gebhart/patrepeval huggingface dataset:
Anatomy of an Oligourea Six-Helix Bundle (2016)

Non-natural synthetic oligomers that adopt well-defined secondary structures (i.e., foldamers) represent appealing components for the fabrication of bioinspired self-assembled architectures at the nanometer scale. Recently, peptidomimetic N,N'-linked oligourea helices have been designed de novo with the ability to fold into discrete helix bundles in aqueous conditions. In order to gain better insight into the determinants of oligourea helix bundle formation, we have investigated the sequence-to-structure relationship of an 11-mer oligourea previously shown to assemble into a six-helix bundle. Using circular dichroism, NMR spectroscopy, native mass-spectrometry and X-ray crystallography, we studied how bundle formation was affected by systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains. The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies.
Optimization of Amide-Based Inhibitors of Soluble Epoxide Hydrolase with Improved Water Solubility (2005)

Soluble epoxide hydrolase (sEH) plays an important role in the metabolism of endogenous chemical mediators involved in the regulation of blood pressure and inflammation. 1,3-Disubstituted ureas with a polar group located on the fifth atom from the carbonyl group of urea function are active inhibitors of sEH both in vitro and in vivo. However, their limited solubility in water and relatively high melting point lead to difficulties in formulating the compounds and poor in vivo efficacy. To improve these physical properties, the effect of structural modification of the urea pharmacophore on the inhibition potencies, water solubilities, octanol/water partition coefficients (log P), and melting points of a series of compounds was evaluated. For murine sEH, no loss of inhibition potency was observed when the urea pharmacophore was modified to an amide function, while for human sEH 2.5-fold decreased inhibition was obtained in the amide compounds. In addition, a NH group on the right side of carbonyl group of the amide pharmacophore substituted with an adamantyl group (such as compound 14) and a methylene carbon present between the adamantyl and amide groups were essential to produce potent inhibition of sEH. The resulting amide inhibitors have 10-30-fold better solubility and lower melting point than the corresponding urea compounds. These findings will facilitate synthesis of sEH inhibitors that are easier to formulate and more bioavailable.
Escherichia coli RNA Polymerase Activity Observed Using Atomic Force Microscopy (1997)

Fluid tapping-mode atomic force microscopy (AFM) was used to observe Escherichia coli RNA polymerase (RNAP) transcribing two different linear double-stranded (ds) DNA templates. The transcription process was detected by observing the translocation of the DNA template by RNAP on addition of ribonucleoside 5'-triphosphates (NTPs) in sequential AFM images. Stalled ternary complexes of RNAP, dsDNA and nascent RNA were adsorbed onto a mica surface and imaged under continuously flowing buffer. On introduction of all four NTPs, we observed some DNA molecules being pulled through the RNAP, some dissociating from the RNAP and others which did not move relative to the RNAP. The transcription rates were observed to be approximately 0.5-2 bases/s at our NTP concentrations, approximately 5 microM. The RNA transcripts were not unambiguously imaged in fluid. However, in experiments using a small single-stranded (ss) circular DNA template, known as a rolling circle, transcripts up to 1 or 2 microns long could be observed with tapping mode AFM once the samples were dried and imaged in air. This confirmed our observations of the transcriptional activity of RNAP adsorbed onto mica. This work illustrates that the development of tapping-mode in fluid has made it possible to use AFM to follow biological processes at the molecular level and get new insights about the variability of activity of individual molecules bound to a surface.
In Vitro Generation of Long-lived Human Plasma Cells (2012)

