gebhart/patrepeval huggingface dataset:
Standardization may suffice for licensure of conjugate vaccines. (1998)

Standardization schemes devised by Control Agencies have followed clinical trials of experimental vaccines. The wealth of information about the pathogenesis of and immunity to bacteria, whose surface polysaccharides are protective antigens, now permits standardization to predict the efficacy of polysaccharide-based vaccines. There has been tacit acceptance of this notion with the licensure of groups Y and W135 meningococcal vaccines and of many of the pneumococcal types whose frequency in patients was too low for statistical significance to be assigned for their clinical efficacy. In fact, this was also the case for licensure of polio virus type 2 vaccine. We can reliably measure the level of anti-polysaccharide antibodies for meningococci, pneumococci, GBS and the Vi of S. typhi. Haemophilus type b conjugates have been reliably standardized by physico-chemical assays. New conjugates, therefore, may be licensed by data provided by standardization without awaiting the results of costly and time-consuming efficacy trials. Adoption of this scientifically-based approach to licensure will hasten the implementation of new and more effective vaccines.
RILLKKMPSV Influences the Vasculature, Neurons and Glia, and (Pro)Renin Receptor Expression in the Retina (2010)

The (pro)renin receptor [(P)RR] is implicated in organ pathology. We examined the cellular location of the (P)RR and whether a putative (P)RR antagonist, RILLKKMPSV, corresponding to the handle region of the prorenin prosegment (handle region peptide [HRP]) influences angiogenesis, inflammation, and neuronal and glial function in rat retina. The (P)RR was localized to retinal vessels, endothelial cells, and pericytes, but most immunolabeling was in ganglion cells and glia. HRP (1 mg/kg per day by IP injection) reduced physiological angiogenesis in developing retina. Moreover, HRP (0.1 mg/kg per day by subcutaneous minipump) reduced pathological retinal angiogenesis, inflammation, and vascular endothelial growth factor and intercellular adhesion molecule-1 mRNA in rats with oxygen-induced retinopathy (OIR) to an extent similar to valsartan (10 mg/kg per day, IP). In contrast to its effects on vasculature, HRP compromised the electroretinogram in shams and OIR and increased phosphorylated extracellular-signal-related protein kinase 1/2 immunolabeling in shams but not in OIR, whereas valsartan did not affect the electroretinogram and reduced extracellular-signal-related protein kinase 1/2 immunolabeling in OIR. Retinal (P)RR mRNA levels were increased in OIR; HRP, but not valsartan, increased (P)RR mRNA levels in shams, whereas both HRP and valsartan reduced (P)RR mRNA levels in OIR. A control peptide (VSPMKKLLIR, 0.1 mg/kg per day) did not influence retinal vasculopathy or function. Circulating HRP levels in rats administered 1 mg/kg per day HRP were undetectable (<3 pmol/L). We conclude that HRP had protective effects on the retinal vasculature similar to those of valsartan; however, unlike valsartan, HRP injured neuro-glia, which may involve the (P)RR, although the undetectable circulating HRP level makes a direct effect of HRP on retinal (P)RR function unlikely.
Pharmacological and psychotherapeutic interventions for management of obsessive-compulsive disorder in adults: a systematic review and network meta-analysis (2016)

National Institute for Health Research.
VUV and UV excilamps and their applications (2006)

The extraordinary characteristics of excilamps (excimer and exciplex lamps) led to a great many of applications, which had been demonstrated in a number of previous studies. This review is principally dedicated to our advances in application of UV/VUV capacitive and barrier discharge excilamps in photoscience (photochemistry and photomedicine). In the present paper, the review of the basic results obtained at the Laboratory of Optical Radiation at High Current Electronics Institute SB RAS during 2003-2005 years is presented.
Comparison of costs of weed control treatments in the pineapple culture in Rio Grande do Sul, Brazil. (2010)

