gebhart/patrepeval huggingface dataset:
Stem Cell Biomarkers in Chronic Myeloid Leukemia (2008)

Chronic myeloid leukemia (CML) is a clonal multi-step myeloproliferative disease that is initially produced and ultimately sustained by a rare subpopulation of BCR-ABL+ cells with multi-lineage stem cell properties. These BCR-ABL+ CML stem cells are phenotypically similar to normal hematopoietic stem cells which are also maintained throughout the course of the disease at varying levels in different patients. Defining the unique properties of the leukemic stem cells that produce the chronic phase of CML has therefore had to rely heavily on access to samples from rare patients in which the stem cell compartment is dominated by leukemic elements. Here we review past and ongoing approaches using such samples to identify biologically and clinically relevant biomarkers of BCR-ABL+ stem cells that explain their unusual biology and that may help to design, or at least predict, improved treatment responses in CML patients. These studies are of particular interest in light of recent evidence that chronic phase CML stem cells are not only innately resistant to imatinib mesylate and other drugs that target the BCR-ABL oncoprotein, but are also genetically unstable.
Treatment of severe Crohn's disease with anti‐CD4 monoclonal antibody (1996)

In this uncontrolled open trial, monoclonal anti-CD4 B-F5 antibody was not successful in severe Crohn's disease.
Structurally Divergent Human T Cell Receptor γ Proteins Encoded by Distinct Cγ Genes (1987)

The human T cell receptor (TCR) gamma polypeptide occurs in structurally distinct forms on certain peripheral blood T lymphocytes. Complementary DNA clones representing the transcripts of functionally rearranged TCR gamma genes in these cells have been analyzed. The expression of a disulfide-linked and a nondisulfide-linked form of TCR gamma correlates with the use of the C gamma 1 and C gamma 2 constant-region gene segments, respectively. Variability in TCR gamma polypeptide size and disulfide linkage is determined by the number of copies and the sequence of a repeated segment of the constant region. Thus C gamma 1 and C gamma 2 are used to generate structurally distinct, yet functional, T3-associated receptor complexes on peripheral blood lymphocytes. Tryptic peptide mapping suggests that the T3-associated TCR gamma and delta peptides in the nondisulfide-linked form are distinct.
Differential sensitivities of viruses in red cell suspensions to methylene blue photosensitization (1994)

MB-based protocols would require the use of high-efficiency (> 6log10) white cell-reduction filters or additional inactivation steps to deplete or inactivate intracellular virus.
Phase I trial of BAY 43–9006 (sorafenib) combined with dacarbazine (DTIC) in metastatic melanoma patients (2005)

7508 Background: BAY 43–9006 (BAY) prevents tumor cell proliferation and angiogenesis via blockade of the RAF/MEK/ERK pathway at the level of RAF (RAF-1, wild-type B-RAF, V599E B-RAF) kinase and inhibition of the receptor tyrosine kinases VEGFR-2 and PDGFR-β. In phase I/II trials, BAY was generally well tolerated as a single agent or with concomitant chemotherapy. Methods: This single-centre, open-label, phase I, dose-escalation study was performed to determine the safety profile and maximum tolerated dose (MTD) of BAY administered at 200 (cohort 1) or 400 (cohort 2) mg bid in combination with repeated 21-day cycles of DTIC 1000 mg/m2. In an extension phase (cohort 3), patients (pts) received the MTD of BAY plus DTIC 1000 mg/m2. Results: Pts with metastatic melanoma were enrolled (ECOG PS 0–1) into cohorts 1 (n=3) 2 (n=6) and 3 (n=3). 1 pt died due to PD. The most common drug-related AEs were dermatologic (rash, flushing, hand-foot skin reaction [HFS]); gastrointestinal (nausea, diarrhoea, constipation, vomiting), constitutional (fatigue/lethargy) or blood/bone-marrow-related, and were generally grade (gr) 1–2 in severity and transient. 1 pt in cohort 2 experienced dose-limiting toxicity of gr 3 HFS. No drug-related gr 3/4 AEs occurred in cohort 1. Gr 3/4 drug-related AEs in cohort 2 were mostly resolved and included gr 4 hypercalcemia; gr 3 low hemoglobin; gr 3 pancreatic hemorrhage; gr 3 pancreatitis; gr 3 leucopenia that occurred in 1 pt each and gr 3/4 neutropenia in 2 pts. Gr 3/4 laboratory abnormalities were rare. According to RECIST, of the 11 evaluable pts after cycle 2, 2 pts had PR; 2 pts had response not reaching PR; 1 pt had SD; and 6 pts had PD. Conclusions: Continuous BAY 400 mg bid is safe and well tolerated and shows preliminary anti-tumor activity in combination with DTIC 1000 mg/m2. The MTD of BAY is 400 mg bid in combination with DTIC 1000 mg/m2. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer, Bayer Healthcare Bayer, CFSB, Deutsche Bank, Medacorp AstraZeneca, Bayer AG Bayer Bayer
IDEC-C2B8 (Rituximab) Anti-CD20 Monoclonal Antibody Therapy in Patients With Relapsed Low-Grade Non-Hodgkin's Lymphoma (1997)

