gebhart/patrepeval huggingface dataset:
Preventing Retinal Detachment–Associated Photoreceptor Cell Loss in Bax-Deficient Mice (2004)

Apoptosis is a major mechanism leading to photoreceptor cell death after RD. Blockage of the activity of the proapoptotic molecule Bax in a knockout mouse model prevents photoreceptor cell apoptosis and cell loss. These data suggest that the Bax-mediated apoptotic signaling pathway plays a critical role in RD-associated photoreceptor cell death.
Solid-Phase Combinatorial Synthesis of Peptide−Biphenyl Hybrids as Calpain Inhibitors, (2004)

The combinatorial parallel synthesis of peptide-biphenyl hybrids on solid support using state of the art of peptide synthesis is reported. Key steps were the N to C addition of an amino moiety, hydrolysis of the methyl ester, and the absence of cross-linked compounds when the 2,2‘-diamino-1,1‘-biphenyl was incorporated. When tested for activity as calpain inhibitors, some of the compounds exhibited IC50 values in the nanomolar range.
IgA-containing immune complexes in the urine of IgA nephropathy patients (2006)

The amounts of urinary IgA-IgG-containing immune complexes were significantly higher in patients with IgAN than in patients with non-IgA nephropathies or healthy controls.
Measurement of Urea in Human Serum by Isotope Dilution Mass Spectrometry: A Reference Procedure (1999)

This reference measurement procedure allows values to be assigned to controls and calibrators that are traceable to the primary urea reference material of NIST and, therefore, to the Système International unit "mole" with a low degree of uncertainty. This procedure provides a tool for the highly accurate determination of urea in control materials as well as in patient sera.
A Memory Efficient Multiple Pattern Matching Architecture for Network Security (2008)

Pattern matching is one of the most important components for the content inspection based applications of network security, and it requires well designed algorithms and architectures to keep up with the increasing network speed. For most of the solutions, AC and its derivative algorithms are widely used. They are based on the DFA model but utilize large amount of memory because of so many transition rules. An algorithm, called ACC, is presented in this paper for multiple pattern matching. It uses a novel model, namely cached deterministic finite automate (CDFA). In ACC, by using CDFA, only 4.1% transition rules for ClamAV (20.8% for Snort) are needed to represent the same function using DFA built by AC. This paper also proposes a new scheme named next-state addressing (NSA) to store and access transition rules of DFA in memory. Using this method, transition rules can be efficiently stored and directly accessed. Finally the architecture for multiple pattern matching is optimized by several approaches. Experiments show our architecture can achieve matching speed faster than 10 Gbps with very efficient memory utilization, i.e., 81KB memory for 1.8 K Snort rules with total 29 K characters, and 9.5 MB memory for 50 K ClamAV rules with total 4.44 M characters. A single architecture is memory efficient for large pattern set, and it is possible to support more than 10 M patterns with at most half amount of the memory utilization compared to the state-of-the-art architectures.
Somatomedin-C Levels in Children and Adolescents with Gonadal Dysgenesis: Differences from Age-Matched Normal Females and Effect of Chronic Estrogen Replacement Therapy* (1985)

The factors responsible for the elevation of circulating somatomedin-C/insulin-like growth factor I (Sm-C) during normal pubertal development are uncertain. To assess the role of ovarian estrogen secretion during puberty, we examined the effect of estrogen deficiency due to primary hypogonadism on Sm-C levels in late childhood and early adolescence. The concentration of immunoreactive Sm-C was measured in 36 untreated patients with gonadal dysgenesis (age, 4-16 yr); results were compared with the pattern of change in Sm-C in 153 age-matched normal girls. Between ages 4-9 yr, patients with gonadal dysgenesis had Sm-C levels similar to those in the age-matched normal subjects. In contrast to the normal girls, Sm-C levels in patients with gonadal dysgenesis did not rise after 10 yr of age and were significantly lower than those in normal girls at 11-16 yr of age. The effect of low dose estrogen therapy was assessed in eight patients with Turner's syndrome. Their Sm-C levels were measured before and during 2-12 months of treatment with ethinyl estradiol (90-220 ng/kg X day). The mean Sm-C concentration rose from 0.72 +/- 0.06 U/ml (+/- SEM) before treatment to 1.17 +/- 0.17 U/ml during estrogen treatment (P less than 0.04). In three patients who had a similar increase in Sm-C during estrogen treatment, interruption of therapy was associated with a fall in Sm-C concentrations; when estrogen therapy was reinstituted in two of these patients, Sm-C levels rose again. These results suggest that increasing endogenous estrogen production is a major determinant of the rise of circulating Sm-C that occurs during pubertal development in normal girls. Chronic estrogen deficiency, as in untreated patients with gonadal dysgenesis, is associated with failure to manifest the elevation of Sm-C that occurs during normal puberty.
Disruption of the Mouse μ-Calpain Gene Reveals an Essential Role in Platelet Function (2001)

