gebhart/patrepeval huggingface dataset:
Homology modelling and protein engineering strategy of subtilases, the family of subtilisin-like serine proteinases (1991)

Subtilases are members of the family of subtilisin-like serine proteases. Presently, greater than 50 subtilases are known, greater than 40 of which with their complete amino acid sequences. We have compared these sequences and the available three-dimensional structures (subtilisin BPN', subtilisin Carlsberg, thermitase and proteinase K). The mature enzymes contain up to 1775 residues, with N-terminal catalytic domains ranging from 268 to 511 residues, and signal and/or activation-peptides ranging from 27 to 280 residues. Several members contain C-terminal extensions, relative to the subtilisins, which display additional properties such as sequence repeats, processing sites and membrane anchor segments. Multiple sequence alignment of the N-terminal catalytic domains allows the definition of two main classes of subtilases. A structurally conserved framework of 191 core residues has been defined from a comparison of the four known three-dimensional structures. Eighteen of these core residues are highly conserved, nine of which are glycines. While the alpha-helix and beta-sheet secondary structure elements show considerable sequence homology, this is less so for peptide loops that connect the core secondary structure elements. These loops can vary in length by greater than 150 residues. While the core three-dimensional structure is conserved, insertions and deletions are preferentially confined to surface loops. From the known three-dimensional structures various predictions are made for the other subtilases concerning essential conserved residues, allowable amino acid substitutions, disulphide bonds, Ca(2+)-binding sites, substrate-binding site residues, ionic and aromatic interactions, proteolytically susceptible surface loops, etc. These predictions form a basis for protein engineering of members of the subtilase family, for which no three-dimensional structure is known.
Transdermal lontophoretic Delivery of Enkephalin Formulated in Liposomes (1996)

Transdermal iontophoretic transport of a liposomal formulation of [Leu5]enkephalin, across human cadaver skin, was investigated. Franz (vertical) cells were supplied with 0.5 mA/cm2 current density via silver/silver chloride electrodes from a Scepter power supply. Enkephalin spiked with [3H]enkephalin was transported across skin from anode or cathode, depending on the charge on the molecule. Liposomes or their constituents were shown to penetrate into the skin. Enkephalin, when delivered iontophoretically at its isoelectric point, from liposomes carrying positive or negative charge on their surface, resulted in permeation of radioactivity which was same or less than that of the controls when analyzed by liquid scintillation counting. When analyzed by radiochromatography detector on HPLC, degradation of enkephalin during transport was observed, with several degradation peaks in the chromatogram. The degradation was less in liposome formulations, as compared to controls. This is the first report of the combined use of liposomes and iontophoresis for transdermal delivery.
PACAP38 induces migraine-like attacks in patients with migraine without aura (2008)

Experimental studies have shown that infusion of vasoactive neurotransmitters may trigger headache or migraine-like attacks in man. Pituitary adenylate cyclase activating peptide-38 (PACAP38) is a strong vasodilator found in trigeminal sensory and parasympathetic perivascular nerve fibers. We therefore hypothesized that infusion of PACAP38 would cause headache in healthy subjects and migraine-like attacks in migraine patients. Twelve healthy subjects and 12 migraine patients were examined in two separate studies. All subjects were allocated to receive 10 pmol/kg/min PACAP38 and placebo in a randomized, double-blind crossover study design. Headache was scored on a verbal rating scale (VRS) during hospital (0-2 h) and post-hospital (2-12 h) phases. Mean blood flow velocity in the middle cerebral artery (V(MCA)) by transcranial Doppler (TCD) and diameter of the superficial temporal artery (STA) by high resolution ultrasonography were recorded during hospital phase in migraineurs. PACAP38 infusion caused headache in all healthy subjects and 11 out of 12 migraine patients. Seven migraine patients experienced migraine-like attacks after PACAP38 and none after placebo (P = 0.016). Most of attacks (6 out of 7) occurred during the post-hospital phase [mean time 6 h (range 2-11)]. Two healthy subjects reported migraine-like attacks after PACAP38 during the hospital phase and none during the post-hospital phase. In the hospital phase, the area under the curve (AUC) for headache score was larger during PACAP38 infusion compared to placebo in healthy subjects (P = 0.005) and tended to be larger in migraineurs (P = 0.066). In the post-hospital phase, the AUC for headache was larger after PACAP38 infusion compared to placebo in both healthy subjects (P = 0.005) and migraine patients (P = 0.013). In migraine patients, PACAP38 caused a peak decrease of 16.1% in V(MCA) and a 37.5% increase in STA diameter at 20 min after start of infusion. In conclusion, PACAP38 infusion caused headache and vasodilatation in both healthy subjects and migraine patients. In migraine sufferers, PACAP38 caused delayed migraine-like attacks. The findings stimulate further investigation of the neuronal and vascular mechanisms of PACAP38.
Molecular Signature of High Yield (Growth) Influenza A Virus Reassortants Prepared as Candidate Vaccine Seeds (2013)