Aiming to reduce production costs we studied the agroeconomic efficiency (&amp;gt; productivity, &amp;lt; cost) of weed control treatments in an experiment lead since 27 Mar 05 to 23 Jul 07 at Fepagro Litoral Norte, Maquiné, RS, in a randomized complete block design, five repetitions of the weed control treatments: T1-Weeding; T2-Glyphosate (2,5 La.i. ha-1); T3-Diuron (2,4 L a.i. ha-1) T4-Diuron+Glyphosate (2,4 + 2,5 L a.i. ha-1); T5-Atrazine+Simazine (3,0 L a.i. ha-1).The cost of T1-W was calculated based on daily payment of a worker and T2, T3, T4 and T5 from the average price of g mL-1 of the active ingredients of the used herbicides, and the gross income was calculated from commercial fruits and price. The price of g mL-1 of atrazine + simazine varied 25 %, glyphosate 32 % and diuron 107 %. The treatments costs was: T1= R$ 2736,00; T5= R$ 653,00; T2= R$ 629,00; T4= R$ 621,00 and T3= R$ 468,00 per hectare per year,respectively 9, 3, 6, 5 and 2 % of the income. The weed control in the pineapple culture with herbicides costed 22 % of the T1-W cost. The T3-D (diuron), applicated by 55 days intervals, was the treatment of higher agroeconomic efficiency and costed 74 % of the average price of the other treatments with herbicides.
Functional overlap but differential expression of CSF-1 and IL-34 in their CSF-1 receptor-mediated regulation of myeloid cells (2010)

CSF-1 is broadly expressed and regulates macrophage and osteoclast development. The action and expression of IL-34, a novel CSF-1R ligand, were investigated in the mouse. As expected, huIL-34 stimulated macrophage proliferation via the huCSF-1R, equivalently to huCSF-1, but was much less active at stimulating mouse macrophage proliferation than huCSF-1. Like muCSF-1, muIL-34 and a muIL-34 isoform lacking Q81 stimulated mouse macrophage proliferation, CSF-1R tyrosine phosphorylation, and signaling and synergized with other cytokines to generate macrophages and osteoclasts from cultured progenitors. However, they respectively possessed twofold and fivefold lower affinities for the CSF-1R and correspondingly, lower activities than muCSF-1. Furthermore, muIL-34, when transgenically expressed in a CSF-1-dependent manner in vivo, rescued the bone, osteoclast, tissue macrophage, and fertility defects of Csf1(op)/(op) mice, suggesting similar regulation of CSF-1R-expressing cells by IL-34 and CSF-1. Whole-mount IL34 in situ hybridization and CSF-1 reporter expression revealed that IL34 mRNA was strongly expressed in the embryonic brain at E11.5, prior to the expression of Csf1 mRNA. QRT-PCR revealed that compared with Csf1 mRNA, IL34 mRNA levels were lower in pregnant uterus and in cultured osteoblasts, higher in most regions of the brain and heart, and not compensatorily increased in Csf1(op/op) mouse tissues. Thus, the different spatiotemporal expression of IL-34 and CSF-1 allows for complementary activation of the CSF-1R in developing and adult tissues.
ROLE OF LEUKOCYTES IN DISSEMINATED INTRAVASCULAR COAGULATION SYNDROME ASSOCIATED WITH SEPSIS (1996)

Disseminstaed intravascular coagulation syndrome(DIC) is a potentially lethal disorder in which microthombi form systemically. In the pathogenesis of DIC, tissue innjury and endothelial injury appeear to be two major mecanisms invovli Tissue injury refers to the pathologic conditions such as obstetrical complications or multiple taruma. In such cases, release of tissue factor, a triggering substance for the extrinsic pathway of coagulation, induces intravascular coagulation. Endothelial injury is induced mainly by such cytokines as tumor necrosis factor-alpha (TNF- a ) or interleukin-10 or by the inflammatory mediators such as granulocyte proteases or oxygen free radicals that are derived from activated leukocytes in the pathophysiology of sepsis. The activated leukocyte-induced endothelial injury may deeply related to the pathogenesis of DIC and adult respiratory distress syndrome(ARDS) in sepsis. ARDS as well as DIC can irdluence the outcome of patients with sepsis. Antithrombin IlI (AT III) and activated protein C (APC) prevent the endotoxin-induced pulmonary vascular injury in animals independent on their anticoagulant properties, but dependent on their inhibitory activities on cytokine production by monocytes. Gabexate mesilate (GM), a synthetic inhibitor for the proteases generated within the coagulation cascade, also prevents the endotoxin-induced pulmonary vascular injury as well as the coagulation abnormalities mainly by inhibiting TNF- a prcduction by monocytes, Although heparin prevents the endotoxin-induced coagulation abnormalities, it does not prevent the pulmonary vascular injury. These observations strongly suggest that AT III, APC, and GM, but not heparin, may be useful in treating both the activated leukocyte-induced coagulation abnormalities and endothelial injury in patients with DIC associated with sepsis.
Observation of bistability in a Vertical-Cavity Semiconductor Optical Amplifier (VCSOA) (2002)