Plasma cells (PCs), the terminal effectors of humoral immunity, are short-lived unless supported by niche environments in which they may persist for years. No model system has linked B cell activation with niche function to allow the in vitro generation of long-lived PCs. Thus, the full trajectory of B cell terminal differentiation has yet to be investigated in vitro. In this article, we describe a robust model for the generation of polyclonal long-lived human PCs from peripheral blood B cells. After a proliferative plasmablast phase, PCs persist in the absence of cell division, with viability limited only by elective culture termination. Conservative predictions for PC life expectancy are 300 d, but with the potential for significantly longer life spans for some cells. These long-lived PCs are preferentially derived from memory B cells, and acquire a CD138(high) phenotype analogous to that of human bone marrow PCs. Analysis of gene expression across the system defines clusters of genes with related dynamics and linked functional characteristics. Importantly, genes in these differentiation clusters demonstrate a similar overall pattern of expression for in vitro and ex vivo PCs. In vitro PCs are fully reprogrammed to a secretory state and are adapted to their secretory load, maintaining IgG secretion of 120 pg/cell/day in the absence of XBP1 mRNA splicing. By establishing a set of conditions sufficient to allow the development and persistence of mature human PCs in vitro, to our knowledge, we provide the first platform with which to sequentially explore and manipulate each stage of human PC differentiation.
Global model for high pressure electronegative radio-frequency discharges (1997)

We develop a global model for high pressure (0.1–1 Torr) electronegative rf discharges and apply it to model a capacitively driven plasma etcher. The molecular gases considered consist of either pure chlorine species or a mixture of chlorine and helium species. The charged and neutral heavy particle densities together with the electron density and electron temperature are calculated by using the equations of particle balance and power balance for the input discharge parameters rf power or rf current, inlet pressure, gas flow rates, reactor diameter, and gap spacing. The power is deposited in the electrons via ohmic heating and in those ions accelerated across the dc sheath potential. The voltage across the sheath is calculated self-consistently with the densities and the electron temperature by using a collisional Child law sheath model. Analytic scaling laws for the dependence of charged and neutral particle densities, electron temperature, rf voltage and current, sheath width, and plasma impedance on pressure and absorbed rf power are presented and used to explain the numerical results obtained from the global model. The model results are compared to recent experimental measurements in a chlorine discharge over a range of absorbed power Pabs=20–180 W at an inlet pressure pin=0.4 Torr and a range of pressure 0.1–1.6 Torr with a fixed input power of 100 W. We obtain reasonable agreement for Pabs&amp;lt;200 W and for 0.2 Torr&amp;lt;pin&amp;lt;1 Torr.
Phosphate Starvation-Inducible Proteins of Bacillus subtilis : Proteomics and Transcriptional Analysis (2000)

The phosphate starvation response in Bacillus subtilis was analyzed using two-dimensional (2D) polyacrylamide gel electrophoresis of cell extracts and supernatants from phosphate-starved cells. Most of the phosphate starvation-induced proteins are under the control of sigma(B), the activity of which is increased by energy depletion. In order to define the proteins belonging to the Pho regulon, which is regulated by the two-component regulatory proteins PhoP and PhoR, the 2D protein pattern of the wild type was compared with those of a sigB mutant and a phoR mutant. By matrix-assisted laser desorption ionization-time of flight mass spectrometry, two alkaline phosphatases (APases) (PhoA and PhoB), an APase-alkaline phosphodiesterase (PhoD), a glycerophosphoryl diester phosphodiesterase (GlpQ), and the lipoprotein YdhF were identified as very strongly induced PhoPR-dependent proteins secreted into the extracellular medium. In the cytoplasmic fraction, PstB1, PstB2, and TuaD were identified as already known PhoPR-dependent proteins, in addition to PhoB, PhoD, and the previously described PstS. Transcriptional studies of glpQ and ydhF confirmed the strong PhoPR dependence. Northern hybridization and primer extension experiments showed that glpQ is transcribed monocistronically from a sigma(A) promoter which is overlapped by four putative TT(A/T)ACA-like PhoP binding sites. Furthermore, ydhF might be cotranscribed with phoB initiating from the phoB promoter. Only a small group of proteins remained phosphate starvation inducible in both phoR and sigB mutant and did not form a unique regulation group. Among these, YfhM and YjbC were controlled by sigma(B)-dependent and unknown PhoPR-independent mechanisms. Furthermore, YtxH and YvyD seemed to be induced after phosphate starvation in the wild type in a sigma(B)-dependent manner and in the sigB mutant probably via sigma(H). YxiE was induced by phosphate starvation independently of sigma(B) and PhoPR.
Biological cell (pollen grain) refractive index tomography with digital holographic microscopy (2006)

