gebhart/patrepeval huggingface dataset:
Effector Mechanisms of Recombinant IgA Antibodies against Epidermal Growth Factor Receptor (2007)

IgA is the most abundantly produced Ab isotype in humans, but its potential as immunotherapeutic reagent has hardly been explored. In this study, we describe anti-tumor mechanisms of mouse/human chimeric IgA Abs against the epidermal growth factor receptor (EGF-R). EGF-R Abs of IgG isotype are currently approved for the treatment of colon or head and neck cancers. As expected, the human IgG1, IgA(1), and IgA(2) variants of the 225 Ab demonstrated similar binding to EGF-R. Furthermore, IgA Abs were as effective as IgG in mediating direct effector mechanisms such as blockade of EGF binding, inhibition of EGF-R phosphorylation, and induction of growth inhibition. None of the three variants induced complement-mediated lysis. Human IgG1 effectively recruited MNC for ADCC, but activated PMN only weakly, whereas both IgA isoforms proved to be effective in triggering neutrophils. Interestingly, the IgA(2) isoform was significantly superior to its IgA(1) counterpart in recruiting PMN as effector cells. Because neutrophils constitute the most abundant effector cell population in human blood, this enhanced neutrophil recruitment lead to increased killing of EGF-R expressing tumor cells in whole blood assays. This killing was further enhanced when blood from G-CSF-primed donors was compared with healthy donor blood. Together, these data suggest EGF-R Abs of human IgA isotype to bear promise for therapeutic use in cancer.
Transferrin receptors and cation-independent mannose-6-phosphate receptors deliver their ligands to two distinct subpopulations of multivesicular endosomes. (1989)

The distribution of transferrin receptors (Tf-R) was determined in Clone 9 hepatocytes and compared to that of 215 kDa, cation-independent mannose-6-phosphate receptors (M6P-R) by double labeling. Cells were allowed to take up exogenous human transferrin (Tf) for 5 to 30 min, after which Tf, Tf-R, and M6P-R were localized by immunofluorescence using specific antibodies. All these proteins were found to be concentrated in the juxtanuclear or Golgi region. When Clone 9 cells were treated with NH4Cl to trap M6P-R in endosomes (Brown, W. J., J. Goodhouse, M. G. Farquhar: J. Cell Biol. 103, 1235-1247 (1986)), the distribution of the two receptors differed: Tf-R remained the same as in controls, but M6P-R were localized in large vacuolated endosomes. To carry out double labeling experiments at the electron microscope level, transferrin gold conjugates (Tf-Au) were prepared, and M6P-R were detected by immunoperoxidase labeling. Tf-Au binding to the cell surface was specific as it was reduced approximately 70 to 79% in the presence of excess native Tf. When Clone 9 cells were incubated with Tf-Au at 37 degrees C for 5 to 30 min, or binding of Tf-Au was carried out at 4 degrees C followed by warming to 37 degrees C, Tf-Au was found within a peripheral tubulovesicular network and within multivesicular endosomes that were not labeled with anti-M6P-R. Other multivesicular endosomes of similar size and morphology were heavily labeled for M6P-R but contained little or no Tf-Au. Tf-Au and M6P-R were also found in separate endosomes in cells treated with NH4Cl. Native Tf was localized in the same compartments as Tf-Au by immunoperoxidase labeling of both Clone 9 cells and mouse myeloma cells. We conclude that in Clone 9 hepatocytes, Tf/Tf-R internalized from the cell surface and M6P-R bearing newly synthesized lysosomal enzymes from the Golgi deliver their ligands to two different subpopulations of multivesicular endosomes. The endosomal subpopulation visited by Tf/Tf-R is known to correspond kinetically to early endosomes. The endosomal subpopulation heavily labeled for M6P-R presumably represent a later endosomal compartment which serves as the junction point where endocytosed ligands and newly synthesized lysosomal enzymes enroute to lysosomes meet.
Rate-constrained picture-adaptive quantization for JPEG baseline coders (1993)

