gebhart/patrepeval huggingface dataset:
Sizing up the heart: development redux in disease (2003)

￻￻ Following gastrulation and establishment of the three embryonic germ layers, the first definitive organ to form in the embryo is the heart, whose morphogenesis, growth, and integrated function are essential to embryonic survival, even by midgestation. Abnormalities in heart development result in congenital heart disease, the most frequent form of birth defects in humans. At the opposite end of the temporal spectrum, adult cardiac disease is the most common cause of death in the industrialized world, with congestive heart failure and inadequate pump function the end result of diverse disorders intrinsic to cardiac muscle cells, cardiac valves, systemic blood pressure, and the coronary blood supply. Despite recent therapeutic advances and mechanical devices to sustain cardiac function, only a minority of heart failure patients lives longer than 5yr. Death from heart disease therefore comprises an epidemic more prevalent than all cancers combined (Ries et al. 2003). Recent studies have begun to reveal the cellular circuitry that controls cardiac growth during development and disease. Intriguingly, many of the molecules and mechanisms that regulate growth of the embryonic heart are redeployed in the adult heart in response to stress signals that provoke cardiac enlargement and heart failure. Thus, understanding the mechanisms involved in heart development promises to provide insights into the molecular basis for pathogenesis of the adult heart, as well as to reveal novel therapeutic targets. In this review, we consider three aspects of cardiac development with significant implications for adult heart disease: (1) normal growth during organogenesis, (2) a “fetal” cardiac gene program reactivated in hypertrophy, and (3) restorative growth by undifferentiated progenitor cells that have cardiogenic potential. Each of these aspects of cardiac growth could be, itself, the subject of an in-depth review. Our goal, however, is not to comprehensively review these areas, but to identify common themes in developmental biology that are reiterated in settings of abnormal growth and dysfunction of the adult heart. Although we focus on development and disease of the myocardium, many of the same principles of allometric growth and homeostasis apply to other organs whose structure and function are influenced by physiological and pathological signaling.
A comprehensive strategy for the analysis of acoustic compressibility and optical deformability on single cells (2016)

We realized an integrated microfluidic chip that allows measuring both optical deformability and acoustic compressibility on single cells, by optical stretching and acoustophoresis experiments respectively. Additionally, we propose a measurement protocol that allows evaluating the experimental apparatus parameters before performing the cell-characterization experiments, including a non-destructive method to characterize the optical force distribution inside the microchannel. The chip was used to study important cell-mechanics parameters in two human breast cancer cell lines, MCF7 and MDA-MB231. Results indicate that MDA-MB231 has both higher acoustic compressibility and higher optical deformability than MCF7, but statistical analysis shows that optical deformability and acoustic compressibility are not correlated parameters. This result suggests the possibility to use them to analyze the response of different cellular structures. We also demonstrate that it is possible to perform both measurements on a single cell, and that the order of the two experiments does not affect the retrieved values.
Infection with Trichomonas vaginalis Increases the Risk of HIV‐1 Acquisition (2007)

We conducted a prospective study among women in Mombasa, Kenya, to determine whether Trichomonas vaginalis infection was associated with an increased risk of human immunodeficiency virus type 1 (HIV-1) infection. At monthly follow-up visits, laboratory screening for HIV-1 and genital tract infections was conducted. Among 1335 HIV-1-seronegative women monitored for a median of 566 days, there were 806 incident T. vaginalis infections (23.6/100 person-years), and 265 women seroconverted to HIV-1 (7.7/100 person-years). Trichomoniasis was associated with a 1.52-fold (95% confidence interval, 1.04-2.24-fold) increased risk of HIV-1 acquisition after adjustment for potential confounding factors. Treatment and prevention of T. vaginalis infection could reduce HIV-1 risk in women.
Experimental Reproduction of Severe Disease in CD/CD Pigs Concurrently Infected with Type 2 Porcine Circovirus and Porcine Reproductive and Respiratory Syndrome Virus (2001)

