bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards Copper(I) Clusters for Photo‐Induced Oxidation of Biological Thiols in Living Cells**
Authors: Gourdon‐Grünewaldt Lisa , Blacque Olivier , Gasser Gilles , Cariou Kevin
Published: September 2023

The cell redox balance can be disrupted by the oxidation of biological peptides, eventually leading to cell death, which provides opportunities to develop cytotoxic drugs. With the aim of developing compounds capable of specifically inducing fatal redox reactions upon light irradiation, we have developed a library of copper compounds. This metal is abundant and considered essential for human health, making it particularly attractive for the development of new anticancer drugs. Copper(I) clusters with thiol ligands (including 5 novel ones) have been synthesized and characterized. Structures were elucidated by X‐ray diffraction and showed that the compounds are oligomeric clusters. The clusters display high photooxidation capacity towards cysteine – an essential amino acid – upon light irradiation in the visible range (450 nm), while remaining completely inactive in the dark. This photoredox activity against a biological thiol is very encouraging for the development of anticancer photoredox drugs.The in vitro assay on murine colorectal cancer cells (CT26) did not show any toxicity – whether in the dark or when exposed to 450 nm light, likely because of the poor solubility of the complexes in biological medium.
One‐Pot Access to Boron‐Doped Fused Heterocycles via Domino Cyclization of Bis‐Diazidoboranes with Isonitrile
Authors: Liu Tong‐Tong , Cui Yun‐Shu
Published: September 2023

Boron‐doped fused heterocycles have shown great potential in the field of functional materials. This study reports on the synthesis of a new class of bis‐diazidoboranes and the discovery of their cycloaddition reaction with isonitriles. Triply fused boron‐doped heterocyclic compounds were constructed in a one‐pot process through a domino cycloaddition, providing an effective route for constructing complex boron‐doped heterocyclic systems.
PROTOCOL: Non‐pharmacological interventions for older people with a diagnosis of depression: An evidence and gap map
Authors: Shang Wenru , Guo Liping , Liu Yujia , Li Yanfei , Wei Qian , Guo Ke , Yang Minyan , Wei Lili , Xu Zheng , Niu Junqiang , Li Xiuxia , Yang Kehu
Published: September 2023

This is the protocol for an evidence and gap map. The objectives are as follows: To map available randomized control trials, economic evaluations, and systematic reviews that assess the effectiveness and cost‐effectiveness of non‐pharmacological interventions for older people with a diagnosis of depression and identify any existing gaps in the evidence that can inform future research.
Green Synthesis of 3,4‐Unsubstituted Isoquinolones through Rhodium(III)‐Catalyzed C−H Activation and Annulation in Ethanol
Authors: Kumar Vikash , Gandeepan Parthasarathy
Published: September 2023

A mild and convenient synthesis of 3,4‐unsubstituted isoquinolones has been achieved from N‐methoxybenzamides and vinylene carbonate as an acetylene surrogate with a versatile rhodium(III) catalyst. The reaction proceeded at room temperature in biomass derived ethanol solvent. This protocol avoids the use of stoichiometric external oxidant, as the vinylene carbonate served as the internal oxidant. The C−H/N−H activation and annulation manifold proceeded with broad substrate scope and excellent levels of regioselectivities. The preliminary mechanistic studies suggest facile and reversible chelation‐assisted C−H rhodation. Diversification of 3,4‐unsubstituted isoquinolones provide access to 4‐substituted isoquinolones and 3,4‐unsubstituted isoquinolines, which are complementary to the previously reported protocols.
Ultrasensitive assay of atrazine in food and water samples
Authors: Stefan‐van Staden Raluca‐Ioana , Niculae Roxana Andreea , van Staden Jacobus (Koos) Frederick
Published: September 2023

Atrazine is the pesticide that is found in surface water sources more frequently than any other pesticide. Therefore, the paper describes ultrasensitive detection of atrazine from fruit and water samples, using on‐site screening platforms incorporating stochastic microsensors based on graphite powder modified with 4‐tert‐butylcalix [4] arene and with calix [4] arene‐25,26,27,28‐tetrol. Limits of determination of 0.1 fmol L−1 were recorded while the sensors could have been used on wide concentration ranges, between 0.1 fmol L−1 and 0.1 mmol L−1. Recoveries higher than 95.00 % were recorded when used for the assay of atrazine in water, fruits and vegetables.
Toward maximum energy density enabled by anode‐free lithium metal batteries: Recent progress and perspective
Authors: Park Cheol‐Young , Kim Jinuk , Lim Won‐Gwang , Lee Jinwoo
Published: September 2023

Owing to the emergenceof energy storage and electric vehicles, the desire for safe high‐energy‐density energy storage devices has increased research interest in anode‐free lithium metal batteries (AFLMBs). Unlike general lithium metal batteries (LMBs), in which excess Li exists to compensate for the irreversible loss of Li, only the current collector is employed as an anode and paired with a lithiated cathode in the fabrication of AFLMBs. Owing to their unique cell configuration, AFLMBs have attractive characteristics, including the highest energy density, safety, and cost‐effectiveness. However, developing AFLMBs with extended cyclability remains an issue for practical applications because the high reactivity of Li with limited inventory causes severely low Coulombic efficiency (CE), poor cyclability, and dendrite growth. To address these issues, tremendous effort has been devoted to stabilizing Li metal anodes for AFLMBs. In this review, the importance and challenges of AFLMBs are highlighted. Then, diverse strategies, such as current collectors modification, advanced electrolytes, cathode engineering, and operation protocols are thoroughly reviewed. Finally, a future perspective on the strategy is provided for insight into the basis of future research. It is hoped that this review provides a comprehensive understanding by reviewing previous research and arousing more interest in this field.
Cryogenesis of granites and gneisses in South Yakutia
Authors: Melnikov Andrei , Zhang Ze
Published: September 2023

