gebhart/patrepeval huggingface dataset:
Fibroblast-dependent induction of a murine skin lesion similar to human nevus sebaceus of Jadassohn. (1997)

Using a nude mouse grafting model, we have demonstrated that normal-haired skin is regenerated in a graft containing hair buds and dissociated dermis. Altering the dermal component leads to changes typical of the human nevus sebaceus of Jadassohn (NSJ). The murine lesion is characterized by sebaceous gland hyperplasia, abortive hair follicles, and epidermal hyperplasia. The development of the NSJ-like lesion is independent of the epidermal component but dependent on a specific dermal fibroblast combination, namely, a hair-inductive follicular papilla fibroblast cell line plus BALB/c 3T3 fibroblasts. Non-hair-inductive follicular papilla cell lines in combination with BALB/c 3T3 fibroblasts are unable to induce the NSJ-like structure, indicating that hair-inductive signals play a central role in its pathogenesis. BALB/c 3T3 fibroblasts in combination with total cells from dissociated neonatal dermis produce abortive hair follicles, but the sebaceous gland hyperplasia is suppressed, suggesting the presence of suppressive endogenous dermal factors. The data suggest that (a) pilosebaceous induction is a multistep process and (b) the pathogenesis of NSJ involves perturbation of a complex array of inductive mesenchymal (dermal) signals. This paper describes the first animal model of NSJ and provides evidence that development of the human lesion could depend entirely on aberrant dermal cells.
Poliovirus concentration from tap water with electropositive adsorbent filters (1980)

Simple, reliable, and efficient concentration of poliovirus from tap water was obtained with two types of electropositive filter media, one of which is available in the form of a pleated cartridge filter (Virozorb 1MDS). Virus adsorption from tap water between pH 3.5 and 7.5 was more efficient with electropositive filters than with Filterite filters. Elution of adsorbed viruses was more efficient with beef extract in glycine, pH 9.5, than with glycine-NaOH, pH 11.0. In paired comparative studies, electropositive filters, with adsorption at pH 7.5 and no added polyvalent cation salts, gave less variable virus concentration efficiencies than did Filterite filters with adsorption at pH 3.5 plus added MgCl2. Recovery of poliovirus from 1,000-liter tap water volumes was approximately 30% efficient with both Virozorb 1MDS and Filterite pleated cartridge filters, but the former were much simpler to use. The virus adsorption behavior of these filters appears to be related to their surface charge properties, with more electropositive filters giving more efficient virus adsorption from tap water at higher pH levels.
Ocular biodistribution of bevasiranib following a single intravitreal injection to rabbit eyes. (2008)

These studies demonstrate distribution of bevasiranib throughout the eye following intravitreal injection, including extensive uptake into the retina.
UniNovo: a universal tool for de novo peptide sequencing (2013)

UniNovo is implemented in JAVA and tested on Windows, Ubuntu and OS X machines. UniNovo is available at http://proteomics.ucsd.edu/Software/UniNovo.html along with the manual.
Quantitative Measure for the “Nakedness” of Fluoride Ion Sources (2003)

A quantitative measure for the donor strength or "nakedness" of fluoride ion donors is presented. It is based on the free energy change associated with the transfer of a fluoride ion from the donor to a given acceptor molecule. Born-Haber cycle calculations were used to calculate both the free energy and the enthalpy change for this process. The enthalpy change is given by the sum of the fluoride ion affinity of the acceptor (as defined in strict thermodynamic convention) and the lattice energy difference (DeltaU(POT)) between the fluoride ion donor and the salt formed with the acceptor. Because, for a given acceptor, the fluoride affinity has a constant value, the relative enthalpy (and also the corresponding free energy) changes are governed exclusively by the lattice energy differences. In this study, BF(3), PF(5), AsF(5), and SbF(5) were used as the acceptors, and the following seven fluoride ion donors were evaluated: CsF, N(CH(3))(4)F (TMAF), N-methylurotropinium fluoride (MUF), hexamethylguanidinium fluoride (HMGF), hexamethylpiperidinium fluoride (HMPF), N,N,N-trimethyl-1-adamantylammonium fluoride (TMAAF), and hexakis(dimethylamino)phosphazenium fluoride (HDMAPF). Smooth relationships between the enthalpy changes and the molar volumes of the donor cations were found which asymptotically approach constant values for infinitely large cations. Whereas CsF is a relatively poor F(-) donor [(U(POT)(CsF) - U(POT)(CsSbF(6))) = 213 kJ mol(-)(1)], when compared to N(CH(3))(4)F [(U(POT)(TMAF) - U(POT)(TMASbF(6))) = 69 kJ mol(-)(1)], a 4 times larger cation (phosphazenium salt) and an infinitely large cation are required to decrease DeltaU(POT) to 17 and 0 kJ mol(-)(1), respectively. These results clearly demonstrate that very little is gained by increasing the cation size past a certain level and that secondary factors, such as chemical and physical properties, become overriding considerations.
Gadolinium-Loaded Polychelating Polymer-Containing Cancer Cell-Specific Immunoliposomes (2006)

