gebhart/patrepeval huggingface dataset:
Effect of Granulocyte Colony-Stimulating Factor on Neutropenia and Associated Morbidity Due to Chemotherapy for Transitional-Cell Carcinoma of the Urothelium (1988)

We evaluated the ability of human recombinant granulocyte colony-stimulating factor (rhG-CSF) to prevent chemotherapy-induced neutropenia or to accelerate recovery from this complication and thus allow patients to receive full doses of antineoplastic agents on time, according to protocol design. Twenty-seven patients with transitional-cell carcinoma of the urothelium who were undergoing treatment with methotrexate, doxorubicin, vinblastine, and cisplatin were given rhG-CSF (up to 60 micrograms per kilogram of body weight per day) before their first cycle of combination chemotherapy, during the first cycle, or at both points. Treatment with rhG-CSF before chemotherapy resulted in a dose-dependent increase in the absolute neutrophil count. Treatment with rhG-CSF after chemotherapy significantly reduced the number of days (91 percent) per patient on which the absolute neutrophil count was 1000 per microliter or less (P = 0.0039), reduced the number of days (1 vs. 35) on which antibiotics were used to treat fever and neutropenia, and significantly increased the percentage (100 vs. 29 percent) of patients qualified to receive planned chemotherapy on day 14 of the treatment cycle (P = 0.0015). In addition, the incidence of mucositis was significantly decreased (11 vs. 44 percent, P = 0.041), as was its severity. These findings demonstrate that rhG-CSF is a potent stimulus of normal neutrophil proliferation and maturation. In addition, its administration can reduce both the hematopoietic and oral toxicity of chemotherapy.
Steric Hindrance as a Basis for Structure-Based Design of Selective Inhibitors of Protein-Tyrosine Phosphatases (2001)

Utilizing structure-based design, we have previously demonstrated that it is possible to obtain selective inhibitors of protein-tyrosine phosphatase 1B (PTP1B). A basic nitrogen was introduced into a general PTP inhibitor to form a salt bridge to Asp48 in PTP1B and simultaneously cause repulsion in PTPs containing an asparagine in the equivalent position [Iversen, L. F., et al. (2000) J. Biol. Chem. 275, 10300-10307]. Further, we have recently demonstrated that Gly259 in PTP1B forms the bottom of a gateway that allows easy access to the active site for a broad range of substrates, while bulky residues in the same position in other PTPs cause steric hindrance and reduced substrate recognition capacity [Peters, G. H., et al. (2000) J. Biol. Chem. 275, 18201-18209]. The current study was undertaken to investigate the feasibility of structure-based design, utilizing these differences in accessibility to the active site among various PTPs. We show that a general, low-molecular weight PTP inhibitor can be developed into a highly selective inhibitor for PTP1B and TC-PTP by introducing a substituent, which is designed to address the region around residues 258 and 259. Detailed enzyme kinetic analysis with a set of wild-type and mutant PTPs, X-ray protein crystallography, and molecular modeling studies confirmed that selectivity for PTP1B and TC-PTP was achieved due to steric hindrance imposed by bulky position 259 residues in other PTPs.
The Influence of Planting and Digging Dates on Yield, Value, and Grade of Four Virginia-type Peanut Cultivars1 (1991)

Abstract Obtaining maximum yield, value, and grade of peanut (Arachis hypogaea L.) by deciding the correct planting and digging date of various cultivars is a complex management decision. The influence of planting and digging dates on four large-seeded virginia-type cultivars was determined in a non-irrigated field study at the Tidewater Agricultural Experiment Station in Suffolk, Virginia, from 1983 through 1986. Florigiant, NC 7, NC 9, and VA 81B cultivars were planted at four 10-day intervals beginning about 23 April and harvested at five 10-day intervals beginning about 12 September. Significant differences occurred among cultivars and digging dates each year. NC 7 produced the highest yield, value, extra large kernels, and total kernels. Later digging dates produced higher yield, value, total kernels, and extra large kernels in 1983. The same was true in 1984 through digging date four when the yield and value declined for the fifth digging, while grade characteristics remained the same as digging date four. No significant changes in yield or value occurred after the second digging date in 1986 (22 September); however, total kernels and extra large kernels increased through the fourth digging date. Planting date affected yield only in 1983 (under moisture stress conditions) when each 10-day delay in planting after 29 April resulted in reduced yield and value, while in 1984 the earliest planting date of 20 April (under adverse weather conditions) was the lowest in yield and value. Significant digging date × planting date, digging date × cultivar, and planting date × cultivar interactions were obtained. These results indicate that cultivar selection and digging dates are more important than planting dates in normal years. However, since environmental stress conditions cannot be anticipated, early planting dates would seem to be an advantage when soil temperatures and moisture levels are conducive to good germination and seedling growth.
Implications of Comorbidity for Genetic Studies of Bipolar Disorder: P300 and Eye Tracking as Biological Markers for Illness (1996)

