gebhart/patrepeval huggingface dataset:
Fluorescent-Protein Stabilization and High-Resolution Imaging of Cleared, Intact Mouse Brains (2015)

In order to observe and quantify long-range neuronal connections in intact mouse brain by light microscopy, it is first necessary to clear the brain, thus suppressing refractive-index variations. Here we describe a method that clears the brain and preserves the signal from proteinaceous fluorophores using a pH-adjusted non-aqueous index-matching medium. Successful clearing is enabled through the use of either 1-propanol or tert-butanol during dehydration whilst maintaining a basic pH. We show that high-resolution fluorescence imaging of entire, structurally intact juvenile and adult mouse brains is possible at subcellular resolution, even following many months in clearing solution. We also show that axonal long-range projections that are EGFP-labelled by modified Rabies virus can be imaged throughout the brain using a purpose-built light-sheet fluorescence microscope. To demonstrate the viability of the technique, we determined a detailed map of the monosynaptic projections onto a target cell population in the lateral entorhinal cortex. This example demonstrates that our method permits the quantification of whole-brain connectivity patterns at the subcellular level in the uncut brain.
AF17q25, a putative septin family gene, fuses the MLL gene in acute myeloid leukemia with t(11;17)(q23;q25). (1999)

The t(11;17) has been described in patients with acute myeloid leukemia (AML), and the AF17 gene was previously cloned as a fusion partner of the MLL gene in t(11;17)(q23;q21)-AML. We analyzed one patient with de novo AML and one with therapy-related AML with t(11;17)(q23;q25) and identified the AF17q25 gene on chromosome 17q25, a putative septin family gene, fused with MLL. AF17q25 encoded at least three kinds of proteins [type I (568 a.a.), type II (594 a.a.), and type III (574 a.a.)] that contained two kinds of different amino acid sequences at the COOH terminus. The MLL-AF17q25 fusion transcript consisted of type I AF17q25 transcript. The AF17q25 protein is homologous to septin family proteins, including H5, NEDD5, CDC10, and hCDCrel, which is one of the fusion partners of MLL in t(11;22)(q23;q11)-AML. These results suggest that AF17q25 and hCDCrel might define a new septin family particularly involved in the pathogenesis of 11q23-associated leukemia.
cAMP Evokes Long-Term Facilitation in Aplysia Sensory Neurons That Requires New Protein Synthesis (1988)

Behavioral sensitization leads to both short- and long-term enhancement of synaptic transmission between the sensory and motor neurons of the gill-withdrawal reflex in Aplysia. Serotonin (5-HT), a transmitter important for short-term sensitization, can evoke long-term enhancement of synaptic strength detected 1 day later. Because 5-HT mediates short-term facilitation through adenosine 3',5'-monophosphate (cAMP)-dependent protein phosphorylation, the role of cAMP in the long-term modulation of this identified synapse was examined. Like 5-HT, cAMP can also evoke long-term facilitation lasting 24 hours. Unlike the short-term change, the long-lasting change is blocked by anisomycin, a reversible inhibitor of protein synthesis, and therefore must involve the synthesis of gene products not required for the short-term change.
Inversion with a grain of salt (1985)

Abstract Although least–squares inversion is a useful tool in data analysis, nonuniqueness is an inevitable problem. This problem can be analyzed by considering the sensitivity of a model response to the parameter estimates. Such sensitivity methods produce extremal solutions which barely satisfy some resolution (or stability) criteria. Two closely related methods for producing such solutions are the “Edgehog” and “Most Squares” methods due to Jackson (1973, 1976). These techniques, which evaluate the “degree of nonuniqueness” in a least–squares inversion, require only the information computed in a singular value decomposition (SVD) solution. While the “edgehog” and “most squares” techniques are mathematically similar, the “most squares” estimate is the simpler to compute. Both methods show that the credibility of an inversion depends on both the specified error criterion as well as on the properties of the Jacobian matrix associated with the least–squares solution. The similar performance of these two closely related methods is demonstrated with the traveltime inversion of both synthetic and real vertical seismic profiles (VSPs). The sensitivity analysis of this inversion problem provides a quantitative measure of solution reliability.
An experimental 2-bit/cell storage DRAM for macrocell or memory-on-logic application (1989)

