at baseline and 4, 8, and 12 months. Matrix metalloprotanase-3 (MMP-3), Disease Activity Score-28 C-reactive protein (DAS28-CRP), Simplified Disease Activity Index (SDAI), and Health Assessment Questionnaire-Disability Index (HAQ-DI) were assessed before treatment and at 12 months to evaluate RA conditions. The study results showed that BAP, TRACP-5b, and NTX were significantly decreased, but tended to return to pre-treatment levels around 6 and 12 months in both groups. While L-BMD and H-BMD substantially increased in both groups, H-BMD had become significantly higher in the combination group at 12 months (<i>p</i> < 0.01) as compared with the denosumab group. There were no significant differences between the groups regarding MMP-3, DAS28-CRP, SDAI, or HAQ-DI. Compared with denosumab monotherapy, combination therapy of denosumab with vitamin D and calcium significantly increased H-BMD in patients having OP with RA.
Advanced thin-film silicon-on-sapphire technology: microwave circuit applications (1998)

This paper reviews the prospects of thin-film silicon-on-sapphire (TFSOS) CMOS technology in microwave applications in the 1-5 GHz regime and beyond and presents the first demonstration of microwave integrated circuits based on this technology, MOSFET's optimized for microwave use, with 0.5-/spl mu/m optically defined gate lengths and a T-gate structure, have f/sub t/ values of 25 GHz (14 GHz) and f/sub max/ values of 66 GHz (41 GHz) for n-channel (p-channel) devices and have noise figure values below 1 db at 2 GHz, some of the best reported performance characteristics of any silicon-based MOSFET's to date. On-chip spiral inductors exhibit quality factors above ten. Circuit performance compares favorably with that of other CMOS-based technologies and approach performance levels similar to those obtained by silicon bipolar technologies. The results demonstrate the significant potential of this technology for microwave applications.
Piecemeal Microautophagy of Nucleus in Saccharomyces cerevisiae (2003)

Nucleus-vacuole (NV) junctions in Saccharomyces cerevisiae are formed through specific interactions between Vac8p on the vacuole membrane and Nvj1p in the nuclear envelope. Herein, we report that NV junctions in yeast promote piecemeal microautophagy of the nucleus (PMN). During PMN, teardrop-like blebs are pinched from the nucleus, released into the vacuole lumen, and degraded by soluble hydrolases. PMN occurs in rapidly dividing cells but is induced to higher levels by carbon and nitrogen starvation and is under the control of the Tor kinase nutrient-sensing pathway. Confocal and biochemical assays demonstrate that Nvj1p is degraded in a PMN-dependent manner. PMN occurs normally in apg7-delta cells and is, therefore, not dependent on macroautophagy. Transmission electron microscopy reveals that portions of the granular nucleolus are often sequestered into PMN structures. These results introduce a novel mode of selective microautophagy that targets nonessential components of the yeast nucleus for degradation and recycling in the vacuole.
Intelligent multi robot systems for contemporary shopping malls (2010)

The objective of this paper is to show a new concept of robust and adaptive cooperative-collaborative multi-robot service architecture for contemporary mega stores. The research aim is design and devlopment of methods and technologies for integration of cognitive characteristics of cooperative robots with advanced recognition techniques (vision, RFID). The particular objectives includes the development of methods for cooperative perception and SLAM, the development of task allocation algorithms and navigation strategies, as well as development of cooperative learning. The porposed multirobot platform enables the different functional scenarios: cooperative distribution stock monitoring, cooperative RFID inventory control, cooperative robot formations, human-robot assistance.
Bluetooth and WAP push based location-aware mobile advertising system (2004)

Advertising on mobile devices has large potential due to the very personal and intimate nature of the devices and high targeting possibilities. We introduce a novel B-MAD system for delivering permission-based location-aware mobile advertisements to mobile phones using Bluetooth positioning and Wireless Application Protocol (WAP) Push. We present a thorough quantitative evaluation of the system in a laboratory environment and qualitative user evaluation in form of a field trial in the real environment of use. Experimental results show that the system provides a viable solution for realizing permission-based mobile advertising.
Rapid imaging, using a cooled charge‐coupled‐device, of fluorescent two‐dimensional polyacrylamide gels produced by labelling proteins in the first‐dimensional isoelectric focusing gel with the fluorophore 2‐methoxy‐2,4‐diphenyl‐3(2H)furanone (1988)