In the era of application of reverse genetics to alter influenza A virus genomes, the mutations identified in the HYR gene segments associated with high growth in ovo may be of great practical benefit to modify PR8 and/or wt virus gene sequences for improved growth of vaccine 'seed' viruses.
pH-Sensitive Gating by Conformational Change of a Polypeptide Brush Grafted onto a Porous Polymer Membrane (1997)

Benzyl glutamate NCA was graft-polymerized onto a porous poly(tetrafluoroethylene) membrane in order to study the effects of pH and ionic strength on permeation rate. The membrane was first glow-discharged in the presence of ammonia in order to produce amino groups on the surface. Following graft polymerization the graft chains were hydrolyzed to yield poly(glutamic acid). The rate of water permeation through this poly(glutamic acid)-grafted polymer membrane was pH-dependent and found to be slow under high-pH conditions and fast under low-pH conditions. Under high-pH conditions, randomly coiled graft chains extend to close the pores. The chains form a helix structure and open the pores under low-pH conditions. The magnitude of the permeation rate was dependent upon the length and density of graft chains. Ionic strength also affected the permeation rate.
An eugeneodontid elasmobranch from the Late Paleozoic of Kansas (1996)

A tooth battery, palatoquadrate, and a gill-arch element of Bobbodus schaefferi were collected from Late Pennsylvanian/Early Permian (Asselian) rocks near Manhattan, Kansas. Depending on the placement of the Pennsylvanian–Permian boundary, this specimen extends the upper limit of the species from the Virgilian (Gzelian) into the Gearyan (Asselian). The new range thus is Kasimovian to Asselian, a 15 my interval. Based on features of the palatoquadrate, the diagnoses of the order Eugeneodontida and the superfamily Caseodontoidea are revised. Bobbodus is the most primitive genus of the order Eugeneodontida.
Regulator of G Protein Signaling 5 Is Highly Expressed in Parathyroid Tumors and Inhibits Signaling by the Calcium-Sensing Receptor (2011)

The molecular mechanisms responsible for aberrant calcium signaling in parathyroid disease are poorly understood. The loss of appropriate calcium-responsive modulation of PTH secretion observed in parathyroid disease is commonly attributed to decreased expression of the calcium-sensing receptor (CaSR), a G protein-coupled receptor. However, CaSR expression is highly variable in parathyroid adenomas, and the lack of correlation between CaSR abundance and calcium-responsive PTH kinetics indicates that mechanisms independent of CaSR expression may contribute to aberrant calcium sensing in parathyroid disease. To gain a better understanding of parathyroid tumors and the molecular determinants that drive parathyroid adenoma development, we performed gene expression profiling on a panel of 64 normal and neoplastic parathyroid tissues. The microarray data revealed high-level expression of genes known to be involved in parathyroid biology (PTH, VDR, CGA, CaSR, and GCM2). Moreover, our screen identified regulator of G protein signaling 5 (RGS5) as a candidate inhibitor of CaSR signaling. We confirmed RGS5 to be highly expressed in parathyroid adenomas relative to matched-pair normal glands. Transient expression of RGS5 in cells stably expressing CaSR resulted in dose-dependent abrogation of calcium-stimulated inositol trisphosphate production and ERK1/2 phosphorylation. Furthermore, we found that RGS5-nullizygous mice display reduced plasma PTH levels, an outcome consistent with attenuated opposition to CaSR activity. Collectively, these data suggest that RGS5 can act as a physiological regulator of calcium sensing by CaSR in the parathyroid gland. The abnormally elevated expression of RGS5 observed in parathyroid adenomas could thus represent a novel mechanism of CaSR desensitization in patients with primary hyperparathyroidism.
Infrared controlled waxes for liquid handling and storage on a CD-microfluidic platform (2010)