Based on field and laboratory studies of the rock massifs in South Yakutia using remote earth sensing technologies, methods of scanning electron microscopy, X‐ray 3D tomography, lithological‐mineralogical and optical‐petrographic studies, quantitative data on the intensity of cryogenesis of granites and gneisses in this area were obtained. A 16%–20% increase in the fracturing of rocks at the near‐surface part of the rock massif was shown to have occurred over a 10‐year period; during this time, vertical landforms, represented by granites and gneisses, retreated at a rate of 3 mm per year. However, no variations in the chemical and mineral composition of these rock types were identified over the study period.
Group‐level brain decoding with deep learning
Authors: Csaky Richard , van Es Mats W. J. , Jones Oiwi Parker , Woolrich Mark
Published: September 2023

Decoding brain imaging data are gaining popularity, with applications in brain‐computer interfaces and the study of neural representations. Decoding is typically subject‐specific and does not generalise well over subjects, due to high amounts of between subject variability. Techniques that overcome this will not only provide richer neuroscientific insights but also make it possible for group‐level models to outperform subject‐specific models. Here, we propose a method that uses subject embedding, analogous to word embedding in natural language processing, to learn and exploit the structure in between‐subject variability as part of a decoding model, our adaptation of the WaveNet architecture for classification. We apply this to magnetoencephalography data, where 15 subjects viewed 118 different images, with 30 examples per image; to classify images using the entire 1 s window following image presentation. We show that the combination of deep learning and subject embedding is crucial to closing the performance gap between subject‐ and group‐level decoding models. Importantly, group models outperform subject models on low‐accuracy subjects (although slightly impair high‐accuracy subjects) and can be helpful for initialising subject models. While we have not generally found group‐level models to perform better than subject‐level models, the performance of group modelling is expected to be even higher with bigger datasets. In order to provide physiological interpretation at the group level, we make use of permutation feature importance. This provides insights into the spatiotemporal and spectral information encoded in the models. All code is available on GitHub (https://github.com/ricsinaruto/MEG-group-decode).
Ability for fine needle aspiration and frozen section to predict extent of parotidectomy
Authors: Ali Hawa M. , Sankar George B. , Stickney Emily A. , Johns Heather L. , Whaley Rumeal D. , Rivera Michael , Lohse Christine M. , Tasche Kendall K. , Price Daniel L. , Van Abel Kathryn M. , Yin Linda X. , Moore Eric J.
Published: September 2023

Introduction

Several diagnostic modalities with various sensitivity and specificities can be used to evaluate a parotid mass. The aims of this project were to compare the diagnostic actionability, accuracy, and ability to accurately predict extent of surgery for FNA and frozen section during the evaluation of a parotid mass.

Methods

A retrospective chart review of patients who underwent parotidectomy for a parotid mass from January 1, 2015 to January 30, 2022 was conducted. Actionability was defined as a pathology diagnosis or the histologic grade of a lesion, as this provided clear and useful information for the surgeon to act upon. Diagnostic accuracy was determined by comparing FNA and frozen section results to final pathology. Accuracy of extent of surgery was determined by comparing predicted extent of surgery from the FNA or frozen section result to the extent of surgery predicted by the final pathology.

Results

A total of 626 patients were included in this study. FNA was obtained in 396 (63%) patients, while all neoplasms were evaluated by frozen section analysis. FNA diagnosis was actionable in 318 (80%), while frozen section diagnosis was actionable in 616 (98%) patients. Exactly 294 (92.5%) FNA diagnoses were accurate compared with 600 (98%) frozen section diagnoses. The FNA diagnosis predicted appropriate extent of surgery in 294 (74%) while the frozen section diagnosis predicted appropriate extent of surgery in 600 (96%). Among the 396 patients with FNA, frozen section was significantly more likely to accurately predict appropriate extent of surgery compared with FNA (p < 0.001).

Conclusion

Frozen section is more likely to yield actionable and accurate results compared with FNA. Additionally, frozen section is better than FNA in predicting the appropriate extent of surgery.
Second‐Line Antirheumatic Drugs in the Elderly with Rheumatoid Arthritis: A Post Hoc Analysis of Three Controlled Trials
Authors: Dahl Stephen L. , Samuelson Cecil O. , Williams H. James , Ward John R. , Karg Miki
Published: September 2023

