gebhart/patrepeval huggingface dataset:
Structure of the 4-1BB/4-1BBL complex and distinct binding and functional properties of utomilumab and urelumab (2018)

4-1BB (CD137, TNFRSF9) is an inducible costimulatory receptor expressed on activated T cells. Clinical trials of two agonist antibodies, utomilumab (PF-05082566) and urelumab (BMS-663513), are ongoing in multiple cancer indications, and both antibodies demonstrate distinct activities in the clinic. To understand these differences, we solved structures of the human 4-1BB/4-1BBL complex, the 4-1BBL trimer alone, and 4-1BB bound to utomilumab or urelumab. The 4-1BB/4-1BBL complex displays a unique interaction between receptor and ligand when compared with other TNF family members. Furthermore, our ligand-only structure differs from previously published data. Utomilumab, a ligand-blocking antibody, binds 4-1BB between CRDs 3 and 4. In contrast, urelumab binds 4-1BB CRD-1, away from the ligand binding site. Finally, cell-based assays demonstrate utomilumab is a milder agonist than urelumab. Collectively, our data provide a deeper understanding of the 4-1BB signaling complex, providing a template for future development of next generation 4-1BB targeted biologics.
Unusual Haplotype Structure at the Proximal Breakpoint of In(2L)t in a Natural Population of Drosophila melanogaster (1999)

The existence of temporally stable frequency clines for In(2L)t in natural populations of Drosophila melanogaster suggests a role for selection in the maintenance of this polymorphism. We have collected nucleotide polymorphism data from the proximal breakpoint junction regions of In(2L)t to infer its evolutionary history. The finding of a novel LINE-like element near the In(2L)t breakpoint junction in sampled inverted chromosomes supports a transposable element-mediated origin for this inversion. An analysis of nucleotide variation in a Costa Rican population sample of standard and inverted chromosomes indicates a unique and relatively recent origin for In(2L)t. Additional In(2L)t alleles from three geographically diverse populations reveal no detectable geographic differentiation. Low levels of In(2L)t nucleotide polymorphism suggest a recent increase in the inversion's frequency in tropical populations. An unusual feature of our sample of standard alleles is a marked heterogeneity in levels of linkage disequilibrium among polymorphic sites across the breakpoint region. We introduce a test of neutral equilibrium haplotype structure that corrects both for multiple tests and for an arbitrarily chosen window size. It reveals that an approximately 1.4-kb region immediately spanning the breakpoint has fewer haplotypes than expected under the neutral model, given the expected level of recombination in this genomic region. Certain features of our data suggest that the unusual pattern in standard chromosomes is the product of selection rather than demography.
Evidence for Mitochondrial Respiratory Deficiency in Rat Rhabdomyosarcoma Cells (2010)

A defect in the regulation of mitochondrial biogenesis and mitochondrial metabolism may thus be an epigenetic mechanism that may contribute to the tumoral behavior of R1H cells. Our data underline the importance of mitochondria in the regulation of myogenic differentiation.
Vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 expression in squamous cell carcinomas of the head and neck (2003)

The broad expression of VEGF C and VEGFR3 in HNSCC suggests involvement in tumor lymph angiogenesis and vascular angiogenesis, promoting tumor growth and propagation of cancer cells. This implies that inhibitors of lymph angiogenesis could become effective therapeutic options similar to classical angiogenesis inhibitors.
Anti‐musk antibody myasthenia gravis: Clinical findings and response to treatment in two large cohorts (2011)

MuSK-MG has a marked female predominance with frequent oculobulbar weakness and crises. Many patients deteriorate rapidly early in the disease, and PLEX is usually the preferred treatment. Long-term outcomes are similar to those of patients with AChR-Ab(+) MG.
A broadly cross-protective monoclonal antibody binding to Escherichia coli and Salmonella lipopolysaccharides (1993)

