gebhart/patrepeval huggingface dataset:
The anti‐emetic effects of CP‐99,994 in the ferret and the dog: role of the NK1 receptor (1995)

1. The selective NK1 receptor antagonist, CP-99,994, produced dose-related (0.1-1.0 mg kg-1, s.c.) inhibition of vomiting and retching in ferrets challenged with central (loperamide and apomorphine), peripheral (CuSO4) and mixed central and peripheral (ipecac, cisplatin) emetic stimuli. 2. Parallel studies with the enantiomer, CP-100,263 (1 mg kg-1, s.c.), which is > 1,000 fold less potent as a NK1 antagonist, indicated that it was without significant effect against CuSO4, loperamide, cisplatin and apomorphine-induced emesis. Against ipecac, it inhibited both retching and vomiting, expressing approximately 1/10th the potency of CP-99,994. 3. The 5-HT3 receptor antagonist, tropisetron (1 mg kg-1, s.c.) inhibited retching and vomiting to cisplatin and ipecac, but not CuSO4 or loperamide. 4. CP-99,994 (1 mg kg-1, i.v.) blocked retching induced by electrical stimulation of the ventral abdominal vagus without affecting the cardiovascular response, the apnoeic response to central vagal stimulation or the guarding and hypertensive response to stimulation of the greater splanchnic nerves. CP-99,994 (1 mg kg-1, i.v.) did not alter baseline cardiovascular and respiratory parameters and it failed to block the characteristic heart rate, blood pressure and respiratory rate/depth changes in response to i.v. 2-methyl-5-HT challenge (von Bezold-Jarisch reflex). 5. Using in vitro autoradiography, [3H]-substance P was shown to bind to several regions of the ferret brainstem with the density of binding in the nucleus tractus solitarius being much greater than in the area postrema. This binding was displaced by CP-99,994 in a concentration-related manner. 6. In dogs, CP-99,994 (40 micrograms kg-1 bolus and 300 micrograms kg-1 h-1, i.v.) produced statistically significant reductions in vomiting to CuSO4 and apomorphine as well as retching to CuSO4. 7. Together, these studies support the hypothesis that the NK1 receptor antagonist properties of CP-99,994 are responsible for its broad spectrum anti-emetic effects. They also suggest that CP-99,994 acts within the brainstem, most probably within the nucleus tractus solitarius although the involvement of the area postrema could not be excluded.
Optimization of 454 Sequencing Library Preparation from Small Amounts of DNA Permits Sequence Determination of Both DNA Strands (2009)

To increase the yield of DNA sequence generated by the 454 technology from small amounts of starting DNA, we investigated the efficiency of each step in the 454 library preparation process. We find that the last step, when the single-stranded library is released by NaOH, is inefficient and highly variable. When this step is replaced with heat treatment, library amounts dramatically increase. Furthermore, when sequencing templates are first isolated by NaOH treatment and subsequently by heat treatment, the sequences of both strands of individual template DNA molecules can be determined. Using this approach, we confirm that C/G base pairs observed as T/A base pairs in Neanderthal DNA sequences are due to a modification of the cytosine rather than guanine residues.
Baculovirus Expression of the Human Papillomavirus Type 16 Capsid Proteins: Detection of L1-L2 Protein Complexes (1991)

The human papillomavirus (HPV) type 16 major capsid proteins L1 and L2 have been produced in a baculovirus expression system. Both proteins are expressed at a high level and can be readily solubilized. The L1 capsid protein migrates close to its expected Mr of 60K. On the other hand L2 exhibits a much higher Mr migrating at 73K, which is considerably greater than its predicted Mr of 50K. The identity of both proteins has been confirmed also by Western blot analysis. Both proteins are produced in drastically reduced amounts in the presence of tunicamycin. In addition both L1 and L2 show interesting patterns of phosphorylation. L1 is phosphorylated only weakly and this appears to be quite labile, whereas L2 is very heavily phosphorylated and this, in contrast, appears to be very stable. We have also made use of a dual expression vector for co-expressing the L1 and L2 proteins within the same baculovirus-infected cell. The results obtained from this system demonstrate the presence of protein complexes forming between the two capsid proteins. These studies indicate that at least the initial events in capsid assembly of HPVs can occur in the absence of viral DNA.
Livenet: Health and lifestyle networking through distributed mobile devices (2004)

