gebhart/patrepeval huggingface dataset:
Spontaneous, pH-Dependent Membrane Insertion of a Transbilayer α-Helix (1997)

A question of fundamental importance concerning the biosynthesis of integral membrane proteins is whether transmembrane secondary structure can insert spontaneously into a lipid bilayer. It has proven to be difficult to address this issue experimentally because of the poor solubility in aqueous solution of peptides and proteins containing these extremely hydrophobic sequences. We have identified a system in which the kinetics and thermodynamics of alpha-helix insertion into lipid bilayers can be studied systematically and quantitatively using simple spectroscopic assays. Specifically, we have discovered that a 36-residue polypeptide containing the sequence of the C-helix of the integral membrane protein bacteriorhodopsin exhibits significant solubility in aqueous buffers free of both detergents and denaturants. This helix contains two aspartic acid residues in the membrane-spanning region. At neutral pH, the peptide associates with lipid bilayers in a nonhelical and presumably peripheral conformation. With a pKa of 6.0, the peptide inserts into the bilayer as a transbilayer alpha-helix. The insertion reaction proceeds rapidly at room temperature and is fully reversible.
Interleukin‐10 gene transfer activates interferon‐γ and the interferon‐γ‐inducible genes Gbp1/Mag1 and Mig1 in mammary tumors (1999)

Expression of IL-10 as a transgene inhibits murine mammary tumor growth and metastasis. Using differential display methodology, we sought genes whose expression was modulated by IL-10. We compared mRNA isolated from parental murine mammary 66.1 tumors, as well as tumors derived from neor-transfected cells and 6 different IL-10-expressing cell lines. We identified 2 cDNA products that were up-regulated in all 6 IL-10-expressing tumors in comparison to parental and 66-neo tumors. One cDNA corresponds to the murine guanylate-binding protein gene Gbp-1/Mag-1. The other cDNA corresponds to the chemokine Mig-1 (monokine induced by IFN-γ). Both genes were originally identified in IFN-γ-activated macrophages or macrophage cell lines. We now report that cultured mammary epithelial tumor cell lines also express both genes in response to treatment with IFN-γ and LPS. Furthermore, IFN-γ mRNA is elevated in IL-10-expressing tumors in comparison with parental or neo-transfected tumors. Thus, high-level expression of IL-10 as a transgene results in activation rather than suppression of IFN-γ as well as 2 IFN-γ-inducible genes. Up-regulation of host IFN-γ is critical to anti-tumor activity since IL-10 no longer inhibits tumor growth in hosts with a deletion in the IFN-γ gene. Additionally, Gbp-1/Mag-1 and Mig-1 gene induction no longer occur in IFN-γ mutant mice. Int. J. Cancer 80:624–629, 1999. © 1999 Wiley-Liss, Inc.
Characterizing absolute lymphocyte count profiles in dimethyl fumarate–treated patients with MS (2016)

Lymphocyte monitoring provides effective means for early identification of patients at risk for developing severe, prolonged lymphopenia.
Pathway engineering for production of aromatics in Escherichia coli: Confirmation of stoichiometric analysis by independent modulation of AroG, TktA, and Pps activities (1995)

The synthesis of 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) is the first commitment of resources toward aromatics production in Escherichia coli. DAHP is produced during a condensation reaction between phosphoenolpyruvate (PEP) and erythrose 4-phosphate (E4P) catalyzed by DAHP synthases (coded by aroF, aroG, and aroH). Stoichiometric analysis has shown a severe PEP limitation in the theoretical yield of DAHP production from glucose due to the phosphotransferase system (PTS) for sugar uptake. This limitation can be relieved by (i) the recycling of pyruvate from PEP using PEP synthase (Pps) or (ii) use of non-PTS sugars such as xylose. Previous studies have shown the usefulness of overexpressing tktA (encoding transketolase), aroG, and pps (PEP synthase) for DAHP production in an aroB strain unable to utilize DAHP further. In the present study we confirm the predictions of the stoichiometric analysis by introducing pps, tktA, and aroG into vectors under independently controlled promoters. In glucose medium, although TktA has some positive effect on the final DAHP concentration, it has no effect on the yield (percent conversion). With Pps overexpression, the DAHP concentration produced from glucose is increased almost twofold and the yield is approaching the theoretical maximum, as predicted by the stoichiometric analysis. However, this Pps effect is observed only in the presence of both increased AroG and TktA. In xylose mimimal medium, the final DAHP concentration and the yield are completely determined by the AroG activity. TktA and Pps play no or insignificant roles, and the yield can reach the theoretical maximum without overexpression of these two enzymes. The results shown here are important for both rational design of metabolic pathways and industrial production of aromatics such as tryptophan, phenylalanine, indigo, quinic acid, and catechol.
Safety and efficacy of cryopreserved autologous tumor infiltrating lymphocyte therapy (LN-144, lifileucel) in advanced metastatic melanoma patients previously treated with at least one prior systemic therapy. (2019)