In large families with affective illness, identification of a biological variable is needed that reflects brain dysfunction at an earlier point than symptom development. Eye movement disorder, a possible vulnerability marker in schizophrenia, is less clearly associated with affective illness, although a subgroup of affective disorders shows smooth-pursuit eye movement disorder. The auditory P300 event-related potential may be a useful marker for risk to schizophrenia, but a role in bipolar illness is less certain. The distribution of these two biological variables and their association with symptoms in two multiply affected bipolar families is described. In a single, five-generation family identified for linkage studies through two bipolar I (BPI) probands, 128 members (including 20 spouses) were interviewed. The 108 related individuals had diagnoses of BPI (7), bipolar II (2), cyclothymia (3), or major depressive disorder (19). Eight others had generalised anxiety (1), minor depression (5), intermittent depression (1), or alcoholism (1). Sixty-nine subjects had no psychiatric diagnosis. P300 latency (81) and eye tracking (71) were recorded from a subgroup of relatives within the pedigree. Eye tracking was abnormal in 11 of 71 relatives (15.5%) and was bimodally distributed. In these 11 relatives, clinical diagnoses included minor depression (1), alcoholism (1) and generalised anxiety disorder (1). P300 latency was normally distributed and did not differ from controls. In a second family in which five of seven siblings have BPI illness, P300 latency and eye movement disorder were found in affected relatives and in some unaffected offspring. In these large families, clinical diagnoses of general anxiety, alcoholism and minor depression, when associated with eye tracking abnormality, may be considered alternative clinical manifestations of the same trait that in other relatives is expressed as bipolar illness.
Accelerated reconstitution of platelets and erythrocytes after syngeneic transplantation of bone marrow cells derived from thrombopoietin pretreated donor mice (1995)

The recent cloning of the ligand of the c-Mpl hematopoietin receptor has indicated a major role for this cytokine in the development of megakaryocytes. In this study we have applied c-Mpl ligand (thrombopoietin [TPO]) in the setting of syngeneic transplantation in an attempt to accelerate the reconstitution of platelets. Donor mice were treated with 20 kilounits (kU)/d TPO intraperitoneally (ip) for 5 days. This resulted in a 2.5-fold increment in platelet counts from 1,119 x 10(9)/L to 2,582 x 10(9)/L (mean, n = 7). Total numbers of hematopoietic progenitor cells in bone marrow (BM) and spleen, as assessed in a colony-forming unit-granulocyte erythroid monocyte macrophage (CFU-GEMM) colony assay (55.3 v 38.6 x 10(3) CFU/femur; 27.3 v 16.3 x 10(3) CFU/spleen, mean, n = 7) as well as total numbers of burst-forming unit-erythroid (BFU-E) (24.0 v 16.4 x 10(3)/femur; 10.2 v 1.9 x 10(3)/spleen, mean, n = 7), were significantly higher in TPO-treated donors than in saline-treated controls. Female Balb-C mice were lethally (8.5 Gy) irradiated and transplanted with 10(5) BM cells. After transplantation, groups of mice were treated with recombinant murine TPO at a dose of 20 to 30 kU/d ip or subcutaneously (SC) for 5 to 14 days. Using this dose and schedule, TPO did not stimulate the recovery of platelets in comparison with control animals transplanted with equal cell numbers but given vehicle alone. In other experiments, 10(5) BM cells were procured from TPO-treated donor mice and transplanted into lethally irradiated recipient mice. In comparison with animals transplanted with an equal number of BM cells derived from saline-treated controls, recipients of TPO-treated BM cells had significantly faster platelet recovery and higher platelet nadir counts (88 v 30 x 10(9)/L, mean, n = 20). Transplantation of TPO-treated BM cells also resulted in an accelerated recovery of erythrocytes and increased erythrocyte nadir counts (7.2 v 5.0 x 10(12)/L, mean, n = 20). At the day of platelet nadir (day 12 after transplantation) these animals had higher numbers of BFU-Es (770 v 422, mean, n = 5) in the marrow and also had higher reticulocyte counts (44 / 1000 v 8 / 1000 mean, n = 5) in the blood. Therefore, the accelerated recovery of erythrocytes may be a direct effect of TPO on erythropoiesis.(ABSTRACT TRUNCATED AT 400 WORDS)
Direct Method for Optimized Effective Potentials in Density-Functional Theory (2002)