Three-week-old cesarean-derived colostrum-deprived (CD/CD) pigs were inoculated with porcine circovirus type 2 (PCV2, n = 19), porcine reproductive and respiratory syndrome virus (PRRSV, n = 13), concurrent PCV2 and PRRSV (PCV2/PRRSV, n = 17), or a sham inoculum (n = 12) to compare the independent and combined effects of these agents. Necropsies were performed at 7, 10, 14, 21, 35, and 49 days postinoculation (dpi) or when pigs became moribund. By 10 dpi, PCV2/PRRSV-inoculated pigs had severe dyspnea, lethargy, and occasional icterus; after 10 dpi, mortality in this group was 10/11 (91%), and all PCV2/ PRRSV-inoculated pigs were dead by 20 dpi. PCV2-inoculated pigs developed lethargy and sporadic icterus, and 8/19 (42%) developed exudative epidermitis; mortality was 5/19 (26%). PRRSV-inoculated pigs developed dyspnea and mild lethargy that resolved by 28 dpi. Microscopic lesions consistent with postweaning multisystemic wasting syndrome (PMWS) were present in both PCV2- and PCV2/PRRSV-inoculated pigs and included lymphoid depletion, necrotizing hepatitis, mild necrotizing bronchiolitis, and infiltrates of macrophages that occasionally contained basophilic intracytoplasmic inclusion bodies in lymphoid and other tissues. PCV2/ PRRSV-inoculated pigs also had severe proliferative interstitial pneumonia and more consistent hepatic lesions. The most severe lesions contained the greatest number of PCV2 antigen-containing cells. PRRSV-inoculated pigs had moderate proliferative interstitial pneumonia but did not develop bronchiolar or hepatic lesions or lymphoid depletion. All groups remained seronegative to porcine parvovirus. The results indicate that 1) PCV2 coinfection increases the severity of PRRSV-induced interstitial pneumonia in CD/CD pigs and 2) PCV2 but not PRRSV induces the lymphoid depletion, granulomatous inflammation, and necrotizing hepatitis characteristic of PMWS.
All-around contact for carbon nanotube field-effect transistors made by ac dielectrophoresis (2006)

Carbon nanotube field-effect transistors (CNFETs) are fabricated by depositing one bundle of single-walled carbon nanotubes (SWNTs) per device between a pair of predefined Pd electrodes using ac dielectrophoresis. By repeating the process for the formation of the Pd electrodes after the bundle deposition, all-around Pd contacts are made to the SWNT bundles. After the formation of all-around contact, the CNFETs with only semiconducting SWNTs in the bundles retain a strong gate modulation with a high ratio of on to off current Ion∕Ioff⩾106. For the CNFETs with at least one metallic SWNT in the bundles, their gate modulation disappears and carbon nanotube resistors (CNRs) are obtained. The on current Ion of CNFETs is found to be sensitive to the process for the formation of all-around contact. In contrast, the two-probe resistance of CNRs is consistently reduced after the all-around contacts. The electrical measurements also indicate the presence of an interlayer residing at the SWNT/Pd contacts.
Conditional immune-gene suppression of honeybees parasitized by Varroa mites (2005)

The ectoparasitic mite, Varroa destructor, is the most destructive parasite of managed honeybee colonies worldwide. Since V. destructor transfers pathogens to honeybees, it may be adaptive for bees to respond to mite infestation by upregulating their immune responses. Mites, however, may overcome the host's immune responses by suppressing them, which could facilitate the mite's ability to feed on hemolymph. A humoral immune response of bees parasitized by V. destructor may be detected by studying the expression levels of antibacterial peptides, such as abaecin and defensin, known to be immune-responsive. Expression levels for these two antibacterial peptides changed non-linearly with respect to the number of mites parasitizing honeybee pupae. Bees exposed to low or moderate number of mites had fewer immune-related transcripts than pupae that were never parasitized or pupae with high mite loads. Although many of the pupae tested indicated the presence of bacteria, no correlation with mite numbers or immune-response levels existed. All bees tested negative for acute paralysis and Kashmir bee viruses known to be vectored by V. destructor.
A secreted Delta1‐Fc fusion protein functions both as an activator and inhibitor of Notch1 signaling (2002)