Abstract IDEC-C2B8 is a chimeric monoclonal antibody (MoAb) directed against the B-cell–specific antigen CD20 expressed on non-Hodgkin's lymphomas (NHL). The MoAb mediates complement and antibody-dependent cell-mediated cytotoxicity and has direct antiproliferative effects against malignant B-cell lines in vitro. Phase I trials of single doses up to 500 mg/m2 and 4 weekly doses of 375 mg/m2 showed clinical responses with no dose-limiting toxicity. We conducted a phase II, multicenter study evaluating four weekly infusions of 375 mg/m2 IDEC-C2B8 in patients with relapsed low-grade or follicular NHL (Working Formulation groups A-D). Patients were monitored for adverse events, antibody pharmacokinetics, and clinical response. Thirty-seven patients with a median age of 58 years (range, 29 to 81 years) were treated. All patients had relapsed after chemotherapy (median of 2 prior regimens) and 54% had failed aggressive chemotherapy. Infusional side effects (grade 1-2) consisting of mild fever, chills, respiratory symptoms, and occasionally hypotension were observed mostly with the initial antibody infusion and were rare with subsequent doses. Peripheral blood B-cell depletion occurred rapidly, with recovery beginning 6 months posttreatment. There were no significant changes in mean IgG levels and infections were not increased over what would be expected in this population. Clinical remissions were observed in 17 patients (3 complete remissions and 14 partial remissions), yielding an intent to treat response rate of 46%. The onset of these tumor responses was as soon as 1 month posttreatment and reached a maximum by 4 months posttreatment. In the 17 responders, the median time to progression was 10.2 months (5 patients exceeding 20 months). Likelihood of tumor response was associated with a follicular histology, with the ability to sustain a high serum level of antibody after the first infusion, and with a longer duration of remission to prior chemotherapy. One patient developed a detectable but not quantifiable immune response to the antibody that had no clinical significance. IDEC-C2B8 in a dose of 375 mg/m2 weekly for 4 weeks has antitumor activity in patients with relapsed low-grade or follicular NHL. Results with this brief, outpatient treatment compare favorably with results with standard chemotherapy, and IDEC-C2B8 has a better safety profile. Further studies evaluating IDEC-C2B8 in other types of lymphoma either alone or combined with chemotherapy are warranted.
Demonstration of sandwich and competitive modulated supraparticle fluoroimmunoassay applied to cardiac proteinbiomarkermyoglobin (2008)

