gebhart/patrepeval huggingface dataset:
Multicenter Phase 2 Trial of Rituximab for Waldenström Macroglobulinemia (WM): An Eastern Cooperative Oncology Group Study (E3A98) (2004)

Waldenström macroglobulinemia (WM) is a low-grade lymphoplasmacytic lymphoma that strongly expresses CD20 on the cell surface. This study was undertaken to determine the response rate of patients with untreated or previously treated WM to the monoclonal antibody rituximab, which is directed against CD20+ expressed by B-cell lymphomas. Thirty-four untreated and thirty-five previously treated patients received rituximab 375 mg/m2 weekly for 4 consecutive weeks by intravenous infusion on days 1, 8, 15, and 22. Sixty-nine patients were evaluable for response; 19 (27.5%) achieved an objective response and 17 (24.6%) achieved a minor response. The overall response rate was 52.2% (90% CI [41.6%, 62.6%]). Of previously untreated patients 35.3% vs. 20% of previously treated patients achieved an objective response. Median response duration was not significantly different between previously untreated (27 months) and previously treated patients (not reached, P = 0.8). Rituximab produced objective or minor responses in 52.2% of patients and is an active agent in the treatment of WM. Grade 4 toxicity was seen in 11%.
HPV E6, E6AP and cervical cancer (2008)

Every year, approximately 470,000 new cases of cervical cancer are diagnosed and approximately 230,000 women worldwide die of the disease, with the majority (approximately 80%) of these cases and deaths occurring in developing countries. Human papillomaviruses (HPVs) are the etiological agents in nearly all cases (99.7%) of cervical cancer, and the HPV E6 protein is one of two viral oncoproteins that is expressed in virtually all HPV-positive cancers. E6 hijacks a cellular ubiquitin ligase, E6AP, resulting in the ubiquitylation and degradation of the p53 tumor suppressor, as well as several other cellular proteins. While the recent introduction of prophylactic vaccines against specific HPV types offers great promise for prevention of cervical cancer, there remains a need for therapeutics. Biochemical characterization of E6 and E6AP has suggested approaches for interfering with the activities of these proteins that could be useful for this purpose. PUBLICATION HISTORY : Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).
Efficient transplantation of BCR-ABL-induced chronic myelogenous leukemia-like syndrome in mice. (1993)

Lethally irradiated mice reconstituted with bone marrow expressing P210 BCR-ABL can develop myeloproliferative syndromes that resemble the initial phase of human chronic myelogenous leukemia (CML). Mice that develop the CML-like syndrome can be segregated into two groups based on the latency with which the granulocytic disease appears--early onset (&lt; 20 weeks) and late onset (&gt; 20 weeks). Only cells from mice exhibiting the late-onset CML-like syndrome can efficiently propagate the disease when transplanted into sublethally irradiated syngeneic recipients. Mice engrafted with late-onset murine CML cells develop a range of hematopoietic disorders that originate from multipotent stem cells. The chronic granulocytic hyperplasia can be propagated by serial transplantation into secondary and tertiary recipient mice. The majority of transplanted mice succumb to acute myeloid and B- and T-lymphoid leukemias. These data support the idea that late-onset murine CML originates from a multipotent progenitor cell with a high replicating capacity. The inability to transplant the disease from mice developing the early-onset CML-like syndrome suggests that this disorder may originate from more differentiated progenitor cells with limited replication capacity that have undergone clonal expansion but are not immortalized. Although both early- and late-onset CML-like syndromes exhibit granulocytic hyperplasia, these disorders represent distinct diseases that appear to originate from different hematopoietic cell types. The late-onset CML-like disease and transfer to secondary recipients provides a useful murine model with features of the chronic and acute phases of human CML.
Liquid Biopsy Detects Relapse Five Months Earlier than Regular Clinical Follow-Up and Guides Targeted Treatment in Breast Cancer (2019)

