gebhart/patrepeval huggingface dataset:
Solid-State Characterization of Paclitaxel (1997)

The purpose of this work was to characterize the solid-state properties of anhydrous paclitaxel and paclitaxel dihydrate. Paclitaxel I (anhydrous) was suspended in water for 24 h to convert it to paclitaxel.2H2O. Both forms were analyzed by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). X-ray powder diffraction (XRPD) patterns were obtained at 25, 100, and 195 degrees C. Dissolution profiles of both forms were obtained in water at 37 degrees C over h. DSC of paclitaxel.2H2O showed two endothermic peaks below 100 degrees C, corresponding to dehydration. The resulting solid phase was termed "dehydrated paclitaxel.2H2O". At 168 degrees C, a solid-solid transition was observed in which dehydrated paclitaxel.2H2O was converted to a semicrystalline material called "paclitaxel I/am". The solid-solid transition was followed by melting at 220 degrees C. TGA of paclitaxel.2H2O showed a corresponding biphasic weight loss below 100 degrees C, which was equivalent to the weight of 2 mol of water. DSC of paclitaxel I showed no transitions before melting at 220 degrees C, and no weight loss was observed by TGA. Quenching of paclitaxel I from the melt produced amorphous paclitaxel with a glass transition at 152 degrees C. XRPD confirmed that paclitaxel I, paclitaxel.2H2O, and dehydrated paclitaxel.2H2O had different crystal structures. The X-ray patterns of paclitaxel I and paclitaxel I/am were similar, however the two forms of paclitaxel did not behave identically when analyzed by DSC. The bulk dissolution studies with paclitaxel I showed a rapid increase in concentration to 3 micrograms/mL in 4 h, which decreased to 1 microgram/mL after 12 h, corresponding to the solubility of paclitaxel.2H2O. The solubility of paclitaxel.2H2O was 1 microgram/mL. The data demonstrate the existence of a dihydrate form of paclitaxel that is the stable form in equilibrium with water at 37 degrees C but which dehydrates at temperatures > 45 degrees C.
Normal development and growth of mice carrying a targeted disruption of the alpha 1 retinoic acid receptor gene. (1993)

Three unlinked genes encode receptors for retinoic acid (RAR alpha, -beta, and -gamma). Each gene expresses two major protein isoforms differing in the amino terminal A domain by alternative promoter use, fused to common exons encoding most of the receptor protein. The two RAR alpha transcripts (RAR alpha 1 and -alpha 2) are differentially expressed and evolutionarily conserved, as are the RAR beta and -gamma transcripts, suggesting that each isoform may have specific functions in the development of animals. To address the biological function of the alpha 1 receptor, we have disrupted the portion of the RAR alpha gene encoding this isoform by homologous recombination in mouse embryonic stem cells. Surprisingly, offspring homozygous for this mutation were viable and showed no apparently altered phenotype. RNA analysis confirmed that the RAR alpha 1 transcript was absent in homozygous tissues, and no evidence for a compensatory increase of RAR alpha 2 or of another RAR gene was obtained to account for the vitality of the mutant animals. These results clearly demonstrate that loss of RAR alpha 1 function does not disrupt embryonic development and argue for combinatorial or overlapping functions among the RAR isoforms.
Comparison of pathogenic and non-pathogenic murine antibodies to DNA: antigen binding and structural characteristics (1994)

Three pathogenic and two non-pathogenic NZB/NZW F1 mAbs to DNA were compared. Pathogenicity was defined as the ability to induce nephritis in BALB/c mice. All mAbs were IgG2a or 2b, had high avidity for double-stranded DNA and fixed complement well. All three pathogens expressed idiotype IdGN2. Mice receiving pathogenic mAbs (compared with non-pathogenic) had more glomerular IgG deposits. The unique properties of two of the pathogens were: strong homogeneous staining of Hep-2 nuclei and the ability to bind (i) nucleosomes, (ii) histone (after mAb complexed with DNA), (iii) heparan sulfate in renal basement membranes (after complexing with DNA/histone) and (iv) nuclei in vivo. Comparison of nucleotide and amino acid sequences of the V regions of heavy and light Ig chains showed use of multiple VHDJH and V kappa J kappa gene families, with representation of several anti-DNA 'families' described by others. Arginine (R) occurred in the CDR2 or CDR3 of VH chains in all pathogens; R was absent in the CDRs of VH chains of non-pathogens. Positively and negatively charged AA were more frequent in VH CDR of pathogens than of non-pathogens. We hypothesize that the tertiary structure of mAbs determined by VH CDR regions permits stronger binding to negatively charged antigens (DNA and heparan sulfate) and to positively charged molecules (histone) in pathogens compared with non-pathogens.
P-glycoprotein expression and prognostic value in acute myeloid leukemia. (1998)

