gebhart/patrepeval huggingface dataset:
Nuclear morphology measurements with angle-resolved low coherence interferometry for application to cell biology and early cancer detection. (2011)

The study of intact, living cells using non-invasive optical spectroscopic methods offers the opportunity to assess cellular structure and organization in a way that is not possible with commonly used cell biology imaging techniques. We have developed a novel spectroscopic technique for diagnosing disease at the cellular level based on using low-coherence interferometry (LCI) to detect the angular distribution of scattered light. Angle-resolved LCI (a/LCI) combines the ability of LCI to isolate scattering from sub-surface tissue layers with the ability of light scattering spectroscopy to obtain structural information on sub-wavelength scales. In application to examining cellular structure, a/LCI enables quantitative measurements of changes in the size and texture of cell nuclei. These quantitative measurements are characteristic of different pathological states. The capabilities of a/LCI were demonstrated using a clinical system that can be applied in endoscopic surveillance of esophageal tissue, producing high sensitivity and specificity for detecting dysplastic tissues in vivo. Experiments with in vitro cell samples also show the utility of a/LCI in observing structural changes due to environmental stimuli as well as detecting apoptosis due to chemotherapeutic agents.
Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation (2006)

Poor T lymphocyte reconstitution limits the use of haploidentical stem cell transplantation (SCT) because it results in a high mortality from viral infections. One approach to overcome this problem is to infuse donor T cells from which alloreactive lymphocytes have been selectively depleted, but the immunologic benefit of this approach is unknown. We have used an anti-CD25 immunotoxin to deplete alloreactive lymphocytes and have compared immune reconstitution after allodepleted donor T cells were infused at 2 dose levels into recipients of T-cell-depleted haploidentical SCT. Eight patients were treated at 10(4) cells/kg/dose, and 8 patients received 10(5) cells/kg/dose. Patients receiving 10(5) cells/kg/dose showed significantly improved T-cell recovery at 3, 4, and 5 months after SCT compared with those receiving 10(4) cells/kg/dose (P < .05). Accelerated T-cell recovery occurred as a result of expansion of the effector memory (CD45RA(-)CCR-7(-)) population (P < .05), suggesting that protective T-cell responses are likely to be long lived. T-cell-receptor signal joint excision circles (TRECs) were not detected in reconstituting T cells in dose-level 2 patients, indicating they are likely to be derived from the infused allodepleted cells. Spectratyping of the T cells at 4 months demonstrated a polyclonal Vbeta repertoire. Using tetramer and enzyme-linked immunospot (ELISPOT) assays, we have observed cytomegalovirus (CMV)- and Epstein-Barr virus (EBV)-specific responses in 4 of 6 evaluable patients at dose level 2 as early as 2 to 4 months after transplantation, whereas such responses were not observed until 6 to 12 months in dose-level 1 patients. The incidence of significant acute (2 of 16) and chronic graft-versus-host disease (GVHD; 2 of 15) was low. These data demonstrate that allodepleted donor T cells can be safely used to improve T-cell recovery after haploidentical SCT and may broaden the applicability of this approach.
Experimental investigation of the compressibility behaviour of cement-solidified/stabilised zinc-contaminated kaolin clay (2014)

Heavy metal contamination has become a major environmental pollution issue in China, especially under the process of rapid urbanisation. Zinc contaminants are reported to be especially harmful for local ecosystems and biodiversity. In this study, a cement-based solidification/stabilisation technique was adopted to remediate zinc-contaminated kaolin clay and a series of one-dimensional oedometer tests was performed to investigate the compressibility of cement-stabilised zinc-contaminated soils. Compression curves were analysed using a simulation of the logistic function, and the yield stress (σ′ vp ), swelling index (C s ) at the pre-yield state and compression index (C c ) at the post-yield state were derived on the basis of the mathematical simulation. The effects of zinc concentration on σ′ vp , C s and C c are discussed. It is found that relatively high zinc concentrations (i.e. &gt;0·1%) significantly influence the compression parameters and hence deteriorate the resistance to compression of the stabilised soils. The reduction in resistance to compression at high zinc concentrations is intrinsically attributed to the destruction of cementation structure/bonding in the stabilised soils. Physicochemically, this is attributed to the retardation effect of zinc contaminants on cement hydration processes.
Subclasses of cyclic GMP-specific phosphodiesterase and their role in regulating the effects of atrial natriuretic factor. (1990)

