gebhart/patrepeval huggingface dataset:
Cisplatin-associated neurotoxicity (1995)

Neurotoxicity remains the major dose-limiting toxicity of cisplatin. Peripheral sensory neuropathy, the primary type of cisplatin neurotoxicity, has been reported in 30-100% of patients with clinical symptoms typically developing after cumulative cisplatin doses of > or = 300 mg/m2. Several clinical studies have established an important dose-response, dose intensity-response and cumulative total dose-response relationship for cisplatin in the treatment of head and neck, testicular, melanoma, and ovarian cancers. In patients with these tumor types, the occurrence of moderate or severe neuropathy presents an important therapeutic dilemma. Several types of agents--including micleophilic sulfur thiols, neurotrophic factors, phosphonic acid antibiotics and free oxygen radical scavengers--have been investigated for amelioration of cisplatin-related neurotoxicity. Of these, amifostine is likely to be the first neuroprotective agent widely used to enhance the clinical effectiveness of cisplatin. Recently reported results from a multicenter phase III trial of women with advance ovarian cancer receiving combination chemotheraphy with cisplatin plus cyclophosphamide showed that amifostine pretreatment was associated with moderate but significant reductions in cisplatin-associated peripheral neuropathy, tinnitus and nephrotoxicity, while achieving equivalent pathological response rates and median survival. Preclinical data suggest that several additional agents, especially the neurotropic factors nerve growth factor, insulin-like growth factor-I and neurotrophin-3, merit further investigation. Nerve growth factor is the only agent reported to prevent, rather than partially protect, cisplatin-induced neuropathy in an experimental model.
<title>Integration of LEDs and VCSELs using fluidic self-assembly</title> (1998)

In this paper the integration of LEDs and VCSELs with silicon electronics using fluidic self-assembly (FSA) is reviewed. FSA is a micromechanical technique in which devices fabricated in one substrate can be integrated with systems on a target substrate. The devices to be integrated are etched into shapes or 'blocks' that match receptor sites or 'holes' in the target substrate. After etching, the blocks are suspended in a slurry. This slurry is placed in a recirculation pump along with the target substrate. The pump moves the slurry over the target substrate where the blocks fall into the holes or are swept off the substrate to be circulated again. FSA has been demonstrated with yields &gt; 99 percent for devices of 30 micrometers and larger. Smaller devices have yet to be tested. A five mask process has been developed that successfully integrates GaAs/AlGaAs LEDs and VCSELs on silicon. The critical steps are: 1) etching the receptor sites in the silicon, 2) isolating the sites from the remainder of the substrate, and 3) bonding/contacting the blocks after assembly. The latter bonding step involves thin film metal multilayers on the block and in the receptor that form a hard solder after a low temperature bake step. The remaining steps of planarizing and interconnecting the devices are similar to those used for VLSI.
Cell surface CCR5 density determines the postentry efficiency of R5 HIV-1 infection (2002)

We have recently reported that the mean number of CCR5 coreceptors at the surface of CD4(+) T cells (CCR5 density) correlates with viral load and disease progression in HIV-1-infected persons. Here, we definitively establish that CCR5 density determines the level of virus production and identify the stages of HIV-1 replicative cycle modulated by this effect. We show, by transducing the CCR5 gene into CCR5(+) cells, that CCR5 overexpression resulted in an HIV-1 overinfectability. We sorted HOS-CD4(+)-CCR5(+) cells into two subpopulations, HOS(high) and HOS(low), the former expressing seven times more cell surface CCR5 molecules than the latter. Virus production was 30-80 times higher in HOS(high) cells than in HOS(low) cells after a single round of infection. In contrast, only twice as many viral particles entered the cytosol of HOS(high) cells as compared with the cytosol of HOS(low) cells. Yet, seven times as many early, and 24 times as many late, reverse transcription products were found in HOS(high) cells as compared with HOS(low) cells. Moreover, a 24- to 30-fold difference in the number of copies of integrated HIV-1 DNA was observed. No difference in HIV-1 LTR activation between the two cell lines was evident. Finally, we show that the higher virus production observed in HOS(high) cells is inhibited by pertussis toxin, a Galphai protein inhibitor. Thus, CCR5 density mainly modulates postentry steps of the virus life cycle, particularly the reverse transcription. These data explain why CCR5 density influences HIV-1 disease progression and underline the therapeutic interest of lowering CCR5 expression.
CD163: A Specific Immunohistochemical Marker for Acute Myeloid Leukemia With Monocytic Differentiation (2008)

