gebhart/patrepeval huggingface dataset:
HIV-1 drug resistance: can we overcome? (2002)

Highly active antiretroviral therapy (HAART) targeting the viral reverse transcriptase and protease enzymes has advanced the treatment of HIV/AIDS. Nucleoside and non-nucleoside reverse transcriptase inhibitors and protease inhibitors used in combination can suppress viral replication thereby delaying disease progression. Emergence of HIV-1 mutated strains, resistant to one or more antiretroviral inhibitors or drug classes, remains one of the leading causes of treatment failure among patients living with HIV/AIDS. While advances in genotypic and phenotypic testing allow for drug resistance guided therapeutic management, the increasing prevalence of multi-drug resistance and an absence of new drug classes forewarn new problems in sustaining the effectiveness of HAART. One promising hope for continued benefit of antiretroviral therapy despite emergent resistance is the observed reduction in replicative ability or 'fitness' of multimutated viruses. This review discusses the development and influence of known drug mutations on drug susceptibility versus viral fitness.
Single Self-Injection-Locked Radar With Two Antennas for Monitoring Vital Signs With Large Body Movement Cancellation (2017)

This paper presents a novel self-injection-locked radar with two antennas to transmit and retransmit a continuous wave to opposite sides of a human body for monitoring vital signs in real time with large body movements. The system can prevent the nonlinear effects of large Doppler phase shifts on the cancellation of body motion artifacts, to extract accurate vital signs from the received Doppler-shifted signal. However, the effectiveness of the cancellation is limited by the received clutter echoes in this system. Therefore, the system also has a clutter effect elimination circuit to improve substantially the detection of vital signs in an examinee at various positions between the two antennas even when the examinee moves often by more than one wavelength.
Measuring Risk and Performance over Alternative Investment Horizons (1984)

(1984). Measuring Risk and Performance over Alternative Investment Horizons. Financial Analysts Journal: Vol. 40, No. 2, pp. 61-68.
Highlights of Semi-synthetic Developments from Erythromycin A (2000)

Earlier semi-synthetic studies of erythromycin A culminated in the discovery of two successful second generation macrolide antibiotics, azithromycin and clarithromycin, for the treatment of community-acquired bacterial infections. More recent structural modifications of erythromycin A have resulted in the discovery of novel ketolide antibiotics and new motilide prokinetic agents. This review is an account of the semi-synthetic developments from erythromycin A by chemical transformations.
Randomized, double-blind, placebo-controlled clinical trial of loperamide plus simethicone versus loperamide alone and simethicone alone in the treatment of acute diarrhea with gas-related abdominal discomfort (2007)

LOP/SIM was well-tolerated and more efficacious than LOP alone, SIM alone, or placebo for acute nonspecific diarrhea and gas-related abdominal discomfort.
Radiosensitizer conjugation to the carcinoma 19-9 monoclonal antibody. (1987)

Misonidazole was covalently conjugated (3-68 mol drug/mol antibody) to 19-9 monoclonal antibody directed against a colorectal carcinoma tumor-associated antigen as a method for targeting radiosensitizing agents. This attachment was accomplished by the mixed anhydride method using the hemisuccinate derivative of misonidazole. Evaluation of conjugates in vitro shows a loss of antibody binding activity with increasing loading levels; however, significant binding activity is retained even at relatively high sensitizer/antibody ratios. This observation was consistent in three binding assays: a competitive radioimmunoassay; an enzyme immunoassay; and an affinity column assay. From these studies, it was concluded that the optimal loading factor for misonidazole-antibody conjugates, when it is used for immunochemotherapy lies between 8 and 15. In vitro release studies indicated that conjugates are hydrolytically stable (t1/2 = 4 days) under physiological conditions.
Genetic reassortment of mammalian reoviruses in mice (1985)

Reassortments between type 1 (Lang) and type 3 (Dearing) reoviruses were isolated from suckling mice infected perorally with an inoculum containing both type 1 and type 3 viruses. A total of five distinct reassortants (designated as E1 through E5) were isolated from animals during the course of the experiment. Two reassortants (E1 and E2) represented the majority of the reassortants isolated. The majority of genes of types E1 and E2 were derived from type 1 (Lang). However, E1 had an M2 gene and an S1 gene derived from type 3 (Dearing), while E2 had M2 and S2 genes derived from type 3 (Dearing). Thus, nonrandom reassortment between mammalian reoviruses can be demonstrated in vivo.
Full Resistance of Herpes Simplex Virus Type 1-Infected Primary Human Cells to Alpha Interferon Requires both the Us11 and γ 1 34.5 Gene Products (2004)

