gebhart/patrepeval huggingface dataset:
Dual purinergic synaptic transmission in the human enteric nervous system (2007)

Based on findings in rodents, we sought to test the hypothesis that purinergic modulation of synaptic transmission occurs in the human intestine. Time series analysis of intraneuronal free Ca(2+) levels in submucosal plexus (SMP) from Roux-en-Y specimens was done using Zeiss LSM laser-scanning confocal fluo-4 AM Ca(2+) imaging. A 3-s fiber tract stimulation (FTS) was used to elicit a synaptic Ca(2+) response. Short-circuit current (I(sc) = chloride secretion) was recorded in mucosa-SMP in flux chambers. A distension reflex or electrical field stimulation was used to study I(sc) responses. Ca(2+) imaging was done in 1,222 neurons responding to high-K(+) depolarization from 61 surgical cases. FTS evoked synaptic Ca(2+) responses in 62% of recorded neurons. FTS caused frequency-dependent Ca(2+) responses (0.1-100 Hz). FTS Ca(2+) responses were inhibited by Omega-conotoxin (70%), hexamethonium (50%), TTX, high Mg(2+)/low Ca(2+) (< or = 100%), or capsaicin (25%). A P2Y(1) receptor (P2Y(1)R) antagonist, MRS-2179 or PLC inhibitor U-73122, blocked FTS responses (75-90%). P2Y(1)R-immunoreactivity occurred in 39% of vasoactive intestinal peptide-positive neurons. The selective adenosine A(3) receptor (AdoA(3)R) agonist 2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide (2-Cl-IBMECA) caused concentration- and frequency-dependent inhibition of FTS Ca(2+) responses (IC(50) = 8.5 x 10(-8) M). The AdoA(3)R antagonist MRS-1220 augmented such Ca(2+) responses; 2-Cl-IBMECA competed with MRS-1220. Knockdown of AdoA(1)R with 8-cyclopentyl-3-N-(3-{[3-(4-fluorosulphonyl)benzoyl]-oxy}-propyl)-1-N-propyl-xanthine did not prevent 2-Cl-IBMECA effects. MRS-1220 caused 31% augmentation of TTX-sensitive distension I(sc) responses. The SMP from Roux-en-Y patients is a suitable model to study synaptic transmission in human enteric nervous system (huENS). The P2Y(1)/Galphaq/PLC/inositol 1,3,5-trisphosphate/Ca(2+) signaling pathway, N-type Ca(2+) channels, nicotinic receptors, and extrinsic nerves contribute to neurotransmission in huENS. Inhibitory AdoA(3)R inhibit nucleotide or cholinergic transmission in the huENS.
COMPREHENSION AND APPRECIATION OF HUMOROUS MATERIAL FOLLOWING BRAIN DAMAGE (1975)

The effects of brain damage on cognitive and affective status have been assessed separately; however, a dearth of information exists about the interaction of these facets in the brain-damaged patient. Because appreciation of humour involves both cognitive and affective dimensions, an investigation of response to humorous materials should yield information relevant to this issue. In addition, a study of response to humour in aphasic patients can reveal the extent to which appreciation of humour is dependent upon an intact language system. Accordingly a test of humour, in which an individual chose the "funniest" of four cartoons, was administered to a population of brain-damaged and control patients. Ability to detect the most humorous cartoon was impaired in all brain-damaged patients, more in severe than in mild aphasics, but there was no significant difference between patients with left and right hemisphere lesions in their overall performance on the test. A different order of difficulty across items, and a different profile of "mirth" responses to the items did, however, correlate with site of lesion. Right hemisphere patients tended either to laugh throughout or, more frequently, not at all; they often confabulated answers to made impossible inferences; and they performed better on items with captions. Their cognitive reactions appeared "dissociated" from their affective responses. In contrast left hemisphere patients performed better on the captionless items and behaved in a manner which more closely approximated normal subjects in their humorous reactions, their order of item difficulty, and their explanations. All brain-damaged patients found it relatively easier to locate the humorous cartoons when the members of a set differed appreciably from one another. These results provide information about the altered cognitive and affective states of brain-damaged patients, the impairment of cognitive operations in aphasic patients, and the respective "life-spaces" of left and right hemisphere injured patients.
Human hepatic glyceraldehyde-3-phosphate dehydrogenase binds to the poly(U) tract of the 3′ non-coding region of hepatitis C virus genomic RNA (1999)

