gebhart/patrepeval huggingface dataset:
Real‐time PCR for detection and quantitation of hepatitis B virus DNA (2001)

A sensitive and reproducible real-time PCR assay based on TaqMan technology was developed for the detection and quantitation of hepatitis B virus (HBV) DNA in serum, and compared with an "in-house" qualitative PCR assay. HBV DNA was measured in 125 serum samples from 76 hepatitis B patients, consisting of 22 patients with an acute infection, 20 patients with a previous history of hepatitis B infection, and 34 patients with a chronic hepatitis B. Four patients with a chronic infection were treated with either an IFN-alpha monotherapy or a combination of IFN-alpha and lamivudine. Twenty-nine sera from healthy individuals and non-hepatitis B patients served as negative controls. The assay was validated by using a 10-fold dilution series of the World Virological Quality Control (VQC) sample containing 3.73 x 10(7) genome equivalents per ml. The detection limit for the real-time PCR was 3.73 x 10(2) genome equivalents per ml (geq/ml), while it was 3.73 x 10(3) geq/ml for the in-house PCR. The real-time PCR assay had an 8-logarithm dynamic range spanning from 10(2) to 10(10) geq/ml. In clinical serum samples, the real-time PCR and the in-house PCR detected HBV DNA in 81% (101/125) and 66% (83/125) of samples, respectively. HBV DNA was not detected among the negative controls by either of these assays. In conclusion, real-time PCR is a sensitive, specific, and a reproducible approach for the detection and quantitation of HBV DNA in clinical serum samples, useful also for monitoring the efficacy of antiviral treatment.
Fast and Accurate Deep Network Learning by Exponential Linear Units (ELUs) (2015)

We introduce the "exponential linear unit" (ELU) which speeds up learning in deep neural networks and leads to higher classification accuracies. Like rectified linear units (ReLUs), leaky ReLUs (LReLUs) and parametrized ReLUs (PReLUs), ELUs alleviate the vanishing gradient problem via the identity for positive values. However, ELUs have improved learning characteristics compared to the units with other activation functions. In contrast to ReLUs, ELUs have negative values which allows them to push mean unit activations closer to zero like batch normalization but with lower computational complexity. Mean shifts toward zero speed up learning by bringing the normal gradient closer to the unit natural gradient because of a reduced bias shift effect. While LReLUs and PReLUs have negative values, too, they do not ensure a noise-robust deactivation state. ELUs saturate to a negative value with smaller inputs and thereby decrease the forward propagated variation and information. Therefore, ELUs code the degree of presence of particular phenomena in the input, while they do not quantitatively model the degree of their absence. In experiments, ELUs lead not only to faster learning, but also to significantly better generalization performance than ReLUs and LReLUs on networks with more than 5 layers. On CIFAR-100 ELUs networks significantly outperform ReLU networks with batch normalization while batch normalization does not improve ELU networks. ELU networks are among the top 10 reported CIFAR-10 results and yield the best published result on CIFAR-100, without resorting to multi-view evaluation or model averaging. On ImageNet, ELU networks considerably speed up learning compared to a ReLU network with the same architecture, obtaining less than 10% classification error for a single crop, single model network.
A Genetically Distinct Thymidine Kinase in Mammalian Mitochondria (1973)

Abstract A thymidine kinase (EC 2.7.1.21) associated with mitochondria has been demonstrated in tissue culture both in wild type mouse cells and in cells which lack the cytoplasmic thymidine kinase. The mitochondrial thymidine kinase represents approximately 1% of the total cell thymidine kinase activity in wild type cells grown in culture and all of the activity of the mutant cells. The mitochondrial enzyme can be distinguished from the cytoplasmic enzyme on the basis of its Km for thymidine and its localization on the mitochondrial membrane. Furthermore, the presence of the enzyme in the mitochondria of the mutant cells results in exclusive labeling of mitochondrial DNA when the cells are grown in the presence of [3H]thymidine. Labeling studies in the presence and absence of methotrexate (an inhibitor of dihydrofolate reductase) demonstrate that, in the presence of exogenously added thymidine, both the product of the mitochondrial thymidine kinase and thymidine nucleotides synthesized in the cell cytoplasm are incorporated into mitochondrial DNA.
A phase I dose-escalation study of PEP02 (irinotecan liposome injection) in combination with 5-fluorouracil and leucovorin in advanced solid tumors (2016)

