scholarly journals Analysis of the Ex-vivo transformation of Semen, Saliva and Urine as they dry out using ATR-FTIR spectroscopy and chemometric Approach

2021 ◽  
Author(s):  
Tanurup Das ◽  
Abhimanyu Harshey ◽  
Ankit Srivast ◽  
Kriti Nigam ◽  
Vijay Yadav ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Ex Vivo ◽  
Body Fluids ◽  
Biochemical Changes ◽  
Partial Least Square ◽  
Least Square ◽  
Slow Phase ◽  
Potential Marker ◽  
Dry Out

Abstract The ex-vivo biochemical changes of different body fluids are potential marker for the estimation of TSD. Infrared spectroscopy has great potential to reveal the biochemical changes in these fluids as previously reported by several researchers. Present study is focused to analyze the spectral changes in the ATR-FTIR spectra of three body fluids, commonly encountered in violent crimes i.e., Semen, Saliva and Urine as they dry out. The whole analytical timeline is divided into relatively slow phase I due to major contribution of water and faster Phase II due significant evaporation of water. Two spectral regions i.e., 3200-3400 cm-1 and 1600-1000 cm-1 are the major contributor to the spectra of these fluids. Several peaks in the spectral region between 1600-1000 cm-1 showed highly significant regression equation with higher coefficient of determination values in the Phase II in contrary to the slow passing Phase I. Principal component and Partial Least Square Regression analysis are the two chemometric tool used to estimate the TSD of the aforesaid fluids as they dry out. This study potentially estimates the TSD of an offence at the early stages after is occurrence as well as work as the precursor for further studies on extended timeframe.

scholarly journals Analysis of the ex-vivo transformation of semen, saliva and urine as they dry out using ATR-FTIR spectroscopy and chemometric approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tanurup Das ◽  
Abhimanyu Harshey ◽  
Ankit Srivastava ◽  
Kriti Nigam ◽  
Vijay Kumar Yadav ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Ex Vivo ◽  
Body Fluids ◽  
Biochemical Changes ◽  
Partial Least Square ◽  
The Body ◽  
Slow Phase ◽  
Time Since Deposition ◽  
Dry Out

AbstractThe ex-vivo biochemical changes of different body fluids also referred as aging of fluids are potential marker for the estimation of Time since deposition. Infrared spectroscopy has great potential to reveal the biochemical changes in these fluids as previously reported by several researchers. The present study is focused to analyze the spectral changes in the ATR-FTIR spectra of three body fluids, commonly encountered in violent crimes i.e., semen, saliva, and urine as they dry out. The whole analytical timeline is divided into relatively slow phase I due to the major contribution of water and faster Phase II due to significant evaporation of water. Two spectral regions i.e., 3200–3400 cm−1 and 1600–1000 cm−1 are the major contributors to the spectra of these fluids. Several peaks in the spectral region between 1600 and 1000 cm−1 showed highly significant regression equation with a higher coefficient of determination values in Phase II in contrary to the slow passing Phase I. Principal component and Partial Least Square Regression analysis are the two chemometric tool used to estimate the time since deposition of the aforesaid fluids as they dry out. Additionally, this study potentially estimates the time since deposition of an offense from the aging of the body fluids at the early stages after its occurrence as well as works as the precursor for further studies on an extended timeframe.

Tibial Tuberosity Transposition Fixation with a Locking Plate during Medial Patellar Luxation Surgery: An Ex Vivo Mechanical Study

2021 ◽  
Author(s):  
Esa V. Eskelinen ◽  
Ari P. Suhonen ◽  
Juha V. Virolainen ◽  
William D. Liska
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Locking Plate ◽  
Ex Vivo ◽  
Tibial Tuberosity ◽  
Tension Band ◽  
Patellar Ligament ◽  
Raccoon Dog ◽  
Tension Band Wire ◽  
Lower Load

