gebhart/patrepeval huggingface dataset:
Non‐uniform assembly of the Bacillus anthracis exosporium and a bottle cap model for spore germination and outgrowth (2007)

Spores of Bacillus anthracis are enclosed by an exosporium composed of a basal layer and an external hair-like nap. The nap is formed by a collagen-like glycoprotein called BclA, while the basal layer contains many different proteins, one of which is a spore-specific alanine racemase (Alr). In this study, we employed fluorescence microscopy and a fluorescently labelled anti-Alr monoclonal antibody (mAb) to examine the distribution of Alr within the exosporium. Binding of the mAb occurred over approximately three-quarters of the exosporium but not in a cap-like region at one end of the spore, indicating the absence or inaccessibility of Alr in this region. We also determined that the cap-like region, or cap, corresponds to the first part of the exosporium assembled within the mother cell during sporulation and the only part of the exosporium assembled in a DeltaexsY mutant strain of B. anthracis. Our results provide the first direct evidence that exosporium assembly is a non-uniform process and suggest that exosporium formation is discontinuous. Finally, we demonstrated that during spore germination and outgrowth, the outgrowing cell always escapes from its exosporium shell by popping through the cap, suggesting that the cap is designed to facilitate the emergence of the outgrowing cell.
The precursor of Alzheimer??s disease amyloid A4 protein resembles a cell-surface receptor (1987)

Kang, J; Lemaire, H-G; Unterbeck, A; Salbaum, JM; Masters, CL; Grzeschik, K-H; Multhaup, G; Beyreuther, K; Müller-Hill, B
Response Rates in Patients with Acute Myeloid Leukemia (AML), Treated with Azacitidine, Using WHO and International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS). (2005)

Abstract The CALGB conducted a series of clinical trials with azacitidine (Vidaza®) administered subcutaneously or intravenously in patients with MDS using the FAB classification (JCO2002;20:2429). Since completion of these CALGB studies (8421, 8921, 9221), a new classification system was developed by the WHO that distinguishes MDS from AML (blasts &gt; 20%). Although studies with azacitidine in patients with AML had previously shown activity, the 75 mg/m2/day dose in the CALGB studies was lower than previously studied. Using the WHO system, the diagnosis for CALGB study patients was redefined and patients with AML were analyzed separately. Most of the 105 patients were previously considered refractory anemia with excess blasts in transformation (RAEB-T). Also, new treatment response criteria for MDS were published by the IWG (Blood2000; 96:3671). Using IWG response criteria, azacitidine patients with WHO AML in studies 8421, 8921, or 9221 had an overall response rate (CR+PR+HI) of 48% (12/25), 32% (9/28), and 37% (10/27), respectively. Best Response using IWG Response Criteria for WHO AML Patients in Studies 8421, 8921, and 9221 Median duration of any response (CR, PR or HI) in the 33 azacitidine-treated responders was 279 days (range: 61 to 724 days). The median duration of CR in the 8 azacitidine-treated responders was not achieved; however, the 25th percentile was 115 days (range: 92 to 274+ days). In Study 9221, the median duration of transfusion independence (defined as ≥56 days) in patients independent at baseline was significantly longer in the azacitidine group compared with supportive care for red blood cells (azacitidine [n=8]: 411 days vs. supportive care [n=9]: 133 days, p=0.02) and platelets (azacitidine [n=13]: 363 days vs. supportive care [n=18]: 125 days, p=0.004). In the azacitidine group, 22% (6/27) of patients had a hemoglobin improvement to &gt;11 g/dL that was maintained for ≥56 days compared with 8% (2/25) in the supportive care group (p=0.2). The proportions of patients with ANC &gt;1500/m3 and platelets &gt;100,000/mm3 lasting for ≥56 days were similar between the treatment arms. Azacitidine patients with WHO AML had a longer median survival (19.3 months) compared with the supportive care group (12.9 months) (p=0.2). Further studies investigating azacitidine in patients with AML with dysplasia are warranted.
Peptide-directed Suppression of a Pro-inflammatory Cytokine Response (2000)

