gebhart/patrepeval huggingface dataset:
Analysis of the efficacy of measures to reduce pain after subcutaneous administration of epoetin alfa (1994)

Pain at the injection site with subcutaneous administration of epoetin alfa preparations is a common adverse event, and sometimes precludes self-administration. The pain is caused mainly by the vehicle. The present studies were designed to assess whether pain after subcutaneous administration of the vehicle can be influenced by making the solution iso-osmotic, or by diluting the vehicle by the bacteriostatic agent benzyl alcohol saline (BAS). The volumes injected were 1 ml. We also determined whether reduction of the injected volume of 1 ml to 0.33 ml or to 0.1 ml could be of clinical importance. One millilitre of normal saline served as a placebo control. The studies were done in a double-blind, placebo-controlled, randomized order, cross-over fashion in healthy volunteers. Pain scores were obtained from visual analogue pain scales with no divisions and from 5-point verbal descriptive pain scales. Dilution of the vehicle with BAS resulted in significantly less pain (P < 0.0001) after subcutaneous injection, comparable to levels obtained with normal saline. Making the vehicle iso-osmotic had no effects. Injection of smaller volumes of the vehicle was beneficial with 0.1 ml (P < 0.0001), but the reduction to 0.33 ml was not statistically significant.
Microstimulation of spinal motoneurons: a model study (2002)

A computer model of a cat spinal motoneuron was developed and used to study neuronal excitation by extracellular electric fields. The model included a myelinated axon, initial segment, axon hillock, a three compartment model of the soma, and a tapering dendrite. The extracellular space was modeled as an infinite homogeneous medium, and the electrode by a point current source. Threshold profiles were generated for electrode to neuron distances between 50 /spl mu/m and 1 mm. The results demonstrate that the model reproduced excitation patterns documented in single cell mapping experiments. The threshold profile along the axon had a distinct sinusoidal shape with peaks at the center of the internodes and valleys at the nodes. The depth of modulation of this sinusoidal pattern was dependent on the distance from the electrode to the neural structure. The relationship between the threshold current and the electrode to fiber distance was non-linear. The slope of the relationship was steeper for the excitation of the cell body compared to excitation of the axon.
Repression Domains of Class II ERF Transcriptional Repressors Share an Essential Motif for Active Repression (2001)

We reported previously that three ERF transcription factors, tobacco ERF3 (NtERF3) and Arabidopsis AtERF3 and AtERF4, which are categorized as class II ERFs, are active repressors of transcription. To clarify the roles of these repressors in transcriptional regulation in plants, we attempted to identify the functional domains of the ERF repressor that mediates the repression of transcription. Analysis of the results of a series of deletions revealed that the C-terminal 35 amino acids of NtERF3 are sufficient to confer the capacity for repression of transcription on a heterologous DNA binding domain. This repression domain suppressed the intermolecular activities of other transcriptional activators. In addition, fusion of this repression domain to the VP16 activation domain completely inhibited the transactivation function of VP16. Comparison of amino acid sequences of class II ERF repressors revealed the conservation of the sequence motif (L)/(F)DLN(L)/(F)(x)P. This motif was essential for repression because mutations within the motif eliminated the capacity for repression. We designated this motif the ERF-associated amphiphilic repression (EAR) motif, and we identified this motif in a number of zinc-finger proteins from wheat, Arabidopsis, and petunia plants. These zinc finger proteins functioned as repressors, and their repression domains were identified as regions that contained an EAR motif.
Redundancy of myostatin and growth/differentiation factor 11 function (2009)

These results provide evidence that myostatin and Gdf11 have redundant functions in regulating skeletal patterning in mice but most likely not in regulating muscle size.
Role of viral antigens in destructive cellular immune responses to adenovirus vector-transduced cells in mouse lungs (1996)

