gebhart/patrepeval huggingface dataset:
Why is one Bacillus alpha-amylase more resistant against irreversible thermoinactivation than another? (1988)

Half-lives of Bacillus alpha-amylases at 90 degrees C and pH 6.5 greatly increase in the series from Bacillus amyloliquefaciens to Bacillus stearothermophilus to Bacillus licheniformis, e.g. the difference in thermostability between the first and the third enzymes exceeds 2 orders of magnitude. This stabilization is achieved by lowering the rate constant of monomolecular conformational scrambling, which is the cause of irreversible thermoinactivation of B. amyloliquefaciens and B. stearothermophilus alpha-amylases, so that for B. licheniformis alpha-amylase, another process, deamidation of Asn/Gln residues, emerges as the cause of inactivation. The extra thermostability of the thermophilic enzyme was found to be mainly due to additional salt bridges involving a few specific lysine residues (Lys-385 and Lys-88 and/or Lys-253). These stabilizing electrostatic interactions reduce the extent of unfolding of the enzyme molecule at high temperatures, consequently making it less prone to forming incorrect (scrambled) structures and thus decreasing the overall rate of irreversible thermoinactivation. The implications of these findings for protein engineering are discussed.
All-D amino acid-containing channel-forming antibiotic peptides. (1990)

The D enantiomers of three naturally occurring antibiotics--cecropin A, magainin 2 amide, and melittin--were synthesized. In addition, the D enantiomers of two synthetic chimeric cecropin-melittin hybrid peptides were prepared. Each D isomer was shown by circular dichroism to be a mirror image of the corresponding L isomer in several solvent mixtures. In 20% hexafluoro-2-propanol the peptides contained 43-75% alpha-helix. The all-D peptides were resistant to enzymatic degradation. The peptides produced single-channel conductances in planar lipid bilayers, and the D and L enantiomers caused equivalent amounts of electrical conductivity. All of the peptides were potent antibacterial agents against representative Gram-negative and Gram-positive species. The D and L enantiomers of each peptide pair were equally active, within experimental error. Sheep erythrocytes were lysed by both D- and L-melittin but not by either isomer of cecropin A, magainin 2 amide, or the hybrids cecropin A-(1-13)-melittin-(1-13)-NH2 or cecropin A-(1-8)-melittin-(1-18)-NH2. The infectivity of the bloodstream form of the malaria parasite Plasmodium falciparum was also inhibited by the D and L hybrids. It is suggested that the mode of action of these peptides on the membranes of bacteria, erythrocytes, plasmodia, and artificial lipid bilayers may be similar and involves the formation of ion-channel pores spanning the membranes, but without specific interaction with chiral receptors or enzymes.
New treatment options for patients with melanoma: review of melanoma-derived T-cell epitope-based peptide vaccines (1996)

Human melanoma represents the principal cause of death in patients with skin cancer in the United States and Europe. Tumour infiltrating lymphocytes recognizing melanoma have been used to identify the tumour antigens recognized by T-cells in the context of MHC class I or class II molecules. Such antigens include MAGE-1, MAGE-3, MART-1/Melan-A, gp100, tyrosinase, the tyrosinase-related antigen gp75, the antigen gp15 and the mutated CDK4 and beta-catenin gene-products. The identification of these T-cell epitopes provides us with novel reagents for the development of state-of-the-art treatments and for the (immuno-)monitoring of patients with melanoma. In order for treatments, including peptide-based vaccines, to be successful, several conceptual criteria must be met: (1) The patient's tumour must present the relevant epitope(s) integrated into the vaccine, (2) the tumour should express the appropriate restricting major histocompatibility complex (MHC) molecule(s) required for patient cytotoxic T lymphocyte (CTL) reactivity, and (3) the patient's T-cell repertoire should be able to react productively against the melanoma antigens present in the vaccine. Clinical trials implementing peptide-based vaccines or whole protein therapies have been initiated in the United States and Europe. We suggest that such treatments should include the careful monitoring of anti-tumour T-cell responses. This should include examination of melanoma antigen and MHC class I allele expression in the individual patient's tumour, assessment of the status of the peptide transporter molecules TAP1/TAP2 and evaluation of T-cell mediated immune responses reactive against peptides and autologous melanoma. Evaluation of clinical parameters (such as disease-free survival) in conjunction with an examination of immunological parameters may facilitate our understanding of the immune responses against T-cell antigens that are shared among melanoma and normal melanocytes, and may ultimately help to identify the most effective immunotherapy for patients with melanoma.
Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting (2007)