Incorporating new healthcare technologies for proactive health and elder care will become a major priority over the next decade, as medical care systems world-wide become strained by the aging boomer population. We present MIThril LiveNet, a flexible distributed mobile platform that can be deployed for a variety of proactive healthcare applications. The LiveNet system allows people to receive real-time feedback from their continuously monitored and analyzed health state, as well as communicate health information with care-givers and other members of an individual’s social network for support and interaction.
Semi-supervised learning of multi-factor models for face de-identification (2008)

With the emergence of new applications centered around the sharing of image data, questions concerning the protection of the privacy of people visible in the scene arise. Recently, formal methods for the de-identification of images have been proposed which would benefit from multi-factor coding to separate identity and non-identity related factors. However, existing multi-factor models require complete labels during training which are often not available in practice. In this paper we propose a new multi-factor framework which unifies linear, bilinear, and quadratic models. We describe a new fitting algorithm which jointly estimates all model parameters and show that it outperforms the standard alternating algorithm. We furthermore describe how to avoid overfitting the model and how to train the model in a semi-supervised manner. In experiments on a large expression-variant face database we show that data coded using our multi-factor model leads to improved data utility while providing the same privacy protection.
Class Switching in B Cells Lacking 3′ Immunoglobulin Heavy Chain Enhancers (1998)

The 40-kb region downstream of the most 3' immunoglobulin (Ig) heavy chain constant region gene (Calpha) contains a series of transcriptional enhancers speculated to play a role in Ig heavy chain class switch recombination (CSR). To elucidate the function of this putative CSR regulatory region, we generated mice with germline mutations in which one or the other of the two most 5' enhancers in this cluster (respectively referred to as HS3a and HS1,2) were replaced either with a pgk-neor cassette (referred to as HS3aN and HS1,2N mutations) or with a loxP sequence (referred to as HS3aDelta and HS1,2Delta, respectively). B cells homozygous for the HS3aN or HS1,2N mutations had severe defects in CSR to several isotypes. The phenotypic similarity of the two insertion mutations, both of which were cis-acting, suggested that inhibition might result from pgk-neor cassette gene insertion rather than enhancer deletion. Accordingly, CSR returned to normal in B cells homozygous for the HS3aDelta or HS1,2Delta mutations. In addition, induced expression of the specifically targeted pgk-neor genes was regulated similarly to that of germline CH genes. Our findings implicate a 3' CSR regulatory locus that appears remarkably similar in organization and function to the beta-globin gene 5' LCR and which we propose may regulate differential CSR via a promoter competition mechanism.
Management of the Brown Recluse Spider Bite to the Glans Penis (1996)

A significant number of people are bitten by the brown recluse spider (BRS) each year. Medical treatment regimens are sometimes unsatisfactory and surgical intervention is often necessary to debride the necrotic wound. This case study reports the treatment given to a 19-year-old active duty United States Army soldier who suffered a BRS bite to the glans penis. This patient received immediate medical attention and was started on intravenously administered diphenhydramine, methylprednisolone, calcium gluconate, and famotidine. Oral dapsone treatment was begun in the emergency room. Within 24 hours after his injury, the patient received his first hyperbaric oxygen treatment, which was continued twice daily for 5 days. Skin necrosis was avoided, the patient did not require any surgical intervention, and he was discharged after 8 days without sequelae.
A framework for semantic gossiping (2002)