Liposome loading with Gd via the membrane-incorporated polychelating amphiphilic polymers (PAPs) significantly increases the Gd content and relaxivity (T1 parameter) of PEGylated liposomes, which can be used as contrast agents for magnetic resonance imaging (MRI). Here, we demonstrate that such Gd-containing liposomes can be additionally modified with the monoclonal anticancer antibody 2C5 (mAb 2C5) possessing the nucleosome(NS)-restricted specificity via the PEG spacer. Liposome-bound antibody preserves its specific activity (ELISA) and such Gd-loaded PEGylated 2C5-immunoliposomes specifically recognize various cancer cells in vitro and target an increased amount of Gd to their surface compared to antibody-free Gd-liposomes or Gd-liposomes modified with tumor nonspecific antibody. Gd-loaded cancer cell-targeted immunoliposomes may represent promising agents for enhanced tumor MRI.
L-743, 726 (DMP-266): a novel, highly potent nonnucleoside inhibitor of the human immunodeficiency virus type 1 reverse transcriptase (1995)

The clinical benefit of the human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) is limited by the rapid selection of inhibitor-resistant viral variants. However, it may be possible to enhance the clinical utility of this inhibitor class by deriving compounds that express both high levels of antiviral activity and an augmented pharmacokinetic profile. Accordingly, we developed a new class of NNRTIs, the 1, 4-dihydro-2H-3, 1-benzoxazin-2-ones. L-743, 726 (DMP-266), a member of this class, was chosen for clinical evaluation because of its in vitro properties. The compound was a potent inhibitor of the wild-type HIV-1 RT (Ki = 2.93 nM) and exhibited a 95% inhibitory concentration of 1.5 nM for the inhibition of HIV-1 replicative spread in cell culture. In addition, L-7743, 7726 was found to be capable of inhibiting, with 95% inhibitory concentrations of < or = 1.5 microM, a panel of NNRTI-resistant mutant viruses, each of which expressed a single RT amino acid substitution. Derivation of virus with notably reduced susceptibility to the inhibitor required prolonged cell culture selection and was mediated by a combination of at least two RT amino acid substitutions. Studies of L-743, 726 in rats, monkeys, and a chimpanzee demonstrated the compound's potential for good oral bioavailability and pharmacokinetics in humans.
Interaction of povidone-iodine compounds, phagocytic cells, and microorganisms (1982)

The interaction between povidone-iodine, phagocytic cells, and microorganisms was studied. Three preparations of povidone-iodine were investigated: commercially available povidone-iodine solution Betadine, pure high-molecular-weight povidone-iodine as used in Betadine, and a low-molecular-weight povidone-iodine. Low concentrations of povidone-iodine (approximately 0.005%) have considerable activity in vitro. The concentrations used clinically (0.1 to 20%) are toxic for granulocytes and monocytes. Leukocytes reduce the in vitro microbicidal activity of povidone-iodine. No differences of any importance were found between the three preparations of povidone-iodine.
Estrogen Stimulates Neuronal Nitric Oxide Synthase Protein Expression in Human Neutrophils (1999)