Signal-dependent nuclear translocation of transcription factor nuclear factor kappaB (NF-kappaB) is required for the activation of downstream target genes encoding the mediators of immune and inflammatory responses. To inhibit this inducible signaling to the nucleus, we designed a cyclic peptide (cSN50) containing a cell-permeable motif and a cyclized form of the nuclear localization sequence for the p50-NF-kappaB1 subunit of NF-kappaB. When delivered into cultured macrophages treated with the pro-inflammatory agonist lipopolysaccharide, cSN50 was a more efficient inhibitor of NF-kappaB nuclear import than its linear analog. When delivered into mice challenged with lipopolysaccharide, cSN50 potently blocked the production of proinflammatory cytokines (tumor necrosis factor alpha and interferon gamma) and significantly reduced the lethality associated with ensuing endotoxic shock. Based on specificity studies conducted with a mutated form of cSN50, a functional nuclear localization motif is required for this protective effect. Taken together, our findings demonstrate effective targeting of a cell-permeable peptide that attenuates cytokine signaling in vivo. This new class of biological response modifiers may be applicable to the control of systemic inflammatory reactions.
The range and distribution of murine central nervous system cells infected with the gamma(1)34.5- mutant of herpes simplex virus 1 (1997)

Wild-type herpes simplex virus 1 (HSV-1) multiplies, spreads, and rapidly destroys cells of the murine central nervous system (CNS). In contrast, mutants lacking both copies of the gamma(1)34.5- gene have been shown to be virtually lacking in virulence even after direct inoculation of high-titered virus into the CNS of susceptible mice (J. Chou, E. R. Kern, R. J. Whitley, and B. Roizman, Science 250:1262-1266, 1990). To investigate the host range and distribution of infected cells in the CNS of mice, 4- to 5-week-old mice were inoculated stereotaxically into the caudate/putamen with 3 x 10(5) PFU of the gamma(1)34.5- virus R3616. Four-micrometer-thick sections of mouse brains removed on day 3, 5, or 7 after infection were reacted with a polyclonal antibody directed primarily to structural proteins of the virus and with antibodies specific for neurons, astrocytes, or oligodendrocytes. This report shows the following: (i) most of the tissue damage caused by R3616 was at the site of injection, (ii) the virus spread by retrograde transport from the site of infection to neuronal cell nuclei at distant sites and to ependymal cells by cerebrospinal fluid, (iii) the virus infected neurons, astrocytes, oligodendrocytes, and ependymal cells and hence did not discriminate among CNS cells, (iv) viral replication in some neurons could be deduced from the observation of infected astrocytes and oligodendrocytes at distant sites, and (v) infected cells were being efficiently cleared from the nervous system by day 7 after infection. We conclude that the gamma(1)34.5- attenuation phenotype is reflected in a gross reduction in the ability of the virus to replicate and spread from cell to cell and is not due to a restricted host range. The block in viral replication appears to be a late event in viral replication.
Wyner-ziv video coding with hash-based motion compensation at the receiver (2005)

In the current interframe video compression systems, the encoder performs predictive coding to exploit the similarities of successive frames. The Wyner-Ziv theorem on source coding with side information available only at the decoder suggests that an asymmetric video codec, where individual frames are encoded separately, but decoded conditionally (given temporally adjacent frames) could achieve similar efficiency. In the previous work we propose a Wyner-Ziv coding scheme for motion video that uses intraframe encoding instead of interframe decoding. In this paper we improve on our Wyner-Ziv video codec by sending hash codewords of the current frame to aid the decoder in accurately estimating the motion. This allows us to implement a low-delay system where only the previous reconstructed frame is used to generate the side information of a current frame. Simulation results show significant gains above conventional DCT-based intraframe coding. The Wyner-Ziv video codec with hash-based motion compensation at the receiver enables low-complexity encoding while achieving high compression efficiency.
Identification of a Nonbasic Melanin Hormone Receptor 1 Antagonist as an Antiobesity Clinical Candidate (2014)

Identification of MCHR1 antagonists with a preclinical safety profile to support clinical evaluation as antiobesity agents has been a challenge. Our finding that a basic moiety is not required for MCHR1 antagonists to achieve high affinity allowed us to explore structures less prone to off-target activities such as hERG inhibition. We report the SAR evolution of hydroxylated thienopyrimidinone ethers culminating in the identification of 27 (BMS-819881), which entered obesity clinical trials as the phosphate ester prodrug 35 (BMS-830216).
Ceramide Synthesis Correlates with the Posttranscriptional Regulation of the Sterol-Regulatory Element-Binding Protein (2004)