Genetic alterations in circulating tumor DNA (ctDNA) are an emerging biomarker for the early detection of relapse and have the potential to guide targeted treatment. ctDNA analysis is often performed by droplet digital PCR; however, next-generation sequencing (NGS) allows multigene testing without having to access a tumor sample to identify target alterations. Here, we report the case of a stage III hormone receptor-positive breast cancer patient who remained symptomless after receiving surgery and adjuvant chemotherapy. Liquid biopsy analysis by NGS revealed the presence of a ctDNA <i>PIK3CA</i> N345K mutation five months before the detection of relapse with multiple liver metastases by regular clinical follow-up. To date, clinical implications of the <i>PIK3CA</i> N345K variant remain insufficiently investigated; however, everolimus treatment resulted in the shrinkage of tumor lesions and decreased the levels of tumor markers. Four months after treatment initiation, a second ctDNA analysis suggested a relapse, and the patient clinically progressed after five months of everolimus therapy. This case report demonstrates the value of ctDNA analysis by NGS for the early detection of relapse in breast cancer patients. The study further indicates its usefulness for the choice of targeted treatments, suggesting that the variant <i>PIK3CA</i> N345K might be associated with everolimus sensitivity.
Transferrin Is an Insulin-Like Growth Factor-Binding Protein-3 Binding Protein1 (2001)

Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) possesses both growth-inhibitory and -potentiating effects on cells that are independent of IGF action and are mediated through specific IGFBP-3 binding proteins/receptors located at the cell membrane, cytosol, or nuclear compartments and in the extracellular matrix. We have here characterized transferrin (Tf) as one of these IGFBP-3 binding proteins. Human serum was fractionated over an IGFBP-3 affinity column, and a 70-kDa protein was eluted, sequenced, and identified (through database searching and Western immunoblot) as human Tf. Tf bound IGFBP-3 but had negligible affinity to the other five IGFBPs, and iron-saturated holo-Tf bound IGFBP-3 more avidly than unsaturated Tf. Biosensor interaction analysis confirmed that this interaction is specific and sensitive, with a high association rate similar to IGF-I, and suggested that binding occurs in the vicinity of the IGFBP-3 nuclear localization site. As an independent confirmation of this interaction, using a yeast two-hybrid system, we cloned Tf from a human liver complementary DNA library as an IGFBP-3 protein partner. Tf treatment blocked IGFBP-3-induced cell proliferation in bladder smooth muscle cells, and IGFBP-3-induced apoptosis in prostate cancer cells. In summary, we have employed a combination of techniques to demonstrate that Tf specifically binds IGFBP-3, and we showed that this interaction has important physiological effects on cellular events.
Algorithm optimizations for low-complexity eye tracking (2009)

This paper investigates techniques for reducing computational complexity of tracking eyes of computer user. By empirical evaluation of a number of techniques we define a technology capable of monitoring eyes of computer user in real time with high accuracy and very low computational overhead.
Handbook of Equity Derivatives (1994)

Equity derivatives offer more flexibilty and hedging opportunities than ever before. In this handbook, readers will find a synthesis of the equity derivatives market and its instruments, from classic warrants, options and futures to the new and innovative PERCS, equity swaps, and equity-link bonds. The editors have assembled dozens of experts from academia and Wall Street to examine the growing variety of financial products--and the investment strategies for making them work.
Alphavirus vectors for vaccine production and gene therapy (2003)

Alphavirus vectors demonstrate high expression of heterologous proteins in a broad range of host cells. Replication-deficient as well as replication-competent variants exist. Systemic delivery of many viral antigens has elicited strong antibody responses in immunized mice and primates, and protection against challenges with lethal viruses was obtained. Similarly, prophylactic vaccination was established against tumor challenges. Attention has been paid to the engineering of improved targeting to immunologically active cells, such as dendritic cells. In the area of gene therapy, intratumoral injections of alphavirus vectors have resulted in potentially promising tumor rejection. Moreover, encapsulation of alphavirus particles into liposomes demonstrated efficient tumor targeting in mice with severe combined immunodeficiency, which permitted the initiation of clinical trials for patients with advanced kidney carcinoma and melanoma.
Methanogenesis in McLean Bog, an Acidic Peat Bog in Upstate New York: Stimulation by H2/CO2in the Presence of Rifampicin, or by Low Concentrations of Acetate (2004)