A novel active valving technique, whereby paraffin wax plugs in microchannels on a centrifugal microfluidic platform are actuated using focused infrared (IR) radiation is demonstrated in this report. Microchannels were simultaneously or sequentially opened using a stationary IR source by forming wax plugs with similar or differing melting points. The presented wax plugs offer key advantages over current active valving techniques, including a less involved fabrication procedure, a simpler actuation process, and the ability to multiplex experiment with active valves. In addition, a new technique for automated liquid reagent storage and release on the microfluidic disc platform, based on the formation and removal of a wax layer, is demonstrated. Overall, the techniques presented in this report offer novel methods for liquid handling, separation, and storage on the centrifugal microfluidic disc platform.
Microfluidic crystallization (2008)

Microfluidics offers a wide range of new tools that permit one to revisit the formation of crystals in solution and yield insights into crystallization processes. We review such recent microfluidic devices and particularly emphasize lab-on-chips dedicated to the high-throughput screening of crystallization conditions of proteins with nanolitre consumption. We also thoroughly discuss the possibilities offered by the microfluidic tools to acquire thermodynamic and kinetic data that may improve industrial processes and shed a new light on nucleation and growth mechanisms.
Algorithms+Data Structures = Programs (2024)

Learn with confidence with this hands-on undergraduate textbook for CS2 courses. Active-learning and real-world projects underpin each chapter, briefly reviewing programming fundamentals then progressing to core data structures and algorithms topics including recursion, lists, stacks, trees, graphs, sorting, and complexity analysis. Creative projects and applications put theoretical concepts into practice, helping students master the fundamentals. Dedicated project chapters supply further programming practice using real-world, interdisciplinary problems which students can showcase in their own online portfolios. Example Interview Questions sections prepare students for job applications. The pedagogy supports self-directed and skills-based learning with over 250 'Try It Yourself' boxes, many with solutions provided, and over 500 progressively challenging end-of-chapter questions. Written in a clear and engaging style, this textbook is a complete resource for teaching the fundamental skills that today's students need. Instructor resources are available online, including a test bank, solutions manual, and sample code.
Structural Determination of the Principal Byproduct of the Lithium-Ammonia Reduction Method of Methamphetamine Manufacture (2004)

Abstract One common method- of illicit methamphetamine manufacture utilizes an alkali metal, typically lithium, and liquid ammonia to chemically reduce ephedrine or pseudoephedrine to form methamphetamine. This method is often referred to as the lithium-ammonia reduction method or the Birch reduction method. While the hydroxyl group of ephedrine is more reactive than the aromatic ring, excess alkali metal and the presence of a proton source allow the formation of a cyclohexadiene byproduct not found in samples of methamphetamine produced from other manufacturing methods. A sample enriched in this byproduct was generated and characterized using nuclear magnetic resonance (NMR) spectroscopy, gas chromatography-mass spectrometry (GC-MS), infrared (IR) spectrophotometry, and ultraviolet (UV) spectrophotometry. The chemical structure of this byproduct was determined to be 1-(1ʹ,4ʹ-cyclohexadienyl)-2-methylaminopropane (CMP).
A Novel Anti-Herpes Simplex Virus Type 1-Specific Herpes Simplex Virus Type 1 Recombinant (1999)

A recombinant herpes simplex virus (HSV) capable of inhibiting its own replication as well as the replication of wild-type virus would have greatly increased safety as a general purpose vector for in vivo gene transfer, antitumor therapy, and viral vaccine against HSV infection. By using a tetracycline repressor (tetR)-mediated HSV-1 viral replication switch [Yao and Eriksson (1999). Hum. Gene Ther. 10, 419-427], we have generated a novel anti-HSV-1-specific HSV-1 recombinant (CJ83193) that expresses a trans-dominant negative HSV-1 UL9 origin-binding protein, UL9-C535C. The de novo synthesis of CJ83193 can be suppressed by UL9-C535C by at least 1 x 10(6)-fold in non-tetR-expressing cells, and is subject to tetracycline regulation over a range of four to five orders of magnitude in a tetR-expressing osteosarcoma line. In particular, the UL9-C535C peptides expressed from the CJ83193 genome can inhibit the replication of wild-type HSV-1 by 100- to 200-fold in single-step growth assays. The construction of CJ83193 creates a new general strategy for developing recombinant viral vectors able to function as an intracellular therapy against wild-type viral infections.
Interleukin 7 receptor α as a potential therapeutic target in transplantation (2009)