Abstract Objectives The purpose of this study was to compare the load at failure, stiffness and mode of failure between three types of tibial tuberosity transposition fixation techniques: (a) pin and figure-8 tension band wire (Pin-TBW), (b) locking plate with pin and a tension band wire (Plate-Pin-TBW) and (c) locking plate with a pin (Plate-Pin). Methods Six pairs of raccoon dog cadaveric tibiae were tested in Phase I Pin-TBW versus Plate-Pin-TBW and seven pairs in Phase II Plate-Pin-TBW versus Plate-Pin. One limb of each pair was randomly assigned to one of two groups for each phase. A tensile force was applied to the patellar ligament until construct failure. Results Pin-TBW (342N ± 54.7N) failed at a lower load than Plate-Pin-TBW (469N ± 77.3N), p = 0.00748, with all Pin-TBW failing by fracture and the majority of Plate-Pin-TBW failing by rupture of patellar ligament. Pin-TBW group Phase I, normalized with Plate-Pin-TBW Phase I, failed at a lower load than Plate-Pin group Phase II, normalized with Plate-Pin-TBW Phase II, p = 0.00467. There was no significant difference in mean load at failure, stiffness or mode at failure between the groups in the Phase II study. Clinical Significance Although ex vivo mechanical testing does not replicate the postoperative live dog or cat, these results demonstrate lower construct strength of the Pin-TBW construct compared with the Plate-Pin construct in the raccoon dog cadaver model.

Phase I Dose-Escalation Trial of Checkpoint Kinase 1 Inhibitor MK-8776 As Monotherapy and in Combination With Gemcitabine in Patients With Advanced Solid Tumors

2015 ◽  
Vol 33 (9) ◽  
pp. 1060-1066 ◽  
Author(s):  
Adil I. Daud ◽  
Michelle T. Ashworth ◽  
Jonathan Strosberg ◽  
Jonathan W. Goldman ◽  
David Mendelson ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Phase I ◽  
Phase Ii ◽  
Ex Vivo ◽  
Dose Intensity ◽  
Median Number ◽  
Qtc Prolongation ◽  
Checkpoint Kinase ◽  
Checkpoint Kinase 1 ◽  
Recommended Phase Ii Dose

Purpose We determined the safety, pharmacokinetics, pharmacodynamics, and recommended phase II dose of MK-8776 (SCH 900776), a potent, selective checkpoint kinase 1 (Chk1) inhibitor, as monotherapy and in combination with gemcitabine in a first-in-human phase I clinical trial in patients with advanced solid tumor malignancies. Patients and Methods Forty-three patients were treated by intravenous infusion with MK-8776 at seven dose levels ranging from 10 to 150 mg/m2 as monotherapy and then in combination with gemcitabine 800 mg/m2 (part A, n = 26) or gemcitabine 1,000 mg/m2 (part B, n = 17). Forty percent of patients had three or more prior treatment regimens, and one third of patients had previously received gemcitabine. Results As monotherapy, MK-8776 was well tolerated, with QTc prolongation (19%), nausea (16%), fatigue (14%), and constipation (14%) as the most frequent adverse effects. Combination therapy demonstrated a higher frequency of adverse effects, predominantly fatigue (63%), nausea (44%), decreased appetite (37%), thrombocytopenia (32%), and neutropenia (24%), as well as dose-related, transient QTc prolongation (17%). The median number of doses of MK-8776 administered was five doses, with relative dose-intensity of 0.96. Bioactivity was assessed by γ-H2AX ex vivo assay. Of 30 patients evaluable for response, two showed partial response, and 13 exhibited stable disease. Conclusion MK-8776 was well tolerated as monotherapy and in combination with gemcitabine. Early evidence of clinical efficacy was observed. The recommended phase II dose is MK-8776 200 mg plus gemcitabine 1,000 mg/m2 on days 1 and 8 of a 21-day cycle.

Tensile stress relaxation of wood impregnated with different ACQ formulations at various temperatures

Holzforschung ◽  
2010 ◽  
Vol 64 (1) ◽  
Author(s):  
Lili Yu ◽  
Jinzhen Cao ◽  
Guangjie Zhao
Keyword(s):  
Stress Relaxation ◽  
Tensile Stress ◽  
Phase I ◽  
Phase Ii ◽  
Initial Period ◽  
Molar Ratio ◽  
Slow Phase ◽  
Orthogonal Experimental Design ◽  
Rapid Phase ◽  
Relaxation Curves