This study assessed the relative efficacy and toxicity of second‐line antirheumatic drugs in patients 65 years of age or older compared to younger counterparts. The results of three prospective, double‐blind, parallel, randomized, multicenter trials were reanalyzed, stratifying outcomes by intervention and patient age. Efficacy was assessed by categorizing patient responses as follows: important improvement, no meaningful change, or progressive disease. Toxicity was analyzed by comparing withdrawal rates due to adverse effects. The three trials compared the following treatments: (1) d‐penicillamine 10–12 mg/day versus azathioprine 1.25‐1.5 mg/kg/day; (2) gold sodium thiomalate 50 mg intramuscularly weekly versus auranofin 6 mg/day versus placebo; and (3) pulse oral methotrexate 7.5–15.0 mg weekly versus placebo. At baseline, 103 patients age 65 or older were similar to 485 patients less than 65 years of age, with the exception of disease duration in all studies and erythrocyte sedimentation rate in one study. For patients completing each study, efficacy outcomes based on age were not significantly different. Withdrawal rates due to adverse drug reactions were also not significantly different.
Pharmacotherapy of Obsessive‐Compulsive Disorder
Authors: Jermain Donna M. , Crismon M. Lynn
Published: September 2023

Obsessive‐compulsive disorder (OCD) is a potentially devastating illness, both to the patient and family members. Its etiology is unclear, but some evidence points toward dysfunction in an orbitofrontal striatal‐limbic neuronal loop. Although many agents have been used, clomipramine, a tricyclic antidepressant, appears to be the most promising therapy. Clomipramine was approved by the Food and Drug Administration and released for general use in early 1990 under the brand name Anafranil. Clomipramine's adverse effect profile is similar to that of currently marketed tricyclic antidepressants; however, it is associated with a higher frequency of seizures, estimated to be 0.7%. Although other serotonergic agents such as fluoxetine have shown promise in OCD, they have been studied only in a limited number of patients. Other agents, with the possible exception of monoamine oxidase inhibitors, either have resulted in inconsistent improvement or have been reported in an anecdotal fashion.
Role of Nerve Growth Factor‐like Protein in the Paracrine Regulation of Prostate Growth
Authors: DJAKIEW DANIEL
Published: September 2023

ABSTRACT: Prostate cancer is the most commonly diagnosed form of malignant neoplasia in men. Considerable evidence has accumulated suggesting that paracrine interactions between stromal cells and epithelial cells mediate, in part, the growth and development of the prostate. A nerve growth factor‐like protein secreted by stromal cells has been implicated in the paracrine regulation of prostate epithelial tumor cell growth in vitro. This prostate‐derived nerve growth factor‐like protein differs from the known members of the neurotrophin family of proteins, and may represent a prostate‐specific form of this family of gene products. Furthermore, corresponding nerve growth factor receptors have been localized to the epithelial cells of the human prostate in vivo, consistent with a role of the receptors and the adjacent nerve growth factor‐like protein secreted by stromal cells, in the paracrine regulation of prostate growth and neoplasia.
The Human Sperm Acrosome Reaction Does Not Depend on Arachidonic Acid Metabolism via the Cyclooxygenase and Lipoxygenase Pathways
Authors: MACK STEPHEN R. , HAN HUI‐LING , de JONGE CHRISTOPHER J. , ANDERSON ROBERT A. , ZANEVELD LOURENS J.D.
Published: September 2023

ABSTRACT: The objective of this study was to determine whether the metabolism of arachidonic acid via the cyclooxygenase pathway, the lipoxygenase pathway, or both has a pivotal role in the human sperm acrosome reaction. To do so, the stimulatory effect of arachidonic acid and a number of its metabolites, as well as the inhibitory effect of cyclooxygenase and lipoxygenase inhibitors on the acrosome reaction, was evaluated. Arachidonic acid, prostaglandin E2, and prostacyclin (PGI2) induced the acrosome reaction when added to 3‐hour preincubated (capacitated) spermatozoa. The arachidonic acid‐induced acrosome reaction was dependent upon extracellular calcium. Leukotriene B4 and 15‐HPETE only induced the acrosome reaction when present throughout the preincubation period, indicating that they may enhance the capacitation process rather than the acrosome reaction. Thromboxane did not affect the acrosome reaction under any of the conditions tested. Inhibitors of cyclooxygenase (indomethacin, phenylbutazone) and lipoxygenase (phenidone, nordihydroguiaretic acid) or FPL 55712 (a leukotriene antagonist) did not prevent the arachidonic acid‐stimulated acrosome reaction. Furthermore, 5,8,11,14‐eicosatetraynoic acid (ETYA), the acetylenic analog of arachidonic acid that inhibits arachidonic acid metabolism, induced an acrosome reaction equivalent to that of arachidonic acid. These results strongly suggest that the acrosome reaction induced by exogenous arachidonic acid is not mediated via either the cyclooxygenase pathway or the lipoxygenase pathway. Since these pathways may be involved in other mechanisms that lead to the acrosome reaction, the effect of inhibitors on the dibutyryl cyclic adenosine monophosphate (Bu2‐cAMP)‐ and the ionophore A23187‐induced acrosome reaction was also tested. Although some of the inhibitors prevented the reaction, the results were nonspecific and inconsistent with a role of cyclooxygenase and lipoxygenase. It is concluded that arachidonic acid metabolism via the cyclooxygenase and lipoxygenase pathways is not an important mechanism in the human sperm acrosome reaction.
Glycosidic Specificity of Fucosyltransferases Present in Rat Epididymal Spermatozoa
Authors: RAYCHOUDHURY SAMIR S. , MILLETTE CLARKE F.
Published: September 2023