Two subclasses of cyclic guanosine monophosphate (GMP)-specific phosphodiesterases were identified in vascular tissue from several beds. The activity of one subclass (phosphodiesterase IB) was stimulated severalfold by calmodulin and selectively inhibited by the phosphodiesterase inhibitor TCV-3B. The activity of the other subclass (phosphodiesterase IC) was not stimulated by calmodulin and was selectively inhibited by the phosphodiesterase inhibitor M&amp;B 22,948. To assess the involvement of both subclasses in regulating cyclic GMP-dependent responses, the ability of TCV-3B and M&amp;B 22,948 to potentiate the in vitro and in vivo responses to the endogenous guanylate cyclase stimulator atrial natriuretic factor (ANF) was evaluated. Both TCV-3B and M&amp;B 22,948 relaxed isolated rabbit aortic and pulmonary artery rings and also potentiated the relaxant effect of ANF. In addition, both inhibitors produced small increases in urine flow and sodium excretion in anesthetized rats and potentiated the diuretic and natriuretic responses to exogenous ANF. M&amp;B 22,948 (30 micrograms/kg/min) produced a threefold increase in the natriuretic response to simultaneously administered ANF, and TCV-3B (10 micrograms/kg/min) produced a twofold increase in the response to ANF. The results of the present experiments suggest that both the calmodulin-sensitive and calmodulin-insensitive subclasses of cyclic GMP-specific phosphodiesterase play a role in regulating the in vitro and in vivo response to ANF.
Amelioration of effects of hypertension and diabetes on myocardium by cardiac glycoside (1992)

To determine whether digoxin protects the myocardium during the initial phases of hypertension and diabetes combined, adult male Wistar rats with two-kidney, one-clip renal hypertension and streptozotocin-induced diabetes mellitus were treated with digoxin (500 micrograms.kg-1.day-1) by gavage for 10 wk immediately after the onset of hypertension and diabetes. Systemic arterial blood pressures, ventricular pressures, the first time derivative of left ventricular pressure, diastolic wall stress, and the quantitative analysis of the number and distribution of myocardial lesions and capillary density of the myocardium were measured. In comparison to untreated hypertensive-diabetic animals, digoxin-treated rats showed a lesser elevation in left ventricular end-diastolic pressure and diastolic and systolic wall stress despite comparable degrees of hypertension and blood glucose levels. In addition, chamber diameter was smaller and the diffusion distance for oxygen was within normal values in animals treated with this glycoside. However, the numerical density of the foci of replacement fibrosis was similar to that found in untreated hypertensive-diabetic animals. In conclusion, digoxin reduces the magnitude of ventricular remodeling and diastolic wall stress in this model of hypertension and diabetes.
Distinct Associations of Motor Domains in Relatives of Schizophrenia Patients—Different Pathways to Motor Abnormalities in Schizophrenia? (2018)

Taken together, schizophrenia patients have motor abnormalities in all tested domains. Thus, motor abnormalities are a key element of the disorder. Likewise, first-degree relatives presented motor deficits in two domains. A clear difference between relatives and healthy controls was found for NSS and FT. Thus, NSS and FT may be potential markers of vulnerability for schizophrenia. The lack of association between genetic risk and dyskinesia or Parkinsonism suggests distinct pathobiological mechanisms in the various motor abnormalities in schizophrenia.
Use of a Liver-Specific Promoter Reduces Immune Response to the Transgene in Adenoviral Vectors (1999)