The unique poly(U/UC) tract, the middle part of the tripartite 3' non-coding region (3'NCR) of hepatitis C virus (HCV) genomic RNA, may represent a recognition signal for the HCV replicase complex. In this study, several proteins binding specifically to immobilized ribooligonucleotide r(U)(25) mimicking this structure were identified using cytosolic extracts from HCV-negative or -positive liver explants, and a prominent 36 kDa protein was studied further. Competition experiments including homoribopolymers revealed binding affinities in the order: oligo/poly(U)>(A)>(C)>(G). The protein was identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a multifunctional protein known to bind RNA. GAPDH bound efficiently to the full-length HCV RNA and binding to various 3'NCR constructs revealed critical dependence upon the presence of the middle part of the 3'NCR. Polypyrimidine tract-binding protein, described previously to bind the 3'NCR, did not bind efficiently to the middle part of 3'NCR and was captured from liver extracts in considerably smaller quantities.
Antenna array pattern synthesis via convex optimization (1997)

We show that a variety of antenna array pattern synthesis problems can be expressed as convex optimization problems, which can be (numerically) solved with great efficiency by recently developed interior-point methods. The synthesis problems involve arrays with arbitrary geometry and element directivity, constraints on far- and near-field patterns over narrow or broad frequency bandwidth, and some important robustness constraints. We show several numerical simulations for the particular problem of constraining the beampattern level of a simple array for adaptive and broadband arrays.
Frameshift errors initiated by nucleotide misincorporation. (1990)

Studies presented here on the fidelity of DNA synthesis in vitro support the hypothesis that a classical base-substitution intermediate (i.e., a misincorporated nucleotide) can yield a frameshift mutation. By using a fidelity assay specifically designed to detect minus-one-base errors, nucleotide substrate pool imbalances that have previously been shown to increase the rate of misincorporation are now shown to also increase minus-one-base frameshift error rates. Examination of the specificity of the errors produced in reactions with various dNTP pool imbalances and various DNA templates revealed that template nucleotides were preferentially lost when they had as a 5' neighbor a nucleotide complementary to the dNTP provided in excess. This suggests that when a misincorporated nucleotide is complementary to the next nucleotide in the template, a misaligned intermediate containing a correct terminal base pair can form and be extended by a DNA polymerase, leading to a frameshift mutation. We present evidence that the proposed mechanism may operate in vivo and discuss the implications of this model for frameshift mutations induced by DNA damage.
A Novel Mutation within the CentralListeria monocytogenesRegulator PrfA That Results in Constitutive Expression of Virulence Gene Products (2004)

The PrfA protein of Listeria monocytogenes functions as a key regulatory factor for the coordinated expression of many virulence genes during bacterial infection of host cells. PrfA activity is controlled by multiple regulatory mechanisms, including an apparent requirement for either the presence of a cofactor or some form of posttranslational modification that regulates the activation of PrfA. In this study, we describe the identification and characterization of a novel PrfA mutation that results in constitutive activation of the PrfA protein. The PrfA L140F mutation was found to confer high-level expression of PrfA-regulated genes and to be functionally dominant over the wild-type allele. The presence of the PrfA L140F mutation resulted in the aggregation of L. monocytogenes in broth culture and, unlike previously described prfA mutations, appeared to be slightly toxic to the bacteria. High-level PrfA-dependent gene expression showed no additional increase in L. monocytogenes strains containing an additional copy of prfA L140F despite a >4-fold increase in PrfA protein levels. In contrast, the introduction of multiple copies of the wild-type prfA allele to L. monocytogenes resulted in a corresponding increase in PrfA-dependent gene expression, although overall expression levels remained far below those observed for PrfA L140F strains. These results suggest a hierarchy of PrfA regulation, such that the relative levels of PrfA protein present within the cell correlate with the levels of PrfA-dependent gene expression when the protein is not in its fully activated state; however, saturating levels of the protein are then quickly reached when PrfA is converted to its active form. Regulation of the PrfA activation status must be an important facet of L. monocytogenes survival, as mutations that result in constitutive PrfA activation may have deleterious consequences for bacterial physiology.
Mass determination of human immunoglobulin IgM using matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (1994)