A recursive algorithm is presented for generating quantization tables in JPEG (Joint Photographic Experts Group) baseline coders from the actual statistics of the input image. Starting from a quantization table with large step sizes, corresponding to low bit rate and high distortion, one entry of the quantization table is updated at a time so that, at each step, the ratio of decrease in distortion to increase in bit rate is approximately maximized. This procedure is repeated until a target bit rate is reached. Simulation results demonstrate that, with picture-adaptive quantization tables designed by the proposed algorithm, the JPEG DCT (discrete cosine transform) coder is able to compress images with better rate-distortion performance than that achievable with conventional empirically designed quantization tables.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
CATH: comprehensive structural and functional annotations for genome sequences (2014)

The latest version of the CATH-Gene3D protein structure classification database (4.0, http://www.cathdb.info) provides annotations for over 235,000 protein domain structures and includes 25 million domain predictions. This article provides an update on the major developments in the 2 years since the last publication in this journal including: significant improvements to the predictive power of our functional families (FunFams); the release of our 'current' putative domain assignments (CATH-B); a new, strictly non-redundant data set of CATH domains suitable for homology benchmarking experiments (CATH-40) and a number of improvements to the web pages.
The treatment of indolent lymphomas: watchful waiting v aggressive combined modality treatment. (1988)

Patients with advanced indolent lymphoma often have long survival (median, 4 to 8 years) in spite of frequent relapses. The inability of combination chemotherapy or radiation therapy (RT) to render patients disease free has led to radically divergent treatment approaches. Initial treatment may vary from aggressive combined modality therapy to no initial treatment. We sought to evaluate these two divergent approaches in a randomized trial of advanced indolent lymphomas (nodular, poorly differentiated lymphocytic; nodular mixed; diffuse, well-differentiated lymphocytic; diffuse, intermediately differentiated lymphocytic; and diffuse, poorly differentiated lymphocytic). A total of 104 patients were entered: 44 were randomly assigned to "watch and wait" in which only carefully defined, limited RT was administered if necessary; 45 were randomly assigned to aggressive combined modality treatment with prednisone, methotrexate, doxorubicin, cyclophosphamide, plus etoposide plus mechlorethamine, vincristine, procarbazine, prednisone (ProMACE-MOPP), followed by total nodal irradiation (TNI); and 15, with symptoms requiring initial therapy, received the identical combined treatment but were not randomly assigned. Of 41 evaluable patients on watch and wait, 23 (56%) have still not required systemic therapy, although 16 (39%) have received limited RT. Median time to crossover was 34 months. Of 18 patients crossed over, seven of the 16 who completed therapy (43%) achieved CR; two (11%) have relapsed. Histologic progression was seen in six (15%) of 41 patients on watch and wait without intervening chemotherapy. Of 45 patients randomly assigned to chemotherapy, 37 (82%) have completed induction therapy, and 29 of the 37 (78%) achieved CR. Twenty-five of those 29 patients (86%) are still in their first remission. Median duration of initial remission has not been reached but will exceed 4 years.(ABSTRACT TRUNCATED AT 250 WORDS)
3, 4-diaryl-coumarins, chromenes and choromans as novel anti-inflammatory agents. (1987)

A number of 3,4-diaryl-coumarins, chromenes and chromans (8,9,13,14,20& 25) have been found to possess significant anti-inflammatory activity in rats. Synthesis and biological activity of these novel anti-inflammatory agents are reported.
Development and testing of a cobalt dicarbollide based solvent extraction process for the separation of cesium and strontium from acidic tank waste (2002)

