gebhart/patrepeval huggingface dataset:
Targeted Disruption of the FGF2 Gene Does Not Prevent Choroidal Neovascularization in a Murine Model (1998)

Choroidal neovascularization (CNV) is the major cause of severe visual loss in patients with age-related macular degeneration. Laser treatment is helpful for a minority of patients with CNV, and development of new treatments is hampered by a poor understanding of the molecular signals involved. Several lines of evidence have suggested that basic fibroblast growth factor (FGF2) plays a role in stimulating CNV. In this study, we tested this hypothesis using mice with targeted disruption of the FGF2 gene in a newly developed murine model of laser-induced CNV. One week after krypton laser photocoagulation in C57BL/6J mice, 34 of 60 burns (57%) showed fluorescein leakage and 13 of 16 (81%) showed histopathological evidence of CNV. At 2 weeks, CNV was detected in 9 of 10 burns (90%) in which a bubble had been observed at the time of the laser treatment. Electron microscopy showed fenestrated vessels with large lumens within choroidal neovascular lesions. Two weeks after laser-induced rupture of Bruch's membrane, 27 of 36 burns (75%) contained CNV in FGF2-deficient mice compared with 26 of 30 (87%) in wild-type control mice, a difference that is not statistically significant. This study demonstrates that FGF2 is not required for the development of CNV after laser-induced rupture of Bruch's membrane and provides a new model to investigate molecular mechanisms and anti-angiogenic therapy in CNV.
Standby Automatic Defibrillator (1970)

A laboratory model of an automatic standby defibrillator has been designed, developed, and tested successfully on dogs. Approximately 50 seconds after a sensor located in the right ventricle detects ventricular fibrillation, a discharge of the order of 30 to 50 wattseconds is delivered automatically to the heart through two electrodes, one which represents an integral part of the intracardiac sensing catheter, and the other positioned under the skin or on the surface of the anterior chest wall. In the event of successful defibrillation the device reverts to a standby condition. It is suggested that this device, when adapted for clinical use, might be implanted temporarily or permanently in selected patients particularly prone to develop ventricular fibrillation and thus provide them with some degree of protection from sudden coronary death.
Activation of ribonuclease L by (2'-5')(A)4-poly(L)-lysine) conjugates in intact cells (1986)

Molecular hybrids were synthesized by coupling (2'-5')(A)n oligoadenylates or 2-5A, an intracellular mediator involved in antiviral activity of interferons (IFNs), with poly(L-lysine) used as a membrane carrier. (2'-5')(A)n in its free form was not taken up by cells, probably because of its ionic character. Conjugation with the polypeptide carrier overcame this problem and enabled its pharmacological properties to be developed. The alpha-glycol group of individual (2'-5')(A)n oligomers was oxidized by periodate oxidation and conjugated by an amino reductive reaction to poly(L-lysine), Mr 14 000, in a molar ratio of 5:1. These hybrid molecules left the biologically active 5' end moiety of the (2'-5')(A)n molecule unchanged, and in particular its triphosphate group, and stabilized the molecule by increasing its resistance to phosphodiesterase hydrolysis. A dose-dependent inhibition of virus growth was observed on concomitant incubation of (2'-5')(A)n-poly(L-lysine) conjugates with vesicular stomatitis virus infected L1210 cell cultures. This was a result of the activation of the (2'-5')(A)n-dependent endoribonuclease (RNase L) by intracellularly delivered (2'-5')(A)n as in some IFN-treated virus-infected cells. Indeed, (2'-5')(A)n-poly(L-lysine) conjugates bind RNase L effectively as can be seen from their ability to compete with authentic (2'-5')(A)n in a cell-free radiobinding assay. Moreover, (2'-5')(A)n-poly(L-lysine) conjugates promote transient inhibition of protein synthesis and a characteristic cleavage pattern of ribosomal RNAs in intact cells.(ABSTRACT TRUNCATED AT 250 WORDS)
A Biomechanical Assessment of Thoracic Spine Stapling (2007)

Our results imply that staples are able to significantly restrict motion while not achieving motion reductions that one would achieve with fusion-promoting instrumentation. The choice between double- and single-prong staples remains a matter of preference. Neither staple variant provided a mechanical advantage. The single-prong staple did allow more control in the placement of the staple over the disc space. The addition of an anterior staple significantly reduced the overall flexion-extension ROM.
Carcinogenicity Predictions for a Group of 30 Chemicals Undergoing Rodent Cancer Bioassays Based on Rules Derived from Subchronic Organ Toxicities (1996)