136 Background: While immunotherapies including checkpoint inhibitors and targeted therapies (BRAF/MEK inhibitors) are options for patients with metastatic melanoma, many patients still develop progressive disease. These patients have few treatment options available including high dose IL-2 and chemotherapy with reported second line response rates of 4-10%. Adoptive cell therapy utilizing tumor-infiltrating lymphocytes (TIL) is recognized as an effective treatment in metastatic melanoma, able to elicit durable and complete responses in even heavily pretreated patients. We provide preliminary data for lifileucel TIL (LN-144) in heavily pre-treated metastatic melanoma patients who progressed on multiple checkpoint and BRAF/MEK inhibitors. Methods: C-144-01 is an ongoing global Phase 2, open-label, multicenter study of efficacy and safety of lifileucel in patients with unresectable metastatic melanoma. We report on Cohort 2 (N = 47) patients who received cryopreserved lifileucel. Tumors resected at local institutions were processed at central GMP facilities in a 22-day manufacturing process. The final product was cryopreserved and shipped to sites. Patients received a one week cyclophosphamide/fludarabine preconditioning lymphodepletion regimen, a single lifileucel infusion, followed by up to 6 doses of iv IL-2 (600,000 IU/kg). Results: Patients with Stage IIIC/IV melanoma had 3.3 mean prior therapies (range: 1-9) and high baseline tumor burden, reflected by a mean sum of diameters of target lesions of 112 mm. Preliminary efficacy results: ORR = 38% (1 CR, 13 PR, 4 uPR), DCR = 77%, and median DOR 6.4 mo (range: 1.3 to 13.7) with median follow-up 6.0 mo. Longer follow-up led to improved responses in some patients including the CR. Frequency of AEs decreased over time, a potentially important benefit of one-time TIL treatment. Conclusions: Preliminary data support lifileucel TIL as an efficacious and well-tolerated therapeutic option for patients with metastatic melanoma who have failed multiple lines of prior therapies including checkpoint inhibitors and BRAF/MEK inhibitors. Clinical trial information: NCT02360579.
Recombinant Interferon Enhances Monoclonal Antibody-Targeting of Carcinoma Lesions in Vivo (1987)

Heterogeneity in the expression of tumor-associated antigens, as defined by the binding of monoclonal antibodies, is a characteristic common to most, if not all, human carcinoma cell populations. Antigen-negative cells within the population can escape detection and therapy by their failure to bind the appropriate antibody. Therefore, the extent of antigenic heterogeneity is an important consideration when designing protocols for the management of cancer by administration of monoclonal antibodies. One approach to counteracting the effect of antigenic heterogeneity is the use of clone A of recombinant human leukocyte interferon (Hu-IFN-alpha A). Administration of Hu-IFN-alpha A in vivo effectively increased the amount of tumor antigen expressed by a human colon xenograft in situ and augmented the localization of a radiolabeled monoclonal antibody to the tumor site. Concomitant administration of Hu-IFN-alpha A and monoclonal antibody may thus be effective in overcoming the antigenic heterogeneity of carcinoma cell populations and in enhancing the efficacy of monoclonal antibodies in the detection and treatment of carcinoma lesions.
Tomographic Inversion In Reflection Seismology (1990)

Recently there has been much interest in performing tomographic inversion on data acquired in seismic reflection configurations. Several approaches to dealing with the unknown geometry of reflectors have evolved, the most natural of which seems to be to parametrize them in a manner consistent with the velocity field discretization. The inversion may then be formulated to treat both sets of parameters equally, avoiding the possibility of in-built bias. One appropriate formulation may be a least-squares optimization with a priori and step-length damping terms, which may be accomplished by a multiple-parameter class subspace method. Unfortunately a standard, ‘naive’ application of such an optimization method appears to fall foul of trade-offs between reflector depth and near-reflector velocities. These are manifested in the poor reconstruction of the lower portion of test models from synthetic data. Considerations of determinacy, strategies for non-linear problems and regularization inspired the idea of a multiple-stage approach, in which successive stages admit progressively shorter scale lengths of variation in both velocity field and reflector. An algorithm implementing this approach demonstrates a significant improvement in the reconstruction of longer-wavelength components of test models. However the tests also suggest that the shorter-wavelength velocity-depth trade-offs at the reflector are unresolvable without further information.
Purification and properties of a small latent matrix metalloproteinase of the rat uterus. (1988)