The gamma(1)34.5 gene product is important for the resistance of herpes simplex virus type 1 (HSV-1) to interferon. However, since the inhibition of protein synthesis observed in cells infected with a gamma(1)34.5 mutant virus results from the combined loss of the gamma(1)34.5 gene product and the failure to translate the late Us11 mRNA, we sought to characterize the relative interferon sensitivity of mutants unable to produce either the Us11 or the gamma(1)34.5 polypeptide. We now demonstrate that primary human cells infected with a Us11 mutant virus are hypersensitive to alpha interferon, arresting translation upon entry into the late phase of the viral life cycle. Furthermore, immediate-early expression of Us11 by a gamma(1)34.5 deletion mutant is sufficient to render translation resistant to alpha interferon. Finally, we establish that the Us11 gene product is required for wild-type levels of replication in alpha interferon-treated cells and, along with the gamma(1)34.5 gene, is an HSV-1-encoded interferon resistance determinant.
Antibody-conjugated MHC class I tetramers can target tumor cells for specific lysis by T lymphocytes (2000)

To demonstrate that antibody-guided targeting of antigenic MHC class I-peptide tetramer on tumor cells can render them susceptible to lysis by relevant cytotoxic T lymphocytes (CTL), biotinylated HLA-A*0201/Flu matrix peptide complexes were tetramerized on streptavidin molecules previously coupled to Fab' fragments from monoclonal antibodies (mAb) specific for cell surface markers such as carcinoembryonic antigen (CEA), ErbB-2 or CD20. Flow cytometry analysis showed that coating of the HLA-A2-peptide complexes on the four HLA-A2-negative human cancer lines tested (including a CEA-positive colon carcinoma, an ErbB-2(+) breast carcinoma and two CD20(+) B lymphomas) was entirely dependent upon the specificity of the conjugated antibody fragments. More importantly, HLA-A2-restricted Flu matrix peptide-specific CTL were then found to lyse specifically and efficiently the MHC-coated target cells. These results open the way to the development of new immunotherapy strategies based on antibody targeting of MHC class I-peptide complexes.
The effect of calcineurin inhibitors and corticosteroids on the differentiation of human dendritic cells (2000)

Corticosteroids and the calcineurin inhibitors cyclosporin A (CsA) and FK506 have been studied extensively regarding their effects on T lymphocytes, but their effects on dendritic cells (DC) are relatively unknown. Monocytes are one of the precursors of DC that differentiate into CD14-CD1a+ immature DC upon culture with IL-4 and GM-CSF. The presence of CsA or FK506 during differentiation did not affect DC development. In contrast, the presence of corticosteroids, either dexamethasone (Dex) or prednisolone (Pred), for as little as the first 48 h of culture blocked the generation of immature DC. Dex-DC were unresponsive to signals inducing maturation (CD40 ligand, lipopolysaccharide), as demonstrated by the absence of CD83, CD80/CD86 and HLA-DR up-regulation and their strongly reduced T cell stimulatory capacity. Furthermore, Dex-DC showed a decreased CD40 ligand-induced IL-6 and TNF-alpha production, a complete block in IL-12p40 production, while IL-10 production was unaffected. CsA-DC and FK506-DC showed a partial reduction in the production of TNF-alpha, whereas all other functional activities appeared to be similar to control DC. These data show that, when compared to calcineurin inhibitors, corticosteroids have a unique and profound inhibitory effect on the generation and function of DC.
TRANSPLANTATION IN THE NINETIES1 (1992)

Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio 45267–0585 1 Presidential Address given at the 10th Annual Meeting of the American Society of Transplant Physicians, May 28–29, 1991, Chicago, IL.
Bibliophilie contemporaine (2015)