Acute myeloid leukemias (AMLs) with monocytic differentiation with or without recurring cytogenetic abnormalities have prognostic significance. Therefore, it is important to recognize such cases. Monocytic differentiation is identified by morphology and confirmed by cytochemical stains or flow cytometry. However, the materials for such analyses are not always available (air-dried aspirate smears, touch preparations, fresh cells). Thus, the utility of CD163, a hemoglobin scavenger molecule present on monocytes/macrophages, in identifying a monocytic component in AML in fixed, paraffin-embedded bone marrows was assessed. Using tissue microarrays, 31 cases of AML with monocytic differentiation and 35 cases without monocytic differentiation were evaluated in a blinded fashion for CD163 positivity and compared with CD68. Diagnoses were previously well established using cytochemistry and flow cytometry techniques. CD163 immunoreactivity was seen in 49% of AML cases with and 6% (2/35) without monocytic differentiation. CD68 was positive in 81% of AML cases with and 17% without monocytic differentiation. CD163 showed superior specificity for a monocytic component in AML compared with CD68 (94% vs. 83%). However, the suboptimal sensitivity (49%) limits its utility as a definitive marker of monocytic differentiation if negative in paraffin sections. These findings demonstrate that CD163 is helpful for the evaluation of a monocytic component in AML. When positive, correlation and evaluation for an associated recurring cytogenetic abnormality is warranted.
Microglial Physiology: Unique Stimuli, Specialized Responses (2009)

Microglia, the macrophages of the central nervous system parenchyma, have in the normal healthy brain a distinct phenotype induced by molecules expressed on or secreted by adjacent neurons and astrocytes, and this phenotype is maintained in part by virtue of the blood-brain barrier's exclusion of serum components. Microglia are continually active, their processes palpating and surveying their local microenvironment. The microglia rapidly change their phenotype in response to any disturbance of nervous system homeostasis and are commonly referred to as activated on the basis of the changes in their morphology or expression of cell surface antigens. A wealth of data now demonstrate that the microglia have very diverse effector functions, in line with macrophage populations in other organs. The term activated microglia needs to be qualified to reflect the distinct and very different states of activation-associated effector functions in different disease states. Manipulating the effector functions of microglia has the potential to modify the outcome of diverse neurological diseases.
Gene targeting and gene trap screens using embryonic stem cells: New approaches to mammalian development (1991)

Mouse embryonic stem cell lines offer an attractive route for introducing rare genetic alternations into the gene pool since the cells can be pre-screened in culture and the mutations then transmitted into the germline through chimera production. Two applications of this technique that seem ideally suited for a genetic analysis of development are enhancer and gene trap screens for loci expressed during gastrulation and production of targeted mutations using homologous recombination. These approaches should greatly increase the number of mouse developmental mutants available and help to elucidate the genetic hierarchy controlling embryogenesis.
The Structure of Ceramic Foams Prepared from Polyurethane-Ceramic Suspensions (1995)

Abstract The effect of ascending additions of fine TiO2 powder on the porosity of a hand mixed polyurethane foam system was studied. Voidage was sustained in the 95% region up to 20 vol% powder addition based on the polymer. Loss of powder from the windows occurred below this level and a reticulate structure was obtained on sintering. Above 20 vol%, the windows remained mainly closed on sintering. The implications of the results for polymer foam opacifiers and flame retardants and for ceramic foam fabrication are considered.
PCR-Introduced Loop Structure as Primer in DNA Sequencing (1998)

The need for a primer hybridization step before sequencing has been eliminated using a stem-loop structure generated by PCR. The loop structure is obtained by careful design of the PCR primer or by cloning the target DNA into a dedicated vector (pRIT 28HP). After solid-phase capture of the PCR product, the loop is formed by elution of the non-bound strand. Here, we show that both the immobilized and the eluted strand can be analyzed using conventional Sanger DNA sequencing and the novel pyrosequencing method as described previously. By using a stem-loop structure as a primer for DNA sequencing, the risk for mispriming is minimized.
Electrochemical behaviour and ESR spectra of nitro substituted mono- and dibenzoylmethylenebenzthiazolines and selenazolines (1979)

