gebhart/patrepeval huggingface dataset:
Phase 1b Study Of Otlertuzumab (TRU-016), An Anti-CD37 ADAPTIR™ Protein, In Combination With Rituximab In Patients With Previously Untreated Chronic Lymphocytic Leukemia (CLL) (2013)

Abstract Background CD37 is a tetraspanin protein expressed on the surface of normal and transformed B-cells across a wide range of maturational stages and demonstrates death signaling via SHP1. Otlertuzumab is a CD37-specific therapeutic protein built on the ADAPTIR™(modular protein technology) platform that has shown significantly greater direct killing of CLL cells than rituximab and higher levels of Fc-mediated cellular cytotoxicity of CLL cells than either alemtuzumab or rituximab in pre-clinical models. This phase 1b trial was conducted to evaluate the safety and efficacy of otlertuzumab in combination with rituximab in patients with previously untreated CLL. Methods Patients with untreated CLL that required treatment, had adequate organ function, ECOG ≤2, and absolute neutrophil count ≥800/μL were eligible. Patients were ineligible for chemotherapy as first-line therapy due to patient age, comorbidity, or patient refusal of chemotherapy Patients received otlertuzumab (20 mg/kg) weekly by IV infusion for two 28-day cycles then once a month for 4 months. Rituximab (375 mg/m2 the first dose then 500 mg/m2) was administered after otlertuzumab by IV infusion on the same schedule. Safety was evaluated using CTCAE and IWCLL 2008 Grading scale for Hematologic Toxicity in CLL Studies. Response was determined using the 1996 NCI and the 2008 IWCLL Criteria. Results 24 patients have been treated. Patient characteristics and adverse events are shown in the table. The majority of the patients have not completed 6 cycles of therapy. The preliminary response by investigator assessment using NCI criteria at the last assessment is an ORR 88% (21/24); 2 patients have had PD. Six patients have had CT scans and bone marrow assessments 3 months after their last dose of study drug; by IWCLL criteria 1 has a CR, 4 have a PR and 1 has SD. The patient with a CR was MRD negative by five color flow cytometry of bone marrow aspirate. One patient discontinued therapy for a systemic inflammatory response. Severe (Grade 3 or 4) neutropenia was reported in 13% of patients; the incidence of severe infections was low (8%). Serious adverse events were reported for 4 patients: pneumonia, systemic inflammatory response, and deep vein thrombosis in 1 patient; and lymph node pain, worsening sinusitis, and fever in 1 patient each. Conclusions The preliminary response rate with otlertuzumab in combination with rituximab is promising. Follow-up is ongoing and the IWCLL response rate will be presented. Disclosures: O'Brien: Emergent Product Development: Research Funding. Stromatt:Emergent Biosolutions: Employment. Awan:Lymphoma Research Foundation - Research Funding: Research Funding, Speakers Bureau; Spectrum Pharmaceuticals, Inc. - Speakers bureau: Research Funding, Speakers Bureau.
Induction of antibody synthesis in vitro by immunogenic RNA. (1975)

Spleen cells (SpC) from nonimmunized CFW mice were converted into antibody plaque-forming cells (PFC) by incubation with RNA extracted from livers and spleens of immunized mice (4 days after a single intravenous injection of 0.2 ml of 5% sheep red blood cells (SRBC). RNA was extracted by the phenol-detergent procedure only when sensitization determined by the technique of Jerne showed at least one PFC per 1,500 SpC. Immunogenic activity of RNA from lives of immunized mice was identical with that of RNA from spleens. Immunogenic RNA was inactivated by RNase but not by DNase or pronase, indicating that induction of antibody synthesis requires intact RNA. Newly synthesized antibodies were specific for the SRBC injected antigen; plaques did not occur when other RBC were used in place of SRBC for the in vitro test. The influence of antibiotics on this phenomenon is also discussed.
Synthetic detergents from animal fats. VIII. The ethenoxylation of fatty acids and alcohols (1957)