A new method for visualising proteins in two-dimensional polyacrylamide gels was developed. Proteins were labelled with the fluorophore 2-methoxy-2,4-diphenyl-3(2H)furanone (MDPF) while present in the first-dimensional gel after isoelectric focusing and subsequently electrophoresed into the second-dimensional gel. High resolution spot patterns were produced and compared with other methods of visualisation. A new rapid imaging system based on a cooled charge-coupled-device was used to view the two-dimensional fluorescent protein spot patterns. The method allows the immediate and rapid imaging of two-dimensional gels at the end of electrophoresis with no further processing.
Synthesis and Drug‐Delivery Behavior of Chitosan‐Functionalized Graphene Oxide Hybrid Nanosheets (2010)

Abstract Chitosan‐functionalized graphene oxides (FGOCs) were successfully synthesized. FGOCs were found to significantly improve the solubility of the GO in aqueous acidic media. The presence of organic groups was confirmed by means of XPS and TGA. Restoration of the sp 2 carbon network and exfoliation of graphene sheets were confirmed by Raman spectroscopy, UV‐visible spectroscopy and WAXD. The SEM and AFM investigations of the resultant FGOCs showed that most of the graphene sheets were individual and few were layered. Controlled release behavior of Ibuprofen and 5‐fluorouracil was then investigated. We found that FGOCs are a promising new material for biological and medical applications. magnified image
Sporadic amplification of the insulin-like growth factor 1 receptor gene in human breast tumors. (1992)

A principal difference between malignant and normal cells is the aberrant expression of oncogenes. Previously, we have reported on the expression of the insulin-like growth factor 1 receptor (IGF-1-R) in 93% of the human primary breast cancers studied. In the present study, we observed an increased gene copy number of the IGF-1-R in only 19 (2%) of 975 cases studied. The gene copy number of tumors with an amplified IGF-1-R gene varies between 3 and 56 (median, 24 copies). In 11 breast tumor samples with high (greater than or equal to 20 copies) IGF-1-R gene copy numbers, an additional amplification of either the c-myc gene (n = 3) or int-2/bcl-1 genes (n = 5) was observed, whereas no amplification of the HER2/neu gene was detected. The c-fes gene (like the IGF-1-R gene located on chromosome 15q25-qter), was found coamplified with the IGF-1-R in two cases, in one case to the same high extent (38 gene copies, each) and in the other case to only a moderate extent (4 copies of the c-fes gene and 21 copies of the IGF-1-R gene). Tumors with an amplified IGF-1-R gene showed a noticeable increased expression of the IGF-1-R as measured by ligand binding assays on membrane preparations. The median amount of the IGF-1-R protein of the amplified tumors was observed to be 35 times higher when compared to nonamplified tumors (P less than 0.001). Patients with tumors containing a high (greater than or equal to 20 copies) IGF-1-R gene copy number tend to have a shorter median overall survival (42 months; range, 14-120+; n = 8) than patients with tumors having a low amplified (3-10 copies) IGF-1-R gene copy number (median, 77 months; range, 19.5-98+; n = 4).
Enzymic O‐sulfation of tyrosine residues in hirudins by sulfotransferase from Eubacterium A‐44 (1994)

The enzymic O-sulfation of Tyr residues in a recombinant hirudin variant-1 (rHV-1) and its analog in which Glu61 and Glu62 were replaced by Tyr, [E61Y, E62Y]rHV-1, was carried out by use of sulfotransferase isolated from an anaerobic bacterium from the human intestine, Eubacterium A-44. Although rHV-1 was not sulfated by this enzyme, the sulfation of [E61Y, E62Y]rHV-1 was observed, and three kinds of sulfated analog, whose C-terminal six amino acid residues were -PYY(SO3H)YLQ, -PYYY(SO3H)LQ, and -PYY(SO3H)Y(SO3H)LQ, were obtained. Among the sulfated hirudin analogs tested here, the Tyr62 and Tyr63 bisulfated [E61Y, E62Y]rHV-1 showed the strongest thrombin inhibition with the inhibition constant (Ki) of 0.0430 pM, followed by the Tyr63 monosulfated analog (Ki = 0.0593 pM) and the Tyr62 monosulfated one (Ki = 0.158 pM). The Tyr63 monosulfated analog and Tyr62 and Tyr63 bisulfated one were more potent inhibitors of thrombin than unsulfated rHV-1. The increase in affinity caused by sulfation was predominantly due to an increase in the association-rate constant.
Steroid-unresponsive acute attacks of inflammatory bowel disease: immunomodulation by tacrolimus (FK506) (1998)