Conventional calpains are ubiquitous calcium-regulated cysteine proteases that have been implicated in cytoskeletal organization, cell proliferation, apoptosis, cell motility, and hemostasis. There are two forms of conventional calpains: the mu-calpain, or calpain I, which requires micromolar calcium for half-maximal activation, and the m-calpain, or calpain II, which functions at millimolar calcium concentrations. We evaluated the functional role of the 80-kDa catalytic subunit of mu-calpain by genetic inactivation using homologous recombination in embryonic stem cells. The mu-calpain-deficient mice are viable and fertile. The complete deficiency of mu-calpain causes significant reduction in platelet aggregation and clot retraction but surprisingly the mutant mice display normal bleeding times. No detectable differences were observed in the cleavage pattern and kinetics of calpain substrates such as the beta3 subunit of alphaIIbbeta3 integrin, talin, and ABP-280 (filamin). However, mu-calpain null platelets exhibit impaired tyrosine phosphorylation of several proteins including the beta3 subunit of alphaIIbbeta3 integrin, correlating with the agonist-induced reduction in platelet aggregation. These results provide the first direct evidence that mu-calpain is essential for normal platelet function, not by affecting the cleavage of cytoskeletal proteins but by potentially regulating the state of tyrosine phosphorylation of the platelet proteins.
The Inhibitor of Apoptosis, cIAP2, Functions as a Ubiquitin-Protein Ligase and Promotes in VitroMonoubiquitination of Caspases 3 and 7 (2000)

The inhibitor of apoptosis, cIAP2, contains a putative Ring finger motif at the C terminus. Using <i>in vitro</i> ubiquitination assays, we found that the Ring finger of cIAP2 alone possesses intrinsic ubiquitin ligase activity and promotes substrate-independent ubiquitination. It also promotes ubiquitination of caspases 3 and 7 but not caspase-1. The Ring fingers of c-Cbl and Apc11 failed to promote caspase-7 ubiquitination, suggesting that the Ring finger of cIAP2 itself is involved in substrate recognition.
Recurrent Highway Networks (2016)

Many sequential processing tasks require complex nonlinear transition functions from one step to the next. However, recurrent neural networks with 'deep' transition functions remain difficult to train, even when using Long Short-Term Memory (LSTM) networks. We introduce a novel theoretical analysis of recurrent networks based on Gersgorin's circle theorem that illuminates several modeling and optimization issues and improves our understanding of the LSTM cell. Based on this analysis we propose Recurrent Highway Networks, which extend the LSTM architecture to allow step-to-step transition depths larger than one. Several language modeling experiments demonstrate that the proposed architecture results in powerful and efficient models. On the Penn Treebank corpus, solely increasing the transition depth from 1 to 10 improves word-level perplexity from 90.6 to 65.4 using the same number of parameters. On the larger Wikipedia datasets for character prediction (text8 and enwik8), RHNs outperform all previous results and achieve an entropy of 1.27 bits per character.
Effectiveness of Nonpeptide Clinical Inhibitor TMC-114 on HIV-1 Protease with Highly Drug Resistant Mutations D30N, I50V, and L90M (2006)

The potent new antiviral inhibitor TMC-114 (UIC-94017) of HIV-1 protease (PR) has been studied with three PR variants containing single mutations D30N, I50V, and L90M, which provide resistance to the major clinical inhibitors. The inhibition constants (K(i)) of TMC-114 for mutants PR(D30N), PR(I50V), and PR(L90M) were 30-, 9-, and 0.14-fold, respectively, relative to wild-type PR. The molecular basis for the inhibition was analyzed using high-resolution (1.22-1.45 A) crystal structures of PR mutant complexes with TMC-114. In PR(D30N), the inhibitor has a water-mediated interaction with the side chain of Asn30 rather than the direct interaction observed in PR, which is consistent with the relative inhibition. Similarly, in PR(I50V) the inhibitor loses favorable hydrophobic interactions with the side chain of Val50. TMC-114 has additional van der Waals contacts in PR(L90M) structure compared to the PR structure, leading to a tighter binding of the inhibitor. The observed changes in PR structure and activity are discussed in relation to the potential for development of resistant mutants on exposure to TMC-114.
Two Case Studies of Patients with Major Depressive Disorder Given Low-Dose (Subanesthetic) Ketamine Infusions (2006)