Summary A laboratory survey of the properties of a series of ethenoxylated fatty acids and alcohols containing about 10, 15, 20, 30, and 40 ethenoxy groups per molecule has brought together information on solubility, cloud point, surface and interfacial tension, detergency, and wetting, foaming and emulsifying properties. Ethenoxylated alcohols were generally more soluble and had better wetting and foaming properties than the acids. Ethenoxylated acids had generally lower surface and interfacial tension values. Both types of nonionics appeared to be excellent emulsifying agents. Most of the ethenoxylated acids and alcohols were equally effective as built detergents. Built ethenoxylated oleic acid (n=10) and built hydroxy‐, dihydroxy‐, phenyl‐, and xylylstearic acids (n=20) were the best detergents. Nonionic surface‐active agents derivable from animal fats appeared to have an optimum range in the average number of ethenoxy groups per molecule, with respect to certain properties. The optimum was in the range of about 14 to 18 for wetting properties, the foaming properties of ethenoxylated alcohols, and the interfacial tension of ethenoxylated acids. This range is about equal to the value suggested for adequate solubility [3 less than the number of carbon atoms in the parent alcohol (3)] but somewhat higher than the general rule for maximum detergency [2/3 the number of carbon atoms in the parent acid or alcohol (1,5)]. The rate of the reaction of octadecanol and stearic acid with ethylene oxide was compared. The alcohol reacted faster, in a non‐specific manner. The acidity of the carboxyl group of stearic acid promoted conversion to ethylene glycol monostearate before further ethenoxylation occurred. After disappearance of the carboxylic acid the rate of the reaction of the ethenoxylated acid approached that for octadecanol. A reaction mechanism consistent with these results is proposed.
Divergent effect of cyclosporine on Th1/Th2 type cytokines in patients with severe, refractory rheumatoid arthritis. (2000)

Our results suggest that the therapeutic effect of cyclosporine is achieved by correcting a Th1/Th2 imbalance (a shift of Th1 type to Th2 type), which may be involved in the pathogenesis of RA; and that circulating IL-10 is useful to assess the clinical improvements in patients with RA after administration of cyclosporine.
Basic Fibroblast Growth Factor Increased Regional Myocardial Blood Flow and Limited Infarct Size of Acutely Infarcted Myocardium in Dogs (1998)

Basic fibroblast growth factor (bFGF), a growth factor potent in promoting angiogenesis, has been shown to reduce infarct size in experimentally induced acute myocardial infarction. However, the effect of bFGF on regional myocardial blood flow (Qm) in the acutely infarcted myocardium has not been well clarified. In 20 open-chest dogs, the left anterior descending (LAD) coronary artery was occluded and animals were maintained in this condition for 4 weeks. In eight of these dogs, bFGF (300 microg) was injected into the myocardium supplied by the LAD and the artery was ligated (bFGF group), and in the other 12 dogs, saline was injected (control group). Nonradioactive colored microspheres were used to measure Qm. The amount of viable myocardium as percent of visual field in the microscope and the extent of fibrosis scored histologically from 0 to 5 in the infarcted area 4 weeks after occlusion were measured. In the outer layer, the Qm values immediately after and 4 weeks after occlusion were 26 +/- 2% and 70 +/- 6%, respectively, in the control group, and 46 +/- 5% and 121 +/- 13%, respectively, in the bFGF group. The Qm at both times in the bFGF group was significantly higher than the corresponding control group values (p < 0.01). The Qm at 4 weeks in the inner and the middle layers also significantly increased in the bFGF group. There was more viable myocardium (control vs bFGF group; 41 +/- 5 vs 61 +/- 7%, p < 0.05) and less fibrosis (3.1 +/- 0.2 vs 2.0 +/- 0.4, p < 0.01) at the outer layer in the bFGF group. It was found that bFGF caused a marked increase in Qm, an increase of viable myocardium, and a decrease of fibrosis in the infarcted myocardium in dogs.
Impedance spectroscopy using maximum length sequences: Application to single cell analysis (2007)

A maximum length sequence (MLS) is used to perform broadband impedance spectroscopy on a dielectric sample. The method has a number of advantages over other pulse-based or frequency sweep techniques. It requires the application of a very short sequence of voltage steps in the microsecond range and therefore allows the measurement of time-dependent impedance of a sample with high temporal resolution over a large bandwidth. The technique is demonstrated using a time-invariant passive RC network. The impedance of single biological cell flowing in a microfluidic channel is also measured, showing that MLS is an ideal method for high speed impedance analysis.
区位优势对跨国公司转让定价的影响（下）——兼谈中国人对欧洲名品手袋的偏爱和印度低廉的生产成本 (2014)