A small metalloproteinase that digests Azocoll was found in the uterus of the rat. Its activity increased to high levels during the postpartum period in parallel with the breakdown of the extracellular matrix exclusive of collagen (Sellers, A., and Woessner, J.F., Jr. (1980) Biochem. J. 189, 521-531). This enzyme has now been purified almost 7,000-fold to homogeneity from 12 g of tissue using molecular sieve chromatography, blue sepharose chromatography, and zinc-chelate chromatography. Gel electrophoresis with sodium dodecyl sulfate and dithiothreitol gives Mr = 28,000 for the latent form of the enzyme and Mr = 19,000 for the active form that arises spontaneously or by treatment with aminophenylmercuric acetate. The enzyme digests components of the extracellular matrix including gelatins of types I, III, IV, and V, fibronectin, and proteoglycan. It digests the alpha 2(I) chain of gelatin in preference to the alpha 1(I) chain and cleaves dinitrophenyl-Pro-Leu-Gly-Ile-Ala-Gly-Pro-D-Arg. It cleaves the B chain of insulin at two points: Ala14-Leu15 and Tyr16-Leu17. It has no action on collagens of types I, III, IV, or V at 26 degrees C and no action on elastin or phenylazo-Pro-Leu-Gly-Pro-D-Arg. The pH optimum is at pH 7 and the pI at 5.9. The enzyme requires zinc and calcium ions for activity; cobalt and strontium can partially replace these metal ions. The enzyme is not inhibited by low levels of phosphoramidon or Zincov. Its properties clearly distinguish it from collagenase, gelatinase (matrix metalloproteinase 2), and stromelysin (matrix metalloproteinase 3); it therefore constitutes a further member of the family of extracellular matrix metalloendopeptidases. The name matrix metalloproteinase 7 is proposed.
Role of PI3K/Akt signaling in insulin‐like growth factor‐1 (IGF‐1) skin tumor promotion (2005)

Overexpression of human IGF-1 with the bovine keratin 5 (BK5) promoter (BK5.IGF-1 transgenic mice) induces persistent epidermal hyperplasia and leads to spontaneous skin tumor formation. In previous work, PI3K and Akt activities were found to be elevated in the epidermis of BK5.IGF-1 transgenic mice compared to nontransgenic littermates. In the present study, we examined the importance of the PI3K/Akt signaling pathway in mediating the skin phenotype and the skin tumor promoting action of IGF-1 in these mice. Western blot analyses with epidermal lysates showed that signaling components downstream of PI3K/Akt were altered in epidermis of BK5.IGF-1 mice. Increased phosphorylation of GSK-3 (Ser(9/21)), TSC2(Thr(1462)), and mTOR(Ser(2448)) was observed. In addition, hypophosphorylation and increased protein levels of beta-catenin were observed in the epidermis of BK5.IGF-1 mice. These data suggested that components downstream of Akt might be affected, including cell cycle machinery in the epidermis of BK5.IGF-1 mice. Protein levels of cyclins (D1, E, A), E2F1, and E2F4 were all elevated in the epidermis of BK5.IGF-1 mice. Also, immunoprecipitation experiments demonstrated an increase in cdk4/cyclin D1 and cdk2/cyclin E complex formation, suggesting increased cdk activity in the epidermis of transgenic mice. In further studies, the PI3K inhibitor, LY294002, significantly blocked IGF-1-mediated epidermal proliferation and skin tumor promotion in DMBA-initiated BK5.IGF-1 mice. In addition, inhibition of PI3K/Akt with LY294002 reversed many of the cell cycle related changes observed in untreated transgenic animals. Collectively, the current results supported the hypothesis that elevated PI3K/Akt activity and subsequent activation of one or more downstream effector pathways contributed significantly to the tumor promoting action of IGF-1 in the epidermis of BK5.IGF-1 mice.
A polymer stacking process with 3D electrical routings for flexible temperature sensor array and its heterogeneous integration (2011)

This study presents an unique process to integrate the temperature sensing/heating elements, multi-layer through-hole vias (THVs), and electrical routings on parylene substrate to implement a multi-functional flexible temperature sensor array. Moreover, the polymer-staking processes with 3D electrical routings enable the further integration of various devices. In application, this study also demonstrates the implementation and integration of flexible temperature sensor array by: (1) temperature distribution and contour measurement using 4×4 temperature sensor array, (2) temperature monitoring and control using the integration of Pt-sensor and Pt-heater, (3) heterogeneous integration of temperature sensor array with LED-chip for LED temperature monitoring, and (4) 3D integration of temperature sensor array with LED and micro-lens and micro chamber.
Veterinary Microbiology and Microbial Disease (2011)

Microbiology is one of the core subjects for veterinary students, and since its first publication in 2002, Veterinary Microbiology and Microbial Disease has become an essential text for students of veterinary medicine. Fully revised and expanded, this new edition updates the subject for pre-clinical and clinical veterinary students in a comprehensive manner. Individual sections deal with bacteriology, mycology and virology. Written by an academic team with many years of teaching experience, the book provides concise descriptions of groups of microorganisms and the diseases which they cause. Microbial pathogens are discussed in separate chapters which provide information on the more important features of each microorganism and its role in the pathogenesis of diseases of animals. The international and public health significance of these pathogens are reviewed comprehensively. The final section is concerned with the host and is organized according to the body system affected.