Adenoviruses missing E1 have been used as gene delivery vectors to the lungs for the treatment of cystic fibrosis. Transient expression of the recombinant gene and the development of inflammation have been two major limitations to the application of first-generation recombinant adenoviruses for gene therapy. Studies with mouse models of liver- and lung-directed gene therapy suggested that CD8+ cytotoxic T lymphocytes (CTLs) are effectors that contribute to extinction of transgene expression. The precise antigens responsible for activation of CTLs have not been identified. In this study, we examine the relative contributions of viral proteins versus the transgene product to the activation of CTLs which eliminate transgene-containing cells in mouse lungs. Instillation of a lacZ-expressing virus into the lungs of C57BL/6 mice elicited CTL responses to both viral proteins and the transgene product, beta-galactosidase, which collectively contribute to loss of trans-gene expression in mouse airways. Similar results were obtained in two experimental models in which the animals should be tolerant to the transgene, i.e., lacZ virus delivered to an animal transgenic for lacZ and a virus expressing the liver-specific enzyme ornithine transcarbamylase administered to the lungs of various strains of immune-competent mice. These data confirm the hypothesis that CTLs specific for viral antigens contribute to the problem of transgene instability in mouse lungs and indicate that CTLs specific for transgene product alone cannot account for the observed problem.
Stability of Parenterals (1984)

(1984). Stability of Parenterals. Drug Development and Industrial Pharmacy: Vol. 10, No. 8-9, pp. 1297-1342.
Isolation and characterization of the mouse cardiac myosin heavy chain genes (1991)

Two mouse genomic libraries were probed in order to isolate the murine cardiac myosin heavy chain (MHC) genes. Two overlapping cosmid clones that encode the cardiac genes were isolated. One of them encompasses the entire alpha-cardiac MHC gene, its 5'-flanking region and approximately 10 kilobase pairs (kb) of the 3'-end of the beta-cardiac MHC gene which we determined is located approximately 4 kb upstream of the alpha-cardiac MHC gene. Four clones isolated from a bacteriophage library were found to overlap with the 5'-region of the cosmid clones, and sequence analysis confirmed that the 5'-end of the beta-cardiac MHC gene was contained within one of the clones. Primer extension and polymerase chain reaction (PCR) analyses were used to define the transcriptional start site and the 5'-organization of the alpha-cardiac MHC gene. This region exhibits greater than 90% homology to the corresponding nucleotides of the rat alpha-cardiac MHC gene. To assess the importance of the intergenic region in directing expression of the alpha-cardiac MHC gene, a fragment containing the 3'-end of the beta-cardiac gene and the 5'-end of the alpha-cardiac gene was linked to a chloramphenicol acetyltransferase gene and used to generate transgenic mice. Analyses of the chloramphenicol acetyltransferase (CAT) activity in two lines indicate that the intergenic region is sufficient to properly direct expression in a tissue-specific manner.
Black Water Mystery Uncovered Under Sink (2002)

This article describes a case study that occurred in January 2001 where the water department in Madison Heights, Michigan, received numerous complaints about black water showing up in kitchen sinks and bathroom lavatories in a 200 unit senior citizen high‐rise apartment building. It turned out to be black rubber fibers from the tubing inside the stainless steel braided hoses that connected the stop valves to the faucets in the kitchen sinks. The temperature was found to be a major factor in the softening and deterioration of the rubber tubing.
Mouse notch: expression in hair follicles correlates with cell fate determination. (1993)

Many vertebrate tissues, including skin, are known to develop as a consequence of epithelial-mesenchymal interactions. Much less is known about the role of cell-cell interaction within the epithelial or the mesenchymal compartments in morphogenesis. To investigate cell-cell interactions during skin development, and the potential role of the Notch homolog in this process, we cloned the mouse homolog of Notch (mNotch) and studied its expression pattern, starting as early as mesoderm formation. The novel application of double-labeled in situ hybridization in vertebrates allowed high resolution analysis to follow the fate of mNotch expressing cells directly. In comparison with the distribution of Id mRNA, analysis confirmed that in the hair follicle high levels of mNotch are expressed exclusively in the epithelial compartment. Hair follicle matrix cells start expressing mNotch as different cell types become distinguishable in the developing follicle. mNotch mRNA expression persists throughout the growth phase of the follicle and maintains the same expression profile in the second hair cycle. The cells in the follicle that undergo a phase of high level mNotch expression are in transition from mitotic precursors to several discreet, differentiating cell types. Our observations point out that both in time (during development) and in space (by being removed one cell layer from the dermal papilla) mNotch expression is clearly separated from the inductive interactions. This is a novel finding and suggests that mNotch is important for follicular differentiation and possibly cell fate selection within the follicle.
Biweekly Docetaxel and Vinorelbine in Anthracycline-Resistant Metastatic Breast Cancer (2003)