Our data indicate that P-glycoprotein expression is a reliable marker of resistance to induction treatment in patients with de novo AML.
Hepatitis C virus – T‐cell responses and viral escape mutations (2011)

Hepatitis C virus (HCV) is a small, enveloped RNA virus and the number of HCV-infected individuals worldwide is estimated to be approximately 170 million. Most HCV infections persist, with up to 80% of all cases leading to chronic hepatitis associated with liver fibrosis, cirrhosis, and hepatocellular carcinoma. HCV-host interactions have a crucial role in viral survival, persistence, pathogenicity of infection, and disease progression. Maintenance of a vigorous, sustained cellular immune response recognizing multiple epitopes is essential for viral clearance. To escape immune surveillance, HCV alters its epitopes so that they are no-longer recognized by T cells and neutralizing antibodies, in addition to interfering with host cell cellular components and signaling pathways. The generation of escape variants is one of the most potent immune evasion strategies utilized by HCV. A large body of evidence suggests that single or multiple mutations within HLA-restricted epitopes contribute to viral immune escape and establishment of viral persistence. Further elucidation of the molecular mechanisms underlying immune escape will aid in the design of novel vaccines and therapeutics for the disease.
The Molecular Biology of Axon Guidance (1996)

Neuronal growth cones navigate over long distances along specific pathways to find their correct targets. The mechanisms and molecules that direct this pathfinding are the topics of this review. Growth cones appear to be guided by at least four different mechanisms: contact attraction, chemoattraction, contact repulsion, and chemorepulsion. Evidence is accumulating that these mechanisms act simultaneously and in a coordinated manner to direct pathfinding and that they are mediated by mechanistically and evolutionarily conserved ligand-receptor systems.
Viral Genome Methods (2023)

Retroviruses/HIV/RNA Viruses Retrovirus-Mediated Gene Transfer, B.A. Bunnell and R.A. Morgan Methods for Studying Genetic Variation of the Human Immunodeficiency Virus (HIV), G. Schochetman, S. Subbarao, and M.L. Kalish Methods for HIV/SIV Gene Analysis, A. Adachi, M. Kawamura, K. Tokunaga, and H. Sakai Analysis of Human Immunodeficiency Virus Reverse Transcriptase Function, V.R. Prasad, W.C. Drosopoulos, and Y. Kew Tat Activation Studies: Use of a Reporter Cell Line, E. Aguilar-Cordova, J. Chinen, and J.W. Belmont Characterization of HIV Nef Cell-Specific Effects, J.W. Marsh and S.K. De Detection, Quantitation, and Characterization of Human Retroviruses, S. Rasheed Quantitative Methods to Monitor Viral Load in Simian Immunodeficiency Virus Infections, S.I. Staprans, B.C. Corliss, J.L. Guthrie, and M.B. Feinberg Using Molecular Genetics to Probe the Immune Response to Vesicular Stomatitis Virus, C.S. Reiss, S.A. Oien, and S. Bartido DNA Viruses Transient Genetic Approaches to Studying Multifactor Processes in Complex DNA Viruses, G.S. Pari, A.C. Iskenderian, and D.G. Anders Epstein-Barr Virus: Gene Expression and Regulation, N.D. Sista and J.S. Pagano Functional Analysis of the Herpes Simplex Virus DNA Polymerase, P. Digard, W. Bebrin, C. Chow, and D.M. Coen Molecular Genetics of Adeno-Associated Virus, B.J. Carter Reconstitution of Adenovirus DNA Replication with Purified Replication Proteins, J. Dekker, F.E.J. Coenjaerts, and P.C. van der Vliet Index
<title>Personal viewer: a wide-field low-profile see-through eyewear display</title> (2004)