Monoclonal human immunoglobulin IgM has been analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Using a matrix of sinapinic acid with a laser wavelength of 355 nm, positive ions with 2 to 6 charges were observed in the mass spectra. Two major molecular species were present. The molecular weights estimated from the multiply-charged signals were found to decrease systematically with decrease in the charge state of the ion. This effect was determined to stem from the non-linear influence of the initial kinetic energy of desorption on the final kinetic energy of the multiply-charged species. A method of successive approximations, with the molecular weights and desorption velocities of the analytes as variables, was used to correct for these non-linearities. Mean molecular weights for the two IgM species were found to be 939,000 +/- 2000 and 982,000 +/- 2000 Da. An initial desorption velocity of 565 +/- 10 ms/s was determined for both.
Glucocorticoid-Induced Apoptosis and Regulation of NF-κB Activity in Human Leukemic T Cells* (1998)

Glucocorticoid-induced apoptosis was investigated in glucocorticoid-sensitive 6TG1.1 and resistant ICR27TK.3 human leukemic T cells. Following glucocorticoid treatment of 6TG1.1 cells, chromatin fragmentation was observed after a delay of 24 h. Fragmentation was not observed in ICR27TK.3 cells containing mutant glucocorticoid receptors (L753F) that are activation-deficient but retain the ability to repress AP-1 activity. Nor was fragmentation observed after treatment with RU38486, indicating that repression of AP-1 activity is not involved. As described in other systems, fragmentation required ongoing protein synthesis. However, inhibition of protein synthesis with cycloheximide anytime during the first 18 h of steroid treatment was as effective in blocking chromatin fragmentation as inhibition for the entire period, suggesting that synthesis of a component with a rapid turnover rate is required. Dexamethasone treatment completely blocked 12-O-tetradecanoylphorbol 13-acetate induction of nuclear factor-kappaB (NF-kappaB) activity and elicited an increase in the amount of immunoreactive IkappaB alpha in sensitive 6TG1.1 cells but not in resistant ICR27TK.3 cells. In addition, mild detergent treatment of cell extracts indicated that a substantial amount of cytoplasmic NF-kappaB is complexed with IkappaB alpha or some other inhibitory factor. These results suggest that induction of a labile inhibitory factor such as IkappaB alpha may contribute to glucocorticoid-induced apoptosis.
Safety and Efficacy of a Steerable Temperature Monitoring Microwave Catheter System for Ventricular Myocardial Ablation (2000)

Temperature feedback control systems for microwave ablation using a temperature-controlled system is feasible for myocardial ablation and creates uniform and large lesions; however, such large lesions can be acutely proarrhythmic.
Systemic Flagellin Immunization Stimulates Mucosal CD103+ Dendritic Cells and Drives Foxp3+ Regulatory T Cell and IgA Responses in the Mesenteric Lymph Node (2012)

Mucosal immunity is poorly activated after systemic immunization with protein Ags. Nevertheless, induction of mucosal immunity in such a manner would be an attractive and simple way to overcome the intrinsic difficulties in delivering Ag to such sites. Flagellin from Salmonella enterica serovar Typhimurium (FliC) can impact markedly on host immunity, in part via its recognition by TLR5. In this study, we show that systemic immunization with soluble FliC (sFliC) drives distinct immune responses concurrently in the mesenteric lymph nodes (MLN) and the spleen after i.p. and s.c. immunization. In the MLN, but not the spleen, sFliC drives a TLR5-dependent recruitment of CD103(+) dendritic cells (DCs), which correlates with a diminution in CD103(+) DC numbers in the lamina propria. In the MLN, CD103(+) DCs carry Ag and are the major primers of endogenous and transgenic T cell priming. A key consequence of these interactions with CD103(+) DCs in the MLN is an increase in local regulatory T cell differentiation. In parallel, systemic sFliC immunization results in a pronounced switching of FliC-specific B cells to IgA in the MLN but not elsewhere. Loss of TLR5 has more impact on MLN than splenic Ab responses, reflected in an ablation of IgA, but not IgG, serum Ab titers. Therefore, systemic sFliC immunization targets CD103(+) DCs and drives distinct mucosal T and B cell responses. This offers a potential "Trojan horse" approach to modulate mucosal immunity by systemically immunizing with sFliC.
Limitations of faecal chymotrypsin as a screening test for chronic pancreatitis. (1991)

