gebhart/patrepeval huggingface dataset:
Conditionally replicating herpes vectors for cancer therapy (2000)

The use of genetically engineered viral vectors for tumor therapy initially involved replication-defective vectors, generally derived from retro- or adenoviruses, for the transfer of genes to cause tumor growth inhibition or tumor destruction. However, because of limitations involving vector delivery and relatively low levels of gene transfer, such vectors systems have proven relatively inefficient for the treatment of large solid tumors. In an attempt to overcome this problem, vectors have been developed that can replicate within the tumor and thus increase the efficiency of tumor cell destruction, but appropriate tumor targeting has been a major challenge for such systems. Vectors are needed that replicate within tumor cells and cause tumor cell destruction but that cause no local or systemic toxicity, because they fail to grow within normal tissues. Studies that I and my colleagues performed initially focused on the treatment of malignant brain tumors using local vector delivery to avoid damaging normal brain and associated tissues. We and others have since expanded the scope of this project to target cancers in the nervous system and elsewhere, using targeted or systemically delivered vectors derived from herpes simplex virus-1 (HSV-1) .
Differential gene expression of the three natriuretic peptides and natriuretic peptide receptor subtypes in human liver. (1997)

These data show that NPR transcripts are coexpressed with ANP and CNP mRNA in the human liver. This provides evidence for a local NP system in the human liver.
An Ultrahigh-throughput Microfluidic Platform for Single-cell Genome Sequencing (2018)

Sequencing technologies have undergone a paradigm shift from bulk to single-cell resolution in response to an evolving understanding of the role of cellular heterogeneity in biological systems. However, single-cell sequencing of large populations has been hampered by limitations in processing genomes for sequencing. In this paper, we describe a method for single-cell genome sequencing (SiC-seq) which uses droplet microfluidics to isolate, amplify, and barcode the genomes of single cells. Cell encapsulation in microgels allows the compartmentalized purification and tagmentation of DNA, while a microfluidic merger efficiently pairs each genome with a unique single-cell oligonucleotide barcode, allowing >50,000 single cells to be sequenced per run. The sequencing data is demultiplexed by barcode, generating groups of reads originating from single cells. As a high-throughput and low-bias method of single-cell sequencing, SiC-seq will enable a broader range of genomic studies targeted at diverse cell populations.
Treating Depression in Alzheimer Disease (2003)

Sertraline is superior to placebo for the treatment of major depression in Alzheimer disease. Depression reduction is accompanied by lessened behavior disturbance and improved activities of daily living, but not improved cognition.
A Continuous-Exchange Cell-Free Protein Synthesis System Based on Extracts from Cultured Insect Cells (2014)

In this study, we present a novel technique for the synthesis of complex prokaryotic and eukaryotic proteins by using a continuous-exchange cell-free (CECF) protein synthesis system based on extracts from cultured insect cells. Our approach consists of two basic elements: First, protein synthesis is performed in insect cell lysates which harbor endogenous microsomal vesicles, enabling a translocation of de novo synthesized target proteins into the lumen of the insect vesicles or, in the case of membrane proteins, their embedding into a natural membrane scaffold. Second, cell-free reactions are performed in a two chamber dialysis device for 48 h. The combination of the eukaryotic cell-free translation system based on insect cell extracts and the CECF translation system results in significantly prolonged reaction life times and increased protein yields compared to conventional batch reactions. In this context, we demonstrate the synthesis of various representative model proteins, among them cytosolic proteins, pharmacological relevant membrane proteins and glycosylated proteins in an endotoxin-free environment. Furthermore, the cell-free system used in this study is well-suited for the synthesis of biologically active tissue-type-plasminogen activator, a complex eukaryotic protein harboring multiple disulfide bonds.
Combination Treatment of Invasive Fungal Infections (2005)