Today the problem of semantic interoperability in information search on the Internet is solved mostly by means of centralization, both at a system and at a logical level. This approach has been successful to a certain extent. Peer-to-peer systems as a new brand of system architectures indicate that the principle of decentralization might offer new solutions to many problems that scale well to very large numbers of users.In this paper we outline how the peer-to-peer system architectures can be applied to tackle the problem of semantic interoperability in the large, driven in a bottom-up manner by the participating peers. Such a system can readily be used to study semantic interoperability as a global scale phenomenon taking place in a social network of information sharing peers.
Vaccinia virus encodes a previously uncharacterized mitochondrial-associated inhibitor of apoptosis (2003)

To circumvent apoptotic death, many viruses encode Bcl-2 homologous proteins that function at the mitochondria. Vaccinia virus, the prototypic member of the Poxviridae family, does not encode a Bcl-2 homolog but inhibits the mitochondrial arm of the apoptotic cascade by an unknown mechanism. We now report that F1L, a previously unidentified protein in vaccinia virus, is responsible for the inhibition of apoptosis. Cells infected with vaccinia virus are resistant to staurosporine-mediated cleavage of poly(ADP-ribose) polymerase, caspases 3 and 9, and release of cytochrome c. In contrast, a vaccinia virus deletion mutant, VV811, was unable to inhibit apoptosis; however, the antiapoptotic function was restored by expression of the F1L ORF, which is absent in VV811. Although F1L displays no homology to members of the Bcl-2 family, it localizes to the mitochondria through a C-terminal hydrophobic domain. We show that expression of F1L interferes with apoptosis by inhibiting the loss of the inner mitochondrial membrane potential and the release of cytochrome c.
Membrane connexin 43 acts as an independent prognostic marker in oral squamous cell carcinoma (2014)

The aim of the present study was to evaluate the expression and localization of connexin (Cx) 26, -43 and -45 in a group of 35 patients with primary oral squamous cell carcinoma (OSCC) with the objective of making a more accurate disease prognosis. We analysed the expression of connexins in tissue samples of primary OSCC, matching oral mucosa free of dysplasia, and its associated lymph node metastases (LNM) by semi-quantitative immunohistochemistry of membrane, cytoplasmic and nuclear connexin expression. The levels of expression were correlated with the overall survival time (OS). Cx43 was overexpressed in tumour cells compared to epithelia in dysplasia-free mucosa. High membrane expression of Cx43 on tumour cells was the only statistically significant and independent prognostic factor of short OS (P=0.0088). Membrane expression of Cx43 in matching dysplasia-free mucosa acted similarly, but did not reach statistical significance (P=0.059). No correlation was found between the Cx26, Cx45 expression and OS. We conclude that Cx43 expression in dysplasia-free mucosa may indicate a very early stage of tumour promotion. Although overexpression of Cx43 is found in invasive tumours we only found membrane Cx43 expression to correlate with OS. This observation suggests that cytoplasmic Cx43 serves as storage and only membrane translocation may promote the formation of gap junctions and gap junctional intercellular communication (GJIC) with prognostic relevance.
Predicting students' ratings of the importance of strategies to facilitate self‐directed distance learning in Taiwan (2000)

Distance students' ratings of the importance of strategies to facilitate self‐directed learning were evaluated. Students from an open university in Taiwan (449 current and 140 inactive) participated in this study. Current students scored significantly higher than inactive students on internal motivation, insight about self, and self‐directed learning readiness. A combination of high internal and external motivation and high self‐directed learning readiness predicted ratings of the importance of five sets of strategies for helping students become self‐directed learners. The study provides information to help distance learning professionals enhance the effectiveness of self‐directed learning and reduce the number of students who become inactive.
Morphologies and Surface Plasmon Resonance Properties of Monodisperse Bumpy Gold Nanoparticles (2008)

The influence of the morphology of gold nanoparticles on the surface plasmon resonance was investigated experimentally and theoretically. Highly monodisperse bumpy gold nanoparticles of increasing size were synthesized, and the surface plasmon resonance wavelength shifted to longer wavelengths more rapidly with increasing particle size for bumpy particles than for spherical gold nanoparticles. The detailed surface morphology of bumpy gold nanoparticles was characterized by AFM, TEM, and SEM, and the optical properties were investigated on a single particle level. The comparison of the plasmon resonant properties between bumpy and spherical gold nanoparticles was also examined with a theoretical model.
Large transgenic mammals (1995)