A fission product solvent extraction technology for the simultaneous extraction of Cs and Sr from acidic tank waste has been developed as a collaborative effort of the Idaho National Engineering and Environmental Laboratory (INEEL) and the Khlopin Radium Institute in St. Petersburg, Russia. The process is being developed as a potential method for treating the current five million liter inventory of acidic tank waste stored at the INEEL. The fission product extraction process is based on an immiscible organic phase comprised of chlorinated cobalt dicarbollide (CCD, Cs extractant) and polyethylene glycol (PEG, Sr extractant) dissolved in a poly-fluorinated sulfone diluent. Batch contact experiments and preliminary flowsheet testing were used to define potential solvent composition and flowsheet configuration. This information was used to specify an initial flowsheet for countercurrent testing with simulated tank waste using a 3.3-cm diameter centrifugal contactor pilot plant at the INEEL. The initial extractant composition was 0.08 M CCD, 0.6 vol% PEG-400 in a phenyl trifluoromethyl sulfone (FS-13) diluent. Approximately 1.5 L of solvent was used (with continuous recycle) to treat 43 L of simulated tank waste during 75 hr of continuous operation. Greater than 99.992% of the Sr and 97.45% of the Cs were extracted from the simulated tank waste and recovered in the strip product. The matrix components Ba (>99.6%), Pb (99.8%), and Ca (10.6%) were also extracted from the simulated tank waste and recovered in the strip product. Less than 1% of the K, Na, Fe, Zr, and Mo were extracted from the tank waste simulant. Finally, none of the analytically determined waste components were observed to build up in the organic solvent.
Molecular-genetic imaging: current and future perspectives (2003)

Medical imaging has undergone a revolution in the past decade. This is largely due to improved technology involving all the major imaging modalities: MRI, computed tomography (CT), positron emission tomography (PET), ultrasound, and optical imaging. These advances and improvements in technology are being rapidly translated into the clinic and have established new standards of medical practice. Cancer imaging was identified as one of six “extraordinary scientific opportunities” by the National Cancer Institute in 1997–1998, and the institute’s subsequent funding initiatives have provided a major stimulus for further developments. A major target of these initiatives has been development of and support for molecular imaging.

Molecular-genetic imaging provides visualization in space and time of normal as well as abnormal cellular processes at a molecular or genetic level. Needless to say, current gamma camera, PET, MRI, and optical technologies do not visualize individual cells, much less molecules. Perhaps the most exciting aspect of this emerging new field are the novel imaging paradigms being developed — paradigms that image molecular-genetic processes rather than anatomy. These paradigms can be successful within the inherent spatial-resolution limits of existing imaging systems, provided that the volume element, or voxel, of the tissue (cells) is relatively homogenous. This review will focus primarily on radionuclide imaging, although many of the principles described are directly applicable to optical and MRI technology as well. A more extensive discussion of these issues was recently published (1).

Molecular imaging has its roots in molecular biology and cell biology as well as in imaging technology. Three different noninvasive, in vivo imaging technologies have developed more or less in parallel: (a) MRI (2–6); (b) nuclear imaging (quantitative autoradiography, gamma camera, and PET) (7–11); and (c) optical imaging of small animals (12–14). The convergence of these disciplines is at the heart of the molecular imaging success story and constitutes the wellspring for further advances in the field. The development of versatile and sensitive assays that do not require tissue samples will be of considerable value for monitoring of molecular-genetic and cellular processes in animal models of human disease, as well as for studies in human subjects. Noninvasive imaging of molecular-genetic and cellular processes will complement established ex vivo molecular-biological assays that require tissue sampling; it also provides a spatial as well as a temporal dimension to our understanding of various diseases.
Association Mapping of Main Tomato Fruit Sugars and Organic Acids (2016)

Association mapping has been widely used to map the significant associated loci responsible for natural variation in complex traits and are valuable for crop improvement. Sugars and organic acids are the most important metabolites in tomato fruits. We used a collection of 174 tomato accessions composed of Solanum lycopersicum (123 accessions) and S. lycopersicum var cerasiforme (51 accessions) to detect significantly associated loci controlling the variation of main sugars and organic acids. The accessions were genotyped with 182 SSRs spreading over the tomato genome. Association mapping was conducted on the main sugars and organic acids detected by gas chromatography-mass spectrometer (GC-MS) over 2 years using the mixed linear model (MLM). We detected a total of 58 significantly associated loci (P < 0.001) for the 17 sugars and organic acids, including fructose, glucose, sucrose, citric acid, malic acid. These results not only co-localized with several reported QTLs, including fru9.1/PV, suc9.1/PV, ca2.1/HS, ca3.1/PV, ca4.1/PV, and ca8.1/PV, but also provided a list of candidate significantly associated loci to be functionally validated. These significantly associated loci could be used for deciphering the genetic architecture of tomato fruit sugars and organic acids and for tomato quality breeding.
Cerebral blood flow of patients with age-associated memory impairment and the early stage of Alzheimer's disease. A study by SPECT using the ARG method. (1998)