A design for a low cost, wide field, low profile, light weight, full color, stereoscopic, see-through eyewear display called the personal viewer (PV) is presented. After a brief review of current methods and popular products, the principles of operation of the personal viewer are presented and several of the difficulties faced in implementation are discussed. Specifically, imaging is accomplished by covering each eye with a transparent semi-reflective half-ellipsoid, approximately 6cm in diameter and 7cm in length, with its lower focus at the user pupil and the upper focus at a two-axis scanner just above the user's brow. A 1mm collimated optical beam is directed onto the scanner mirror, from which a raster pattern is projected onto the inside surface of the ellipsoid and reflected into the user's pupil. The perceived source of the beam is the point of reflection, providing a 120 degree field breadth at each eye with a 60 degree overlap of the right and left fields where stereo fusion is available. Finally, a reduced bandwidth teleoperation support architecture is described where orientation sensors on the viewer control a dynamic mapping of the viewer display space onto a 360 degree image in response to user head motion.© (2004) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Localization of “non-extractable” acetylcholinesterase to the vertebrate neuromuscular junction. (1993)

Asymmetric forms of acetylcholinesterase (AChE) are thought to be the predominant forms of this enzyme at vertebrate neuromuscular junctions where they attach to the synaptic basal lamina via a collagen-like tail. High salt and heparin-containing buffers are capable of solubilizing asymmetric AChE molecules from skeletal muscle; however, detachment of AChE specifically from synaptic basal lamina using these procedures has not been demonstrated. To determine whether AChE can be solubilized from mature neuromuscular junctions, adult quail muscle fibers were extracted with buffered detergent solutions containing either 0.05 M NaCl, 1 m NaCl, 0.5-2 mg/ml heparin, 8 M urea, or 4 m guanidine HCl, and the remaining AChE molecules were localized by indirect immunofluorescence. Analysis of extracted AChE oligomeric forms showed that low salt buffers containing heparin and high salt buffers were capable of solubilizing substantial amounts of catalytically active collagen-tailed AChE, whereas none of these buffers were capable of detaching AChE from synaptic basal lamina. In contrast, digestion with purified collagenase detached asymmetric forms from the non-extractable fraction and removed the AChE from the neuromuscular junctions. Parallel experiments using rat gastrocnemius muscle and enzyme histochemistry to detect AChE gave similar results. These studies indicate that the junctional AChE molecules are firmly attached to the extracellular matrix and that all the conventional extraction buffers used to solubilize the asymmetric collagen-tailed forms of AChE are incapable of detaching this enzyme from the synaptic basal lamina.
Remission of Cancer Chemotherapy-Induced Emesis During Antidepressant Therapy with Nefazodone (1998)

This case report suggests that the remission of emesis could be related to the 5-hydroxytryptamine (5-HT) antagonistic property of nefazodone.
Kinetics of internalization and recycling of the asialoglycoprotein receptor in a hepatoma cell line. (1982)

The presence of a large number of functional asialoglycoprotein receptors in the human hepatoma cell line Hep 6 2 has allowed us to determine the parameters which define ligand binding to the surface receptor, ligand receptor internalization, and receptor recycling.We have developed a simple kinetic model which encompasses all of these processes.These cells contain 226,000 functional asialoglycoprotein receptors, and at 37 "C uptake at a half-saturating concentration (2 pg/ ml) of '251-asialoorosomucoid (ASOR) is linear for several hours at a rate of 15,000 molecules/cell/min.Neither the rate of '261-ASOR binding at 4 "C nor the rate of uptake at 37 "C was altered under conditions in which protein synthesis was completely inhibited.Thus each receptor recycles a ligand, on the average, every 16 min.The rate of binding of '251-ASOR to cells at 37 "C, independent of internalization, was measured in the presence of 10-12 m~ azide.The rate of internalization at 37 "C was determined from cells, prebound with ligand at 4 "C, by following EDTA-resistant cellassociated "%ASOR.The distribution of functional receptors within the cell was assessed from ligand binding at 4 "C and ligand uptake at 37 "C in cells pretreated with trypsin to remove all surface receptors.In growing Hep G2 cells 87% of the receptors are on the cell surface, and over 88% of these are unoccupied with ligand.During steady state internalization of '"1-ASOR, the number of surface ASOR receptors decreases 17%.At 2 pg/ml of '261-ASOR, an unoccupied surface receptor requires a mean time of 8.7 min to bind a ligand, and a mean time of 2.2-2.3 min is required to internalize a surface receptor-ligand complex.An additional 4.2 min is required for ligand to dissociate from an internalized receptor and for the receptor to return to the cell surface.We have been able to determine or calculate most of these parameters of receptor recyclindby two or more independent sets of measurements.Many serum glycoproteins and peptide hormones are bound to the cell surface by specific protein receptors.The subsequent fate of the ligand and of the receptor is dependent on the rates and extents of the following reactions: the binding of
IFN‐α1 gene transfection completely abolishes the tumorigenicity of murine B16 melanoma cells in allogeneic DBA/2 mice and decreases their tumorigenicity in syngeneic C57BL/6 mice (1995)