Modulated supraparticle structures are used to improve sandwich and competitive fluoroimmunoassays. The improved methods are demonstrated on myoglobin, a key diagnostic protein for detection of heart damage. The resulting method uses microliter volumes with bovine serum samples doped with varying concentrations of equine myoglobin. These immunoassays use micron-diameter iron oxide particles as a solid phase for antibody anchoring. Introduction of a magnetic field creates dipole moments on the particles, which attracts them to each other to form rod-like supraparticle structures. These structures can rotate within an alternating magnetic field generating convective flow and a periodic signal that can be analyzed with lock-in amplification enabling more sensitive detection. The system is demonstrated on a target associated with acute myocardial infarction (AMI). This disease causes decreased oxygen delivery to the heart resulting in tissue death and the release of cardiac myoglobin into the bloodstream. Studies have shown that the assessment and monitoring of serum myoglobin concentrations is important when making an early diagnosis of AMI. Early diagnosis is crucial since treatment is most effective when done within the first two hours of symptoms. The modulated assay is rapid, accurate, and sensitive for myoglobin assessment of small-volume serum samples. Using a cut-off value of 5.0 nM (85 ng/mL) for AMI induced myoglobin, the modulated competitive assay was able to diagnose AMI-like conditions in serum doped with myoglobin after an incubation time of only 10 min. The standard curve developed for the modulated sandwich assay was linear over a range of zero to 1 nM (17 ng/mL) with a lower limit of detection at 50 pM (0.85 ng/mL).
Digital watermarking of images and video using direct sequence spread spectrum techniques (2003)

We analyze the spread spectrum technique of watermarking images and video. The technique can be used for both spatial and spectral domain watermarking. The watermarking procedure could be incorporated with the standard compression algorithm or could be performed on already available JPEG or MPEG streams after partial decoding. The spread spectrum method has the advantage that the watermark extraction is possible without using the original unmarked image. The simulation results show the robustness of the watermark to image degradations such as lossy compression as in JPEG and MPEG, spatial filtering, cropping, etc.
Stimulated secretion of endothelial von Willebrand factor is accompanied by rapid redistribution to the cell surface of the intracellular granule membrane protein GMP-140 (1989)

We have examined the cell activation-dependent redistribution of the intracellular granule membrane protein GMP-140 of human endothelial cells. By dual-label immunofluorescence, the distribution of GMP-140 within cultured human umbilical vein endothelial cells was found to coincide with the distribution of von Willebrand factor (vWF), suggesting that GMP-140 is located in the membranes of vWF-containing storage granules. Stimulation of vWF secretion resulted in an increase in GMP-140 on the cell surface, as detected by increased binding of the monoclonal antibody S12 which recognizes the extracytoplasmic domain of GMP-140. For each agonist tested (histamine, thrombin, phorbol 12-myristate 13-acetate, and the calcium ionophore A23187) a dose-dependent redistribution of GMP-140 to the endothelial surface was observed which closely paralleled the dose-dependent secretion of vWF into the cell supernatant. When cells were maximally stimulated by histamine in the presence of antibody S12, a 4-fold increase in S12 uptake by the cells was observed. This increase occurred rapidly and reached a plateau by 10 min. In contrast, when histamine-stimulated cells were first fixed with paraformaldehyde or chilled to 4 degrees C before addition of antibody S12, only a transient increase in cell surface GMP-140 was detected. Under these conditions of arrested membrane turnover during antibody binding, cell surface GMP-140 was maximal 3 min after histamine stimulation and then declined to control levels by 20 min. These data suggest that stimulated secretion of vWF from endothelial cells entails fusion of vWF-containing storage granules with the plasma membrane. Once inserted into the plasma membrane, GMP-140 is subsequently removed from the endothelial surface, most likely by an endocytic mechanism.
“Long-Term Returns on the Original S&P 500 Companies”: Author Response (2006)

This material comments on “Long-Term Returns on the Original S&P 500 Companies.”
Using the shortwave infrared to image middle ear pathologies (2016)

Significance Imaging with shortwave infrared (SWIR) light has great potential for visualizing biological structures previously undetectable with visible light. To demonstrate the clinical potential of SWIR imaging, we developed a medical otoscope sensitive to SWIR light. We show that the unique transmission of SWIR light through tissue improves resolution of anatomical structures lying behind thin tissue membranes like the ear drum. We therefore significantly improve imaging of underlying middle ear anatomy. SWIR imaging also allows identification of disease characterized by fluid accumulation, as in the diagnosis of otitis media. With successful diagnosis of otitis media estimated at 51% for US pediatricians, objectifying this diagnosis could curb the antibiotic resistance associated with an estimated 2 million overdiagnoses each year.
Skin hydration state estimation using a fiber-optic refractometer (1994)