Abstract Acidic peat bog soils produce CH4 and although molecular biological studies have demonstrated the presence of diverse methano-genic populations in them, few studies have sustained methanogenesis by adding the CH4 precursors H2/CO2 or acetate, and few indigenous methanogens have been cultured. McLean Bog is a small (ca. 70 m across), acidic (pH 3.4–4.3) Sphagnum -dominated bog in upstate New York. Although addition of H2/CO2 or 10 mM acetate stimulated methanogenesis in soils from a nearby circumneutral-pH fen, neither of these substrates led to sustained methanogenesis in McLean Bog soil slurries. After a brief period of stimulation by H2/CO2, methanogenesis in McLean Bog soil declined, which could be attributed to buildup of large amounts of acetic acid produced from the H2/CO2 by acetogens. Addition of the antibiotic rifampicin inhibited acetogenesis (carried out by Bacteria) and allowed methanogenesis (carried out by Archaea) to continue. Using rifampicin, we were able to study effects of temperature, pH, and salts on methanogenesis from H2/CO2 in McLean Bog soil samples. The enriched H2/CO2-utilizing methanogens showed an optimum for activity near pH 5, and a temperature optimum near 35°C. Methanogenesis was not stimulated by addition of 10 mM acetate, but it was stimulated by 1 mM acetate, and multiple additions were consumed at increasing rates and nearly stoichiometrically converted to CH4. In conclusion, we have found that both hydrogentrophic and aceticlastic methanogens are present in McLean Bog soils, and that methanogenic activity can be stimulated using H2/CO2 in the presence of rifampicin, or using low concentrations of acetate. The USA National Science Foundation provided support of this research through a Microbial Observatories program grant (0132049), and also provided partial support of SB through the NSF Research training Grant in Biogeochemistry awarded to Cornell. The publication does not necessarily reflect the views of NSF, which did not review the material before publication We would like to thank our undergraduate assistant, Craig Bierle, for analyses of the Chicago Bog samples, and Janice Thies for advice on soil handling.
A dynamic programming algorithm for haplotype block partitioning (2002)

We develop a dynamic programming algorithm for haplotype block partitioning to minimize the number of representative single nucleotide polymorphisms (SNPs) required to account for most of the common haplotypes in each block. Any measure of haplotype quality can be used in the algorithm and of course the measure should depend on the specific application. The dynamic programming algorithm is applied to analyze the chromosome 21 haplotype data of Patil et al. [Patil, N., Berno, A. J., Hinds, D. A., Barrett, W. A., Doshi, J. M., Hacker, C. R., Kautzer, C. R., Lee, D. H., Marjoribanks, C., McDonough, D. P., et al. (2001) Science 294, 1719-1723], who searched for blocks of limited haplotype diversity. Using the same criteria as in Patil et al., we identify a total of 3,582 representative SNPs and 2,575 blocks that are 21.5% and 37.7% smaller, respectively, than those identified using a greedy algorithm of Patil et al. We also apply the dynamic programming algorithm to the same data set based on haplotype diversity. A total of 3,982 representative SNPs and 1,884 blocks are identified to account for 95% of the haplotype diversity in each block.
Specific Recognition of Cruciform DNA by Nuclear Protein HMG1 (1989)

Cruciform DNA, a non-double helix form of DNA, can be generated as an intermediate in genetic recombination as well as from palindromic sequences under the effect of supercoiling. Eukaryotic cells are equipped with a DNA-binding protein that selectively recognizes cruciform DNA. Biochemical and immunological data showed that this protein is HMG1, an evolutionarily conserved, essential, and abundant component of the nucleus. The interaction with a ubiquitous protein points to a critical role for cruciform DNA conformations.
Cardiac thromboxane A2 receptor activation does not directly induce cardiomyocyte hypertrophy but does cause cell death that is prevented with gentamicin and 2-APB (2014)

Our data suggests that TXA2 does not induce cardiac hypertrophy, but does induce cell death that is mediated in part by IP3 signaling pathways. These findings may provide important therapeutic targets for inflammatory-induced cardiac apoptosis that can lead to heart failure.
Hemi-Cube Ray-Tracing: A Method for Generating Soft Shadows (1990)

This paper presents a new ray-tracing technique for generating soft shadows. The technique treats scenes consisting of light sources and opaque objects which are polygons or polyhedra of arbitrary shape and size. To determine the intensity at a point on a surface, the hemisphere is sampled extensively through the use of hemi-cubes. So-called item-buffer boxes, a combination of itembuffers and buffer boxes, are used to calculate ray intersections as well as to suppress image aliasing. Several methods for reducing aliasing caused by hemi-cubes are discussed. The uniform treatment of rays allows for a straightforward extension of the algorithm to produce fuzzy reflections. The success of the new technique depends on a fast implementation of a visible surface algorithm as provided by today’s high-end graphics workstations. The results are images of realistically illuminated synthetic environments.
Reversible Hydrogels from Self-Assembling Artificial Proteins (1998)