Yongwon Lee, Bruce G. Buchanan, Herbert S. Rosenkranz, Carcinogenicity Predictions for a Group of 30 Chemicals Undergoing Rodent Cancer Bioassays Based on Rules Derived from Subchronic Organ Toxicities, Environmental Health Perspectives, Vol. 104, Supplement 5 (Oct., 1996), pp. 1059-1063
DDB1 Stimulates Viral Transcription of Hepatitis B Virus via HBx-Independent Mechanisms (2016)

DDB1 constitutes a cullin-based ubiquitin E3 ligase, where DDB1 serves as an adaptor linking the cullin scaffold to the substrate receptor. Previous findings that the DDB1-binding ability of HBx is essential for HBx-stimulated viral DNA replication led to the hypothesis that HBx could downregulate host restriction factors that limit HBV replication through the cullin ubiquitin E3 ligase that requires the DDB1-HBx interaction. Consistent with this hypothesis, recent work identified Smc5/6 as a host restriction factor that is regulated by the viral cullin ubiquitin E3 ligase. In contrast, here we found that the DDB1-HBx interaction is largely dispensable for HBx-stimulated viral DNA replication. Instead, our results clearly showed that DDB1, regardless of HBx expression, enhances viral transcription. Overall, besides its role in the viral cullin ubiquitin E3 ligase, DDB1 itself stimulates viral transcription via HBx-independent mechanisms.
Differential chemokine response of murine macrophages stimulated with cytokines and infected with Listeria monocytogenes (1998)

During inflammatory processes the infected macrophage is a rich source of chemokines which induce infiltration of leukocytes to the site of infection. We investigated the regulation of chemokine production by murine macrophages in response to infection with the intracellular bacterial pathogen, Listeria monocytogenes. As a source of quiescent macrophages, murine bone marrow-derived macrophages (BMM) cultured under serum-free conditions were used. With RT-PCR, we detected induction of RNA message for the chemokines macrophage inflammatory protein (MIP)-2, KC, MIP-1alpha, MIP-1beta, IFN-gamma-inducible protein-10 and RANTES in L. monocytogenes-infected macrophages. Accordingly, ELISA-detectable MIP-1alpha, MIP-2 and KC protein was induced by infection with L. monocytogenes. In contrast, L. monocytogenes infection of BMM alone failed to induce considerable expression of monocyte chemoattractant protein (MCP)-1 at the mRNA or protein level, but co-treatment with IFN-gamma was necessary. Release of infection-triggered MIP-2, MIP-1alpha and KC was negatively regulated by IFN-gamma. Similarly, IL-4 stimulated MCP-1 release by infected macrophages but reduced production of MIP-1alpha, MIP-2 and KC. IL-10 turned out to be a general deactivator in terms of macrophage chemokine production. IL-13 had no effect on MIP-1alpha, MIP-2 and KC production by infected BMM, but slightly reduced MCP-1 release. By using IFN-gamma and IL-4 gene deletion mutant mice, in vivo regulation of these chemokines by IL-4 and IFN-gamma in listeriosis was studied. In summary, our results show that chemokines are produced by macrophages infected with L. monocytogenes, and that chemokine release is differentially regulated by the macrophage modulators IFN-gamma, IL-4, IL-10 and IL-13.
The dynamics and control of a haptic interface device (1994)

Haptic interface devices are machines that are controlled by the human arm contact forces. These devices are necessary elements of virtual reality machines. These devices may be programmed to give the human arm the sensation of forces associated with various arbitrary maneuvers. As examples, these devices can give the human the sensation that he/she is maneuvering a mass, or pushing onto a spring or a damper. In general, these devices may be programmed for any trajectory-dependent force. To illustrate and verify the analysis of these machines, a two-degree-of-freedom electrically-powered haptic interface device was designed and built at the Human Engineering Laboratory (HEL) of the University of California-Berkeley.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray (1995)

A high-capacity system was developed to monitor the expression of many genes in parallel. Microarrays prepared by high-speed robotic printing of complementary DNAs on glass were used for quantitative expression measurements of the corresponding genes. Because of the small format and high density of the arrays, hybridization volumes of 2 microliters could be used that enabled detection of rare transcripts in probe mixtures derived from 2 micrograms of total cellular messenger RNA. Differential expression measurements of 45 Arabidopsis genes were made by means of simultaneous, two-color fluorescence hybridization.
Modeling Competitive Bidding: A Critical Essay (1994)