Physicians who care for pain also must manage comorbid depression, which if not treated, may affect the outcome of pain treatment. When treating patients suffering from complex regional pain syndrome (CRPS) with a low-dose (subanesthetic) ketamine infusion [1–3], it was observed that some patients made a significant recovery from associated depression. This recovery was not formally documented, as the primary concern was the treatment of the patient's pain. Needless to say, it was not possible to quantify to what degree depression recovery was secondary to the patient's recovery from CRPS. Based on this result, it was thought that a low-dose (subanesthetic) infusion of ketamine was worth a trial in patients who were suffering from treatment-resistant depression without other physical or psychiatric illness. Approval for this trial was obtained from the hospital research and ethics committee.

Ketamine was infused intravenously to patients commencing at 15–20 mg/h (0.1–0.2 mg/kg/h) and the dose increased until a maximum tolerated dose was achieved. This dose was assumed to be a therapeutic dose and was maintained for 5 days. Patients were able to eat, drink, watch television, or read. They could feel inebriated and/or unsteady when walking. If hallucinations occurred, the dose was to be reduced. The patient's normal medications were continued as it was feared that stopping them may result in a severe depressive episode.

Before and following each treatment with ketamine, at patient clinic visits, the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Score (HAMD-17) were obtained.

The first two patients are described in detail:

Patient A is a 39-year-old, 101 kg woman with an 18-month history of depression. Her illness resulted in her …
The Tyrosine Kinase Negative Regulator c-Cbl as a RING-Type, E2-Dependent Ubiquitin-Protein Ligase (1999)

Ubiquitination of receptor protein-tyrosine kinases (RPTKs) terminates signaling by marking active receptors for degradation. c-Cbl, an adapter protein for RPTKs, positively regulates RPTK ubiquitination in a manner dependent on its variant SRC homology 2 (SH2) and RING finger domains. Ubiquitin-protein ligases (or E3s) are the components of ubiquitination pathways that recognize target substrates and promote their ligation to ubiquitin. The c-Cbl protein acted as an E3 that can recognize tyrosine-phosphorylated substrates, such as the activated platelet-derived growth factor receptor, through its SH2 domain and that recruits and allosterically activates an E2 ubiquitin-conjugating enzyme through its RING domain. These results reveal an SH2-containing protein that functions as a ubiquitin-protein ligase and thus provide a distinct mechanism for substrate targeting in the ubiquitin system.
Cellular and Molecular Mechanisms in the Induction Phase of Contact Sensitivity (1995)

During the induction phase of contact sensitivity, hapten-specific Th1 cells are primed by epidermal Langerhans cells. These Langerhans cells present hapten on MHC class II molecules and provide costimulatory signals. This presentation discusses the induction of cytokines in Langerhans cells and keratinocytes by haptens and their regulatory effects on contact sensitivity. Haptens were painted on the skin of normal BALB/c mice and epidermal cells were prepared at various times thereafter. Langerhans cell-derived interleukin (IL)-1 beta mRNA was observed as early as 15 min after hapten paining. In keratinocytes, tumor necrosis factor-alpha, IL-1 alpha, IP-10, MIP-2 and IL-10 were found to be up-regulated. IL-1 beta appeared to be a 'master' cytokine since it was able to mimic the effects of haptens, such as the increase of MHC class II expression in Langerhans cells and activation of the cytokine cascade. Injection of anti-IL-1 beta monoclonal antibody prior to hapten application completely prevented epicutaneous sensitization. In vivo application of IL-10 by intradermal injection prior to epicutaneous application of TNCB induced antigen-specific tolerance and impeded the induction of proinflammatory cytokines.
Fettsäuren (2010)