A multiple-level 2-bit/cell storage technique for DRAMs (dynamic random-access memories) has been developed. The total RAM area is reduced and the cell array is cut in half. Since the memory cell area is especially defect-sensitive, this technique is highly effective for process yield improvement. Reasonable access time has been realized with this technique: 170 ns is still fast enough for many ASIC (application-specific integrated circuit) memory applications. This technique meets the requirement of high density and moderate speed. It was found that the 2-bit/cell storage technique is suitable for macrocell or memory-on-logic type application.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Vocal Recording (2017)

The preservation of vocalizations for acoustic analysis and playback has provided biologists, psychologists, and anthropologists with important insights into communication. Although primate vocal recordings date back to the 1890s and were used by Carpenter in the 1930s, widespread interest in the method was delayed until the 1960s and corresponded with technological advances in equipment portability and visual representations of sound (spectrograms). Modern primatologists increasingly incorporate vocalizations into research, given the wide availability of inexpensive equipment and bioacoustic software. Beyond simply documenting repertoires, contemporary projects cover topics from ontogeny, phylogeny, propagation, and production mechanisms, to honest signaling, group coordination, heterospecific eavesdropping, and geographic variation. The appropriateness of primate model systems for understanding human language evolution remains controversial, but results have challenged traditional notions about the simplicity of primate communication systems. Although easily incorporated into field studies, recordists should seek out published resources to ensure quality of study design, recording techniques, and acoustic analyses.
Autoradiographic and histological studies of postnatal neurogenesis. I. A longitudinal investigation of the kinetics, migration and transformation of cells incoorporating tritiated thymidine in neonate rats, with special reference to postnatal neurogenesis in some brain regions (1966)

Abstract Neonate rats were injected systemically with thymidine‐H 3 and killed after different periods of survival. Cell proliferation, migration and transformation in the brain were studied autoradiographically. It was established that cells multiplying in the ependymal and subependymal walls of the olfactory ventricle migrate outward into the olfactory bulb, where they become differentiated into granule cells. These postnatally formed granule cells contribute to the formation of the granular and several other layers of the olfactory bulb. Cells multiplying at a high rate in the wall of the lateral ventricle migrate to the hippocampus and contribute to the formation of the granule cells in the granular layer of the dentate gyrus. Cells multiplying at a high rate in the external and internal granular layers of the cerebellum become differentiated into granule cells, and, to a lesser extent, other types of nerve cells of the cerebellar cortex. Evidence was also obtained of the postnatal origin of many of the granule cells of the cochlear nucleus. Postnatal neurogenesis is restricted to these short‐axoned granule cells or microneurons; the long‐axoned nerve cells or macroneurons of the brain are formed prenatally.
Comparative biochemical analysis of three bacterial prolyl endopeptidases: implications for coeliac sprue (2004)

Prolyl endopeptidases have potential for treating coeliac sprue, a disease of the intestine caused by proteolytically resistant peptides from proline-rich prolamins of wheat, barley and rye. We compared the properties of three similar bacterial prolyl endopeptidases, including the known enzymes from Flavobacterium meningosepticum (FM) and Sphingomonas capsulate (SC) and a novel enzyme from Myxococcus xanthus (MX). These enzymes were interrogated with reference chromogenic substrates, as well as two related gluten peptides (PQPQLPYPQPQLP and LQLQPFPQPQLPYPQPQLPYPQPQLPYPQPQPF), believed to play a key role in coeliac sprue pathogenesis. In vitro and in vivo studies were conducted to evaluate the activity, specificity and acid/protease stability of the enzymes. All peptidases were relatively resistant to acid, pancreatic proteases and membrane peptidases of the small intestinal mucosa. Although their activities against reference substrates were similar, the enzymes exhibited substantial differences with respect to chain length and subsite specificity. SC hydrolysed PQPQLPYPQPQLP well, but had negligible activity against LQLQPFPQPQLPYPQPQLPYPQPQLPYPQPQPF. In contrast, the FM and MX peptidases cleaved both substrates, although the FM enzyme acted more rapidly on LQLQPFPQPQLPYPQPQLPYPQPQLPYPQPQPF than MX. Whereas the FM enzyme showed a preference for Pro-Gln bonds, SC cleaved both Pro-Gln and Pro-Tyr bonds with comparable efficiency, and MX had a modest preference for Pro-(Tyr/Phe) sites over Pro-Gln sites. While a more comprehensive understanding of sequence and chain-length specificity may be needed to assess the relative utility of alternative prolyl endopeptidases for treating coeliac sprue, our present work has illustrated the diverse nature of this class of enzymes from the standpoint of proteolysing complex substrates such as gluten.
MHC class I and II expression in prostate carcinoma and modulation by interferon-alpha and -gamma (1997)

