gebhart/patrepeval huggingface dataset:
TheArabidopsis thalianaHomolog of YeastBRE1Has a Function in Cell Cycle Regulation during Early Leaf and Root Growth (2007)

Chromatin modification and transcriptional activation are novel roles for E3 ubiquitin ligase proteins that have been mainly associated with ubiquitin-dependent proteolysis. We identified HISTONE MONOUBIQUITINATION1 (HUB1) (and its homolog HUB2) in Arabidopsis thaliana as RING E3 ligase proteins with a function in organ growth. We show that HUB1 is a functional homolog of the human and yeast BRE1 proteins because it monoubiquitinated histone H2B in an in vitro assay. Hub knockdown mutants had pale leaf coloration, modified leaf shape, reduced rosette biomass, and inhibited primary root growth. One of the alleles had been designated previously as ang4-1. Kinematic analysis of leaf and root growth together with flow cytometry revealed defects in cell cycle activities. The hub1-1 (ang4-1) mutation increased cell cycle duration in young leaves and caused an early entry into the endocycles. Transcript profiling of shoot apical tissues of hub1-1 (ang4-1) indicated that key regulators of the G2-to-M transition were misexpressed. Based on the mutant characterization, we postulate that HUB1 mediates gene activation and cell cycle regulation probably through chromatin modifications.
Containerless Solidification of Undercooled Nd2Fe14B by Electrostatic Levitation Furnace (2002)

Containerless solidification of undercooled Nd2Fe14B was investigated using the electrostatic levitation furnace developed by the National Space Development Agency of Japan. Spherical samples with diameters close to 2 mm were laser melted and radiatively cooled in vacuum at rates between 100 K/s and 50 K/s. Two recalescence peaks were observed in the cooling curves. They were respectively attributed to phase segregation of primary Fe and solidification of the Nd2Fe14B (ϕ) phase. The sample that solidified with the higher undercooling level showed a more refined microstructure and a higher saturation magnetization than that solidified with the lower undercooling level.
über die Herstellung von 17α‐Oxy‐20‐keto‐Steroiden aus 17(20)‐En‐20‐acetamino‐Steroiden (1955)

Abstract Ausgehend von 20‐Ketimino‐Steroiden ist es möglich, sowohl gesättigte wie ungesättigte 17α‐Oxy‐20‐ketone herzustellen. Hierzu werden Ketimine (VII), die aus 20‐Aminen leicht zugänglich sind, mit Acetanhydrid acetyliert, wobei sie unter Umlagerung in 17(20)‐En‐20‐monoacetylamine (VIII) oder unter energischeren Bedingungen in 17 (20)‐En‐20‐diacetylamine (IX) übergehen. An die Monoacetylamine läßt sich mit Benzopersäure Sauerstoff addieren. Die so erhaltenen 17.20‐Oxido‐20‐acetylamine (X) ergeben bei alkalischer Hydrolyse 17α‐Oxy‐20‐ketone (XI). Enacetylamine mit einer Δ 5 ‐3‐Acetoxy‐, Δ 5 ‐3‐Oxy‐ oder einer Δ 4 ‐3‐Keto‐Gruppierung können partiell an der semicyclischen Doppelbindung mit Benzopersäure umgesetzt werden. 20‐Acetamino‐pregnadien‐(5.17 (20))‐ol‐(3β) (XVII) und sein 3‐Acetat (XII) sowie 20‐Acetamino‐pregnadien‐(4.17 (20))‐on‐(3) (XIX) reagieren so mit einem äquivalent Benzopersäure unter Bildung der 17.20‐Oxyde (XIV, XVIII, XX). Ihre alkalische Verseifung ergibt 17α‐Oxypregnen‐(5)‐ol‐(3β)‐on‐(20) (XV) bzw. 17α‐Oxy‐progesteron (XXI). Die Unterschiede im reaktiven Verhalten von 17 (20)‐En‐20‐ol‐acetaten und 17 (20)‐En‐20‐acetylaminen werden diskutiert.
Nonneutralizing Antibodies Are Able To Inhibit Human Immunodeficiency Virus Type 1 Replication in Macrophages and Immature Dendritic Cells (2006)