Fettsäuren sind die Hauptbestandteile der in der Nahrung sowie im tierischen und menschlichen Organismus vorkommenden Fette. In der Öffentlichkeit haben sie einen schlechten Ruf, da sie als „Dickmacher“ und Risikofaktor für Erkrankungen wie Arteriosklerose, Herzinfarkt und Schlaganfall gelten. Diese Betrachtungsweise ist jedoch einseitig. Fette erfüllen in Zellen und Geweben lebenswichtige Funktionen. Sie sind wichtige Energieträger und stellen die mengenmäßig bedeutendste Energiereserve des Menschen dar. Sie sind Quelle essenzieller Fettsäuren, unersetzliche Baustoffe von Biomembranen und dienen der mechanischen und elektrischen Isolierung von Zellen. Metabolite der Fette wie Prostaglandine und Leukotriene sind hormonähnliche Substanzen mit wichtigen Regulationsfunktionen.
Manufacturing collaboration resource discovery system (McRDS) (2002)

We present the details of a product prototype we are building to support collaboration and resource discovery in product development efforts. McRDS consists of a framework that integrates CAD, CAE, and office automation tools over various networking infrastructures (Internet, CORBA, etc.). Additionally, it consists of a resource discovery system which is a virtual database, whose data is physically distributed worldwide among heterogeneous product information databases. The collaboration framework supports semantic messaging and information brokering while the information discovery system performs semantic unification in order to respond to queries submitted by users. We use Knowledge Query Manipulation Language (KQML) as the information messaging protocol and PDES/STEP application protocols to express the content of these messages.
Binding of a new monoclonal antibody against N-terminal heptapeptide of fibrin α-chain to fibrin polymerization site ‘A’ (1993)

A novel murine monoclonal antibody against the fibrin α-chain N-terminus is presented, which reacts with desAA- and desAABB-fibrin. In immunoblot procedures, the antibody reacted with fibrin degradation products X and Y of non-crosslinked fibrin, and fragment E. No binding was observed to the fibrin fragment D-dimer, and fibrinogen fragments D and E. Minor binding to fibrinogen fragments X, and Y, and desBB-fibrin were presumably due to minor contamination with (desAA)-fibrin. A prerequisite for binding was release of fibrinopeptides A (FpA), the binding site being a fibrin-specific neo-epitope. No binding was observed to fibrinogen or to thrombin-treated dysfibrinogen MANNHEIM III (Aα 16 Arg Cys) molecules, which do not release FpA. The antibody bound to abnormal fibrin molecules prepared from dysfibrinogen MANNHEIM I (Aα 19 Arg→Gly), albeit to a lesser extent than to normal fibrin. Binding of the antibody to the fibrin cpitope was greatly enhanced by denaturation, e.g. by heat, or by treatment with chaotropic ions. Soluble fibrin in clinical samples is generally found as a complex with fibrinogen, since polymerization sites ‘A’ exposed by release of FpA react with complementary binding sites ‘a’ on the D-domains of other fibrin and fibrinogen molecules. Treatment of samples with NaSCN caused dissociation of fibrin monomer complexes. Reassociation was prevented by denaturation of both polymerization sites ‘A’ and ‘a’. The antibody in combination with NaSCN-treatment of samples was useful for specific detection of fibrin monomer in plasma samples. Measurement was not influenced by fibrinogen degradation products, whereas fibrin degradation products at very high concentration caused some underestimation of fibrin monomer concentration.
Engineered Phagemids for Nonlytic, Targeted Antibacterial Therapies (2015)

The increasing incidence of antibiotic-resistant bacterial infections is creating a global public health threat. Because conventional antibiotic drug discovery has failed to keep pace with the rise of resistance, a growing need exists to develop novel antibacterial methodologies. Replication-competent bacteriophages have been utilized in a limited fashion to treat bacterial infections. However, this approach can result in the release of harmful endotoxins, leading to untoward side effects. Here, we engineer bacterial phagemids to express antimicrobial peptides (AMPs) and protein toxins that disrupt intracellular processes, leading to rapid, nonlytic bacterial death. We show that this approach is highly modular, enabling one to readily alter the number and type of AMPs and toxins encoded by the phagemids. Furthermore, we demonstrate the effectiveness of engineered phagemids in an in vivo murine peritonitis infection model. This work shows that targeted, engineered phagemid therapy can serve as a viable, nonantibiotic means to treat bacterial infections, while avoiding the health issues inherent to lytic and replicative bacteriophage use.
Effects on selective excitation and phase uniformity of concomitant field gradient components (1992)