（接上期）四、国际案例（一）美国：康柏（Compaq）案康柏案（1999）涉及知名跨国公司康柏在休斯顿进行的个人电脑（PC）制造活动。这些PC的部分零配件制造地点被调整到位于新加坡的关联企业（康柏亚洲），以实现成本节约。在亚洲市场上，康柏亚洲是惟一能够满足康柏质量标准和需求的生产商。
Poly(ADP-Ribose) polymerase (PARP) inhibitors: Exploiting a synthetic lethal strategy in the clinic (2011)

Poly(ADP-ribose) polymerase (PARP) is an attractive antitumor target because of its vital role in DNA repair. The homologous recombination (HR) DNA repair pathway is critical for the repair of DNA double-strand breaks and HR deficiency leads to a dependency on error-prone DNA repair mechanisms, with consequent genomic instability and oncogenesis. Tumor-specific HR defects may be exploited through a synthetic lethal approach for the application of anticancer therapeutics, including PARP inhibitors. This theory proposes that targeting genetically defective tumor cells with a specific molecular therapy that inhibits its synthetic lethal gene partner should result in selective tumor cell killing. The demonstration of single-agent antitumor activity and the wide therapeutic index of PARP inhibitors in BRCA1 and BRCA2 mutation carriers with advanced cancers provide strong evidence for the clinical application of this approach. Emerging data also indicate that PARP inhibitors may be effective in sporadic cancers bearing HR defects, supporting a substantially wider role for PARP inhibitors. Drugs targeting this enzyme are now in pivotal clinical trials in patients with sporadic cancers. In this article, the evidence supporting this antitumor synthetic lethal strategy with PARP inhibitors is reviewed, evolving resistance mechanisms and potential molecular predictive biomarker assays are discussed, and the future development of these agents is envisioned.
On the theory of tumor self-seeding: implications for metastasis progression in humans (2010)

Metastasis remains the leading cause of death among cancer patients because few effective treatment options are available. A recent paper proposes a new twist on metastasis. The paper shows that circulating tumor cells can return to the primary tumor, a process termed tumor self-seeding or cross-seeding, and that this helps breeding tumor cells that give rise to aggressive metastatic variants. A viewpoint presented here addresses the implications of these studies for human cancer metastasis.
Antitumor Efficacy of Intermittent Treatment Schedules with the Rapamycin Derivative RAD001 Correlates with Prolonged Inactivation of Ribosomal Protein S6 Kinase 1 in Peripheral Blood Mononuclear Cells (2004)

The orally bioavailable rapamycin derivative RAD001 (everolimus) targets the mammalian target of rapamycin pathway and possesses potent immunosuppressive and anticancer activities. Here, the antitumor activity of RAD001 was evaluated in the CA20948 syngeneic rat pancreatic tumor model. RAD001 demonstrated dose-dependent antitumor activity with daily and weekly administration schedules; statistically significant antitumor effects were observed with 2.5 and 0.5 mg/kg RAD001 administered daily [treated tumor versus control tumor size (T/C), 23% and 23-30%, respectively], with 3-5 mg/kg RAD001 administered once weekly (T/C, 14-36%), or with 5 mg/kg RAD001 administered twice weekly (T/C, 36%). These schedules were well tolerated and exhibited antitumor potency similar to that of the cytotoxic agent 5-fluorouracil (T/C, 23%). Moreover, the efficacy of intermittent treatment schedules suggests a therapeutic window allowing differentiation of antitumor activity from the immunosuppressive properties of this agent. Detailed biochemical profiling of mammalian target of rapamycin signaling in tumors, skin, and peripheral blood mononuclear cells (PBMCs), after a single administration of 5 mg/kg RAD001, indicated that RAD001 treatment blocked phosphorylation of the translational repressor eukaryotic initiation factor 4E-binding protein 1 and inactivated the translational activator ribosomal protein S6 kinase 1 (S6K1). The efficacy of intermittent treatment schedules was associated with prolonged inactivation of S6K1 in tumors and surrogate tissues (> or =72 h). Furthermore, detailed analysis of the dose dependency of weekly treatment schedules demonstrated a correlation between antitumor efficacy and prolonged effects (> or =7 days) on PBMC-derived S6K1 activity. Analysis of human PBMCs revealed that S6K1 also underwent a concentration-dependent inactivation after RAD001 treatment ex vivo (>95% inactivation with 20 nM RAD001). In contrast, human PBMC-derived eukaryotic initiation factor 4E-binding protein 1 was present predominantly in the hypophosphorylated form and was unaffected by RAD001 treatment. Taken together, these results demonstrate a correlation between the antitumor efficacy of intermittent RAD001 treatment schedules and prolonged S6K1 inactivation in PBMCs and suggest that long-term monitoring of PBMC-derived S6K1 activity levels could be used for assessing RAD001 treatment schedules in cancer patients.
Practical applications of voice input to machines (1976)