Abstract The reactions between constituents of alkaline copper quat (ACQ) and of wood were investigated by a tensile stress relaxation approach. Small samples were stressed and impregnated with various ACQ solutions, in which the ratios of monoethanolamine (MEA), ACQ, and didecyl dimethyl ammonium chloride (DDAC) were varied. The other parameters included temperature and concentration of the treating solutions. The stress relaxation curves of wood were recorded during the impregnation period and the effects of impregnation parameters were investigated by an orthogonal experimental design (OED). The effects of water, MEA, and DDAC on stress relaxation of the samples were also observed. The bulking effect of water was tested separately in samples treated with distilled water without stretching. The results showed that the stress relaxes dramatically in the initial period and then changes slightly over a long period, which is readily visible in double logarithmic plots of f (t)/f (0) versus time (t). There are complex interactions between the components of ACQ solutions and wood matrix: (1) in rapid phase I, the splitting of the easily accessible hydrogen bonds (mainly in the amorphous hemicelluloses) are prevalent by interaction with components of ACQ solution; (2) in slow phase II, Cu penetrates deeper in less accessible regions (e.g., in paracrystalline regions of cellulose) and renders possible further relaxation. The results of range and variance analysis reveal that the molar ratio of Cu to MEA and temperature of ACQ solution have significant effects on the rate of reaction during phase I, whereas in phase II only the temperature of ACQ solution has a significant effect. The stress relaxation curves of samples impregnated in water, MEA, and DDAC all showed a quasi one phase stress relaxation rate, which suggests that phase II is mostly related to Cu in ACQ formulations. It is concluded that the formation of complexes with Cu is still the major reaction in wood although there is competition among ACQ constituents for reaction sites.

Immunotherapy of Hormone-Refractory Prostate Cancer With Antigen-Loaded Dendritic Cells

2000 ◽  
Vol 18 (23) ◽  
pp. 3894-3903 ◽  
Author(s):  
Eric J. Small ◽  
Paige Fratesi ◽  
David M. Reese ◽  
George Strang ◽  
Reiner Laus ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Fusion Protein ◽  
Phase I ◽  
Phase Ii ◽  
Ex Vivo ◽  
Hormone Refractory Prostate Cancer ◽  
Tissue Antigen ◽  
Hormone Refractory

PURPOSE: Provenge (Dendreon Corp, Seattle, WA) is an immunotherapy product consisting of autologous dendritic cells loaded ex vivo with a recombinant fusion protein consisting of prostatic acid phosphatase (PAP) linked to granulocyte-macrophage colony-stimulating factor. Sequential phase I and phase II trials were performed to determine the safety and efficacy of Provenge and to assess its capacity to break immune tolerance to the normal tissue antigen PAP. PATIENTS AND METHODS: All patients had hormone-refractory prostate cancer. Dendritic-cell precursors were harvested by leukapheresis in weeks 0, 4, 8, and 24, loaded ex vivo with antigen for 2 days, and then infused intravenously over 30 minutes. Phase I patients received increasing doses of Provenge, and phase II patients received all the Provenge that could be prepared from a leukapheresis product. RESULTS: Patients tolerated treatment well. Fever, the most common adverse event, occurred after 15 infusions (14.7%). All patients developed immune responses to the recombinant fusion protein used to prepare Provenge, and 38% developed immune responses to PAP. Three patients had a more than 50% decline in prostate-specific antigen (PSA) level, and another three patients had 25% to 49% decreases in PSA. The time to disease progression correlated with development of an immune response to PAP and with the dose of dendritic cells received. CONCLUSION: Provenge is a novel immunotherapy agent that is safe and breaks tolerance to the tissue antigen PAP. Preliminary evidence for clinical efficacy warrants further exploration.

Ventilatory and gas exchange kinetics during exercise in chronic airways obstruction

1982 ◽  
Vol 53 (6) ◽  
pp. 1594-1602 ◽  
Author(s):  
L. E. Nery ◽  
K. Wasserman ◽  
J. D. Andrews ◽  
D. J. Huntsman ◽  
J. E. Hansen ◽  
...  
Keyword(s):  
Gas Exchange ◽  
Phase I ◽  
Phase Ii ◽  
Cardiovascular Response ◽  
Phase Iii ◽  
Slow Phase ◽  
Initial Increase ◽  
O2 Pulse ◽  
Exchange Kinetics ◽  
Gas Exchange Kinetics