The aim of this study was to determine the efficacy and toxicity of a biweekly combination of docetaxel and vinorelbine in patients with metastatic breast cancer (MBC) previously treated with anthracyclines. Eligible patients (n = 49) with MBC received vinorelbine, 25 mg/m2, followed by docetaxel, 60 mg/m2. Cycles were repeated every 14 days for a total of 8 planned cycles. Response rate was evaluated every 4 cycles. All 49 patients were evaluable for safety and 44 for efficacy. Vinorelbine plus docetaxel resulted in an overall response rate of 45% (CI 95%: 31-60) with 2 (4%) complete responses and 18 (41%) partial responses. Patients with visceral metastasis achieved a lower response rate than those without (33% versus 60%, p = 0.044). Time to progression was 11.0 months (CI 95%: 8.6-13.5), and median overall survival was 12.7 months (CI 95%: 9.0-16.4). The most common grade III to IV hematologic adverse events was neutropenia (65% of patients). Febrile neutropenia was observed in 9 cycles (3%) and in 7 patients (14%). Grade III to IV nonhematologic toxicity was rare. Biweekly combination of docetaxel and vinorelbine is an effective and well-tolerated regimen in anthracycline-resistant MBC.
Coverage Algorithms for WiFO: A Hybrid FSO-WiFi Femtocell Communication System (2017)

We study coverage algorithms for deployment of WiFO - a hybrid femtocell architecture based on WiFi and Free Space Optical (FSO) technologies to significantly increase wireless throughput of existing WiFi networks. In contrast with existing WiFi networks, WiFO incorporates small cell size, line of sight transmissions, and the Gaussian attenuation model of light intensity into the design of the coverage algorithms. Specifically, two types of coverage scenarios - the non- overlapped and the overlapped coverage are presented. For the non-overlapped coverage, we show the bounds of coverage efficiency for a finite rectangle area based on a simple model. For the overlapped coverage, user's SNR profiles are assumed to be given. Using these, three algorithms for determining the optimized deployment based on user's SNR profiles and Gaussian light attenuation models are proposed and evaluated. Simulations results are provided to verify the proposed algorithms.
B Cell Differentiation and Immunoregulatory T Cell Function in Human Cord Blood Lymphocytes (1980)

The functional maturity of T and B lymphocyte populations from human newborns was evaluated using a reverse hemolytic plaque assay to detect immunoglobulin-secreting cells generated in in vitro cultures stimulated with pokeweed mitogen (PWM), a T cell-dependent polyclonal activator, and the Epstein-Barr virus (EBV), a T cell-independent B cell activator. Cord blood lymphocytes failed to produce immunoglobulin in response to PWM, but did respond with immunoglobulin synthesis to stimulation with EBV. Co-culture experiments demonstrated that cord blood T cells would inhibit immunoglobulin production by adult cells stimulated with PWM, but not with EBV. Cord blood T cells did suppress immunoglobulin production by cord blood B cells when stimulated with a mixture of EBV and PWM, indicating that cord blood, in contrast to adult blood, contains a population of suppressor T cell precursors that are easily activated by PWM. Irradiation of the cord blood T cells with 2,000 rad eliminated the suppressor activity and revealed normal helper function for immunoglobulin (Ig) G, A, and M when these T cells were co-cultured with adult B cells. Cord blood B cells co-cultured with adult T cells or irradiated cord blood T cells did produce immunoglobulin in response to PWM, but the response was significantly lower than that of adult B cells, and only IgM was produced in these cultures. These studies demonstrate that both the T and B cells of the human newborn have significant functional differences compared with the functions of T and B lymphocyte populations in adults.
Tyrosine kinase inhibitor CEP-701 blocks the NTRK1/NGF receptor and limits the invasive capability of prostate cancer cells in vitro (2007)