Il se fait de très beaux livres au Québec, et ça ne date pas d’hier. Parallèlement au monde de l’édition prospère, celui qui s’occupe des manuels scolaires et des best-sellers que chaque éditeur espère, il y a un monde discret, celui de la bibliophilie. Il est peuplé de gens qui font du livre leur plaisir. C’est ce monde que nous allons tenter de cerner.
A review of telemedicine (1999)

Moving the information instead of the patient is often sufficient and telemedicine is a useful and potentially powerful tool which fulfils this idea. It has changed the classical form of health-care delivery by providing those people living in rural and remote areas with comparable services to those in urban areas. Equally, remote hospitals can obtain specialist consultations and diagnosis without the need for the patient to travel. We have reviewed the present status of telemedicine and its future possibilities.
A Cytokine Cascade Including Prostaglandin E2, IL-4, and IL-10 Is Responsible for UV-Induced Systemic Immune Suppression (1998)

Even though all of the energy contained with the UV wavelengths of solar radiation is absorbed within the epidermis and upper layers of the dermis, UV irradiation can suppress immune responses to Ag introduced at distant nonirradiated sites. In addition, data from a number of laboratories have suggested that one consequence of UV exposure is suppressed Th1 cell activation with normal or enhanced Th2 cell activation, resulting in a shift to a Th2-like phenotype. Cytokines secreted by UV-irradiated keratinoctyes, particularly IL-10, have been shown to play a major role in the induction of systemic immune suppression and differential activation of T helper cell subsets. Although IL-10 can influence Th1 cell activation by altering Ag presentation and suppressing IFN-gamma secretion, the major signal for the development of a Th2 response is IL-4. Here we tested the hypothesis that UV irradiation induces IL-4 secretion. UV irradiation induced serum IL-4 in a dose-dependent fashion. Injecting UV-irradiated mice with anti-IL-4 blocked immune suppression. We could find no evidence, however, supporting secretion of IL-4 by UV-irradiated keratinocytes. Rather, we suggest that prostaglandins released by irradiated keratinocytes induce serum IL-4 since treating UV-irradiated mice with a cyclooxygenase-2 inhibitor blocked its production. Moreover, we found that treating UV-irradiated mice with anti-IL-4 suppressed serum IL-10 levels. In addition, injecting normal mice with PGE2 induced serum IL-4 and IL-10. We suggest that UV exposure activates a cytokine cascade (PGE2 --> IL-4 --> IL-10) that ultimately results in systemic immune suppression.
A new therapeuthical approach to block cancer cachexia: focusing inhibition of STAT3 (2013)

Cachexia is a devastating complication of cancer. The mechanisms by which cancers cause cachexia are unclear and there are few successful therapeutic options. In muscles from mouse models of cancer cachexia, we found increased STAT3 phosphorylation associated with muscle atrophy. In muscle cells (C2C12 myotubes) incubated with media from cultured Lewis lung carcinoma (LLC) or Colon 26 (C26) tumor cells, we found rapid phosphorylation of STAT3 and progressive myotube atrophy. We created mice with muscle‐specific STAT3 knockout (KO) with implanted tumor cells. We found a prevention of body and muscle weight loss in KO mice compared to control mice injected with LLC tumors. We treated C2C12 cells and mice with a small molecule inhibitor of STAT3 (C188–9). C2C12 myotubes were incubated with C188–9 and conditioned media from C26 colon tumors and after 24 hours, the STAT3 phosphorylation was suppressed and the wasting of myotubes was blocked. In CD2F1 mice bearing C26 xenografts, daily i.p. administration of C188–9 (6.25mg/kg) over 14 days significantly reduced loss of body weight and muscle mass compared to tumor‐bearing mice injected with the diluent. The increase in muscle mass of C188–9‐treated mice was due to increased protein synthesis and decreased protein degradation. Thus, small‐molecule inhibition of STAT3 represents a novel therapeutic strategy for preventing cachexia‐induced muscle atrophy.
Indoleamine 2,3-dioxygenase and tumor-induced tolerance (2007)