The trial was retrospectively registered ( NCT02884128 ) with date of registration: August 12, 2016.
Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. (1998)

BEP and VIP produce comparable favorable response rate and survival in patients with poor-risk germ cell tumors. The substitution of ifosfamide for bleomycin, however, was associated with significantly greater toxicity. Four courses of BEP remain the standard treatment for advanced disseminated germ cell tumors.
Characterization of the Agrobacterium vitis pehA gene and comparison of the encoded polygalacturonase with the homologous enzymes from Erwinia carotovora and Ralstonia solanacearum (1997)

DNA sequencing of the Agrobacterium vitis pehA gene revealed a predicted protein with an M(r) of 58,000 and significant similarity to the polygalacturonases of two other plant pathogens, Erwinia carotovora and Ralstonia (= Pseudomonas or Burkholderia) solanacearum. Sequencing of the N terminus of the PehA protein demonstrated cleavage of a 34-amino-acid signal peptide from pre-PehA. Mature PehA accumulated primarily in the periplasm of A. vitis and pehA+ Escherichia coli cells during exponential growth. A. vitis PehA released dimers, trimers, and monomers from polygalacturonic acid and caused less electrolyte leakage from potato tuber tissue than did the E. carotovora and R. solanacearum polygalacturonases.
Phase I/II study of immunotherapy using tumor antigen-pulsed dendritic cells in patients with hepatocellular carcinoma (2012)

Dendritic cells (DCs) are increasingly used as adjuvants for vaccination strategies; however, there has been very little development in DC vaccines for patients with hepatocellular carcinoma (HCC). In this study, we assessed the safety, feasibility and efficacy of a multiple tumor-associated antigen (TAA)-pulsed DC vaccine in 5 patients with advanced HCC. DCs were generated by culturing blood monocytes in the presence of granulocyte macrophage-colony stimulating factor and interleukin-4 for 5 days. The DC vaccine was prepared by pulsing DCs with cytoplasmic transduction peptide-attached α-fetoprotein, glypican-3 and MAGE-1 recombinant fusion proteins and cultivating them in the presence of maturation cocktail. DCs were injected subcutaneously near the inguinal lymph nodes, followed by topical application of toll-like receptor-7 agonist around the injection site. We showed that our DC vaccine was safe and well-tolerated over 6 vaccinations in 5 patients. All 5 patients showed T cell responses against TAAs. Clinical benefit was observed in one of the 5 patients. In conclusion, the feasibility, safety and immune activity of DCs pulsed with TAAs were confirmed in HCC patients. However, clinical response was detected only in one patient. Future trials may consider applying this therapy in a less advanced stage to obtain better clinical responses.
Wound repair and proliferation of bronchial epithelial cells regulated by CTNNAL1 (2007)

Adhesion molecules play vital roles in airway hyperresponsiveness (AHR) or airway inflammation. Our previous study indicated that adhesion molecule catenin alpha-like 1 (CTNNAL1) is relevant closely to asthma susceptibility, but its biological function or significance is still unclear. In the present study, we observed the temporal and spatial distribution of CTNNAL1 expression in mouse lung tissue with the OVA-sensitized asthma model and found that the level of CTNNAL1 mRNA showed a prominent negative correlation with pulmonary resistance (R(L)). To study the function of CTNNAL1 in airway, effects of CTNNAL1 on proliferation and wound repair activity of human bronchial epithelial cells (HBEC) was investigated with antisense oligonucleotide (ASO) technique. The results showed that: (1) CTNNAL1 ASO could decelerate the repairing velocity and proliferation of HBEC; (2) CTNNAL1 expression was increased on the edge cells of mechanic wounded area in culture; (3) extracellular matrix component fibronectin (Fn) obviously promoted wound repair activity and proliferation of HBEC, which could be blocked by CTNNAL1 ASO; (4) Western blot showed that Fn could promote FAK phosphorylation, which also be inhibited by CTNNAL1 ASO. In conclusion, the level of CTNNAL1 mRNA expression is highly correlated to airway resistance; CTNNAL1 may contribute to the wound repair and proliferation of HBEC. Furthermore, it may serve to Fn mediated cell-extracellular adhesion and its signal transduction.
Temperature-aware microarchitecture (2003)