The present findings, taken together with previous studies, are most consistent with the expression of neoantigens by PCa, which are recognized and appropriately eliminated by the cellular immune system. This selective pressure favors outgrowth of cells which down-regulate or lose class I and/or class II expression. Understanding PCa immunobiology will help in the development of effective immunotherapy for this disease.
Two polymorphs of a covalent complex between papain and a diazomethylketone inhibitor* (2004)

The three-dimensional structure of two polymorphs of a ZLFG-CH2-papain covalent complex has been determined by X-ray crystallography. The structures indicate that: (i) the methylene carbon atom of the inhibitor is covalently bound to the Sgamma atom of Cys25 of papain; (ii) the hydrophobic S2 pocket formed by Pro68, Val133, Val157, and Asp158 is occupied by the inhibitor's phenylalanyl P2 side chain; (iii) extensive hydrogen bonding and hydrophobic interactions are responsible for the interaction of the inhibitor with the enzyme. Comparison with similar structures suggests that in covalent complexes preservation of main chain-main chain interactions between the enzyme and the inhibitor may have higher priority than the P-S interactions.
Novel Anti-carbohydrate Antibodies Reveal the Cooperative Function of Sulfated N- and O-Glycans in Lymphocyte Homing (2010)

Cell surface glycans play pivotal roles in immune cell trafficking and immunity. Here we present an efficient method for generating anti-carbohydrate monoclonal antibodies (mAbs) using gene-targeted mice and describe critical glycans in lymphocyte homing. We immunized sulfotransferase GlcNAc6ST-1 and GlcNAc6ST-2 doubly deficient mice with sulfotransferase-overexpressing Chinese hamster ovary cells and generated two mAbs, termed S1 and S2. Both S1 and S2 bound high endothelial venules (HEVs) in the lymphoid organs of humans and wild-type mice, but not in those of doubly deficient mice. Glycan array analysis indicated that both S1 and S2 specifically bound 6-sulfo sialyl Lewis X and its defucosylated structure. Interestingly, S2 inhibited lymphocyte homing to peripheral lymph nodes by 95%, whereas S1 inhibited it by only 25%. S2 also significantly inhibited contact hypersensitivity responses and L-selectin-dependent leukocyte adhesion to HEVs. Immunohistochemical and Western blot analyses indicated that S1 preferentially bound sulfated O-glycans, whereas S2 bound both sulfated N- and O-glycans in HEVs. Furthermore, S2 strongly inhibited the N-glycan-dependent residual lymphocyte homing in mutant mice lacking sulfated O-glycans, indicating the importance of both sulfated N- and O-glycans in lymphocyte homing. Thus, the two mAbs generated by a novel method revealed the cooperative function of sulfated N- and O-glycans in lymphocyte homing and immune surveillance.
Small-Molecule Inhibitors of GSK-3: Structural Insights and Their Application to Alzheimer's Disease Models (2012)

The world health organization (WHO) estimated that 18 million people are struck by Alzheimer's disease (AD). The USA, France, Germany, and other countries launched major programmes targeting the identification of risk factors, the improvement of caretaking, and fundamental research aiming to postpone the onset of AD. The glycogen synthase kinase 3 (GSK-3) is implicated in multiple cellular processes and has been linked to the pathogenesis of several diseases including diabetes mellitus, cancer, and AD. Inhibition of GSK-3 leads to neuroprotective effects, decreased β-amyloid production, and a reduction in tau hyperphosphorylation, which are all associated with AD. Various classes of small molecule GSK-3 inhibitors have been published in patents and original publications. Herein, we present a comprehensive summary of small molecules reported to interact with GSK-3. We illustrate the interactions of the inhibitors with the active site. Furthermore, we refer to the biological characterisation in terms of activity and selectivity for GSK-3, elucidate in vivo studies and pre-/clinical trials.
Functional Organization of Repeat Addition Processivity and DNA Synthesis Determinants in the Human Telomerase Multimer (2004)