During the last decade, episodes of sepsis have increased and Escherichia coli has remained the most frequent clinical isolate. Lipopolysaccharides (LPS; endotoxin) are the major toxic and antigenic components of gram-negative bacteria and qualify as targets for therapeutic interventions. Molecules that neutralize the toxic effects of LPS are actively investigated. In this paper, we describe a murine monoclonal antibody (MAb; WN1 222-5), broadly cross-reactive and cross-protective for smooth (S)-form and rough (R)-form LPS. As shown in enzyme-linked immunosorbent assay and the passive hemolysis assay, WN1 222-5 binds to the five known E. coli core chemotypes, to Salmonella core, and to S-form LPS having these core structures. In immunoblots, it is shown to react with both the nonsubstituted core LPS and with LPS carrying O-side chains, indicating the exposure of the epitope in both S-form and R-form LPS. This MAb of the immunoglobulin G2a class is not lipid A reactive but binds to E. coli J5, an RcP+ mutant which carries an inner core structure common to many members of the family Enterobacteriaceae. Phosphate groups present in the inner core contribute to the epitope but are not essential for the binding of WN1 222-5 to complete core LPS. Cross-reactivity for clinical bacterial isolates is broad. WN1 222-5 binds to all E. coli clinical isolates tested so far (79 blood isolates, 80 urinary isolates, and 21 fecal isolates) and to some Citrobacter, Enterobacter, and Klebsiella isolates. This pattern of reactivity indicates that its binding epitope is widespread among members of the Enterobacteriaceae. WN1 222-5 exhibits biologically relevant activities. In vitro, it inhibits the Limulus amoebocyte lysate assay activity of S-form and R-form LPS in a dose-dependent manner and it neutralizes the LPS-induced release of clinically relevant monokines (interleukin 6 and tumor necrosis factor). In vivo, WN1 222-5 blocks endotoxin-induced pyrogenicity in rabbits and lethality in galactosamine-sensitized mice. The discovery of WN1 222-5 settles the long-lasting controversy over the existence of anti-core LPS MAbs with both cross-reactive and cross-protective activity, opening new possibilities for the immunotherapy of sepsis caused by gram-negative bacteria.
Surgical Correction of Breast Deformities Following Long-lasting Complications of Polyurethane-covered Implants (1990)

Breast deformities following long-lasting complications associated with the use of polyurethane prostheses are encountered with increasing frequency in our practice. Patients with this problem often feel frustrated after a long period of unsuccessful treatment and multiple operations. The anatomopathological bases of the deformity in such patients can be summarized as follows: volumetric mammary defect, soft tissue deficiency, and distortion and fibrosis of residual breast tissues. The reconstructive procedure should provide adequate aesthetic results with permanent or long-lasting symmetry, possibly in a single operative stage. The procedures employed in 12 patients are reviewed, and 3 representative cases are described in detail. The best aesthetic results in difficult cases have been achieved with either a latissimus dorsi muscular flap raised through minimal posterior incisions and transposed anteriorly to cover a permanent, expandable implant, or a suitably tailored, partly deepithelialized transverse rectus abdominis musculocutaneous flap.
Swift Development of Protective Effector Functions in Naive Cd8+ T Cells against Malaria Liver Stages (2001)

We generated T cell receptor transgenic mice specific for the liver stages of the rodent malaria parasite Plasmodium yoelii and studied the early events in the development of in vivo effector functions in antigen-specific CD8(+) T cells. Differently to activated/memory cells, naive CD8(+) T cells are not capable of exerting antiparasitic activity unless previously primed by parasite immunization. While naive cells need to differentiate before achieving effector status, the time required for this process is very short. Indeed, interferon (IFN)-gamma and perforin mRNA are detectable 24 h after immunization and IFN-gamma secretion and cytotoxic activity are detected ex vivo 24 and 48 h after immunization, respectively. In contrast, the proliferation of CD8(+) T cells begins after 24 h and an increase in the total number of antigen-specific cells is detected only after 48 h. Remarkably, a strong CD8(+) T cell-mediated inhibition of parasite development is observed in mice challenged with viable parasites only 24 h after immunization with attenuated parasites. These results indicate that differentiation of naive CD8(+) T cells does not begin only after extensive cell division, rather this process precedes or occurs simultaneously with proliferation.
A novel β‐globin gene mutation HBB.c.22 G>C produces a hemoglobin variant (Hb Vellore) mimicking HbS in HPLC (2012)

