gebhart/patrepeval huggingface dataset:
Larotaxel (L) in combination with trastuzumab in patients with HER2 + metastatic breast cancer (MBC): Interim analysis of an open phase II label study (2008)

1070 Background: Larotaxel (L), a semi-synthetic taxoid, has shown preclinical and clinical activity against taxane-resistant BC, and it presents the ability to cross the blood brain barrier. In HER2 + BC, trastuzumab (H) combined with taxanes is highly active, particularly in early stage BC. However, there is a need to develop new combinations for HER2+ pts who develop metastatis (mets), especially brain mets. Methods: MBC pts, < 1 prior chemotherapy (Ct) for metastatic disease, measurable disease, HER2 + (IHC ≥ 3+ and/or FISH +), baseline LVEF≥ 50%, were eligible to receive 90 mg/m2 L, 1-hour infusion and 6 mg/kg (8 mg/kg loading dose) H, every 3 weeks(w). Inclusion of patients with asymptomatic brain mets (mandatory baseline CTscan ) was allowed. Main objectives: activity of LH combination (ORR as per RECIST), progression free-survival, CNS outcome or occurrence, overall survival, safety and pharmacokinetic (PK) profiles. Tumor assessments and LVEF were done every 2 cycles(cy). Results: As of Dec. 2007, 41/50 pts were treated. The first 26 evaluable pts are presented in this per-protocol interim analysis: median age of 55.5 y (30–78), 19 pts (73%) with > 2 organs involved (including 4 with brain mets), 17pts with prior Ct for metastatic disease (prior taxane: 13 and prior H:15). The median number of cy was 6 (1–12). Most common gr 3–4 adverse events: febrile neutropenia/neutropenic infection (4), diarrhea (2), asthenia (6). Eleven (42.3%) confirmed partial responses (PR) were reported in 1st or in 2nd line with 1 PR and 3 stable disease (SD) lasting ≥18 w in pts with brain mets. Preliminary PK results: clearance of L at cy1 and 6 are similar to those observed in monotherapy. Conclusions: L and H at full doses can be combined with a manageable toxicity. Preliminary data suggest good activity in pretreated pts with high tumor burden, including pts with brain mets. PK analysis will be presented on the whole population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis
Structure around C6−C7 Bond of the Chromophore in Bathorhodopsin:  Low-Temperature Spectroscopy of 6s-cis-Locked Bicyclic Rhodopsin Analogs (1996)

To elucidate the structural changes near the beta-ionone ring region of the chromophore during the photobleaching process of rhodopsin, the photochemical and subsequent thermal reactions of rhodopsin analogs, whose retinylidene chromophores were fixed in a 6s-cis form with a five-membered ring (6,5-rhodopsin) and a seven-membered ring (6,7-rhodopsin), respectively, were investigated by low-temperature spectroscopy. Like rhodopsin, both the rhodopsin analogs convert to the respective batho-intermediates upon absorption of light at -190 degrees C. The extinction coefficient of batho-intermediate of 6,5-rhodopsin is similar to that of bathorhodopsin, while that of 6,7-rhodopsin is considerably smaller than that of bathorhodopsin. Like bathorhodopsin, the batho-intermediate of 6,5-rhodopsin directly converts to lumi-intermediate, while that of 6,7-rhodopsin first converts to a blue-shifted intermediate and then to lumi-intermediate. These results strongly suggest that the structure around the beta-ionone ring region of the bathorhodopsin chromophore resembles 6,5-retinal rather than 6,7-retinal. From the comparison of the structural features among retinal, 6,5-retinal, and 6,7-retinal, a possible conformation around C6-C7 bond of the bathorhodopsin chromophore is discussed.
Functional Interactions of Cu-ATPase ATP7B with Cisplatin and the Role of ATP7B in the Resistance of Cells to the Drug (2009)

