gebhart/patrepeval huggingface dataset:
Current techniques for single-cell lysis (2008)

Owing to the small quantities of analytes and small volumes involved in single-cell analysis techniques, manipulation strategies must be chosen carefully. The lysis of single cells for downstream chemical analysis in capillaries and lab-on-a-chip devices can be achieved by optical, acoustic, mechanical, electrical or chemical means, each having their respective strengths and weaknesses. Selection of the most appropriate lysis method will depend on the particulars of the downstream cell lysate processing. Ultrafast lysis techniques such as the use of highly focused laser pulses or pulses of high voltage are suitable for applications requiring high temporal resolution. Other factors, such as whether the cells are adherent or in suspension and whether the proteins to be collected are desired to be native or denatured, will determine the suitability of detergent-based lysis methods. Therefore, careful selection of the proper lysis technique is essential for gathering accurate data from single cells.
Mechanism of tumor rejection with doublets of CTLA-4, PD-1/PD-L1, or IDO blockade involves restored IL-2 production and proliferation of CD8+ T cells directly within the tumor microenvironment (2014)

Our data suggest that the therapeutic effect of these immunotherapies was mainly mediated through direct reactivation of T cells in situ. These three combinations are attractive to pursue clinically, and the ability of intratumoral CD8(+) T cells to produce IL-2 and to proliferate could be an important biomarker to integrate into clinical studies.
C-Jun NH2 terminal kinase (JNK) is an essential mediator of Toll-like receptor 2-induced corneal inflammation (2008)

TLRs play an important role in the host inflammatory response to bacteria and bacterial products by activating a cascade of intracellular events leading to production of proinflammatory and chemotactic cytokines. To determine the role of MAPKs in TLR- induced corneal inflammation, we stimulated human corneal epithelial (HCE) cells with TLR2 ligands, tripalmitoyl-S-glycero-Cys-(Lys)4 (Pam3Cys) or inactivated Staphylococcus aureus, and examined the time course of expression of MAPKs and the effect of MAPK inhibition on IkBalpha degradation and CXC chemokine production. We found that S. aureus and Pam3Cys stimulate phosphorylation of JNK, p38 MAPK, and ERK within 4 h and that blockade of JNK, but not p38 or ERK phosphorylation, had an inhibitory effect on IkBalpha degradation and CXC chemokine production. To determine if JNK is also important in TLR2-induced corneal inflammation in vivo, we examined JNK1(-/-) mice and pharmacological inhibitors in a murine model of TLR2-induced corneal inflammation which is characterized by neutrophil recruitment to the corneal stroma and development of corneal haze. We found that corneal inflammation was significantly impaired in JNK1(-/-) mice compared with control mice, and in mice treated with the JNK inhibitor compared with vehicle control. Taken together with results from HCE cells, these findings demonstrate that JNK has an essential role in TLR2-induced corneal inflammation.
Multipotent Neural Stem Cells Reside into the Rostral Extension and Olfactory Bulb of Adult Rodents (2002)

The lateral walls of the forebrain lateral ventricles are the richest source of stem cells in the adult mammalian brain. These stem cells give rise to new olfactory neurons that are renewed throughout life. The neurons originate in the subventricular zone (SVZ), migrate within the rostral extension (RE) of the SVZ along the rostral migratory stream (RMS) within tube-like structures formed of glial cells, to eventually reach the olfactory bulb (OB). We demonstrate that, contrary to the current view, multipotential (neuronal-astroglial-oligodendroglial) precursors with stem cell features can be isolated not only from the SVZ but also from the entire RE, including the distal portion within the OB. Specifically, these stem cells do not derive from the migratory neuroblasts coming from the SVZ. Interestingly, stem cells isolated from the proximal RE generate significantly more oligodendrocytes, and those from the distal RE proliferate significantly more slowly than stem cells derived from the SVZ and other RE regions. These findings demonstrate that stem cells are not confined to the forebrain periventricular region and indicate that stem cells endowed with different functional characteristics occur at different levels of the SVZ-RE pathway.
Defective Reticuloendothelial System Fc-Receptor Function in Patients with Acquired Immunodeficiency Syndrome (1985)