Drugs targeting memory lymphocytes may allow for a better control of rejection in transplantation, particularly in immunized patients. In this article the rationale of targeting interleukin 7 receptor alpha (IL-7Ralpha), a molecule expressed by both memory and naive T cells, is reviewed in the context of transplantation. Whereas naive T cells are partly responsible for acute rejection and are targeted by current immunosuppressive drugs that block costimulatory signals (cyclosporine A, anti-CD3 antibody, anti-CD52 antibody, anti-thymocyte globulin, etc.), memory T cells are resistant to costimulation blockade. As such, memory cells are an obstacle to experimental tolerance induction and may be involved in chronic rejection. There is thus much scientific interest in developing molecules able to target these cells. The role of the IL-7/IL-7Ralpha pathway in transplantation rejection has been suggested by the effect of an anti-IL-7 monoclonal antibody which, when associated with costimulation blockade, prolonged heart allograft survival in mice. Here the hypothesis that targeting IL-7Ralpha would preserve effector T cells that are less dependent on IL-7 for survival while sparing regulatory CD4+ CD25high IL-7Ralpha(low) T cells is discussed. An anti-IL-7Ralpha antibody could also help achieve allograft tolerance by reducing alloreactive cells.
Promoting Therepeutic Objectives through LB 518: A Sane Amendment to Nebraska Law Governing the Disposition of Insanity Acquittees (1993)

LB 518 represents the most recent proposal to amend Nebraska law governing disposition of individuals acquitted of crimes by reason of insanity. The bill proposes to change the kind of evidence relevant to evaluating the dangerousness of an insanity acquittee. Additionally, the bill provides courts with authority to order a variety of treatment programs. This Note examines the provisions of LB 518 in light of issues encompassed by the growing body of scholarship known as therapeutic jurisprudence. First, the Note introduces the background, procedural history, and substantive provisions of LB 518. Second, the Note analyzes the bill's provisions from a therapeutic jurisprudential perspective. Specifically, the Note focuses on promotion of psychological dysfunction, promotion of therapeutic objectives, therapeutic aspects of legal procedures, and therapeutic aspects of judicial actions. The Note concludes that LB 518 has great potential to promote therapeutic objectives, limited only by judicial application of the bill's provisions.
RNA cleaving '10-23' DNAzymes with enhanced stability and activity (2003)

'10-23' DNAzymes can be used to cleave any target RNA in a sequence-specific manner. For applications in vivo, they have to be stabilised against nucleolytic attack by the introduction of modified nucleotides without obstructing cleavage activity. In this study, we optimise the design of a DNAzyme targeting the 5'-non-translated region of the human rhinovirus 14, a common cold virus, with regard to its kinetic properties and its stability against nucleases. We compare a large number of DNAzymes against the same target site that are stabilised by the use of a 3'-3'-inverted thymidine, phosphorothioate linkages, 2'-O-methyl RNA and locked nucleic acids, respectively. Both cleavage activity and nuclease stability were significantly enhanced by optimisation of arm length and content of modified nucleotides. Furthermore, we introduced modified nucleotides into the catalytic core to enhance stability against endonucleolytic degradation without abolishing catalytic activity. Our findings enabled us to establish a design for DNAzymes containing nucleotide modifications both in the binding arms and in the catalytic core, yielding a species with up to 10-fold enhanced activity and significantly elevated stability against nucleolytic cleavage. When transferring the design to a DNAzyme against a different target, only a slight modification was necessary to retain activity.
Using Kansas Study and National Community College Benchmark Project Information for Assessment of General Education. (2007)