Recent studies have postulated the contribution of nitric oxide (NO) released by the endothelium to the beneficial effects of estrogen. Despite a neuronal-type NO synthase (nNOS) described in neutrophils, less is known about the effect of estrogen in these cells. The aim of the present study was to analyze the expression of nNOS protein in human neutrophils under different estrogenic conditions. We first analyzed nNOS expression in neutrophils obtained from premenopausal women. During the first 2 days of the follicular phase (low circulating estrogen concentrations), nNOS expression in neutrophils was reduced with respect to that found in neutrophils obtained from the same donors during the ovulatory phase (high circulating estrogen concentrations). Moreover, the expression of nNOS protein in neutrophils obtained from postmenopausal women after transdermal estrogen therapy was markedly enhanced with respect to that observed before the treatment. In vitro incubation of neutrophils derived from men for 6 hours with 17beta-estradiol (10(-10) to 10(-8) mol/L) upregulated the expression of nNOS protein. The 17beta-estradiol receptor antagonists, tamoxifen (10(-8) mol/L) and ICI 182780 (10(-8) mol/L), inhibited the upregulation of nNOS protein induced by 17beta-estradiol. The putative functional implication was denoted by a reduced expression of the CD18 antigen on the surface of 17beta-estradiol-incubated neutrophils, which was accompanied by a decreased adhesive capacity. Both effects were prevented by an NO antagonist. In conclusion, the in vivo levels of circulating estrogen concentrations seem to be associated with the level of nNOS protein expression in neutrophils from women. Moreover, low doses of 17beta-estradiol upregulate nNOS protein expression in neutrophils from men. The increased ability of 17beta-estradiol-incubated neutrophils derived from men to produce NO reduced their adhesive properties.
Homogeneous chemical derivatisation of carbon particles: a novel method for funtionalising carbon surfaces (2002)

The homogeneous reduction of diazonium salts by hypophosphorous acid, provides an easy methodology for the derivatisation of carbon powder. The resulting derivatised carbon was characterised electrochemically showing the behaviour expected of a surface bound species. This procedure provides an easy, inexpensive methodology for functionalising carbon which might find applications in ion-exchange resins or combinatorial chemistry.
Automatic and Robust Delineation of the Fiducial Points of the Seismocardiogram Signal for Noninvasive Estimation of Cardiac Time Intervals (2016)

The presented algorithm could be used for accurate and non-invasive estimation of cardiac time intervals.
Transcriptome Analysis Reveals Distinct Patterns of Long Noncoding RNAs in Heart and Plasma of Mice with Heart Failure (2013)

We reveal stable expression of LncRNAs in plasma during HF, which suggests a newly described component in plasma. The distinct expression patterns of circulatory LncRNAs during HF indicate that LncRNAs may actively respond to stress and thus serve as biomarkers of HF diagnosis and treatment.
Increased bioavailability and improved efficacy, in severe psoriasis, of a new microemulsion formulation of cyclosporin* (1996)

Cyclosporin, as the microemulsion formulation Neoral, was given to two groups of patients with severe psoriasis (Psoriasis Area and Severity Index: PASI > 12.0). Group A (10 patients) were receiving the traditional formulation of cyclosporin, Sandimmun, at the start of the study, with a partial clinical response, and were switched to Neoral at the same dose (3.3 mg/kg per day). Group B patients, who had previously been treated with Sandimmun but were treatment failures, were given Neoral, 3.5 mg/kg per day. This led to rapid improvement in psoriasis in both groups. In Group A mean PASI fell from 22.3 to 11.6 on Sandimmun, after 82 +/- 30 weeks, and to 4.0 (P < 0.05) after 32 weeks of Neoral. In Group B mean PASI decreased from 20.3 to 3.7 (P < 0.05) at a dose of 3.1 mg/kg per day. Pharmacokinetic data demonstrated significant decrease in tmax from 2.3 to 1.4 hours. After 2 weeks Cmax and the area under the curve (AUC) (0-4 h) were significantly increased by 41% and 61%, respectively. Further pharmacokinetic data at 3 months showed similar results. No significant changes in renal function from pre-treatment status were seen in either group. None of the patients developed hypertension. No serious adverse events were reported. The microemulsion formulation of cyclosporin showed greater efficacy and bioavailability. Improved outcome was seen at doses which were on average 15% lower than with the traditional formulation, leading to a reduction in cost of treatment.
Archaic African and Asian lineages in the genetic ancestry of modern humans. (1997)