Journal Article Defective Reticuloendothelial System Fc-Receptor Function in Patients with Acquired Immunodeficiency Syndrome Get access Bradley S. Bender, Bradley S. Bender Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael M. Frank, Michael M. Frank Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas J. Lawley, Thomas J. Lawley Search for other works by this author on: Oxford Academic PubMed Google Scholar William J. Smith, William J. Smith Search for other works by this author on: Oxford Academic PubMed Google Scholar Chaim M. Brickman, Chaim M. Brickman Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas C. Quinn Thomas C. Quinn Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 152, Issue 2, August 1985, Pages 409–412, https://doi.org/10.1093/infdis/152.2.409 Published: 01 August 1985 Article history Received: 25 October 1984 Revision received: 08 January 1985 Published: 01 August 1985
Anti–B-Cell Monoclonal Antibody Treatment of Severe Posttransplant B-Lymphoproliferative Disorder: Prognostic Factors and Long-Term Outcome (1998)

B-lymphoproliferative disorder (BLPD) is a rare but severe complication of organ and bone marrow transplantation (BMT). Profound cytotoxic T-cell deficiency is thought to allow the outgrowth of Epstein-Barr virus-transformed B cells. When possible, reduction of immunosuppressive treatment or surgery for localized disease may cure BLPD. Therapeutic approaches using chemotherapy or antiviral drugs have limited effects on survival. Adoptive immunotherapy with donor T-cell infusions has given promising results in BMT recipients. We previously reported that administration of two monoclonal anti-B-cell antibodies (anti-CD21 and anti-CD24) could contribute to the control of oligoclonal BLPD. Here we report the long-term results of treatment with these monoclonal anti-B-cell antibodies for cases of severe BLPD. In an open multicenter trial, 58 patients in whom aggressive B-cell lymphoproliferative disorder developed after BMT (n = 27) or organ (n = 31) transplantation received 0.2 mg/kg/d of specific anti-CD21 and anti-CD24 murine monoclonal antibodies (MoAbs) for 10 days. The treatment was well tolerated. Thirty-six of the 59 episodes of BLPD in the 58 patients presented complete remission (61%). The relapse rate was low (3 of 36, 8%). Multivariate analysis identified the following risk factors for partial or no response to anti-B-cell MoAb therapy: multivisceral disease (P </= .005), central nervous system involvement (P </= .05), and late onset of BLPD (P </= .005). The overall long-term survival was 46% (median follow-up, 61 months); it was lower among BMT patients (35%) than organ transplant patients (55%). None of the patients who had received BMT for hematological malignancy survived for 1 year. Eight of these 11 patients presented monoclonal BLPD. Tumor burden was the only other variable that contributed significantly to poor survival. Thus, as assessed from this long-term study, the use of anti-B-cell MoAbs therefore appears to be a safe and relatively effective therapy for severe posttransplant BLPD.
Infections, Infertility, and Assisted Reproduction (2004)

ART treatment is vulnerable to the hazard of potential infection from many different sources: patients, samples, staff and the environment. Culture of gametes and embryos in vitro provides multiple targets for transmission of potential infection, including the developing embryo, neighbouring gametes and embryos, the couple undergoing treatment and other couples being treated during the same period. This unique situation, with multifaceted opportunities for microbial growth and transmission, makes infection and contamination control absolutely crucial in the practice of assisted reproduction, and in the laboratory in particular. Originally published in 2004, this practical book provides a basic overview of microbiology in the context of ART, providing a guide to infections in reproductive medicine. The relevant facets of the complex and vast field of microbiology are condensed and focused, highlighting information that is crucial for safe practice in both clinical and laboratory aspects of ART.
Evidence of Altered Posteromedial Cortical fMRI Activity in Subjects at Risk for Alzheimer Disease (2010)