Only five monoclonal antibodies (MAbs) neutralizing a broad range of primary isolates (PI) have been identified up to now. We have found that some MAbs with no neutralizing activities according to the "conventional" neutralization assay, involving phytohemagglutinin-stimulated peripheral blood mononuclear cells as targets, efficiently inhibit the replication of human immunodeficiency virus type 1 (HIV-1) PI in macrophages and immature dendritic cells (iDC). The mechanism of inhibition is distinct from the neutralization of infectivity occurring via Fab fragments and involves the interaction of the F portion with the FcgammaRs present on macrophages and iDC. We propose that, if such nonneutralizing inhibitory antibodies limit mucosal HIV transmission, they should be induced by vaccination.
Minimal "Self" Peptides That Inhibit Phagocytic Clearance and Enhance Delivery of Nanoparticles (2013)

Foreign particles and cells are cleared from the body by phagocytes that must also recognize and avoid clearance of "self" cells. The membrane protein CD47 is reportedly a "marker of self" in mice that impedes phagocytosis of self by signaling through the phagocyte receptor CD172a. Minimal "Self" peptides were computationally designed from human CD47 and then synthesized and attached to virus-size particles for intravenous injection into mice that express a CD172a variant compatible with hCD47. Self peptides delay macrophage-mediated clearance of nanoparticles, which promotes persistent circulation that enhances dye and drug delivery to tumors. Self-peptide affinity for CD172a is near the optimum measured for human CD172a variants, and Self peptide also potently inhibits nanoparticle uptake mediated by the contractile cytoskeleton. The reductionist approach reveals the importance of human Self peptides and their utility in enhancing drug delivery and imaging.
Fusion of visible and synthesised near infrared information for face authentication (2010)

Changes in illumination conditions can cause drastic variations in face appearance and affect the performance of a face authentication system. Near infrared (NIR) face imaging systems have been proposed as a promising way towards illumination invariant face verification. We show that when NIR face images cannot be observed, learning the relationship between NIR information and the corresponding visible images can provide useful complementary information about visible light image data. In particular, we use Canonical Correlation Analysis (CCA) to synthesise the NIR eigenfaces from their corresponding visible ones. In this paper, the verification performance of a CCA-based synthesising algorithm is developed first. Although, synthesised NIR images do not perform as well as the real NIR, it is shown that by fusing the visible and synthesised near infrared information at the score level, the performance of the authentication system considerably improves.
IIP2 Calibration by Injecting DC Offset at the Mixer in a Wireless Receiver (2007)

A major contributor to degraded input-referred second-order intercept point (IIP2) in integrated RF systems-on-chips is local oscillator (LO) leakage to the input of RF circuits. In this brief, we present a digital calibration technique for improving IIP2 by injecting controlled dc offset at the mixer output through a three-port network of switched-capacitor filters. The dc offset at mixer output gets up-converted to LO frequency at the input of RF circuits due to poor reverse isolation of the receiver front-end. By controlling the amplitude of the injected dc, IIP2 degradation due to LO leakage at the input of RF amplifiers can be compensated. Mathematical analysis is presented and supported by measurement data from a quad-band GSM/GPRS receiver implemented in 90-nm digital CMOS process. Calibrated IIP2 of 50 dBm is reported for the receiver at low-noise amplifier input.
Assessment of High-Affinity Hybridization, RNase H Cleavage, and Covalent Linkage in Translation Arrest by Antisense Oligonucleotides (1998)

Antisense oligonucleotides (ONs) are designed to hybridize target mRNA in a sequence-specific manner and inhibit gene expression by preventing translation, either by activation of RNase H or steric blockage of the ribosome complex. Second-generation ONs, which possess greater binding affinity for target RNA relative to the isosequential phosphodiester (PO) ONs, have been developed and include, among others, peptide nucleic acids (PNA) and N3' P5' phosphoramidate oligonucleotides (npONs). In the present study, PNA and npON derivatives were targeted to the coding portion of the complementary mRNA of the N protein of the vesicular stomatitis virus (VSV) in order to evaluate their ability to arrest translation in an in vitro rabbit reticulocyte lysate system. High-affinity hybridization of ONs lacking RNase H activity was not sufficient to block translation in this test system. Only antisense ONs acting via an RNase H mechanism or by steric hindrance through covalent attachment (via transplatin modification) to the target mRNA were found to definitively arrest translation in this study.
Sensitive and adaptable pharmacological control of CAR T cells through extracellular receptor dimerization (2019)