ABSTRACT: We have recently demonstrated multiple fucosyttrans‐ferase (FT) activity In rat spermatogenic cells. To complement these findings, here we Identify and partially characterize the glycosidic linkage specificity of FTs present in spermatozoa from caput and cauda epididymides. Analysis of the acceptor substrate specificity of the FTs by thin‐layer chromatography indicated that both caput and cauda sperm expressed α(1–2)‐, α(1–3)‐, α(1–4)‐FTs as demonstrated by fucose Incorporation into phenyl‐β‐D‐galactoside, 2′‐fucosyllactose, and lacto‐N‐fucopentaose‐l, respectively. Spermatozoa from the cauda epididymidis exhibited significant decreases in the levels of α(1–2)‐, α(1–3)‐, α(1–4)‐FTs, and of total soluble FTs in comparison to spermatozoa from the caput epididymidis. The relative ratio of α(1–3)‐FT to total FT activity appeared to be significantly higher than those of α(1–2)‐ or α(1–4)‐FTs, in spermatozoa both from caput and cauda epididymides. Using different types of low molecular weight acceptors and the selective inhibition of the FT by N‐ ethyl‐maleimide, we have demonstrated that at least α(1–2)‐FT is different from α(1–3)‐ or α(1–4)‐FTs. Kinetic studies also showed that α(1–2)‐FT is different from α(1–3)‐ or α(1–4)‐FTs as demonstrated by apparent Km and Vmax values. Moreover, α(1–3)‐and α(1–4)‐FT activities in cauda sperm were found to be highly sensitive to Mn2+ but showed differential responses to divalent cations. In contrast, both α(1–3)‐ and α(1–4)‐FTs seemed to be relatively less sensitive to Mg2+. Thus, these results not only demonstrate the presence of multiple FTs in rat epididymal sperm but also differentiate Individual FTs with regard to their kinetic properties and sensitivity to both inhibitor and divalent cations.
The Effects of Aging on Basement Membrane in the Testis
Authors: RICHARDSON LAURA L. , KLEINMAN HYNDA K. , DYM MARTIN
Published: September 2023

ABSTRACT: Age‐related increases in basement membrane thickness have been noted in many tissues, including the testis. The current investigation examined the morphology of the basement membrane in the aged Brown Norway rat and sought to determine whether the accumulation of basement membrane was the result of an increase in the expression of the basement membrane genes. The aged testis was characterized by atrophy of the seminiferous tubules. Closer examination of the degenerated tubules revealed that the seminiferous epithelium was completely devoid of germ cells and that the basement membrane of these tubules was thickened and highly convoluted. In some animals, there was a measurable increase in basement membrane thickness in tubules of normal diameter together with an apparently normal epithelium, suggesting that the thickening is not solely due to a shrinkage of the tubules. To determine whether an increase in basement membrane synthesis was responsible for the thickening, the expression of the genes for laminin, collagen IV, heparan sulfate proteoglycan, and fibronectin was analyzed by Northern blot. There were no changes in the expression of the genes for the laminin B1 and B2 chains, heparan sulfate proteoglycan, or fibronectin that could be correlated with increasing age. Surprisingly, however, the levels of mRNA for the laminin A chain and collagen IV decreased with age. Thus, it appears that the increased thickening of the basement membrane may not be due to increased synthesis of its components, although due to the chronic nature of the aging process, small or transient increases in gene expression may not have been detected. It is also possible that other mechanisms, such as decreased turnover, may play an important role in the age‐related thickening of the basement membrane in the testis.
The Contraceptive Effects of Etoprine on Male Mice and Rats
Authors: MALIK NASIR S. , MATLIN STEPHEN A. , FRIED JOSEF , PAKYZ RUTH E. , CONSENTINO M. JAMES
Published: September 2023

ABSTRACT: We had previously found that 2,4‐diaminopyrimidines affected spermatogenesis, possibly through the inhibition of testicular dihydrofolate reductase (DHFR). The current study examined the effects of etoprine, a highly lipophilic 2,4‐diaminopyrimidine that is also a potent DHFR inhibitor, on the fertility of male mice at various dosages (0.1–50 mg/kg/day) for 55 days and male rats at 5 mg/kg/day for 65 days. Two other substituted diaminopyrimidines were tested at dosages of 50 mg/kg/day for 55 days. Results of breeding trials along with assessment of various parameters indicative of male fertility were noted. We found that of the compounds tested, etoprine is a potent antifertility agent that causes complete infertility at doses of ≥5 mg/kg/day in mice with a threshold of effectiveness occurring between 1 and 5 mg/kg/day. The antifertility action of etoprine may be related to its capacity to inhibit testicular DHFR and its high degree of lipophilicity.
Levels of Hepatocyte Growth Factor/Scatter Factor (HGF/SF) in Seminal Plasma of Patients With Andrological Diseases
Authors: DEPUYDT CHRISTOPHE E. , de POTTER CHRISTIAN R. , ZALATA ADEL , BAEKELANDT ELSJE , BOSMANS EUGÈNE , COMHAIRE FRANK H.
Published: September 2023