Human telomerase is a multimer containing two human telomerase RNAs (hTRs) and most likely two human telomerase reverse transcriptases (hTERTs). Telomerase synthesizes multiple telomeric repeats using a unique repeat addition form of processivity. We investigated hTR and hTERT sequences that were essential for DNA synthesis and processivity using a direct primer extension telomerase assay. We found that hTERT consists of two physically separable functional domains, a polymerase domain containing RNA interaction domain 2 (RID2), reverse transcriptase (RT), and C-terminal sequences, and a major accessory domain, RNA interaction domain 1 (RID1). RID2 mutants defective in high-affinity hTR interactions and an RT catalytic mutant exhibited comparable DNA synthesis defects. The RID2-interacting hTR P6.1 helix was also essential for DNA synthesis. RID1 interacted with the hTR pseudoknot-template domain and hTERT's RT motifs and putative thumb and was essential for processivity, but not DNA synthesis. The hTR pseudoknot was essential for processivity, but not DNA synthesis, and processivity was reduced or abolished in dimerization-defective pseudoknot mutants. trans-acting hTERTs and hTRs complemented the processivity defects of RID1 and pseudoknot mutants, respectively. These data provide novel insight into the catalytic organization of the human telomerase complex and suggest that repeat addition processivity is one of the major catalytic properties conferred by telomerase multimerization.
Strain relief by periodic misfit arrays for low defect density GaSb on GaAs (2006)

We demonstrate the growth of a low dislocation density, relaxed GaSb bulk layer on a (001) GaAs substrate. The strain energy generated by the 7.78% lattice mismatch is relieved by a periodic array of 90° misfit dislocations. The misfit array is localized at the GaSb∕GaAs interface and has a period of 5.6nm which is determined by transmission electron microscope images. No threading dislocations are visible. The misfits are identified as 90°, rather than 60°, using Burger’s circuit analysis, and are therefore not associated with generation of threading dislocations. A low dislocation density and planar growth mode is established after only 3 monolayers of GaSb deposition as revealed by reflection high-energy electron diffraction patterns. Calculations corroborate the materials characterization and indicate the strain energy generated by the 7.78% lattice mismatch is almost fully dissipated by the misfit array. The low dislocation density bulk GaSb material on GaAs enabled by this growth mode will lead to new devices, especially in the infrared regime, along with novel integration schemes.
Adeno-Associated Virus Serotype 8 Gene Therapy Leads to Significant Lowering of Plasma Cholesterol Levels in Humanized Mouse Models of Homozygous and Heterozygous Familial Hypercholesterolemia (2012)

Familial hypercholesterolemia (FH) is a life-threatening genetic disease caused by mutations in the gene encoding low-density lipoprotein receptor (LDLR). As a bridge to clinical trials, we generated a "humanized" mouse model lacking LDLR and apolipoprotein B (ApoB) mRNA editing catalytic polypeptide-1 (APOBEC-1) expression and expressing a human ApoB100 transgene in order to permit more authentic simulation of in vivo interactions between the clinical transgene product, human LDLR (hLDLR), and its endogenous ligand, human ApoB100. On a chow diet, the humanized LDLR-deficient mice have substantial hypercholesterolemia and a lipoprotein phenotype more closely resembling human homozygous FH (hoFH) than in previous mouse models of FH. On injection of an adeno-associated virus serotype 8 (AAV8) vector encoding the human LDLR cDNA, significant correction of hypercholesterolemia was realized at doses as low as 1.5 × 10(11) genome copies (GC)/kg. Given that some patients with heterozygous FH (heFH) cannot be adequately treated with current therapy, we then extended our studies to similarly "humanized" mice that were heterozygous for LDLR deficiency, and that have a lipoprotein phenotype resembling heterozygous FH. Injection of AAV8-hLDLR brought about significant reduction in total and LDL cholesterol at doses as low as 5 × 10(11) GC/kg. Collectively, these data demonstrate the safety and efficacy of the liver-specific AAV8-hLDLR vector in the treatment of humanized mice modeling both hoFH and heFH.
Yeats et la France (1993)