Hemoglobinopathies are highly prevalent in Indian population. DNA analysis to detect causative mutations is required for identifying rare hemoglobin variants or when hematological results are discordant with the clinical phenotype. In this report, we describe a novel hemoglobin variant caused by a mutation in beta-globin gene, Codon 7 GAG→CAG (Glu→Gln) that elutes in the position of sickle haemoglobin (HbS) in cation exchange high performance liquid chromatography. This report highlights possible diagnostic pitfalls in interpreting data solely based on haemoglobin analysis and usefulness of mutation screening in definitive diagnosis of hemoglobinopathies.
Design-Build: How to Increase Its Usage and Its Impact on Architects and Contractors in Singapore (2012)

The purpose of this paper is to explore the ways to increase the usage of design-build (DB). The scope covers how project managers (local and foreign) can play a role in increasing DB usage in Singapore. It is found that owners would adopt DB if their requirements can be properly met. This is achieved by having clear and comprehensive bid documents, having sketch designs prepared by client appointed consultants, and engaging experienced DB contractors. Clients also need to engage project managers and consultant quantity surveyors to manage the DB projects, but the liability for design rests on DB contractors. Clients want DB contractors to provide warranty for fitness for purpose. The conclusion is that clients welcome the use of DB if some concrete steps are taken to make it meet their needs better. This study also concludes that consulting and contracting companies welcome DB, as this procurement method does not have a significantly negative impact on them.
A Flexible RNA Backbone within the Polypyrimidine Tract Is Required for U2AF65 Binding and Pre-mRNA Splicing InVivo (2010)

The polypyrimidine tract near the 3' splice site is important for pre-mRNA splicing. Using pseudouridine incorporation and in vivo RNA-guided RNA pseudouridylation, we have identified two important uridines in the polypyrimidine tract of adenovirus pre-mRNA. Conversion of either uridine into pseudouridine leads to a splicing defect in Xenopus oocytes. Using a variety of molecular biology methodologies, we show that the splicing defect is due to the failure of U2AF(65) to recognize the pseudouridylated polypyrimidine tract. This negative impact on splicing is pseudouridine specific, as no effect is observed when the uridine is changed to other naturally occurring nucleotides. Given that pseudouridine favors a C-3'-endo structure, our results suggest that it is backbone flexibility that is key to U2AF binding. Indeed, locking the key uridine in the C-3'-endo configuration while maintaining its uridine identity blocks U2AF(65) binding and splicing. This pseudouridine effect can also be applied to other pre-mRNA polypyrimidine tracts. Thus, our work demonstrates that in vivo binding of U2AF(65) to a polypyrimidine tract requires a flexible RNA backbone.
Development of a K562 cell-based assay for screening anticancer agents. (2001)

The high-throughput method using K562 cell line is fast, economical, effective, and practical in identifying inhibitors as potential therapeutic agents for cancer.
OAO5-04. Gp96-Ig-SIV vaccines induce predominant immune responses at mucosal sites (2009)

Background We have developed a vaccine design that utilizes the unique property of the endoplasmic reticulum chaperon, heat shock protein (HSP) gp96, to bind antigenic peptides and deliver them to APCs. Cell-based gp96-Ig vaccines, by prolonged in vivo secretion of gp96-Ig peptide, imitate viral replication and provide immune stimuli comparable to attenuated viruses. In model systems in mice we have shown that gp96-Ig transfected, antigen expressing cells secrete gp96-Ig in vivo and stimulate both systemic and strong mucosal immunity. The aim of our study was to evaluate safety and systemic and mucosal SIV-immunity with secreted gp96-Ig-SIV vaccines in non-human primates.
Simultaneous self-calibration of a projector and a camera using structured light (2011)

We propose a method for geometric calibration of an active vision system, composed of a projector and a camera, using structured light projection. Unlike existing methods of self-calibration for projector-camera systems, our method estimates the intrinsic parameters of both the projector and the camera as well as extrinsic parameters except a global scale without any calibration apparatus such as a checker-pattern board. Our method is based on the decomposition of a radial fundamental matrix into intrinsic and extrinsic parameters. Dense and accurate correspondences are obtained utilizing structured light patterns consisting of Gray code and phase-shifting sinusoidal code. To alleviate the sensitivity issue in estimating and decomposing the radial fundamental matrix, we propose an optimization approach that guarantees the possible solution using a prior for the principal points. We demonstrate the stability of our method using several examples and evaluate the system quantitatively and qualitatively.
Load Transfer from Bored, Cast-in-Situ Piles in London Clay (1979)