The persistence of high morbidity and mortality from systemic fungal infections despite the availability of novel antifungals points to the need for effective treatment strategies. Treatment of invasive fungal infections is often hampered by drug toxicity, tolerability, and specificity issues, and added complications often arise due to the lack of diagnostic tests and to treatment complexities. Combination therapy has been suggested as a possible approach to improve treatment outcome. In this article, we undertake a historical review of studies of combination therapy and also focus on recent studies involving newly approved antifungal agents. The limitations surrounding antifungal combinations include nonuniform interpretation criteria, inability to predict the likelihood of clinical success, strain variability, and variations in pharmacodynamic/pharmacokinetic properties of antifungals used in combination. The issue of antagonism between polyenes and azoles is beginning to be addressed, but data regarding other drug combinations are not adequate for us to draw definite conclusions. However, recent data have identified potentially useful combinations. Standardization of assay methods and adoption of common interpretive criteria are essential to avoid discrepancies between different in vitro studies. Larger clinical trials are needed to assess whether combination therapy improves survival and treatment outcome in the most seriously debilitated patients afflicted with life-threatening fungal infections.
A Recombinant Human Parainfluenza Virus Type 3 (PIV3) in Which the Nucleocapsid N Protein Has Been Replaced by That of Bovine PIV3 Is Attenuated in Primates (2000)

The shipping fever (SF) and Kansas (Ka) strains of bovine parainfluenza virus type 3 (BPIV3) are restricted in their replication in rhesus monkeys 100- to 1,000-fold compared to human parainfluenza virus type 3 (HPIV3), and the Ka strain also was shown to be attenuated in humans. To initiate an investigation of the genetic basis of the attenuation of BPIV3 in primates, we produced viable chimeric HPIV3 recombinants containing the nucleoprotein (N) open reading frame (ORF) from either BPIV3 Ka or SF in place of the HPIV3 N ORF. These chimeric recombinants were designated cKa-N and cSF-N, respectively. Remarkably, cKa-N and cSF-N grew to titers comparable to those of their HPIV3 and BPIV3 parents in LLC-MK2 monkey kidney and Madin-Darby bovine kidney cells. Thus, the heterologous nature of the N protein did not impede replication in vitro. However, cKa-N and cSF-N were each restricted in replication in rhesus monkeys to a similar extent as Ka and SF, respectively. This identified the BPIV3 N protein as a determinant of the host range restriction of BPIV3 in primates. These chimeras thus combine the antigenic determinants of HPIV3 with the host range restriction and attenuation phenotype of BPIV3. Despite their restricted replication in rhesus monkeys, the chimeric viruses induced a level of resistance to HPIV3 challenge in these animals which was indistinguishable from that conferred by immunization with HPIV3. The infectivity, attenuation, and immunogenicity of these BPIV3/HPIV3 chimeras suggest that the modified Jennerian approach described in the present report represents a novel method to design vaccines to protect against HPIV3-induced disease in humans.
Pyruvate Dehydrogenase Complex from Higher Plant Mitochondria and Proplastids: Regulation (1977)

The activity of the pyruvate dehydrogenase complex from pea (Pisum sativum L.) mitochondria is inhibited when MgATP is added to the reaction mixture; 50% inhibition occurs at 4 mm ATP. The inhibition does not increase with time and is higher in the more highly purified preparations. Crude preparations of the complex show a time-dependent inactivation when incubated with 7.5 mm MgATP alone but this is not found with the more highly purified complex. This inactivation does not occur at 0 C. The complex could not be reactivated by high concentrations of Mg(2+). It is suggested that a phosphorylation-dephosphorylation mechanism may occur in plants, but the phosphatase and kinase are not tightly bound to the complex and are lost on isolation. The complex does not respond in a significant manner to energy charge. The NAD(+) to NADH ratio is the principal means of regulation of the complex, NADH being competitive with NAD(+) for the dihydrolipoamide component. The CoA to acetyl-CoA ratio is not important in regulation.The castor bean (Ricinus communis L.) proplastid complex is inhibited by the addition of 2 mm MgATP to the assay mixture. The inhibition is immediate, suggesting that phosphorylation of the enzyme is not involved or must be very rapid. Incubation of the complex with 20 mm MgCl(2) causes an activation of the complex. Maximum activity is not expressed in this case for 30 minutes. A similar activation can be achieved by preincubating the complex with 1 mm pyruvate. These data suggest that the complex is not fully activated on isolation.
Tracking mesoderm induction and its specification to the hemangioblast during embryonic stem cell differentiation (2003)