With power density and hence cooling costs rising exponentially, processor packaging can no longer be designed for the worst case, and there is an urgent need for runtime processor-level techniques that can regulate operating temperature when the package's capacity is exceeded. Evaluating such techniques, however, requires a thermal model that is practical for architectural studies.This paper describes HotSpot, an accurate yet fast model based on an equivalent circuit of thermal resistances and capacitances that correspond to microarchitecture blocks and essential aspects of the thermal package. Validation was performed using finite-element simulation. The paper also introduces several effective methods for dynamic thermal management (DTM): "temperature-tracking" frequency scaling, localized toggling, and migrating computation to spare hardware units. Modeling temperature at the microarchitecture level also shows that power metrics are poor predictors of temperature, and that sensor imprecision has a substantial impact on the performance of DTM.
Beneficial Role of Erythrocyte Adenosine A2B Receptor–Mediated AMP-Activated Protein Kinase Activation in High-Altitude Hypoxia (2016)

Together, human and mouse studies reveal novel mechanisms of hypoxia adaptation and potential therapeutic approaches for counteracting hypoxia-induced tissue damage.
Strictly Target Cell-dependent Activation of T Cells by Bispecific Single-chain Antibody Constructs of the BiTE Class (2007)

Bispecific antibodies have been extensively studied in vitro and in vivo for their use in redirected tumor cell lysis. A particular challenge of bispecific antibody constructs that recognize the invariant CD3 signaling complex is a controlled polyclonal activation of T cells that, ideally, is exquisitely dependent on the presence of target cells. Otherwise, overt production of inflammatory cytokines and secondary reactions may occur as side effects, as can be observed with constitutively T-cell activating monoclonal antibodies to CD3 or CD28, and with bispecific antibodies bearing Fc gamma portions. Here we analyzed 2 distinct bispecific single-chain antibody constructs of the BiTE class, called MT110 and MT103 (or MEDI-538), for conditional T-cell activation. In the presence of target-expressing cell lines, low picomolar concentrations of the BiTE molecules were sufficient to stimulate a high percentage of peripheral human T cells to express cytokines and surface activation markers, enter into cell cycle, and induce redirected lysis of target cells. However, in the absence of target cells, the 2 BiTE molecules even at high concentrations did not detectably activate T cells. Our data show that T cell activation by monomeric forms of MT110 and MT103 is highly conditional in that it is strictly dependent on the presence of cells expressing the proper target antigen. BiTE molecules therefore qualify for a highly controlled polyclonal T-cell therapy of cancer.
Inherent Instability of the Retinitis Pigmentosa P23H Mutant Opsin (2014)

The P23H opsin mutation is the most common cause of autosomal dominant retinitis pigmentosa. Even though the pathobiology of the resulting retinal degeneration has been characterized in several animal models, its complex molecular mechanism is not well understood. Here, we expressed P23H bovine rod opsin in the nervous system of Caenorhabditis elegans. Expression was low due to enhanced protein degradation. The mutant opsin was glycosylated, but the polysaccharide size differed from that of the normal protein. Although P23H opsin aggregated in the nervous system of C. elegans, the pharmacological chaperone 9-cis-retinal stabilized it during biogenesis, producing a variant of rhodopsin called P23H isorhodopsin. In vitro, P23H isorhodopsin folded correctly, formed the appropriate disulfide bond, could be photoactivated but with reduced sensitivity, and underwent Meta II decay at a rate similar to wild type isorhodopsin. In worm neurons, P23H isorhodopsin initiated phototransduction by coupling with the endogenous Gi/o signaling cascade that induced loss of locomotion. Using pharmacological interventions affecting protein synthesis and degradation, we showed that the chromophore could be incorporated either during or after mutant protein translation. However, regeneration of P23H isorhodopsin with chromophore was significantly slower than that of wild type isorhodopsin. This effect, combined with the inherent instability of P23H rhodopsin, could lead to the structural cellular changes and photoreceptor death found in autosomal dominant retinitis pigmentosa. These results also suggest that slow regeneration of P23H rhodopsin could prevent endogenous chromophore-mediated stabilization of rhodopsin in the retina.
Gene expression patterns in blood leukocytes discriminate patients with acute infections (2006)