Recombinant DNA methods were used to create artificial proteins that undergo reversible gelation in response to changes in pH or temperature. The proteins consist of terminal leucine zipper domains flanking a central, flexible, water-soluble polyelectrolyte segment. Formation of coiled-coil aggregates of the terminal domains in near-neutral aqueous solutions triggers formation of a three-dimensional polymer network, with the polyelectrolyte segment retaining solvent and preventing precipitation of the chain. Dissociation of the coiled-coil aggregates through elevation of pH or temperature causes dissolution of the gel and a return to the viscous behavior that is characteristic of polymer solutions. The mild conditions under which gel formation can be controlled (near-neutral pH and near-ambient temperature) suggest that these materials have potential in bioengineering applications requiring encapsulation or controlled release of molecular and cellular species.
Delivery of nanogram payloads using magnetic porous silicon microcarriers (2006)

A transport and delivery system for nanogram quantities of molecular species that does not use microfluidic channels, pumps, or valves is described. Microparticles consisting of magnetic porous silicon are prepared, and loading and delivery of an enzymatic payload are demonstrated. The high porosity (60%) porous Si host particles are made magnetic by infusion of superparamagnetic iron oxide nanoparticles (30 nm-diameter magnetite, Fe(3)O(4)) under oxidative conditions. After magnetite incorporation, the porous microparticle is still empty enough to accommodate nanogram quantities of a molecular payload; the enzymes horseradish peroxidase or pronase E are used in the present work. The assembly can be transported to a microliter water droplet containing the enzyme substrate with the aid of an external magnetic field. The enzyme is released into the droplet upon contact. The particles can be transported through air or a hydrocarbon liquid without loss in enzymatic activity of the payload.
Expression and Functional Study of Wild-Type and Mutant Human Cytochrome P450c21 in Saccharomyces cerevisiae (1991)

The most common cause of congenital adrenal hyperplasia is deficiency of cytochrome P450c21 (21-hydroxylase), which catalyzes the synthesis of adrenal steroids. We have cloned the human P450c21 cDNA into yeast expression vectors under the control of either the glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) promoter or the aldehyde-dehydrogenase (ADH) promoter. P450c21 RNA, protein, and enzyme activity can be detected, indicating that both promoters drive the synthesis of P450c21. The expressed P450c21 catalyzes the conversion of both of its substrates, with Km and Vmax values of 0.33 microM and 280 nmoles/hr.nmole of P450c21 protein for progesterone, and 0.23 microM and 450 nmoles/hr.nmole for 17-hydroxyprogesterone. These kinetic properties are similar to those of human P450c21 expressed in COS-1 cells. The microsomal fraction containing P450c21 exhibited an absorption peak at 450 nm upon binding to CO, demonstrating its hemoprotein nature. The CO-difference spectra indicated that there were about 0.08 nmole P450c21 hemoprotein/mg microsomal protein. Coupling this expression system with site-directed mutagenesis, the Asn-172 mutant of P450c21 had about 20-100 lower Vmax values; yet it retained normal affinity toward both substrates. This mutant protein also exhibited an altered absorbance with a peak at 420 nm rather than at 450 nm.
A New Strategy To Stabilize Oxytocin in Aqueous Solutions: II. Suppression of Cysteine-Mediated Intermolecular Reactions by a Combination of Divalent Metal Ions and Citrate (2012)

A series of studies have been conducted to develop a heat-stable liquid oxytocin formulation. Oxytocin degradation products have been identified including citrate adducts formed in a formulation with citrate buffer. In a more recent study we have found that divalent metal salts in combination with citrate buffer strongly stabilize oxytocin in aqueous solutions (Avanti, C.; et al. AAPS J.2011, 13, 284-290). The aim of the present investigation was to identify various degradation products of oxytocin in citrate-buffered solution after thermal stress at a temperature of 70 °C for 5 days and the changes in degradation pattern in the presence of divalent metal ions. Degradation products of oxytocin in the citrate buffer formulation with and without divalent metal ions were analyzed using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). In the presence of divalent metal ions, almost all degradation products, in particular citrate adduct, tri- and tetrasulfides, and dimers, were greatly reduced in intensity. No significant difference in the stabilizing effect was found among the divalent metal ions Ca(2+), Mg(2+), and Zn(2+). The suppressed degradation products all involve the cysteine residues. We therefore postulate that cysteine-mediated intermolecular reactions are suppressed by complex formation of the divalent metal ion and citrate with oxytocin, thereby inhibiting the formation of citrate adducts and reactions of the cysteine thiol group in oxytocin.
Epitaxial Growth of Undoped and Mg-Doped GaN (1976)