Compounds of the type of 2-(4'-nitrobenzoyl)methylene-3-ethylbenzothiazoline ( I ) and 2-bis-( p -nitrobenzoyl)methylene-3-ethylbenzothiazoline ( II ) were studied polarographically and by ESR spectroscopy to obtain informations about their electrochemical and follow-up reactions and their conformation. Whereas with compounds of the type I the conjugation in their molecules is preserved, with type II the coplanarity of the molecules is disturbed, which is manifested in the values of the splitting constants of the ESR spectra and a slow electron transfer between both nitrophenyl substituents. These conclusions are supported by NMR spectroscopic studies.
BCL-6, a POZ/zinc-finger protein, is a sequence-specific transcriptional repressor. (1996)

Approximately 40% of diffuse large cell lymphoma are associated with chromosomal translocations that deregulate the expression of the BCL6 gene by juxtaposing heterologous promoters to the BCL-6 coding domain. The BCL6 gene encodes a 95-kDa protein containing six C-terminal zinc-finger motifs and an N-terminal POZ domain, suggesting that it may function as a transcription factor. By using a DNA sequence selected for its ability to bind recombinant BCL-6 in vitro, we show here that BCL-6 is present in DNA-binding complexes in nuclear extracts from various B-cell lines. In transient transfectin experiments, BCL6 can repress transcription from promoters linked to its DNA target sequence and this activity is dependent upon specific DNA-binding and the presence of an intact N-terminal half of the protein. We demonstrate that this part of the BCL6 molecule contains an autonomous transrepressor domain and that two noncontiguous regions, including the POZ motif, mediate maximum transrepressive activity. These results indicate that the BCL-6 protein can function as a sequence-specific transcriptional repressor and have implications for the role of BCL6 in normal lymphoid development and lymphomagenesis.
Infusion-Related Reactions With Pegloticase, a Recombinant Uricase for the Treatment of Chronic Gout Refractory to Conventional Therapy (2014)

Phase 3 trial data combined with post hoc analyses demonstrated that knowledge of sUA preceding each pegloticase infusion and cessation of therapy when urate-lowering efficacy is lost provide a means to optimize the safety of pegloticase in clinical practice.
Learning hierarchical object maps of non-stationary environments with mobile robots (2002)

Building models, or maps, of robot environments is a highly active research area; however, most existing techniques construct unstructured maps and assume static environments. In this paper, we present an algorithm for learning object models of non-stationary objects found in office-type environments. Our algorithm exploits the fact that many objects found in office environments look alike (e.g., chairs, trash bins). It does so through a two-level hierarchical representation, which links individual objects with generic shape templates of object classes. We derive an approximate EM algorithm for learning shape parameters at both levels of the hierarchy, using local occupancy grid maps for representing shape. Additionally, we develop a Bayesian model selection algorithm that enables the robot to estimate the total number of objects and object templates in the environment. Experimental results using a real robot indicate that our approach performs well at learning object-based maps of simple office environments. The approach outperforms a previously developed non-hierarchical algorithm that models objects but lacks class templates. 1
Cleavage of cruciform DNA structures by an activity from Saccharomyces cerevisiae. (1985)

Protein extracts from Saccharomyces cerevisiae have been fractionated to reveal a nuclease activity that cleaves cruciform structures in DNA. Negatively supercoiled plasmids that contain inverted repeats that are extruded into cruciform structures have been used as DNA substrates. The sites of cleavage of pColIR215 DNA are located within the extruded cruciform stems and are symmetrically opposed to each other across the cruciform junction. Neither relaxed duplex DNA nor single-stranded DNA serve as substrates. The native molecular weight of the activity was estimated to be approximately equal to 200,000 by gel filtration.
Sequence heterogeneities among 16S ribosomal RNA sequences, and their effect on phylogenetic analyses at the species level (1996)