Previous studies using adenoviral (Ad) vectors expressing human alpha1-antitrypsin (hAAT) under the control of ubiquitous promoters (RSV, mPGK) elicited the production of antibodies to hAAT in some mouse strains (C3H/HeJ and BALB/c) but not in others (C57BL/6J). In contrast, when a helper-dependent Ad vector (AdSTK109) with all viral coding sequences deleted and expressing hAAT from human genomic DNA with the endogenous promoter was used, C3H/HeJ mice failed to develop antibodies and demonstrated long-term expression. These results suggested that promoter choice and/or properties of the vector itself might influence the host immune response to the transgene product. Direct comparison of first-generation vectors expressing the hAAT cDNA from a ubiquitous mouse PGK promoter rather than from a liver-specific mouse albumin promoter demonstrated that an antibody response to hAAT occurred with the mPGK promoter but not with the albumin promoter in C3H/HeJ mice. As expected, neither vector elicits an antibody response in C57BL/6J mice. Coinjection of the two first-generation vectors containing the mPGK and albumin promoter in C3H/HeJ mice induced an antibody response with resulting loss of detectable hAAT from the sera of the injected mice in 3-4 weeks. From these data, we conclude that under certain conditions, the choice of promoter with its associated liver-specific expression can modulate the host immune response to the transgene independent of viral backbone.
Metabolic Clearance Rate of Dehydroepiandrosterone Sulfate, Its Metabolism to Testosterone, and Its Intrafollicular Metabolism to Dehydroepiandrosterone, Androstenedione, Testosterone, and Dihydrotestosteronein Vivo* (1991)

At the time of surgery, women were infused with [3H]dehydroepiandrosterone sulfate ([3H]DS)/[14C]testosterone ([14C]T) for 6 h; blood samples were obtained from an artery the ovarian veins, and a peripheral vein; and fluid was obtained from ovarian follicles. Both blood and follicular fluid samples were analyzed for radioactivity as DS, dehydroepiandrosterone (D), androstenedione (delta 4A). T, and dihydrotestosterone (DHT), and the blood was also analyzed for the concentration of nonisotopic DS by RIA. In other subjects the concentrations of D and DS were measured in paired samples of blood and follicular fluid. From these data, values of 13.6 +/- 0.69 L/day four (mean +/- SE; n = 4) for MCRDS, 607 +/- 90 L/day (n = 3) for MCRT, and 0.0190 +/- 0.0089 (n = 3) for [p]DS-T (fraction of plasma DS metabolized to plasma T) were obtained. The ratio of the concentration of the tracer-labeled steroid in the follicular fluid to the concentration in the arterial plasma sample was elevated significantly above 1 for three 3H-labeled and three [14C-labeled metabolites: [3H]D (21-fold; P less than 0.001), [3H]T (81-fold; P less than 0.001), [3H]DHT (19-fold; P less than 0.001), [14C]T (4-fold; P less than 0.025), [14C]DHT (21-fold; P less than 0.01), and [14C]delta 4A (50-fold; P less than 0.001). The estimated concentrations of steroids in follicular fluid derived from DS based on specific activity calculations were as follows: [geometric mean (95% confidence limits; n)]: DS, 5600 (4800-6500 nmol/L; 12); D, 370 (88-1500 nmol/L; 10); delta 4 A, 120 (67-220 nmol/L; 12); T, 130 (39-450 nmol/L; 10); and DHT, 64 (35-120 nmol/L; 8). Comparison of these data to known follicular fluid steroid concentrations shows that DS from the intravascular pool can be used as an ovarian prehormone.
Persistence of Anaplasma marginale (Rickettsiales: Anaplasmataceae) in Male Dermacentor andersoni (Acari: Ixodidae) Transferred Successively from Infected to Susceptible Calves (1992)

The persistence of Anaplasma marginale Theiler in male Dermacentor andersoni Stiles ticks exposed to the organism as adults was studied as the ticks were successively transferred to five susceptible calves. All calves fed upon by these ticks rapidly developed clinical anaplasmosis; incubation periods of infection ranged from 19 to 26 d and did not change significantly with successive feedings. Development of A. marginale in tick midgut and salivary glands was followed daily during tick feeding (total, 35 d) with light microscopy and DNA hybridization. With microscopy, A. marginale colonies persisted in midgut cells throughout the experiment. Large colonies were observed in gut muscle cells on days 8 through 35 and were the predominant infected cell type during this part of feeding. Colonies were seen in salivary gland acini from day 2 throughout the 35-d experiment. The DNA probe confirmed the presence of Anaplasma DNA in midgut and salivary glands throughout the experiment. Quantitative estimates of infection intensity in tissues of individual ticks approximated 10(7) initial body equivalents, confirming heavy infections. A marginale in midgut tissues decreased with feeding time, whereas the estimated number of organisms in salivary glands remained constant. These data demonstrate that D. andersoni males are efficient vectors of A. marginale and may be potential reservoirs of infection for ruminants for extended periods.
Trastuzumab-DM1 causes tumour growth inhibition by mitotic catastrophe in trastuzumab-resistant breast cancer cells in vivo (2011)