ABSTRACT: Hepatocyte growth factor/scatter factor (HGF/SF) has all the characteristics of a molecule suitable for functioning in regulatory networks of motility, such as the spermatogenic epithelium, where spermatogenic cells must migrate between the cells of Sertoli, and it exerts its effect through binding of its high‐affinity receptor (c‐met). Considering the findings that c‐met receptor is expressed in the human testis and on spermatozoa, and that HGF/SF in seminal plasma consists of pro‐HGF/SF, mature αβ‐HGF/SF, and less active forms of HGF/SF, we investigated the concentration and biological activity of HGF/SF in seminal plasma and their correlation with parameters of spermatogenesis to obtain better insight into mechanisms that may be involved in the pathogenesis of male infertility. We also evaluated the potential value of assessment of hepatocyte growth factor concentration and its bioactivity for the diagnosis of certain pathological conditions of male reproduction. We studied the concentration and biological activity of HGF/SF in seminal plasma of normal men and of patients with a range of andrological diseases or conditions by measuring HGF/SF in seminal plasma by enzyme‐linked immunosorbent assay and by scatter assay using Madin‐Darby canine kidney epithelial cells. We identified three sources of HGF/SF in seminal plasma. In samples from vasectomized men (n = 30; 2.01 ng/ml) and in split ejaculate samples (n = 6; 1° fraction 2.75 ng/ml, 2° fraction 1.62 ng/ml), a prostatic origin can be certified. This HGF/SF has low biological activity (133.3 U/ml). In inflammation of the accessory sex glands (n = 40), a high amount of HGF/SF (3.04 ng/ml) can be generated by white blood cells and has moderate scatter activity (426.7 U/ml). In normozoospermic samples, there is a lower amount of HGF/SF (1.12 ng/ml), with strong scatter activity (1280.0 U/ml). Finally, the clear difference between the low amount of HGF/SF (1.06 ng/ml) with poor scatter activity (106.6 U/ml) in oligozoospermic samples (n = 28) and the high amount of HGF/SF (3.35 ng/ml) with strong scatter activity (853.3 U/ml) in samples from men with azoospermia of primary testicular failure (n = 18) suggests a mainly testicular origin, with different activity in different pathological conditions.
Influence of Centrifugation Regimes on Motility, Yield, and Cell Associations of Mouse Spermatozoa
Authors: KATKOV IGOR I. , MAZUR PETER
Published: September 2023

ABSTRACT: Mouse sperm are exceptionally sensitive to mechanical forces associated with pipetting and mixing. This characteristic raised the question of the sensitivity of mouse sperm to centrifugation, a step necessary in the removal of cryoprotectants and a common component in the general manipulation of sperm suspensions for experimental purpose. Epididymal spermatozoa from ICR mice were isolated and manipulated to minimize pipetting and mixing damage. The centrifugal accelerations studied were 200, 400, 600, and 800×g (measured with a stroboscope) for 5, 10, or 15 minutes of centrifugation time. The number of cells and the number of motile cells were counted. The percent motility and longevity, total yield, and motile yield were calculated. Centrifugation at 200 and 400×g for short times (5 minutes) caused only a small loss in either immediate or 2.5‐hour motility, but centrifugation at 600 and 800×g for 15 minutes produced up to a fivefold loss. Low speed/short time centrifugation pelleted only about half of the cells; the others were lost when the supernatant was removed. The maximum number of motile sperm (motile yield) was obtained at intermediate centrifugal forces (∼400×g for 10–12 minutes), and it is the total number of motile sperm (and not the percent motility) that is important in the use of cryopreserved sperm to regenerate cryopreserved mutant lines. Relative centrifugal force and centrifugation time exhibit reciprocity (e.g., 200×g for 10 minutes produces similar results to 400×g for 5 minutes). The spermatozoa must be centrifuged under carefully defined conditions to minimize the damage and to maximize the recovery of viable cells.
Pituitary Adenylate Cyclase‐Activating Polypeptide (PACAP): Effects on Blood Flow in the Testis and Caput Epididymidis of the Rat
Authors: LISSBRANT ERIK , COLLIN OLA , BERGH ANDERS
Published: September 2023

ABSTRACT:Pituitary adenylate cyclase–activating polypeptide (PACAP) is synthesized in developing germ cells in the testis and may act as a paracrine modulator of spermatogenesis and/or participate in tubule–interstitial interactions. Despite the abundance of PACAP in the organ, its role in testicular function has not yet been studiedin vivo. Using laser Doppler flowmetry, the effects of PACAP on blood flow in the testis and caput epididymidis were studied on anesthetized adult rats. When given intratesticularly as 5‐ and 50‐ng doses, PACAP increased blood flow by 55 ± 21% (mean ± SEM,P< 0.05) and by 68 ± 11% at 5 mm from the injection site, respectively. Whereas 5 ng PACAP did not influence blood flow 15 mm from the site of injection, flow was reduced (‐7 ± 3;P< 0.05) at this site following treatment with 50 ng. Injection of 50 ng PACAP into the caput epididymidis increased epididymal blood flow by 18 ± 4% (P< 0.05) at 1 mm from the injection site. None of the treatments above significantly affected the mean arterial blood pressure. Using immunohistochemistry, PACAP was observed in elongated spermatids and in the acrosomes of round spermatids in some, but not all, seminiferous tubules. Also, distinct PACAP immunoreactivity was seen in epithelial cells, particularly in clear cells, of the caput epididymidis. In conclusion, PACAP can induce vasodilatation in both testicular and epididymal microvessels and may be involved in regulating blood flow in these organs. Whereas the vasodilatory effect of PACAP is strong in the testis, the epididymal response appears to be more moderate.
Follicle‐Stimulating Hormone and Testosterone Stimulation of Immature and Mature Sertoli Cells in vitro: Inhibin and N‐cadherin Levels and Round Spermatid Binding
Authors: LAMPA JOHN , HOOGERBRUGGE JOS W. , BAARENDS WILLY M. , STANTON PETER G. , PERRYMAN KRISTEN J. , GROOTEGOED J. ANTON , ROBERTSON DAVID M.
Published: September 2023