This paper present a novel approach to perform the tomography of biological specimen based on Digital Holographic Microscopy (DHM). A hologram results from the interference between a reference wave and an object wave reflected from or transmitted through a sample. In the hologram, both amplitude and phase of the field transmitted through the object are registered. In DHM, the object field is recovered when the hologram is processed by a digitally computed replica of the reference wave, allowing quantitative measurement of both phase and amplitude. Phase measurements provide high accuracy optical path length measurements across the specimen along the optical axis. To proceed to a tomographic reconstruction of the refractive index of the sample based on this quantitative phase measurement, such 2-dimentionnal data must be recorded for different sample orientations covering an angle of 180° to cover all the object spatial frequencies in the reciprocal space. The representation of the data in function of the angle is known as a sinogram. The 3-dimentionnal refractive index can then be reconstructed from the sinograms by a filtered backprojection algorithm. In our system, the specimen is inserted in a glass micropipette to permit its rotation. To our knowledge, a quantitative tomography of the refractive index of a pollen cell with a resolution in the micron range is presented for the first time.
Analysis of bone marrow transplantation data in man. (1986)

The use of bone marrow transplantation has increased rapidly since 1970; more than 2500 transplants will be performed in 1986. In this review I consider alternative approaches to analysis of data of bone marrow transplantation in man. The advantages and limitations of single-centre and pooled data analyses are considered. I suggest that both are needed and are complementary. Finally, I review the activities of the International Bone Marrow Transplant Registry and indicate future directions for collaborative research.
Improved survival of patients with homozygous familial hypercholesterolaemia treated with plasma exchange. (1985)

Plasma exchange was undertaken in five patients with homozygous familial hypercholesterolaemia at intervals of two weeks for a mean of 8.4 years. These patients had survived an average of 5.5 years longer than their five respective homozygous siblings (p = 0.3), each of whom must have had a matching genetic defect but who died untreated. The 37% decrease in peak serum cholesterol concentrations maintained by plasma exchange presumably reduced progression of atherosclerosis in the treated patients and thus lessened their risk of premature death.
Western blot (immunoblot) assay of small, round-structured virus associated with an acute gastroenteritis outbreak in Tokyo (1989)

Small, round-structured virus (SRSV) was detected in a stool specimen of a patient during an acute gastroenteritis outbreak in Tokyo and was tentatively named SRSV-9. SRSV-9 was purified by sucrose velocity gradient centrifugation after CsCl density gradient centrifugation. The buoyant density of SRSV-9 appeared to be 1.36 g/ml in CsCl. A Western blot (immunoblot) assay using the biotin-avidin system revealed that SRSV-9 was antigenically related to the Hawaii agent but distinct from the Norwalk agent and contained a single major structural protein with a molecular size of 63.0 +/- 0.6 kilodaltons. The prevalence of SRSV-9 infection in Tokyo was surveyed by the Western blot antibody assay by using a crude virus preparation as the antigen. Seroconversion was observed in 56.5% of the patients involved in the outbreaks from which SRSV was detected by electron microscopy.
Immunotherapy for multiple myeloma (2014)

The potential potency of the immune system in targeting malignant plasma cells in multiple myeloma is best demonstrated in the allogeneic transplant setting, where durable responses can be achieved. However, allogeneic transplantation is associated with significant morbidity and mortality related to graft versus host disease, due to the non-specific nature of allo-reactive T cell responses mediated by donor lymphocytes. Immunotherapeutic approaches that more specifically target the malignant plasma cells have the potential to improve outcomes in multiple myeloma. The development of clinically efficacious immunotherapy in multiple myeloma is dependent on achieving a greater understanding of the complex interactions between the immunologic milieu and the growth of the malignant plasma cell clone. A number of antigens have been identified on malignant plasma cells that may be targeted by both humoral and cell mediated immunotherapeutic strategies. Encouraging results have been demonstrated both pre-clinically and in clinical trials. In this review, we summarize the clinical data evaluating immunotherapeutic approaches for the treatment of multiple myeloma.
Background estimation and removal based on range and color (2003)