Cisplatin is a widely used chemotherapeutic agent for treatment of ovarian, testicular, lung, and stomach cancers. The initial response to the drug is robust; however, tumor cells commonly develop resistance to cisplatin, which complicates treatment. Recently, overexpression of the Cu-ATPase ATP7B in ovary cells was linked to the increased cellular resistance to cisplatin; and the role for Cu-ATPases in the export of cisplatin from cells was proposed. Our results support functional interactions between cisplatin and ATP7B but argue against the active transport through the copper translocation pathway as a mechanism of drug resistance. In hepatocytes, we observed no correlation between the levels of endogenous ATP7B and the resistance of cells to cisplatin. Unlike copper, cisplatin does not induce trafficking of ATP7B in hepatoma cells, neither does it compete with copper in a transport assay. However, cisplatin binds to ATP7B and stimulates catalytic phosphorylation with EC(50) similar to that of copper. Mutations of the first five N-terminal copper-binding sites of ATP7B do not inhibit the cisplatin-induced phosphorylation of ATP7B. In contrast, the deletion of the first four copper-binding sites abolishes the effect of cisplatin on the ATP7B activity. Thus, cisplatin binding to ATP7B and/or general changes in cellular copper homeostasis are likely contributors to the increased resistance to the drug. The link between changes in copper homeostasis and cisplatin resistance was confirmed by treating the Huh7 cells with copper chelator and increasing their resistance to cisplatin.cisplatin.
Radical b-Fragmentation of Bicyclic[3.3.0]carbinolamides: Synthesis of Five- and Eight-membered Cyclic Imides (1995)

The influence of 4-alkyl or 4-aryl substituents in the regioselectivity of the P-fragmentation of carbinolamidyl radicals generated from the corresponding carbinolamides (7-13) by irradiation with visible light in the presence of (diacetoxyiodo)benzene and iodine is described.In the case of the less hindered carbino-' ) Yields are in pare&esis.d, Only one isomeric iodine was obtained and the C-3 stereochemistry remains undetermined.* * * and adjacent carbons in a plane.For a structure such as (25) the relative configuration is 2R , 3S , 1's .I * *Consequently, the relative configuration of the macroimide ( 24) is 2R , 3R , 1's .
Quantitative Capillary Electrophoresis/Ion Spray Tandem Mass Spectrometry Determination of EDTA in Human Plasma and Urine (1997)

A quantitative method has been developed for the determination of EDTA in human plasma and urine. The samples are prepared with automated anion-exchange solid-phase extraction using 100 microL of human plasma. The extracts are analyzed by capillary electrophoresis/mass spectrometry using selected reaction monitoring in the negative ion mode. Large-volume injections (10% of the CE capillary volume) are used to improve the concentration level of detection via field-amplified sample injection. The first reported validation of a CE/MS/MS technique was carried out for this method. Using a 13C stable-label isotope for the internal standard, the lower level of detection and lower level of quantitation were determined to be 7.3 and 14.6 ng/mL EDTA in human plasma, respectively. The injection precision had a relative standard deviation (RSD) of 6.1%. The intra-assay precision was less than 15% RSD. The intra-assay accuracy was less than +/- 12% bias from the nominal concentration. The interassay precision was less than 18% RSD and the interassay accuracy was less than +/- 9% bias from the nominal concentration.
A quorum-sensing molecule acts as a morphogen controlling gas vesicle organelle biogenesis and adaptive flotation in an enterobacterium (2011)

Gas vesicles are hollow intracellular proteinaceous organelles produced by aquatic Eubacteria and Archaea, including cyanobacteria and halobacteria. Gas vesicles increase buoyancy and allow taxis toward air-liquid interfaces, enabling subsequent niche colonization. Here we report a unique example of gas vesicle-mediated flotation in an enterobacterium; Serratia sp. strain ATCC39006. This strain is a member of the Enterobacteriaceae previously studied for its production of prodigiosin and carbapenem antibiotics. Genes required for gas vesicle synthesis mapped to a 16.6-kb gene cluster encoding three distinct homologs of the main structural protein, GvpA. Heterologous expression of this locus in Escherichia coli induced copious vesicle production and efficient cell buoyancy. Gas vesicle morphogenesis in Serratia enabled formation of a pellicle-like layer of highly vacuolated cells, which was dependent on oxygen limitation and the expression of ntrB/C and cheY-like regulatory genes within the gas-vesicle gene cluster. Gas vesicle biogenesis was strictly controlled by intercellular chemical signaling, through an N-acyl homoserine lactone, indicating that in this system the quorum-sensing molecule acts as a morphogen initiating organelle development. Flagella-based motility and gas vesicle morphogenesis were also oppositely regulated by the small RNA-binding protein, RsmA, suggesting environmental adaptation through physiological control of the choice between motility and flotation as alternative taxis modes. We propose that gas vesicle biogenesis in this strain represents a distinct mechanism of mobility, regulated by oxygen availability, nutritional status, the RsmA global regulatory system, and the quorum-sensing morphogen.
Primary prevention of periodontitis: managing gingivitis (2015)