Genetic deletion studies have shown that haploinsufficiency of Delta-like ligand (Dll) 4, a transmembrane ligand for the Notch family of receptors, results in major vascular defects and embryonic lethality. To better define the role of Dll4 during vascular growth and differentiation, we selected the postnatal retina as a model because its vasculature develops shortly after birth in a highly stereotypic manner, during which time it is accessible to experimental manipulation. We report that Dll4 expression is dynamically regulated by VEGF in the retinal vasculature, where it is most prominently expressed at the leading front of actively growing vessels. Deletion of a single Dll4 allele or pharmacologic inhibition of Dll4/Notch signaling by intraocular administration of either soluble Dll4-Fc or a blocking antibody against Dll4 all produced the same set of characteristic abnormalities in the developing retinal vasculature, most notably enhanced angiogenic sprouting and increased endothelial cell proliferation, resulting in the formation of a denser and more highly interconnected superficial capillary plexus. In a model of ischemic retinopathy, Dll4 blockade also enhanced angiogenic sprouting and regrowth of lost retinal vessels while suppressing ectopic pathological neovascularization. Our data demonstrate that Dll4 is induced by VEGF as a negative feedback regulator and acts to prevent overexuberant angiogenic sprouting, promoting the timely formation of a well differentiated vascular network.
Disulfide-crosslinked heparin-pluronic nanogels as a redox-sensitive nanocarrier for intracellular protein delivery (2011)

Improving the efficacy of drug delivery via nanocarriers has been a major issue in the field of intravenous delivery. In this study, a polymeric nanogel was developed to enhance the stability, redox responsiveness, and the efficacy for intracellular protein delivery. The thiolated heparin-Pluronic conjugate was self-assembled and oxidized to form a disulfide-crosslinked nanogel network under a diluted aqueous condition. The disulfide-crosslinked heparin-Pluronic (DHP) nanogels with encapsulated RNase A were characterized by in vitro release and cytotoxicity tests depending on the existence of glutathione (GSH). The DHP nanogels exhibited reduced hydrodynamic size, higher encapsulation degree, and augmentable release responding to the GSH concentration. The ctotoxicity data confirmed that DHP nanogels were more effective for the intracellular delivery of RNase A compared to non-crosslinked nanogel.
DNA sequence of the murine gamma 1 switch segment reveals novel structural elements. (1986)

Immunoglobulin heavy chain switch regions are segments of DNA considered to be important in mediating class switching in B lymphocytes. Whereas these segments vary in length among the different murine isotypes, their structural organization schemes are all based on the tandem repetition of unit sequences. We previously showed that the S gamma 1 segment unexpectedly contains sequence elements that differ significantly from its prevalent unit repeat (49mer). Here we extend this preliminary characterization by determining the complete nucleotide sequence of the cloned S gamma 1 segment from BALB/c DNA. We find that S gamma 1 consists of more than 120 tandemly repeated 49mers. In addition, we show that the previously identified non-49mer sequences are part of a direct repeat element about 350 bp in length (DR II), which exists in two copies at the 5' end of S gamma 1. We also show that another unrelated direct repeat element about 500 bp long (DR I) exists near the 5' and 3' ends of S gamma 1. Thus, the structure of the S gamma 1 segment might be may be abbreviated as 5'-DRII-(49mer)15-DRI-DRII-(49mer)n-DRI , where n is between 40 and 160. Our results of Southern hybridization experiments suggest that this basic structural scheme is maintained in eight different Igh haplotypes, although S gamma 1 segments in different Igh haplotypes include different numbers of 49mer elements. Other murine S gamma segments differ in size among various Igh loci, but to a lesser extent than S gamma 1. At the level of tandemly repeated sequences, S gamma 1, S gamma 3, and S gamma 2b represent three distinct, nonoverlapping sets of sequences.
Co-localization of oestrogen receptor beta and leukocyte markers in the human cervix (2001)