This paper presents some measurements of the distribution of load transfer from the shafts of instrumented, bored, cast-in-situ concrete piles formed in London clay using a limited number of installation techniques. The measurements were included in a study of whether the use of bentonite slurries to stabilize open bore holes prior to concreting inhibits the development of friction on the shafts of piles in stiff clays. The instrumentation consisted of rod extensometers of various lengths and vibrating-wire gages clamped to the reinforcing cages. Devices attached to the bottom of each reinforcing cage prevented the development of any bearing forces at the pile bases. A method of correcting the extensometer observations for bending of the laterally unsupported length of shaft cased through fill is described, and the results are compared with a finite element analysis of the pile-soil system.
Sensing Using Piezoelectric Chiral Polymer Fiber (2012)

To realize a new polymer sensor fabricated from a piezoelectric chiral polymer fiber, we attempted to detect the response signal induced by the shear piezoelectricity of the chiral polymer poly(L-lactic acid) (PLLA) under the application of stress and strain, and we confirmed that the piezoelectric response signal was sufficiently large for use as a sensor signal. We then prepared a left-hand helical torsion coil (PLLA fiber left-hand coil), which was formed by drawing a PLLA fiber ten times. It was observed that, when twisted and released suddenly, the coil exhibited a torsion vibration, and we confirmed that the piezoelectric response signal followed the torsion vibration. Next, we prepared a system in which a PLLA fiber coil was linked to a personal computer used for simple image processing. The PLLA fiber left- and right-hand coils were placed on the arm of a subject, and the inward rotation and outward rotation of the forearm and upper arm were measured. Finally, using this system, we were able to visualize the rotation of the forearm and upper arm.
Targeted Proteomics for Metabolic Pathway Optimization (2012)

A crucial part of optimization of metabolically engineered organisms is producing balanced levels of pathway proteins. Typically, protein levels are monitored by Western blot analysis; however, application to multiple enzyme pathways can be difficult without unique antibodies for each enzyme in the pathway. Furthermore, it can be time consuming, and cost prohibitive during exploratory stages of pathway design when many different proteins must be monitored simultaneously. We present here a targeted proteomics approach that uses selected-reaction monitoring (SRM) mass spectrometry to quantify multiple proteins in a sample. SRM methods provide high selectivity and high sensitivity to enable rapid quantification of multiple proteins in an engineered pathway regardless of sequence or organism of origin.
In situ hybridization analysis of anterior pituitary hormone gene expression during fetal mouse development. (1994)

We used 35S-labeled oligonucleotides and cRNAs (riboprobes) to detect the temporal order and spatial pattern of anterior pituitary hormone gene expression in (B6CBF1 x B6CBF1)F2 fetal mice from embryonic Day 9.5 (E9.5) to postnatal Day 1 (P1). Pro-opiomelanocortin (POMC) mRNA was expressed in the basal diencephalon on Day E10.5, in the ventromedial zone of the pars distalis on Day E12.5, and in the pars intermedia on Day E14.5. The common alpha-glycoprotein subunit (alpha-GSU) mRNA first appeared in the anterior wall of Rathke's pouch on Day E11.5 and extended to the pars tuberalis and ventromedial zone of the pars distalis on Day E12.5. Thyroid-stimulating hormone-beta (TSH beta) subunit mRNA was expressed initially in both the pas tuberalis and ventromedial pars distalis on Day E14.5, with an identical spatial distribution to alpha-GSU at the time. In contrast, luteinizing hormone-beta (LH beta) subunit and follicle-stimulating hormone beta (FSH beta) subunit mRNAs were detected initially only in the ventromedial pars distalis on Days E16.5 and E17.5, respectively, in an identical distribution to each other. POMC-, alpha-GSU-, TSH beta, LH beta-, and FSH beta-positive cells within the pars distalis all increased in number and autoradiographic signal with differing degrees of spatial expansion posteriorly, laterally, and dorsally up to Day P1. POMC expression was typically the most intense and extended circumferentially to include the entire lateral and dorsal surfaces of the pars distalis. The expression of both growth hormone (GH) and prolactin (PRL) started coincidentally on Day E15.5. However PRL cells localized in the ventromedial area similarly to POMC and the glycoprotein hormone subunits, whereas GH cells were found initially in a more lateral and central distribution within the lobes of the pars distalis. Somatotrophs increased dramatically in number and autoradiographic signal, extending throughout the pars distalis except for the most peripheral layer of cells on Day E17.5. Mammotrophs also increased in number but less abundantly than somatotrophs, and PRL expression remained more confined to central-medial and ventrolateral areas of the pars distalis up to Day P1. These data demonstrate distinctive patterns of expression for each of the major anterior pituitary hormone genes during development of the mouse pituitary gland and suggest that different groups of committed cells are the immediate precursors to the terminally differentiated hormone-secreting cell types.
Systems Biology and New Technologies Enable Predictive and Preventative Medicine (2004)