The influence of chronic obstructive pulmonary disease (COPD) on exercise ventilatory and gas exchange kinetics was assessed in nine patients with stable airway obstruction (forced expired volume at 1 s = 1.1 +/- 0.33 liters) and compared with that in six normal men. Minute ventilation (VE), CO2 output (VCO2), and O2 uptake (VO2) were determined breath-by-breath at rest and after the onset of constant-load subanaerobic threshold exercise. The initial increase in VE, VCO2, and VO2 from rest (phase I), the subsequent slow exponential rise (phase II), and the steady-state (phase III) responses were analyzed. The COPD group had a significantly smaller phase I increase in VE (3.4 +/- 0.89 vs. 6.8 +/- 1.05 liters/min), VCO2 (0.10 +/- 0.03 vs. 0.22 +/- 0.03 liters/min), VO2 (0.10 +/- 0.03 vs. 0.24 +/- 0.04 liters/min), heart rate (HR) (6 +/- 0.9 vs. 16 +/- 1.4 beats/min), and O2 pulse (0.93 +/- 0.21 vs. 2.2 +/- 0.45 ml/beat) than the controls. Phase I increase in VE was significantly correlated with phase I increase in VO2 (r = 0.88) and HR (r = 0.78) in the COPD group. Most patients also had markedly slower phase II kinetics, i.e., longer time constants (tau) for VE (87 +/- 7 vs. 65 +/- 2 s), VCO2 (79 +/- 6 vs. 63 +/- 3 s), and VO2 (56 +/- 5 vs. 39 +/- 2 s) and longer half times for HR (68 +/- 9 vs. 32 +/- 2 s) and O2 pulse (42 +/- 3 vs. 31 +/- 2 s) compared with controls. However, tau VO2/tau VE and tau VCO2/tau VE were similar in both groups. The significant correlations of the phase I VE increase with HR and VO2 are consistent with the concept that the immediate exercise hyperpnea has a cardiodynamic basis. The slow ventilatory kinetics during phase II in the COPD group appeared to be more closely related to a slowed cardiovascular response rather than to any index of respiratory function. O2 breathing did not affect the phase I increase in VE but did slow phase II kinetics in most subjects. This confirms that the role attributed to the carotid bodies in ventilatory control during exercise in normal subjects also operates in patients with COPD.

scholarly journals Long-Term Follow-Up of Mesothelioma Patients Treated with Dendritic Cell Therapy in Three Phase I/II Trials

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 525
Author(s):  
Daphne W. Dumoulin ◽  
Robin Cornelissen ◽  
Koen Bezemer ◽  
Sara J. Baart ◽  
Joachim G. J. V. Aerts
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Survival Data ◽  
Ex Vivo ◽  
Tumor Cell Line ◽  
Autologous Tumor ◽  
Term Survival ◽  
Long Term Survival ◽  
Three Phase

Background: Malignant pleural mesothelioma (MPM) is a fatal neoplasm with, if untreated, poor survival of approximately nine months from diagnosis. Until recently, phase II–III immunotherapy trials did not show any significant benefit. The lack of immunotherapy efficacy can be explained by the fact that mesothelioma is a tumor with an “immune desert” phenotype, meaning a non-inflamed tumor characterized by low T-cell infiltration. By administration of DCs, which were ex-vivo cultured, exposed to (tumor-associated) antigens, and subsequently activated, this “immune desert” phenotype might be turned into an “inflamed” phenotype. Three phase I/II studies have been performed and published using activated DCs, which support this concept. We here report on the long-term survival of patients treated with DCs in three phase I/II studies. Methods: Survival data of the phase I/II trials using DC therapy in MPM patients were obtained and subsequently analyzed. In the first two trials, DCs were loaded with autologous tumor lysate. In the third trial, DCs were loaded with allogeneic mesothelioma tumor cell line lysate. Results: In the three studies combined, 29 patients with MPM were treated with DC vaccination between 2006 and 2015. At data cut-off, the median OS was 27 months (95% CI: 21–47 months). OS at 2 years was 55.2% (95% CI: 39.7–76.6%), and OS at 5 years was 20.7% (95% CI: 10.1–42.2%). Conclusions: The long-term survival of DC therapy in MPM in these three trials is promising, which is the basis for the randomized phase II/III DENIM study. This DENIM study is currently enrolling, and the results of which have to be awaited for definite conclusions.