In analyzing bidding, modeling matters. This paper is a critical analysis of the models available to aid competitive bidding decision making—bidding strategy and auction design—in real transactions. After an introductory overview, this paper describes the contexts in which auctions arise, reviews the “mainstream” theory of single, isolated auctions and discusses the important work involved in enrichment of this theory. In doing so, it indicates results that have been obtained and the sort of changes in analytical approach that are needed to tackle other critical enrichments. The paper summarizes briefly what is known about the direct use of models by bidders and auction designers. A general theme of this paper is that enriched models are needed to bring bidding theory closer to direct applicability in decision making.
Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy (2014)

Adenovirus vectors are the most commonly employed vector for cancer gene therapy. They are also used for gene therapy and as vaccines to express foreign antigens. Adenovirus vectors can be replication-defective; certain essential viral genes are deleted and replaced by a cassette that expresses a foreign therapeutic gene. Such vectors are used for gene therapy, as vaccines, and for cancer therapy. Replication-competent (oncolytic) vectors are employed for cancer gene therapy. Oncolytic vectors are engineered to replicate preferentially in cancer cells and to destroy cancer cells through the natural process of lytic virus replication. Many clinical trials indicate that replication-defective and replication-competent adenovirus vectors are safe and have therapeutic activity.
Khellinone Derivatives as Blockers of the Voltage-Gated Potassium Channel Kv1.3:  Synthesis and Immunosuppressive Activity (2004)

The voltage-gated potassium channel Kv1.3 constitutes a promising new target for the treatment of T-cell-mediated autoimmune diseases such as multiple sclerosis. In this study, we report the discovery of two new classes of Kv1.3 blockers based on the naturally occurring compound khellinone, 5-acetyl-4,7-dimethoxy-6-hydroxybenzofuran: (1) khellinone dimers linked via the alkylation of the 6-hydroxy groups and (2) chalcone derivatives of khellinone formed by Claisen-Schmidt condensation of the 5-acetyl group with aryl aldehydes. In particular, the chalcone 3-(4,7-dimethoxy-6-hydroxybenzofuran-5-yl)-1-phenyl-3-oxopropene (16) and several of its derivatives inhibited Kv1.3 with K(d) values of 300-800 nM and a Hill coefficient of 2, displayed moderate selectivity over other Kv1-family K(+) channels, suppressed T-lymphocyte proliferation at submicromolar concentrations, and showed no signs of acute toxicity in mice. Because of their relatively low molecular weight and lipophilicity and their high affinity to Kv1.3, aryl-substituted khellinone derivatives represent attractive lead compounds for the development of more potent and selective Kv1.3 blocking immunosuppressants.
Fluorescence correlation spectroscopy: Lead discovery by miniaturized HTS (1999)

Abstract Miniaturized high-throughput screening offers great promise for increasing the productivity of the pharmaceutical drug discovery process. By monitoring interactions of single molecules in femtoliter volumes, fluorescence correlation spectroscopy (FCS) offers the highest potential as the detection technique in the nanoscale. The authors ( Appendix A ) summarize the current status of practical experiences with FCS assays for HTS and explore the scope for further developments.
Phase 2 study of pembrolizumab as first-line therapy for PD-L1–positive metastatic triple-negative breast cancer (mTNBC): Preliminary data from KEYNOTE-086 cohort B. (2017)