The possibility of expressing foreign genes in mammals by gene transfer has opened new dimensions in the genetic manipulation of animals. The basic techniques of gene transfer were developed in mice, which have been most extensively used in such experiments because they are ideal for studying gene expression during development and for establishing animal models of carcinogenesis and other diseases. Additional applications include analysis of mutations and the use of the transgene as a genetic marker (Jaenisch 1988).
Can We Obtain a Noninvasive and Continuous Estimation of Cardiac Output? Comparison Between Three Noninvasive Methods (2013)

Cardiac output (CO) is often desirable for assessing the hemodynamic condition of a patient, especially in critically ill cardiac patients. Various noninvasive methods are available for this purpose. Inert gas rebreathing (IGR) and 2D-Doppler echocardiography methods have been validated. Based on the relationship between pulse wave transit time and stroke volume, the VISMO® provides an estimated continuous cardiac output (esCCO) measurement using only an electrocardiogram, pulse oximeter wave, and cuff arterial blood pressure. Doppler echocardiography is being currently used in every day practice in this setting and IGR is a validated method, thus we wanted to assess the agreement between these 3 methods for noninvasive CO calculation and reproducibility of esCCO. Patients followed in our cardiology department received on the same day a CO analysis by esCCO, Doppler echocardiography and IGR. Thirty-four patients were included (16 women, mean age 65 ± 15 years). Bland and Altman plots showed a good agreement between IGR and 2D-Doppler echocardiography (bias = 0.31 L/minute). Though there was also an agreement between esCCO and the other 2, the bias was rather large: 1.18 L/minute with IGR and 1.51 L/min with 2D-Doppler echo. The intraclass correlation coefficient was poor whatever the methods. However, esCCO had a satisfactory reproducibility and accuracy compared rather well with the other 2. This method could be suitable for patient screening and monitoring.
Anti-prostate immunotoxins: Cytotoxicity of E4 antibody–pseudomonas exotoxin constructs (1998)

E4 is a monoclonal antibody (MAb) that reacts with a surface antigen present on normal prostate and prostate cancers. Using this antibody, 2 immunotoxins were generated, one being a chemical conjugate with a mutant truncated form of Pseudomonas exotoxin A (PE), E4-PE35KDEL. The other is a recombinant single chain immunotoxin, E4(Fv)-PE38KDEL. The affinity of the conjugated immunotoxin was similar to the hybridoma-produced MAb E4, revealing that conjugation did not impair the binding ability. The affinity of the recombinant immunotoxin (10 nM) was 10-fold lower than that of the MAb, probably reflecting differences of bivalent (MAb) vs. monovalent (Fv) binding. Antigen positive prostate, breast and colon carcinoma cell lines showed cytotoxic response to the E4 immunotoxins while antigen negative cells were not affected. The IC50 value, representing a 50% inhibition of cellular protein synthesis, ranged from 0.3 to 20 ng/ml for E4-PE35KDEL and from 2 to 100 ng/ml for E4(Fv)-PE38KDEL. Therefore, the E4-derived immunotoxins may be useful for the treatment of prostate as well as breast and colon cancers.
The development and evaluation of head probes for optical imaging of the infant head (2007)