We report, the first time to our knowledge, an observation of optical bistability in a Vertical-Cavity Semiconductor Optical Amplifier (VCSOA) operated in reflection mode. Counterclockwise hysteresis loops are obtained over a range of initial phase detuning and bias currents. One hysteresis loop is observed experimentally with an input power as low as 2 ìW when the device is biased at 98% of its lasing threshold. We also numerically simulate the optical bistability and obtain good agreement with our experimental observations. Bistable VCSOAs significantly advances the prospect of dense 2-D array of low switching-intensity all-optical logic and memory elements.
Worse Comes to Worst: Bananas and Panama Disease—When Plant and Pathogen Clones Meet (2015)

This article deals with: Bananas: their origin and global rollout; genetic diversity of Fusarium oxysporum f.sp. cubense, the causal agent of Panama Disease; Panama Disease: history repeats itself; tropical race 4, a single pathogen clone, threatens global banana production; strategies for sustainable Panama Disease management.
Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity (2005)

Huntington disease (HD) is characterized by the preferential loss of striatal medium-sized spiny neurons (MSNs) in the brain. Because MSNs receive abundant glutamatergic input, their vulnerability to excitotoxicity may be largely influenced by the capacity of glial cells to remove extracellular glutamate. However, little is known about the role of glia in HD neuropathology. Here, we report that mutant huntingtin accumulates in glial nuclei in HD brains and decreases the expression of glutamate transporters. As a result, mutant huntingtin (htt) reduces glutamate uptake in cultured astrocytes and HD mouse brains. In a neuron-glia coculture system, wild-type glial cells protected neurons against mutant htt-mediated neurotoxicity, whereas glial cells expressing mutant htt increased neuronal vulnerability. Mutant htt in cultured astrocytes decreased their protection of neurons against glutamate excitotoxicity. These findings suggest that decreased glutamate uptake caused by glial mutant htt may critically contribute to neuronal excitotoxicity in HD.
Development of Anti-VEGF Therapies for Intraocular Use: A Guide for Clinicians (2011)

Angiogenesis is the process by which new blood vessels form from existing vessel networks. In the past three decades, significant progress has been made in our understanding of angiogenesis; progress driven in large part by the increasing realization that blood vessel growth can promote or facilitate disease. By the early 1990s, it had become clear that the recently discovered "vascular endothelial growth factor" (VEGF) was a powerful mediator of angiogenesis. As a result, several groups targeted this molecule as a potential mediator of retinal ischemia-induced neovascularization in disorders such as diabetic retinopathy and retinal vein occlusion. Around this time, it also became clear that increased intraocular VEGF production was not limited to ischemic retinal diseases but was also a feature of choroidal vascular diseases such as neovascular age-related macular degeneration (AMD). Thus, a new therapeutic era emerged, utilizing VEGF blockade for the management of chorioretinal diseases characterized by vascular hyperpermeability and/or neovascularization. In this review, we provide a guide for clinicians on the development of anti-VEGF therapies for intraocular use.
Extremely high electron mobility in Si/GexSi1−x structures grown by molecular beam epitaxy (1991)

A modulation-doped Si/GexSi1−x structure was fabricated in which a thin Si layer is employed as the conduction channel for the two-dimensional electron gas. The strained heterostructure is fabricated on top of a low threading dislocation density, totally relaxed, GexSi1−x buffer layer with a linearly graded Ge concentration profile. The mobility of the two-dimensional electron gas as determined from Hall measurements was 1600 cm2/V s at 300 K and 96 000 cm2/V s at 4.2 K. Recently, a 4.2 K mobility of 125 000 cm2/V s was observed from a similar sample.
4-Hydroxytamoxifen Trans-Represses Nuclear Factor-κB Activity in Human Osteoblastic U2-OS Cells through Estrogen Receptor (ER)α, and Not through ERβ* (2001)