The conventional optimized effective potential method is based on a difficult-to-solve integral equation. In the new method, this potential is constructed as a sum of a fixed potential and a linear combination of basis functions. The energy derivatives with respect to the coefficients of the linear combination are obtained. This enables calculations by optimization methods. Accurate atomic and molecular calculations with Gaussian basis sets are presented for exact exchange functionals. This efficient and accurate method for the optimized effective potential should play an important role in the development and application of density functionals.
Retinoic acid-producing DCs and gut-tropic FOXP3+regulatory T cells in the induction of oral tolerance (2013)

The systemic unresponsiveness of the immune system to orally administered antigens is known as oral tolerance. Recent findings describe a new step for the induction of oral tolerance, consisting in the homing of FOXP3<sup>+</sup> regulatory T cells to the small bowel and the local acquisition of full immunosuppressive capacities, a process in which retinoic acid-producing dendritic cells might play a crucial role.
Effect of lym-1 radioimmunoconjugate on refractory chronic lymphocytic leukemia (1994)

Although the data raise the possibility of a role for 131I-Lym-1 monoclonal antibody in the treatment of chronic lymphocytic leukemia, strategies to address the radionuclide-induced thrombocytopenia are essential before this intervention can become a clinically useful therapeutic modality for chronic lymphocytic leukemia.
Memory during subclinical hippocampal seizures (1989)

We performed neuropsychological testing in 2 patients during subclinical hippocampal seizures recorded with depth electrodes. Neither subject showed impairment of consciousness, orientation, motor skills, or verbal fluency. The rapidity of recall of a well-learned word list was impaired in 1 subject during ictal fast spiking in the left hippocampus. Subclinical seizure activity may be responsible for a portion of the memory deficits found in patients with epilepsy.
Carboxylation mechanism and stereochemistry of crotonyl-CoA carboxylase/reductase, a carboxylating enoyl-thioester reductase (2009)

Chemo- and stereoselective reductions are important reactions in chemistry and biology, and reductases from biological sources are increasingly applied in organic synthesis. In contrast, carboxylases are used only sporadically. We recently described crotonyl-CoA carboxylase/reductase, which catalyzes the reduction of (E)-crotonyl-CoA to butyryl-CoA but also the reductive carboxylation of (E)-crotonyl-CoA to ethylmalonyl-CoA. In this study, the complete stereochemical course of both reactions was investigated in detail. The pro-(4R) hydrogen of NADPH is transferred in both reactions to the re face of the C3 position of crotonyl-CoA. In the course of the carboxylation reaction, carbon dioxide is incorporated in anti fashion at the C2 atom of crotonyl-CoA. For the reduction reaction that yields butyryl-CoA, a solvent proton is added in anti fashion instead of the CO(2). Amino acid sequence analysis showed that crotonyl-CoA carboxylase/reductase is a member of the medium-chain dehydrogenase/reductase superfamily and shares the same phylogenetic origin. The stereospecificity of the hydride transfer from NAD(P)H within this superfamily is highly conserved, although the substrates and reduction reactions catalyzed by its individual representatives differ quite considerably. Our findings led to a reassessment of the stereospecificity of enoyl(-thioester) reductases and related enzymes with respect to their amino acid sequence, revealing a general pattern of stereospecificity that allows the prediction of the stereochemistry of the hydride transfer for enoyl reductases of unknown specificity. Further considerations on the reaction mechanism indicated that crotonyl-CoA carboxylase/reductase may have evolved from enoyl-CoA reductases. This may be useful for protein engineering of enoyl reductases and their application in biocatalysis.
Personal Photo Organizer Based on Automated Annotation Framework (2009)