Background estimation and removal based on the joint use of range and color data produces superior results than can be achieved with either data source alone. This is increasingly relevant as inexpensive, real-time, passive range systems become more accessible through novel hardware and increased CPU processing speeds. Range is a powerful signal for segmentation which is largely independent of color and hence not effected by the classic color segmentation problems of shadows and objects with color similar to the background. However range alone is also not sufficient for the good segmentation: depth measurements are rarely available at all pixels in the scene, and foreground objects may be indistinguishable in depth when they are close to the background. Color segmentation is complementary in these cases. Surprisingly, little work has been done to date on joint range and color segmentation. We describe and demonstrate a background estimation method based on a multidimensional (range and color) clustering at each image pixel. Segmentation of the foreground in a given frame is performed via comparison with background statistics in range and normalized color. Important implementation issues such as treatment of shadows and low confidence measurements are discussed in detail.
Expression of ykdA , Encoding a Bacillus subtilis Homologue of HtrA, Is Heat Shock Inducible and Negatively Autoregulated (2000)

ABSTRACT There are three members of the HtrA family of serine proteases, YkdA, YvtA, and YyxA, encoded in the chromosome of Bacillus subtilis . In this study, we report on the promoter structure and regulation of ykdA expression. The ykdA gene is heat inducible, exhibiting a biphasic pattern of expression during a 60-min interval after heat shock. Increased expression after heat shock occurs at the transcriptional level. The heat-shock-inducible promoter has a single mismatch with a SigA-type −10 motif, but does not exhibit similarity to a SigA −35 region. There are six octamer repeats with a consensus TTTTCACA positioned at, and upstream of, the normal position of a −35 region. While repeats V and VI appear dispensable, repeat IV is essential for normal thermoinducible expression. This promoter structure is also found in the control region of yvtA , encoding a second member of this family of proteases. Expression of ykdA is negatively autoregulated both during the growth cycle and during heat shock. Our evidence suggests that YkdA protease activity is not required for this form of regulation. Null mutants of ykdA display increased tolerance to heat and are 80-fold more resistant to 10 mM hydrogen peroxide than wild-type cells. However, ykdA expression is not induced by hydrogen peroxide. These results indicate that the regulon to which YkdA belongs is linked to the oxidative stress response in B. subtilis .
Genetically engineered negative signaling molecules in the immunomodulation of allergic diseases (2004)

The balance between positive and negative signaling controls mast cell and basophil reactivity, which is critical in the expression of human allergic diseases. This approach using a human Fc gamma-Fc epsilon fusion protein to co-aggregate Fc epsilon RI with the Fc gamma RII holds promise as a new therapeutic platform for the immunomodulation of allergic diseases and potentially other mast cell/basophil-dependent disease states.
Growth and Tolerance of Preterm Infants Fed a New Extensively Hydrolyzed Liquid Human Milk Fortifier (2015)

Both fortifiers showed excellent weight gain (grams per kilograms per day), tolerance, and low incidence of morbidity outcomes with the infants who were strict protocol followers fed LE-HMF having improved growth during the study. These data point to the safety and suitability of this new concentrated liquid HMF (LE-HMF) in preterm infants. Growth with this fortifier closely matches the recent recommendations for a weight gain of >18 g · kg(-1) · day(-1).
Altered processing of thawed red cells to improve the in vitro quality during postthaw storage at 4°C (2007)

Leukoreduced, deglycerolized RBCs can be stored for 48 hours in SAGM. Improved ATP levels during refrigerated storage can be observed with thawed cells, resuspended in AS-3, when PBS is used as a washing solution.
The neglected 95%: Why American psychology needs to become less American. (2008)