Signaling induced through interactions between DSL (Delta, serrate, LAG-2) ligand-signaling cells and Notch-responding cells influences the developmental fate of a wide variety of invertebrate and vertebrate cell types. Consistently with a requirement for direct cell-cell interactions, secreted DSL ligands expressed in flies do not appear to activate Notch signaling but rather produce phenotypes reminiscent of losses in Notch signaling. In contrast, secreted DSL ligands expressed in Caenorhabditis elegans or supplied to mammalian cells in culture produce effects indicative of Notch activation. In fact, engineered secreted DSL ligands have been used to study Notch signaling in neurogenesis, gliogenesis, hematopoeisis, neurite morphogenesis and ligand-induced nuclear translocation of the Notch intracellular domain. Using a recombinant, secreted form of the DSL ligand Delta1, we found that antibody-induced oligomerization (termed "clustering") was required for this soluble ligand to bind specifically to Notch1-expressing cells, undergo internalization, and activate downstream signaling. Interestingly, clustering with either limiting or excess antibody led to ligand binding in the absence of Notch signaling, indicating that ligand binding is necessary but not sufficient for activation of Notch signaling. Moreover, such antibody clustering conditions blocked Notch1 signaling induced by membrane-bound DSL ligands. We propose that multimerization influences whether ligand binding to Notch results in activation or inhibition of downstream signaling and suggest that differences in ligand presentation might account for why secreted forms of DSL ligands have been reported to function as agonists and antagonists of Notch signal transduction.
Imaging and analysis of subsurface Cu interconnects by detecting backscattered electrons in the scanning electron microscope (2005)

Cu – Si O 2 – Si N x interconnects that were located 0.65–2.7-μm below the surface of silicon-integrated circuits were imaged in a scanning electron microscope and a transmission electron microscope with a scanning attachment by detecting backscattered electrons (BSEs) with an incident electron-beam energy (Eo) in the range of 30–400keV. BSE images could be used to detect voids in subsurface Cu interconnects, even in regions covered with upper level Cu lines or vias. As Eo was increased from 30to400keV, structures could be seen as a result of atomic number (Z) contrast farther below the surface while structures closer to the surface had reduced Z contrast. The subsurface beam diameter was measured from BSE images as a function of Eo and depth below the surface. For all Eo, the subsurface beam diameter initially rapidly increased with SiO2 overlayer thickness but, for 150keV, a leveling off in the beam spread was seen for depths &amp;gt;1.7μm. Beam broadening affected whether the TaN∕Ta liners that surrounded the Cu conductors could be seen at the edges of the lines; this contrast was observed only when the subsurface beam diameter was ⩽1.5× the liner thickness. The BSE information depth for imaging 0.2-μm-sized voids in subsurface Cu–SiO2–SiNx interconnect structures at 30 and 150keV was estimated to be 0.65 and 3μm, respectively.
Acquired Resistance to Rituximab Is Associated with Chemotherapy Resistance Resulting from Decreased Bax and Bak Expression (2008)

Whereas a single or limited exposure of lymphoma cells to rituximab may lead to a favorable ratio of proapoptotic to antiapoptotic Bcl-2 family proteins, repeated exposure to rituximab is associated with a therapy-resistant phenotype via modulation of Bax and Bak expression.
Identification of Omi/HtrA2 as a Mitochondrial Apoptotic Serine Protease That Disrupts Inhibitor of Apoptosis Protein-Caspase Interaction (2002)

To identify human proteins that bind to the Smac and caspase-9 binding pocket on the baculoviral inhibitor of apoptosis protein (IAP) repeat 3 (BIR3) domain of human XIAP, we used BIR3 as an affinity reagent, followed by elution with the BIR3 binding peptide AVPIA, microsequencing, and mass spectrometry. The mature serine protease Omi (also known as HtrA2) was identified as a mitochondrial direct BIR3-binding protein and a caspase activator. Like mature Smac (also known as Diablo), mature Omi contains a conserved IAP-binding motif (AVPS) at its N terminus, which is exposed after processing of its N-terminal mitochondrial targeting sequence upon import into the mitochondria. Mature Omi is released together with mature Smac from the mitochondria into the cytosol upon disruption of the outer mitochondrial membrane during apoptosis. Finally, mature Omi can induce apoptosis in human cells in a caspase-independent manner through its protease activity and in a caspase-dependent manner via its ability to disrupt caspase-IAP interaction. Our results provide clear evidence for the involvement of a mitochondrial serine protease in the apoptotic pathway, emphasizing the critical role of the mitochondria in cell death.
Specific autoantibodies precede the symptoms of rheumatoid arthritis: A study of serial measurements in blood donors (2004)

Approximately half of patients with RA have specific serologic abnormalities several years before the onset of symptoms. A finding of an elevated serum level of IgM-RF or anti-CCP in a healthy individual implies a high risk for the development of RA. We conclude that IgM-RF and anti-CCP testing with appropriately high specificity may assist in the early detection of RA in high-risk populations.
B and T Lymphocyte Attenuator Exhibits Structural and Expression Polymorphisms and Is Highly Induced in Anergic CD4+ T Cells (2005)