Yeats se rendit souvent à Paris à partir de 1894 : il connaissait bien certains quartiers – on rappelle toujours qu'il rencontra Synge à l'hôtel Corneille près du Luxembourg. Il décrit le logement de Verlaine en termes réalistes : "I found him in a little room at the top of a tenement house in the Rue St Jacques, sitting in an easy chair, with his bad leg swaddled in many bandages". La maîtresse de Verlaine a donné à la pièce son caractère particulier : "her canary birds, of which there were ...
Mammalian capping enzyme binds RNA and uses protein tyrosine phosphatase mechanism (1998)

Mammalian capping enzymes are bifunctional proteins with both RNA 5'-triphosphatase and guanylyltransferase activities. The N-terminal 237-aa triphosphatase domain contains (I/V)HCXXGXXR(S/T)G, a sequence corresponding to the conserved active-site motif in protein tyrosine phosphatases (PTPs). Analysis of point mutants of mouse RNA 5'-triphosphatase identified the motif Cys and Arg residues and an upstream Asp as required for activity. Like PTPs, this enzyme was inhibited by iodoacetate and VO43- and independent of Mg2+, providing additional evidence for phosphate removal from RNA 5' ends by a PTP-like mechanism. The full-length, 597-aa mouse capping enzyme and the C-terminal guanylyltransferase fragment (residues 211-597), unlike the triphosphatase domain, bound poly (U) and were nuclear in transfected cells. RNA binding was increased by GTP, and a guanylylation-defective, active-site mutant was not affected. Ala substitution at positions required for the formation of the enzyme-GMP capping intermediate (R315, R530, K533, or N537) also eliminated poly (U) binding, while proteins with conservative substitutions at these sites retained binding but not guanylyltransferase activity. These results demonstrate that the guanylyltransferase domain of mammalian capping enzyme specifies nuclear localization and RNA binding. Association of capping enzyme with nascent transcripts may act in synergy with RNA polymerase II binding to ensure 5' cap formation.
Policing, Detention, Deportation, and Resistance: Situating Immigrant Justice and Carcerality in the 21st Century (2009)

ington Post reported that since 2001, the number of immigrant detainees over the course of each year has more than tripled, to 311,000 (Priest and Goldstein, 2008). The New Yorker reported that whole families, many of whom have committed no crime, are incarcerated in the privately run Hutto immigration prison located in a remote area of south Texas (Talbot, 2008). The Washington Post reported numerous abuses of immigration detainees, ranging from inadequate or improper health care and rape of female detainees to the adverse psychological effects of detention on children (Berestein, 2008). Situating the Problem In many ways, passage of the 1986 Immigration Reform and Control Act (IRCA) was a pivotal point in the criminalization of migrants, setting the stage for increases in deportation and detention, as well as the abuses that immigrants endure once detained. IRCA was the first major legislation to initiate the militarization of the border, while also contributing to the increased presence of migrants in the United States by providing amnesty to over two million people and allowing for
Biochemical mechanisms of tumor invasion and metastasis. (1987)

Cancer invasion and metastases is a complex multi-step process. In order for a tumor cell to successfully traverse all the steps of this process and initiate a metastatic colony, it must express the right combination of gene products. Such gene products may include proteins which regulate cell interaction with the basement membrane and cell motility. Tumor cells attach to the basement membrane glycoprotein laminin via the cell surface laminin receptor. The human laminin receptor was purified and molecularly cloned. The level of laminin receptor mRNA in a variety of human carcinoma cells correlated with the number of laminin receptors on the surface of these cells. Following attachment to the basement membrane, the tumor cell next secretes proteases which may degrade type IV collagen. A genetic linkage between type IV collagenase secretion and metastases was collagen. A genetic linkage between type IV collagenase secretion and metastases was studied using our new genetic system for inducing metastases by employing the ras oncogene. Following attachment and local proteolysis, the third step of invasion is tumor cell motility. We have isolated a tumor cell autocrine motility factor (AMF). This factor is secreted by the tumor cells and binds to a cell surface receptor, resulting in a profound (greater than 100 x) stimulation of cell locomotion. AMF may play a major role in the autonomous invasive behavior of tumor cells.