This article proposes that psychological research published in APA journals focuses too narrowly on Americans, who comprise less than 5% of the world's population. The result is an understanding of psychology that is incomplete and does not adequately represent humanity. First, an analysis of articles published in six premier APA journals is presented, showing that the contributors, samples, and editorial leadership of the journals are predominantly American. Then, a demographic profile of the human population is presented to show that the majority of the world's population lives in conditions vastly different from the conditions of Americans, underlining doubts of how well American psychological research can be said to represent humanity. The reasons for the narrowness of American psychological research are examined, with a focus on a philosophy of science that emphasizes fundamental processes and ignores or strips away cultural context. Finally, several suggestions for broadening the scope of American psychology are offered.
The membrane proteins of the vacuolar system I. Analysis of a novel method of intralysosomal iodination. (1980)

A method has been developed to deliver an idoinating system into the confines of the phagolysosome, allowing us to study the nature of the phagolysosomal membrane. Lactoperoxidase (LPO) is covalently coupled to carboxylated latex spheres (LPO-latex) in a stable, enzymatically active form. The addition of LPO-latex to cultured macrophages leads to their rapid attachment, ingestion, and enclosure in a plasma membrane-derived phagocytic vacuole. These organelles rapidly fuse with preexisting lysosomes and are converted to phagolysosomes (PL) that demonstrates both acid phosphatase and lactoperoxidase activities. The exposure of LPO-latex containing cells to 125I- and an extracellular peroxide-generating system, glucose oxidase-glucose, at 4 degrees C leads to incorporation of label into TCA-precipitable material. The incorporated cel-associated label was present as monoiodotyrosine, and negligible amounts were found in lipids. Cell viability remained > 99%. Autoradiography at both the light and EM level revealed that > 97% of the cells were labeled, and quantitative analysis demonstrated the localization of grains to LPO-latex containing PL. PL were separated on sucrose gradients, and their radiolabel was confined almost exclusively to the membrane rather than soluble contents. SDS-polyacrylamide gel electrophoretic analysis of the peptides iodinated from within PL demonstrated at least 24 species with molecular weights ranging from 12,000 to 250,000. A very similar group of proteins was identified on the plasma membrane (PM) after surface iodination, and on latex phagosomes derived from iodinated PM. No novel proteins were detected in PL, either immediately after phagosome-lysosome fusion or after 1 h of intracytoplasmic residence. We conclude that the membrane proteins accessible to LPO-catalyzed iodination on the luminal surface of the PL and on the external face of the PM are similar, if not identical.
Orally Active Fusion Inhibitor of Respiratory Syncytial Virus (2004)

BMS-433771 was found to be a potent inhibitor of respiratory syncytial virus (RSV) replication in vitro. It exhibited excellent potency against multiple laboratory and clinical isolates of both group A and B viruses, with an average 50% effective concentration of 20 nM. Mechanism-of-action studies demonstrated that BMS-433771 inhibits the fusion of lipid membranes during both the early virus entry stage and late-stage syncytium formation. After isolation of resistant viruses, resistance was mapped to a series of single amino acid mutations in the F1 subunit of the fusion protein. Upon oral administration, BMS-433771 was able to reduce viral titers in the lungs of mice infected with RSV. This new class of orally active RSV fusion inhibitors offers potential for clinical development.
Reaction of diazonium salt with tyrosine residues in polypeptides (1975)

Abstract Some copolymers of L ‐glutamic acid and L ‐tyrosine are treated with p ‐carboxybenzenediazonium chloride. Monoazotyrosine chromophores can be obtained along the polypeptide chains in the presence of a stoichiometric quantity of the reagent, whereas an excess of the reagent gives rise to the formation of a mixture of mono‐ and bis‐azoderivatives. In all the cases only a part of the total number of the tyrosine residues can be modified. The results are discussed on the basis of the p K a values for the ionization of tyrosine and azo‐tyrosine OH‐groups.