B and T lymphocyte attenuator (BTLA) was initially identified as expressed on Th1 cells and B cells, but recently reported to be expressed by macrophages, dendritic cells, and NK cells as well. To address this discrepancy we generated a panel of BTLA-specific mAbs and characterized BTLA expression under various activation conditions. We report the existence of three distinct BTLA alleles among 23 murine strains, differing both in Ig domain structure and cellular distribution of expression on lymphoid subsets. The BALB/c and MRL/lpr alleles differ at one amino acid residue, but C57BL/6 has nine additional differences and alters the predicted cysteine bonding pattern. The BALB/c BTLA allele is also expressed by B cells, T cells, and dendritic cells, but not macrophages or NK cells. However, C57BL/6 BTLA is expressed on CD11b+ macrophages and NK cells. Finally, in CD4+ T cells, BTLA is expressed most highly following Ag-specific induction of anergy in vivo, and unlike programmed death-1 and CTLA-4, not expressed by CD25+ regulatory T cells. These results clarify discrepancies regarding BTLA expression, suggest that structural and expression polymorphisms be considered when analyzing BTLA in various murine backgrounds, and indicate a possible role in anergic CD4+ T cells.
Molecular cloning of a somatostatin-28 receptor and comparison of its expression pattern with that of a somatostatin-14 receptor in rat brain. (1992)

The tetradecapeptide somatotropin-release inhibiting factor somatostatin-14 regulates the release of peptide hormones and also functions as neurotransmitter. The octacosapeptide somatostatin-28, the N-terminally extended form of somatostatin-14, shows similar biological activities yet with different potencies. Both peptides most likely function through distinct receptors. Here we report on the molecular and functional characterization of a somatostatin-28 receptor (SSR-28) cloned from a rat brain cDNA library. The nucleotide sequence contains an open reading frame for a protein of 428 amino acid residues with a predicted molecular mass of 47 kDa. Binding assays using radiolabeled somatostatin-14 and membranes from COS cells transfected with the cloned cDNA show that this receptor, SSR-28, has a higher binding affinity for somatostatin-28 (IC50 = 0.24 nM) than for somatostatin-14 (IC50 = 0.89 nM). RNA blot analysis reveals a 4.4-kilobase mRNA in rat cerebellum and at significantly lower abundance in other brain regions. In situ hybridization indicates that SSR-28 mRNA is present in the granular and Purkinje cell layers of the cerebellum and in the large cells of the hypoglossal nucleus of the brain stem. Signals for SSR-28 mRNA do not overlap with those of a previously cloned rat receptor that preferentially binds somatostatin-14 (SSR-14). SSR-14 mRNA is found in the medial cerebellar nucleus, horizontal limb of the diagonal band, various hypothalamic nuclei, and in layers IV and V of the cortex. In the rat cerebellum, SSR-14 and SSR-28 mRNAs are developmentally regulated; the levels of the former are highest around birth and levels of the latter are highest at the adult stage.
High sensitivity trace gas sensor for planetary atmospheres: miniaturized Mars methane monitor (2014)

Highly sensitive trace gas measurements in planetary atmospheres can yield information about a planet’s atmosphere and surface. One prominent example is methane in the Martian atmosphere, which could originate biogenically and provides answers to one of the most intriguing questions in planetary science: “Does life currently exist on Mars?” Recently, in situ measurements by the Mars Science Laboratory (MSL) have resulted in an upper limit of 1300 parts per trillion by volume (pptv), whereas previous measurements using terrestrial telescopes and an instrument orbiting Mars reported significantly higher values of 10,000 pptv or more. These results are not necessarily contradictory, due to the possibility of spatial and temporal variability of the trace gas concentration. Thus, more measurements will be required to gain clarity. The concept of a miniaturized Mars methane monitor, a high spectral resolution, midinfrared spectrometer observing the sun through the Mars atmosphere from either the Mars surface, a Mars balloon or plane, or a Mars orbiting satellite is presented. The instrument would measure atmospheric methane and water vapor volume mixing ratios with equal or higher precision than the tunable laser spectrometer on MSL. The spectrometer concept uses the spatial heterodyne spectroscopy technique, which has previously been used for ground- and space-based observations of the Earth’s atmosphere.
T cell receptor-o deletion in human T cells (1996)