Each infectious agent represents a unique combination of pathogen-associated molecular patterns that interact with specific pattern-recognition receptors expressed on immune cells. Therefore, we surmised that the blood immune cells of individuals with different infections might bear discriminative transcriptional signatures. Gene expression profiles were obtained for 131 peripheral blood samples from pediatric patients with acute infections caused by influenza A virus, Gram-negative (Escherichia coli) or Gram-positive (Staphylococcus aureus and Streptococcus pneumoniae) bacteria. Thirty-five genes were identified that best discriminate patients with influenza A virus infection from patients with either E coli or S pneumoniae infection. These genes classified with 95% accuracy (35 of 37 samples) an independent set of patients with either influenza A, E coli, or S pneumoniae infection. A different signature discriminated patients with E coli versus S aureus infections with 85% accuracy (34 of 40). Furthermore, distinctive gene expression patterns were observed in patients presenting with respiratory infections of different etiologies. Thus, microarray analyses of patient peripheral blood leukocytes might assist in the differential diagnosis of infectious diseases.
Two low‐dose OKT3 induction regimens following renal transplantation – clinical experience at a single center (1998)

Experience with quadruple-drug induction therapy with two regimens of low-dose OKT3 in renal transplant patients was evaluated. Group I received 5.0 mg OKT3 in the operating room and on day 1, followed by 2.5 mg/d for a total dose and duration of 40 mg and 14 d, respectively, and group II received 14 d of OKT3 2.5 mg/d (a total dose of 35 mg). Rejection episodes developed in 21% of patients: 29% of group I vs. 17% of group II. In groups I and II, the mean number of days until first rejection was 134 and 119 d, respectively, and delayed graft function was observed in 24 vs. 13% of patients, respectively. Cytokine release syndrome was noted in 95% of group I patients and in 78% of group II patients. The overall incidence of infections did not differ significantly between the two groups; however, the incidence of oral candidiasis was higher in group II (30 vs. 11% in group I, p = 0.021) and the incidence of herpes simplex virus infection was higher in group I (13 vs. 1% in group II, p = 0.015). The average length of hospital stay was 6.7 d in group I and 6.2 d in group II. The current pharmacy charge for a 2.5-mg vial of OKT3 is 28% lower for a 5.0-mg vial. Our study suggests that by using either low-dose OKT3 regimen renal transplant patients can be safely treated with shortened hospital stays, lower pharmacy costs, and without increased incidence of graft loss or patient morbidity.
A Review of the Molecular and Cellular Biology of Butyrophilin, the Major Protein of Bovine Milk Fat Globule Membrane (1993)

The molecular and cellular biology of the milk protein butyrophilin is reviewed. Butyrophilin constitutes more than 40% by weight of the total protein associated with the fat globule membrane of bovine milk. Closely related proteins are abundant in the fat globule membranes of many other species. Butyrophilin is synthesized as a peptide of 526 amino acids with an amino-terminal hydrophobic signal sequence of 26 amino acids, which is cleaved before secretion in association with the fat globule membrane. Hydropathy analysis and in vitro translation of butyrophilin mRNA indicate that the protein associates with membranes in a type I orientation via a single stretch of 27 hydrophobic amino acids in the approximate middle of the sequence. Evidence that butyrophilin is incorporated into fat globule membrane as a transmembrane protein and as a cytoplasmically oriented peripheral component is discussed. The carboxy-terminal sequence of butyrophilin is significantly homologous to two other proteins: ret finger protein and the 52-kDa nuclear antigen A of Sjögren's syndrome. Expression of bovine butyrophilin mRNA correlates with the onset of milk fat secretion toward the end of pregnancy and is maintained throughout lactation. The possible function of butyrophilin in the secretion of milk lipid droplets is discussed.
The Control of Corporal Smooth Muscle Tone, the Coordination of Penile Erection, and the Etiology of Erectile Dysfunction: The Devil is in the Details (1998)