In the prostate, cellular growth and differentiation are finely regulated by a complex interaction between stromal and epithelial cells under the control of both autocrine and paracrine regulatory factors such as the nerve growth factor (NGF). However, the role of NGF and its receptors including the high-affinity p-140 TrkA and the low-affinity p75 NTR receptors remains controversial. Moreover prostate tissues stored other neutrophins such as NT3, NT4 and brain derived neutrophic factor (BDNF) as well as the corresponding receptors (NTRs). Different members of NTRs are expressed during prostate cancer (PCa) progression, suggesting their involvement in cell proliferation, anoikis protection and malignancy. Therefore, we analyzed the expression of NTRs including NTRK1 (TrkA), NTRK2 (TrkB), NTRK3 (TrkC) and p75 NGFR in a panel of 7 well-characterized PCa cell lines and 12 cell derivatives from PC3 (4), DU145 (2), CWR22R (4) and LnCap (2) cell lines possessing different proliferative/invasive capabilities. We evaluated also the role of NGF, BDNF and NT3 in the modulation of cell migration and invasion and, finally, the effects of a pan Trk inhibitor, CEP-701 which has been included in some clinical trials for the treatment of PCa. We observed the following: i) TrkA and TrkB expression was significantly higher in AR-negative compared to AR-positive cells; ii) TrkA and TrkB expression was related to the invasive capacity/malignancy of PCa cells; iii) p75 NGFR could be considered a tumor suppressor gene which is present at high levels only in AR-positive cells; and iv) that NGF and BDNF (targeting TrkA/p75 NTR and TrKB, respectively) induced cell migration and this was inhibited by the CEP-701 treatment. In conclusion, the malignancy of PCa seems to be accompanied by increased TrkA and TrkB signaling (with a reduction of p75 NGFR expression) and CEP-701 could be used to reduce the metastasis formation in advanced PCa. CEP-701 is a trademark of Cephalon Inc., West Chester, PA, USA.
Tuning the Reactivity of Glycosides: Efficient One-pot Oligosaccharide Synthesis1 (1995)

Tuning the reactivity of glycosyl donors by selective introduction of different protecting and leaving groups enabled highly efficient oligosaccharide synthesis. Utilising both phenylseleno and ethylthio glycosides in combination with the cyclohexane-1,2-diacetal (CDA) protecting group provided four different levels of reactivity. One-pot sequential glycosidation of three components gave trisaccharides and tetrasaccharides.
Synthesis of Janus Compounds for the Recognition of G-U Mismatched Nucleobase Pairs (2013)

The design and synthesis of two Janus-type heterocycles with the capacity to simultaneously recognize guanine and uracyl in G-U mismatched pairs through complementary hydrogen bond pairing is described. Both compounds were conveniently functionalized with a carboxylic function and efficiently attached to a tripeptide sequence by using solid-phase methodologies. Ligands based on the derivatization of such Janus compounds with a small aminoglycoside, neamine, and its guanidinylated analogue have been synthesized, and their interaction with Tau RNA has been investigated by using several biophysical techniques, including UV-monitored melting curves, fluorescence titration experiments, and (1)H NMR. The overall results indicated that Janus-neamine/guanidinoneamine showed some preference for the +3 mutated RNA sequence associated with the development of some tauopathies, although preliminary NMR studies have not confirmed binding to G-U pairs. Moreover, a good correlation has been found between the RNA binding affinity of such Janus-containing ligands and their ability to stabilize this secondary structure upon complexation.
Permeability Barrier of Gram-Negative Cell Envelopes and Approaches To Bypass It (2015)

Gram-negative bacteria are intrinsically resistant to many antibiotics. Species that have acquired multidrug resistance and cause infections that are effectively untreatable present a serious threat to public health. The problem is broadly recognized and tackled at both the fundamental and applied levels. This paper summarizes current advances in understanding the molecular bases of the low permeability barrier of Gram-negative pathogens, which is the major obstacle in discovery and development of antibiotics effective against such pathogens. Gaps in knowledge and specific strategies to break this barrier and to achieve potent activities against difficult Gram-negative bacteria are also discussed.
Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II, VII, IX, and X; proteins S and C; and γ-glutamyl carboxylase) gene variants with warfarin sensitivity (2003)