Tables, boxes and flow diagrams provide information in an easily assimilated format. This edition contains new chapters on molecular diagnostics and on infectious conditions of the skin, cardiovascular system, urinary tract and musculoskeletal system. Many new colour diagrams are incorporated into this edition and each chapter has been updated.
A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancer (2013)

PEP02 demonstrates moderate antitumour activity with a manageable side effect profile for metastatic, gemcitabine-refractory pancreatic cancer patients. Given the limited treatment options available to this patient population, a phase 3 trial of PEP02 (MM-398), referred to as NAPOLI-1, is currently underway.
Phosphate-starvation-inducible proteins in Bacillus subtilis: a two-dimensional gel electrophoresis study (1996)

A two-dimensional (2-D) gel electrophoresis study of Bacillus subtilis strain 168 identified 20 proteins that are strongly induced in response to phosphate starvation. The induction of nine of these phosphate-starvation-induced (Psi) proteins was dependent on a functional PhoR protein. PhoR is the histidine sensor-kinase component of a phosphate-concentration-sensing two-component regulatory system which, together with its partner response regulator PhoP, controls the expression of genes in the Pho regulon. Genes encoding PhoR-dependent Psi proteins are therefore likely to be members of the Pho regulon. Spo0A approximately P, the response regulator of the signal transduction pathway required for the induction of sporulation, has previously been shown to negatively affect the induction of the Pho regulon by repressing the phoP-phoR operon. The induction pattern of some PhoR-dependent Psi proteins was altered in a spo0A mutant such that their synthesis continued for longer than was found with the wild-type. The most abundant Psi protein, Psi1-3, was characterized by N-terminal sequencing of internal peptide fragments and shown to have a high similarity to an Escherichia coli protein which is involved in phosphate uptake during phosphate starvation.
Production of erythroid-potentiating activity by a human T-lymphoblast cell line. (1980)

We derived a human T-lymphoblast cell line (Mo) that constitutively elaborates certain lymphokines. The Mo cells produce a colony-stimulating factor necessary for the growth of human granulocyte-monocyte precursors in vitro as well as an erythroid-potentiating activity (EPA) that enhances the proliferation of human erythroid progenitors in vitro. In the presence of serum, the EPA in Mo-conditioned medium stimulated the growth of small and large erythroid colonies almost 2-fold. EPA was also produced in serum-free medium, and, when assayed in serum-free cultures of human erythroid progenitors, it stimulated colony growth about 3-fold. The EPA produced by the Mo cell line did not stimulate normal murine erythroid progenitors (CFU-E) or Friend erythroleukemia cell growth in vitro. EPA was inactivated by protease treatment but was remarkably heat stable, with most of the activity recovered after boiling for 15 min. Preliminary biochemical characterization suggests that EPA is an acidic glycoprotein with molecular weight approximately 45,000. EPA is clearly separable from colony-stimulating factor on the basis of heat stability and gel-filtration chromatography. The present observations provide strong support for the concept that activated T cells produce humoral factors important in the regulation of erythropoiesis. The availability of a cell line producing human EPA should facilitate the characterization of the protein and permit definitive studies of its biologic effects.
Silicon Photonics for Exascale Systems (2014)

With the extraordinary growth in parallelism at all system scales driven by multicore architectures, computing performance is increasingly determined by how efficiently high-bandwidth data is communicated among the numerous compute resources. High-performance systems are especially challenged by the growing energy costs dominated by data movement. As future computing systems aim to realize the Exascale regime-surpassing 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">18</sup> operations per second-achieving energy efficient high-bandwidth communication becomes paramount to scaled performance. Silicon photonics offers the possibility of delivering the needed communication bandwidths to match the growing computing powers of these highly parallel architectures with extremely scalable energy efficiency. However, the insertion of photonic interconnects is not a one-for-one replacement. The lack of practical buffering and the fundamental circuit switched nature of optical data communications require a holistic approach to designing system-wide photonic interconnection networks. New network architectures are required and must include arbitration strategies that incorporate the characteristics of the optical physical layer. This paper reviews the recent progresses in silicon photonic based interconnect devices along with the system level requirements for Exascale. We present a co-design approach for building silicon photonic interconnection networks that leverages the unique optical data movement capabilities and offers a path toward realizing future Exascale systems.