Penile erection is a complex neurovascular event with hemodynamic features analogous to those observed in vascular tissues throughout the vascular tree. A spate of recent basic research activity into the mechanistic basis for the control of penile erection and the etiology of erectile dysfunction has highlighted the central role of the corporal smooth muscle cell in this process. It is now clear that penile erection is highly dependent not only on the integrity of the corporal smooth muscle cells that comprise the vast majority of the corporal parenchyma, but also on their ability to respond to stimuli for both contraction and relaxation in a coordinated and syncytial fashion. As such, further elaboration of the precise mechanistic details concerning the physiology and pathophysiology of the control of corporal smooth muscle tone represents the greatest remaining barrier to the improved understanding, diagnosis, and treatment of erectile dysfunction. It is anticipated that multidisciplinary basic research studies that utilize the vertical approach—that is, incorporate studies ranging from examination of the patient in the clinic, to physiological/pharmacological studies of isolated corporal tissue strips from these same patients, to biochemical and electrophysiological studies of the cells derived from tissues of these same patients, to studies of protein and gene expression in their corresponding cells—will allow the quickest transition from “the bench to the bedside.” In particular, it would appear that the success of such translational research will be closely linked to progress/developments in the field of molecular biology/genetics, and their applicability/relevance to the diagnosis and treatment of erectile dysfunction. One such application, namely genetic therapy for the treatment of erectile dysfunction, seems especially appealing and probable.
Molecular cloning, chromosomal mapping and tissue-specific expression of a novel human 1,2-mannosidase gene involved in N-glycan maturation (1998)

Class I alpha1,2-mannosidases play an essential role in the elaboration of complex and hybrid N -glycans in mammalian cells. Using degenerate primers based on amino acid sequences conserved in all members of this enzyme family for RT-PCR, two distinct PCR products were obtained from placenta and lymphocyte cDNAs. One of these was related to the previously cloned human and murine alpha1, 2-mannosidase IA whereas the other was very similar to murine alpha1, 2-mannosidase IB. Northern blot analysis of human tissues with these two alpha1,2-mannosidase probes revealed very different patterns of tissue-specific expression. Similar tissue-specific expression of alpha1,2-mannosidase IA and IB was also observed on Northern blots of adult mouse tissues. A human placenta cDNA library was screened and PCR of brain, placenta, and lymphocyte cDNAs was performed in order to isolate the human alpha1,2-mannosidase IB cDNA. This cDNA encodes a type II membrane protein of 73 kDa that is 94% identical in amino acid sequence to the murine alpha1,2-mannosidase IB (Herscovics et al., 1994, J. Biol. Chem., 269, 9864-9871). A truncated soluble form of the human alpha1,2-mannosidase IB lacking its N -terminal transmembrane domain was expressed as a secreted protein in Pichia pastoris . The recombinant enzyme was incubated with [3H]Man9GlcNAc and [3H]Man8GlcNAc (isomer B), and high performance liquid chromatography analysis of the products showed that [3H]Man9GlcNAc was readily converted to [3H]Man6GlcNAc and much more slowly to [3H]Man5GlcNAc, whereas [3H]Man8GlcNAc was rapidly trimmed to [3H]Man5GlcNAc. The human alpha1,2-mannosidase IB gene was isolated from a P1 human genomic library and shown to be at least 60 kb in size and to contain at least 13 exons. The gene was localized by fluorescence in situ hybridization to human chromosome 1p13, a region that undergoes many aberrations in various types of human cancers. These results show that there are at least two Class I alpha1,2-mannosidases in the human and murine genomes with very distinct transcriptional regulation in different tissues.
CD4+T Helper Cell Responses against Human Bocavirus Viral Protein 2 Viruslike Particles in Healthy Adults (2008)

Data suggest the presence of HBoV-specific immune responses in adults and strongly support a high prevalence of HBoV among humans.
A mouse gene knockout model for juvenile ceroid-lipofuscinosis (batten disease) (1999)

The human hereditary ceroid-lipofuscinoses are a group of autosomal recessively inherited diseases characterized by massive accumulations of autofluorescent lysosomal storage bodies in the cells of many tissues and by neuronal degeneration throughout the central nervous system. There are a number of clinically and genetically distinct forms of ceroid-lipofuscinosis, the most common of which is the juvenile type, also known as Batten disease and CLN3. To study the mechanisms that lead to pathology in CLN3 and to evaluate potential therapies, a mouse model has been generated by targeted disruption of the mouse ortholog of the CLN3 gene (Cln3). As in affected humans, mice homozygous for the disrupted Cln3 allele show accumulation of autofluorescent storage material in neurons and other cell types. The storage material consists of membrane-bounded intracellular inclusions with ultrastructural features typical of the ceroid-lipofuscinoses. The accumulation of this storage material validates the Cln3 knockout mice as a model for the human disorder.