A U-shaped fiber-optic refractometer is used to estimate the hydration state of human skin. The validity of the sensor in this application has been investigated by comparing the sensor output with the conductance of the skin to a high-frequency electrical current of 3.5 MHz, which has been reported to be a good measure of the skin hydration state. Results indicate that there is a relatively close relationship between the optical sensor output and the electrical conductance. A water sorption-desorption test conducted to confirm the above relationship has revealed that the fiber-optic probe can provide a convenient means for estimating the skin hydration state in an easy manner.
Place of Nanofiltration for Assuring Viral Safety of Biologicals (2005)

Viruses are nanometer size organisms (range from 18 to 250 nm) that can potentially contaminate the feedstocks from animal or human origins used to manufacture biopharmaceutical products. Various measures are taken to ensure the optimal viral safety of this class of products. Selection and screening of starting materials play an important role in safeguarding from the introduction of viruses into the downstream processing but they have limits in specificity and sensitivity. Purification methods of protein biopharmaceutical products may also contribute to viral reduction, but since viruses exhibit a wide range of biochemical characteristics and resistance to physico-chemical treatments, complete elimination of infectious agents is not guaranteed. Therefore, the viral safety of animal derived biopharmaceutical products is well recognized to rely largely upon the use of deliberately introduced and validated viral inactivation and/or removal steps. A major progress in viral safety has been made recently by the development and availability of biocompatible viral filtration (also known as nanofiltration) systems using membranes of a pore size as small as 15 nm; these systems are specifically designed to allow, depending upon membrane used, typically over 4 to 6 logs of virus removal under conditions ensuring good protein permeability and recovery. Validation studies and production experience throughout the world have demonstrated that viral nanofiltration is a robust and reliable viral reduction technique that can be applied to essentially all biological products. This review analyzes the virus risks of biopharmaceutical products (human plasma derivatives, horse and sheep plasma-derived products, recombinant proteins and monoclonal antibodies), the various viral inactivation methods used at present, and the increasing role that viral nanofiltration is playing in assuring the safety of biopharmaceutical products.
Oral field cancerization: carcinogen-induced independent events or micrometastatic deposits? (2000)

Patients with a head and neck squamous cell carcinoma (HNSCC) often develop multiple (pre)malignant lesions. This finding led to the field cancerization theory, which hypothesizes that the entire epithelial surface of the upper aerodigestive tract has an increased risk for the development of (pre)malignant lesions because of multiple genetic abnormalities in the whole tissue region. Demonstration of alterations in histologically normal tumor-adjacent mucosa from HNSCC patients supported this hypothesis. Currently, the question has been raised whether multiple lesions develop independently from each other or from migrated malignant or progenitor cells. The majority of the mucosal alterations appear to be related to the exposure to alcohol and/or tobacco. Moreover, almost all primary remote tumors from HNSCC patients appear to be clonally unrelated. Therefore, there is more evidence that field cancerization is due to multiple independent events than to migration of genetically altered cells.
Engineering of a bispecific affibody molecule towards HER2 and HER3 by addition of an albumin‐binding domain allows for affinity purification and in vivo half‐life extension (2014)

Emerging strategies in cancer biotherapy include the generation and application of bispecific antibodies, targeting two tumor-associated antigens for improved tumor selectivity and potency. Here, an alternative format for bispecific molecules was designed and investigated, in which two Affibody molecules were linked by an albumin-binding domain (ABD). Affibody molecules are small (6 kDa) affinity proteins and this new format allows for engineering of molecules with similar function as full-length bispecific antibodies, but in a dramatically smaller size (around eight-fold smaller). The ABD was intended to function both as a tag for affinity purification as well as for in vivo half-life extension in future preclinical and clinical investigations. Affinity-purified bispecific Affibody molecules, targeting HER2 and HER3, showed simultaneous binding to the three target proteins (HER2, HER3, and albumin) when investigated in biosensor assays. Moreover, simultaneous interactions with the receptors and albumin were demonstrated using flow cytometry on cancer cells. The bispecific Affibody molecules were also able to block ligand-induced phosphorylation of the HER receptors, indicating an anti-proliferative effect. We believe that this compact and flexible format has great potential for developing new potent bispecific affinity proteins in the future, as it combines the benefits of a small size (e.g. improved tissue penetration and reduced cost of goods) with a long circulatory half-life.
Urinary excretion of hydroxylysine and its glycosides as an index of collagen degradation. (1977)