The murine B16 melanoma (H-2b) was transfected with a retroviral vector containing the mouse IFN-alpha 1 gene. IFN-alpha 1-transfected cells produced IFN-alpha in vitro and exhibited an altered phenotype characterized by a decreased rate of multiplication, enhanced expression of H-2 antigens, an antiviral state to VSV, and decreased pigmentation. Control and IFN-alpha 1-transfected cells were tested for their ability to grow in syngeneic (H-2b) C57Bl/6 and allogeneic (H-2d) DBA/2 mice. IFN-alpha 1-producing B16 clones were less tumorigenic after s.c., i.p., and i.v. routes of injection than IFN-non-producer B16 clones in syngeneic C57Bl/6 mice. IFN-alpha 1-producing B16 cells were, however, totally rejected by allogeneic DBA/2 mice regardless of the routes and inocula tested, while control B16 cells grew in and killed DBA/2 mice. The total rejection of IFN-alpha 1-transfected B16 cells in allogeneic mice appeared to be dependent on T cells as these cells grew in DBA/2 nude mice. Incubation of IFN-alpha-producing clones with anti-mouse IFN-alpha/beta prior to injection into C57Bl/6 mice did not enhance their tumorigenicity. Likewise, injection of C57Bl/6 and DBA/2 mice with antibody to IFN-alpha/beta did not enhance the tumorigenicity of IFN-alpha 1-transfected cells. C57Bl/6 mice immunized with irradiated IFN-alpha 1 cells were only slightly protected against a subsequent challenge with parental B16 cells. In contrast, DBA/2 mice immunized with irradiated IFN-alpha 1 cells exhibited tumor-specific, long-lasting immunity to subsequent challenge with parental B16 cells.
[Open therapeutic trial of anti-T CD4 monoclonal antibody in multiple sclerosis]. (1995)

Twenty-one patients with active multiple sclerosis (16 progressive and 5 recurrent forms) were treated with murine monoclonal anti-T CD4/BF5 antibodies in an open trial. Tolerance was relatively good; 11 patients had side effects including facial swellings, skin eruptions and trembling which occurred only at the first infusion. Treatment had to be stopped in one female patient. Nine months after initiating treatment, no relapse had occurred in any of the 5 patients with a recurrent form and improvement was observed in 3 patients with a progressive form. At the end of the treatment period, there was a clear drop in the number of CD3+ cells and particularly in CD4+ cells, a decrease which was less after one month. All the patients who had side effects showed an increased level of serum IL6 and alpha TNF. These findings demonstrate that this type of long-term treatment is possible in patients with multiple sclerosis and suggest that in another trial it would be important to evaluate the effect in recurrent forms.
Performance-Based Physical Function and Future Dementia in Older People (2006)

Lower levels of physical performance were associated with an increased risk of dementia and AD. The study suggests that poor physical function may precede the onset of dementia and AD and higher levels of physical function may be associated with a delayed onset.
Downregulation of neuropilin‐1 in patients with acute myeloid leukemia treated with thalidomide (2007)

Our data provide evidence of increased NRP-1 expression in relapsed or refractory AML. Additionally, our results suggest that thalidomide-induced antileukemic properties might at least in part be mediated by NRP-1 downregulation.
Assessing fitness costs for transgenicAedes aegyptiexpressing the GFP marker and transposase genes (2004)