Chimeric antigen receptor (CAR) T cell therapies have achieved promising outcomes in several cancers, however more challenging oncology indications may necessitate advanced antigen receptor designs and functions. Here we describe a bipartite receptor system comprised of separate antigen targeting and signal transduction polypeptides, each containing an extracellular dimerization domain. We demonstrate that T cell activation remains antigen dependent but can only be achieved in the presence of a dimerizing drug, rapamycin. Studies performed in vitro and in xenograft mouse models illustrate equivalent to superior anti-tumor potency compared to currently used CAR designs, and at rapamycin concentrations well below immunosuppressive levels. We further show that the extracellular positioning of the dimerization domains enables the administration of recombinant re-targeting modules, potentially extending antigen targeting. Overall, this novel regulatable CAR design has exquisite drug sensitivity, provides robust anti-tumor responses, and is uniquely flexible for multiplex antigen targeting or retargeting, which may further assist the development of safe, potent and durable T cell therapeutics.
Vitamin D: Physiology, Molecular Biology, and Clinical Applications (2010)

1 Evolution, Biologic Functions, and Recommended Dietary Allowances for Vitamin D -- 2 Photobiology of Vitamin D -- 3 Functional Metabolism and Molecular Biology of Vitamin D Action -- 4 Metabolism and Catabolism of Vitamin D, Its Metabolites, and Clinically Relevant Analogs -- 5 The Enzymes Responsible for Metabolizing Vitamin D -- 6 The Vitamin D Binding Protein and Its Clinical Significance -- 7 Molecular Biology of the Vitamin D Receptor -- 8 Vitamin D Receptor Translocation -- 9 Molecular Recognition and Structure—Activity Relations in Vitamin D-Binding Protein and Vitamin D Receptor -- 10 Mechanism of Action of 1,25-Dihydroxyvitamin D3 on Intestinal Calcium Absorption and Renal Calcium Transport -- 11 Biologic and Molecular Effects of Vitamin D on Bone -- 12 Nongenomic Rapid Effects of Vitamin D -- 13 Noncalcemic Actions of 1,25-Dihydroxyvitamin D3 and Clinical Implications -- 14 Regulation of Parathyroid Hormone Gene Expression and Secretion by Vitamin D -- 15 Vitamin D Assays and Their Clinical Utility -- 16 Rickets and Vitamin D Deficiency -- 17 Vitamin D and Bone Health in Adults and the Elderly -- 18 Inherited Defects of Vitamin D Metabolism -- 19 Molecular Defects in the Vitamin D Receptor Associated with Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets -- 20 Extrarenal Production of 1,25-Dihydroxyvitamin D and Clinical Implications -- 21 Clinical Utility of 1,25-Dihydroxyvitamin D3 and Its Analogs for the Treatment of Psoriasis and Other Skin Diseases -- 22 Epidemiology of Cancer Risk and Vitamin D -- 23 Chemotherapeutic and Chemopreventive Actions of Vitamin D3 and Analogs -- 24 Vitamin D and Breast Cancer -- 25 Anticancer Activity of Vitamin D Analogs.
Molecular cloning and expression of a human heat shock factor, HSF1. (1991)

Human cells respond to heat stress by inducing the binding of a preexisting transcriptional activator (heat shock factor, HSF) to DNA. We have isolated recombinant DNA clones for a human HSF (HSF1) by screening cDNA libraries with a human cDNA fragment. The human HSF1 probe was produced by the PCR with primers deduced from conserved amino acids in the Drosophila and yeast HSF sequences. The human HSF1 mRNA is constitutively expressed in HeLa cells under nonshock conditions and encodes a protein with four conserved leucine zipper motifs. Like its counterpart in Drosophila, human HSF1 produced in Escherichia coli in the absence of heat shock is active as a DNA binding transcription factor, suggesting that the intrinsic activity of HSF is under negative control in human cells. Surprisingly, an independently isolated human HSF clone, HSF2, is related to but significantly different from HSF1 [Schuetz, T. J., Gallo, G. J., Sheldon, L., Tempst, P. & Kingston, R. E. (1991) Proc. Natl. Acad. Sci. USA 88, 6911-6915].
Renal nerves and cation excretion after acute reduction in functioning renal mass in the rat (1984)