Faecal chymotrypsin was measured in patients with chronic pancreatitis and in healthy black urban and rural control subjects. In the patients, significantly lower values of faecal chymotrypsin were obtained (mean (SD) 2.4 1.79 U/g stool) whereas in urban control subjects, values were within the normal range (mean (SD) 13.2 (11.9)). In rural black control subjects, however, the faecal chymotrypsin value was significantly lower (mean (SD) 7.1 (5.1)) than in urban black control subjects. It is suggested that faecal pH may influence faecal chymotrypsin values. The mean faecal pH in rural black subjects (pH 6.14) was significantly lower than that in urban control subjects (pH 6.77) and in patients with chronic pancreatitis (pH 6.61). Moreover, mean faecal chymotrypsin is high (20.0 U/g stool) at a pH greater than 7. Between pH 6 and 7 the mean value drops to 8.6 U/g stool and below pH 6 mean faecal chymotrypsin is in the abnormal range (4.4 U/g stool). Hence, low values for faecal chymotrypsin may be due to lower faecal pH (less than 6) in healthy control subjects. For diagnostic purposes, the faecal pH value should be determined if a low faecal chymotrypsin value is obtained.
Resonance Raman Evidence for an Fe-O-Fe Center in Stearoyl-ACP Desaturase. Primary Sequence Identity with Other Diiron-Oxo Proteins (1994)

The stearoyl-ACP delta 9 desaturase from plants is a new example of a growing number of proteins that contain oxo- or hydroxo-bridged diiron clusters. On the basis of differences in primary sequence motifs providing the cluster ligands and upon structural differences elucidated by X-ray crystallography, we now propose that the presently known, soluble diiron-oxo proteins can be grouped into two classes, I and II. Class I contains hemerythrin, myohemerythrin, and, possibly, purple acid phosphatase. Class II contains ribonucleotide reductases, bacterial hydrocarbon hydroxylases (methane monooxygenase, toluene-4-monooxygenase, and phenol hydroxylase), rubrerythrin, and stearoyl-ACP desaturases. Through the use of resonance Raman spectroscopy, we have detected symmetric (vs = 519 cm-1) and asymmetric (vas = 747 cm-1) vibrational modes in the castor stearoyl-ACP delta 9 desaturase, which are typical of oxo-bridged diiron clusters. These frequencies shift by -18 and -34 cm-1, respectively, in H218O, proving that the bridging ligand is readily exchangeable with solvent (t1/2 = 7 min). Calculation of an approximately 123 degrees Fe-O-Fe angle from the position of vs and vas and from the 18O-dependent shift in these frequencies suggests that the diiron-oxo cluster in the desaturase is triply bridged in the diferric state. In the diferrous state, the two iron sites of the cluster are structurally inequivalent, as shown by differential temperature dependence of the Mössbauer quadrupole splittings. For the class II diiron-oxo proteins, primary sequence alignments reveal conserved amino acid residues which act as iron cluster ligands, participate in a hydrogen-bonding network, and are potentially involved in O2 binding and activation. Based on this conservation, a structural model for the stearoyl-ACP delta 9 desaturase active site is proposed that has strong similarity to both ribonucleotide reductase and methane monooxygenase. However, after single turnover of the diferous state with 18O2, 18O is not detected in the oxo bridge of the castor desaturase. This is in contrast to the outcome observed for ribonucleotide reductase, suggesting the desaturase and ribonucleotide reductase differ in certain aspects of their respective O2-activation reactions.
Svenska moraliska mirakel och invandrade rötägg. (Swedish Moral Miracles and Immigrated Black Sheep) (1997)

Svenska moraliska mirakel och invandrade rotagg. (Swedish Moral Miracles and Immigrated Black Sheep)
Multiple kernel learning SVM and statistical validation for facial landmark detection (2011)

In this paper we present a robust and accurate method to detect 17 facial landmarks in expressive face images. We introduce a new multi-resolution framework based on the recent multiple kernel algorithm. Low resolution patches carry the global information of the face and give a coarse but robust detection of the desired landmark. High resolution patches, using local details, refine this location. This process is combined with a bootstrap process and a statistical validation, both improving the system robustness. Combining independent point detection and prior knowledge on the point distribution, the proposed detector is robust to variable lighting conditions and facial expressions. This detector is tested on several databases and the results reported can be compared favorably with the current state of the art point detectors.
Dehydroepiandrosterone sulphate concentrations in asthmatic patients: pilot study. (1984)