In order to further understand the pathology of Alzheimer's disease (AD), we have utilized image analysis in diagnosing the early stages of AD in patients with cognitive disorders. CT and MRI, however, have not been feasible since only atrophy is seen and it is difficult to differentiate the changes in AD from age associated changes. In this study we tried to determine whether regional cerebral blood flow (rCBF) measurements using single photon emission CT (SPECT) are feasible for the early diagnosis of AD. Regional CBF (rCBF) was measured using SPECT in three subject groups: Age-associated memory impairment (AAMI. n = 9), mild AD (n = 16), and normal aged patients (mean age = 68.3; n = 20). The subjects were then observed for three years. The region of interest (ROI) for the medial temporal lobe was set at OM-30 degrees to cover the maximum area of the hippocampus. The absolute values of rCBF in the frontal, temporal, and parietal lobes and the cerebellum were significantly lower in the mild AD subjects than in the normal aged subjects. A significant decrease in rCBF was also seen in the medial temporal lobe in both the AD and the AAMI subjects compared to the normal controls. During the three years of follow up, no cases of dementia were seen in the AAMI subjects. However, there were two patients who appeared to have difficulty in adapting to daily life due to amnesia, one with a decrease in rCBF of the medial temporal lobe on the second SPECT, and the other showing a low rCBF the first time. This study suggests that AAMI subjects may comprise both AD and normal subjects. Therefore a more prospective study is needed.
Increased plasma level of interleukin-6 in disseminated intravascular coagulation (1993)

Plasma interleukin-6 (IL-6) was higher in patients with disseminated intravascular coagulation (DIC) than in those without DIC. Levels of IL-1 beta and TNF alpha were also significantly higher in patients with DIC. Plasma IL-6 was highest in patients with underlying sepsis and was also high in those with advanced solid cancer. Levels were high in some patients with acute promyelocytic leukaemia and were significantly higher in patients with organ failure than in those without this complication. Plasma IL-6 was higher in DIC patients showing a poor response to therapy than in those with a good response. Incubation with IL-6 caused significant increases in tissue factor activity in mononuclear cells and release of plasminogen activator-1 antigen from human umbilical vein endothelial cells. As increases in IL-6 might give rise to hypercoagulable and hypofibrinolytic states, this may be a cause of DIC and be related to prognosis and organ failure.
Distinctive current-induced magnetization switching in a current-perpendicular-to-plane giant-magnetoresistance nanopillar with a synthetic antiferromagnet free layer (2005)

We investigated current-induced magnetization switching (CIMS) in two types of pseudo-spin-valve nanopillars with current-perpendicular-to-plane giant magnetoresistance (CPP-GMR); Co90Fe10(10nm)∕Cu(10nm)∕Co90Fe10(2.5nm) (conventional type) and Co90Fe10(10nm)∕Cu(10nm)∕Co90Fe10(1.5nm)∕Ru(0.45nm)∕Co90Fe10(2.5nm) (synthetic antiferromagnet; SyAF type). We observed the CIMS in the both CPP-GMR structures at room temperature. In particular for the SyAF type nanopillars, the CIMS was observed only in a negative current regime. We also discovered that the applied magnetic field dependence of the CIMS shows absolutely different behavior from that of the conventional type. These peculiar CIMS behaviors with the SyAF free layer are attributed to majority electron spin transfer torque from the thick to the thin Co90Fe10 layers, enhanced by the presence of a Ru layer.
On the benefits and pitfalls of extending a statically typed language JIT compiler for dynamic scripting languages (2012)