scholarly journals Pathways of peroxynitrite oxidation of thiol groups

1997 ◽  
Vol 322 (1) ◽  
pp. 167-173 ◽  
Author(s):  
Celia QUIJANO ◽  
Beatriz ALVAREZ ◽  
Reynaldo M. GATTI ◽  
Ohara AUGUSTO ◽  
Rafael RADI
Keyword(s):  
Oxygen Consumption ◽  
Phase I ◽  
Phase Ii ◽  
Thiol Group ◽  
Second Order ◽  
Slow Phase ◽  
Acidic Ph ◽  
Fast Phase ◽  
Rate Of Oxygen Consumption ◽  
Phase Phase

Peroxynitrite mediates the oxidation of the thiol group of both cysteine and glutathione. This process is associated with oxygen consumption. At acidic pH and a cysteine/peroxynitrite molar ratio of ≤ 1.2, there was a single fast phase of oxygen consumption, which increased with increasing concentrations of both cysteine and oxygen. At higher molar ratios the profile of oxygen consumption became biphasic, with a fast phase (phase I) that decreased with increasing cysteine concentration, followed by a slow phase (phase II) whose rate of oxygen consumption increased with increasing cysteine concentration. Oxygen consumption in phase I was inhibited by desferrioxamine and 5,5-dimethyl-1-pyrroline N-oxide, but not by mannitol; superoxide dismutase also inhibited oxygen consumption in phase I, while catalase added during phase II decreased the rate of oxygen consumption. For both cysteine and glutathione, oxygen consumption in phase I was maximal at neutral to acidic pH; in contrast, total thiol oxidation was maximal at alkaline pH. EPR spin-trapping studies using N-tert-butyl-α-phenylnitrone indicated that the yield of thiyl radical adducts had a pH profile comparable with that found for oxygen consumption. The apparent second-order rate constants for the reactions of peroxynitrite with cysteine and glutathione were 1290ŷ30 M-1ƃs-1 and 281ŷ6 M-1ƃs-1 respectively at pH 5.75 and 37 ŶC. These results are consistent with two different pathways participating in the reaction of peroxynitrite with low-molecular-mass thiols: (a) the reaction of the peroxynitrite anion with the protonated thiol group, in a second-order process likely to involve a two-electron oxidation, and (b) the reaction of peroxynitrous acid, or a secondary species derived from it, with the thiolate in a one-electron transfer process that yields thiyl radicals capable of initiating an oxygen-dependent radical chain reaction.

scholarly journals Developing an Algorithm for Discriminating Oral Cancerous and Normal Tissues Using Raman Spectroscopy

2021 ◽  
Vol 11 (11) ◽  
pp. 1165
Author(s):  
Mukta Sharma ◽  
Ming-Jer Jeng ◽  
Chi-Kuang Young ◽  
Shiang-Fu Huang ◽  
Liann-Be Chang
Keyword(s):  
Raman Spectroscopy ◽  
Surgical Resection ◽  
Ex Vivo ◽  
Spectroscopic Method ◽  
Principal Component ◽  
Partial Least Square ◽  
Least Square ◽  
Validation Dataset ◽  
Linear Discriminant

The aim of this study was to investigate the clinical potential of Raman spectroscopy (RS) in detecting oral squamous cell carcinoma (OSCC) in tumor and healthy tissues in surgical resection specimens during surgery. Raman experiments were performed on cryopreserved specimens from patients with OSCC. Univariate and multivariate analysis was performed based on the fingerprint region (700–1800 cm−1) of the Raman spectra. One hundred thirty-one ex-vivo Raman experiments were performed on 131 surgical resection specimens obtained from 67 patients. The principal component analysis (PCA) and partial least square (PLS) methods with linear discriminant analysis (LDA) were applied on an independent validation dataset. Both models were able to differentiate between the tissue types, but PLS–LDA showed 100% accuracy, sensitivity, and specificity. In this study, Raman measurements of fresh resection tissue specimens demonstrated that OSCC had significantly higher nucleic acid, protein, and several amino acid contents than adjacent healthy tissues. The specific spectral information obtained in this study can be used to develop an in vivo Raman spectroscopic method for the tumor-free resection boundary during surgery.

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