Tumors arise from normal cells of the body through genetic mutation. Although such genetic mutation often leads to the expression of abnormal antigens, the immune system fails to respond effectively to these antigens; that is, it is tolerant of these antigens. This acquired state of tolerance must be overcome for cancer immunotherapy to succeed. Indoleamine 2,3-dioxygenase (IDO) is one molecular mechanism that contributes to tumor-induced tolerance. IDO helps create a tolerogenic milieu in the tumor and the tumor-draining lymph nodes, both by direct suppression of T cells and enhancement of local Treg-mediated immunosuppression. It can also function as an antagonist to other activators of antitumor immunity. Therefore, strategies to block IDO might enhance the effectiveness of tumor immunotherapy.
Grain Improvement in Triticum Durum Through Interspecific Hybridization (1987)

Interspecific hybridization was used to diversify the genetic base of the Indian durum wheats for various yield contributing traits. Significant improvement has been achieved for grain characters in the durum derivatives of these interspecific hybrids. T. timopheevi and T. carthlicum contribute significantly in improving grain characters like size, hardness, lustre, non-mottling nature and uniformity; while T. dicoccum and T. carthlicum simultaneously improve grain weight and grain protein.
Deamidation and Isoaspartate Formation in Smeared Tau in Paired Helical Filaments (1999)

An extensive loss of a selected population of neurons in Alzheimer's disease is closely related to the formation of paired helical filaments (PHFs). The most striking characteristic of PHFs upon Western blotting is their smearing. According to a previously described protocol (Morishima-Kawashima, M., Hasegawa, M., Takio, K., Suzuki, M., Titani, K., and Ihara, Y. (1993) Neuron 10, 1151-1160), smeared tau was purified, and its peptide map was compared with that of soluble (normal) tau. A CNBr fragment from soluble tau (CN5; residues 251-419 according to the 441-residue isoform) containing the microtubule-binding domain migrated at 15 and 18 kDa on SDS-polyacrylamide gel electrophoresis, whereas that from smeared tau exhibited two larger, unusually broad bands at approximately 30 and approximately 45 kDa, presumably representing dimers and trimers of CN5. In the peptide map of smeared tau-derived CN5, distinct peaks eluting at unusual locations were noted. Amino acid sequence and mass spectrometric analyses revealed that these distinct peptides bear isoaspartate at Asn-381 and Asp-387. Because no unusual peptides other than aspartyl or isoaspartyl peptide were found in the digests of smeared tau-derived CN5, it is likely that site-specific deamidation and isoaspartate formation are involved in its dimerization and trimerization and thus in PHF formation in vivo.
Micrometer-Scale Resolution Imaging of the Anterior Eye In Vivo With Optical Coherence Tomography (1994)

Optical coherence tomography has potential as a diagnostic tool for applications in noncontact biometry, anterior chamber angle assessment, identification and monitoring of intraocular masses and tumors, and elucidation of abnormalities of the cornea, iris, and crystalline lens.
Genetics of complex human diseases: genome screening, association studies and fine mapping (1998)

Positional cloning has been applied successfully to many Mendelian disorders. Because of the public health significance, there is strong interest in mapping susceptibility genes for common disorders, such as asthma and allergy, that have a genetic component. Genome-wide screening has been very useful in detecting regions of the genome likely to contain susceptibility genes. There are multiple chromosomal regions implicated in asthma and now the difficult process of finding the genes and relevant mutations is underway. Two approaches that are being utilized are those of association studies in candidate genes, and haplotype sharing or identical by descent (IBD) mapping. Although these are useful approaches, it is important to realize the strengths and limitations of each. The level of significance needed for an initial study or a replication study should be considered in light of the prior evidence for studying a specific gene polymorphism. Haplotype-sharing approaches, although difficult to use in outbred heterogeneous populations, may provide important insight into fine mapping and gene localization.
Scratchpad allocation for concurrent embedded software (2010)