Data support the belief that professionally administered plaque control significantly improves gingival inflammation and lowers plaque scores, with some evidence that reinforcement of oral hygiene provides further benefit. Re-chargeable power toothbrushes provide small but statistically significant additional reductions in gingival inflammation and plaque levels. Flossing cannot be recommended other than for sites of gingival and periodontal health, where inter-dental brushes (IDBs) will not pass through the interproximal area without trauma. Otherwise, IDBs are the device of choice for interproximal plaque removal. Use of local or systemic anti-inflammatory agents in the management of gingivitis has no robust evidence base. We support the almost universal recommendations that all people should brush their teeth twice a day for at least 2 min. with fluoridated dentifrice. Expert opinion is that for periodontitis patients 2 min. is likely to be insufficient, especially when considering the need for additional use of inter-dental cleaning devices. In patients with gingivitis once daily inter-dental cleaning is recommended and the adjunctive use of chemical plaque control agents offers advantages in this group.
Rapid isolation of long cDNA clones from existing libraries (1991)

Obtaining full-length or even near full-length cDNA clones has been a time-consuming and labor-intensive step in the analysis of cloned genes. Recent methods which use PCR as a preparative tool for cloning (1,2) have made this step considerably more rapid, but may introduce sequence errors in the resulting clones due to numerous sequential rounds of in vitro replication. We describe a method for identifying long cDNA clones from existing cDNA libraries using PCR purely as a diagnostic tool.
Age Effects on Preattentive and Early Attentive Auditory Processing of Redundant Stimuli: Is Sensory Gating Affected by Physiological Aging? (2011)

The frontal hypothesis of aging predicts an age-related decline in cognitive functions requiring inhibitory or attentional regulation. In Alzheimer's disease, preattentive gating out of redundant information is impaired. Our study aimed to examine changes associated with physiological aging in both pre- and early attentive inhibition of recurrent acoustic information. Using a passive double-click paradigm, we recorded mid-latency (P30-P50) and late-latency (N100 and P200) evoked potentials in healthy young (26 ± 5 years) and healthy elderly subjects (72 ± 5 years). Physiological aging did not affect auditory gating in amplitude measures. Both age groups exhibited clear inhibition in preattentive P50 and attention-modulated (N100) components, whereas P30 was not attenuated. Irrespective of age, the magnitude of inhibition differed significantly, being most pronounced for N100 gating. Inhibition of redundant information seems to be preserved with physiological aging. Early attentive N100 gating showed the maximum effect. Further studies are warranted to evaluate sensory gating as a suitable biomarker of underlying neurodegenerative disease.
RP105, a novel B cell surface molecule implicated in B cell activation, is a member of the leucine-rich repeat protein family. (1995)

The RP105 Ag is a murine B cell surface molecule that transmits an activation signal into B cells following ligation with anti-RP105 mAb. The activation leads to protection of B cells from irradiation- or dexamethasone-induced apoptosis, and to B cell proliferation. A cDNA encoding the RP105 Ag was isolated. An encoded protein is a type I transmembrane protein consisting of 641 amino acids in a mature form. Northern hybridization with a probe specific for the cDNA clone detected a transcript with a size of approximately 3 kb. The transcript was observed in spleen, but not in thymus, kidney, muscle, heart, brain, or liver. Stable transfection of the cDNA clone conferred the expression of the RP105 Ag on a pro-B cell line, which was confirmed by immunofluorescence staining and immunoprecipitation with anti-RP105 mAb. The RP105 molecule possesses 22 tandem repeats of a leucine-rich motif. These repeated motifs are observed in members of the leucine-rich repeat protein family, and have been implicated in protein-protein interactions, such as cell adhesion or receptor-ligand binding. Amino- and carboxyl-flanking regions that are characteristically conserved among members of the family are located on both sides of tandemly repeated leucine-rich motifs in RP105 molecule. These results demonstrate that RP105 is a novel member of the leucine-rich repeat protein family, and the first member that is specifically expressed on B cells.
Design for sequentially timed all-optical mapping photography with optimum temporal performance (2015)