Voice input to machine is the most natural form of man-machine communications. In this type of system the machine responds to the mode of communications preferred by the user, rather than vice versa. Many practical applications exist today for limited capability voice input systems. The first operational voice input systems have taken place with limited vocabulary, isolated word voice input systems. Most of these initial systems were for industrial applications in which the users' hands or eyes were already busy with their normal work requirements. Future developments in both new applications and increased capability voice input systems can be expected to considerably expand the usage of this form of man-machine communications.
Intravenous Polyclonal Immunoglobulin Administration to Sepsis Syndrome Patients: A Prospective Study in a Pediatric Intensive Care Unit (2005)

Life-threatening infections account for about 25 per cent of children requiring admission to pediatric intensive care units (PICU). The results of the use of polyclonal intravenous immunoglobulins as an adjuvant in pediatric sepsis syndrome therapy are conflicting. A prospective study of 100 sepsis syndrome PICU patients aged 1-24 months and divided into two matching groups (septic cases and control, 50 patients each) was performed. All patients were treated according to the routine protocol PICU therapy. Only the cases group received, in addition, polyclonal IVIG (Pentaglobin, Biotest) in a dose of 400 mg/kg for 3 days. All cases were evaluated for PRISM III score 8 h after admission; routine blood, urine, stool and cerebrospinal fluid (whenever appropriate) culture. Daily laboratory examination (blood gases, electrolytes, liver and renal functions, complete blood picture and C-reactive protein) were performed for the first 5 days. Blood samples were obtained for evaluation of tumor necrosis factor-alpha (TNF-alpha) daily for the first 5 days. Referral site (ward or casuality), length of PICU stay (LOS) and outcome (discharged or deceased), the number and percentage of cases who progressed to complications were recorded. Results showed that group I had a significantly higher percentage of discharged cases (72 per cent vs. 44 per cent), significantly shorter LOS (6.1 days vs. 9.1 days), and a significantly lower percentage of progress to complications (8 per cent vs. 32 per cent) especially disseminated intravascular coagulation (4 per cent vs. 24 per cent). TNF-alpha was significantly reduced among septic cases on discharge (2.24 vs. 3.6 mg/dl, p<0.001). A multiple logistic regression model revealed that treatment with IVIG, LOS, severity of sepsis and lymphocyte percentage (L per cent) on admission were significant predictors for survival. In summary the study revealed that the use of polyclonal IVIG among PICU sepsis syndrome showed a significant reduction in mortality, LOS and less progress to complications. A multicenter study is recommended to confirm these results.
Modifications of retinal neurons in a mouse model of retinitis pigmentosa (2000)

Animal models of retinitis pigmentosa include the rd mouse, in which a mutation of a rod-specific phosphodiesterase leads to the rapid loss of photoreceptors during the early postnatal life. Very little is known about changes occurring in inner retinal neurons after photoreceptor loss. These changes are important in view of the possibility of restoring vision in retinas with photoreceptor degeneration by means of cell transplantation or direct stimulation of inner layers. In this paper, we show that bipolar and horizontal cells of the rd mouse retina undergo dramatic morphological modifications accompanying photoreceptor loss, demonstrating a dependence of second order neurons on these cells. While describing modifications of the rd retina, we also provide quantitative information about neurons of the wild-type mouse retina, useful for future studies on genetically altered animals.
Deficit and nondeficit forms of schizophrenia: the concept (1988)