Ceramide synthesis correlates with the generation of transcriptionally active SREBP and SRE-mediated gene transcription. Inhibition of ceramide synthesis decreases levels of transcriptionally active SREBP and SRE-mediated gene transcription. It is hypothesized that the process of ongoing ceramide synthesis contributes to the physiological processing of SREBP, perhaps affecting ER-to-Golgi trafficking. Taken together, modification of ceramide synthesis could be a novel target for drug development in the pharmacologic modification of SRE-dependent pathways.
Shedding light: laser physics and mechanism of action (2010)

Lasers have affected health care in many ways. Clinical applications have been found in a number of medical and surgical specialities. In particular, applications of laser technology in phlebology has made it essential for vein physicians to obtain a fundamental knowledge of laser physics, laser operation and also to be well versed in laser safety procedures. This article reviews recommended text books and current literature to detail the basics of laser physics and its application to venous disease. Laser safety and laser side effects are also discussed.
Broadband gain flattened Raman amplifier to extend operation in the third telecommunication window (2002)

We report the gain flattening of dual stage dual wavelength pumped fibre Raman amplifiers flattening the gain using long period fibre grating and a first order interferometric filter. A flattened gain of 60 nm and an average gain of 15.9 dB were achieved.
Dimethyl fumarate treatment induces adaptive and innate immune modulation independent of Nrf2 (2016)

Dimethyl fumarate (DMF) (BG-12, Tecfidera) is a fumaric acid ester (FAE) that was advanced as a multiple sclerosis (MS) therapy largely for potential neuroprotection as it was recognized that FAEs are capable of activating the antioxidative transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. However, DMF treatment in randomized controlled MS trials was associated with marked reductions in relapse rate and development of active brain MRI lesions, measures considered to reflect CNS inflammation. Here, we investigated the antiinflammatory contribution of Nrf2 in DMF treatment of the MS model, experimental autoimmune encephalomyelitis (EAE). C57BL/6 wild-type (WT) and Nrf2-deficient (Nrf2(-/-)) mice were immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 (p35-55) for EAE induction and treated with oral DMF or vehicle daily. DMF protected WT and Nrf2(-/-) mice equally well from development of clinical and histologic EAE. The beneficial effect of DMF treatment in Nrf2(-/-) and WT mice was accompanied by reduced frequencies of IFN-γ and IL-17-producing CD4(+) cells and induction of antiinflammatory M2 (type II) monocytes. DMF also modulated B-cell MHC II expression and reduced the incidence of clinical disease in a B-cell-dependent model of spontaneous CNS autoimmunity. Our observations that oral DMF treatment promoted immune modulation and provided equal clinical benefit in acute EAE in Nrf2(-/-) and WT mice, suggest that the antiinflammatory activity of DMF in treatment of MS patients may occur through alternative pathways, independent of Nrf2.
Structures of Isobutyryl-CoA Dehydrogenase and Enzyme-Product Complex (2004)

The acyl-CoA dehydrogenases are a family of mitochondrial flavoproteins involved in the catabolism of fatty and amino acids. Isobutyryl-CoA dehydrogenase (IBD) is involved in the catabolism of valine and catalyzes the conversion of isobutyryl-CoA to methacrylyl-CoA. The crystal structure of IBD with and without substrate has been determined to 1.76-A resolution. The asymmetric unit contains a homotetramer with substrate/product bound in two monomers. The overall structure of IBD is similar to those of previously determined acyl-CoA dehydrogenases and consists of an NH2-terminal alpha-helical domain, a medial beta-strand domain and a C-terminal alpha-helical domain. The enzyme-bound ligand has been modeled in as the reaction product, methacrylyl-CoA. The location of Glu-376 with respect to the C-2-C-3 of the bound product and FAD confirms Glu-376 to be the catalytic base. IBD has a shorter and wider substrate-binding cavity relative to short-chain acyl-CoA dehydrogenase, permitting the optimal binding of the isobutyryl-CoA substrate. The dramatic lateral expansion of the binding cavity seen in isovaleryl-CoA dehydrogenase is not observed in IBD. The conserved tyrosine or phenylalanine that defines a side of the binding cavity in other acyl-CoA dehydrogenases is replaced by a leucine (Leu-375) in the current structure. Substrate binding changes the position of some residues lining the binding pocket as well as the position of the loop containing the catalytic glutamate and subsequent helix. Three clinical mutations have been modeled to the structure. The mutations do not affect substrate binding but instead appear to disrupt protein folding and/or stability.
Social street view (2016)