ABSTRACT: The in vitro response of Sertoli cells isolated from adult rat testes to testosterone (T) and follicle‐stimulating hormone (FSH) treatment was investigated. Sertoli cells from >70‐day‐old Sprague‐Dawley rats were isolated by a combined enzymatic treatment followed by the removal of the majority of contaminating germ cells with immobilized peanut agglutinin lectin. Sertoli cells were then cultured for 6–10 days, forming a confluent layer with a cell viability of >83% and 74–77% purity. The contaminating cells were peritubular cells (4–6%), pachytene spermatocytes (4–5%), round spermatids (<2%), elongated spermatids (<1%), and degenerating germ cells (14.8%). The proportion of degenerating germ cells decreased from 14.8% to 8.6% between days 6 and 10 in culture. After a prestimulation culture period of 4 days, FSH treatment over a 2‐day period resulted in a dose‐related increase of inhibin with a median effective dose (ED,50) value of 36.7 ± 20.4 ng/ml in comparison with an ED50 value of 4.4 ± 0.9 ng/ml obtained with immature Sertoli cell cultures from 20‐day‐old rats. Mature Sertoli cells, in contrast to immature Sertoli cells, were unresponsive to combined FSH + T treatment for the production of the cell adhesion protein N‐cadherin. FSH treatment promoted the in vitro binding of round spermatids isolated from adult testis to adult Sertoli cells in coculture. It is concluded that mature Sertoli cells in culture are responsive to FSH in terms of inhibin production and roundspermatid binding. The lack of an FSH + T‐induced increase in N‐cadherin or round spermatid binding is attributed to either a reduced sensitivity, or an alteration in the regulation of mature Sertoli cells by FSH + T.
What Is A Requirement?
Authors: Harwell Richard , Aslaksen Erik , Mengot Roy , Hooks Ivy , Ptack Ken
Published: September 2023

Each contract specialist, lawyer, engineer, systems engineer, manager, or anyone else involved in the transition of vision into product, has his or her own definition of a requirement. With the rare exception, all are applicable and meaningful – but most are forgotten or ignored in the crunch to produce an effective requirements document under constrained schedule and funding environments. Yet, the need for effective requirements generation is probably the number one priority today in product development needs. Rather than approaching this problem from the theoretical or apriori standpoint, this paper examines the nature of a requirement through a process of identifying key characteristics and relationships from the viewpoint of the requirements manager/analyst and the requirements user (design team). It also discusses the importance of determining that requirements convey a need (as opposed to a directed solution), and ascertaining quality in terms of contextual adequacy.
FIRST‐ORDER SYSTEMS ENGINEERING: A CASE STUDY
Authors: Jackson Scott , Renton Meg
Published: September 2023

This paper stresses the importance of the System Engineering (SE) process in the contractor funded R&D phase of a project. This practice, first, permits major decisions to be made before extensive resources are committed to hardware and software designs. Secondly, it directs R&D efforts for following years. Finally, it saves money by concentrating on technical content rather than formal documentation. Examples are shown for the McDonnell Douglas Aerospace funded Lunar Base Reference Design study. Sample formats are shown for simplified documentation. The process is called First‐Order Systems Engineering (FOSE).
RE‐ENGINEERING THE SYSTEMS ENGINEERING PROCESS
Authors: Hudak George J.
Published: September 2023

Throughout AT&T Federal Systems Advanced Technologies (FSAT), many systems engineering processes were used by the various organizations, making it difficult to compare measures of effectiveness for each project's process. About one year ago, FSAT management chartered a Process Management Team (PMT) to develop a standard Systems Engineering process for FSAT. After one year, the PMT issued a generic Systems Engineering process document that will be used by all projects within FSAT. The process can be tailored to either commercial or government contracts and conforms to MIL‐STD‐499B. The standard process has been modeled in a computer‐aided engineering tool and is available to new projects on a computer disc. To support the process, special courses were developed to teach process fundamentals and give projects a jump‐start. In addition, a metrics program has been established that monitors and provides feedback to all projects using the standard or tailored process.
TQM DEVELOPMENT OF A SYSTEMS ENGINEERING PROCESS
Authors: Honour Eric C.
Published: September 2023

The paper documents a successful method used to define and improve a systems engineering process. Using the group consensus, employee‐oriented techniques of the Total Quality Management method, Harris Information Systems Division has standardized and significantly improved their systems engineering process over a four‐year period. The development of the standard process uses a ten‐step improvement method previously applied only in manufacturing areas. The Systems Engineering process team, consisting of experienced systems engineers, sequentially defined process outputs, internal/external customers, process requirements, the detailed process, and metrics.
SYNERGE: A Tool for Managing System Engineering Information
Authors: Neely Michael C. , Hartley Jonathan
Published: September 2023

This paper describes the development of an information management tool, called SYNERGE, to provide a low‐cost, desktop‐based, generalized user interface to a project information base. SYNERGE enables the management and analysis of interrelated requirements, tests, system elements, organizations, activities, resources, and other types of system engineering information, thus integrating a variety of activities and facilitating analysis of impacts of changes to the baseline. By making the project information base accessible to all process participants, SYNERGE will encourage an institutional transition to the more extensive use of automation, including high‐capability COTS products.
REQUIREMENTS TRACEABILITY ON THE F‐22 PROGRAM
Authors: Reed Michael A.
Published: September 2023