Urimary excretion of hydroxyprolin (Hyp) is one index of total collagen degradation, from all sources. Since some of the Hyp released from collagen may be further metabolized before it is excreted, other markers are necessary to measure collagen breakdown. Excretion of the glycosides of hydroxylysine (Hyl), glucosyl galactosyl hydroxylysine (Hy1[Gl)cGa1]), and galactosyl hydroxylysine (Hyl[Ga)]), more accurately reflects collagen metabolism since these products occur in specificratios in different tissue collagens and are themselves metabolized only to a minor degree. The ratios of total Hy1/Hyp and Hyl(GlcGal)/Hyl(Ga1) were measured in the urine of norma. subjects and of patients with Paget's disease of bone, hyperphosphatasia, and extensive thermal burns. In patients with extensive thermal burns the pattern of urinary Hy1 and its glycosides was consistent with degradation of collagen in dermis and fascia. When bone collagen degradation was dominant, the pattern of urinary metabolites reflected that source. Pagetic bone collagen has an amino acid composition similar to normal bone and Hy1(G1cGa1/Hyl(G1) of 0.396-0.743,vs. normal of 0.474+/-0.088. In untreated patients with severe Paget's disease of bone or hyperphosphatasia (urinary Hyp greater than 2.0 micronmol/mg creatinine) urinary Hyl/Hyp averaged 0.052+/-0.042 (0.042+/-0.009 in normal bone) and Hy1(G1cGa1)/Hy1(Ga1) 0.601+/-0.017 (0.47+/-0.009 in normal bone). When bone resorption was decreased sufficiently with calcitonin or disodium etidronate in these patients, both the urinary ratios of Hy1/Hyp and Hy1(G1cGa1)/Hyl(Gal) rose. In normal subjects treated with calcitonin and excreting relatively little Hyp, the ratio of Hy1/H)P approached 0.7 and Hy1(G1ycGa1)/Hy1(Ga1) approached 3.5. There increased ratios reveal the existence of a source of collagen breakdown other than skin or bone. The first subcompoent of complement, Clq, which has collagen-like sequences, relatively high amounts of Hy1, and most of the glycosylated Hy1 as Hy1(G1cGa1), could be the source of these metabolites.
Isolation of a strong Arabidopsis guard cell promoter and its potential as a research tool (2008)

The pGC1 promoter described here drives strong reporter expression in guard cells of Arabidopsis and tobacco plants. It provides a potent research tool for targeted guard cell expression or gene silencing. It is also applicable to reduce specific gene expression in guard cells, providing a method for circumvention of limitations arising from genetic redundancy and lethality. These advances could be very useful for manipulating signaling pathways in guard cells and modifying plant performance under stress conditions. In addition, new guard cell and mesophyll cell-specific 23,000 gene microarray data are made publicly available here.
Overcoming browser cookie churn with clustering (2012)

Many large Internet websites are accessed by users anonymously, without requiring registration or logging-in. However, to provide personalized service these sites build anonymous, yet persistent, user models based on repeated user visits. Cookies, issued when a web browser first visits a site, are typically employed to anonymously associate a website visit with a distinct user (web browser). However, users may reset cookies, making such association short-lived and noisy. In this paper we propose a solution to the cookie churn problem: a novel algorithm for grouping similar cookies into clusters that are more persistent than individual cookies. Such clustering could potentially allow more robust estimation of the number of unique visitors of the site over a certain long time period, and also better user modeling which is key to plenty of web applications such as advertising and recommender systems.