The hematopoietic and endothelial lineages derive from mesoderm and are thought to develop through the maturation of a common progenitor, the hemangioblast. To investigate the developmental processes that regulate mesoderm induction and specification to the hemangioblast, we generated an embryonic stem cell line with the green fluorescent protein (GFP) targeted to the mesodermal gene, brachyury. After the in vitro differentiation of these embryonic stem cells to embryoid bodies, developing mesodermal progenitors could be separated from those with neuroectoderm potential based on GFP expression. Co-expression of GFP with the receptor tyrosine kinase Flk1 revealed the emergence of three distinct cell populations, GFP(-)Flk1(-), GFP(+)Flk1(-) and GFP(+)Flk1(+) cells, which represent a developmental progression ranging from pre-mesoderm to prehemangioblast mesoderm to the hemangioblast.
Toward a Unified Scheme for the Aggregation of Tau into Alzheimer Paired Helical Filaments (2002)

Alzheimer's disease is characterized by aggregates of tau protein. Attempts to study the conditions for aggregation in vitro have led to different experimental systems, some of which appear mutually exclusive (e.g., oxidative vs reductive conditions, induction by polyanions vs fatty acids). We show here that different approaches and pathways can be viewed in a common framework, and that apparent differences can be explained by variations in the kinetics of subreactions. A unified view of PHF aggregation should help to analyze the causes of PHF aggregation and devise methods to prevent it.
16S rRNA sequences of Bartonella bacilliformis and cat scratch disease bacillus reveal phylogenetic relationships with the alpha-2 subgroup of the class Proteobacteria (1991)

The primary structures of 16S rRNAs of Bartonella bacilliformis, an isolate of the cat scratch disease (CSD) bacillus, and a strain phenotypically similar to the CSD bacillus were determined by reverse transcriptase sequencing. These microorganisms were found to be members of the alpha-2 subgroup of the class Proteobacteria. The sequence from B. bacilliformis was most closely related to the rRNA of Rochalimaea quintana (91.7% homology), the etiologic agent of trench fever. The sequence from the isolate of the CSD bacillus showed the greatest homology with Brucella abortus (89.7%) and, when compared with oligonucleotide catalog data, formed a cluster with Rhodopseudomonas palustris, Pseudomonas carboxidovorans, Nitrobacter species, and Bradyrhizobium species. The 16S rRNA sequence was also determined for the Cleveland Clinic isolate, which was previously shown to be phenotypically similar to and approximately 30% related, by DNA hybridization, to the CSD bacillus. The Cleveland Clinic isolate was isolated from a patient not diagnosed with CSD. The rRNAs from these bacteria exhibited 98.2% homology, confirming that this isolate is a second species in the same genus as the CSD bacillus. Our data suggest that neither B. bacilliformis nor the CSD bacillus is the etiologic agent of bacillary epithelioid angiomatosis.
Building Institutional Repositories in Bangladesh Using DSpace: A New Paradigm of Scholarly Communication (2011)

Institutional Repository (IR) and Digital Library (DL), are relatively new concepts in Bangladesh. IR may be considered as the first step of open access to research output. Library professionals in Bangladesh understand and realize the benefits of open access, yet open access initiatives have been very few at higher learning institutions. The Government of Bangladesh also issued the Right to Information (RTI) Act 2009 in the Bangladesh Gazette on 6 April 2009, encouraging open access. However, there are many challenges, difficulties, resources constraints, and other limitations in establishing IR and DL. Despite these difficulties, some research organizations and institutions, such as the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) and BRAC University (BU) have taken initiatives to build IR and DL using DSpace software. In this article, an attempt has been taken to describe the current status of IR and DL in Bangladesh. The two above-mentioned institutions already started their project and have made significant progress in building the IR. To provide a detailed analysis of the literature on IR and digital resources, many webliographic sources, institutional librarians, and organizations were consulted. Then the situation analysis of institutional repositories, their documentary sources, workshop experience, and direct observations in understanding the current status has been performed. This paper shares the experience of ICDDR,B and BU as well as opinion of other institutions with regards to establishment of IR and DL in Bangladesh using open source soft ware DSpace. Researchers are also encouraged to get free online access to research outcomes. The open access movement and IR could contribute significantly to economic growth of the respective country by providing access to scholarly materials without the economic barriers that currently exist in scholarly publishing.
Adaptive run-to-run control and monitoring for a rapid thermal processor (2003)