A recently developed ultrafast burst imaging method known as sequentially timed all-optical mapping photography (STAMP) [Nat. Photonics8, 695 (2014)10.1038/nphoton.2014.163] has been shown effective for studying a diverse range of complex ultrafast phenomena. Its all-optical image separation circumvents mechanical and electronic restrictions that traditional burst imaging methods have long struggled with, hence realizing ultrafast, continuous, burst-type image recording at a fame rate far beyond what is achievable with conventional methods. In this Letter, considering various design parameters and limiting factors, we present an optimum design for STAMP in terms of temporal properties including exposure time and frame rate. Specifically, we first derive master equations that can be used to predict the temporal performance of a STAMP system and then analyze them to realize optimum conditions. This Letter serves as a general guideline for the camera parameters of a STAMP system with optimum temporal performance that is expected to be of use for tackling problems in science that are previously unsolvable with conventional imagers.
Newborn Screening Program Practices in the United States: Notification, Research, and Consent (2002)

There is wide variation in practice among the US newborn screening programs. Because the programs collectively manage a comprehensive nationwide genomic databank, careful consideration of how information technology and high-throughput genomic analysis are used will be essential to allow progress in clinical care, public health, and research while protecting individual privacy.
FTIR investigations of the adsorption and disproportionation of NO on Cu-exchanged silicoaluminophosphate of type 34 (1998)

Novel copper exchanged silicoaluminophosphates of chabazite type catalyst have been prepared. Conventional techniques such as elemental analysis, X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy, nitrogen sorption capacity (BET) have been employed for the characterization of the materials. X-Ray photoelectron spectroscopy results identified the presence of both CuI and CuII species on the catalyst. A detailed FTIR study was carried out on the disproportionation reaction of nitric oxide over the Cu-SAPO-34 catalyst. The spectra indicated the formation of nitrous oxide, mono- and di-nitrosyl complexes of CuI and of CuII and nitrate species. The types of NO sites on the Cu-SAPO-34 are similar to those seen on other copper exchanged zeolites, in particular Cu-ZSM-5. Effects of the pressure, temperature and evacuation on these nitric oxide species have been studied. The concentration and distribution of NO complexes varies with the NO pressure, reaction temperature and evacuation. The adsorption of nitric oxide on the copper exchanged silicoaluminophosphate have been compared with the copper exchanged high silica pentasil zeolite catalyst under identical experimental conditions.
The strong efficiency of the Escherichia coli gapA P1 promoter depends on a complex combination of functional determinants (2004)

The Escherichia coli multi-promoter region of the gapA gene ensures a high level of GAPDH (glyceraldehyde-3-phosphate dehydrogenase) production under various growth conditions. In the exponential phase of growth, gapA mRNAs are mainly initiated at the highly efficient gapA P1 promoter. In the present study, by using site-directed mutagenesis and chemical probing of the RPo (open complex) formed by Esigma70 (holoenzyme associated with sigma70) RNAP (RNA polymerase) at promoter gapA P1, we show that this promoter is an extended -10 promoter that needs a -35 sequence for activity. The -35 sequence compensates for the presence of a suboptimal -10 hexamer. A tract of thymine residues in the spacer region, which is responsible for a DNA distortion, is also required for efficient activity. We present the first chemical probing of an RPo formed at a promoter needing both a -10 extension and a -35 sequence. It reveals a complex array of RNAP-DNA interactions. In agreement with the fact that residue A-11 in the non-template strand is flipped out in a protein pocket in previously studied RPos, the corresponding A residue in gapA P1 promoter is protected in RPo and is essential for activity. However, in contrast with some of the previous findings on RPos formed at other promoters, the -12 A:T pair is opened. Strong contacts with RNAP occur both with the -35 sequence and the TG extension, so that the sigma4 and sigma2 domains may simultaneously contact the promoter DNA. RNAP-DNA interactions were also detected immediately downstream of the -35 hexamer and in a more distal upstream segment, reflecting a wrapping of RNAP by the core and upstream promoter DNA. Altogether, the data reveal that promoter gapA P1 is a very efficient promoter sharing common properties with both extended -10 and non-extended -10 promoters.
Mouth Dissolving Tablets I: An Overview of Formulation Technology (2009)