Dehydroepiandrosterone sulphate (DHEA-SO4) values were measured as a guide to adrenal function in 72 asthmatic patients admitted to the Waikato Hospital with severe bronchospasm. In a reference sample 700 micrograms/l was taken as the lower limit of the reference range for DHEA-SO4 concentrations. All DHEA-SO4 values in 20 patients with known primary or secondary adrenal insufficiency were less than this value. In the asthmatic group, 10 of 14 DHEA-SO4 values were low in patients taking oral steroid therapy, eight of 23 values in patients taking inhaled steroids, and six of 29 values in patients on no known steroid therapy. Five of six patients who had been on oral steroids within a month of admission also had low values. In total 40% of all values were less than 700 micrograms/l. These data provide inferential evidence of possible adrenal suppression in a substantial number of patients requiring hospital admission for treatment of severe bronchospasm.
Pulmonary metastases neutralization and tumor rejection byin vivo administration of β glucan and bispecific antibody (1996)

Bispecific antibody (BsAb) with specificity for tumor cell surface antigen and the CD3 molecule on T cells can redirect activated T cells to lyse tumor cells. Since the ex vivo expansion and activation of T cells is impractical and ineffective for treating established tumors, we tested whether the immune stimulant beta glucan could in situ-activate T cells, which could secondarily be retargeted with BsAbs to lyse tumor cells. To test for tumor neutralization, C3H/HeN mice were injected i.v. with Cl-62 melanoma cells and immediately treated with i.p. beta glucan and/or anti-CD3 (500A2) x anti-p97 (96.5) F(ab')2 BsAb i.v. Pulmonary metastases were counted 14 days later. To test for tumor rejection and survival in a solid tumor model, mice were injected s.c. and i.p. with Cl-62 cells and 7 days later administered beta glucan i.p. and/or F(ab')2 BsAb i.v. In the neutralization model, there was a significant reduction in the number of metastases in the beta glucan + BsAb group, as compared with controls, and with beta glucan alone. In the established tumor model, beta glucan + BsAb reduced the incidence of s.c. tumors as compared with control, with BsAb alone and with beta glucan alone. It also prolonged survival of tumor-bearing mice compared with control, BsAb alone and beta glucan alone. We conclude that T cells can be activated in vivo by beta glucan and retargeted with F(ab')2 BsAb.
Divergent influences of leukotrienes C4, D4, and E4 on mesenteric and renal blood flow (1984)

Influences of leukotrienes C4 (LTC4), D4 (LTD4), and E4 (LTE4) on mesenteric and renal blood flow were investigated in the anesthetized dog. Blood flow was measured with noncannulating electromagnetic flow probes, and all agonists were injected as a bolus close arterially. When injected into the superior mesenteric artery, LTC4 (0.1-3.0 ng), LTD4 (0.1-1.0 ng), and LTE4 (1-30 ng) produced dose-dependent decreases in blood flow in absence of a change in mean arterial pressure. When compared with intestinal vasoconstrictor responses caused by angiotension II, which was most active, and norepinephrine, which was least active, the leukotrienes were intermediate between these two well-known vasoactive hormones. LTD4 was more active than LTC4, and both were considerably more active than LTE4. In contrast to the intestine, injection of leukotrienes (1,000 ng) into the kidney resulted in little to no change in renal blood flow or mean arterial pressure, but mesenteric flow decreased 10-15 s later. Administration of indomethacin (5 mg/kg iv) did not alter mesenteric vasoconstrictor responses produced by LTD4. However, mesenteric vasoconstrictor responses to prostaglandin (PG)D2 were reduced after indomethacin, whereas renal vasodilation caused by PGD2 was unaffected. These results demonstrate that LTC4, LTD4, and LTE4 differentially affect blood flow in the intestine and kidney and suggest that if circulating levels of leukotrienes are increased, blood flow would be expected to be diverted away from the intestine. These data are thus compatible with the hypothesis that leukotrienes may participate in regulation of peripheral regional blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
The T-box gene family: emerging roles in development, stem cells and cancer (2014)

The T-box family of transcription factors exhibits widespread involvement throughout development in all metazoans. T-box proteins are characterized by a DNA-binding motif known as the T-domain that binds DNA in a sequence-specific manner. In humans, mutations in many of the genes within the T-box family result in developmental syndromes, and there is increasing evidence to support a role for these factors in certain cancers. In addition, although early studies focused on the role of T-box factors in early embryogenesis, recent studies in mice have uncovered additional roles in unsuspected places, for example in adult stem cell populations. Here, I provide an overview of the key features of T-box transcription factors and highlight their roles and mechanisms of action during various stages of development and in stem/progenitor cell populations.