Software-controlled scratchpad memory is increasingly employed in embedded systems as it offers better timing predictability compared to caches. Previous scratchpad allocation algorithms typically consider single-process applications. But embedded applications are mostly multitasking with real-time constraints, where the scratchpad memory space has to be shared among interacting processes that may preempt each other. In this work, we develop a novel dynamic scratchpad allocation technique that takes these process interferences into account to improve the performance and predictability of the memory system. We model the application as a Message Sequence Chart (MSC) to best capture the interprocess interactions. Our goal is to optimize the Worst-Case Response Time (WCRT) of the application through runtime reloading of the scratchpad memory content at appropriate execution points. We propose an iterative allocation algorithm that consists of two critical steps: (1) analyze the MSC along with the existing allocation to determine potential interference patterns, and (2) exploit this interference information to tune the scratchpad reloading points and content so as to best improve the WCRT. We present various alternative scratchpad allocation heuristics and evaluate their effectiveness in reducing the WCRT. The scheme is also extended to work on Message Sequence Graph models. We evaluate our memory allocation scheme on two real-world embedded applications controlling an Unmanned Aerial Vehicle (UAV) and an in-orbit monitoring instrument, respectively.
Separation of endo‐ and exo‐type cellulases using a new affinity chromatography method (1984)

A new efficient biospecific adsorbent for the purification of cellulases was prepared from p ‐aminobenzyl 1‐thio‐β‐D‐cellobioside and Affigel‐10 (Biorad). The two exocellobiohydrolases, CBH I and CBH II, from Trichoderma reesei QM 9414 were adsorbed, whereas the endoglucanase activities were unretarded. The adsorbed CBH I can be displaced selectively by elution with lactose, whereas cellobiose elutes the CBH II.
Defining target antigens for CD25+FOXP3+IFN‐γ− regulatory T cells in chronic hepatitis C virus infection (2007)

The mechanism behind the apparent lack of effective antiviral immune responses in chronic hepatitis C virus (HCV) patients is poorly understood. It remains unclear if natural regulatory T cells (Treg) contribute to the induction and maintenance of HCV persistence. We herein report for the first time that CD25(high)IFN-gamma(-)FOXP3(high) Tregs can be rapidly induced by culturing peripheral blood mononuclear cells (PBMCs) of HCV-positive patients with HCV protein-derived peptides. The HCV-specific Tregs, generally CD4(+)CD45RO(+), did not proliferate in response to HCV peptide and failed to produce interferon (IFN)-gamma, in distinct contrast to antiviral effector cells. Stimulation of healthy donor PBMCs with HCV peptides did not result in CD25 and FOXP3 upregulation above non-antigen background. To further investigate the antigen specificity of these potentially disease-associated natural Tregs, CD25(+) cells were isolated from PBMCs, labeled with carboxyfluorescein diacetate succinimidylester and added back to CD25-depleted PBMCs, and the co-cultures were then stimulated with individual peptides derived from the HCV core protein. We found that the actual peptide that can stimulate Treg varied between patients, but within any given subject only a small number of the peptides were able to stimulate Treg, suggesting the existence of dominant Treg epitopes. Although functional experiments for these peptides are ongoing in our laboratory, data presented here suggests that HCV-specific natural Tregs are abundant in infected individuals, in contrast to the extremely low frequency of anti-HCV effector T cells, supporting the view that natural Treg may be implicated in host immune tolerance during HCV infection.
Cost-Effectiveness of Carotid Plaque MR Imaging as a Stroke Risk Stratification Tool in Asymptomatic Carotid Artery Stenosis (2015)

MR imaging IPH can be used as a cost-effective tool to identify patients with asymptomatic carotid artery stenosis most likely to benefit from carotid endarterectomy.
Odevixibat and partial external biliary diversion showed equal improvement of cholestasis in a patient with progressive familial intrahepatic cholestasis (2020)

Untreated progressive familial intrahepatic cholestasis (PFIC) type 2, or bile salt exporter protein deficiency, frequently leads to severe pruritus, impaired growth and progressive liver fibrosis with risk of organ failure. We describe a 15-month-old male patient with severe pruritus diagnosed with PFIC type 2 enrolled in an open-label phase 2 study who received 4 weeks of treatment with odevixibat, an ileal bile acid transporter inhibitor under development for cholestatic liver disease treatment. The patient experienced reductions in serum bile acids and improvement in itching and sleep scores, and odevixibat was well tolerated. After the odevixibat study, symptoms returned and the patient underwent partial external biliary diversion (PEBD). Odevixibat treatment and PEBD produced similar normalisation of serum bile acid levels and improvements in pruritus and sleep disruptions. Thus, odevixibat appeared to be as effective as invasive PEBD in treating serum bile acids and cholestatic pruritus in this patient.