Cervical ripening during parturition is associated with rapid production of catabolic enzymes by invading leukocytes and increased collagen metabolism. The recruitment of leukocytes is regulated by various factors including inflammatory mediators, prostaglandins and matrix metalloproteinases. Sex steroids may be indirectly or directly involved in this process. This study aimed to evaluate the expression of oestrogen receptor beta (ER beta) in blood cells infiltrating the cervix during pregnancy and parturition. Cervical biopsies were obtained from term pregnant, post-partal and non-pregnant women. The ER beta protein and leukocyte markers CD45 and CD68 were evaluated by single and double labelling immunohistochemistry. Quantitative values were assessed using a microscope and a high-resolution camera connected to a computer with image analysis program. The number of CD45(+) and CD68(+) cells in the cervix increased in term pregnancy and post-partum compared with the non-pregnant state. The ER beta antigen was co-localized with CD45 leukocyte common antigen and CD68 macrophage specific antigen in blood leukocytes infiltrating the cervical tissue. The presence of ER beta in the cervical leukocytes suggests that oestrogen may directly regulate leukocyte functions in the cervix.
Five‐color immunophenotyping plus DNA content analysis by laser scanning cytometry (1998)

Laser scanning cytometry is a new laboratory technology similar to flow cytometry but with advantages for certain clinical and research applications (7). To date, laser scanning cytometry has been successfully used to perform three-color immunophenotypic analysis of hematologic specimens, single-color immunophenotyping plus DNA content analysis of numerous specimen types, and automated analysis of fluorescence in situ hybridization specimens (1–5,9,10). Several other interesting applications are also in development (6). In general, advantages of laser scanning cytometry include reduced specimen size requirements, simplified methodologies, and the ability to microscopically examine individual cells—allowing for the direct correlation of cytologic morphology with objective fluorescence measurements. In this report, we describe a method which more fully takes advantage of the laser scanning cytometer's capabilities for immunophenotypic analysis of hematologic specimens. Specifically, we have devised a method to increase the number of fluorescent parameters from three to a total of six, five representing binding of immunofluorescent antibodies and one for stoichiometric measurements of DNA content. As with most laser scanning cytometric applications, this technique can be utilized on extremely small specimens and enables direct correlation of all of the measured fluorescent parameters with light microscopic cytologic morphology. Cytometry (Comm. Clin. Cytometry) 34:36–38, 1998. © 1998 Wiley-Liss, Inc.
Distinct Expression of CCR1 and CCR5 in Glomerular and Interstitial Lesions of Human Glomerular Diseases (2000)

We investigated the presence of CCR1- and CCR5-positive cells immunohistochemically in the kidneys of 38 patients with several renal diseases, including 13 crescentic glomerulonephritis patients. In addition, we determined cell phenotypes of CCR1- and CCR5-positive cells using a dual immunostaining technique. Urinary levels of their ligands, for CCR1 and CCR5; macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and regulated upon activation in normal T cells expressed and secreted (RANTES) were evaluated by enzyme-linked immunosorbent assay. CCR1- and CCR5-positive cells were detected in both glomeruli and interstitium of the diseased kidneys. Using a dual immunostaining technique, these positive cells were CD68-positive macrophages (MPhi) and CD3-positive T cells. The number of CCR1-positive cells in glomeruli was correlated with urinary levels of MIP-1alpha. The number of CCR1-positive cells in the interstitium was correlated with both urinary MIP-1alpha and RANTES levels. CCR1-positive cells in the interstitium remained after glucocorticoid therapy, most of which were MPhi, and were correlated with the intensity of interstitial fibrosis and tubular atrophy. Glomerular CCR5-positive cells were well correlated with extracapillary lesions and urinary MIP-1alpha levels, while interstitial CCR5-positive cells, mainly CD3-positive T cells, were correlated with interstitial lesions and urinary RANTES levels. Renal CCR5-positive cells were dramatically decreased during convalescence induced by glucocorticoids. These results suggest that chemokine receptor signaling may be pivotal for human renal diseases through the recruitment and activation of MPhi and T cells; CCR5-positive cells may participate in glomerular lesions including extracapillary lesions via MIP-1alpha and in interstitial lesions via RANTES. CCR1 may be involved in interstitial lesions in resolving phase after glucocorticoid therapy.
Application of Redox Enzymes for Probing the Antigen−Antibody Association at Monolayer Interfaces:  Development of Amperometric Immunosensor Electrodes (1996)