A 3-kb region encompassing the beta-globin gene has been analyzed for allelic sequence polymorphism in nine populations from Africa, Asia, and Europe. A unique gene tree was constructed from 326 sequences of 349 in the total sample. New maximum-likelihood methods for analyzing gene trees on the basis of coalescence theory have been used. The most recent common ancestor of the beta-globin gene tree is a sequence found only in Africa and estimated to have arisen approximately 800,000 years ago. There is no evidence for an exponential expansion out of a bottlenecked founding population, and an effective population size of approximately 10,000 has been maintained. Modest differences in levels of beta-globin diversity between Africa and Asia are better explained by greater African effective population size than by greater time depth. There may have been a reduction of Asian effective population size in recent evolutionary history. Characteristically Asian ancestry is estimated to be older than 200,000 years, suggesting that the ancestral hominid population at this time was widely dispersed across Africa and Asia. Patterns of beta-globin diversity suggest extensive worldwide late Pleistocene gene flow and are not easily reconciled with a unidirectional migration out of Africa 100,000 years ago and total replacement of archaic populations in Asia.
A liver microphysiological system of tumor cell dormancy and inflammatory responsiveness is affected by scaffold properties (2016)

Distant metastasis is the major cause of breast cancer-related mortality, commonly emerging clinically after 5 or more years of seeming 'cure' of the primary tumor, indicating a quiescent dormancy. The lack of relevant accessible model systems for metastasis that recreate this latent stage has hindered our understanding of the molecular basis and the development of therapies against these lethal outgrowths. We previously reported on the development of an all-human 3D ex vivo hepatic microphysiological system that reproduces several features of liver physiology and enables spontaneous dormancy in a subpopulation of breast cancer cells. However, we observed that the dormant cells were localized primarily within the 3D tissue, while the proliferative cells were in contact with the polystyrene scaffold. As matrix stiffness is known to drive inflammatory and malignant behaviors, we explored the occurrence of spontaneous tumor dormancy and inflammatory phenotype. The microphysiological system was retrofitted with PEGDa-SynKRGD hydrogel scaffolding, which is softer and differs in the interface with the tissue. The microphysiological system incorporated donor-matched primary human hepatocytes and non-parenchymal cells (NPCs), with MDA-MB-231 breast cancer cells. Hepatic tissue in hydrogel scaffolds secreted lower levels of pro-inflammatory analytes, and was more responsive to inflammatory stimuli. The proportion of tumor cells entering dormancy was markedly increased in the hydrogel-supported tissue compared to polystyrene. Interestingly, an unexpected differential response of dormant cells to varying chemotherapeutic doses was identified, which if reflective of patient pathophysiology, has important implications for patient dosing regimens. These findings highlight the metastatic microphysiological system fitted with hydrogel scaffolds as a critical tool in the assessment and development of therapeutic strategies to target dormant metastatic breast cancer.
Stereospecific elimination of hydrogen at C-10 in eicosapentaenoic acid during the conversion to leukotriene C5. (1983)

(10L)- and (10D)-[1-14C, 10-3H]5,8,11,14,17-eicosapentaenoic acids were synthesized to investigate mechanistic and stereochemical aspects of leukotriene biosynthesis. Experiments with mastocytoma cells showed that a hydrogen is stereospecifically eliminated from C-10 during the conversion of eicosapentaenoic acid to leukotriene C5. The hydrogen lost has the pro-S (D) configuration. 5-Hydroxy-6,8,11,14,17-eicosapentaenoic acid, formed in the same experiments, was enriched in tritium when the (10D), but not when the (10L), isomer of labeled eicosapentaenoic acid was used. This indicates that oxygenation of the acid at C-5 occurred before the elimination of hydrogen and suggests that removal of the pro-S hydrogen at C-10 in 5-hydroperoxy-6,8,11,14,17-eicosapentaenoic acid initiates its transformation to trans-5(S),6(S)-oxido-7,9-trans-11,14,17-cis-eicosapentaenoic acid (leukotriene A5).
Interleukin-4-Dependent Pulmonary Eosinophil Infiltration in a Murine Model of Asthma (1994)