Systems approaches to disease are grounded in the idea that disease-perturbed protein and gene regulatory networks differ from their normal counterparts; we have been pursuing the possibility that these differences may be reflected by multiparameter measurements of the blood. Such concepts are transforming current diagnostic and therapeutic approaches to medicine and, together with new technologies, will enable a predictive and preventive medicine that will lead to personalized medicine.
Acetoacetate metabolism in rat brain. Development of acetoacetyl-coenzyme A deacylase and 3-hydroxy-3-methylglutaryl-coenzyme A synthase (1978)

1. Data are provided that indicate that the rat brain acetoacetyl-CoA deacylase is almost exclusively mitochondrial. Developmental studies show that this enzyme more than doubles its activity during suckling (0–21 days) and then maintains this activity in adults (approx. 1.1 units/g wet wt.). 2. Kinetic studies (on the acetoacetyl-CoA deacylase) in a purified brain mitochondrial preparation give a Vmax. of 47 nmol/min per mg of protein, and a Km for acetoacetyl-CoA of 5.2 micron and are compatible with substrate inhibition by acetoacetyl-CoA above concentrations of 47 micron. 3. The total brain 3-hydroxy-3-methyl-glutaryl-CoA synthase remains constant in the developing and adult rat brain (approx. 1.2 units/g wet wt.). This enzyme is located in both the mitochondrial and cytosolic fractions. During suckling (0–21 days) the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase represents approx. one-third of the total, but this increases markedly to about 60% of the total in the adult. The cytosolic enzyme correspondingly falls to approx. 40% of the total. 4. The role of the acetoacetyl-CoA deacylase in providing cytosolic acetoacetate for biosynthetic activities in the developing brain is discussed.
Epitope conservation and immunohistochemical localization of the guanylin/stable toxin peptide receptor, guanylyl cyclase C (1997)

The heat-stable enterotoxins (ST) are a family of cysteine-rich low-molecular weight peptides produced by pathogenic bacteria, and are one of the major causes of watery diarrhea all over the world. These toxins mediate their action by binding to an intestinal cell surface receptor that is a membrane-associated guanylyl cyclase (GCC). This receptor also serves as the receptor for the recently characterised endogenous ligand, guanylin. We have expressed various domains of the receptor in Escherichia coli and used purified proteins for the generation of both polyclonal and monoclonal antibodies. While polyclonal antibodies were able to partially inhibit ST binding to the native receptor present in the T84 human colonic cell line, GCC:B10 monoclonal antibody did not interfere with ligand binding. Western blot analysis, using membranes prepared from human colonic T84 cells, detected two bands of size 160 and 140 kDa, representing alternately glycosylated forms of the receptor. Using the recombinant proteins, we could map the epitope of GCC:B10 monoclonal antibody to the intracellular domain of the receptor. We used the antibody to localize the receptor throughout the rat intestine, and in the porcine and bonnet monkey colon. We could detect receptor expression in the villus and the crypts of the duodenum, jejunum, ileum, and caecum, and in the crypts of the colon. Receptor expression was observed in cells that had earlier been shown to express cGMP-dependent kinase, but not the cystic fibrosis transmembrane regulator, a known downstream target of cGMP/G-kinase, which suggests that GCC/ cGMP could regulate additional cellular signal transduction machinery.