The posteromedial cortices and other regions of the "default network" are particularly vulnerable to the pathology of Alzheimer disease (AD). In this study, we performed functional magnetic resonance imaging (fMRI) to investigate whether the presence of apolipoprotein E (APOE) epsilon allele and degree of memory impairment were associated with the dysfunction of these brain regions. Seventy-five elderly subjects ranging from cognitively normal to mild AD, divided into epsilon carriers and noncarriers, underwent fMRI during a memory-encoding task. Across all subjects, posteromedial and ventral anterior cingulate cortices (key components of the default network) as well as right middle and inferior prefrontal regions demonstrated reduced task-induced deactivation in the epsilon carriers relative to noncarriers. Even among cognitively normal subjects, epsilon carriers demonstrated reduced posteromedial deactivation compared with the noncarriers in the same regions which demonstrated failure of deactivation in AD patients. Greater failure of posteromedial deactivation was related to worse memory performance (delayed recall) across all subjects and within the range of cognitively normal subjects. In summary, the posteromedial cortical fMRI response pattern is modulated both by the presence of APOE epsilon and episodic memory capability. Altered fMRI activity of the posteromedial areas of the brain default network may be an early indicator of risk for AD.
Donor DNA Utilization During Gene Targeting with Zinc-Finger Nucleases (2013)

Gene targeting is the term commonly applied to experimental gene replacement by homologous recombination (HR). This process is substantially stimulated by a double-strand break (DSB) in the genomic target. Zinc-finger nucleases (ZFNs) are targetable cleavage reagents that provide an effective means of introducing such a break in conjunction with delivery of a homologous donor DNA. In this study we explored several parameters of donor DNA structure during ZFN-mediated gene targeting in Drosophila melanogaster embryos, as follows. 1) We confirmed that HR outcomes are enhanced relative to the alternative nonhomologous end joining (NHEJ) repair pathway in flies lacking DNA ligase IV. 2) The minimum amount of homology needed to support efficient HR in fly embryos is between 200 and 500 bp. 3) Conversion tracts are very broad in this system: donor sequences more than 3 kb from the ZFN-induced break are found in the HR products at approximately 50% of the frequency of a marker at the break. 4) Deletions carried by the donor DNA are readily incorporated at the target. 5) While linear double-stranded DNAs are not effective as donors, single-stranded oligonucleotides are. These observations should enable better experimental design for gene targeting in Drosophila and help guide similar efforts in other systems.
An Optimal Radial Profile Order Based on the Golden Ratio for Time-Resolved MRI (2007)

In dynamic magnetic resonance imaging (MRI) studies, the motion kinetics or the contrast variability are often hard to predict, hampering an appropriate choice of the image update rate or the temporal resolution. A constant azimuthal profile spacing (111.246 degrees), based on the Golden Ratio, is investigated as optimal for image reconstruction from an arbitrary number of profiles in radial MRI. The profile order is evaluated and compared with a uniform profile distribution in terms of signal-to-noise ratio (SNR) and artifact level. The favorable characteristics of such a profile order are exemplified in two applications on healthy volunteers. First, an advanced sliding window reconstruction scheme is applied to dynamic cardiac imaging, with a reconstruction window that can be flexibly adjusted according to the extent of cardiac motion that is acceptable. Second, a contrast-enhancing k-space filter is presented that permits reconstructing an arbitrary number of images at arbitrary time points from one raw data set. The filter was utilized to depict the T1-relaxation in the brain after a single inversion prepulse. While a uniform profile distribution with a constant angle increment is optimal for a fixed and predetermined number of profiles, a profile distribution based on the Golden Ratio proved to be an appropriate solution for an arbitrary number of profiles.
Tumour‐suppressive microRNA‐29s directly regulate LOXL2 expression and inhibit cancer cell migration and invasion in renal cell carcinoma (2015)