Some effects of the so-called concomitant gradients in NMR imaging which accompany the bipolar gradients used in flow and diffusion measurements have been studied by Norris and Hutchinson (1990). They concluded that the concomitant magnetic field gradients give rise to a positionally dependent image plane. If the direction of the concomitant gradient is perpendicular to the plane then there will be a phase variation through each voxel that will increase as the square of the voxel thickness. This can lead to signal loss due to dephasing of isochromats within a voxel. There will be a phase gradient across the plane if the concomitant gradient lies within it. In the present work, the effects of these concomitant gradients on selective excitation are considered, along with their impact on the intrinsic phase uniformity of an imaging system using selective pulses. Since analytic solutions to the Bloch equations are not obtainable, the authors have used a numerical simulation to calculate the results.
Catalytic Domain Structures of MT-SP1/Matriptase, a Matrix-degrading Transmembrane Serine Proteinase (2002)

The type II transmembrane multidomain serine proteinase MT-SP1/matriptase is highly expressed in many human cancer-derived cell lines and has been implicated in extracellular matrix re-modeling, tumor growth, and metastasis. We have expressed the catalytic domain of MT-SP1 and solved the crystal structures of complexes with benzamidine at 1.3 A and bovine pancreatic trypsin inhibitor at 2.9 A. MT-SP1 exhibits a trypsin-like serine proteinase fold, featuring a unique nine-residue 60-insertion loop that influences interactions with protein substrates. The structure discloses a trypsin-like S1 pocket, a small hydrophobic S2 subsite, and an open negatively charged S4 cavity that favors the binding of basic P3/P4 residues. A complementary charge pattern on the surface opposite the active site cleft suggests a distinct docking of the preceding low density lipoprotein receptor class A domain. The benzamidine crystals possess a freely accessible active site and are hence well suited for soaking small molecules, facilitating the improvement of inhibitors. The crystal structure of the MT-SP1 complex with bovine pancreatic trypsin inhibitor serves as a model for hepatocyte growth factor activator inhibitor 1, the physiological inhibitor of MT-SP1, and suggests determinants for the substrate specificity.
Drug-Resistant HIV Infection among Drug-Naive Patients in Israel (2004)

Drug-resistant virus was detected in 14.8% of patients with new diagnoses of HIV infection but in 28.6% of patients known to have been infected in Israel. The implications include a need for pretreatment resistance testing and for better programs aimed at prevention of transmission, directed particularly at patients. We did not find significant differences in transmission of resistant virus between those infected with subtypes B and C, despite the different demographic background. A conclusive analysis and interpretation should await a more extensive study.
Using Genetically Engineered Mouse Models of Cancer to Aid Drug Development: An Industry Perspective (2006)

Recent developments in the generation and characterization of genetically engineered mouse models of human cancer have resulted in notable improvements in these models as platforms for preclinical target validation and experimental therapeutics. In this review, we enumerate the criteria used to assess the accuracy of various models with respect to human disease and provide some examples of their prognostic and therapeutic utility, focusing on models for cancers that affect the largest populations. Technological advancements that allow greater exploitation of genetically engineered mouse models, such as RNA interference in vivo, are described in the context of target and drug validation. Finally, this review discusses stratagems for, and obstacles to, the application of these models in the drug development process.
Fluorescence resonance energy transfer microscopy: a mini review (2001)

Fluorescence resonance energy transfer (FRET) microscopy is a better method than the x-ray diffraction, nuclear magnetic resonance, or electron microscopy for studying the structure and localization of proteins under physiological conditions. In this paper, we describe four different light microscopy techniques to visualize the interactions of the transcription factor CAATT/enhancer binding protein alpha (C/EBPalpha) in living pituitary cells. In wide-field, confocal, and two-photon microscopy the FRET image provides two-dimensional spatial distribution of steady-state protein-protein interactions. The two-photon imaging technique provides a better FRET signal (less bleedthrough and photobleaching) compared to the other two techniques. This information, although valuable, falls short of revealing transient interactions of proteins in real time. The fluorescence lifetime methods allow us to monitor FRET signals at the moment of the protein interactions at a resolution on the order of subnanoseconds, providing high temporal, as well as spatial resolution. This paper will provide a brief review of the above-mentioned FRET techniques.