Our results suggest mitotic catastrophe as a previously undescribed mechanism of action of T-DM1. T-DM1 was found effective even on breast cancer cell lines with moderate HER2 expression levels and cross-resistance to trastuzumab and lapatinib (MDA-453 and JIMT-1).
Methanogenic Flora Is Associated With Altered Colonic Transit but Not Stool Characteristics in Constipation Without IBS (2009)

Presence of methanogenic flora is associated with CC. Methane production after carbohydrate challenge and its prevalence were higher in ST than NT, although stool characteristics were similar in both groups. Methane production correlated with colonic transit, suggesting an association with stool transport but not with stool characteristics.
Modification of spontaneous emission lifetimes in the presence of corrugated metallic surfaces (1999)

We report the results of measurements of the spontaneous emission lifetime of a ${\mathrm{Eu}}^{3+}$ complex in the presence of a nearby metal surface. The excited-state lifetime of the ions are measured as a function of their separation from both planar and periodically corrugated metallic surfaces. Several corrugated silver surfaces were used, each having a different combination of pitch and amplitude. No significant difference is found between data obtained for ions situated above a planar silver surface and those above corrugated surfaces that have pitches greater than the emission wavelength. However, for surfaces with a pitch less than the emission wavelength, differences are seen, and are shown to increase with increasing corrugation amplitude. Possible explanations for the observed differences are given, including a discussion of the role of surface plasmon polariton modes on corrugated metallic surfaces.
Autoimmunity in inflammatory bowel disease: a case of ulcerative colitis with diabetes mellitus, autoimmune hepatitis and autoimmune hypothyroidism. (2014)

Ulcerative colitis (UC) is a form of inflammatory bowel disease, which occasionally can be associated with autoimmune disorders. Herein, a two-year-old male infant with UC under sulfasalazine therapy is presented, who consequently developed type I diabetes mellitus, autoimmune hepatitis and autoimmune hypothyroidism. Although presence of concurrent autoimmune diseases with UC is a rare condition, it could highlight the role of immune-related mechanisms as a pathogenesis of disease.
Minocycline inhibits caspase-independent and -dependent mitochondrial cell death pathways in models of Huntington's disease (2003)

Minocycline is broadly protective in neurologic disease models featuring cell death and is being evaluated in clinical trials. We previously demonstrated that minocycline-mediated protection against caspase-dependent cell death related to its ability to prevent mitochondrial cytochrome c release. These results do not explain whether or how minocycline protects against caspase-independent cell death. Furthermore, there is no information on whether Smac/Diablo or apoptosis-inducing factor might play a role in chronic neurodegeneration. In a striatal cell model of Huntington's disease and in R6/2 mice, we demonstrate the association of cell death/disease progression with the recruitment of mitochondrial caspase-independent (apoptosis-inducing factor) and caspase-dependent (Smac/Diablo and cytochrome c) triggers. We show that minocycline is a drug that directly inhibits both caspase-independent and -dependent mitochondrial cell death pathways. Furthermore, this report demonstrates recruitment of Smac/Diablo and apoptosis-inducing factor in chronic neurodegeneration. Our results further delineate the mechanism by which minocycline mediates its remarkably broad neuroprotective effects.
Small-molecule inhibitors of the human epidermal receptor family (2009)

Recent data have highlighted the importance of mutations and amplifications of receptors within the HER family. Amplification of HER2 often translates into responses in anti-HER2 therapy. Mutations either enhance sensitivity or confer resistance to small-molecule inhibitors. Other mechanisms of resistance are being elucidated which should lead to the ability to predict both responses and resistance to HER family inhibitors and should translate into improvements in patient care.
Specific killing of lymphoma cells by cytotoxic T-cells mediated by a bispecific diabody (1996)