This paper presents the requirements traceability approach taken on the Engineering Manufacturing and Development (EMD) phase of the F‐22 Program, formerly known as the Advanced Tactical Fighter Program (ATF). Traceability was implemented through the incorporation of an automated CASE tool to track hierarchial requirements, vertically and laterally, to individual requirement verifications and test plans. Limitations in CASE tool integration and team incorporation of new technologies are discussed.
TOWARDS A NEW GENERATION EDUCATION: AN APPLICATION OF SYSTEMS ENGINEERING PRINCIPLES
Authors: Ottenberg Mark A. , Asbjornsen O. Andreas
Published: September 2023

As the world's technical development proceeds with increasing speed, and the society becomes ever more complex, it seems that our education system lags further and further behind with its old traditions and cultures. This paper shows that a proper application of Systems Engineering Principles in the design and development of education offers interesting and radical suggestions for changing the way education is traditionally structured and practised. “The Fifth Discipline” by Senge (Senge, 1990), which is the ability to continuously learn and develop from experience, experiments, and observations while working as part of a multi‐disciplinary team, when combined with knowledge in different fields, is really systems engineering at its best.
STRATEGIES FOR PREVENTING FUTURE “REQUIREMENTS CREEP”
Authors: Manos Kerry L.
Published: September 2023

“Requirements Creep,” the gradual increase in the average number of requirements specified for a given type of system, poses a formidable challenge to the future of systems engineering efforts. In such cases where the number of system‐level requirements reaches into the hundreds (or even thousands), the tasks of identifying, decomposing, allocating, documenting and providing traceability of requirements quickly becomes a bookkeeping nightmare. Moreover, the critical tasks of identifying alternative system architectures, synthesizing design concepts and performing trade‐offs against an overwhelming array of criteria are becoming so complex as to confound and confuse even the most capable of systems engineers. And equally insidious is the impact of large numbers of requirements on system cost– since the term “requirement” has traditionally referred to a need that must be satisfied despite cost.

In this paper, the author proposes that, in addition to developing the means to work effectively with large sets of requirements (e.g., computer data bases, modeling and simulation tools, etc.) systems engineering methodology should encompass strategies for limiting the number of requirements specified in the first place. The author then discusses a number of possible approaches, including elements of Quality Function Deployment, Analytic Hierarchy Processing and the so‐called “Eighty‐Twenty Rule,” and proposes how these might be applied collectively to determine the appropriate domain of requirements for a particular system. Although most readily applicable to non‐contract commercial or consumer system developments, such strategies could form a basis for future requirements definition efforts for government contract programs.
Development of a System Engineering Process Model Template
Authors: Tronstad Y.D. , Peterson J. , Shreve S.
Published: September 2023

The main problem facing the development of any large system today is complexity. The generalized process guidelines in the current MilStd life cycle specifications are based to a large extent on document production which falls short of capturing the system design data necessary to accommodate later upgrades. An executable model based approach to system engineering with one underlying formal representation for development of both system and process description is a better means for understanding the system and ultimately fulfilling the operational objectives within budget and schedule constraints.
SYSTEMS ENGINEERING IN A TECHNOLOGY DEVELOPMENT EFFORT: A CASE STUDY
Authors: Carlson Stephen O. , Matich Nicholas T.
Published: September 2023

This study discusses the System Engineering approach used to transition a medium‐sized (75 people) U.S. Government Research & Development (R&D) project from Concept Exploration (CE) to Demonstration and Validation (Dem/Val). The study presents a brief history of the project and discusses the Systems Engineering processes and techniques used to formalize system requirements, integrate the components, ensure proper testing, and produce complete documentation. Human factors issues observed in implementing formal Systems Engineering are discussed and lessons learned are presented. The use of a CASE tool is discussed.
CASE STUDIES: APPLICATIONS OF QUALITY FUNCTION DEPLOYMENT IN ACCORD WITH MILITARY STANDARD 499B
Authors: Bellagamba Laurence , Gernand Joseph , Tribble Alan
Published: September 2023

Quality function deployment is a methodology to relate what needs to be done to how to do it. The methodology is used to implement the requirements for the systems engineering process established in Military Standard 499B in conjunction with Integrated Product Development teams. Examples are presented for two divergent applications: payload design for an upper atmosphere research satellite and investment strategy design for a division's research and technology program.
Risk Expectation Management for Building Secure Information Systems
Authors: Howe Donald M.
Published: September 2023

This paper describes the process of building Information Systems that integrate security mechanisms to protect from unauthorized access and mistreatment Risk expectation management for information systems is associated with security requirements‐policy‐architecture‐risk analysis and synthesis. Cognizance of threat is the most important part of developing secure information systems. The paper organizes the complexity of information security principles into a structured approach intended to minimize the expected security risk. An example is presented in the appendix.
DISTRIBUTED DESIGN OF COMPUTER‐BASED SYSTEMS: TRACEABILITY
Authors: White Stephanie
Published: September 2023