Current researches toward solving personal photo management suffered two problems: (1) lacking of training data, and (2) no consolidated reference for classification. In this paper, we propose an automated annotation framework to address these problems. The framework was composed by three main components: the context information generator, the semantic concept detector, and the face recognition model. By assigning multi-labels for each photo, the framework makes the photo collection more structured and searchable. Our experimental results show that the techniques used in this framework are promising.
Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses (2016)

Stimulator of interferon genes (STING) is known be involved in control of DNA viruses but has an unexplored role in control of RNA viruses. During infection with DNA viruses STING is activated downstream of cGAMP synthase (cGAS) to induce type I interferon. Here we identify a STING-dependent, cGAS-independent pathway important for full interferon production and antiviral control of enveloped RNA viruses, including influenza A virus (IAV). Further, IAV interacts with STING through its conserved hemagglutinin fusion peptide (FP). Interestingly, FP antagonizes interferon production induced by membrane fusion or IAV but not by cGAMP or DNA. Similar to the enveloped RNA viruses, membrane fusion stimulates interferon production in a STING-dependent but cGAS-independent manner. Abolishment of this pathway led to reduced interferon production and impaired control of enveloped RNA viruses. Thus, enveloped RNA viruses stimulate a cGAS-independent STING pathway, which is targeted by IAV.
ChemInform Abstract: THE REACTION OF SOME 2‐THIENYLLITHIUM DERIVATIVES WITH SOME ALKYL TOSYLATES (1981)

Abstract Die lithiierten Verbindungen (I) reagieren mit Butyltosylat bzw. Propandiolditosylat bevorzugt unter Bildung der Sulfone (II).
Case‐finding in Fabry disease: experience from the North of England (2013)

The advent of effective therapy for Fabry disease (FD) creates two challenges: (1) how do we identify individuals with the condition early in its natural history, and (2) how many people have the condition and require expensive therapy? Between 1981 and 2011, 17 new FD families were referred to the Northern Genetics Service in the North of England, the majority between 2005 and 2001. Since 2009 we have employed biochemical screening in dried blood spots from individuals with high risk phenotypes, such as left ventricular hypertrophy and unexplained renal failure, to identify four of the new index cases; and we have offered comprehensive cascade genetic testing to identify pre-symptomatic and symptomatic cases of FD in their 233 'at risk' relatives. Overall, this combined approach identified a further 23 symptomatic cases of FD and 38 asymptomatic cases. The uptake of cascade genetic testing in this cohort was 48%, which is similar to other inherited disorders for which there is an effective intervention. The minimum prevalence of GLA mutation in the North of England population at the end of 2011 was 1 in 40,800 and the prevalence of symptomatic FD was 1 in 64,600. Improved uptake of cascade genetic testing would increase these estimates to a maximum of 1 in 21,800 and 1 in 49,000 respectively. We suggest that any protocol for case identification should consist of targeted biochemical screening and coordinated cascade genetic testing.
Novel Selective PDE IV Inhibitors as Antiasthmatic Agents. Synthesis and Biological Activities of a Series of 1-Aryl-2,3-bis(hydroxymethyl)naphthalene Lignans (1996)

A series of 1-aryl-2,3-bis(hydroxymethyl)naphthalene lignans have been synthesized and evaluated for their ability to selectively inhibit PDE IV isolated from guinea pig. Replacement of the 1-phenyl ring by a pyridone ring led to marked improvement of their selectivity for PDE IV over PDE III. The compounds that were most potent and selective involved those bearing an N-alkylpyridone ring at C-1. These compounds also showed potent antispasmogenic activity without causing significant changes in heart rate in the guinea pig. The most potent compound was 6,7-diethoxy-2, 3-bis(hydroxymethyl)-1-[1-(2-methoxyethyl)-2-oxo-pyrid-4-yl]nap hth alene (17f), ED50 values of histamine-induced and antigen-induced bronchoconstriction in the guinea pig being 0.08 and 2.3 mg/kg iv, respectively. This compound was chosen as a candidate for further pharmacological evaluation.
[Effect of the combined use of antibiotic-resistant bifidobacteria and the corresponding antibiotics on the survivability of irradiated mice]. (1982)