Estrogens are important mediators of bone homeostasis, and postmenopausal estrogen replacement therapy is extensively used to prevent osteoporosis. The biological effects of estrogen are mediated by receptors belonging to the superfamily of steroid/thyroid nuclear receptors, estrogen receptor (ER)alpha and ER beta. ER alpha, not only trans-activates target genes in a hormone-specific fashion, but it can also neutralize other transcriptional activators, such as nuclear factor (NF)-kappa B, causing repression of their target genes. A major mechanism by which estrogens prevent osteoporosis seems to be repression of transcription of NF-kappa B target genes, such as the osteoclast-activating cytokines interleukin-6 and interleukin-1. To study the capacity of both ERs in repression of NF-kappa B signaling in bone cells, we first carried out transient transfections with ER alpha or ER beta of the human osteoblastic U2-OS cell line, in which endogenous NF-kappa B was stimulated by tumor necrosis factor alpha. Repression by ER alpha was already observed without 17 beta-estradiol, whereas addition of the ligand increased repression to 90%. ER beta, however, was able to repress NF-kappa B activity only in the presence of ligand. Because it is known that some antiestrogens can also display tissue-specific agonistic properties, 4-hydroxytamoxifen was tested for its capacity in repressing NF-kappa B activity and was found to be active (albeit less efficient than 17 beta-estradiol) and, interestingly, only with ER alpha. The pure antagonist ICI 164,384 was incapable of repressing through any ER subtypes. Deletion analysis and the use of receptor ER alpha/ER beta-chimeras showed that the A/B domain, containing activation function-1, is essential for this suppressive action. Next, we developed stable transfectants of the human osteoblastic U2-OS cell line containing ER alpha or ER beta in combination with an NF-kappa B luciferase reporter construct. In these cell lines, repression of NF-kappa B activity was only mediated through ER alpha and not through ER beta. These findings offer new insights into the specific role of both ER subtypes in bone homeostasis and could eventually help in developing more specific medical intervention strategies for osteoporosis.
A phase II study of high-dose continuous infusion interleukin-2 with lymphokine-activated killer cells in patients with metastatic melanoma. (1991)

Thirty-three patients with metastatic melanoma were treated in a phase II study with an intravenous continuous infusion (IVCI) of interleukin-2 (IL2) given with lymphokine-activated killer (LAK) cells. The dose of IL2 was the optimal priming dose for LAK-cell induction, followed by the maximally tolerated LAK-cell dose that could be given by an IVCI schedule as determined by a previous phase I trial. The CI schedule was chosen for evaluation because of a postulated reduction in toxicity with the possibility of administering a more prolonged IL2 infusion and because greater rebound lymphocytosis and LAK-cell generation had been reported using this dose and schedule. The 33 patients were similar in age, performance status, and sites of disease to those treated in previous IL2 trials. All patients were assessable for response and toxicity. One patient (3%) achieved a partial response of 10 months duration. There were no other clinically significant responses. Significant toxicity included hypotension requiring pressors (45%), dyspnea (36%), renal insufficiency (24%), hepatic dysfunction (66%), and cardiac arrhythmias (18%). These toxicities reversed with cessation of the infusion. There were four deaths during the first 30 days of treatment, three from infection (one related to central line, one related to LAK cells, one related to tumor), and one from tumor-related hemorrhage. Toxicity was unexpectedly high and at least comparable to that seen in previous studies using a high-dose IV bolus schedule of IL2. When comparing the IVCI schedule with high-dose bolus IL2 to LAK cells in nonrandomized but sequential studies in patients with advanced melanoma, it appears that CI IL2 is less efficacious.
High-Throughput Protein Expression Using Cell-Free System (2008)