Insulation of the electrical contact between a redox protein and an electrode surface upon association of an antibody to an antigen monolayer assembled on the electrode is used to develop immunosensor devices. In one configuration, a mixed monolayer consisting of the N epsilon-(2,4-dinitrophenyl)lysine antigen and ferrocene units acting as electron transfer mediators is applied to sense the dinitrophenyl antibody (DNP-Ab) in the presence of glucose oxidase (GOx) and glucose. In the absence of DNP-Ab, the mixed monolayer electrode stimulates the mediated electrocatalyzed oxidation of glucose that results in an amplified amperometric response. Association of the DNP-Ab to the modified electrode blocks the electrocatalytic transformation. The extent of the electrode insulation by the DNP-Ab is controlled by the Ab concentration in the sample. In the second configuration, a N epsilon-(2,4-dinitrophenyl)lysine antigen monolayer assembled on a Au electrode is applied to sense the DNP-Ab in the presence of a redox-modified GOx, exhibiting electrical communication with the electrode surface. Two kinds of redox-modified "electrically wired" GOx are applied: GOx modified by N-(ferrocenylmethyl)caproic acid, Fc-GOx, and a novel electrobiocatalyst generated by reconstitution of apo-GOx with a ferrocene-modified FAD semisynthetic cofactor. Electrocatalytic oxidation of glucose by the electrically wired biocatalysts proceeds in the presence of the antigen monolayer electrode, giving rise to an amplified amperometric signal. The electrocatalytic transformation is blocked upon association of the DNP-Ab to the monolayer electrode. The extent of electrode insulation toward the bioelectrocatalytic oxidation of glucose is controlled by the DNP-Ab concentrations in the samples. The application of biocatalysts for amperometric sensing of antigen-antibody interactions at the electrode surface makes the electrode insensitive to microscopic pinhole defects in the monolayer assembly. The antigen monolayer electrode is applied to sense the DNP-Ab in the concentration range 1-50 micrograms mL-1.
Using a cutoff of <10 ppm for breath hydrogen testing: a review of five years' experience. (1999)

To assess the clinical use of the breath hydrogen test in a large community hospital using a <10 ppm cutoff, we reviewed 222 tests performed over a 5-year period to evaluate patients for disaccharidase deficiency or bacterial overgrowth of the small intestine. Of these, the vast majority (195) were for lactose malabsorption, although fructose (17), sucrose (8) and lactulose (2) were also occasionally administered. One hundred eleven tests (50 percent) were positive, with an increase of at least 10 ppm hydrogen above the fasting level and a maximum value most commonly observed (42.3 percent of the time) at 3 hours post-administration. Only 34 patients (15.3 percent) had symptoms noted during the test, as compared with 185 (83.3 percent) who had experienced persistent intestinal problems prior to the test. Recent conditions which may have caused intestinal distress, such as transient disaccharidase deficiency, infections, surgery or other disorders like Crohn's disease, ulcerative colitis or food poisoning, were recorded in only 14 cases. Patterns consistent with bacterial overgrowth of the small intestine were observed in only 3 cases. Of 111 positives, 9 cases had increases between 10 and 20 ppm hydrogen and 7 showed the increase in the 3-hour sample, possibly reflecting a delayed transit through the intestine. Final diagnoses in 6 of these where information was available were for conditions other than malabsorption. We conclude that using a rise of 10 ppm to interpret a positive test does not contribute significantly to an increased frequency of false positives, but that patients with increases between 10 and 20 ppm probably are not lactase deficient.
Lattice strain effects on CO oxidation on Pt(111) (2006)

Surface strain plays a major role in determining the rate limiting step and catalytic activity of platinum for CO oxidation.
Third-order intermodulation distortion in capacitively-driven CC-beam micromechanical resonators (2002)

The mechanism behind third order intermodulation distortion (IM 3 ) in capacitively driven clamped-clamped beam micromechanical ("CC-beam µmechanical") resonators is shown to arise mainly from nonlinear interactions between applied off-resonance electrical signals and the mechanical displacements they induce.Analytical formulations for the third-order input intercept point (IIP 3 ) are then presented, first with simplifications that allow a closed form expression, then with additional complexities to account for second-order effects, such as beam bending due to an applied dc-bias voltage.Using this analytical formulation, predicted voltage IIP 3 's of 1.8V and 6.5V for 9.2 MHz and 17.4 MHz µmechanical resonators, respectively, closely match measured values of 1.8V and 6.3V.Extensive data on the dependence of IIP 3 on dc-bias voltage, resonator Q, and resonator center frequency, are also included to lend further insight into the trade-offs involved when designing for a specific linearity requirement.
MHC class Ia molecules alone control NK-mediated bone marrow graft rejection (1999)