Tacrolimus induced rapid remission in steroid resistant inflammatory bowel disease in the majority of cases. It appears to be an effective treatment modality that may be superior to cyclosporine with respect to maintenance of remission.
Sizing Up Cell-Free DNA (2012)

In 1947, Mandel and Metais discovered the unusual phenomenon of circulating cell-free DNA (1). Although one might naively think that DNA is found only in the nuclei of cells, it turns out that a substantial amount of small DNA fragments circulates within the blood. These molecules are not part of intact cells but are the detritus of dead and apoptosed cells that have spilled their guts into the blood. Their genomes are chewed up into little pieces, the presence of which can be measured like any other blood analyte. Although great effort has been expended to try to understand how the relative concentrations of these DNA species may correlate with health, their greatest value has been to measure the proportion of foreign genomes within an individual. In certain cases that is quite straightforward: Cancer-related mutations can be used to some extent to determine the progress of disease (2), male chromosomal markers can be used for prenatal sex determination (3), and, in a similar fashion, women who have received organ transplants from males can be monitored for the amount of organ-specific DNA (4, 5).

The cell-free DNA phenomenon might have …
High speed milling of titanium (1983)

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 1983.
Genetic Background Determines the Extent of Atherosclerosis in ApoE-Deficient Mice (1999)

Two strains of ApoE-deficient mice were found to have markedly different plasma lipoprotein profiles and susceptibility to atherosclerosis when fed either a low-fat chow or a high-fat Western-type diet. FVB/NJ ApoE-deficient (FVB E0) mice had higher total cholesterol, HDL cholesterol, ApoA1, and ApoA2 levels when compared with C57BL/6J ApoE-deficient (C57 E0) mice. At 16 weeks of age, mean aortic root atherosclerotic lesion area was 7- to 9-fold higher in chow diet-fed C57 E0 mice and 3.5-fold higher in Western diet-fed C57 E0 mice compared with FVB E0 mice fed similar diets. Lesion area in chow diet-fed first-generation mice from a strain intercross was intermediate in size compared with parental values. The distribution of the lesion area in 150 chow diet-fed second-generation progeny spanned the range of the lesion area in both parental strains. There were no correlations between total cholesterol, non-HDL cholesterol, HDL cholesterol, ApoA1, ApoA2, ApoJ, or anti-cardiolipin antibodies and lesion area in the second-generation progeny. Thus, a genomic approach may succeed in identifying the genes responsible for the variation in atherosclerosis susceptibility in these 2 strains of ApoE-deficient mice, which could not be explained by measured plasma parameters.
Cathepsin B: association with plasma membrane in metastatic tumors. (1986)

The subcellular localization of cathepsin B activity (EC 3.4.22.1) in three murine melanomas of increasing metastatic potential (Cloudman less than B16-F1 less than B16 amelanotic) was determined. Cathepsin B activity was localized in the heavy mitochondrial fraction of normal murine liver but in the light mitochondrial fraction of the metastatic melanomas; the localization of three other lysosomal hydrolases did not shift. Further purification of the light mitochondrial fraction into L-1 (density = 1.045 g/ml) and L-2 (density = 1.07 g/ml) fractions was achieved on a 30% iso-osmotic Percoll gradient. The L-1 fraction of liver and melanomas contained Na+, K+-ATPase activity; the L-2 fraction of liver contained four lysosomal hydrolase (cathepsins B and H, N-acetyl-beta-glucosaminidase, and beta-glucuronidase) and glucose-6-phosphatase activities. Ultrastructural examination revealed that the L-1 fraction consisted of membrane vesicles and the L-2 fraction of secondary lysosomes. In the B16 melanomas cathepsin B and N-acetyl-beta-glucosaminidase activities were found in both L-1 and L-2 fractions. Specific activities of the two enzymes in the plasma membrane (L-1) fractions increased in correspondence with metastatic potential. Cathepsin H and beta-glucuronidase activities were not localized in the plasma membrane fractions of the B16 melanomas. Localization of hydrolytic enzymes in the plasma membrane of metastatic tumor cells could result in focal dissolution of the extracellular matrix and thereby invasion and metastasis.
Restricting the Selection of Antibiotic‐Resistant Mutant Bacteria: Measurement and Potential Use of the Mutant Selection Window (2002)