Process reproducibility is a challenging problem in semiconductor manufacturing as the component size shrinks and the manufacturing complexity increases. This article proposes a new adaptive run-to-run controller for intermittent batch operations and applies it to a rapid thermal annealing (RTA) process at Advanced Micro Devices. The adaptive controller has a self-monitoring component and requires little process knowledge to set up. The success of the controller is demonstrated on an AST SHS 2800 RTA system. Improvement was made to reduce the first wafer effects and lot-to-lot variability due to disturbances.
Controlling the Location and Spatial Extent of Nanobubbles Using Hydrophobically Nanopatterned Surfaces (2005)

The presence of nanobubbles-as imaged with tapping-mode atomic force microscopy-is controlled using nanopatterned surfaces possessing repeating patterns of polystyrene (hydrophobic domains) and poly(methyl methacrylate) (hydrophilic domains). For nanobubbles to be present, we find that, in addition to controlling the degree of surface hydrophobicity, it is important for the spatial dimensions of the hydrophobic domains on the nanopatterned surface to be commensurate with the equilibrium topology of the nanobubbles.
Acetate excretion during growth of Salmonella enterica on ethanolamine requires phosphotransacetylase (EutD) activity, and acetate recapture requires acetyl-CoA synthetase (Acs) and phosphotransacetylase (Pta) activities (2005)

This report shows that Salmonella enterica catabolizes ethanolamine to acetyl-CoA (Ac-CoA), which enters the glyoxylate bypass and tricarboxylic acid cycle for the generation of energy and central metabolites. During growth on ethanolamine, S. enterica excreted acetate, whose recapture depended on Ac-CoA synthetase (Acs) and the housekeeping phosphotransacetylase (Pta) enzyme activities. The Pta enzyme did not play a role in acetate excretion during growth of S. enterica on ethanolamine. It is proposed that during growth on ethanolamine, acetate excretion is necessary to maintain a pool of free CoA. Acetate excretion requires the eut operon-encoded phosphotransacetylase (EutD) and acetate kinase (Ack) enzymes. EutD function was not required for growth on ethanolamine, and an eutD strain showed only a slight reduction in growth rate. The existence of an as-yet-unidentified system that releases acetate was revealed during growth of a strain lacking Acs, the housekeeping phosphotransacetylase (Pta), and EutD. The functions of pyruvate oxidase (PoxB), Ack and STM3118 protein [a homologue of the Saccharomyces cerevisiae Ac-CoA hydrolase (Ach1p) enzyme] were not involved in the release of acetate by the acs pta eutD strain.
Synthesis and Antiviral Activity of Ethidium−Arginine Conjugates Directed Against the TAR RNA of HIV-1 (1999)

The regulatory protein Tat is essential for viral gene expression and replication of the human immunodeficiency virus type 1 (HIV-1). Tat transactivates the HIV-1 long terminal repeat (LTR) via its binding to the transactivation responsive element (TAR) and increases the viral transcription. Studies have shown that the binding of arginine and arginine derivatives induces a conformational change of the TAR RNA at the Tat-binding site. The unpaired A17 residue delimits a small cavity which constitutes a receptor site for small molecules, especially for ethidium bromide. These binding characteristics have prompted us to design a series of ethidium-arginine conjugates capable of interacting with the TAR RNA. Here we report the synthesis of six ethidium derivatives equipped with arginine side chains. These molecules were biologically evaluated, and two compounds (17 and 20) exhibited in vitro anti-HIV-1 activity at micromolar concentration, without toxicity (up to 100 microM concentration). Melting temperature studies indicated that the most active molecule (20) bound strongly to TAR in vitro. RNase protection experiments agreed with the molecular modeling studies which suggested that the ethidium moiety of 20 was inserted next to the A17 residue while the arginine side chain occupied the pyrimidine bulge.
Crystal Structure of Kunitz Domain 1 (KD1) of Tissue Factor Pathway Inhibitor-2 in Complex with Trypsin (2005)