We evaluated the role of the renal nerves in the increased cation excretion by the contralateral kidney after acute unilateral nephrectomy (AUN) or unilateral ureteral occlusion (UUO) in anesthetized rats. Both AUN and UUO caused large increases in sodium (UNaV) and potassium excretion (UKV) by the control kidney without change in glomerular filtration rate or mean arterial pressure. Prior denervation of either the ipsilateral (experimental) kidney or the control kidney completely prevented the increase in UNaV and UKV after UUO. Prior denervation of either kidney also prevented the increase in UNaV after AUN. However, a significant kaliuresis persisted after AUN despite unilateral denervation although reduced in magnitude when compared with the increase in UKV after AUN with both kidneys innervated. These results indicate that the renal nerves play a major role in the excretory response of the control kidney after acute reduction in functioning renal mass. This role of the renal nerves may be through the activation of a renorenal reflex. The reflex is activated by afferents from the ipsilateral kidney; the efferent limb is composed of the renal nerves to the control kidney. This reflex can entirely account for the compensatory increase in cation excretion after UUO. However, a separate mechanism, not dependent on the renal nerves, contributes to UKV after AUN.
Bcl-2–family proteins and hematologic malignancies: history and future prospects (2008)

BCL-2 was the first antideath gene discovered, a milestone that effectively launched a new era in cell death research. Since its discovery more than 2 decades ago, multiple members of the human Bcl-2 family of apoptosis-regulating proteins have been identified, including 6 antiapoptotic proteins, 3 structurally similar proapoptotic proteins, and several structurally diverse proapoptotic interacting proteins that operate as upstream agonists or antagonists. Bcl-2-family proteins regulate all major types of cell death, including apoptosis, necrosis, and autophagy. As such, they operate as nodal points at the convergence of multiple pathways with broad relevance to biology and medicine. Bcl-2 derives its name from its original discovery in the context of B-cell lymphomas, where chromosomal translocations commonly activate the BCL-2 protooncogene, endowing B cells with a selective survival advantage that promotes their neoplastic expansion. The concept that defective programmed cell death contributes to malignancy was established by studies of Bcl-2, representing a major step forward in current understanding of tumorigenesis. Experimental therapies targeting Bcl-2 family mRNAs or proteins are currently in clinical testing, raising hopes that a new class of anticancer drugs may be near.
Interferon-stimulated genes in interferon-sensitive and -resistant chronic myelogenous leukemia patients. (1992)

alpha-Interferon induces hematological and cytogenetic remissions in some individuals with newly diagnosed Philadelphia-positive chronic myelogenous leukemia. However, interferon-resistant disease occurs in a consistent patient subset (primary resistance) and develops during therapy in additional patients (secondary resistance). Several alpha-interferon-inducible genes have been characterized. In interferon-resistant cell line variants, defects in these genes have been implicated in the mechanisms mediating resistance. We have, therefore, evaluated mRNA expression of four interferon-stimulated genes (ISGs) following alpha-interferon therapy. Twenty-seven chronic myelogenous leukemia patients (ten interferon-sensitive patients, 17 interferon-resistant patients) were studied. Peripheral blood samples were collected prior to and 1 to 7 days after starting interferon therapy and analyzed for the expression of 2'-5' oligoadenylate synthetase, ISG-15, ISG-54, and 6-16 transcripts. Following therapy with alpha-interferon, 2'-5' oligoadenylate synthetase, ISG-54, and 6-16 transcripts were discerned in all patients regardless of their response to interferon. The ISG-15 message was detected in eight of nine interferon-sensitive and in 15 of 16 interferon-resistant patients, as well. Overall, no consistent defect in the ISG system could be identified. Therefore, lack of induction of these genes cannot explain resistance to alpha-interferon in chronic myelogenous leukemia patients. Other mechanisms such as posttranslational modification, leading to defects in the ISG corresponding proteins, may play a role in the development of resistance.
Audio Coding Based on Long Temporal Contexts (2006)

We describe novel audio coding technique designed to be utilized at medium bit-rates. Unlike classical state-of-the-art audio coders that are based on short-term spectra, our approach uses relatively long temporal segments of audio signal in critical-band-sized sub-bands. We apply auto-regressive model to approximate Hilbert envelopes in frequency sub-bands. Residual signals (Hilbert carriers) are demodulated and thresholding functions are applied in spectral domain. The Hilbert envelopes and carriers are quantized and transmitted to the decoder. Our experiments focused on designing audio coder to provide broadcast radio-like quality audio around $10-20$kbps. Objective quality measures indicate comparable performance with the 3GPP-AMR speech codec standard for both speech and non-speech signals.
Common Genetic Variation at PTEN and Risk of Sporadic Breast and Prostate Cancer (2006)