The authors provide a rationale for distinguishing the primary, enduring negative symptoms of schizophrenia (termed "deficit symptoms") from the more transient negative symptoms secondary to other factors. They argue that the former are more likely to provide a basis for meaningful subtyping of the schizophrenic syndrome, while the latter are more likely to respond to currently available treatments. They describe their experience in using clinical judgment based on longitudinal observations to identify deficit and nondeficit subtypes of schizophrenic patients and propose criteria for defining schizophrenia with the deficit syndrome.
Leukocyte adhesion deficiency syndromes: adhesion and tethering defects involving β 2 integrins and selectin ligands (2002)

Leukocyte adhesion deficiency (LAD) syndromes are failures of innate host defenses against bacteria, fungi, and other microorganisms resulting from defective tethering, adhesion, and targeting of myeloid leukocytes to sites of microbial invasion. LAD I and variant LAD I syndromes are caused by mutations that impair expression or function of integrins of the beta 2 class (CD11/CD18 integrins, or "leukocyte" integrins). In contrast, subjects with LAD II have similar clinical features but intact leukocyte integrin expression and function. The molecular basis for LAD II is defective glycosylation of ligands on leukocytes recognized by the selectin family of adhesion molecules as well as defective glycosylation of other glycoconjugates. The defect has recently been attributed to mutations in a novel fucose transporter localized to the Golgi apparatus. Establishing the molecular basis for LAD syndromes has generated insights into mechanisms of leukocyte accumulation relevant to a broad variety of immunodeficiency syndromes as well as to diseases and disorders of unregulated inflammation that result in tissue damage.
Chemical and biological weapons: new questions, new answers. (1999)

The words "chemical and biological weapons" (CBW) send a shiver down most spines these days. With the end of the Cold War, the possibility of a massive nuclear confrontation appears remote, so today many popular doomsday scenarios center on the aggressive use of chemical or biological warfare by rogue nations or terrorist groups. As exaggerated as some of the accounts are, with CBW cast as the latest unseen, unstoppable enemy, the threat posed by these weapons is all too real, and growing.
Local production of the p40 subunit of interleukin 12 suppresses T-helper 1-mediated immune responses and prevents allogeneic myoblast rejection. (1996)

The p40 subunit of interleukin 12 (IL-12p40) has been known to act as an IL-12 antagonist in vitro. We here describe the immunosuppressive effect of IL-12p40 in vivo. A murine myoblast cell line, C2C12, was transduced with retro-virus vectors carrying the lacZ gene as a marker and the IL-12p40 gene. IL-12p40 secreted from the transfectant inhibited the IL-12-induced interferon gamma (IFN-gamma) production by splenocytes in vitro. Survival of C2C12 transplanted into allogeneic recipients was substantially prolonged when transduced with IL-12p40. Cytokine (IL-2 and IFN-gamma) production and cytotoxic T lymphocyte induction against allogeneic C2C12 were impaired in the recipients transplanted with the IL-12p40 transfectant. Delayed-type hypersensitivity response against C2C12 was also diminished in the IL-12p40 recipients. Furthermore, serum antibodies against beta-galactosidase of the T-helper 1-dependent isotypes (IgG2 and IgG3) were decreased in the IL-12p40 recipients. These results indicate that locally produced IL-12p40 exerts a potent immunosuppressive effect on T-helper 1-mediated immune responses that lead to allograft rejection. Therefore, IL-12p40 gene transduction would be useful for preventing the rejection of allografts and genetically modified own cells that are transduced with potentially antigenic molecules in gene therapy.
Immunobiology of gastrointestinal nematodes of ruminants. (1987)

Parasitoids are ubiquitous in natural ecosystems. Parasitic strategies are highly diverse among parasitoid species, yet their underlying genetic bases are poorly understood. Here, we focus on the divergent adaptation of a specialist and a generalist drosophilid parasitoids. We find that a novel protein (Lar) enables active immune suppression by lysing the host lymph glands, eventually leading to successful parasitism by the generalist. Meanwhile, another novel protein (Warm) contributes to a passive strategy by attaching the laid eggs to the gut and other organs of the host, leading to incomplete encapsulation and helping the specialist escape the host immune response. We find that these diverse parasitic strategies both originated from lateral gene transfer, followed with duplication and specialization, and that they might contribute to the shift in host ranges between parasitoids. Our results increase our understanding of how novel gene functions originate and how they contribute to host adaptation.