Methods to improve patient’s compliance have always attracted scientists towards the development of fancy oral drug delivery systems. Among them, mouth dissolving drug delivery systems (MDDDS) have acquired an important position in the market by overcoming previously encountered administration problems and contributing to extension of patent life. MDDDS have the unique property of rapidly disintegrating and/or dissolving and releasing the drug as soon as they come in contact with saliva, thus obviating the requirement of water during administration. Therefore, these dosage forms have lured the market for a certain section of the patient population which include dysphagic, bed ridden, psychic, geriatric and paediatric patients. Several techniques have been developed in the recent past, to improve the disintegration quality of these delicate dosage forms without affecting their integrity. This article focuses on the technologies available and the advances made so far in the field of fabrication of mouth dissolving tablets. Apart from the conventional methods of fabrication, this review also provides the detailed concept of some unique patented technologies like Zydis, Lyoc, Quicksolv, Orasolv, Durasolv, Flashtab, Oraquick, Wowtab and Ziplet alongwith their advantages and limitations.
Light Propagation with Phase Discontinuities: Generalized Laws of Reflection and Refraction (2011)

Conventional optical components rely on gradual phase shifts accumulated during light propagation to shape light beams. New degrees of freedom are attained by introducing abrupt phase changes over the scale of the wavelength. A two-dimensional array of optical resonators with spatially varying phase response and subwavelength separation can imprint such phase discontinuities on propagating light as it traverses the interface between two media. Anomalous reflection and refraction phenomena are observed in this regime in optically thin arrays of metallic antennas on silicon with a linear phase variation along the interface, which are in excellent agreement with generalized laws derived from Fermat's principle. Phase discontinuities provide great flexibility in the design of light beams, as illustrated by the generation of optical vortices through use of planar designer metallic interfaces.
Heterogeneous memory management for embedded systems (2001)

This paper presents a technique for the efficient compiler management of software-exposed heterogeneous memory. In many lower-end embedded chips, often used in micro-controllers and DSP processors, heterogeneous memory units such as scratch-pad SRAM, internal DRAM, external DRAM and ROM are visible directly to the software, without automatic management by a hardware caching mechanism. Instead the memory units are mapped to different portions of the address space. Caches are avoided because of their cost and power consumption, and because they make it difficult to guarantee real-time performance. For this important class of embedded chips, the allocation of data to different memory units to maximize performance is the responsibility of the software.Current practice typically leaves it to the programmer to partition the data among the different memory units. We present a compiler strategy that automatically partitions the data among the memory units. We show that this strategy is optimal among all static partitions for global and stack data, and a good heuristic for heap data. For global and stack data, the scheme is provably equal to or better than any other compiler scheme or set of programmer annotations. Preliminary results show the benefits of optimal allocation: with just 20% of the data in SRAM, the formulation is able to decrease the runtime by 39% on average for our benchmarks vs. allocating all data to slow memory, without any programmer involvement. For some programs, less than 5% of data in SRAM achieves a similar speedup.
Stretching single polypeptides: The effect of rotational constraints in the backbone (2010)

Polypeptides consist of three types of backbone bonds that are distinguished by the degree to which their dihedral rotation is hindered. We discuss the effect of this inhomogeneous rotational restriction on the stretching response as measurable by single-molecule force spectroscopic experiments. The ab initio-derived molecular backbone structure yields geometric input parameters. For the cases where one or two out of three bonds are rotationally frozen, which are two extreme cases of the actual peptidic backbone statistics, we derive analytic and numerical results and show that the Kuhn and persistence lengths are substantially increased. A simple explicit formula is derived that accurately describes the extension over the entire force range.
High Efficiency Collectors For Solar Energy Applications: Analysis And Preliminary Experimental Results. (1989)

Non metallic concentrators with tapered input sections are carefully investigated for solar energy applications. In addition, preliminary experimental results are compared with the numerical analysis in order to derive the basic criteria for their optimum design.