Here, we found that members of the microRNA-29 family (miR-29a/b/c; "miR-29s") were significantly reduced in clear cell renal cell carcinoma (ccRCC) tissues, suggesting that they functioned as tumour suppressors. Restoration of all mature members of the miR-29 family inhibited cancer cell proliferation, migration and invasion. LOXL2 was a direct target gene of miR-29s, as shown by genome-wide gene expression analysis and luciferase reporter assay. Overexpressed LOXL2 was confirmed in ccRCC clinical specimens, and silencing of LOXL2 inhibited cancer cell migration and invasion in ccRCC cell lines. Our data demonstrated that the miR-29s-LOXL2 axis contributed to cancer cell migration and invasion in ccRCC.
Poliovirus Cell Entry: Common Structural Themes in Viral Cell Entry Pathways (2002)

Structural studies of polio- and closely related viruses have provided a series of snapshots along their cell entry pathways. Based on the structures and related kinetic, biochemical, and genetic studies, we have proposed a model for the cell entry pathway for polio- and closely related viruses. In this model a maturation cleavage of a capsid protein precursor locks the virus in a metastable state, and the receptor acts like a transition-state catalyst to overcome an energy barrier and release the mature virion from the metastable state. This initiates a series of conformational changes that allow the virus to attach to membranes, form a pore, and finally release its RNA genome into the cytoplasm. This model has striking parallels with emerging models for the maturation and cell entry of more complex enveloped viruses such as influenza virus and HIV.
TVM: End-to-End Optimization Stack for Deep Learning (2018)

Scalable frameworks, such as TensorFlow, MXNet, Caffe, and PyTorch drive the current popularity and utility of deep learning. However, these frameworks are optimized for a narrow range of server-class GPUs and deploying workloads to other platforms such as mobile phones, embedded devices, and specialized accelerators (e.g., FPGAs, ASICs) requires laborious manual effort. We propose TVM, an end-to-end optimization stack that exposes graph-level and operator-level optimizations to provide performance portability to deep learning workloads across diverse hardware back-ends. We discuss the optimization challenges specific to deep learning that TVM solves: high-level operator fusion, low-level memory reuse across threads, mapping to arbitrary hardware primitives, and memory latency hiding. Experimental results demonstrate that TVM delivers performance across hardware back-ends that are competitive with state-of-the-art libraries for low-power CPU and server-class GPUs. We also demonstrate TVM's ability to target new hardware accelerator back-ends by targeting an FPGA-based generic deep learning accelerator. The compiler infrastructure is open sourced.
Regulation between O‐GlcNAcylation and phosphorylation of neurofilament‐M and their dysregulation in Alzheimer disease (2007)

The medium subunit of neurofilament (NF-M) is extensively modified by phosphate and O-linked beta-N-acetylglucosamine (O-GlcNAc). Phosphorylation of NF-M plays a critical role in regulating its translocation, filament formation, and function. However, the regulation of NF-M phosphorylation and the role of NF-M O-GlcNAcylation (a modification by which GlcNAc is attached to the serine/threonine residues of a protein via an O-linked glycosidic bond) are largely unknown. Here, we demonstrate that O-GlcNAcylation and phosphorylation of NF-M regulate each other reciprocally in cultured neuroblastoma cells and in metabolically active rat brain slices. In animal models of fasting rats, which mimicked the decreased glucose uptake/metabolism observed in brains of individuals with Alzheimer disease (AD), we found a decrease in O-GlcNAcylation and increase in phosphorylation of NF-M. We also observed decreased O-GlcNAcylation and an increased phosphorylation of NF-M in AD brain. These results suggest that O-GlcNAcylation and phosphorylation of NF-M are regulated reciprocally and that the hyperphosphorylation and accumulation of NF-M in AD brain might be caused by impaired brain glucose uptake/metabolism via down-regulation of NF-M O-GlcNAcylation.
Saturating the region of the polycystic kidney disease gene with NotI linking clones. (1991)

A NotI-linking library was constructed from a radiation hybrid containing fragments of human chromosome 16. The clones were mapped on a panel of somatic cell hybrids, and 10 different NotI site-containing clones were localized close to and between genetic markers flanking the PKD1 locus. With pulsed-field gel analysis the clones were shown to be distributed over four adjacent ClaI fragments covering 1,200 kb.
Colonization of broiler chickens by waterborne Campylobacter jejuni (1993)