This paper presents an immersive geo-spatial social media system for virtual and augmented reality environments. With the rapid growth of photo-sharing social media sites such as Flickr, Pinterest, and Instagram, geo-tagged photographs are now ubiquitous. However, the current systems for their navigation are unsatisfyingly one- or two-dimensional. In this paper, we present our prototype system, Social Street View, which renders the geo-tagged social media in its natural geo-spatial context provided by immersive maps, such as Google Street View. This paper presents new algorithms for fusing and laying out the social media in an aesthetically pleasing manner with geospatial renderings, validates them with respect to visual saliency metrics, suggests spatio-temporal filters, and presents a system architecture that is able to stream geo-tagged social media and render it across a range of display platforms spanning tablets, desktops, head-mounted displays, and large-area room-sized curved tiled displays. The paper concludes by exploring several potential use cases including immersive social storytelling, learning about culture and crowd-sourced tourism.
Nitrosative stress in primary glial cultures after induction of the inducible isoform of nitric oxide synthase (i-NOS) (2000)

Primary glial cultures are able to express the inducible isoform of nitric oxide synthase (i-NOS) upon stimulation by bacterial lipopolysaccharides (LPS) and gamma-interferon (gamma-IfN). Immunocytochemical studies revealed, that under our experimental conditions i-NOS is expressed exclusively by the microglial cells and not in the astrocytes. Nitric oxide (NO) formation represents an oxidative load for the microglial cells, as observed by the oxidation rate of the ROS- and peroxynitrite indicator dichloro-dihydrofluorescein (DCF-H) in these cells. However, cell viability was not affected by the nitric oxide formation, indicating some form of protection against the higher oxidative load. Upregulation of Mn-SOD in the mitochondria in the course of the induction of i-NOS and, compared to the astrocytes, higher GSH levels in the microglial cells probably explain the resistance of the cultures against nitrosative stress. Increased SOD-activities in the mitochondria could lower the superoxide concentration in this organelle and may prevent an oxidative and/or nitrosative damage via a decreased peroxynitrite formation. The higher GSH-levels in the microglial cells of unstimulated cultures represents a buffer which, under the conditions of i-NOS catalyzed NO-formation, prevents a decline of the microglial GSH-levels below that of the astrocytes.
The Matrix Metalloproteinase GeneGmMMP2Is Activated in Response to Pathogenic Infections in Soybean (2001)

Matrix metalloproteinases (MMPs) play an important role in host defense responses against pathogens in mammals where their activities lead to the production of antimicrobial peptides. We have identified a novel soybean (Glycine max) metalloproteinase gene, GmMMP2, that is transcriptionally up-regulated in infected tissues. The deduced amino acid sequence indicates that this gene belongs to the MMP family. It is a preproprotein containing an N-terminal signal peptide, a cysteine switch, a zinc-binding catalytic motif, and a C-terminal transmembrane domain. The GmMMP2 expressed in and purified from Escherichia coli exhibited an in vitro enzymatic activity in digesting myelin basic protein. All plant metalloproteinases reported so far have no known functions. However, they have been suggested to be involved in extracellular cell matrix degradation during development or senescence. Our investigations demonstrate that the GmMMP2 transcript levels were rapidly increased in compatible and incompatible interactions of soybean tissues with the oomycete pathogen Phytophthora sojae or the bacterial pathogen Pseudomonas syringae pv. glycinea. In agreement with the GmMMP2 activation, a metalloproteinase activity was gradually increased in suspension-cultured cells following the bacterial infection. GmMMP2 was also activated in response to wounding and dehydration. However, GmMMP2 activation did not correlate with the oxidative burst leading to the hypersensitive response cell death or the tissue senescence progress that involves programmed cell death. Our investigations suggest that GmMMP2 may be involved in a novel defense response of soybean against pathogenic infections.
Persistent Echovirus Infection of Mouse Cells Expressing the Viral Receptor VLA-2 (1997)