We analyzed mutations of 7 vitamin K-dependent protein and cytochrome P450 2C9 genes in 45 patients and investigated whether any contribute to the large interpatient variability in the warfarin dose-effect relationship. Total clearance and daily dose, INR and INR/Cp, were used as pharmacokinetic and pharmacodynamic indexes, respectively. Patients were grouped by genotype based on a single polymorphism and combinations of polymorphisms. Among the 30 sequence variants identified, CYP2C9*3, 165Thr-->Met of the factor II gene, -402G-->A, (37-bp repeat)n, and -746T-->C of the factor VII gene, and (CAA repeat)n of the gamma-glutamyl carboxylase gene were selected as candidate polymorphisms. As the analysis of single polymorphisms implied, the highest INR/Cp mean values and the lowest warfarin maintenance doses were observed in patients homozygous for the 165Met, -402G, (37-bp repeat)6 and -746T alleles. Multiple regression analysis revealed that warfarin sensitivity was independently associated with -402G-->A, (CAA repeat)n, CYP2C9*3, and 165Thr-->Met, which accounted for 50% of variance. These results suggest that part of the considerable interpatient variation is attributable to genetic variation, and the combined genotyping of CYP2C9 and certain vitamin K-dependent protein genes is useful for predicting anticoagulant responses.
Recent experience with the complement fixation test in the laboratory diagnosis of rickettsial diseases in the United States (1976)

Sera from patients suspected of having rickettsial infections were tested in the complement fixation test with antigens prepared from the rickettsiae of Rocky Mountain spotted fever (SF), rickettsial pox (RP), murine typhus, epidemic typhus, and from Rickettsia canada (RC). Eight units of antigen were used in all cases and two units in man. Only those patients with antibody titers of 1:16 or higher were included in the study. Largely on the basis of comparative titers, the patients were divided into two groups: 102 with SF and 35 with infections by one of the members of the typhus group. The antibody titers were higher with SF antigen than RP antigen in 72% of the SF patients, and in only two SF patients was the RP titer higher, and then by only one tube (twofold dilution). There seemed little advantage in including the RP antigen in the battery of rickettsial antigens. Cross-reaction with at least one of the typhus antigens was observed in the sera from 64% of the SF patients. It was extensive enough to be confusing (within one tube) in 17% with eight units of antigen, but the differentiation was more distinct with two units of antigen. The cross-reaction with typhus antigens was as frequent in children with SF as it was in adults; thus, it is unlikely that these cross-reactions resulted from previous typhus vaccination. The serological differentiation between murine typhus and epidemic typhus was frequently difficult, but the epidemiological background was distinct. Five patients had higher titers to RC antigen, and four of these may possibly have had RC infections.
L-Arginine therapy in cardiovascular pathologies: beneficial or dangerous? (2008)

The effects of L-arginine supplementation on human physiology appear to be multicausal and dose related. Criteria need to be developed to define patients who benefit from L-arginine supplementation.
T cells redirected against CD70 for the immunotherapy of CD70-positive malignancies (2011)

T-cell therapy with genetically modified T cells targeting CD19 or CD20 holds promise for the immunotherapy of hematologic malignancies. These targets, however, are only present on B cell-derived malignancies, and because they are broadly expressed in the hematopoietic system, their targeting may have unwanted consequences. To expand T-cell therapies to hematologic malignancies that are not B cell-derived, we determined whether T cells can be redirected to CD70, an antigen expressed by limited subsets of normal lymphocytes and dendritic cells, but aberrantly expressed by a broad range of hematologic malignancies and some solid tumors. To generate CD70-specific T cells, we constructed a chimeric antigen receptor (CAR) consisting of the CD70 receptor (CD27) fused to the CD3-ζ chain. Stimulation of T cells expressing CD70-specific CARs resulted in CD27 costimulation and recognition of CD70-positive tumor cell lines and primary tumor cells, as shown by IFN-γ and IL-2 secretion and by tumor cell killing. Adoptively transferred CD70-specific T cells induced sustained regression of established murine xenografts. Therefore, CD70-specific T cells may be a promising immunotherapeutic approach for CD70-positive malignancies.
Free-standing, optically pumped, GaN∕InGaN microdisk lasers fabricated by photoelectrochemical etching (2004)

GaN-based, mushroom-shaped microdisk lasers were fabricated using band-gap selective photoelectrochemical etching. The optically pumped microdisks had well-defined, distinct modes at excitation powers ranging from about 8to16W∕cm2. Modal linewidths of 0.09nm were reported, which was near the resolution of the measurement equipment. Quality factors for the microdisks were &amp;gt;4600. The observed lasing threshold was 12.1W∕cm2. At higher excitation powers, heating effects and degradation were observed in the optical response of the microdisks.