Mice with functionally deleted genes encoding MHC class I heavy (H-2K(b), H-2D(b)) and light (beta2-microglobulin) chains were used in bone marrow cell transfer experiments to study the role of class Ia and Ib molecules in NK cell function. Absence of H-2K(b) and absence of H-2D(b) on bone marrow cells resulted in complete and in almost complete NK-mediated rejection, respectively. Absence of either H-2 class Ib (at least when expressed in H-2 class Ia-deficient mice) or cell surface class Ia free heavy chains did not result in bone marrow rejection. Thus, in C57BL/6 adult mice, the inactivation of NK cells required for bone marrow cell engraftment relies entirely upon-H-2 class Ia molecules. These results imply the existence of an inhibitory receptor which recognizes either directly or indirectly H-2D(b) molecules and further suggest that in C57BL/6 mice the NK cells which do not express a H-2K(b) specific inhibitory receptor necessarily express an H-2D(b)-specific one.
Topical therapy for the management of childhood psoriasis: part I. (2008)

Psoriasis represents a potentially life-altering disease that can profoundly impact physical, emotional and social functioning, and overall quality of life. The majority of cases are mild and managed adequately with topical medications. A minor subset of children present with severe, rapidly evolving disease that requires systemic therapy. The choice of treatment in children, as in adults, is determined by disease acuity, morphology, distribution, severity and the presence of comorbidities such as psoriatic arthropathy. Practical considerations such as ease of use, patient acceptability, accessibility, risk to benefit ratio, cost and individual perceptions of disease and quality of life are factored into treatment decisions. Part I of this 2-part series will focus on topical agents, their varying degrees of effectiveness, potential side-effects and applications in clinical practice.
A self-assembled microbonded germanium/silicon heterojunction photodiode for 25 Gb/s high-speed optical interconnects (2013)

A novel technique using surface tension to locally bond germanium (Ge) on silicon (Si) is presented for fabricating high performance Ge/Si photodiodes. Surface tension is a cohesive force among liquid molecules that tends to bring contiguous objects in contact to maintain a minimum surface energy. We take advantage of this phenomenon to fabricate a heterojunction optoelectronic device where the lattice constants of joined semiconductors are different. A high-speed Ge/Si heterojunction waveguide photodiode is presented by microbonding a beam-shaped Ge, first grown by rapid-melt-growth (RMG) method, on top of a Si waveguide via surface tension. Excellent device performances such as an operating bandwidth of 17 GHz and a responsivity of 0.66 and 0.70 A/W at the reverse bias of -4 and -6 V, respectively, are demonstrated. This technique can be simply implemented via modern complementary metal-oxide-semiconductor (CMOS) fabrication technologies for integrating Ge on Si devices.
Polyoxazoline-Based Bottlebrush and Brush-Arm Star Polymers via ROMP: Syntheses and Applications as Organic Radical Contrast Agents (2019)

The synthesis of functional poly(2-alkyl-2-oxazoline) (PAOx) copolymers with complex nanoarchitectures using a graft-through ring-opening metathesis polymerization (ROMP) approach is described. First, well-defined norbornene-terminated poly(2-ethyl-2-oxazoline) (PEtOx) macromonomers (MM) were prepared by cationic ringopening polymerization. ROMP of these MMs produced bottlebrush copolymers with PEtOx side chains. In addition, PEtOx-based branched MMs bearing a terminal alkyne group were prepared and conjugated to an azide-containing bis-spirocyclohexyl nitroxide via Cu-catalyzed azide-alkyne cycloaddition (CuAAC). ROMP of this branched MM, followed by in situ cross-linking, provided PEtOx-based brush-arm star polymers (BASPs) with nitroxide radicals localized at the core-shell interface. These PEtOx-based nitroxide-containing BASPs displayed relaxivity values on par with state-of-the-art polyethylene glycol (PEG)-based nitroxide materials, making them promising as organic radical contrast agents for metal-free magnetic resonance imaging (MRI).