The immune system protects the body against pathogens such as bacteria,\\nviruses, fungi, and parasites, when they pass the first line of body defence such as\\nthe skin or other epithelial and mucosal barriers.\\nAfter penetration into the body, micro-organisms encounter the second line of\\ndefence. This concerns the so-called aspecitlc immune system, which consists of\\nphagocytes, such as macrophages and granulocytes, complement factors, and natural\\nkiller cells. Generally, support by the third line of defence is needed, i.e. the socalled\\nspecific irrunune system.
Effects of dietary seaweed extract supplementation in sows and post-weaned pigs on performance, intestinal morphology, intestinal microflora and immune status (2011)

The present study investigated the effects of dietary supplementation of a seaweed extract (SWE) to sows and weaned pigs on post-weaning growth performance, intestinal morphology, intestinal microflora, volatile fatty acid concentrations and immune status of pigs at days 11 and 117 post-weaning. Gestating sows (n 20) were supplemented with a SWE (0 v. 10·0 g/d) from day 107 of gestation until weaning (day 26). At weaning, pigs (four pigs per sow) were divided into two groups based on sow diet during lactation and supplemented with a SWE (0 v. 2·8 g/kg diet), resulting in four treatment groups: (1) BB (basal sows-basal pigs); (2) BS (basal sows-treated pigs); (3) SB (treated sows-basal pigs); (4) SS (treated sows-treated pigs). Pigs weaned from SWE-supplemented sows had a higher average daily gain (ADG) between days 0 and 21 (P < 0·05) post-weaning compared with pigs weaned from non-SWE-supplemented sows. Pigs offered post-weaning diets (PW) containing SWE had decreased colonic Escherichia coli populations on day 11 (P < 0·01) and decreased colonic Enterobacteriaceae numbers on day 117 (P < 0·05). Pigs offered PW containing SWE had a greater mRNA abundance of MUC2 in the colon at day 11 post-weaning (P < 0·05) compared with pigs offered unsupplemented diets. In conclusion, these results demonstrate that SWE supplementation post-weaning provides a dietary means to improve gut health and to enhance growth performance in starter pigs. Dietary SWE supplementation increased ADG during the grower-finisher (GF) phases. However, there was no growth response to SWE inclusion in GF diets when pigs were weaned from SWE-supplemented sows.
Bone repair induced by bone morphogenetic protein in ulnar defects in dogs (1986)

In dogs, resection of a length of the ulna equal to twice the diameter of the mid-shaft leaves a defect which consistently fails to unite. In response to an implant of 100 mg of bovine bone morphogenetic protein (BMP), the defect becomes filled by callus consisting of fibrocartilage, cartilage and woven bone within four weeks. The cartilage is resorbed and replaced by new bone in four to eight weeks. Woven bone is then resorbed, colonised by bone marrow cells and remodelled into lamellar bone. Union of the defect is produced by 12 weeks. Control defects filled with autogeneic cortical bone chips unite after the same period. In regeneration induced by bone morphogenetic protein (BMP) and in repair enhanced by bone graft, union depends upon the proliferation of cells within and around the bone ends. Our working hypothesis is that BMP induces the differentiation of perivascular connective tissue cells into chondroblasts and osteoprogenitor cells and thereby augments the process of bone regeneration from the cells already present in the endosteum and periosteum.
Phase I study of olaparib in combination with liposomal doxorubicin in patients with advanced solid tumours (2014)

Continuous/intermittent olaparib (up to 400 mg bid) combined with PLD (40 mg m(-2)) was generally tolerated and showed evidence of antitumour activity in ovarian cancer.
Clustering by evidence accumulation on affinity propagation (2008)

Affinity propagation (AP) is a clustering algorithm which has much better performance than traditional clustering approach such as k-means algorithm. In this paper, we present an algorithm called voting partition affinity propagation (voting-PAP) which is a method for clustering using evidence accumulation based on AP. Resulting clusters by voting-PAP are not constrained to be hyper-spherically shaped. Voting-PAP consists of three parts: Partition Affinity propagation (PAP), relaxed multi-root minimum spanning tree (MST) and majority voting. PAP is a method which can produce different exemplar set based on AP. Relaxed multi-root MST is a data point assign algorithm which has better performance than nearest assign rule. Majority voting is a scheme used to find a consistent clustering result of different partitions based on the idea of evidence accumulation. We also discuss how to find an appropriate threshold corresponding to an approximate ideal consistent partition in this paper.