Kunitz domain 1 (KD1) of tissue factor pathway inhibitor-2 inhibits trypsin, plasmin, and factor VIIa (FVIIa)/tissue factor with Ki values of 13, 3, and 1640 nM, respectively. To investigate the molecular specificity of KD1, crystals of the complex of KD1 with bovine beta-trypsin were obtained that diffracted to 1.8 A. The P1 residue Arg-15 (bovine pancreatic trypsin inhibitor numbering) in KD1 interacts with Asp-189 (chymotrypsin numbering) and with the carbonyl oxygens of Gly-219 and Ogamma of Ser-190. Leu-17, Leu-18, Leu-19, and Leu-34 in KD1 make van der Waals contacts with Tyr-39, Phe-41, and Tyr-151 in trypsin, forming a hydrophobic interface. Molecular modeling indicates that this complementary hydrophobic patch is composed of Phe-37, Met-39, and Phe-41 in plasmin, whereas in FVIIa/tissue factor, it is essentially absent. Arg-20, Tyr-46, and Glu-39 in KD1 interact with trypsin through ordered water molecules. In contrast, insertions in the 60-loop in plasmin and FVIIa allow Arg-20 of KD1 to directly interact with Glu-60 in plasmin and Asp-60 in FVIIa. Moreover, Tyr-46 in KD1 electrostatically interacts with Lys-60A and Arg-60D in plasmin and Lys-60A in FVIIa. Glu-39 in KD1 interacts directly with Arg-175 of the basic patch in plasmin, whereas in FVIIa, such interactions are not possible. Thus, the specificity of KD1 for plasmin is attributable to hydrophobic and direct electrostatic interactions. For trypsin, hydrophobic interactions are intact, and electrostatic interactions are weak, whereas for FVIIa, hydrophobic interactions are missing, and electrostatic interactions are partially intact. These findings provide insight into the protease selectivity of KD1.
Upper Airway Collapsibility in Snorers and in Patients with Obstructive Hypopnea and Apnea (1991)

During sleep, mild reduction in inspiratory airflow is associated with snoring, whereas obstructive hypopneas and apneas are associated with more marked reductions in airflow. We determined whether the degree of inspiratory airflow reduction was associated with differences in the collapsibility of the upper airway during sleep. Upper airway collapsibility was defined by the critical pressure (Pcrit) derived from the relationship between maximal inspiratory airflow and nasal pressure. In 10 asymptomatic snorers, six patients with obstructive hypopneas, and 10 patients with obstructive apneas, during nonrapid eye movement sleep, Pcrit ranged from -6.5 +/- 2.7 cm H2O to -1.6 +/- 1.4 and 2.5 +/- 1.5 cm H2O, respectively (mean +/- SD, p less than 0.001). Moreover, higher levels of Pcrit were associated with lower levels of maximal inspiratory airflow during tidal breathing during sleep (p less than 0.005). We conclude that differences in upper airway collapsibility distinguish among groups of normal subjects who snore and patients with periodic hypopneas and apneas. Moreover, the findings suggest that small differences in collapsibility (Pcrit) along a continuum are associated with reduced airflow and altered changes in pattern of breathing.
Effects of Two Treatment Regimes with Synthetic Human Parathyroid Hormone Fragment on Bone Formation and the Tissue Balance of Trabecular Bone in Greyhounds (1983)

The adult greyhound was found to be similar to adult man with respect to kinetic and histomorphometric indices of calcium metabolism. The relationship between trabecular bone tissue balance and the pattern of human PTH fragment 1-34 (hPTH 1-34) administration by daily injections or continuous sc infusions was investigated in this model and the results compared to those from a clinical trial of hPTH 1-34 in involutional osteoporosis (peptide administration by single daily injections). In the dogs, the daily injection regime elevated plasma levels of immunoreactive hPTH 1-34 for no more than 4 h/day. The greyhounds so treated showed significantly increased indices of bone formation (surface osteoid, plasma alkaline phosphatase activity, and skeletal accretion rate of calcium) and resorption (number of osteoclasts, resorption surfaces). Iliac trabecular bone volume increased significantly, as it did in the patients. The infusions did not significantly increase the trabecular bone volume or the 47Ca accretion rate, two parameters which increased in parallel in dogs and patients treated successfully by daily injections. The osteoclastic surfaces, however, were clearly increased by continuous infusions, while the increases in the osteoblastic surfaces were less statistically significant. Since hPTH 1-34 may inhibit osteogenesis in Friedenstein chambers, it is possible that the increased osteoblastic activity induced by the daily injection regime in trabecular bone is dependent on the noncontinuous nature of the PTH stimulus.