Antibody fragments produced by bacterial fermentation lack natural effector functions. Bispecific antibody fragments, however, can be endowed with effector functions, for example cell-mediated killing, by binding to and retargeting of cytotoxic cells. Diabodies are a class of engineered antibody fragments with two antigen binding sites, consisting of two associated chains; each chain consists of heavy and light chain variable domains linked by a short polypeptide linker. In contrast to IgG, or other antibody fragments in which the two binding sites can take up a range of orientations and spacings, the diabody structure is more rigid and compact, with the two binding sites separated by 65 łA (less than half the distance in IgG). To establish whether diabodies could also be used in cell-mediated killing, we have explored the use of a bispecific diabody binding to an idiotypic marker on mouse B-cell lymphoma (BCL-1) and to mouse CD3. The bispecific diabody activated naive T-cells and also mediated the specific killing of the lymphoma cells by cytotoxic T-cells. The diabody was less active in T-cell activation but 10-fold more active (w/v) in killing than an analogous bispecific IgG.
Coherent imaging of biological samples with femtosecond pulses at the free-electron laser FLASH (2010)

Coherent x-ray imaging represents a new window to imaging non-crystalline, biological specimens at unprecedented resolutions. The advent of free-electron lasers (FEL) allows extremely high flux densities to be delivered to a specimen resulting in stronger scattered signal from these samples to be measured. In the best case scenario, the diffraction pattern is measured before the sample is destroyed by these intense pulses, as the processes involved in radiation damage may be substantially slower than the pulse duration. In this case, the scattered signal can be interpreted and reconstructed to yield a faithful image of the sample at a resolution beyond the conventional radiation damage limit. We employ coherent x-ray diffraction imaging (CXDI) using the free-electron LASer in Hamburg (FLASH) in a non-destructive regime to compare images of a biological sample reconstructed using different, single, femtosecond pulses of FEL radiation. Furthermore, for the first time, we demonstrate CXDI, in-line holography and Fourier transform holography (FTH) of the same unicellular marine organism using an FEL and present diffraction data collected using the third harmonic of FLASH, reaching into the water window. We provide quantitative results for the resolution of the CXDI images as a function of pulse intensity, and compare this with the resolutions achieved with in-line holography and FTH.
Biosynthesis of Proteins Incorporating a Versatile Set of Phenylalanine Analogues (2002)

Unnatural amino acids with useful chemical functionality can replace phenylalanine in bacterial proteins. Coexpression of a promiscuous phenylalanine-tRNA synthetase mutant enables the synthesis of target proteins bearing iodophenyl, cyanophenyl, ethynylphenyl, azidophenyl, and pyridyl groups (see general structures). Proteins incorporating the analogues have a range of potential applications, including Pd-mediated conjugation (R=CCH), photoaffinity labeling (R=N3), X-ray phasing (R=I), and novel metal coordination (R=pyridyl). Supporting information for this article is available on the WWW under http://www.chembiochem.com or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Serum thymulin in human zinc deficiency. (1988)

The activity of thymulin (a thymic hormone) is dependent on the presence of zinc in the molecule. We assayed serum thymulin activity in three models of mildly zinc-deficient (ZD) human subjects before and after zinc supplementation: (a) two human volunteers in whom a specific and mild zinc deficiency was induced by dietary means; (b) six mildly ZD adult sickle cell anemia (SCA) subjects; and (c) six mildly ZD adult non-SCA subjects. Their plasma zinc levels were normal and they showed no overt clinical manifestations of zinc deficiency. The diagnosis of mild zinc deficiency was based on the assay of zinc in lymphocytes, granulocytes, and platelets. Serum thymulin activity was decreased as a result of mild zinc deficiency and was corrected by in vivo and in vitro zinc supplementation, suggesting that this parameter was a sensitive indicator of zinc deficiency in humans. An increase in T101-, sIg-cells, decrease in T4+/T8+ ratio, and decreased IL 2 activity were observed in the experimental human model during the zinc depletion phase, all of which were corrected after repletion with zinc. Similar changes in lymphocyte subpopulation, correctable with zinc supplementation, were also observed in mildly ZD SCA subjects. Inasmuch as thymulin is known to induce intra- and extrathymic T cell differentiation, our studies provide a possible mechanism for the role of zinc on T cell functions.
Olanzapine in the Treatment of Behavioral Problems Associated with Autism: An Open-Label Trial in Kuwait (2008)

The study shows that olanzapine treatment can be beneficial in alleviating some behavioral symptoms (irritability, hyperactivity/noncompliance and lethargy/withdrawal) associated with autism. The short period of this trial limits inferences about adverse effects such as body weight increase and tardive dyskinesia. Further long-term placebo-controlled studies of olanzapine are required.