PTEN frequently shows loss of heterozygosity in breast and prostate cancers, and mutations in this gene are responsible for Cowden disease, a rare Mendelian syndrome that includes breast cancer as part of its phenotype. Thus, PTEN serves as a candidate susceptibility gene for both breast and prostate cancer risk. Whether common inherited variation (either coding or noncoding) at the PTEN locus contribute to nonfamilial, sporadic breast and prostate cancer risk is not known. In this study, we employed a linkage disequilibrium-based approach to test for association between common genetic variation at the PTEN locus and breast and prostate cancer risk in African-American, Native Hawaiian, Japanese, Latina, and White men and women in the Multiethnic Cohort Study. We genotyped 17 common single nucleotide polymorphisms (SNP; >/=5% frequency in at least one ethnic group) spanning the PTEN gene to define the common alleles in these populations. These SNPs were in strong linkage disequilibrium, indicating that our survey captured most of the common sequence variation across this locus. Eight tagging SNPs were selected to predict the common PTEN haplotypes (>/=0.05 frequency) in these populations (two additional tagging SNPs were required for African Americans). These SNPs were evaluated in a breast cancer case-control study (cases, n = 1,615; controls, n = 1,962) and prostate cancer case-control study (cases, n = 2,320; controls, n = 2,290) nested within the Multiethnic Cohort Study. Multiple testing was explicitly accounted for by applying a permutation-based framework. We found no strong association with any common haplotype in relation to breast or prostate cancer risk. In summary, our results show that common variants in PTEN do not substantially influence risk of these two common cancers.
‘Naked’ and Hydrated Conformers of the Conserved Core Pentasaccharide of N-linked Glycoproteins and Its Building Blocks (2013)

N-glycosylation of eukaryotic proteins is widespread and vital to survival. The pentasaccharide unit -Man3GlcNAc2- lies at the protein-junction core of all oligosaccharides attached to asparagine side chains during this process. Although its absolute conservation implies an indispensable role, associated perhaps with its structure, its unbiased conformation and the potential modulating role of solvation are unknown; both have now been explored through a combination of synthesis, laser spectroscopy, and computation. The proximal -GlcNAc-GlcNAc- unit acts as a rigid rod, while the central, and unusual, -Man-β-1,4-GlcNAc- linkage is more flexible and is modulated by the distal Man-α-1,3- and Man-α-1,6- branching units. Solvation stiffens the 'rod' but leaves the distal residues flexible, through a β-Man pivot, ensuring anchored projection from the protein shell while allowing flexible interaction of the distal portion of N-glycosylation with bulk water and biomolecular assemblies.
MIG (CXCL9) chemokine gene therapy combines with antibody-cytokine fusion protein to suppress growth and dissemination of murine colon carcinoma. (2001)

The induction of a CTL response capable of eradicating disseminated tumor metastases and the establishment of a persistent tumor-protective immunity remain major goals of cancer immunotherapy. Here, we demonstrate for the first time that the combination of interleukin 2 (IL-2) targeted to the tumor microenvironment by a recombinant antibody-IL-2 fusion protein (huKS1/4-IL-2) with gene therapy by the murine chemokine MIG (CXCL9) markedly reduced s.c. tumor burden and decisively suppressed dissemination of experimental lung metastases of CT26-KSA colon carcinoma in syngeneic BALB/c mice. This combined therapy significantly prolonged the life span of these mice 3-4-fold by concurrently delivering MIG and IL-2 to the tumor site and thereby achieving chemoattraction of T cells together with their activation. The antitumor effect obtained was mediated predominantly by MHC class I antigen-restricted CD8(+) T cells with help from MHC class II antigen-restricted CD4(+) T lymphocytes. In addition, the MIG chemokine also induced angiostatic effects in the tumor vasculature. Taken together, this combination of MIG chemokine gene therapy with tumor-targeted cytokine IL-2 provides an approach for the rational design of novel cancer immunotherapy modalities.
Improved Pharmacokinetic and Pharmacodynamic Profile of Rapid-Acting Insulin Using Needle-Free Jet Injection Technology (2011)

Administration of insulin aspart by jet injection enhances insulin absorption and reduces the duration of glucose-lowering action. This profile resembles more closely the pattern of endogenous insulin secretion and may help to achieve better meal insulin coverage and correction of postprandial glucose excursions.