1088 Background: Standard first-line treatment for mTNBC is chemotherapy. However, outcomes are poor, and new treatment options are needed. Cohort B of KEYNOTE-086 (NCT02447003) assessed the safety and antitumor activity of pembrolizumab as first-line therapy for patients (pts) with PD-L1–positive mTNBC. Methods: Men and women with centrally confirmed mTNBC, no prior systemic anticancer therapy for metastatic disease, ECOG PS 0-1, and a tumor PD-L1 combined positive score (CPS) ≥1% received pembrolizumab 200 mg Q3W for 24 mo or until disease progression, intolerable toxicity, or investigator or pt decision. Tumor imaging was performed Q9W for 12 mo and Q12W thereafter. Clinically stable pts with PD could remain on pembrolizumab until PD was confirmed on subsequent assessment. Primary end point was safety. Secondary end points included ORR, DOR, and PFS (RECIST v1.1, central review). Planned enrollment was 80 pts. This analysis included all pts who had ≥18 wk of follow-up as of Nov 10, 2016. Results: 79 of the first 137 pts with PD-L1–evaluable tumors (58%) had PD-L1 CPS ≥1%. Of the first 52 pts enrolled, 100% were women, median age was 53 y, 40% had elevated LDH, 69% had visceral metastases, and 87% received prior (neo)adjuvant therapy. After a median follow-up of 7.0 mo (range 4.4-12.5), 15 (29%) pts remained on pembrolizumab. Treatment-related AEs occurred in 37 (71%) pts, most commonly fatigue (31%), nausea (15%), and diarrhea (13%). 4 (8%) pts experienced 5 grade 3-4 treatment-related AEs: back pain, fatigue, hyponatremia, hypotension, and migraine (n = 1 each). No pts died or discontinued pembrolizumab due to an AE. ORR was 23% (95% CI 14%-36%). Best overall response was CR in 4%, PR in 19%, SD in 17%, PD in 58%, and not assessed in 2%. Median time to response was 8.7 wk (range 8.1-17.7). Median DOR was 8.4 mo (range, 2.1+ to 8.4), with 8 (67%) responses ongoing at cutoff. Median PFS was 2.1 mo (95% CI, 2.0-3.9); estimated 6-mo PFS rate was 29%. Conclusions: Data from the first 52 pts enrolled in KEYNOTE-086 cohort B suggest that pembrolizumab monotherapy has a manageable safety profile and promising antitumor activity as first-line therapy for PD-L1–positive mTNBC. Clinical trial information: NCT02447003.
Recent Advances in the (Molecular) Phylogeny of Vertebrates (2003)

▪ Abstract The analysis of molecular phylogenetic data has advanced the knowledge of the relationships among the major groups of living vertebrates. Whereas the molecular hypotheses generally agree with traditional morphology-based systematics, they sometimes contradict them. We review the major controversies in vertebrate phylogenetics and the contribution of molecular phylogenetic data to their resolution: (a) the mono-paraphyly of cyclostomes, (b) the relationships among the major groups of ray-finned fish, (c) the identity of the living sistergroup of tetrapods, (d) the relationships among the living orders of amphibians, (e) the phylogeny of amniotes with particular emphasis on the position of turtles as diapsids, (f) ordinal relationships among birds, and (g) the radiation of mammals with specific attention to the phylogenetic relationships among the monotremes, marsupial, and placental mammals. We present a discussion of limitations of currently used molecular markers and phylogenetic methods as well as make recommendations for future approaches and sets of marker genes.
Coronavirus Disease 2019 (COVID‐19) and Cardiovascular Disease: A Viewpoint on the Potential Influence of Angiotensin‐Converting Enzyme Inhibitors/Angiotensin Receptor Blockers on Onset and Severity of Severe Acute Respiratory Syndrome Coronavirus 2 Infection (2020)

he prevalence of coronavirus disease 2019 (COVID-19) has posed a great threat to people's health worldwide, bringing a great challenges to the public healthcare systems. A recent study has confirmed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses severe acute respiratory syndrome coronavirus (SARS-CoV) receptor angiotensin-converting enzyme 2 (ACE2) for host cell entry. 1 ACE2 expression was previously found to correlate with susceptibility to SARS-CoV infection in vitro.
Comparison of dynamic multicast routing algorithms for wide-area packet switched (asynchronous transfer mode) networks (2002)

This paper compares three dynamic multipoint routing algorithms for wide-area packet switched networks like asynchronous transfer mode (ATM) networks. The three algorithms compared are the greedy algorithm, the source rooted shortest path (SP) algorithm and the geographic spread dynamic multicast (GSDM) routing algorithm. We present simulation results over random graphs that demonstrate the performance of these algorithms. The algorithms are evaluated via a series of multiple simulations in terms of the number of packet copies per node and their (in)efficiency. A near optimal Steiner tree heuristic algorithm called the KMB algorithm is used as a measure of the (in)efficiency of the algorithms.
Effect of Short Chain Branching on the Coil Dimensions of Polyolefins in Dilute Solution (2001)

This paper deals with the short branch effect in α-olefin copolymers on radius of gyration Rg and intrinsic viscosity [η] in trichlorobenzene at 135 °C. A wide range of structurally uniform copolymers of ethylene with propylene, 1-butene, 1-hexene, and 1-octene were analyzed by size exclusion chromatography with on-line refractive index, low-angle and multiangle light-scattering and viscometry detectors. Variation of refractive index increment with composition was determined, and corrections for finite concentration were applied. Both Rg and [η] are accurately described by power laws Rg = KsMαs and [η] = KvMαv. The coefficients Ks and Kv vary with comonomer type and amount, but the same exponents, αs = 0.58 and αv = 0.695, apply within the measurement uncertainty to all polymers studied. The ratios gSCB = Rg2/(Rg2)PE and g'SCB = [η]/([η])PE vary linearly with comonomer weight fraction, with slopes that depend on the comonomer type. Various explanations for the observations are considered.
[A genetic study of adult polycystic kidney disease]. (1994)