The combined administration of antibiotic-resistant bifidobacterial strains and the corresponding antibiotics (ampicillin, gentamycin or kanamycin) leads to a greater increase in the survival rate of irradiated mice than the administration of antibiotics only and is a promising method for the treatment of post-irradiation intestinal dysbacteriosis.
Controlled Dimerization of ErbB Receptors Provides Evidence for Differential Signaling by Homo- and Heterodimers (1999)

The four members of the ErbB family of receptor tyrosine kinases are involved in a complex array of combinatorial interactions involving homo- and heterodimers. Since most cell types express more than one member of the ErbB family, it is difficult to distinguish the biological activities of different homo- and heterodimers. Here we describe a method for inducing homo- or heterodimerization of ErbB receptors by using synthetic ligands without interference from the endogenous receptors. ErbB receptor chimeras containing synthetic ligand binding domains (FK506-binding protein [FKBP] or FKBP-rapamycin-binding domain [FRB]) were homodimerized with the bivalent FKBP ligand AP1510 and heterodimerized with the bifunctional FKBP-FRB ligand rapamycin. AP1510 treatment induced tyrosine phosphorylation of ErbB1 and ErbB2 homodimers and recruitment of Src homology 2 domain-containing proteins (Shc and Grb2). In addition, ErbB1 and ErbB2 homodimers activated downstream signaling pathways leading to Erk2 and Akt phosphorylation. However, only ErbB1 homodimers were internalized upon AP1510 stimulation, and only ErbB1 homodimers were able to associate with and induce phosphorylation of c-Cbl. Cells expressing AP1510-induced ErbB1 homodimers were able to associate with and induce phosphorylation of c-Cbl. Cells expressing AP1510-induced ErbB1 homodimers were able to form foci; however, cells expressing ErbB2 homodimers displayed a five- to sevenfold higher focus-forming ability. Using rapamycin-inducible heterodimerization we show that c-Cbl is unable to associate with ErbB1 in a ErbB1-ErbB2 heterodimer most likely because ErbB2 is unable to phosphorylate the c-Cbl binding site on ErbB1. Thus, we demonstrate that ErbB1 and ErbB2 homodimers differ in their abilities to transform fibroblasts and provide evidence for differential signaling by ErbB homodimers and heterodimers. These observations also validate the use of synthetic ligands to study the signaling and biological specificity of selected ErbB dimers in any cell type.
Using Runahead Execution to Hide Memory Latency in High Level Synthesis (2017)

Reads and writes to global data in off-chip RAM can limit the performance achieved with HLS tools, as each access takes multiple cycles and usually blocks progress in the application state machine. This can be combated by using data prefetchers, which hide access time by predicting the next memory access and loading it into a cache before it's required. Unfortunately, current prefetchers are only useful for memory accesses with known regular patterns, such as walking arrays, and are ineffective for those that use irregular patterns over application-specific data structures. In this work, we demonstrate prefetchers that are tailor-made for applications, even if they have irregular memory accesses. This is achieved through program slicing, a static analysis technique that extracts the memory structure of the input code and automatically constructs an application-specific prefetcher. Both our analysis and tool are fully automated and implemented as a new compiler flag in LegUp, an open source HLS tool. In this work we create a theoretical model showing that speedup must be between 1x and 2x, we also evaluate five benchmarks, achieving an average speedup of 1.38x with an average resource overhead of 1.15x.
Elevated Plasma YKL-40 Predicts Increased Risk of Gastrointestinal Cancer and Decreased Survival After Any Cancer Diagnosis in the General Population (2008)

In the general population, elevated plasma YKL-40 predicts increased risk of gastrointestinal cancer and decreased survival after any cancer diagnosis.