Antioxidant intake has been suggested to be associated with a reduced osteoporosis risk, but the effect of dietary total antioxidant capacity (TAC) on bone health and the risk of osteoporosis remains unclear. We aimed to assess the hypothesis that dietary TAC is positively associated with bone mass and negatively related to the risk of osteoporosis in Korean women. This cross-sectional study was performed using data from the Korea National Health and Nutrition Examination Survey. Dietary TAC was estimated using task automation and an algorithm with 24-h recall data. In total, 8230 pre- and postmenopausal women were divided into four groups according to quartiles of dietary TAC. Dietary TAC was negatively associated with the risk of osteoporosis (odds ratio, 0.73; 95% confidence interval, 0.54-0.99; <i>p</i>-value = 0.045) in postmenopausal women, but not in premenopausal women. Dietary TAC was positively associated with bone mineral content (BMC) and bone mineral density of the femoral neck and lumbar spine in postmenopausal women and BMC of the total femur and lumbar spine in premenopausal women. Our study suggests that dietary TAC is inversely associated with the risk of osteoporosis in postmenopausal women and positively associated with bone mass in both pre- and postmenopausal women.
Influence of biostimulation on reproduction in postpartum beef cows2 (1992)

Three experiments were conducted to evaluate the effects of biostimulation (exposure to bulls or androgenized females) on various reproductive variables in suckled beef cows. Bulls or testosterone-treated cows (TTC) were introduced to cows, randomly allotted to one of four groups, within 72 h postpartum. In Exp. 1, Groups 1 and 3 were exposed to bulls and Groups 2 and 4 were exposed to TTC. In Exp. 2, Groups 1 and 3 were exposed to bulls and Groups 2 and 4 served as controls (isolated from biostimulation). In Exp. 3, Groups 1 and 3 were exposed to TTC and Groups 2 and 4 served as controls. Mean postpartum intervals to estrus were not different between cows exposed to either bulls or TTC in Exp. 1 (P greater than .10). However, in Exp. 2 and 3, cows exposed to either bulls or TTC had reduced postpartum intervals to estrus (44 and 41 d, respectively) compared with control cows (52 d; P less than .05). Fewer control cows were in estrus at either 40 d (P less than .05; Exp. 2 and 3) or 60 d (P less than .05; Exp. 3) postpartum than were cows exposed to bulls or TTC. No differences were observed between groups in any experiment for postpartum intervals to pregnancy (P greater than .10). These data indicate that cows exposed to biostimulation from either bulls or TTC immediately after calving return to estrus earlier than do cows isolated from biostimulation.
Poxvirus-Based Active Immunotherapy with PD-1 and LAG-3 Dual Immune Checkpoint Inhibition Overcomes Compensatory Immune Regulation, Yielding Complete Tumor Regression in Mice (2016)

Poxvirus-based active immunotherapies mediate anti-tumor efficacy by triggering broad and durable Th1 dominated T cell responses against the tumor. While monotherapy significantly delays tumor growth, it often does not lead to complete tumor regression. It was hypothesized that the induced robust infiltration of IFNγ-producing T cells into the tumor could provoke an adaptive immune evasive response by the tumor through the upregulation of PD-L1 expression. In therapeutic CT26-HER-2 tumor models, MVA-BN-HER2 poxvirus immunotherapy resulted in significant tumor growth delay accompanied by a robust, tumor-infiltrating T cell response that was characterized by low to mid-levels of PD-1 expression on T cells. As hypothesized, this response was countered by significantly increased PD-L1 expression on the tumor and, unexpectedly, also on infiltrating T cells. Synergistic benefit of anti-tumor therapy was observed when MVA-BN-HER2 immunotherapy was combined with PD-1 immune checkpoint blockade. Interestingly, PD-1 blockade stimulated a second immune checkpoint molecule, LAG-3, to be expressed on T cells. Combining MVA-BN-HER2 immunotherapy with dual PD-1 plus LAG-3 blockade resulted in comprehensive tumor regression in all mice treated with the triple combination therapy. Subsequent rejection of tumors lacking the HER-2 antigen by treatment-responsive mice without further therapy six months after the original challenge demonstrated long lasting memory and suggested that effective T cell immunity to novel, non-targeted tumor antigens (antigen spread) had occurred. These data support the clinical investigation of this triple therapy regimen, especially in cancer patients harboring PD-L1neg/low tumors unlikely to benefit from immune checkpoint blockade alone.