The selection of antibiotic-resistant mutant bacteria is proposed to occur in a drug concentration range (the mutant selection window) that extends from the minimum inhibitory concentration (MIC) of susceptible cells to the MIC of the least susceptible, single-step bacterial mutants (the mutant prevention concentration [MPC]). MPCs were estimated for tobramycin, chloramphenicol, rifampicin, penicillin, vancomycin, and several fluoroquinolones by use of Escherichia coli and Staphylococcus aureus. Comparisons among reported serum drug levels indicate that new fluoroquinolones are the least likely to enrich populations of resistant mutant bacteria during monotherapy. These data partly explain the selective enrichment of populations of resistant mutant bacteria in medical practice. The mutant selection window range (MPC:MIC) was narrowed for fluoroquinolones by structure modification, pointing to a new direction in antibiotic refinement. The mutant selection window and the MPC were determined for combinations of rifampicin and tobramycin, using S. aureus, as a guide for combination therapy with compounds that alone cannot block enrichment of mutant bacterial populations.
Enzymatic Activation of Proteasome Inhibitor Prodrugs by Prostate-Specific Antigen as Targeted Therapy for Prostate Cancer (2000)

Abstract : The aim of this proposal is to develop a method to target novel cytotoxic agents specifically to sites of metastatic prostate cancer. In the original proposal, proteasome inhibitors were selected as the cytotoxic agent. Initial studies revealed that this approach was not tenable due to the inherent instability of these compounds. An alternative agent was then selected to continue this targeted prodrug approach. Thapsigargin (TG) induces apoptosis in a proliferation independent manner in prostate cancer cells. This cytotoxicity, however, is not prostate cell type specific and TG could not be given systemically without significant toxicity. To achieve targeted cytotoxicity the TG analogs will be converted to inactive prodrugs by coupling to a peptide carrier that is a substrate for the serine protease activity of Prostate-Specific Antigen (PSA). Since PSA is expressed in high levels only by norrnal and malignant prostate cells, this approach should allow specific targeting of the killing ability of TG to prostate cancer cells. Therefore a series of amine containing TG analogs have been synthesized and characterized for their ability to induce apoptosis in prostate cancer cell lines. The lead TG analog has been chemically linked via a peptide bond to a previously identified PSA-specific peptide (i.e. 6 amino acids) to produce an inactive prodrug. This prodrug can be hydrolyzed by PSA and a 25-fold increase in toxicity is seen in the presence of enzymatically active PSA. In vivo studies using this lead TG prodrug to treat PSA-%roducing human prostate cancers are underway. Additional prodrugs will also be synthesized in order to optimize PSA-targeting.
Octreotide is not Effective in the Acute Treatment of Migraine (2004)

The aim of this study was to determine whether subcutaneous octreotide is effective for the treatment of acute migraine. Patients with migraine with and without aura as classified by the International Headache Society were recruited to a double-blind placebo-controlled crossover study. Patients were instructed to treat two attacks of at least moderate pain severity, with at least a 7 day interval, using subcutaneous 100 microg octreotide or matching placebo. The primary endpoint was the headache response defined as: severe or moderate pain becomes mild or nil, at 2 h. The primary endpoint was analysed using a Multilevel Analysis approach. Secondary end-points included associated symptoms and a four-point functional disability score. The study was powered to detect a 30% difference at an alpha of 0.05 and a beta of 0.8. A total of 51 patients were recruited, of whom 42 provided efficacy data on an attack treated with octreotide and 41 with placebo. Modelling the headache response as a binomial determined by treatment, using the patient as the level 2 variable, and considering a possible period effect, and sex and migraine type as other variables of interest, subcutaneous octreotide was not significantly superior to placebo. The two hour headache response rates were 20% for placebo and 14% for octreotide, whilst the two hour pain free rates were 7% and 2%, respectively. Subcutaneous octreotide 100 microg is not effective in the acute treatment of migraine when compared to placebo.
Stabilization of Pharmaceuticals to Oxidative Degradation (2002)

A guide for stabilization of pharmaceuticals to oxidation is presented. Literature is presented with an attempt to be a ready source for data and recommendations for formulators. Liquid and solid dosage forms are discussed with options including formulation changes, additives, and packaging documented. In particular, selection of and methods for use of antioxidants are discussed including recommended levels.