Distributed computer‐based systems are complex due to their size, heterogeneous nature, and the dynamic interdependency of their components. Hardware and software are usually developed by a number of companies which the prime contractor and customer must rigorously monitor and control. Engineers and managers need traceability for control. They must trace requirements and design decision dependencies to create a complete and consistent design, to understand the impact of change, and to perform re‐engineering without introducing errors. Automatic compilation of software and silicon may eventually eliminate the need for traceability between formal specification and end‐product, but traceability will still be needed for tracing textual requirements and design decisions to formal specifications and test cases. This paper discusses the need for traceability, current practice and feasibility.
SYSTEM DEVELOPMENT PROCESS PLANNING AND MANAGEMENT
Authors: Beck John W. , Hudak George J.
Published: September 2023

This paper describes the planning and management approach used by AT&T Bell Laboratories to systematically establish and manage development processes for diverse types of projects. The approach is based on knowledge of all practices, tools, and training and an efficient method for selecting and tailoring these elements for projects. Planning is supported by a knowledge system that helps them select and tailor the “mosaic” of development tools and aids to produce a project specific development process plan. New projects benefit from the “experience” as other projects complete and update the knowledge system. All projects benefit from plans that are developed better, faster, and cheaper and the subsequent uniform development environment facilitates staff mobility.
THE WORK BREAKDOWN STRUCTURE: Its Much More Than a Cost Reporting Structure
Authors: Lake Jerry
Published: September 2023

For the past 25 years of defense system acquisitions, the business side of government programs has controlled the underlying structure of the product‐oriented work breakdown structure (WBS). As such, little interest has been shown by engineers in discussing or using a WBS to assist system development. In the past year, both Mil‐Std‐881 on work breakdown structures and Mil‐Std‐499 on systems engineering have undergone revision. The revised systems engineering standard creates new purposes and uses for an “engineering” work breakdown structure (EWBS) consistent with concurrent engineering implementation. These purposes and uses expand the historical role of a WBS for establishing, tracking and comparing cost accounts to satisfy management's need to have visibility into program costs. As a result, the structure of an EWBS differs in several aspects from the time honored structure of Mil‐Std‐881.

This paper discusses the central role the engineering WBS takes in accomplishing world class systems engineering. The focus, therefore, is (1) on the major role the EWBS plays in systems engineering and (2) on the differences of the EWBS with the WBS generated to satisfy business needs. The EWBS is explained with respect to its specific roles in structuring the statement of work, assigning integrated product and process teams, and conducting incremental technical reviews. A proposed resolution is recommended for resolving perceived differences between business and engineering work breakdown structures.
3.1.2 Intelligent Agent Technology in the Health Care Environment
Authors: Simons Desiree. J.
Published: September 2023

Most people think of intelligent agent technology and the Internet as being connected because of the awareness brought to search engines by the public's use of the Internet. However, agent technology has always been in existence, as for example in the banking environment where an agent might be the alert agent for detecting when a stock price reaches a certain point. Unfortunately, many of today's Internet agents are not considered “intelligent” mainly because they are incapable of defining their area of search and as such, their applications are somewhat limited. Efforts to make agents work more efficiently have led to the emergence of a new technology called “filtering” which makes use of the speed of computers and the ability of networks to communicate. This paper examines the factors that are driving the development of filtering as well as the role of agent technology in the ever‐changing landscape of computer systems development. Finally, the impact that this kind of technology will have on medical professionals and patients in our future health care environment is illustrated by a description of the Patient Advocate system being developed by Stanford University.
3.1.3 The Application of Systems Engineering to Telemedicine
Authors: Chorley Stephen J.
Published: September 2023

A case study is presented of the application of the systems engineering process of BAE SYSTEMS to a telemedicine project for South Africa. It is an example of the successful transfer of technology from the defence to the civilian sector and shows how the company's systems engineering practices were effectively applied in this field. The conclusion reached is that a good systems engineering process should be adaptable and effective and that technology transfer is an ideal benchmark test for any such process.
3.1.4 Predictive Performance Analysis and System/Software Architecture
Authors: Lacerte Yves
Published: September 2023

The development of long‐lived real‐time embedded software‐intensive systems face unique challenges. It is critical that sound architectural principles be applied toward the development of such complex systems. An essential architectural element in a real‐time system is performance.

Predictive evaluation techniques can be effectively applied as part of the architecture design process. These techniques enable the estimation of performance of a given implementation on a given hardware configuration without having to actually execute it. In addition, it allows the architect to evaluate individual application modules during development instead of waiting for the application to be completely developed before assessing its performance.
7.1.3 Radioactive Material Transportation Requirements for the Department of Energy
Authors: Bolander Thane W. , John Mark E. , Fawcett Rick L.
Published: September 2023

The Department of Energy (DOE) created the National Transportation Program (NTP) whose goal is to ensure the availability of safe, efficient, and timely transportation of DOE materials. The Integration and Planning Group of the NTP, assisted by Global Technologies Incorporated (GTI), was tasked to identify requirements associated with the transport of DOE Environmental Management (EM) radiological waste/material. A systems engineering approach was used to identify source documents, extract requirements, perform a functional analysis, and set up a transportation requirements management database in RDD‐100. Functions and requirements for transporting the following DOE radioactive waste/material are contained in the database: high level radioactive waste (HLW), low‐level radioactive waste (LLW), mixed low‐level radioactive waste (MLLW), nuclear materials (NM), spent nuclear fuel (SNF), and transuranic waste (TRU waste). The requirements will be used in the development of standard transportation protocols for DOE shipping. The protocols will then be combined into a DOE Transportation Program Management Guide, which will be used to standardize DOE transportation processes.