The 3'HVR has been considered as the most useful probe in making the linkage analysis of adult polycystic kidney disease (APKD). We examined three APKD families using this probe. Their polymorphism information was then computed for linkage study using LINKAGE package and computer programme HOMOG for homogeneity test. One family was defined as non PKD 1, because the disease locus was failed to show linkage to the 3'HVR marker. Of the other two families, one can still not be identified as non PKD1, but had distinguishable meiotic recombinations, another was in favour of linkage to 3'HVR and therefore judged to be PKD1. The presence of genetic heterogeneity could significantly reduce the value of linked probe analysis as a tool for gene diagnosis of APKD.
Thermochemical Ethanol via Indirect Gasification and Mixed Alcohol Synthesis of Lignocellulosic Biomass (2007)

This process design and technoeconomic evaluation addresses the conversion of biomass to ethanol via thermochemical pathways that are expected to be demonstrated at the pilot level by 2012.
Identification of novel α7 nicotinic receptor ligands by in silico screening against the crystal structure of a chimeric α7 receptor ligand binding domain (2012)

A hierarchical in silico screening procedure using the crystal structure of an agonist bound chimeric α7/Ls-AChBP protein was successfully applied to both proprietary and commercial databases containing drug-like molecules. An overall hit rate of 26% (pK(i) ≥5.0) was obtained, with an even better hit rate of 35% for the commercial compound collection. Structurally novel and diverse ligands were identified. Binding studies with [(3)H]epibatidine on chimeric α7/5-HT(3) receptors yielded submicromolar inhibition constants for identified hits. Compared to a previous screening procedure that utilized the wild type Ls-AChBP crystal structure, the current study shows that the recently obtained α7/Ls-AChBP chimeric protein crystal structure is a better template for the identification of novel α7 receptor ligands.
Helix Bundle Quaternary Structure from α/β-Peptide Foldamers (2007)

The function of a protein generally depends on adoption of a specific folding pattern, which in turn is determined by the side chain sequence along the polypeptide backbone. Here we show that the sequence-encoded structural information in peptides derived from yeast transcriptional activator GCN4 can be used to prepare hybrid α/β-peptide foldamers that adopt helix bundle quaternary structures. Crystal structures of two hybrid α/β-peptides are reported along with detailed structural comparison to α-peptides of analogous side chain sequence. There is considerable homology between α- and α/β-peptides at the level of helical secondary structure, with modest but significant differences in the association geometry of helices in the quaternary structure.
Novel Liposaccharide Conjugates for Drug and Peptide Delivery (1998)

Sugar-lipid conjugates with general structure 1-4 were prepared by coupling amino sugars with N-Boc-protected lipoamino acids and oligomers. Conjugates with general structure 5 were also prepared from glucuronic acid and methyl 2-aminohexadecanoate. The physicochemical properties of the conjugates were modified by varying the nature and number of sugars or the number of lipoamino acids or their alkyl chain length. The ability of the liposaccharides to aggregate was examined. These preliminary experiments have demonstrated the ability of the liposaccharides to form particulate systems per se and also their ability to be incorporated into conventional liposomal systems. The structure of the respective liposaccharides and the molar ratio of liposaccharide to dimyristoyl lecithin and cholesterol were found to have a profound effect on the type of colloidal systems produced.
The cloning and characterization of human MyD88: a member of an IL‐1 receptor related family1 (1997)

Murine MyD88, an RNA with homology both to the interleukin-1 receptor signaling domain and to 'death-domains', is rapidly upregulated during differentiation of the myeloleukemic cell line M1. We have cloned the human homologue of murine MyD88 and re-evaluated the murine sequence. The open reading frame for both species encodes a 296 amino acid protein, which for murine MyD88 is 53 amino acids longer than originally published. Human MyD88 cDNA is encoded by 5 exons, and maps to chromosome 3p21.3-p22 by fluorescence in situ hybridization (FISH). Overexpression of the death domain region leads to transcriptional activation of the IL-8 promoter.