The objective of this thesis was to develop and evaluate optical imaging probes for mapping oxygenation and haemodynamic changes in the newborn infant brain. Two imaging approaches are being developed at University College London (UCL): optical topography (surface mapping of the cortex) and optical tomography (volume imaging). Both have the potential to provide information about the function of the normal brain and about a variety of neurophysiologies! abnormalities. Both techniques require an array of optical fibres/fibre bundles to be held in contact with the head, for periods of time from tens of seconds to an hour or more. The design of suitable probes must ensure the comfort and safety of the subject, and provide measurements minimally sensitive to external sources of light and patient motion. A series of prototype adaptable helmets were developed for optical tomography of the premature infant brain using the UCL 32-channel time-resolved system. They were required to attach 32 optical fibre bundles over the infant scalp, and were designed to accommodate infants with a variety of head shapes and sizes, aged between 24-weeks gestational age and term. Continual improvements to the helmet design were introduced following the evaluation of each prototype on infants in the hospital. Data were acquired to generate images revealing the concentration and oxygenation of blood in the brain, and the response of the brain to sensory stimulation. This part of the project also involved designing and testing new methods of acquiring calibration data using reference phantoms. The second focus of the project was the development of probes for use with the UCL frequency-multiplexed near-infrared topography system. This is being used to image functional activation in the infant cortex. A series of probes were developed and experiments were conducted to evaluate their sensitivity to patient motion and to compression of the probe. The probes have been used for a variety of functional activation studies.
Lipofuscin accumulation in cultured retinal pigment epithelial cells reduces their phagocytic capacity (1998)

Purpose. Retinal pigment epithelial (RPE) cells slowly accumulate lipofuscin pigment within their acidic vacuolar apparatus as a result of extra- and/or intralysosomal oxidative alterations of phagocytosed photoreceptor outer segments (POS) with consequent imperfect degradation of these structures. In old age, lipofuscin accumulation may become quite substantial. It has been suggested that pronounced accumulation of lipofuscin is related to decreased RPE function and, possibly, to age-related macular degeneration. The aim of the present investigation was to study whether heavy loading with lipofuscin of RPE acidic lysosomes would affect the further phagocytic ability of the cells.Methods. In the first section of the investigation, cultures of rabbit RPE cells were exposed daily to bovine UV-irradiated POS (artificial lipofuscin) for 4 weeks, resulting in a pronounced lipofuscin accumulation of the cells. Fluorescent latex beads (labelled with a red fluorophore) were added to unloaded control cultures at 0 and 4 weeks after their establishment, and to lipofuscin loaded cells after 4 weeks of feeding with artificial lipofuscin. Cellular amounts of lipofuscin, and their phagocytotic activity, were quantified by static fluorometry measuring lipofuscin-specific and red bead-specific fluorescence, respectively. The intracellular location of the beads was verified by confocal laser scanning microscopy.Results. Unloaded, and thus almost lipofuscin-free, control cells exposed to latex beads showed numerous cytoplasmic particles emitting reddish fluorescence, while few particles were taken up by cells initially loaded with artificial, POS-derived, lipofuscin. Measurement of the latex bead-specific fluorescence showed significantly (p < 0.001) higher levels in unloaded control cells than in lipofuscin-loaded ones.In the second part of the investigation, unloaded control cultures and lipofuscin-loaded cultures were exposed to native bovine Texas Red-X-labelled POS 4 weeks after the establishment of the cultures. Unloaded control cells showed a large number of cytopiasmic POS emitting reddish fluorescence, while fewer POS were phagocytosed by cells loaded with artificial lipofuscin. Measurement of the Texas Red-X-specific fluorescence, thus quantifying the phagocytic ability of the cells, showed significantly (p < 0.001) higher levels in control cells than in lipofuscin-loaded ones.Conclusions. Severe lipofuscin accumulation of RPE cells appears to result in a greatly decreased phagocytic capacity. The resulting reduction in ability to cope with the needs of the overlying photoreceptor cells, in order to eliminate the obsolete tips of their POS, may well be of significance in the development of age-related macular degeneration. Curr. Eye Res. 17:851–857, 1998.
Supine sleep and positional sleep apnea after acute ischemic stroke and intracerebral hemorrhage (2012)

Prolonged supine positioning during sleep was highly frequent after stroke, and it was related to stroke severity. Positional sleep apnea was observed in one quarter of stroke patients, which was likely underestimated during the acute phase of stroke. The adequate positioning of patients during sleep during the acute phase of stroke may decrease obstructive respiratory events, regardless of the stroke subtype.