The development of transgenic mosquitoes that are refractory to the transmission of human diseases such as malaria, dengue, and yellow fever has received much interest due to the ability to transform a number of vector mosquito species with transposable elements. Transgenic strains of mosquitoes have been generated with molecular techniques that exhibit a reduced capacity to transmit pathogens. These advancements have led to questions regarding the fitness of transgenic mosquitoes and the ability of transformed mosquitoes to compete and effectively spread beneficial genes through nontransformed field populations, the core requirement of a genetically based control strategy aimed at reducing the spread of mosquito-borne human disease. Here we examine the impact of transgenesis on the fitness of Aedes aegypti, a mosquito that transmits yellow fever. Mosquitoes were altered with two types of transgene, the enhanced GFP gene and two transposase genes from the Hermes and MOS1 transposable elements. We examined the effects of these elements on the survivorship, longevity, fecundity, sex ratio, and sterility of transformed mosquitoes and compared results to the nontransformed laboratory strain. We show that demographic parameters are significantly diminished in transgenic mosquitoes relative to the untransformed laboratory strain. Reduced fitness in transgenic mosquitoes has important implications for the development and utilization of this technology for control programs based on manipulative molecular modification.
Curcumin induces apoptosis in immortalized NIH 3T3 and malignant cancer cell lines (1996)

Curcumin, which is a widely used dietary pigment and spice, has been demonstrated to be an effective inhibitor of tumor promotion in mouse skin carcinogenesis. We report that curcumin induces cell shrinkage, chromatin condensation, and DNA fragmentation, characteristics of apoptosis, in immortalized mouse embryo fibroblast NIH 3T3 erb B2 oncogene-transformed NIH 3T3, mouse sarcoma S180, human colon cancer cell HT-29, human kidney cancer cell 293, and human hepatocellular carcinoma Hep G2 cells, but not in primary culture of mouse embryonic fibroblast C3H 10T1/2, rat embryonic fibroblast, and human foreskin fibroblast cells in a concentration- and time-dependent manner. Many cellular and biochemical effects of curcumin in mouse fibroblast cells have been reported, such as inhibition of protein kinase C (PKC) activity induced by phorbol 12-myristate 13-acetate treatment, inhibition of tyrosine protein kinase activity, and inhibition of arachidonic acid (AA) metabolism. Treatment of NIH 3T3 cells with the PKC inhibitor staurosporine, the tyrosine kinase inhibitor herbimycin A, and the AA metabolism inhibitor quinacrine induces apoptotic cell death. These results suggest that, in some immortalized and transformed cells, blocking the cellular signal transduction might trigger the induction of apoptosis.
Relationship between the antitussic and analgesic activity of substances. (1991)

The authors studied relationship between the antitussic and analgesic activity of substances. The antitussic effect of codeine, tilidine, tramadol and pentazocine has been studied in nonanesthetized healthy cats. The drugs except tilidine, were administered intraperitoneally in a dose of 10 mg/kg body weight. Tilidine was administered intramuscularly in the same dose. Cough induced in nonanesthetized cats by mechanical irritation of laryngopharyngeal and tracheobronchial areas was evaluated by changes of the lateral tracheal pressure. A significant decrease of the subsequent cough parameters was observed after the application of codeine, tilidine, tramadol and pentazocine. Naloxone given 5 min before the application of the drug has not prevented the cough-suppressing effect due to codeine. Naloxone alone administered in a dose of 1 mg/kg body weight has not significantly influenced the experimentally-induced cough reflex in nonanesthetized cats.
Targeted deletion of SAP1 abolishes the expression of infectivity factors necessary for successful malaria parasite liver infection (2008)

Malaria parasite sporozoites prepare for transmission to a mammalian host by upregulation of UIS (Upregulated in Infectious Sporozoites) genes. A number of UIS gene products are essential for the establishment of the intrahepatocytic niche. However, the factors that regulate the expression of genes involved in gain of infectivity for the liver are unknown. Herein, we show that a conserved Plasmodium sporozoite low-complexity asparagine-rich protein, SAP1 (Sporozoite Asparagine-rich Protein 1), has an essential role in malaria parasite liver infection. Targeted deletion of SAP1 in the rodent malaria parasite Plasmodium yoelii generated mutant parasites that traverse and invade hepatocytes normally but cannot initiate liver-stage development in vitro and in vivo. Moreover, immunizations with Pysap1(-) sporozoites confer long-lasting sterile protection against wild-type sporozoite infection. Strikingly, lack of SAP1 abolished expression of essential UIS genes including UIS3, UIS4 and P52 but not the constitutively expressed genes encoding, among others, sporozoite proteins CSP and TRAP. SAP1 localization to the cell interior but not the nucleus of sporozoites suggests its involvement in a post-transcriptional mechanism of gene expression control. These findings demonstrate that SAP1 is essential for liver infection possibly by functioning as a selective regulator controlling the expression of infectivity-associated parasite effector genes.