Gallium nitride was epitaxially grown on {0001} and {102} sapphire by the vapor phase reaction of Ga-HCl-NH3-Ar system. The growth rate on {102} sapphire is ∼12 µm/hr, which is higher than that on {0001} sapphire by a factor of ∼1.5. The crystal on {1102} sapphire has a lower carrier concentration than that of the same thickness on {0001} sapphire by a factor of ∼0.5. The lowest carrier concentration and the highest electron mobility of undoped GaN obtained in this study were 1.6×1019 cm-3 and 78 cm2/V·s, respectively, at 300 K. When heavily doped with Mg, the crystal grown changes markedly in growth morphology. The orientation relationships developed in an undoped or lightly Mg-doped state are {0001}GaN//{0001}sapphire and {110}GaN//{102}sapphire, and in a heavily doped state {114}GaN//{0001}sapphire and {110}GaN//{102}sapphire.
Adaptive disk scheduling in a multimedia DBMS (2003)

In this paper, we present APEX, a disk scheduling framework with QoS support, designed for environments with highly varying disk bandwidth usage. In particular, we focus on a Learning-on-Demand scenario supported by a multimedia database management system, where students can search for, and play back multimedia-based learning material. APEX is based on a two-level scheduling architecture, where the upper level realizes different service classes using a set of queues, while the lower level distributes available disk bandwidth among these queues.In this paper, we focus on the low-level scheduling in APEX, which is based on an extended token bucket algorithm. The disk requests scheduled for service are assembled into batches, which render possible good efficiency for the disk. Combined with a very efficient work-conservation scheme, this enables APEX to apply bandwidth where it is needed, without efficiency loss. We demonstrate, through simulations, that APEX provides both higher throughput and lower response times than other mixed-media disk schedulers, while still avoiding deadline violations for real-time requests. We also show its robustness with respect to misaligned bandwidth allocation.
Role of ET and NO in resuscitative effect of diaspirin cross-linked hemoglobin after hemorrhage in rat (1997)

Diaspirin cross-linked hemoglobin (DCLHb) is a hemoglobin-based therapeutic agent that produces significant cardiovascular effects, possibly due to its actions on vasoactive substances, such as endothelin (ET) and nitric oxide (NO). We have studied the modulation of cardiovascular effects of DCLHb by an NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), and an ETA-receptor antagonist, FR-139317, in hemorrhaged rats. Control rats resuscitated with vehicle [Ringer lactate (RL), 4 ml/kg iv] did not show any improvement in O2 consumption, base deficit, systemic hemodynamics, or regional blood flow after hemorrhage, and the rats survived for < 70 min. Administration of DCLHb (400 mg/kg iv) significantly improved O2 consumption, base deficit, systemic hemodynamics, and regional blood circulation after resuscitation, and the rats survived for > 120 min after hemorrhage. Plasma ET-1 and guanosine 3',5'-cyclic monophosphate (cGMP) concentrations increased after hemorrhage. DCLHb produced an increase in ET-1 and decreased cGMP concentrations in plasma. Pretreatment with L-NAME (10 mg/kg iv) or FR-139317 (4 mg/kg iv) attenuated the DCLHb-induced improvement in survival time, base deficit, systemic hemodynamics, and regional blood circulation. L-NAME (10 mg/kg iv) per se did not produce any resuscitative effect; therefore the NO mechanism may not be contributing toward the efficacy of DCLHb in hemorrhaged rats. However, FR-139317 attenuated the efficacy of DCLHb; therefore an increase in plasma ET-1 concentration by DCLHb may be contributing toward the efficacy of DCLHb in hemorrhage. Hemorrhage-induced increase in cGMP levels could be attenuated by L-NAME, but L-NAME was not effective in resuscitation of hemorrhaged rats, indicating a lack of role of NO in resuscitation. It is concluded that the ET mechanism is more important in the beneficial effect of DCLHb than the NO mechanism in hemorrhage.