The establishment of animal models of asthma is critical to elucidate the mechanisms involved in the pathogenesis of the disease. In the present study, we have used a parasite antigen from Schistosoma mansoni eggs, which induces a TH2 response, to elicit a pulmonary inflammatory reaction that resolves after 3 to 4 days. Histologic examination of the lungs of soluble egg antigens (SEA) or saline vehicle-challenged mice demonstrated a large influx of cells in the antigen- but not vehicle-challenged mice, thus demonstrating an antigen-specific reaction. A characteristic influx of eosinophils could be detected as early as 8 h, with significant increases at 24 to 72 h after challenge. An assessment of the bronchial alveolar lavage (BAL) fluid demonstrated dominant neutrophil infiltration at 8 h, with a subsequent decrease to background by 48 h. In addition, peak monocyte infiltration occurred at 24 h, and peak eosinophil extravasation into the airway was shown at 48 h. The examination of leukocyte infiltrates in the interstitium in dispersed lung preparations again demonstrated early neutrophil and monocyte infiltration at 8 h after challenge, with increases in lymphocyte and eosinophil infiltrates at 24 h. Examination of interleukin-4 (IL-4) production in the BAL fluid demonstrated the presence of IL-4 early in the response, with levels peaking between 8 and 24 h after antigen challenge, with no detectable IL-4 in the saline vehicle-challenged mice. Mice treated with anti-IL-4 antibodies demonstrated a tenfold decrease in BAL eosinophil influx at 48 h after challenge and a reduction in total pulmonary leukocyte cellularity.(ABSTRACT TRUNCATED AT 250 WORDS)
Magnetic Tracking System for Radiation Therapy (2010)

Intensity-modulated radiation therapy (IMRT) requires precise delivery of the prescribed dose of radiation to the target and surrounding tissue. Irradiation of moving body anatomy is possible only if stable, accurate, and reliable information about the moving body structures are provided in real time. This paper presents a magnetic position tracking system for radiation therapy. The proposed system uses only four transmitting coils and an implantable transponder. The four transmitting coils generate a magnetic field which is sensed and measured by a biaxial magnetoresistive sensor in the transponder in the tumor. The transponder transmits the information back to a computer to determine the position of the transponder allowing it to track the tumor in real time. The transmission of the information from the transponder to the computer can be wired or wireless. Measurements using a biaxial sensor agree well with the field strength calculated from the ideal equations. The translation from the measurement data to the 3-D location and orientation requires a numerical technique because the equations are in nonclosed forms. The algorithm of tracking is implemented using MATLAB. Each calculation of the position along the target trajectory takes 30 ms, which makes the proposed system suitable for real-time tracking of the transponder for radiation assessment and delivery. An error of less than 2 mm is achieved in the demonstration.
Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin (2008)

The rod and cone cells of the mammalian retina are the principal photoreceptors for image-forming vision. They transmit information by means of a chain of intermediate cells to the retinal ganglion cells, which in turn send signals from the retina to the brain. Loss of photoreceptor cells, as happens in a number of human diseases, leads to irreversible blindness. In a mouse model (rd/rd) of photoreceptor degeneration, we used a viral vector to express in a large number of retinal ganglion cells the light sensitive protein melanopsin, normally present in only a specialized subset of the cells. Whole-cell patch-clamp recording showed photoresponses in these cells even after degeneration of the photoreceptors and additional pharmacological or Cd(2+) block of synaptic function. Interestingly, similar responses were observed across a wide variety of diverse types of ganglion cell of the retina. The newly melanopsin-expressing ganglion cells provided an enhancement of visual function in rd/rd mice: the pupillary light reflex (PLR) returned almost to normal; the mice showed behavioral avoidance of light in an open-field test, and they could discriminate a light stimulus from a dark one in a two-choice visual discrimination alley. Recovery of the PLR was stable for at least 11 months. It has recently been shown that ectopic retinal expression of a light sensitive bacterial protein, channelrhodopsin-2, can restore neuronal responsiveness and simple visual abilities in rd/rd mice. For therapy in human photodegenerations, channelrhodopsin-2 and melanopsin have different advantages and disadvantages; both proteins (or modifications of them) should be candidates.
Peripheral Nerve Field Stimulation for Chronic Pain: 100 Cases and Review of the Literature (2011)

This prospective 100 consecutive PNFS patient outcome study demonstrates that PNFS can be a safe and effective treatment option for, otherwise, intractable chronic pain conditions. PNFS has the potential to fundamentally change the way we think about pain management.