We have analyzed what phylogenetic signal can be derived by small subunit rRNA comparison for bacteria of different but closely related genera (enterobacteria) and for different species or strains within a single genus (Escherichia or Salmonella), and finally how similar are the ribosomal operons within a single organism (Escherichia coli). These sequences have been analyzed by neighbor-joining, maximum likelihood, and parsimony. The robustness of each topology was assessed by bootstrap. Sequences were obtained for the seven rrn operons of E. coli strain PK3. These data demonstrated differences located in three highly variable domains. Their nature and localization suggest that since the divergence of E. coli and Salmonella typhimurium, most point mutations that occurred within each gene have been propagated among the gene family by conversions involving short domains, and that homogenization by conversions may not have affected the entire sequence of each gene. We show that the differences that exist between the different operons are ignored when sequences are obtained either after cloning of a single operon or directly from polymerase chain reaction (PCR) products. Direct sequencing of PCR products produces a mean sequence in which mutations present in the most variable domains become hidden. Cloning a single operon results in a sequence that differs from that of the other operons and of the mean sequence by several point mutations. For identification of unknown bacteria at the species level or below, a mean sequence or the sequence of a single nonidentified operon should therefore be avoided. Taking into account the seven operons and therefore mutations that accumulate in the most variable domains would perhaps increase tree resolution. However, if gene conversions that homogenize the rRNA multigene family are rare events, some nodes in phylogenetic trees will reflect these recombination events and these trees may therefore be gene trees rather than organismal trees.
Lymphoid cell responses to bacterial cell wall components: polyclonal and immune responses of murine B cells to Streptococcus mutans carbohydrate antigens. (1981)

Abstract The polyclonal response of murine spleen cells to cell wall lysate (CWL) fractions and purified serotype carbohydrate of Streptococcus mutans has been determined by measuring plaque-forming cell (PFC) responses to trinitrophenyl (TNP), sheep (SRBC), and horse (HRBC) erythrocytes and total IgM synthesis. The immunogenicity of TNP-haptenated cell wall carbohydrate in BALB/c and C3H/HeJ mice in vivo and in spleen cell cultures in vitro has also been evaluated. Spleen cell cultures from both C3H/HeJ and BALB/c mice gave good polyclonal responses to M1 c, M1 g, and other cell wall preparations, as manifested by anti-TNP, -SRBC, and -HRBC PFC responses. Polyclonal responses, which were detectable within 2 days of culture, were highest after 3 days of stimulation. The response pattern obtained with an optimal concentration of these S. mutans cell wall preparations was similar to that seen with the B cell polyclonal activator, LPS. Furthermore, good IgM synthesis was induced in 7-day spleen cell cultures incubated with concentrations of S. mutans cell wall carbohydrate that were similar to those used to induce polyclonal PFC responses. Optimal anti-TNP PFC responses to both TNP-M1 c and TNP-M1 g occurred on day 4 after immunization in BALB/c and C3H/HeJ mice when they were given a single i.p. injection of 10 µg of antigen. Good anti-TNP PFC responses were observed when BALB/c nude (nu/nu) and heterozygous (nu/+) mice were immunized with either TNP-M1 c or TNP-M1 g, suggesting that these antigens are thymus-independent. Furthermore, spleen cell cultures from nu/nu mice gave somewhat higher responses to TNP-carbohydrate antigen than did their nu/+ counterparts. Purified B cells from spleens of BALB/c mice also gave good anti-TNP PFC responses. These findings demonstrate that the cell wall serotype carbohydrate of S. mutans is a polyclonal B cell activator and, when haptenated with TNP, is a thymus-independent antigen.
Recombinant follicle‐stimulating hormone (follitropin alfa) for ovulation induction in Japanese patients with anti‐estrogen‐ineffective oligo‐ or anovulatory infertility: results of a phase II dose–response study (2009)

A starting dose of 75 IU r-hFSH was associated with a favorable efficacy and safety profile for OI in Japanese women.
Bulk Purification and Deposition Methods for Selective Enrichment in High Aspect Ratio Single-Walled Carbon Nanotubes (2012)