Whenever the need to compile a new dynamically typed language arises, an appealing option is to repurpose an existing statically typed language Just-In-Time (JIT) compiler (repurposed JIT compiler). Existing repurposed JIT compilers (RJIT compilers), however, have not yet delivered the hoped-for performance boosts. The performance of JVM languages, for instance, often lags behind standard interpreter implementations. Even more customized solutions that extend the internals of a JIT compiler for the target language compete poorly with those designed specifically for dynamically typed languages. Our own Fiorano JIT compiler is an example of this problem. As a state-of-the-art, RJIT compiler for Python, the Fiorano JIT compiler outperforms two other RJIT compilers (Unladen Swallow and Jython), but still shows a noticeable performance gap compared to PyPy, today's best performing Python JIT compiler. In this paper, we discuss techniques that have proved effective in the Fiorano JIT compiler as well as limitations of our current implementation. More importantly, this work offers the first in-depth look at benefits and limitations of the repurposed JIT compiler approach. We believe the most common pitfall of existing RJIT compilers is not focusing sufficiently on specialization, an abundant optimization opportunity unique to dynamically typed languages. Unfortunately, the lack of specialization cannot be overcome by applying traditional optimizations.
Juvenile hormone resistance: ¡ no PASaran ! (1998)

The control of growth, differentiation, metamorphosis, and reproduction in insects is a complex interplay of hormones, with the steroid hormone ecdysone and the sesquiterpenoid juvenile hormone (JH) playing major roles. Molting is controlled by ecdysone, and the type of molt is controlled by JH. The presence of JH maintains the insect in the juvenile (larval) state, hence its name (1), and the relative absence of JH allows metamorphosis to proceed. With the discovery of insect JH came the idea that application of JH or its agonists at an inopportune time, when the insect required the absence of JH for metamorphosis—the “Achilles’ heel” of insect development—would disrupt this complex endocrine machinery. Analogs of JH, developed since the 1970s and euphemistically called “insect growth regulators,” are now among the most environmentally friendly types of insecticides. These chemicals, including methoprene, pyriproxyfen, and fenoxycarb, proved to be excellent mimics of the natural hormone, but, paradoxically, the molecular mode of action of JH has remained very much a mystery (2, 3). Now, studies on the insect’s response to these powerful chemicals—resistance—provide a direct avenue into the mode of action of JH itself.

Ashok et al. (4) report in the current issue of the Proceedings the identity of the Methoprene-tolerant gene of Drosophila melanogaster as a member of the bHLH-PAS family of transcriptional regulators. This significant advance raises many questions, and its implications will be discussed here.

Selection for methoprene-resistant mutants in D. melanogaster led to the definition of a genetic locus, Methoprene-tolerant or Met (5). Flies carrying the Met alleles are up to 100-fold resistant to structurally diverse JH analogs and to JH itself. The Met flies are not only resistant to the lethal effects of JH, but also to all the more subtle morphogenetic signs of hormone excess. For instance, treatment with methoprene …
Adaptive Clinical Trials: Advantages and Disadvantages of Various Adaptive Design Elements (2017)

There is a wide range of adaptive elements of clinical trial design (some old and some new), with differing advantages and disadvantages. Classical interim monitoring, which adapts the design based on early evidence of superiority or futility of a treatment arm, has long been known to be extremely useful. A more recent application of interim monitoring is in the use of phase II/III designs, which can be very effective (especially in the setting of multiple experimental treatments and a reliable intermediate end point) but do have the cost of having to commit earlier to the phase III question than if separate phase II and phase III trials were performed. Outcome-adaptive randomization is an older technique that has recently regained attention; it increases trial complexity and duration without offering substantial benefits to the patients in the trial. The use of adaptive trials with biomarkers is new and has great potential for efficiently identifying patients who will be helped most by specific treatments. Master protocols in which trial arms and treatment questions are added to an ongoing trial can be especially efficient in the biomarker setting, where patients are screened for entry into different subtrials based on evolving knowledge about targeted therapies. A discussion of three recent adaptive clinical trials (BATTLE-2, I-SPY 2, and FOCUS4) highlights the issues.