One of the main challenges in this post genomic era is the development and implementation of efficient methods of protein synthesis. A clear understanding of the role of genes in an organism is to comprehend the biological functions of all of its proteins. Acquiring this knowledge will depend in part on the success of rapid synthesis and purification of proteins. The future of structural genomics and functional proteomics depends on the availability of abundantly expressing, soluble proteins in a high-throughput manner. Conventional cell based methods of protein expression is rather laborious, time consuming and the ways to fail are numerous including solubility, toxicity to the host and instability (e.g. proteolysis). Cell-free or in vitro protein synthesis, on the other hand allows the expression and analysis of protein synthesis, may solve many of these problems. It is a simple open system which lends itself for manipulations and modifications to influence protein folding, disulfide bond formation, incorporation of unnatural amino acids, protein stability (by incorporating protease inhibitors in the system) and even the expression of toxic proteins. Cell-free synthesis can also be used as a reliable screening methodology for subsequent protein expression in vivo. Furthermore, this technology is readily amenable to automation. Here, we present a protocol for expressing recombinant proteins with high yield in a standard 96-well plate format using E. coli cell-free extract in a batch mode.
Specific cytolytic T-cell responses to human CEA from patients immunized with recombinant avipox-CEA vaccine. (2000)

Avipox viruses are replication-defective members of the poxvirus family. Avipox-derived vectors such as ALVAC (canarypox) and fowlpox have the ability to infect mammalian cells, including human cells, but do not replicate. The first clinical trial of an avipox recombinant vaccine for patients with advanced carcinomas has recently been conducted using the ALVAC vector and the human carcinoembryonic antigen (CEA) transgene (designated ALVAC-CEA; J. L. Marshall et al, J. Clin. Oncol., 17: 332-337, 1999). The T-cell responses elicited by patients before and after vaccination with the ALVAC-CEA recombinants are characterized in this report. Pre- and postvaccination peripheral blood mononuclear cells (PMBCs) of the eight patients positive for HLA-class I A2 allele, were incubated with the HLA-A2-CEA peptide CAP-1 and interleukin 2. In no cases using prevaccination PMBCs could cultures be established that had the ability to lyse C1R-A2 target cells pulsed with the CAP-1 peptide. However, T-cell cultures from seven of eight of these same patients, obtained from PBMCs after ALVAC-CEA vaccination, were shown to lyse C1R-A2 cells only when pulsed with CAP-1. Moreover, all seven of these T-cell cultures were shown to lyse allogeneic human carcinoma cell lines (SW1463 and SW480) that were both A2+ and expressed CEA; an allogeneic tumor cell line (LS174T) expressing CEA that was negative for A2 expression was not lysed. HLA-A2+ and CEA+ autologous tumor cells were also capable of being lysed by CEA-specific T cells from this patient. Analysis of this CTL line also revealed the expression of several homing and adhesion-associated molecules. Fluorescence-activated cell sorter analysis of the T-cell lines established from patients after ALVAC-CEA vaccination revealed that most were CD8+/CD4-, but many also had a CD8+/CD4+ component. Analyses of T-cell receptor Vbeta usage of several of the CEA-specific CTL lines showed a relatively diverse Vbeta pattern. These studies demonstrate for the first time the ability to vaccinate cancer patients with an avipox recombinant and derive T cells that are capable of lysing allogeneic and autologous tumor cells in a MHC-restricted manner. These studies thus form the rationale to use such replication-deficient recombinant vaccines in future cancer vaccine trials.
A Mechanistic Tumor Penetration Model to Guide Antibody Drug Conjugate Design (2015)

Antibody drug conjugates (ADCs) represent novel anti-cancer modalities engineered to specifically target and kill tumor cells expressing corresponding antigens. Due to their large size and their complex kinetics, these therapeutic agents often face heterogeneous distributions in tumors, leading to large untargeted regions that escape therapy. We present a modeling framework which includes the systemic distribution, vascular permeability, interstitial transport, as well as binding and payload release kinetics of ADC-therapeutic agents in mouse xenografts. We focused, in particular, on receptor dynamics such as endocytic trafficking mechanisms within cancer cells, to simulate their impact on tumor mass shrinkage upon ADC administration. Our model identified undesirable tumor properties that can impair ADC tissue homogeneity, further compromising ADC success, and explored ADC design optimization scenarios to counteract upon such unfavorable intrinsic tumor tissue attributes. We further demonstrated the profound impact of cytotoxic payload release mechanisms and the role of bystander killing effects on tumor shrinkage. This model platform affords a customizable simulation environment which can aid with experimental data interpretation and the design of ADC therapeutic treatments.