Chickens on a broiler farm in southern England were found to be colonized with Campylobacter jejuni of a single serotype, Lior 1 Penner 4. The farm was the sole supplier of a local slaughterhouse associated with a campylobacter outbreak in 1984 caused by this serotype. The serotype persisted on the farm for at least 18 months after the outbreak; its prevalence in the human population served by the farm remained high until it disappeared from the farm in 1986. The possible sources and routes of transmission of C. jejuni to the broilers on the farm were investigated. The results showed that vertical transmission, feed, litter, small mammals, and environmental or airborne cross-contamination between sheds or successive crops could be excluded as persistent sources of C. jejuni. The predominant source of C. jejuni on the farm was shown to be the water supply. Direct microscopy and fluorescent antibody methods revealed presumptive campylobacters throughout the farm's water system. Campylobacter-free chickens raised in an animal house and given water from the farm supply became colonized with the serotype of C. jejuni endemic on the farm (Lior 1 Penner 4). An intervention program based on water chlorination, shed drinking system cleaning and disinfection, and withdrawal of furazolidone from feed reduced the proportion of birds colonized with campylobacter from 81 to 7% and was associated with a 1,000- to 10,000-fold reduction in campylobacters recoverable from the carcasses. Two months after the end of the intervention program colonization of the birds returned to high levels (84%), indicating that there was a temporal association between intervention and reduced colonization with C. jejuni. Investigations continue to establish the general applicability of these findings.
Dual glucagon recognition by pancreatic beta-cells via glucagon and glucagon-like peptide 1 receptors (1998)

cAMP is required for normal glucose-induced insulin release by pancreatic beta-cells. In a previous study, we showed that cAMP production in beta-cells depends on the expression of receptors for glucagon, glucagon-like peptide 1(7-36) amide [GLP-1(7-36) amide], and glucose-dependent insulinotropic polypeptide. Although the latter two peptides are thought to amplify meal-induced insulin release (incretin effect), the role of glucagon in the regulation of insulin release remains elusive. In the present study, we analyzed the interaction of glucagon with its own receptor and with the glucagon-like peptide 1 (GLP-1) receptor using purified rat beta-cells. Glucagon binding was partially displaced by 1 mu mol/l des-His(1)-[Glu(9)]glucagon-amide, a glucagon receptor antagonist, and by 1 mu mol/l GLP-1. Conversely, GLP-1 binding was competitively inhibited by high glucagon concentrations (K-i = 0.3 mu mol/l). Glucagon-induced cAMP production in beta-cells was inhibited both by 1 mu mol/l des-His(1)-[Glu(9)]glucagon-amide and exendin-(9-39)-amide, a specific GLP-1 receptor antagonist, whereas GLP-1-induced cAMP formation was suppressed only by exendin-(9-39)-amide. Finally, addition of 1 mu mol/l exendin-(9-39)-amide to 20 mmol/l glucose-stimulated beta-cells did not antagonize the potentiating effect of 1 nmol/l glucagon, although it prevented 45% of glucagon potentiation when the peptide was administered at 10 nmol/l. Our data suggest that glucagon recognition via two distinct receptors allows pancreatic beta-cells to detect this peptide both when diluted in the systemic circulation and when concentrated as local signal in the islet interstitium.
OSPFv2 Prefix/Link Attribute Advertisement (2015)

OSPFv2 requires functional extension beyond what can readily be done
with the fixed-format Link State Advertisements (LSAs) as described in
RFC 2328. This document defines OSPFv2 Opaque LSAs based on Type-
Length-Value (TLV) tuples that can be used to associate additional
attributes with prefixes or links. Depending on the application, these
prefixes and links may or may not be advertised in the fixed-format
LSAs. The OSPFv2 Opaque LSAs are optional and fully backward
compatible.