Mouse cells are not susceptible to infection with echovirus 1 (EV-1) because they lack the viral receptor, human VLA-2. Two mouse fibroblast cell lines, L cells and 3T3 cells, were made susceptible to EV-1 infection after transformation with cDNAs of human VLA-2. After EV-1 infection, L cell transformants of human VLA-2 (alpha2beta1 L cells) develop cytopathic effect (CPE) as expected, while 3T3 cell transformants of human VLA-2 (alpha2beta1 3T3 cells) or the alpha2 subunit of human VLA-2 (alpha2 3T3 cells) become persistently infected. The distinct outcome is not a result of differential virus growth on these transformants because one-step growth curve analysis reveals little difference in EV-1 replication in both cell lines. In addition, 3T3 cell transformants expressing the poliovirus receptor (Pvr 3T3 cells) are lysed during poliovirus infection, suggesting that 3T3 cells are not intrinsically resistant to CPE caused by enterovirus infection. The results of limit dilution assays indicate that all EV-1-infected alpha2 3T3 cells produce infectious virus. All EV-1-infected alpha2 3T3 cells remain viable after EV-1 infection, and the kinetics of cell growth were not altered. FACS analysis reveals that receptor down-regulation is not involved in the establishment of persistent infection. Furthermore, inhibition of host protein synthesis was not observed in EV-1-infected alpha2 3T3 or alpha2beta1 L cells. Since alpha2beta1 L cells are lysed by EV-1 infection, these findings suggest that virus-induced translation inhibition is not a determinant of cell killing.
Preclinical Pharmacokinetics of Ranibizumab (rhuFabV2) after a Single Intravitreal Administration (2005)

This study demonstrates that ranibizumab has a PK profile that is favorable for its clinical use in treating neovascular AMD by monthly ITV injection.
Emergence of Virulent Methicillin-Resistant Staphylococcus aureus Strains Carrying Panton-Valentine Leucocidin Genes in The Netherlands (2005)

Methicillin-resistant Staphylococcus aureus (MRSA) strains carrying the Panton-Valentine leucocidin (PVL) genes have been reported worldwide and are a serious threat to public health. The PVL genes encode a highly potent toxin which is involved in severe skin infections and necrotizing pneumonia, even in previously healthy individuals. We assessed the prevalence of PVL-positive MRSA in The Netherlands for two periods of time: (i) 1987 through 1995 and (ii) 2000 and 2002, and determined their characteristics by using multilocus sequence typing and staphylococcal chromosome cassette (SCCmec) typing. It was found that up to 15% of all MRSA isolates detected in The Netherlands harbored the PVL genes. Most PVL-positive MRSA isolates were obtained from severe soft tissue infections in relatively young individuals. The first PVL-positive MRSA described in The Netherlands, isolated in 1988, was a single-locus variant of the "Berlin" epidemic MRSA clone. The 20 PVL-positive MRSA isolates studied in 2000 and 2002 consisted of five different sequence types (STs) that belonged to four clonal complexes. One of the STs, ST80, is considered to be a widespread European clone and was the most predominant ST (60%) in this study, while ST37 had never been found to be associated with PVL-positive MRSA. Most isolates harbored SCCmec type IV, a supposed marker for community-acquired MRSA. The number and type of virulence-associated genes varied among the different STs.
On the temporal decorrelation of feature parameters for noise-robust speech recognition (2000)

We propose a new frame decorrelation method for robust speech recognition in noisy environments. In most cases, signal perturbation is caused by channel distortion and additive background noise, and can be modeled as a slowly varying term in either the log spectral or the linear-spectral domains. Thus, it is effective to deemphasize slowly varying stationary components in the spectral feature domain of speech signals, which can be considered as a temporal decorrelation process. The proposed method presents a well structured high-pass filter using the decorrelation principle, and provides some significant insights into existing high-pass approaches, such as relative spectral (RASTA) processing. The performance of the proposed method was evaluated by speaker-independent isolated-word recognition experiments using the hidden Markov model (HMM). Noisy speech was simulated by adding noise sources taken from the Noisex-92 database. Experimental results showed that the proposed method was effective for speech recognition with significant noise and yielded better performance than other high-pass methods. In addition, we compared the dynamic property of the proposed filter with that of delta features. The feature obtained by the proposed method may offer most of the delta feature property.
Reversible Switching between Superhydrophilicity and Superhydrophobicity (2003)

From soaking wet to bone dry: The concept of reversible switching between superhydrophilicity and superhydrophobicity of a surface (see picture) exploits the thermally responsive wettability of poly(N-isopropylacrylamide), and this property is enhanced by surface roughness.