Aqueous batch processing methods for the concurrent purification of single-walled carbon nanotube (SWNT) soot and enrichment in high aspect ratio nanotubes are essential to their use in a wide variety of electronic, structural, and mechanical applications. This manuscript presents a new route to the bulk purification and enrichment of unbundled SWNTs having average lengths in excess of 2 μm. Iterative centrifugation cycles at low centripetal force not only removed amorphous C and catalyst nanoparticles but also allowed the enhanced buoyancy of surfactant encapsulated, unbundled, high aspect ratio SWNTs to be used to isolate them in the supernatant. UV-vis-NIR and Raman spectroscopy were used to verify the removal of residual impurities from as-produced (AP-grade) arc discharge soot and the simultaneous enrichment in unbundled, undamaged, high aspect ratio SWNTs. The laminar flow deposition process (LFD) used to form two-dimensional networks of SWNTs prevented bundle formation during network growth. Additionally, it further enhanced the quality of deposits by taking advantage of the inverse relationship between the translational diffusion coefficient and length for suspended nanoparticles. This resulted in preferential deposition of pristine, unbundled, high aspect ratio SWNTs over residual impurities, as observed by Raman spectroscopy and atomic force microscopy (AFM).
Anti‐tumor activity of daunorubicin linked to poly‐L‐aspartic acid (1982)

Daunorubicin was bound to poly-L-aspartic acid via the methylketone side chain of the drug to avoid reaction of the sugar amino group believed to be essential for optimal drug activity. Attachment of the drug to the polyamino acid by an ester linkage was achieved by nucleophylic substitution reaction of 14-bromo-daunorubicin. Compared with free daunorubicin, the polymeric derivative was less cytotoxic to HeLa cells in vitro, but more effective against all tumor models tested (P388 leukemia, Gross leukemia, MS-2 sarcoma). The binding to the polypeptide markedly reduced drug toxicity but only slightly decreased drug potency. The daunorubicin-poly-L-aspartic acid conjugate demonstrated antitumor activity comparable to that of doxorubicin in leukemia models, but superior to that of doxorubicin in a solid tumor model (MS-2 sarcoma).
Vinexin, CAP/ponsin, ArgBP2: A Novel Adaptor Protein Family Regulating Cytoskeletal Organization and Signal Transduction. (2002)

Adaptor proteins, composed of two or more protein-protein interacting modules without enzymatic activity, regulate various cellular functions. Vinexin, CAP/ponsin, and ArgBP2 constitute a novel adaptor protein family. They have a novel conserved region homologous to the active peptide sorbin, as well as three SH3 (src homology 3) domains. A number of proteins binding to this adaptor family have been identified. There is accumulating evidence that this protein family regulates cell adhesion, cytoskeletal organization, and growth factor signaling. This review will summarize the structure and the function of proteins in this family.
LeIF: A Recombinant Leishmania Protein That Induces an IL-12-Mediated Th1 Cytokine Profile (1998)

We have evaluated the ability of the Leishmania protein LeIF to influence the Th1/Th2 cytokine responses and the generation of LeIF-specific T cell clones in the absence of adjuvant. We characterized LeIF-specific T cell responses in Leishmania major-infected and uninfected BALB/c mice. These mice develop a strong Th2 response during infection with L. major. When lymph node cells from infected BALB/c mice were stimulated in vitro with LeIF, only IFN-gamma (and no detectable IL-4) was found in the culture supernatant. In addition, LeIF down-regulated Leishmania Ag-specific IL-4 production by lymph node cells from infected BALB/c mice. Subsequently, Th responses were evaluated in naive BALB/c mice following immunization with LeIF. T cell clones derived from mice immunized with LeIF preferentially secreted IFN-gamma. Finally, to understand the basis for the preferential Th1 cytokine bias observed with LeIF, the ability of LeIF to influence the early cytokine profile was evaluated in splenocytes of SCID mice. We found that LeIF stimulated fresh spleen cells from naive SCID mice to secrete IFN-gamma by IL-12/IL-18-dependent mechanisms. The N-terminal half of the molecule (amino acid residues 1-226) maintained the ability to stimulate IFN-gamma from splenocytes of SCID mice. Finally, we also demonstrated that LeIF was able to provide partial protection of BALB/c mice against L. major. Thus, our results suggest the potential of LeIF as a Th1-type adjuvant and as a therapeutic and prophylactic vaccine Ag for leishmaniasis when used with other leishmanial Ags.